Mucin is an amorphous gelatinous substance that is found in a large variety of tissues. There are 2 types of cutaneous mucin: dermal and epithelial. Both types appear as basophilic shreds and granules with hematoxylin and eosin stain.1 Epithelial mucin (sialomucin) is found mainly in the gastrointestinal tract and lungs. In the skin, it is present in the cytoplasm of the dark cells of the eccrine glands and in the apocrine secretory cells. Epithelial mucin contains both neutral and acid glycosaminoglycans, stains positive with Alcian blue (pH 2.5) and periodic acid–Schiff, is resistant to hyaluronidase, and does not stain metachromatically with toluidine blue. Dermal mucin is composed of acid glycosaminoglycans (eg, dermatan sulfate, chondroitin 6-sulfate, chondroitin 4-sulfate, hyaluronic acid) and normally is produced by dermal fibroblasts. Dermal mucin stains positive with Alcian blue (pH 2.5); is periodic acid–Schiff negative and sensitive to hyaluronidase; and shows metachromasia with toluidine blue, methylene blue, and thionine.

Cutaneous mucinosis comprises a heterogeneous group of skin disorders characterized by the deposition of mucin in the interstices of the dermis. These diseases may be classified as primary mucinosis with the mucin deposition as the main histologic feature resulting in clinically distinctive lesions and secondary mucinosis with the mucin deposition as an additional histologic finding within the context of an independent skin disease or lesion (eg, basal cell carcinoma) with deposits of mucin in the stroma. Primary cutaneous mucinosis may be subclassified into 2 groups: degenerative-inflammatory mucinoses and neoplastic-hamartomatous mucinoses. According to the histologic features, the degenerative-inflammatory mucinoses are better divided into dermal and follicular mucinoses.² We describe a case of primary cutaneous dermal mucinosis on herpes zoster (HZ) scars as an isotopic response.

Case Report

A 33-year-old man presented to the dermatology department with slightly pruritic lesions on the left side of the chest and back that had appeared progressively at the site of HZ scars that had healed without treatment 9 months prior. Dermatologic examination revealed sharply defined whitish papules (Figure 1) measuring 2 to 4 mm in diameter with a smooth surface and linear distribution over the area of the left T8 and T9 dermatomes. The patient reported no postherpetic neuralgia and was otherwise healthy. Laboratory tests including a complete blood cell count, biochemistry, urinalysis, and determination of free thyroid hormones were within reference range. Serologic tests for human immunodeficiency virus, hepatitis B and C viruses, and syphilis were negative. Antinuclear antibodies also were negative.

Histopathology demonstrated abundant bluish granular material between collagen bundles of the papillary dermis (Figure 2). No cytopathologic signs of active herpetic infection were seen. The Alcian blue stain at pH 2.5 was strongly positive for mucin, which confirmed the diagnosis of primary cutaneous dermal mucinosis.

Topical corticosteroids were applied for 2 months with no notable improvement. The lesions gradually improved without any other therapy during the subsequent 6 months.

Comment

The occurrence of a new skin disease at the exact site of a prior unrelated cutaneous disorder that had already resolved was first reported by Wyburn-Mason³ in 1955. Forty years later, the term isotopic response was coined by Wolf et al⁴ to describe this phenomenon. Diverse types of skin diseases such as herpes simplex virus,⁵ varicella-zoster infections,⁴ and thrombophlebitis⁴ have been implicated in cases of isotopic response, but the most frequently associated primary disorder by far is cutaneous HZ.

Several benign and malignant disorders may occur at sites of resolved HZ lesions, including granulomatous dermatitis,⁶ granuloma annulare,⁷ fungal granuloma,⁸ fungal folliculitis,⁹ psoriasis,¹⁰ morphea,¹¹ lichen sclerosus,¹² Kaposi sarcoma,¹³ the lichenoid variant of chronic graft-versus-host disease,¹⁴ cutaneous sarcoidosis,¹⁵ granulomatous folliculitis,¹⁶ comedones,¹⁷ furuncles,¹⁸ erythema annulare centrifugum,¹⁹ eosinophilic dermatosis,²⁰ cutaneous pseudolymphoma,²¹ granulomatous vasculitis,²² Rosai-Dorfman disease,¹² xanthomatous changes,²³ tuberculoid granulomas,²⁴ acneform eruption,²⁵ lichen planus,²⁶ acquired reactive perforating collagenosis,²⁷ lymphoma,²⁸ leukemia,²⁹ angiosarcoma,³⁰ basal cell carcinoma,³¹ squamous cell carcinoma, and cutaneous metastasis from internal carcinoma.³² The interval between the acute HZ episode and presentation of the second disease is quite variable, ranging from days to several months. Postzoster isotopic response has been described in individuals with varying degrees of immune response, affecting both immunocompetent¹² and immunocompromised patients.¹⁴ There is no predilection for age, sex, or race. It also seems that antiviral treatment during the active episode does not prevent the development of secondary reactions.Kim et al³³ reported a 59-year-old woman who developed flesh-colored or erythematous papules on HZ scars over the area of the left T1 and T2 dermatomes 1 week after the active viral process. Histopathologic study demonstrated deposition of mucin between collagen bundles in the dermis. The authors established the diagnosis of secondary cutaneous mucinosis as an isotopic response.³³ Nevertheless, we believe that based on the aforementioned classification of cutaneous mucinosis,² both this case and our case are better considered as primary cutaneous dermal mucinosis, as the mucin deposition in the dermis was the main histologic finding resulting in a distinctive cutaneous disorder. In the case reported by Kim et al,³³ a possible relationship between cutaneous mucinosis and postherpetic neuralgia was suggested based on the slow regression of skin lesions in accordance with the improvement of the neuralgic pain; however, our patient did not have postherpetic neuralgia and the lesions persisted unchanged several months after the acute HZ episode. In the literature, there are reports of primary cutaneous dermal mucinosis associated with altered thyroid function³⁴; autoimmune connective tissue diseases, mostly lupus erythematosus³⁵; monoclonal gammopathy³⁶; and human immunodeficiency virus infection,³⁷ but these possibilities were ruled out in our patient by pertinent laboratory studies.

The pathogenesis of the postherpetic isotopic response remains unknown, but several mechanisms have been proposed. Some authors have suggested that postzoster dermatoses may represent isomorphic response of Köbner phenomenon.^13,15 Although isomorphic and isotopic responses share some similarities, these terms describe 2 different phenomena: the first refers to the appearance of the same cutaneous disorder at a different site favored by trauma, while the second manifests a new and unrelated disease at the same location.³⁸ Local anatomic changes such as altered microcirculation, collagen rearrangement, and an imperfect skin barrier may promote a prolonged local inflammatory response. Moreover, the destruction of nerve fibers by the varicella-zoster virus may indirectly influence the local immune system through the release of specific neuropeptides in the skin.³⁹ It has been speculated that some secondary reactions may be the result of type III and type IV hypersensitivity reactions⁴⁰ to viral antigens or to tissue antigens modified by the virus, inducing either immune hypersensitivity or local immune suppression.⁴¹ Some authors have documented the presence of varicella-zoster DNA within early postzoster lesions^6,7 by using polymerase chain reaction in early lesions but not in late-stage and residual lesions.^12,22 Nikkels et al⁴² studied early granulomatous lesions by immunohistochemistry and in situ hybridization techniques and concluded that major viral envelope glycoproteins (glycoproteins I and II) rather than complete viral particles could be responsible for delayed-type hypersensitivity reactions. All these findings suggest that secondary reactions presenting on HZ scars are mainly the result of atypical immune reactions to local antigenic stimuli.

The pathogenesis of our case is unknown. From a theoretical point of view, it is possible that varicella-zoster virus may induce fibroblastic proliferation and mucin production on HZ scars; however, if HZ is a frequent process and the virus may induce mucin production, then focal dermal mucinosis in an HZ scar should be a common finding. In our patient, there was no associated disease favoring the development of the cutaneous mucinosis. These localized variants of primary cutaneous mucinosis usually do not require therapy, and a wait-and-see approach is recommended. Topical applications of corticosteroids, pimecrolimus, or tacrolimus, as well as oral isotretinoin, may have some benefit,⁴³ but spontaneous resolution may occur.⁴⁴ In our patient, topical corticosteroids were applied 2 months following initial presentation without any benefit and the cutaneous lesions gradually improved without any therapy during the subsequent 6 months. Focal dermal mucinosis should be added to the list of cutaneous reactions that may develop in HZ scars.

Mucin is an amorphous gelatinous substance that is found in a large variety of tissues. There are 2 types of cutaneous mucin: dermal and epithelial. Both types appear as basophilic shreds and granules with hematoxylin and eosin stain.1 Epithelial mucin (sialomucin) is found mainly in the gastrointestinal tract and lungs. In the skin, it is present in the cytoplasm of the dark cells of the eccrine glands and in the apocrine secretory cells. Epithelial mucin contains both neutral and acid glycosaminoglycans, stains positive with Alcian blue (pH 2.5) and periodic acid–Schiff, is resistant to hyaluronidase, and does not stain metachromatically with toluidine blue. Dermal mucin is composed of acid glycosaminoglycans (eg, dermatan sulfate, chondroitin 6-sulfate, chondroitin 4-sulfate, hyaluronic acid) and normally is produced by dermal fibroblasts. Dermal mucin stains positive with Alcian blue (pH 2.5); is periodic acid–Schiff negative and sensitive to hyaluronidase; and shows metachromasia with toluidine blue, methylene blue, and thionine.

Cutaneous mucinosis comprises a heterogeneous group of skin disorders characterized by the deposition of mucin in the interstices of the dermis. These diseases may be classified as primary mucinosis with the mucin deposition as the main histologic feature resulting in clinically distinctive lesions and secondary mucinosis with the mucin deposition as an additional histologic finding within the context of an independent skin disease or lesion (eg, basal cell carcinoma) with deposits of mucin in the stroma. Primary cutaneous mucinosis may be subclassified into 2 groups: degenerative-inflammatory mucinoses and neoplastic-hamartomatous mucinoses. According to the histologic features, the degenerative-inflammatory mucinoses are better divided into dermal and follicular mucinoses.² We describe a case of primary cutaneous dermal mucinosis on herpes zoster (HZ) scars as an isotopic response.

Case Report

A 33-year-old man presented to the dermatology department with slightly pruritic lesions on the left side of the chest and back that had appeared progressively at the site of HZ scars that had healed without treatment 9 months prior. Dermatologic examination revealed sharply defined whitish papules (Figure 1) measuring 2 to 4 mm in diameter with a smooth surface and linear distribution over the area of the left T8 and T9 dermatomes. The patient reported no postherpetic neuralgia and was otherwise healthy. Laboratory tests including a complete blood cell count, biochemistry, urinalysis, and determination of free thyroid hormones were within reference range. Serologic tests for human immunodeficiency virus, hepatitis B and C viruses, and syphilis were negative. Antinuclear antibodies also were negative.

Histopathology demonstrated abundant bluish granular material between collagen bundles of the papillary dermis (Figure 2). No cytopathologic signs of active herpetic infection were seen. The Alcian blue stain at pH 2.5 was strongly positive for mucin, which confirmed the diagnosis of primary cutaneous dermal mucinosis.

Topical corticosteroids were applied for 2 months with no notable improvement. The lesions gradually improved without any other therapy during the subsequent 6 months.

Comment

The occurrence of a new skin disease at the exact site of a prior unrelated cutaneous disorder that had already resolved was first reported by Wyburn-Mason³ in 1955. Forty years later, the term isotopic response was coined by Wolf et al⁴ to describe this phenomenon. Diverse types of skin diseases such as herpes simplex virus,⁵ varicella-zoster infections,⁴ and thrombophlebitis⁴ have been implicated in cases of isotopic response, but the most frequently associated primary disorder by far is cutaneous HZ.

Several benign and malignant disorders may occur at sites of resolved HZ lesions, including granulomatous dermatitis,⁶ granuloma annulare,⁷ fungal granuloma,⁸ fungal folliculitis,⁹ psoriasis,¹⁰ morphea,¹¹ lichen sclerosus,¹² Kaposi sarcoma,¹³ the lichenoid variant of chronic graft-versus-host disease,¹⁴ cutaneous sarcoidosis,¹⁵ granulomatous folliculitis,¹⁶ comedones,¹⁷ furuncles,¹⁸ erythema annulare centrifugum,¹⁹ eosinophilic dermatosis,²⁰ cutaneous pseudolymphoma,²¹ granulomatous vasculitis,²² Rosai-Dorfman disease,¹² xanthomatous changes,²³ tuberculoid granulomas,²⁴ acneform eruption,²⁵ lichen planus,²⁶ acquired reactive perforating collagenosis,²⁷ lymphoma,²⁸ leukemia,²⁹ angiosarcoma,³⁰ basal cell carcinoma,³¹ squamous cell carcinoma, and cutaneous metastasis from internal carcinoma.³² The interval between the acute HZ episode and presentation of the second disease is quite variable, ranging from days to several months. Postzoster isotopic response has been described in individuals with varying degrees of immune response, affecting both immunocompetent¹² and immunocompromised patients.¹⁴ There is no predilection for age, sex, or race. It also seems that antiviral treatment during the active episode does not prevent the development of secondary reactions.Kim et al³³ reported a 59-year-old woman who developed flesh-colored or erythematous papules on HZ scars over the area of the left T1 and T2 dermatomes 1 week after the active viral process. Histopathologic study demonstrated deposition of mucin between collagen bundles in the dermis. The authors established the diagnosis of secondary cutaneous mucinosis as an isotopic response.³³ Nevertheless, we believe that based on the aforementioned classification of cutaneous mucinosis,² both this case and our case are better considered as primary cutaneous dermal mucinosis, as the mucin deposition in the dermis was the main histologic finding resulting in a distinctive cutaneous disorder. In the case reported by Kim et al,³³ a possible relationship between cutaneous mucinosis and postherpetic neuralgia was suggested based on the slow regression of skin lesions in accordance with the improvement of the neuralgic pain; however, our patient did not have postherpetic neuralgia and the lesions persisted unchanged several months after the acute HZ episode. In the literature, there are reports of primary cutaneous dermal mucinosis associated with altered thyroid function³⁴; autoimmune connective tissue diseases, mostly lupus erythematosus³⁵; monoclonal gammopathy³⁶; and human immunodeficiency virus infection,³⁷ but these possibilities were ruled out in our patient by pertinent laboratory studies.

The pathogenesis of the postherpetic isotopic response remains unknown, but several mechanisms have been proposed. Some authors have suggested that postzoster dermatoses may represent isomorphic response of Köbner phenomenon.^13,15 Although isomorphic and isotopic responses share some similarities, these terms describe 2 different phenomena: the first refers to the appearance of the same cutaneous disorder at a different site favored by trauma, while the second manifests a new and unrelated disease at the same location.³⁸ Local anatomic changes such as altered microcirculation, collagen rearrangement, and an imperfect skin barrier may promote a prolonged local inflammatory response. Moreover, the destruction of nerve fibers by the varicella-zoster virus may indirectly influence the local immune system through the release of specific neuropeptides in the skin.³⁹ It has been speculated that some secondary reactions may be the result of type III and type IV hypersensitivity reactions⁴⁰ to viral antigens or to tissue antigens modified by the virus, inducing either immune hypersensitivity or local immune suppression.⁴¹ Some authors have documented the presence of varicella-zoster DNA within early postzoster lesions^6,7 by using polymerase chain reaction in early lesions but not in late-stage and residual lesions.^12,22 Nikkels et al⁴² studied early granulomatous lesions by immunohistochemistry and in situ hybridization techniques and concluded that major viral envelope glycoproteins (glycoproteins I and II) rather than complete viral particles could be responsible for delayed-type hypersensitivity reactions. All these findings suggest that secondary reactions presenting on HZ scars are mainly the result of atypical immune reactions to local antigenic stimuli.

The pathogenesis of our case is unknown. From a theoretical point of view, it is possible that varicella-zoster virus may induce fibroblastic proliferation and mucin production on HZ scars; however, if HZ is a frequent process and the virus may induce mucin production, then focal dermal mucinosis in an HZ scar should be a common finding. In our patient, there was no associated disease favoring the development of the cutaneous mucinosis. These localized variants of primary cutaneous mucinosis usually do not require therapy, and a wait-and-see approach is recommended. Topical applications of corticosteroids, pimecrolimus, or tacrolimus, as well as oral isotretinoin, may have some benefit,⁴³ but spontaneous resolution may occur.⁴⁴ In our patient, topical corticosteroids were applied 2 months following initial presentation without any benefit and the cutaneous lesions gradually improved without any therapy during the subsequent 6 months. Focal dermal mucinosis should be added to the list of cutaneous reactions that may develop in HZ scars.

Mucin is an amorphous gelatinous substance that is found in a large variety of tissues. There are 2 types of cutaneous mucin: dermal and epithelial. Both types appear as basophilic shreds and granules with hematoxylin and eosin stain.1 Epithelial mucin (sialomucin) is found mainly in the gastrointestinal tract and lungs. In the skin, it is present in the cytoplasm of the dark cells of the eccrine glands and in the apocrine secretory cells. Epithelial mucin contains both neutral and acid glycosaminoglycans, stains positive with Alcian blue (pH 2.5) and periodic acid–Schiff, is resistant to hyaluronidase, and does not stain metachromatically with toluidine blue. Dermal mucin is composed of acid glycosaminoglycans (eg, dermatan sulfate, chondroitin 6-sulfate, chondroitin 4-sulfate, hyaluronic acid) and normally is produced by dermal fibroblasts. Dermal mucin stains positive with Alcian blue (pH 2.5); is periodic acid–Schiff negative and sensitive to hyaluronidase; and shows metachromasia with toluidine blue, methylene blue, and thionine.

Cutaneous mucinosis comprises a heterogeneous group of skin disorders characterized by the deposition of mucin in the interstices of the dermis. These diseases may be classified as primary mucinosis with the mucin deposition as the main histologic feature resulting in clinically distinctive lesions and secondary mucinosis with the mucin deposition as an additional histologic finding within the context of an independent skin disease or lesion (eg, basal cell carcinoma) with deposits of mucin in the stroma. Primary cutaneous mucinosis may be subclassified into 2 groups: degenerative-inflammatory mucinoses and neoplastic-hamartomatous mucinoses. According to the histologic features, the degenerative-inflammatory mucinoses are better divided into dermal and follicular mucinoses.² We describe a case of primary cutaneous dermal mucinosis on herpes zoster (HZ) scars as an isotopic response.

Case Report

A 33-year-old man presented to the dermatology department with slightly pruritic lesions on the left side of the chest and back that had appeared progressively at the site of HZ scars that had healed without treatment 9 months prior. Dermatologic examination revealed sharply defined whitish papules (Figure 1) measuring 2 to 4 mm in diameter with a smooth surface and linear distribution over the area of the left T8 and T9 dermatomes. The patient reported no postherpetic neuralgia and was otherwise healthy. Laboratory tests including a complete blood cell count, biochemistry, urinalysis, and determination of free thyroid hormones were within reference range. Serologic tests for human immunodeficiency virus, hepatitis B and C viruses, and syphilis were negative. Antinuclear antibodies also were negative.

Histopathology demonstrated abundant bluish granular material between collagen bundles of the papillary dermis (Figure 2). No cytopathologic signs of active herpetic infection were seen. The Alcian blue stain at pH 2.5 was strongly positive for mucin, which confirmed the diagnosis of primary cutaneous dermal mucinosis.

Topical corticosteroids were applied for 2 months with no notable improvement. The lesions gradually improved without any other therapy during the subsequent 6 months.

Comment

The occurrence of a new skin disease at the exact site of a prior unrelated cutaneous disorder that had already resolved was first reported by Wyburn-Mason³ in 1955. Forty years later, the term isotopic response was coined by Wolf et al⁴ to describe this phenomenon. Diverse types of skin diseases such as herpes simplex virus,⁵ varicella-zoster infections,⁴ and thrombophlebitis⁴ have been implicated in cases of isotopic response, but the most frequently associated primary disorder by far is cutaneous HZ.

Several benign and malignant disorders may occur at sites of resolved HZ lesions, including granulomatous dermatitis,⁶ granuloma annulare,⁷ fungal granuloma,⁸ fungal folliculitis,⁹ psoriasis,¹⁰ morphea,¹¹ lichen sclerosus,¹² Kaposi sarcoma,¹³ the lichenoid variant of chronic graft-versus-host disease,¹⁴ cutaneous sarcoidosis,¹⁵ granulomatous folliculitis,¹⁶ comedones,¹⁷ furuncles,¹⁸ erythema annulare centrifugum,¹⁹ eosinophilic dermatosis,²⁰ cutaneous pseudolymphoma,²¹ granulomatous vasculitis,²² Rosai-Dorfman disease,¹² xanthomatous changes,²³ tuberculoid granulomas,²⁴ acneform eruption,²⁵ lichen planus,²⁶ acquired reactive perforating collagenosis,²⁷ lymphoma,²⁸ leukemia,²⁹ angiosarcoma,³⁰ basal cell carcinoma,³¹ squamous cell carcinoma, and cutaneous metastasis from internal carcinoma.³² The interval between the acute HZ episode and presentation of the second disease is quite variable, ranging from days to several months. Postzoster isotopic response has been described in individuals with varying degrees of immune response, affecting both immunocompetent¹² and immunocompromised patients.¹⁴ There is no predilection for age, sex, or race. It also seems that antiviral treatment during the active episode does not prevent the development of secondary reactions.Kim et al³³ reported a 59-year-old woman who developed flesh-colored or erythematous papules on HZ scars over the area of the left T1 and T2 dermatomes 1 week after the active viral process. Histopathologic study demonstrated deposition of mucin between collagen bundles in the dermis. The authors established the diagnosis of secondary cutaneous mucinosis as an isotopic response.³³ Nevertheless, we believe that based on the aforementioned classification of cutaneous mucinosis,² both this case and our case are better considered as primary cutaneous dermal mucinosis, as the mucin deposition in the dermis was the main histologic finding resulting in a distinctive cutaneous disorder. In the case reported by Kim et al,³³ a possible relationship between cutaneous mucinosis and postherpetic neuralgia was suggested based on the slow regression of skin lesions in accordance with the improvement of the neuralgic pain; however, our patient did not have postherpetic neuralgia and the lesions persisted unchanged several months after the acute HZ episode. In the literature, there are reports of primary cutaneous dermal mucinosis associated with altered thyroid function³⁴; autoimmune connective tissue diseases, mostly lupus erythematosus³⁵; monoclonal gammopathy³⁶; and human immunodeficiency virus infection,³⁷ but these possibilities were ruled out in our patient by pertinent laboratory studies.

The pathogenesis of the postherpetic isotopic response remains unknown, but several mechanisms have been proposed. Some authors have suggested that postzoster dermatoses may represent isomorphic response of Köbner phenomenon.^13,15 Although isomorphic and isotopic responses share some similarities, these terms describe 2 different phenomena: the first refers to the appearance of the same cutaneous disorder at a different site favored by trauma, while the second manifests a new and unrelated disease at the same location.³⁸ Local anatomic changes such as altered microcirculation, collagen rearrangement, and an imperfect skin barrier may promote a prolonged local inflammatory response. Moreover, the destruction of nerve fibers by the varicella-zoster virus may indirectly influence the local immune system through the release of specific neuropeptides in the skin.³⁹ It has been speculated that some secondary reactions may be the result of type III and type IV hypersensitivity reactions⁴⁰ to viral antigens or to tissue antigens modified by the virus, inducing either immune hypersensitivity or local immune suppression.⁴¹ Some authors have documented the presence of varicella-zoster DNA within early postzoster lesions^6,7 by using polymerase chain reaction in early lesions but not in late-stage and residual lesions.^12,22 Nikkels et al⁴² studied early granulomatous lesions by immunohistochemistry and in situ hybridization techniques and concluded that major viral envelope glycoproteins (glycoproteins I and II) rather than complete viral particles could be responsible for delayed-type hypersensitivity reactions. All these findings suggest that secondary reactions presenting on HZ scars are mainly the result of atypical immune reactions to local antigenic stimuli.

The pathogenesis of our case is unknown. From a theoretical point of view, it is possible that varicella-zoster virus may induce fibroblastic proliferation and mucin production on HZ scars; however, if HZ is a frequent process and the virus may induce mucin production, then focal dermal mucinosis in an HZ scar should be a common finding. In our patient, there was no associated disease favoring the development of the cutaneous mucinosis. These localized variants of primary cutaneous mucinosis usually do not require therapy, and a wait-and-see approach is recommended. Topical applications of corticosteroids, pimecrolimus, or tacrolimus, as well as oral isotretinoin, may have some benefit,⁴³ but spontaneous resolution may occur.⁴⁴ In our patient, topical corticosteroids were applied 2 months following initial presentation without any benefit and the cutaneous lesions gradually improved without any therapy during the subsequent 6 months. Focal dermal mucinosis should be added to the list of cutaneous reactions that may develop in HZ scars.

Olanzapine is more effective than placebo, in combination with a 5-HT3-receptor antagonist and an NK1-receptor antagonist, in preventing nausea in patients undergoing chemotherapy, according to investigators.

“This large, randomized, double-blind, placebo-controlled, phase III trial showed that it is more effective to combine olanzapine than placebo with an NK1-receptor antagonist, a 5-HT3–receptor antagonist, and dexamethasone for the prevention of nausea and vomiting in patients who have not received previous chemotherapy but are currently receiving highly emetogenic chemotherapy,” reported Rudolph Navari, MD, PhD, of the World Health Organization, Geneva, and his associates (N Engl J Med. 2016;375:134-42).

©monkeybusinessimages/ thinkstockphotos.com

Patients were randomized to receive olanzapine or the placebo, along with a 5-HT3-receptor antagonist (either palonosetron intravenously, granisetron intravenously or orally, or ondansetron intravenously or orally) and an NK1-receptor antagonist (fosaprepitant intravenously or aprepitant orally). The olanzapine (n = 192) and placebo (n = 188) groups were balanced with respect to age, race, sex, and chemotherapy administered.

Patients kept daily records of nausea and episodes of vomiting. The proportion of patients who reported no nausea or who experienced no clinically significant nausea was significantly greater in the olanzapine group than in the placebo group (37% vs. 22%, P = .002 and 67% vs. 49%, P = .001).

Patients receiving olanzapine had significantly increased sedation (severe in 5%) on day 2 compared with baseline, Dr. Navari and his associates reported. The sedation resolved on days 3, 4, and 5 even though patients continued to receive the drug on days 3 and 4. No patients discontinued the study because of sedation.

The National Cancer Institute funded the study. One investigator reported receiving financial support from Merck and Co. The other investigators reported having no disclosures.

[email protected]

On Twitter @jessnicolecraig

Olanzapine is more effective than placebo, in combination with a 5-HT3-receptor antagonist and an NK1-receptor antagonist, in preventing nausea in patients undergoing chemotherapy, according to investigators.

“This large, randomized, double-blind, placebo-controlled, phase III trial showed that it is more effective to combine olanzapine than placebo with an NK1-receptor antagonist, a 5-HT3–receptor antagonist, and dexamethasone for the prevention of nausea and vomiting in patients who have not received previous chemotherapy but are currently receiving highly emetogenic chemotherapy,” reported Rudolph Navari, MD, PhD, of the World Health Organization, Geneva, and his associates (N Engl J Med. 2016;375:134-42).

©monkeybusinessimages/ thinkstockphotos.com

Patients were randomized to receive olanzapine or the placebo, along with a 5-HT3-receptor antagonist (either palonosetron intravenously, granisetron intravenously or orally, or ondansetron intravenously or orally) and an NK1-receptor antagonist (fosaprepitant intravenously or aprepitant orally). The olanzapine (n = 192) and placebo (n = 188) groups were balanced with respect to age, race, sex, and chemotherapy administered.

Patients kept daily records of nausea and episodes of vomiting. The proportion of patients who reported no nausea or who experienced no clinically significant nausea was significantly greater in the olanzapine group than in the placebo group (37% vs. 22%, P = .002 and 67% vs. 49%, P = .001).

Patients receiving olanzapine had significantly increased sedation (severe in 5%) on day 2 compared with baseline, Dr. Navari and his associates reported. The sedation resolved on days 3, 4, and 5 even though patients continued to receive the drug on days 3 and 4. No patients discontinued the study because of sedation.

The National Cancer Institute funded the study. One investigator reported receiving financial support from Merck and Co. The other investigators reported having no disclosures.

[email protected]

On Twitter @jessnicolecraig

Olanzapine is more effective than placebo, in combination with a 5-HT3-receptor antagonist and an NK1-receptor antagonist, in preventing nausea in patients undergoing chemotherapy, according to investigators.

“This large, randomized, double-blind, placebo-controlled, phase III trial showed that it is more effective to combine olanzapine than placebo with an NK1-receptor antagonist, a 5-HT3–receptor antagonist, and dexamethasone for the prevention of nausea and vomiting in patients who have not received previous chemotherapy but are currently receiving highly emetogenic chemotherapy,” reported Rudolph Navari, MD, PhD, of the World Health Organization, Geneva, and his associates (N Engl J Med. 2016;375:134-42).

©monkeybusinessimages/ thinkstockphotos.com

Patients were randomized to receive olanzapine or the placebo, along with a 5-HT3-receptor antagonist (either palonosetron intravenously, granisetron intravenously or orally, or ondansetron intravenously or orally) and an NK1-receptor antagonist (fosaprepitant intravenously or aprepitant orally). The olanzapine (n = 192) and placebo (n = 188) groups were balanced with respect to age, race, sex, and chemotherapy administered.

Patients kept daily records of nausea and episodes of vomiting. The proportion of patients who reported no nausea or who experienced no clinically significant nausea was significantly greater in the olanzapine group than in the placebo group (37% vs. 22%, P = .002 and 67% vs. 49%, P = .001).

Patients receiving olanzapine had significantly increased sedation (severe in 5%) on day 2 compared with baseline, Dr. Navari and his associates reported. The sedation resolved on days 3, 4, and 5 even though patients continued to receive the drug on days 3 and 4. No patients discontinued the study because of sedation.

The National Cancer Institute funded the study. One investigator reported receiving financial support from Merck and Co. The other investigators reported having no disclosures.

[email protected]

On Twitter @jessnicolecraig

Early data hint that immune checkpoint inhibitors may be able to restore antitumor activity in patients with hematologic malignancies that have relapsed after allogeneic transplant.

Among 22 patients with relapsed hematologic cancers following allogeneic hematopoietic stem cell transplantation (HSCT) in a phase I/Ib study, treatment with the anti-CTLA-4 antibody ipilimumab (Yervoy) at a dose of 10 mg/kg was associated with complete responses in five patients, partial responses in two, and decreased tumor burden in six, reported Matthew S. Davids, MD, of the Dana-Farber Cancer Institute in Boston, and his colleagues.

“CTLA-4 blockade was a feasible approach for the treatment of patients with relapsed hematologic cancer after transplantation. Complete remissions with some durability were observed, even in patients with refractory myeloid cancers,” they wrote (N Engl J Med. 2016 Jul 14. doi: 10.1056/NEJMoa1601202).

More than one-third of patients who undergo HSCT for hematologic malignancies such as lymphoma, multiple myeloma, or leukemia will experience a relapse, and most will die within a year of relapse despite salvage therapies or retransplantation, the authors noted.

“Immune escape (i.e., tumor evasion of the donor immune system) contributes to relapse after allogeneic HSCT, and immune checkpoint inhibitory pathways probably play an important role,” they wrote.

Selective CTLA-4 blockade has been shown in mouse models to treat late relapse after transplantation by augmenting graft-versus-tumor response without apparent exacerbation of graft-versus-host disease (GVHD). To see whether the use of a CTLA-4 inhibitor could have the same effect in humans, the investigators instituted a single-group, open-label, dose-finding, safety and efficacy study of ipilimumab in 28 patients from six treatment sites.

The patients had all undergone allogeneic HSCT more than 3 months before the start of the study. The diagnoses included acute myeloid leukemia (AML) in 12 patients (including 3 with leukemia cutis and 1 with a myeloid sarcoma), Hodgkin lymphoma in 7, non-Hodgkin lymphoma in 4, myelodysplastic syndrome (MDS) in 2, and multiple myeloma, myeloproliferative neoplasm, and acute lymphoblastic leukemia in 1 patient each. Eight of the patients had previously had either grade I or II acute GVHD; 16 had had chronic GVHD.

Patients received induction therapy with ipilimumab at a dose of either 3 mg/kg (6 patients), or 10 mg/kg (22 patients) every 3 weeks for a total of 4 doses. Patients who experienced a clinical benefit from the drug could receive additional doses every 12 weeks for up to 60 weeks.

There were no clinical responses meeting study criteria in any of the patients who received the 3-mg/kg dose. Among the 22 who received the 10-mg/kg dose, however, the rate of complete responses was 23% (5 of 22), partial responses 9% (2 of 22), and decreased tumor burden 27% (6 of 22). The remaining nine patients experienced disease progression.

Four of the complete responses occurred in patients with extramedullary AML, and one occurred in a patient with MDS transforming into AML.

The safety analysis, which included all 28 patients evaluable for adverse events, showed four discontinuations due to dose-limiting chronic GVHD of the liver in the 3 patients, and acute GVHD of the gut in 1, and to severe immune-related events in one additional patient, leading to the patient’s death.

Other grade 3 or greater adverse events possibly related to ipilimumab included acute kidney injury (one patient) , corneal ulcer (one), thrombocytopenia (nine), neutropenia (three), anemia and pleural effusion (two).

The investigators point out that therapy to stimulate a graft-versus-tumor effect has the potential to promote or exacerbate GVHD, as occurred in four patients in the study. The GVHD in these patients was effectively managed with glucocorticoids, however.

The National Institutes of Health, Leukemia and Lymphoma Society, Pasquarello Tissue Bank, and Dana-Farber Cancer Institute supported the study. Dr. Davids disclosed grants from ASCO, the Pasquarello Tissue Bank, NIH, NCI, and Leukemia and Lymphoma society, and personal fees from several companies outside the study. Several coauthors disclosed relationships with various pharmaceutical companies, including Bristol-Myers Squibb, maker of ipilimumab.

Early data hint that immune checkpoint inhibitors may be able to restore antitumor activity in patients with hematologic malignancies that have relapsed after allogeneic transplant.

Among 22 patients with relapsed hematologic cancers following allogeneic hematopoietic stem cell transplantation (HSCT) in a phase I/Ib study, treatment with the anti-CTLA-4 antibody ipilimumab (Yervoy) at a dose of 10 mg/kg was associated with complete responses in five patients, partial responses in two, and decreased tumor burden in six, reported Matthew S. Davids, MD, of the Dana-Farber Cancer Institute in Boston, and his colleagues.

“CTLA-4 blockade was a feasible approach for the treatment of patients with relapsed hematologic cancer after transplantation. Complete remissions with some durability were observed, even in patients with refractory myeloid cancers,” they wrote (N Engl J Med. 2016 Jul 14. doi: 10.1056/NEJMoa1601202).

More than one-third of patients who undergo HSCT for hematologic malignancies such as lymphoma, multiple myeloma, or leukemia will experience a relapse, and most will die within a year of relapse despite salvage therapies or retransplantation, the authors noted.

“Immune escape (i.e., tumor evasion of the donor immune system) contributes to relapse after allogeneic HSCT, and immune checkpoint inhibitory pathways probably play an important role,” they wrote.

Selective CTLA-4 blockade has been shown in mouse models to treat late relapse after transplantation by augmenting graft-versus-tumor response without apparent exacerbation of graft-versus-host disease (GVHD). To see whether the use of a CTLA-4 inhibitor could have the same effect in humans, the investigators instituted a single-group, open-label, dose-finding, safety and efficacy study of ipilimumab in 28 patients from six treatment sites.

The patients had all undergone allogeneic HSCT more than 3 months before the start of the study. The diagnoses included acute myeloid leukemia (AML) in 12 patients (including 3 with leukemia cutis and 1 with a myeloid sarcoma), Hodgkin lymphoma in 7, non-Hodgkin lymphoma in 4, myelodysplastic syndrome (MDS) in 2, and multiple myeloma, myeloproliferative neoplasm, and acute lymphoblastic leukemia in 1 patient each. Eight of the patients had previously had either grade I or II acute GVHD; 16 had had chronic GVHD.

Patients received induction therapy with ipilimumab at a dose of either 3 mg/kg (6 patients), or 10 mg/kg (22 patients) every 3 weeks for a total of 4 doses. Patients who experienced a clinical benefit from the drug could receive additional doses every 12 weeks for up to 60 weeks.

There were no clinical responses meeting study criteria in any of the patients who received the 3-mg/kg dose. Among the 22 who received the 10-mg/kg dose, however, the rate of complete responses was 23% (5 of 22), partial responses 9% (2 of 22), and decreased tumor burden 27% (6 of 22). The remaining nine patients experienced disease progression.

Four of the complete responses occurred in patients with extramedullary AML, and one occurred in a patient with MDS transforming into AML.

The safety analysis, which included all 28 patients evaluable for adverse events, showed four discontinuations due to dose-limiting chronic GVHD of the liver in the 3 patients, and acute GVHD of the gut in 1, and to severe immune-related events in one additional patient, leading to the patient’s death.

Other grade 3 or greater adverse events possibly related to ipilimumab included acute kidney injury (one patient) , corneal ulcer (one), thrombocytopenia (nine), neutropenia (three), anemia and pleural effusion (two).

The investigators point out that therapy to stimulate a graft-versus-tumor effect has the potential to promote or exacerbate GVHD, as occurred in four patients in the study. The GVHD in these patients was effectively managed with glucocorticoids, however.

The National Institutes of Health, Leukemia and Lymphoma Society, Pasquarello Tissue Bank, and Dana-Farber Cancer Institute supported the study. Dr. Davids disclosed grants from ASCO, the Pasquarello Tissue Bank, NIH, NCI, and Leukemia and Lymphoma society, and personal fees from several companies outside the study. Several coauthors disclosed relationships with various pharmaceutical companies, including Bristol-Myers Squibb, maker of ipilimumab.

Early data hint that immune checkpoint inhibitors may be able to restore antitumor activity in patients with hematologic malignancies that have relapsed after allogeneic transplant.

Among 22 patients with relapsed hematologic cancers following allogeneic hematopoietic stem cell transplantation (HSCT) in a phase I/Ib study, treatment with the anti-CTLA-4 antibody ipilimumab (Yervoy) at a dose of 10 mg/kg was associated with complete responses in five patients, partial responses in two, and decreased tumor burden in six, reported Matthew S. Davids, MD, of the Dana-Farber Cancer Institute in Boston, and his colleagues.

“CTLA-4 blockade was a feasible approach for the treatment of patients with relapsed hematologic cancer after transplantation. Complete remissions with some durability were observed, even in patients with refractory myeloid cancers,” they wrote (N Engl J Med. 2016 Jul 14. doi: 10.1056/NEJMoa1601202).

More than one-third of patients who undergo HSCT for hematologic malignancies such as lymphoma, multiple myeloma, or leukemia will experience a relapse, and most will die within a year of relapse despite salvage therapies or retransplantation, the authors noted.

“Immune escape (i.e., tumor evasion of the donor immune system) contributes to relapse after allogeneic HSCT, and immune checkpoint inhibitory pathways probably play an important role,” they wrote.

Selective CTLA-4 blockade has been shown in mouse models to treat late relapse after transplantation by augmenting graft-versus-tumor response without apparent exacerbation of graft-versus-host disease (GVHD). To see whether the use of a CTLA-4 inhibitor could have the same effect in humans, the investigators instituted a single-group, open-label, dose-finding, safety and efficacy study of ipilimumab in 28 patients from six treatment sites.

The patients had all undergone allogeneic HSCT more than 3 months before the start of the study. The diagnoses included acute myeloid leukemia (AML) in 12 patients (including 3 with leukemia cutis and 1 with a myeloid sarcoma), Hodgkin lymphoma in 7, non-Hodgkin lymphoma in 4, myelodysplastic syndrome (MDS) in 2, and multiple myeloma, myeloproliferative neoplasm, and acute lymphoblastic leukemia in 1 patient each. Eight of the patients had previously had either grade I or II acute GVHD; 16 had had chronic GVHD.

Patients received induction therapy with ipilimumab at a dose of either 3 mg/kg (6 patients), or 10 mg/kg (22 patients) every 3 weeks for a total of 4 doses. Patients who experienced a clinical benefit from the drug could receive additional doses every 12 weeks for up to 60 weeks.

There were no clinical responses meeting study criteria in any of the patients who received the 3-mg/kg dose. Among the 22 who received the 10-mg/kg dose, however, the rate of complete responses was 23% (5 of 22), partial responses 9% (2 of 22), and decreased tumor burden 27% (6 of 22). The remaining nine patients experienced disease progression.

Four of the complete responses occurred in patients with extramedullary AML, and one occurred in a patient with MDS transforming into AML.

The safety analysis, which included all 28 patients evaluable for adverse events, showed four discontinuations due to dose-limiting chronic GVHD of the liver in the 3 patients, and acute GVHD of the gut in 1, and to severe immune-related events in one additional patient, leading to the patient’s death.

Other grade 3 or greater adverse events possibly related to ipilimumab included acute kidney injury (one patient) , corneal ulcer (one), thrombocytopenia (nine), neutropenia (three), anemia and pleural effusion (two).

The investigators point out that therapy to stimulate a graft-versus-tumor effect has the potential to promote or exacerbate GVHD, as occurred in four patients in the study. The GVHD in these patients was effectively managed with glucocorticoids, however.

The National Institutes of Health, Leukemia and Lymphoma Society, Pasquarello Tissue Bank, and Dana-Farber Cancer Institute supported the study. Dr. Davids disclosed grants from ASCO, the Pasquarello Tissue Bank, NIH, NCI, and Leukemia and Lymphoma society, and personal fees from several companies outside the study. Several coauthors disclosed relationships with various pharmaceutical companies, including Bristol-Myers Squibb, maker of ipilimumab.

Implementation of some MACRA provisions could be delayed, CMS Acting Administrator Andy Slavitt told committee members at a July 13 hearing of the Senate Finance Committee.

Officials at the Centers for Medicare & Medicaid Services are considering “alternative start dates, looking at whether shorter periods could be used, and finding other ways for physicians to get experience with the program before the impact of it really hits them,” Mr. Slavitt testified.

Many of the comments that were submitted by physicians and other stakeholders on the proposed MACRA rule called for delayed implementation, Mr. Slavitt said. Other key themes included ensuring that patients are the focus, simplifying the rules, creating more pathways to advanced payment models, and providing a greater consideration of the needs of small and solo practices, particularly rural ones.

“We need to launch this program so that it begins on the right foot. That means that every physician in the country needs to feel like they are set up for success,” Mr. Slavitt said. He added that CMS may release an interim final rule to allow for more comment on changes stemming from the feedback received on the initial proposal.

Many Senators on the committee asked Mr. Slavitt how the proposed regulations would impact solo and small practices, especially ones in rural areas.

“The focus on small independent practices and their ability to continue to practice independently is a very high priority for us,” Mr. Slavitt said. “I would add that it’s not just small practices, it’s all also any physician that practices in a rural location. They have a very different set of dynamics than other physicians do. ... We need every physician set up for success and the challenges in small practices are far greater.”

He noted that for many small or solo practices, even a small amount of additional paperwork could affect how much time the physician can spend with patients.

Another area of concern in the MACRA regulation comments was the delay in the development of virtual groups that would allow physicians to virtually pool reporting requirements to allow for greater participation in value-based programs. The proposed MACRA rule calls for these groups to be delayed for 1 year .

“I think this going to be a high priority for us, and I think it’s going to be something that is going to need a lot more input from physicians to make sure we get it right,” Mr. Slavitt said. Virtual groups are “a whole new way of reporting, and we need to make a number of decisions, and physicians would need to make a number of decisions and they are not yet used to practicing that way.”

He added that CMS is asking physicians how they want to go about it, and the feedback so far is promising that physicians want to participate, but there needs to be operational and technology infrastructure to make it happen.

“I don’t think this is something that can’t be solved with just a little bit more time, but it’s certainly not something that’s ready to be launched in months,” he said, adding that the agency aims to launch virtual group reporting in the second year of the MACRA implementation.

[email protected]

Implementation of some MACRA provisions could be delayed, CMS Acting Administrator Andy Slavitt told committee members at a July 13 hearing of the Senate Finance Committee.

Officials at the Centers for Medicare & Medicaid Services are considering “alternative start dates, looking at whether shorter periods could be used, and finding other ways for physicians to get experience with the program before the impact of it really hits them,” Mr. Slavitt testified.

Many of the comments that were submitted by physicians and other stakeholders on the proposed MACRA rule called for delayed implementation, Mr. Slavitt said. Other key themes included ensuring that patients are the focus, simplifying the rules, creating more pathways to advanced payment models, and providing a greater consideration of the needs of small and solo practices, particularly rural ones.

“We need to launch this program so that it begins on the right foot. That means that every physician in the country needs to feel like they are set up for success,” Mr. Slavitt said. He added that CMS may release an interim final rule to allow for more comment on changes stemming from the feedback received on the initial proposal.

Many Senators on the committee asked Mr. Slavitt how the proposed regulations would impact solo and small practices, especially ones in rural areas.

“The focus on small independent practices and their ability to continue to practice independently is a very high priority for us,” Mr. Slavitt said. “I would add that it’s not just small practices, it’s all also any physician that practices in a rural location. They have a very different set of dynamics than other physicians do. ... We need every physician set up for success and the challenges in small practices are far greater.”

He noted that for many small or solo practices, even a small amount of additional paperwork could affect how much time the physician can spend with patients.

Another area of concern in the MACRA regulation comments was the delay in the development of virtual groups that would allow physicians to virtually pool reporting requirements to allow for greater participation in value-based programs. The proposed MACRA rule calls for these groups to be delayed for 1 year .

“I think this going to be a high priority for us, and I think it’s going to be something that is going to need a lot more input from physicians to make sure we get it right,” Mr. Slavitt said. Virtual groups are “a whole new way of reporting, and we need to make a number of decisions, and physicians would need to make a number of decisions and they are not yet used to practicing that way.”

He added that CMS is asking physicians how they want to go about it, and the feedback so far is promising that physicians want to participate, but there needs to be operational and technology infrastructure to make it happen.

“I don’t think this is something that can’t be solved with just a little bit more time, but it’s certainly not something that’s ready to be launched in months,” he said, adding that the agency aims to launch virtual group reporting in the second year of the MACRA implementation.

[email protected]

Implementation of some MACRA provisions could be delayed, CMS Acting Administrator Andy Slavitt told committee members at a July 13 hearing of the Senate Finance Committee.

Officials at the Centers for Medicare & Medicaid Services are considering “alternative start dates, looking at whether shorter periods could be used, and finding other ways for physicians to get experience with the program before the impact of it really hits them,” Mr. Slavitt testified.

Many of the comments that were submitted by physicians and other stakeholders on the proposed MACRA rule called for delayed implementation, Mr. Slavitt said. Other key themes included ensuring that patients are the focus, simplifying the rules, creating more pathways to advanced payment models, and providing a greater consideration of the needs of small and solo practices, particularly rural ones.

“We need to launch this program so that it begins on the right foot. That means that every physician in the country needs to feel like they are set up for success,” Mr. Slavitt said. He added that CMS may release an interim final rule to allow for more comment on changes stemming from the feedback received on the initial proposal.

Many Senators on the committee asked Mr. Slavitt how the proposed regulations would impact solo and small practices, especially ones in rural areas.

“The focus on small independent practices and their ability to continue to practice independently is a very high priority for us,” Mr. Slavitt said. “I would add that it’s not just small practices, it’s all also any physician that practices in a rural location. They have a very different set of dynamics than other physicians do. ... We need every physician set up for success and the challenges in small practices are far greater.”

He noted that for many small or solo practices, even a small amount of additional paperwork could affect how much time the physician can spend with patients.

Another area of concern in the MACRA regulation comments was the delay in the development of virtual groups that would allow physicians to virtually pool reporting requirements to allow for greater participation in value-based programs. The proposed MACRA rule calls for these groups to be delayed for 1 year .

“I think this going to be a high priority for us, and I think it’s going to be something that is going to need a lot more input from physicians to make sure we get it right,” Mr. Slavitt said. Virtual groups are “a whole new way of reporting, and we need to make a number of decisions, and physicians would need to make a number of decisions and they are not yet used to practicing that way.”

He added that CMS is asking physicians how they want to go about it, and the feedback so far is promising that physicians want to participate, but there needs to be operational and technology infrastructure to make it happen.

“I don’t think this is something that can’t be solved with just a little bit more time, but it’s certainly not something that’s ready to be launched in months,” he said, adding that the agency aims to launch virtual group reporting in the second year of the MACRA implementation.

[email protected]

NEW YORK – Aortic aneurysm ranks as one of the top 20 causes of death in the United States. Most of these aneurysms are clinically silent until they rupture, but Yale cardiovascular surgeon John A. Elefteriades, MD, has developed a clinical paradigm that identifies eight markers that physicians can use to detect the disease before it strikes.

Dr. Elefteriades calls his paradigm “Guilt by Association.” It is based on an article he published online last year in the journal Open Heart (2015;2:e000169).

“What we need is for our colleagues in affiliated disciplines to recognize the importance of these offenders in indicating the presence of thoracic aortic aneurysm,” he said, reporting on the paradigm at the meeting sponsored by the American Association for Thoracic Surgery. He noted that studies from Japan of people who had died from out-of-hospital cardiac arrest found that 8% of them had a type A aortic dissection (Am J Cardiol 2016;117:1826-30).

He outlined eight “associates” of thoracic aortic aneurysm (TAA): intracranial aneurysm; bovine aortic arch; abdominal aortic aneurysm; simple renal cysts; bicuspid aortic valve; family history; positive thumb-palm test; and temporal arteritis and other autoimmune disorders.

A patient with TAA has a 10% likelihood of harboring an intracranial aneurysm (Am J Cardiol 2010;105:417-20). “It’s even more common in the descending, compared to the ascending group in examples that we’ve identified,” Dr. Elefteriades said. Particularly vulnerable are patients over age 70 and those with an intracranial aneurysm larger than 4 mm: the former has a 9% chance of harboring a TAA, the latter a 6% chance, he said.

The bovine arch had been thought to be benign, but, Dr. Elefteriades said, “We don’t think it is.”

Bovine arch refers to a group of congenital aortic arch vessels with an aberrant origin of the left common carotid artery. “We recently looked at this as a marker for thoracic aortic disease, and please note that 20% of our TAA patients have a bovine arch,” he said. “This is much higher than in the general population.”

Abdominal aortic aneurysm has long been associated with TAA, he said. “When these aneurysms are identified by ultrasound, it’s important that the thoracic aorta be checked as well,” he said.

“This is a message for internists and our vascular colleagues.”

Simple renal cysts have been found in patients with TAA at a “much higher” rate than the general population, as high as 57% of those with descending aortic aneurysms vs. 11%-13.7% of the general population, Dr. Elefteriades said (J. Am. Heart Assoc. 2016;5:e002248). Simple renal cysts are detected by abdominal CT scan. “It’s just a matter of a few more slices with the CT scan to get the entirety of the thoracic aorta evaluated,” he said.

Courtesy Dr. Elefteriades

“We encourage our radiology colleagues to do this when a renal cyst is detected.”

Bicuspid aortic valve mandates “support from our cardiac colleagues when they find one of these to let the patient know he has to be monitored lifelong for later development of this aneurysm,” Dr. Elefteriades said.

Family history of TAA has been known as a strong predictor, but genetic studies have provided clarity on the association (Arch Surg. 1999;134:361‐7). “If the proband has a thoracic aortic aneurysm, there’s 21% likelihood there’s a family member who is affected with an aneurysm somewhere in the body,” he said.

Location of aneurysms in family members is also important, Dr. Elefteriades said. “If the proband has a ascending aortic aneurysm, the kindred also have an ascending aortic aneurysm; but if the proband has a descending aneurysm, the likelihood is that the kindred will have an abdominal aortic aneurysm,” he said. “To identify silent disease, it’s very important we check siblings and children, and now, of course, we’re using whole-exome sequencing.” So far, Dr. Elefteriades has obtained whole-exome sequencing in 200 patients.

The thumb-palm test involves the patient touching the thumb to the palm; the thumb crossing the edge of the flat palm is an indicator of connective tissue disease. “It doesn’t cost anything,” Dr. Elefteriades said. “It is a very simple thing for internists to do to identify those connective tissue diseases.”

Temporal arteritis has become increasingly common in elderly women. “They have a markedly increased likelihood of having a thoracic aortic aneurysm – about 8% in some studies,’ Dr. Elefteriades said. “So we want our neurology colleagues to be aware of this and to look for thoracic aortic aneurysm.”

Dr. Elefteriades disclosed he has received consulting fees from Baxter, Covidien, Datascope, and CryoLife, and a research grant from Medtronic.

NEW YORK – Aortic aneurysm ranks as one of the top 20 causes of death in the United States. Most of these aneurysms are clinically silent until they rupture, but Yale cardiovascular surgeon John A. Elefteriades, MD, has developed a clinical paradigm that identifies eight markers that physicians can use to detect the disease before it strikes.

Dr. Elefteriades calls his paradigm “Guilt by Association.” It is based on an article he published online last year in the journal Open Heart (2015;2:e000169).

“What we need is for our colleagues in affiliated disciplines to recognize the importance of these offenders in indicating the presence of thoracic aortic aneurysm,” he said, reporting on the paradigm at the meeting sponsored by the American Association for Thoracic Surgery. He noted that studies from Japan of people who had died from out-of-hospital cardiac arrest found that 8% of them had a type A aortic dissection (Am J Cardiol 2016;117:1826-30).

He outlined eight “associates” of thoracic aortic aneurysm (TAA): intracranial aneurysm; bovine aortic arch; abdominal aortic aneurysm; simple renal cysts; bicuspid aortic valve; family history; positive thumb-palm test; and temporal arteritis and other autoimmune disorders.

A patient with TAA has a 10% likelihood of harboring an intracranial aneurysm (Am J Cardiol 2010;105:417-20). “It’s even more common in the descending, compared to the ascending group in examples that we’ve identified,” Dr. Elefteriades said. Particularly vulnerable are patients over age 70 and those with an intracranial aneurysm larger than 4 mm: the former has a 9% chance of harboring a TAA, the latter a 6% chance, he said.

The bovine arch had been thought to be benign, but, Dr. Elefteriades said, “We don’t think it is.”

Bovine arch refers to a group of congenital aortic arch vessels with an aberrant origin of the left common carotid artery. “We recently looked at this as a marker for thoracic aortic disease, and please note that 20% of our TAA patients have a bovine arch,” he said. “This is much higher than in the general population.”

Abdominal aortic aneurysm has long been associated with TAA, he said. “When these aneurysms are identified by ultrasound, it’s important that the thoracic aorta be checked as well,” he said.

“This is a message for internists and our vascular colleagues.”

Simple renal cysts have been found in patients with TAA at a “much higher” rate than the general population, as high as 57% of those with descending aortic aneurysms vs. 11%-13.7% of the general population, Dr. Elefteriades said (J. Am. Heart Assoc. 2016;5:e002248). Simple renal cysts are detected by abdominal CT scan. “It’s just a matter of a few more slices with the CT scan to get the entirety of the thoracic aorta evaluated,” he said.

Courtesy Dr. Elefteriades

“We encourage our radiology colleagues to do this when a renal cyst is detected.”

Bicuspid aortic valve mandates “support from our cardiac colleagues when they find one of these to let the patient know he has to be monitored lifelong for later development of this aneurysm,” Dr. Elefteriades said.

Family history of TAA has been known as a strong predictor, but genetic studies have provided clarity on the association (Arch Surg. 1999;134:361‐7). “If the proband has a thoracic aortic aneurysm, there’s 21% likelihood there’s a family member who is affected with an aneurysm somewhere in the body,” he said.

Location of aneurysms in family members is also important, Dr. Elefteriades said. “If the proband has a ascending aortic aneurysm, the kindred also have an ascending aortic aneurysm; but if the proband has a descending aneurysm, the likelihood is that the kindred will have an abdominal aortic aneurysm,” he said. “To identify silent disease, it’s very important we check siblings and children, and now, of course, we’re using whole-exome sequencing.” So far, Dr. Elefteriades has obtained whole-exome sequencing in 200 patients.

The thumb-palm test involves the patient touching the thumb to the palm; the thumb crossing the edge of the flat palm is an indicator of connective tissue disease. “It doesn’t cost anything,” Dr. Elefteriades said. “It is a very simple thing for internists to do to identify those connective tissue diseases.”

Temporal arteritis has become increasingly common in elderly women. “They have a markedly increased likelihood of having a thoracic aortic aneurysm – about 8% in some studies,’ Dr. Elefteriades said. “So we want our neurology colleagues to be aware of this and to look for thoracic aortic aneurysm.”

Dr. Elefteriades disclosed he has received consulting fees from Baxter, Covidien, Datascope, and CryoLife, and a research grant from Medtronic.

NEW YORK – Aortic aneurysm ranks as one of the top 20 causes of death in the United States. Most of these aneurysms are clinically silent until they rupture, but Yale cardiovascular surgeon John A. Elefteriades, MD, has developed a clinical paradigm that identifies eight markers that physicians can use to detect the disease before it strikes.

Dr. Elefteriades calls his paradigm “Guilt by Association.” It is based on an article he published online last year in the journal Open Heart (2015;2:e000169).

“What we need is for our colleagues in affiliated disciplines to recognize the importance of these offenders in indicating the presence of thoracic aortic aneurysm,” he said, reporting on the paradigm at the meeting sponsored by the American Association for Thoracic Surgery. He noted that studies from Japan of people who had died from out-of-hospital cardiac arrest found that 8% of them had a type A aortic dissection (Am J Cardiol 2016;117:1826-30).

He outlined eight “associates” of thoracic aortic aneurysm (TAA): intracranial aneurysm; bovine aortic arch; abdominal aortic aneurysm; simple renal cysts; bicuspid aortic valve; family history; positive thumb-palm test; and temporal arteritis and other autoimmune disorders.

A patient with TAA has a 10% likelihood of harboring an intracranial aneurysm (Am J Cardiol 2010;105:417-20). “It’s even more common in the descending, compared to the ascending group in examples that we’ve identified,” Dr. Elefteriades said. Particularly vulnerable are patients over age 70 and those with an intracranial aneurysm larger than 4 mm: the former has a 9% chance of harboring a TAA, the latter a 6% chance, he said.

The bovine arch had been thought to be benign, but, Dr. Elefteriades said, “We don’t think it is.”

Bovine arch refers to a group of congenital aortic arch vessels with an aberrant origin of the left common carotid artery. “We recently looked at this as a marker for thoracic aortic disease, and please note that 20% of our TAA patients have a bovine arch,” he said. “This is much higher than in the general population.”

Abdominal aortic aneurysm has long been associated with TAA, he said. “When these aneurysms are identified by ultrasound, it’s important that the thoracic aorta be checked as well,” he said.

“This is a message for internists and our vascular colleagues.”

Simple renal cysts have been found in patients with TAA at a “much higher” rate than the general population, as high as 57% of those with descending aortic aneurysms vs. 11%-13.7% of the general population, Dr. Elefteriades said (J. Am. Heart Assoc. 2016;5:e002248). Simple renal cysts are detected by abdominal CT scan. “It’s just a matter of a few more slices with the CT scan to get the entirety of the thoracic aorta evaluated,” he said.

Courtesy Dr. Elefteriades

“We encourage our radiology colleagues to do this when a renal cyst is detected.”

Bicuspid aortic valve mandates “support from our cardiac colleagues when they find one of these to let the patient know he has to be monitored lifelong for later development of this aneurysm,” Dr. Elefteriades said.

Family history of TAA has been known as a strong predictor, but genetic studies have provided clarity on the association (Arch Surg. 1999;134:361‐7). “If the proband has a thoracic aortic aneurysm, there’s 21% likelihood there’s a family member who is affected with an aneurysm somewhere in the body,” he said.

Location of aneurysms in family members is also important, Dr. Elefteriades said. “If the proband has a ascending aortic aneurysm, the kindred also have an ascending aortic aneurysm; but if the proband has a descending aneurysm, the likelihood is that the kindred will have an abdominal aortic aneurysm,” he said. “To identify silent disease, it’s very important we check siblings and children, and now, of course, we’re using whole-exome sequencing.” So far, Dr. Elefteriades has obtained whole-exome sequencing in 200 patients.

The thumb-palm test involves the patient touching the thumb to the palm; the thumb crossing the edge of the flat palm is an indicator of connective tissue disease. “It doesn’t cost anything,” Dr. Elefteriades said. “It is a very simple thing for internists to do to identify those connective tissue diseases.”

Temporal arteritis has become increasingly common in elderly women. “They have a markedly increased likelihood of having a thoracic aortic aneurysm – about 8% in some studies,’ Dr. Elefteriades said. “So we want our neurology colleagues to be aware of this and to look for thoracic aortic aneurysm.”

Dr. Elefteriades disclosed he has received consulting fees from Baxter, Covidien, Datascope, and CryoLife, and a research grant from Medtronic.

Despite achieving significant improvements in blood pressure and cholesterol levels, obese Americans continue to grow fatter, with worsening blood glucose and an increasing incidence of diabetes.

From 1998 to 2014, national health data showed that mean diastolic and systolic blood pressures decreased in obese men and women in all racial and ethnic groups. Mean lipid measurements improved as well, including a “marked” 21-mg/dL decrease in total cholesterol and a significant increase in HDL cholesterol.

But markers of blood glucose health continued to decline over the same period, contributing to an overall worsening of metabolic health and a increase from 11% to 19% in the rate of diabetes, Fangjian Guo, MD, and W. Timothy Garvey, MD, reported in July 13 issue of the Journal of the American Heart Association (J Am Heart Assoc. 2016 Jul 13. 5:e003619 doi: 10.1161/JAHA.116.003619).

The rate of obese adults free of these three cardiovascular disease risk factors – diabetes, elevated cholesterol, and blood pressure – remained stable over the study period at about 15%. But the rate of obese adults with all three risk factors increased by 37% over the same period. By 2014, 22% reported having all three of those risk factors.

“The deteriorated blood glucose health among obese adults in the United States calls for lifestyle interventions (diet and exercise) on a national scale,” wrote Dr. Garvey, chair of nutrition science at the University of Alabama, Birmingham. “Community-based public health intervention programs may help increase physical activity and diet quality to alleviate the problem.”

The investigators examined trends in cardiometabolic health among 18,626 obese adults who participated in National Health and Nutrition Examination Surveys from 1988 to 2014. Over this period, mean body mass index increased significantly, from 34.7 to 36 kg/m². Waist circumference increased as well, from 110 to 114.8 cm.

The picture was much better for blood pressure. Mean systolic pressures decreased about 2 points – from 126.1 to 124.4 mm Hg – in all age, racial and ethnic groups, and in both sexes. Mean diastolic blood pressure also decreased, dropping from 76.6 to 72.5 mm Hg. By 2014, 44% of the men and 51% of the women were below the blood pressure risk threshold.

Lipids also improved over the years, the investigators noted, with significant decreases in mean total cholesterol, from 214.5 to 193.7 mg/dL, and increases in HDL cholesterol, from 45.4 to 47.4 mg/dL.

Blood glucose worsened significantly, however. The mean hemoglobin A1c increased from 5.7% to 5.9%. The measurement rose in all ages, both sexes, and in all racial and ethnic groups except for non-Hispanic blacks.

Perhaps not surprisingly, the incidence of diabetes (a self-reported HbA_1c of 6.5% or more) increased from 11% to 19% from 1988 to 2014. The increase occurred in all age groups and both sexes except for young adults aged 20-39 years. No racial or ethnic group was exempt from the increase.

The number of people having all three risk factors (hypertension, hypercholesterolemia, and hyperglycemia) increased from 16% in 1988 to 22% in 2014.

“The increase occurred in parallel with a decline in the prevalence of healthy blood glucose, which is the predominant explanation accounting for the rise in the prevalence of presence of all three risk factors,” the investigators said.

Only 15% of the study population was free from all of these risk factors – a percentage that remained unchanged during 1988-2014.

The findings should be a wake-up call for physicians and their patients, and a national call for action to improve cardiovascular health among obese adults, the team wrote.

“The increasing trend of obese people with all three cardiovascular risk factors, commensurate with a decline in those with one or two risk factors, suggests an overall deterioration in health among people with obesity. ... These patterns of worsening metabolic health constitute an increase in risk of type 2 diabetes mellitus and underlie increasing prevalence rates for diabetes mellitus,” the investigators wrote.

Aggressive treatment will be necessary to reverse these trends. This might include treatment with weight-loss medications in conjunction with lifestyle interventions, which should be especially targeted at obese individuals who are already metabolically unhealthy and in those who have complications or are at risk for developing them.

“In the context of the current data, those obese adults who are metabolically unhealthy or perhaps those with suboptimal metabolic health represent patients who will benefit most from intensive obesity management … coordinated efforts aligning cardiovascular disease prevention and control activities across the public and private sectors in the United States are needed reduce the burden of cardiovascular disease among the obese population,” Dr. Garvey concluded.

The study was supported by the Department of Veterans Affairs, the National Institutes of Health, and the University of Alabama Diabetes Research Center.

Dr. Guo had no financial disclosures. Dr. Garvey disclosed relationships with multiple pharmaceutical companies.

Despite achieving significant improvements in blood pressure and cholesterol levels, obese Americans continue to grow fatter, with worsening blood glucose and an increasing incidence of diabetes.

From 1998 to 2014, national health data showed that mean diastolic and systolic blood pressures decreased in obese men and women in all racial and ethnic groups. Mean lipid measurements improved as well, including a “marked” 21-mg/dL decrease in total cholesterol and a significant increase in HDL cholesterol.

But markers of blood glucose health continued to decline over the same period, contributing to an overall worsening of metabolic health and a increase from 11% to 19% in the rate of diabetes, Fangjian Guo, MD, and W. Timothy Garvey, MD, reported in July 13 issue of the Journal of the American Heart Association (J Am Heart Assoc. 2016 Jul 13. 5:e003619 doi: 10.1161/JAHA.116.003619).

The rate of obese adults free of these three cardiovascular disease risk factors – diabetes, elevated cholesterol, and blood pressure – remained stable over the study period at about 15%. But the rate of obese adults with all three risk factors increased by 37% over the same period. By 2014, 22% reported having all three of those risk factors.

“The deteriorated blood glucose health among obese adults in the United States calls for lifestyle interventions (diet and exercise) on a national scale,” wrote Dr. Garvey, chair of nutrition science at the University of Alabama, Birmingham. “Community-based public health intervention programs may help increase physical activity and diet quality to alleviate the problem.”

The investigators examined trends in cardiometabolic health among 18,626 obese adults who participated in National Health and Nutrition Examination Surveys from 1988 to 2014. Over this period, mean body mass index increased significantly, from 34.7 to 36 kg/m². Waist circumference increased as well, from 110 to 114.8 cm.

The picture was much better for blood pressure. Mean systolic pressures decreased about 2 points – from 126.1 to 124.4 mm Hg – in all age, racial and ethnic groups, and in both sexes. Mean diastolic blood pressure also decreased, dropping from 76.6 to 72.5 mm Hg. By 2014, 44% of the men and 51% of the women were below the blood pressure risk threshold.

Lipids also improved over the years, the investigators noted, with significant decreases in mean total cholesterol, from 214.5 to 193.7 mg/dL, and increases in HDL cholesterol, from 45.4 to 47.4 mg/dL.

Blood glucose worsened significantly, however. The mean hemoglobin A1c increased from 5.7% to 5.9%. The measurement rose in all ages, both sexes, and in all racial and ethnic groups except for non-Hispanic blacks.

Perhaps not surprisingly, the incidence of diabetes (a self-reported HbA_1c of 6.5% or more) increased from 11% to 19% from 1988 to 2014. The increase occurred in all age groups and both sexes except for young adults aged 20-39 years. No racial or ethnic group was exempt from the increase.

The number of people having all three risk factors (hypertension, hypercholesterolemia, and hyperglycemia) increased from 16% in 1988 to 22% in 2014.

“The increase occurred in parallel with a decline in the prevalence of healthy blood glucose, which is the predominant explanation accounting for the rise in the prevalence of presence of all three risk factors,” the investigators said.

Only 15% of the study population was free from all of these risk factors – a percentage that remained unchanged during 1988-2014.

The findings should be a wake-up call for physicians and their patients, and a national call for action to improve cardiovascular health among obese adults, the team wrote.

“The increasing trend of obese people with all three cardiovascular risk factors, commensurate with a decline in those with one or two risk factors, suggests an overall deterioration in health among people with obesity. ... These patterns of worsening metabolic health constitute an increase in risk of type 2 diabetes mellitus and underlie increasing prevalence rates for diabetes mellitus,” the investigators wrote.

Aggressive treatment will be necessary to reverse these trends. This might include treatment with weight-loss medications in conjunction with lifestyle interventions, which should be especially targeted at obese individuals who are already metabolically unhealthy and in those who have complications or are at risk for developing them.

“In the context of the current data, those obese adults who are metabolically unhealthy or perhaps those with suboptimal metabolic health represent patients who will benefit most from intensive obesity management … coordinated efforts aligning cardiovascular disease prevention and control activities across the public and private sectors in the United States are needed reduce the burden of cardiovascular disease among the obese population,” Dr. Garvey concluded.

The study was supported by the Department of Veterans Affairs, the National Institutes of Health, and the University of Alabama Diabetes Research Center.

Dr. Guo had no financial disclosures. Dr. Garvey disclosed relationships with multiple pharmaceutical companies.

Despite achieving significant improvements in blood pressure and cholesterol levels, obese Americans continue to grow fatter, with worsening blood glucose and an increasing incidence of diabetes.

From 1998 to 2014, national health data showed that mean diastolic and systolic blood pressures decreased in obese men and women in all racial and ethnic groups. Mean lipid measurements improved as well, including a “marked” 21-mg/dL decrease in total cholesterol and a significant increase in HDL cholesterol.

But markers of blood glucose health continued to decline over the same period, contributing to an overall worsening of metabolic health and a increase from 11% to 19% in the rate of diabetes, Fangjian Guo, MD, and W. Timothy Garvey, MD, reported in July 13 issue of the Journal of the American Heart Association (J Am Heart Assoc. 2016 Jul 13. 5:e003619 doi: 10.1161/JAHA.116.003619).

The rate of obese adults free of these three cardiovascular disease risk factors – diabetes, elevated cholesterol, and blood pressure – remained stable over the study period at about 15%. But the rate of obese adults with all three risk factors increased by 37% over the same period. By 2014, 22% reported having all three of those risk factors.

“The deteriorated blood glucose health among obese adults in the United States calls for lifestyle interventions (diet and exercise) on a national scale,” wrote Dr. Garvey, chair of nutrition science at the University of Alabama, Birmingham. “Community-based public health intervention programs may help increase physical activity and diet quality to alleviate the problem.”

The investigators examined trends in cardiometabolic health among 18,626 obese adults who participated in National Health and Nutrition Examination Surveys from 1988 to 2014. Over this period, mean body mass index increased significantly, from 34.7 to 36 kg/m². Waist circumference increased as well, from 110 to 114.8 cm.

The picture was much better for blood pressure. Mean systolic pressures decreased about 2 points – from 126.1 to 124.4 mm Hg – in all age, racial and ethnic groups, and in both sexes. Mean diastolic blood pressure also decreased, dropping from 76.6 to 72.5 mm Hg. By 2014, 44% of the men and 51% of the women were below the blood pressure risk threshold.

Lipids also improved over the years, the investigators noted, with significant decreases in mean total cholesterol, from 214.5 to 193.7 mg/dL, and increases in HDL cholesterol, from 45.4 to 47.4 mg/dL.

Blood glucose worsened significantly, however. The mean hemoglobin A1c increased from 5.7% to 5.9%. The measurement rose in all ages, both sexes, and in all racial and ethnic groups except for non-Hispanic blacks.

Perhaps not surprisingly, the incidence of diabetes (a self-reported HbA_1c of 6.5% or more) increased from 11% to 19% from 1988 to 2014. The increase occurred in all age groups and both sexes except for young adults aged 20-39 years. No racial or ethnic group was exempt from the increase.

The number of people having all three risk factors (hypertension, hypercholesterolemia, and hyperglycemia) increased from 16% in 1988 to 22% in 2014.

“The increase occurred in parallel with a decline in the prevalence of healthy blood glucose, which is the predominant explanation accounting for the rise in the prevalence of presence of all three risk factors,” the investigators said.

Only 15% of the study population was free from all of these risk factors – a percentage that remained unchanged during 1988-2014.

The findings should be a wake-up call for physicians and their patients, and a national call for action to improve cardiovascular health among obese adults, the team wrote.

“The increasing trend of obese people with all three cardiovascular risk factors, commensurate with a decline in those with one or two risk factors, suggests an overall deterioration in health among people with obesity. ... These patterns of worsening metabolic health constitute an increase in risk of type 2 diabetes mellitus and underlie increasing prevalence rates for diabetes mellitus,” the investigators wrote.

Aggressive treatment will be necessary to reverse these trends. This might include treatment with weight-loss medications in conjunction with lifestyle interventions, which should be especially targeted at obese individuals who are already metabolically unhealthy and in those who have complications or are at risk for developing them.

“In the context of the current data, those obese adults who are metabolically unhealthy or perhaps those with suboptimal metabolic health represent patients who will benefit most from intensive obesity management … coordinated efforts aligning cardiovascular disease prevention and control activities across the public and private sectors in the United States are needed reduce the burden of cardiovascular disease among the obese population,” Dr. Garvey concluded.

The study was supported by the Department of Veterans Affairs, the National Institutes of Health, and the University of Alabama Diabetes Research Center.

Dr. Guo had no financial disclosures. Dr. Garvey disclosed relationships with multiple pharmaceutical companies.

Despite achieving significant improvements in blood pressure and cholesterol levels, obese Americans continue to grow fatter, with worsening blood glucose and an increasing incidence of diabetes.

From 1998 to 2014, national health data showed that mean diastolic and systolic blood pressures decreased in obese men and women in all racial and ethnic groups. Mean lipid measurements improved as well, including a “marked” 21-mg/dL decrease in total cholesterol and a significant increase in HDL cholesterol.

But markers of blood glucose health continued to decline over the same period, contributing to an overall worsening of metabolic health and a increase from 11% to 19% in the rate of diabetes, Fangjian Guo, MD, and W. Timothy Garvey, MD, reported in July 13 issue of the Journal of the American Heart Association (J Am Heart Assoc. 2016 Jul 13. 5:e003619 doi: 10.1161/JAHA.116.003619).

The rate of obese adults free of these three cardiovascular disease risk factors – diabetes, elevated cholesterol, and blood pressure – remained stable over the study period at about 15%. But the rate of obese adults with all three risk factors increased by 37% over the same period. By 2014, 22% reported having all three of those risk factors.

“The deteriorated blood glucose health among obese adults in the United States calls for lifestyle interventions (diet and exercise) on a national scale,” wrote Dr. Garvey, chair of nutrition science at the University of Alabama, Birmingham. “Community-based public health intervention programs may help increase physical activity and diet quality to alleviate the problem.”

The investigators examined trends in cardiometabolic health among 18,626 obese adults who participated in National Health and Nutrition Examination Surveys from 1988 to 2014. Over this period, mean body mass index increased significantly, from 34.7 to 36 kg/m². Waist circumference increased as well, from 110 to 114.8 cm.

The picture was much better for blood pressure. Mean systolic pressures decreased about 2 points – from 126.1 to 124.4 mm Hg – in all age, racial and ethnic groups, and in both sexes. Mean diastolic blood pressure also decreased, dropping from 76.6 to 72.5 mm Hg. By 2014, 44% of the men and 51% of the women were below the blood pressure risk threshold.

Lipids also improved over the years, the investigators noted, with significant decreases in mean total cholesterol, from 214.5 to 193.7 mg/dL, and increases in HDL cholesterol, from 45.4 to 47.4 mg/dL.

Blood glucose worsened significantly, however. The mean hemoglobin A1c increased from 5.7% to 5.9%. The measurement rose in all ages, both sexes, and in all racial and ethnic groups except for non-Hispanic blacks.

Perhaps not surprisingly, the incidence of diabetes (a self-reported HbA_1c of 6.5% or more) increased from 11% to 19% from 1988 to 2014. The increase occurred in all age groups and both sexes except for young adults aged 20-39 years. No racial or ethnic group was exempt from the increase.

The number of people having all three risk factors (hypertension, hypercholesterolemia, and hyperglycemia) increased from 16% in 1988 to 22% in 2014.

“The increase occurred in parallel with a decline in the prevalence of healthy blood glucose, which is the predominant explanation accounting for the rise in the prevalence of presence of all three risk factors,” the investigators said.

Only 15% of the study population was free from all of these risk factors – a percentage that remained unchanged during 1988-2014.

The findings should be a wake-up call for physicians and their patients, and a national call for action to improve cardiovascular health among obese adults, the team wrote.

“The increasing trend of obese people with all three cardiovascular risk factors, commensurate with a decline in those with one or two risk factors, suggests an overall deterioration in health among people with obesity. ... These patterns of worsening metabolic health constitute an increase in risk of type 2 diabetes mellitus and underlie increasing prevalence rates for diabetes mellitus,” the investigators wrote.

Aggressive treatment will be necessary to reverse these trends. This might include treatment with weight-loss medications in conjunction with lifestyle interventions, which should be especially targeted at obese individuals who are already metabolically unhealthy and in those who have complications or are at risk for developing them.

“In the context of the current data, those obese adults who are metabolically unhealthy or perhaps those with suboptimal metabolic health represent patients who will benefit most from intensive obesity management … coordinated efforts aligning cardiovascular disease prevention and control activities across the public and private sectors in the United States are needed reduce the burden of cardiovascular disease among the obese population,” Dr. Garvey concluded.

The study was supported by the Department of Veterans Affairs, the National Institutes of Health, and the University of Alabama Diabetes Research Center.

Dr. Guo had no financial disclosures. Dr. Garvey disclosed relationships with multiple pharmaceutical companies.

[email protected]

Despite achieving significant improvements in blood pressure and cholesterol levels, obese Americans continue to grow fatter, with worsening blood glucose and an increasing incidence of diabetes.

From 1998 to 2014, national health data showed that mean diastolic and systolic blood pressures decreased in obese men and women in all racial and ethnic groups. Mean lipid measurements improved as well, including a “marked” 21-mg/dL decrease in total cholesterol and a significant increase in HDL cholesterol.

But markers of blood glucose health continued to decline over the same period, contributing to an overall worsening of metabolic health and a increase from 11% to 19% in the rate of diabetes, Fangjian Guo, MD, and W. Timothy Garvey, MD, reported in July 13 issue of the Journal of the American Heart Association (J Am Heart Assoc. 2016 Jul 13. 5:e003619 doi: 10.1161/JAHA.116.003619).

The rate of obese adults free of these three cardiovascular disease risk factors – diabetes, elevated cholesterol, and blood pressure – remained stable over the study period at about 15%. But the rate of obese adults with all three risk factors increased by 37% over the same period. By 2014, 22% reported having all three of those risk factors.

“The deteriorated blood glucose health among obese adults in the United States calls for lifestyle interventions (diet and exercise) on a national scale,” wrote Dr. Garvey, chair of nutrition science at the University of Alabama, Birmingham. “Community-based public health intervention programs may help increase physical activity and diet quality to alleviate the problem.”

The investigators examined trends in cardiometabolic health among 18,626 obese adults who participated in National Health and Nutrition Examination Surveys from 1988 to 2014. Over this period, mean body mass index increased significantly, from 34.7 to 36 kg/m². Waist circumference increased as well, from 110 to 114.8 cm.

The picture was much better for blood pressure. Mean systolic pressures decreased about 2 points – from 126.1 to 124.4 mm Hg – in all age, racial and ethnic groups, and in both sexes. Mean diastolic blood pressure also decreased, dropping from 76.6 to 72.5 mm Hg. By 2014, 44% of the men and 51% of the women were below the blood pressure risk threshold.

Lipids also improved over the years, the investigators noted, with significant decreases in mean total cholesterol, from 214.5 to 193.7 mg/dL, and increases in HDL cholesterol, from 45.4 to 47.4 mg/dL.

Blood glucose worsened significantly, however. The mean hemoglobin A1c increased from 5.7% to 5.9%. The measurement rose in all ages, both sexes, and in all racial and ethnic groups except for non-Hispanic blacks.

Perhaps not surprisingly, the incidence of diabetes (a self-reported HbA_1c of 6.5% or more) increased from 11% to 19% from 1988 to 2014. The increase occurred in all age groups and both sexes except for young adults aged 20-39 years. No racial or ethnic group was exempt from the increase.

The number of people having all three risk factors (hypertension, hypercholesterolemia, and hyperglycemia) increased from 16% in 1988 to 22% in 2014.

“The increase occurred in parallel with a decline in the prevalence of healthy blood glucose, which is the predominant explanation accounting for the rise in the prevalence of presence of all three risk factors,” the investigators said.

Only 15% of the study population was free from all of these risk factors – a percentage that remained unchanged during 1988-2014.

The findings should be a wake-up call for physicians and their patients, and a national call for action to improve cardiovascular health among obese adults, the team wrote.

“The increasing trend of obese people with all three cardiovascular risk factors, commensurate with a decline in those with one or two risk factors, suggests an overall deterioration in health among people with obesity. ... These patterns of worsening metabolic health constitute an increase in risk of type 2 diabetes mellitus and underlie increasing prevalence rates for diabetes mellitus,” the investigators wrote.

Aggressive treatment will be necessary to reverse these trends. This might include treatment with weight-loss medications in conjunction with lifestyle interventions, which should be especially targeted at obese individuals who are already metabolically unhealthy and in those who have complications or are at risk for developing them.

“In the context of the current data, those obese adults who are metabolically unhealthy or perhaps those with suboptimal metabolic health represent patients who will benefit most from intensive obesity management … coordinated efforts aligning cardiovascular disease prevention and control activities across the public and private sectors in the United States are needed reduce the burden of cardiovascular disease among the obese population,” Dr. Garvey concluded.

The study was supported by the Department of Veterans Affairs, the National Institutes of Health, and the University of Alabama Diabetes Research Center.

Dr. Guo had no financial disclosures. Dr. Garvey disclosed relationships with multiple pharmaceutical companies.

[email protected]

Despite achieving significant improvements in blood pressure and cholesterol levels, obese Americans continue to grow fatter, with worsening blood glucose and an increasing incidence of diabetes.

From 1998 to 2014, national health data showed that mean diastolic and systolic blood pressures decreased in obese men and women in all racial and ethnic groups. Mean lipid measurements improved as well, including a “marked” 21-mg/dL decrease in total cholesterol and a significant increase in HDL cholesterol.

But markers of blood glucose health continued to decline over the same period, contributing to an overall worsening of metabolic health and a increase from 11% to 19% in the rate of diabetes, Fangjian Guo, MD, and W. Timothy Garvey, MD, reported in July 13 issue of the Journal of the American Heart Association (J Am Heart Assoc. 2016 Jul 13. 5:e003619 doi: 10.1161/JAHA.116.003619).

The rate of obese adults free of these three cardiovascular disease risk factors – diabetes, elevated cholesterol, and blood pressure – remained stable over the study period at about 15%. But the rate of obese adults with all three risk factors increased by 37% over the same period. By 2014, 22% reported having all three of those risk factors.

“The deteriorated blood glucose health among obese adults in the United States calls for lifestyle interventions (diet and exercise) on a national scale,” wrote Dr. Garvey, chair of nutrition science at the University of Alabama, Birmingham. “Community-based public health intervention programs may help increase physical activity and diet quality to alleviate the problem.”

The investigators examined trends in cardiometabolic health among 18,626 obese adults who participated in National Health and Nutrition Examination Surveys from 1988 to 2014. Over this period, mean body mass index increased significantly, from 34.7 to 36 kg/m². Waist circumference increased as well, from 110 to 114.8 cm.

The picture was much better for blood pressure. Mean systolic pressures decreased about 2 points – from 126.1 to 124.4 mm Hg – in all age, racial and ethnic groups, and in both sexes. Mean diastolic blood pressure also decreased, dropping from 76.6 to 72.5 mm Hg. By 2014, 44% of the men and 51% of the women were below the blood pressure risk threshold.

Lipids also improved over the years, the investigators noted, with significant decreases in mean total cholesterol, from 214.5 to 193.7 mg/dL, and increases in HDL cholesterol, from 45.4 to 47.4 mg/dL.

Blood glucose worsened significantly, however. The mean hemoglobin A1c increased from 5.7% to 5.9%. The measurement rose in all ages, both sexes, and in all racial and ethnic groups except for non-Hispanic blacks.

Perhaps not surprisingly, the incidence of diabetes (a self-reported HbA_1c of 6.5% or more) increased from 11% to 19% from 1988 to 2014. The increase occurred in all age groups and both sexes except for young adults aged 20-39 years. No racial or ethnic group was exempt from the increase.

The number of people having all three risk factors (hypertension, hypercholesterolemia, and hyperglycemia) increased from 16% in 1988 to 22% in 2014.

“The increase occurred in parallel with a decline in the prevalence of healthy blood glucose, which is the predominant explanation accounting for the rise in the prevalence of presence of all three risk factors,” the investigators said.

Only 15% of the study population was free from all of these risk factors – a percentage that remained unchanged during 1988-2014.

The findings should be a wake-up call for physicians and their patients, and a national call for action to improve cardiovascular health among obese adults, the team wrote.

“The increasing trend of obese people with all three cardiovascular risk factors, commensurate with a decline in those with one or two risk factors, suggests an overall deterioration in health among people with obesity. ... These patterns of worsening metabolic health constitute an increase in risk of type 2 diabetes mellitus and underlie increasing prevalence rates for diabetes mellitus,” the investigators wrote.

Aggressive treatment will be necessary to reverse these trends. This might include treatment with weight-loss medications in conjunction with lifestyle interventions, which should be especially targeted at obese individuals who are already metabolically unhealthy and in those who have complications or are at risk for developing them.

“In the context of the current data, those obese adults who are metabolically unhealthy or perhaps those with suboptimal metabolic health represent patients who will benefit most from intensive obesity management … coordinated efforts aligning cardiovascular disease prevention and control activities across the public and private sectors in the United States are needed reduce the burden of cardiovascular disease among the obese population,” Dr. Garvey concluded.

The study was supported by the Department of Veterans Affairs, the National Institutes of Health, and the University of Alabama Diabetes Research Center.

Dr. Guo had no financial disclosures. Dr. Garvey disclosed relationships with multiple pharmaceutical companies.

[email protected]

Nearly 2% of patients who undergo total knee arthroplasty (TKA) or total hip arthroplasty (THA) develop a periprosthetic joint infection (PJI) within 20 years of surgery, and 41% of these infections occur within the first 2 years.¹ PJI is the most common cause of TKA failure and the third leading complication of THA.² The estimated total hospital cost of treating PJI increased from $320 million in 2001 to $566 million in 2009, which can be extrapolated to $1.62 billion in 2020.³ By 2030, the projected increase in demand for TKA and THA will be 673% and 174% of what it was in 2005, respectively.⁴ Treatment of PJI of the knee is estimated to cost 3 to 4 times more than a primary TKA, and the cost of revision THA for PJI is almost $6000 more than that of revision TKA for PJI.³

In this article, we review the numerous preoperative, intraoperative, and postoperative methods of decreasing PJI incidence after total joint arthroplasty (TJA).

Preoperative Risk Prevention

Medical Comorbidities

Preoperative medical optimization is a key element in PJI prevention (Table 1). An American Society of Anesthesiologists classification score of 3 or more has been associated with doubled risk for surgical site infections (SSIs) after THA.5 Autoimmune conditions confer a particularly higher risk. In a retrospective double-cohort study of 924 subjects, Bongartz and colleagues⁶ found that, compared with osteoarthritis, rheumatoid arthritis tripled the risk of PJI. Small case series originally suggested a higher risk of PJI in patients with psoriasis,^7,8 but more recent studies have contradicted that finding.^9,10 Nevertheless, psoriatic plaques have elevated bacterial counts,¹¹ and planned incisions should circumvent these areas.

Diabetes mellitus is a clear risk factor for PJI.^12-16 Regarding whether preoperative glucose control affects risk, findings have been mixed. Mraovic and colleagues¹⁷ showed preoperative hyperglycemia to be an independent risk factor; Jämsen and colleagues,¹⁵ in a single-center analysis of more than 7000 TJAs, suggested preoperative blood glucose levels were not independently associated with PJI; and Iorio and colleagues¹⁶ found no association between surgical infections and hemoglobin A1c levels.

TJA incidence is higher in patients with chronic kidney disease (CKD) than in the general population.¹⁸ Dialysis users have a post-THA PJI rate as high as 13% to 19%.^19,20 Early clinical data suggested that outcomes are improved in dialysis users who undergo renal transplant, but this finding recently has been questioned.^19,21 Deegan and colleagues²² found an increased PJA rate of 3.5% even in low-level CKD (stage 1, 2, or 3), but this may be confounded by the increased association of CKD with other PJI-predisposing comorbidities.

Given a higher incidence of urinary tract infections (UTIs) among patients with PJI, some surgeons think UTIs predispose to PJIs by hematogenous seeding.^12,23,24 Symptomatic UTIs should be cleared before surgery and confirmed on urinalysis. Obstructive symptoms should prompt urologic evaluation. As asymptomatic pyuria and bacteriuria (colony counts, >1 × 105/mL) do not predispose to PJI, patients without symptoms do not require intervention.^25,26 Past history of malignancy may also have a role in PJI. In a case-control study of the Mayo Clinic arthroplasty experience from 1969 to 1991, Berbari and colleagues¹ found an association between malignancy and PJI (odds ratio, 2.4). They theorized the immunosuppressive effects of cancer treatment might be responsible for this increased risk.

Immunocompromising Medications

Immunocompromising medications are modifiable and should be adjusted before surgery. Stopping any disease-modifying antirheumatic drug (DMARD) more than 4 weeks before surgery is not recommended.²⁷

Corticosteroid use can lead to immunosuppression and increased protein catabolism, which impairs soft-tissue healing. To avoid flares or adrenal insufficiency, however, chronic corticosteroid users should continue their regular doses perioperatively.²⁸ On the day of surgery, they should also receive a stress dose of hydrocortisone 50 to 75 mg (for primary arthroplasty) or 100 to 150 mg (for revision arthroplasty), followed by expeditious tapering over 1 to 2 days.²⁹ DMARDs are increasingly used by rheumatologists. One of the most effective DMARDs is methotrexate. Despite its immunocompromising activity, methotrexate should be continued perioperatively, as stopping for even 2 days may increase flare-related complications.³⁰ Hydroxychloroquine can be continued perioperatively and has even been shown, by Johnson and Charnley,³¹ to prevent deep vein thromboses. Sulfasalazine can also be continued perioperatively—but with caution, as it may elevate international normalized ratio (INR) levels in patients receiving warfarin.²⁹ Most other DMARDs should be temporarily discontinued. Leflunomide and interleukin 1 antagonists, such as anakinra, should be stopped 1 to 2 days before surgery and restarted 10 to 14 days after surgery.²⁹ Rituximab should be stopped 1 week before surgery and restarted 10 to 14 days after surgery. Tumor necrosis factor α inhibitors should be discontinued for 2 half-lives before and after surgery.³² Etanercept has a half-life of 3 to 5 days; infliximab, 8 to 10 days; and adalimumab, 10 to 13 days. Most surgeons schedule surgery for the end of a dosing cycle and discontinue these biologic agents for another 10 to 14 days after surgery.

Metabolic Factors

Obese patients are susceptible to longer surgeries, more extensive dissection, poorly vascularized subcutaneous tissue, and higher requirements of weight-adjusted antibiotic dosing.¹³ Body mass index (BMI) of 40 kg/m² or more (morbid obesity) and BMI over 50 kg/m² have been associated with 9 times and 21.3 times increased risk of PJI, respectively.^13,14 Delaying surgery with dietary consultation has been suggested,^33,34 and bariatric surgery before TKA may decrease infection rates by 3.5 times.³⁵

Nutritional markers are considered before arthroplasty. According to most laboratories, a serum transferrin level under 200 mg/dL, albumin level under 3.5 g/dL, and total lymphocyte count under 1500 cells/mm³ indicate malnourishment, which can increase the incidence of wound complications by 5 to 7 times.³⁶ Patients should also have sufficient protein, vitamin, and mineral supplementation, particularly vitamins A and C, zinc, and copper.³⁷Smokers who cease smoking at least 4 to 6 weeks before surgery lower their wound complication rate by up to 26%.^38,39 When nicotine leaves the bloodstream, vasodilation occurs, oxygenation improves, and the immune system recovers.³⁹ Studies have found more SSIs in patients who abuse alcohol,40 and numerous authors have confirmed this finding in the arthroplasty population.^24,41,42 Alcohol inhibits platelet function and may predispose to a postoperative hematoma. In contrast to smoking cessation evidence, evidence regarding alcohol interventions in preventing postoperative infections is less conclusive.^43,44

MRSA Colonization

Methicillin-resistant Staphylococcus aureus (MRSA) is a particularly difficult bacterium to eradicate in PJI. As the mean cost of treating a single case of MRSA-related prosthetic infection is $107,264 vs $68,053 for susceptible strains,45,46 many infection-containment strategies focus on addressing benign MRSA colonization before surgery.

MRSA is present in the nares of 25 million people in the United States. Nasal colonization increases the risk of bacteremia 4-fold⁴⁷ and SSI 2- to 9-fold.^48,49 Nasal swabs are analyzed with either a rapid polymerase chain reaction (PCR) test, which provides results in 2 hours, or a bacterial culture, which provides results in 1 to 4 days. The PCR test is more expensive.

Eradication of MRSA colonization is increasingly prevalent. Several Scandinavian countries have instituted strict practices by which patients are denied elective surgery until negative nasal swabs are obtained.⁴⁹ Nasal decontamination is one method of colonization reduction. Topical mupirocin, which yields eradication in 91% of nasal carriers immediately after treatment and in 87% after 4 weeks,⁵⁰ is effective in reducing SSI rates only when used in conjunction with a body wash, which is used to clean the axilla and groin.⁵¹ There is no consensus on optimal timing, but Bode and colleagues⁵² found a significant decrease in deep SSIs when decontamination occurred just 24 hours before surgery.

Povidone-iodine showers went out of favor with the realization that chlorhexidine gluconate acts longer on the skin surface.^53,54 Preoperative showers involve rinsing with liquid chlorhexidine soap 24 to 48 hours before surgery. However, chlorhexidine binds preferentially to the cotton in washcloths instead of the skin. Edmiston and colleagues^54,55 found that 4% chlorhexidine liquid soaps achieve much lower skin chlorhexidine concentrations than 2% polyester cloths do. Use of these “chlorhexidine wipes” the night before and the day of surgery has decreased PJI after TKA from 2.2% to 0.6%.^56,57

Intraoperative Risk Prevention

Preparation

Which preoperative antibiotic to use is one of the first operative considerations in PJI prophylaxis (Table 2). Cefazolin is recommended as a first-line agent for its excellent soft-tissue penetration, long half-life, and activity against gram-positive bacteria such as skin flora.⁵⁸ Clindamycin may be considered for patients allergic to β-lactam antibiotics. Vancomycin may be considered for adjunctive use with cephalosporins in cases of known MRSA colonization. Vancomycin infusion should be started earlier than infusion with other antibiotics, as vancomycin must be infused slowly and takes longer to become therapeutic.

Antibiotic dosing should be based on local antibiograms, adjusted dosing weight, or BMI.⁵⁹ For revision arthroplasty, preoperative prophylaxis should not be stopped out of fear of affecting operative cultures.⁶⁰ Some surgeons pause antibiotic use if a preoperative joint aspirate has not been obtained. Infusion within 1 hour of incision is part of the pay-for-performance guidelines established by the US Centers for Medicare & Medicaid Services.⁶¹ An antibiotic should be redosed if the operation will take longer than 2 half-lives of the drug.⁵⁹ Surgeons should consider administering a dose every 4 hours or whenever blood loss exceeds 1000 mL.⁶² Engesæter and colleagues⁶³ found that antibiotic prophylaxis was most effective given 4 times perioperatively (1 time before surgery, 3 times after surgery). Postoperative antibiotics should not be administered longer than 24 hours, as prolonged dosing confers no benefit.⁵⁸ Operating room conditions must be optimized for prophylaxis. More people and operating room traffic in nonsterile corridors increase contamination of instruments open to air.⁶⁴ Laminar airflow systems are commonly used. Although there is little dispute that laminar flow decreases the bacterial load of air, there are mixed results regarding its benefit in preventing PJI.^65-68 Skin preparation may address patient risk factors. Hair clipping is preferred to shaving, which may cause microabrasions and increased susceptibility to skin flora.69 Patients should be prepared with antiseptic solution. One randomized controlled trial found that 2% chlorhexidine gluconate mixed with 70% isopropyl alcohol was superior to 10% povidone-iodine in preventing SSIs.⁷⁰ However, a recent cohort study showed a lower rate of superficial wound infections when 1% povidone-iodine (vs 0.5% chlorhexidine) was used with alcohol.⁷¹ This finding may indicate the need for alcohol preparation, higher concentrations of chlorhexidine, or both.

Proper scrubbing and protective gear are needed to reduce surgeon risk factors. Hand washing is a routine part of any surgery. Alcohol-based hand scrubs are as effective as hand scrubbing.65 They reduce local skin flora by 95% immediately and by 99% with repeated applications.⁷² Lidwell and colleagues⁷³ found a 75% reduction in infection when body exhaust suits were used in combination with laminar flow in a multicenter randomized controlled trial of 8052 patients. Sterile draping with impermeable drapes should be done over properly prepared skin. Ioban drapes (3M) are often used as a protective barrier. Interestingly, a Cochrane review found no benefit in using plastic adhesives impregnated with iodine over sterilely prepared skin.⁷⁴

Operative Considerations

Surgical gloves become contaminated in almost one third of cases, half the time during draping.⁷⁵ For this reason, many surgeons change gloves after draping. In addition, double gloving prevents a breech of aseptic technique should the outer glove become perforated.⁷⁶ Demircay and colleagues⁷⁷ assessed double latex gloving in arthroplasty and found the outer and inner gloves perforated in 18.4% and 8.4% of cases, respectively. Punctures are most common along the nondominant index finger, and then the dominant thumb.^77,78 Perforation is more common when 2 latex gloves are worn—vs 1 latex glove plus an outer cloth glove—and the chance of perforation increases with surgery duration. The inner glove may become punctured in up to 100% of operations that last over 3 hours.⁷⁹ Although Dodds and colleagues⁸⁰ found no change in bacterial counts on surgeons’ hands or gloves after perforation, precautions are still recommended. Al-Maiyah and colleagues⁸¹ went as far as to recommend glove changes at 20-minute intervals and before cementation.

Surgical instruments can be sources of contamination. Some authors change the suction tip every hour to minimize the risk of deep wound infection.^82-85 Others change it before femoral canal preparation and prosthesis insertion during THA.⁸⁶ The splash basin is frequently contaminated, and instruments placed in it should not be returned to the operative field.⁸⁷ Hargrove and colleagues⁸⁸ suggested pulsatile lavage decreases PJI more than bulb syringe irrigation does, whereas others argued that high-pressure lavage allows bacteria to penetrate more deeply, which could lead to retention of more bacteria.⁸⁹ Minimizing operating room time was found by Kurtz and colleagues⁹⁰ and Peersman and colleagues⁹¹ to decrease PJI incidence. Carroll and colleagues⁷¹ correlated longer tourniquet use with a higher rate of infection after TKA; proposed mechanisms include local tissue hypoxia and lowered concentrations of prophylactic antibiotics.

Similarly, minimizing blood loss and transfusion needs is another strategy for preventing infection. Allogenic transfusion may increase the risk of PJI 2 times.^23,71,92 The mechanism seems to be immune system modulation by allogenic blood, which impairs microcirculation and oxygen delivery at the surgical site.^23,75 Transfusions should be approached with caution, and consideration given to preoperative optimization and autologous blood donation. Cherian and colleagues⁹³ reviewed different blood management strategies and found preoperative iron therapy, intravenous erythropoietin, and autologous blood donation to be equally effective in reducing the need for allogenic transfusions. Numerous studies of tranexamic acid, thrombin-based hemostatic matrix (Floseal; Baxter Inc), and bipolar sealer with radiofrequency ablation (Aquamantys; Medtronic Inc) have found no alterations in infection rates, but most have used calculated blood loss, not PJI, as the primary endpoint.^94-105 Antibiotic cement also can be used to block infection.^63,106-110 Although liquid gentamicin may weaken bone cement,¹¹¹ most antibiotics, including powdered tobramycin and vancomycin, do not weaken its fatigue strength.^111-114 A recent meta-analysis by Parvizi and colleagues¹¹⁵ revealed that deep infection rates dropped from 2.3% to 1.2% with use of antibiotic cement for primary THAs. Cummins and colleagues,¹¹⁶ however, reported the limited cost-effectiveness of antibiotic cement in primary arthroplasty. Performing povidone-iodine lavage at the end of the case may be a more inexpensive alternative. Brown and colleagues¹¹⁷ found that rinsing with dilute povidone-iodine (.35%) for 3 minutes significantly decreased the incidence of PJI.

Closure techniques and sutures have been a focus of much of the recent literature. Winiarsky and colleagues³⁴ advocated using a longer incision for obese patients and augmenting closure in fattier areas with vertical mattress retention sutures, which are removed after 5 days. A barbed monofilament suture (Quill; Angiotech Inc) is gaining in popularity. Laboratory research has shown that bacteria adhere less to barbed monofilament sutures than to braided sutures.¹¹⁸ Smith and colleagues¹¹⁹ found a statistically nonsignificant higher rate of wound complications with barbed monofilament sutures, whereas Ting and colleagues120 found no difference in complications. These studies were powered to detect differences in time and cost, not postoperative complications. Skin adhesive (Dermabond; Ethicon Inc), also used in closure, may be superior to staples in avoiding superficial skin abscesses.¹²¹ Although expensive, silver-impregnated dressing has antimicrobial activity that reduces PJI incidence by up to 74%.¹²² One brand of this dressing (Aquacel; ConvaTec Inc) has a polyurethane waterproof barrier that allows it to be worn for 7 days.

Three factors commonly mentioned in PJI prevention show little supporting evidence. Drains, which are often used, may create a passage for postoperative infection and are associated with increased transfusion needs.^123,124 Adding antibiotics to irrigation solution¹²⁵ and routinely changing scalpel blades^126-129 also have little supporting evidence. In 2014, the utility of changing scalpel blades after incision was studied by Lee and colleagues,¹³⁰ who reported persistence of Propionibacterium acnes in the dermal layer after skin preparation. Their study, however, was isolated to the upper back region, not the hip or knee.

Postoperative Risk Prevention

Most arthroplasty patients receive anticoagulation after surgery, but it must be used with caution. Large hematomas can predispose to wound complications. Parvizi and colleagues¹³¹ associated wound drainage, hematoma, and subsequent PJI with an INR above 1.5 in the early postoperative period. Therefore, balanced anticoagulation is crucial. Postoperative glucose control is also essential, particularly for patients with diabetes. Although preoperative blood glucose levels may or may not affect PJI risk,^15,17,132 postoperative blood glucose levels of 126 mg/dL or higher are strongly associated with joint infections.¹³³ Even nondiabetic patients with postoperative morning levels over 140 mg/dL are 3 times more likely to develop an infection.¹⁷

Efforts should be made to discharge patients as soon as it is safe to do so. With longer hospital stays, patients are more exposed to nosocomial organisms and increased antibiotic resistance.^5,23,134 Outpatient antibiotics should be considered for dental, gastrointestinal, and genitourinary procedures. Oral antibiotic prophylaxis is controversial, as there is some evidence that dental procedures increase the risk of PJI only minimally.^10,135-138

Conclusion

PJI is a potentially devastating complication of TJA. For this reason, much research has been devoted to proper diagnosis and treatment. Although the literature on PJI prophylaxis is abundant, there is relatively little consensus on appropriate PJI precautions. Preoperative considerations should include medical comorbidities, use of immunocompromising medications, obesity, nutritional factors, smoking, alcohol use, and MRSA colonization. Surgeons must have a consistent intraoperative method of antibiotic administration, skin preparation, scrubbing, draping, gloving, instrument exchange, blood loss management, cementing, and closure. In addition, monitoring of postoperative anticoagulation and blood glucose management is important. Having a thorough understanding of PJI risk factors may help reduce the incidence of this devastating complication.

Nearly 2% of patients who undergo total knee arthroplasty (TKA) or total hip arthroplasty (THA) develop a periprosthetic joint infection (PJI) within 20 years of surgery, and 41% of these infections occur within the first 2 years.¹ PJI is the most common cause of TKA failure and the third leading complication of THA.² The estimated total hospital cost of treating PJI increased from $320 million in 2001 to $566 million in 2009, which can be extrapolated to $1.62 billion in 2020.³ By 2030, the projected increase in demand for TKA and THA will be 673% and 174% of what it was in 2005, respectively.⁴ Treatment of PJI of the knee is estimated to cost 3 to 4 times more than a primary TKA, and the cost of revision THA for PJI is almost $6000 more than that of revision TKA for PJI.³

In this article, we review the numerous preoperative, intraoperative, and postoperative methods of decreasing PJI incidence after total joint arthroplasty (TJA).

Preoperative Risk Prevention

Medical Comorbidities

Preoperative medical optimization is a key element in PJI prevention (Table 1). An American Society of Anesthesiologists classification score of 3 or more has been associated with doubled risk for surgical site infections (SSIs) after THA.5 Autoimmune conditions confer a particularly higher risk. In a retrospective double-cohort study of 924 subjects, Bongartz and colleagues⁶ found that, compared with osteoarthritis, rheumatoid arthritis tripled the risk of PJI. Small case series originally suggested a higher risk of PJI in patients with psoriasis,^7,8 but more recent studies have contradicted that finding.^9,10 Nevertheless, psoriatic plaques have elevated bacterial counts,¹¹ and planned incisions should circumvent these areas.

Diabetes mellitus is a clear risk factor for PJI.^12-16 Regarding whether preoperative glucose control affects risk, findings have been mixed. Mraovic and colleagues¹⁷ showed preoperative hyperglycemia to be an independent risk factor; Jämsen and colleagues,¹⁵ in a single-center analysis of more than 7000 TJAs, suggested preoperative blood glucose levels were not independently associated with PJI; and Iorio and colleagues¹⁶ found no association between surgical infections and hemoglobin A1c levels.

TJA incidence is higher in patients with chronic kidney disease (CKD) than in the general population.¹⁸ Dialysis users have a post-THA PJI rate as high as 13% to 19%.^19,20 Early clinical data suggested that outcomes are improved in dialysis users who undergo renal transplant, but this finding recently has been questioned.^19,21 Deegan and colleagues²² found an increased PJA rate of 3.5% even in low-level CKD (stage 1, 2, or 3), but this may be confounded by the increased association of CKD with other PJI-predisposing comorbidities.

Given a higher incidence of urinary tract infections (UTIs) among patients with PJI, some surgeons think UTIs predispose to PJIs by hematogenous seeding.^12,23,24 Symptomatic UTIs should be cleared before surgery and confirmed on urinalysis. Obstructive symptoms should prompt urologic evaluation. As asymptomatic pyuria and bacteriuria (colony counts, >1 × 105/mL) do not predispose to PJI, patients without symptoms do not require intervention.^25,26 Past history of malignancy may also have a role in PJI. In a case-control study of the Mayo Clinic arthroplasty experience from 1969 to 1991, Berbari and colleagues¹ found an association between malignancy and PJI (odds ratio, 2.4). They theorized the immunosuppressive effects of cancer treatment might be responsible for this increased risk.

Immunocompromising Medications

Immunocompromising medications are modifiable and should be adjusted before surgery. Stopping any disease-modifying antirheumatic drug (DMARD) more than 4 weeks before surgery is not recommended.²⁷

Corticosteroid use can lead to immunosuppression and increased protein catabolism, which impairs soft-tissue healing. To avoid flares or adrenal insufficiency, however, chronic corticosteroid users should continue their regular doses perioperatively.²⁸ On the day of surgery, they should also receive a stress dose of hydrocortisone 50 to 75 mg (for primary arthroplasty) or 100 to 150 mg (for revision arthroplasty), followed by expeditious tapering over 1 to 2 days.²⁹ DMARDs are increasingly used by rheumatologists. One of the most effective DMARDs is methotrexate. Despite its immunocompromising activity, methotrexate should be continued perioperatively, as stopping for even 2 days may increase flare-related complications.³⁰ Hydroxychloroquine can be continued perioperatively and has even been shown, by Johnson and Charnley,³¹ to prevent deep vein thromboses. Sulfasalazine can also be continued perioperatively—but with caution, as it may elevate international normalized ratio (INR) levels in patients receiving warfarin.²⁹ Most other DMARDs should be temporarily discontinued. Leflunomide and interleukin 1 antagonists, such as anakinra, should be stopped 1 to 2 days before surgery and restarted 10 to 14 days after surgery.²⁹ Rituximab should be stopped 1 week before surgery and restarted 10 to 14 days after surgery. Tumor necrosis factor α inhibitors should be discontinued for 2 half-lives before and after surgery.³² Etanercept has a half-life of 3 to 5 days; infliximab, 8 to 10 days; and adalimumab, 10 to 13 days. Most surgeons schedule surgery for the end of a dosing cycle and discontinue these biologic agents for another 10 to 14 days after surgery.

Metabolic Factors

Obese patients are susceptible to longer surgeries, more extensive dissection, poorly vascularized subcutaneous tissue, and higher requirements of weight-adjusted antibiotic dosing.¹³ Body mass index (BMI) of 40 kg/m² or more (morbid obesity) and BMI over 50 kg/m² have been associated with 9 times and 21.3 times increased risk of PJI, respectively.^13,14 Delaying surgery with dietary consultation has been suggested,^33,34 and bariatric surgery before TKA may decrease infection rates by 3.5 times.³⁵

Nutritional markers are considered before arthroplasty. According to most laboratories, a serum transferrin level under 200 mg/dL, albumin level under 3.5 g/dL, and total lymphocyte count under 1500 cells/mm³ indicate malnourishment, which can increase the incidence of wound complications by 5 to 7 times.³⁶ Patients should also have sufficient protein, vitamin, and mineral supplementation, particularly vitamins A and C, zinc, and copper.³⁷Smokers who cease smoking at least 4 to 6 weeks before surgery lower their wound complication rate by up to 26%.^38,39 When nicotine leaves the bloodstream, vasodilation occurs, oxygenation improves, and the immune system recovers.³⁹ Studies have found more SSIs in patients who abuse alcohol,40 and numerous authors have confirmed this finding in the arthroplasty population.^24,41,42 Alcohol inhibits platelet function and may predispose to a postoperative hematoma. In contrast to smoking cessation evidence, evidence regarding alcohol interventions in preventing postoperative infections is less conclusive.^43,44

MRSA Colonization

Methicillin-resistant Staphylococcus aureus (MRSA) is a particularly difficult bacterium to eradicate in PJI. As the mean cost of treating a single case of MRSA-related prosthetic infection is $107,264 vs $68,053 for susceptible strains,45,46 many infection-containment strategies focus on addressing benign MRSA colonization before surgery.

MRSA is present in the nares of 25 million people in the United States. Nasal colonization increases the risk of bacteremia 4-fold⁴⁷ and SSI 2- to 9-fold.^48,49 Nasal swabs are analyzed with either a rapid polymerase chain reaction (PCR) test, which provides results in 2 hours, or a bacterial culture, which provides results in 1 to 4 days. The PCR test is more expensive.

Eradication of MRSA colonization is increasingly prevalent. Several Scandinavian countries have instituted strict practices by which patients are denied elective surgery until negative nasal swabs are obtained.⁴⁹ Nasal decontamination is one method of colonization reduction. Topical mupirocin, which yields eradication in 91% of nasal carriers immediately after treatment and in 87% after 4 weeks,⁵⁰ is effective in reducing SSI rates only when used in conjunction with a body wash, which is used to clean the axilla and groin.⁵¹ There is no consensus on optimal timing, but Bode and colleagues⁵² found a significant decrease in deep SSIs when decontamination occurred just 24 hours before surgery.

Povidone-iodine showers went out of favor with the realization that chlorhexidine gluconate acts longer on the skin surface.^53,54 Preoperative showers involve rinsing with liquid chlorhexidine soap 24 to 48 hours before surgery. However, chlorhexidine binds preferentially to the cotton in washcloths instead of the skin. Edmiston and colleagues^54,55 found that 4% chlorhexidine liquid soaps achieve much lower skin chlorhexidine concentrations than 2% polyester cloths do. Use of these “chlorhexidine wipes” the night before and the day of surgery has decreased PJI after TKA from 2.2% to 0.6%.^56,57

Intraoperative Risk Prevention

Preparation

Which preoperative antibiotic to use is one of the first operative considerations in PJI prophylaxis (Table 2). Cefazolin is recommended as a first-line agent for its excellent soft-tissue penetration, long half-life, and activity against gram-positive bacteria such as skin flora.⁵⁸ Clindamycin may be considered for patients allergic to β-lactam antibiotics. Vancomycin may be considered for adjunctive use with cephalosporins in cases of known MRSA colonization. Vancomycin infusion should be started earlier than infusion with other antibiotics, as vancomycin must be infused slowly and takes longer to become therapeutic.

Antibiotic dosing should be based on local antibiograms, adjusted dosing weight, or BMI.⁵⁹ For revision arthroplasty, preoperative prophylaxis should not be stopped out of fear of affecting operative cultures.⁶⁰ Some surgeons pause antibiotic use if a preoperative joint aspirate has not been obtained. Infusion within 1 hour of incision is part of the pay-for-performance guidelines established by the US Centers for Medicare & Medicaid Services.⁶¹ An antibiotic should be redosed if the operation will take longer than 2 half-lives of the drug.⁵⁹ Surgeons should consider administering a dose every 4 hours or whenever blood loss exceeds 1000 mL.⁶² Engesæter and colleagues⁶³ found that antibiotic prophylaxis was most effective given 4 times perioperatively (1 time before surgery, 3 times after surgery). Postoperative antibiotics should not be administered longer than 24 hours, as prolonged dosing confers no benefit.⁵⁸ Operating room conditions must be optimized for prophylaxis. More people and operating room traffic in nonsterile corridors increase contamination of instruments open to air.⁶⁴ Laminar airflow systems are commonly used. Although there is little dispute that laminar flow decreases the bacterial load of air, there are mixed results regarding its benefit in preventing PJI.^65-68 Skin preparation may address patient risk factors. Hair clipping is preferred to shaving, which may cause microabrasions and increased susceptibility to skin flora.69 Patients should be prepared with antiseptic solution. One randomized controlled trial found that 2% chlorhexidine gluconate mixed with 70% isopropyl alcohol was superior to 10% povidone-iodine in preventing SSIs.⁷⁰ However, a recent cohort study showed a lower rate of superficial wound infections when 1% povidone-iodine (vs 0.5% chlorhexidine) was used with alcohol.⁷¹ This finding may indicate the need for alcohol preparation, higher concentrations of chlorhexidine, or both.

Proper scrubbing and protective gear are needed to reduce surgeon risk factors. Hand washing is a routine part of any surgery. Alcohol-based hand scrubs are as effective as hand scrubbing.65 They reduce local skin flora by 95% immediately and by 99% with repeated applications.⁷² Lidwell and colleagues⁷³ found a 75% reduction in infection when body exhaust suits were used in combination with laminar flow in a multicenter randomized controlled trial of 8052 patients. Sterile draping with impermeable drapes should be done over properly prepared skin. Ioban drapes (3M) are often used as a protective barrier. Interestingly, a Cochrane review found no benefit in using plastic adhesives impregnated with iodine over sterilely prepared skin.⁷⁴

Operative Considerations

Surgical gloves become contaminated in almost one third of cases, half the time during draping.⁷⁵ For this reason, many surgeons change gloves after draping. In addition, double gloving prevents a breech of aseptic technique should the outer glove become perforated.⁷⁶ Demircay and colleagues⁷⁷ assessed double latex gloving in arthroplasty and found the outer and inner gloves perforated in 18.4% and 8.4% of cases, respectively. Punctures are most common along the nondominant index finger, and then the dominant thumb.^77,78 Perforation is more common when 2 latex gloves are worn—vs 1 latex glove plus an outer cloth glove—and the chance of perforation increases with surgery duration. The inner glove may become punctured in up to 100% of operations that last over 3 hours.⁷⁹ Although Dodds and colleagues⁸⁰ found no change in bacterial counts on surgeons’ hands or gloves after perforation, precautions are still recommended. Al-Maiyah and colleagues⁸¹ went as far as to recommend glove changes at 20-minute intervals and before cementation.

Surgical instruments can be sources of contamination. Some authors change the suction tip every hour to minimize the risk of deep wound infection.^82-85 Others change it before femoral canal preparation and prosthesis insertion during THA.⁸⁶ The splash basin is frequently contaminated, and instruments placed in it should not be returned to the operative field.⁸⁷ Hargrove and colleagues⁸⁸ suggested pulsatile lavage decreases PJI more than bulb syringe irrigation does, whereas others argued that high-pressure lavage allows bacteria to penetrate more deeply, which could lead to retention of more bacteria.⁸⁹ Minimizing operating room time was found by Kurtz and colleagues⁹⁰ and Peersman and colleagues⁹¹ to decrease PJI incidence. Carroll and colleagues⁷¹ correlated longer tourniquet use with a higher rate of infection after TKA; proposed mechanisms include local tissue hypoxia and lowered concentrations of prophylactic antibiotics.

Similarly, minimizing blood loss and transfusion needs is another strategy for preventing infection. Allogenic transfusion may increase the risk of PJI 2 times.^23,71,92 The mechanism seems to be immune system modulation by allogenic blood, which impairs microcirculation and oxygen delivery at the surgical site.^23,75 Transfusions should be approached with caution, and consideration given to preoperative optimization and autologous blood donation. Cherian and colleagues⁹³ reviewed different blood management strategies and found preoperative iron therapy, intravenous erythropoietin, and autologous blood donation to be equally effective in reducing the need for allogenic transfusions. Numerous studies of tranexamic acid, thrombin-based hemostatic matrix (Floseal; Baxter Inc), and bipolar sealer with radiofrequency ablation (Aquamantys; Medtronic Inc) have found no alterations in infection rates, but most have used calculated blood loss, not PJI, as the primary endpoint.^94-105 Antibiotic cement also can be used to block infection.^63,106-110 Although liquid gentamicin may weaken bone cement,¹¹¹ most antibiotics, including powdered tobramycin and vancomycin, do not weaken its fatigue strength.^111-114 A recent meta-analysis by Parvizi and colleagues¹¹⁵ revealed that deep infection rates dropped from 2.3% to 1.2% with use of antibiotic cement for primary THAs. Cummins and colleagues,¹¹⁶ however, reported the limited cost-effectiveness of antibiotic cement in primary arthroplasty. Performing povidone-iodine lavage at the end of the case may be a more inexpensive alternative. Brown and colleagues¹¹⁷ found that rinsing with dilute povidone-iodine (.35%) for 3 minutes significantly decreased the incidence of PJI.

Closure techniques and sutures have been a focus of much of the recent literature. Winiarsky and colleagues³⁴ advocated using a longer incision for obese patients and augmenting closure in fattier areas with vertical mattress retention sutures, which are removed after 5 days. A barbed monofilament suture (Quill; Angiotech Inc) is gaining in popularity. Laboratory research has shown that bacteria adhere less to barbed monofilament sutures than to braided sutures.¹¹⁸ Smith and colleagues¹¹⁹ found a statistically nonsignificant higher rate of wound complications with barbed monofilament sutures, whereas Ting and colleagues120 found no difference in complications. These studies were powered to detect differences in time and cost, not postoperative complications. Skin adhesive (Dermabond; Ethicon Inc), also used in closure, may be superior to staples in avoiding superficial skin abscesses.¹²¹ Although expensive, silver-impregnated dressing has antimicrobial activity that reduces PJI incidence by up to 74%.¹²² One brand of this dressing (Aquacel; ConvaTec Inc) has a polyurethane waterproof barrier that allows it to be worn for 7 days.

Three factors commonly mentioned in PJI prevention show little supporting evidence. Drains, which are often used, may create a passage for postoperative infection and are associated with increased transfusion needs.^123,124 Adding antibiotics to irrigation solution¹²⁵ and routinely changing scalpel blades^126-129 also have little supporting evidence. In 2014, the utility of changing scalpel blades after incision was studied by Lee and colleagues,¹³⁰ who reported persistence of Propionibacterium acnes in the dermal layer after skin preparation. Their study, however, was isolated to the upper back region, not the hip or knee.

Postoperative Risk Prevention

Most arthroplasty patients receive anticoagulation after surgery, but it must be used with caution. Large hematomas can predispose to wound complications. Parvizi and colleagues¹³¹ associated wound drainage, hematoma, and subsequent PJI with an INR above 1.5 in the early postoperative period. Therefore, balanced anticoagulation is crucial. Postoperative glucose control is also essential, particularly for patients with diabetes. Although preoperative blood glucose levels may or may not affect PJI risk,^15,17,132 postoperative blood glucose levels of 126 mg/dL or higher are strongly associated with joint infections.¹³³ Even nondiabetic patients with postoperative morning levels over 140 mg/dL are 3 times more likely to develop an infection.¹⁷

Efforts should be made to discharge patients as soon as it is safe to do so. With longer hospital stays, patients are more exposed to nosocomial organisms and increased antibiotic resistance.^5,23,134 Outpatient antibiotics should be considered for dental, gastrointestinal, and genitourinary procedures. Oral antibiotic prophylaxis is controversial, as there is some evidence that dental procedures increase the risk of PJI only minimally.^10,135-138

Conclusion

PJI is a potentially devastating complication of TJA. For this reason, much research has been devoted to proper diagnosis and treatment. Although the literature on PJI prophylaxis is abundant, there is relatively little consensus on appropriate PJI precautions. Preoperative considerations should include medical comorbidities, use of immunocompromising medications, obesity, nutritional factors, smoking, alcohol use, and MRSA colonization. Surgeons must have a consistent intraoperative method of antibiotic administration, skin preparation, scrubbing, draping, gloving, instrument exchange, blood loss management, cementing, and closure. In addition, monitoring of postoperative anticoagulation and blood glucose management is important. Having a thorough understanding of PJI risk factors may help reduce the incidence of this devastating complication.

Nearly 2% of patients who undergo total knee arthroplasty (TKA) or total hip arthroplasty (THA) develop a periprosthetic joint infection (PJI) within 20 years of surgery, and 41% of these infections occur within the first 2 years.¹ PJI is the most common cause of TKA failure and the third leading complication of THA.² The estimated total hospital cost of treating PJI increased from $320 million in 2001 to $566 million in 2009, which can be extrapolated to $1.62 billion in 2020.³ By 2030, the projected increase in demand for TKA and THA will be 673% and 174% of what it was in 2005, respectively.⁴ Treatment of PJI of the knee is estimated to cost 3 to 4 times more than a primary TKA, and the cost of revision THA for PJI is almost $6000 more than that of revision TKA for PJI.³

In this article, we review the numerous preoperative, intraoperative, and postoperative methods of decreasing PJI incidence after total joint arthroplasty (TJA).

Preoperative Risk Prevention

Medical Comorbidities

Preoperative medical optimization is a key element in PJI prevention (Table 1). An American Society of Anesthesiologists classification score of 3 or more has been associated with doubled risk for surgical site infections (SSIs) after THA.5 Autoimmune conditions confer a particularly higher risk. In a retrospective double-cohort study of 924 subjects, Bongartz and colleagues⁶ found that, compared with osteoarthritis, rheumatoid arthritis tripled the risk of PJI. Small case series originally suggested a higher risk of PJI in patients with psoriasis,^7,8 but more recent studies have contradicted that finding.^9,10 Nevertheless, psoriatic plaques have elevated bacterial counts,¹¹ and planned incisions should circumvent these areas.

Diabetes mellitus is a clear risk factor for PJI.^12-16 Regarding whether preoperative glucose control affects risk, findings have been mixed. Mraovic and colleagues¹⁷ showed preoperative hyperglycemia to be an independent risk factor; Jämsen and colleagues,¹⁵ in a single-center analysis of more than 7000 TJAs, suggested preoperative blood glucose levels were not independently associated with PJI; and Iorio and colleagues¹⁶ found no association between surgical infections and hemoglobin A1c levels.

TJA incidence is higher in patients with chronic kidney disease (CKD) than in the general population.¹⁸ Dialysis users have a post-THA PJI rate as high as 13% to 19%.^19,20 Early clinical data suggested that outcomes are improved in dialysis users who undergo renal transplant, but this finding recently has been questioned.^19,21 Deegan and colleagues²² found an increased PJA rate of 3.5% even in low-level CKD (stage 1, 2, or 3), but this may be confounded by the increased association of CKD with other PJI-predisposing comorbidities.

Given a higher incidence of urinary tract infections (UTIs) among patients with PJI, some surgeons think UTIs predispose to PJIs by hematogenous seeding.^12,23,24 Symptomatic UTIs should be cleared before surgery and confirmed on urinalysis. Obstructive symptoms should prompt urologic evaluation. As asymptomatic pyuria and bacteriuria (colony counts, >1 × 105/mL) do not predispose to PJI, patients without symptoms do not require intervention.^25,26 Past history of malignancy may also have a role in PJI. In a case-control study of the Mayo Clinic arthroplasty experience from 1969 to 1991, Berbari and colleagues¹ found an association between malignancy and PJI (odds ratio, 2.4). They theorized the immunosuppressive effects of cancer treatment might be responsible for this increased risk.

Immunocompromising Medications

Immunocompromising medications are modifiable and should be adjusted before surgery. Stopping any disease-modifying antirheumatic drug (DMARD) more than 4 weeks before surgery is not recommended.²⁷

Corticosteroid use can lead to immunosuppression and increased protein catabolism, which impairs soft-tissue healing. To avoid flares or adrenal insufficiency, however, chronic corticosteroid users should continue their regular doses perioperatively.²⁸ On the day of surgery, they should also receive a stress dose of hydrocortisone 50 to 75 mg (for primary arthroplasty) or 100 to 150 mg (for revision arthroplasty), followed by expeditious tapering over 1 to 2 days.²⁹ DMARDs are increasingly used by rheumatologists. One of the most effective DMARDs is methotrexate. Despite its immunocompromising activity, methotrexate should be continued perioperatively, as stopping for even 2 days may increase flare-related complications.³⁰ Hydroxychloroquine can be continued perioperatively and has even been shown, by Johnson and Charnley,³¹ to prevent deep vein thromboses. Sulfasalazine can also be continued perioperatively—but with caution, as it may elevate international normalized ratio (INR) levels in patients receiving warfarin.²⁹ Most other DMARDs should be temporarily discontinued. Leflunomide and interleukin 1 antagonists, such as anakinra, should be stopped 1 to 2 days before surgery and restarted 10 to 14 days after surgery.²⁹ Rituximab should be stopped 1 week before surgery and restarted 10 to 14 days after surgery. Tumor necrosis factor α inhibitors should be discontinued for 2 half-lives before and after surgery.³² Etanercept has a half-life of 3 to 5 days; infliximab, 8 to 10 days; and adalimumab, 10 to 13 days. Most surgeons schedule surgery for the end of a dosing cycle and discontinue these biologic agents for another 10 to 14 days after surgery.

Metabolic Factors

Obese patients are susceptible to longer surgeries, more extensive dissection, poorly vascularized subcutaneous tissue, and higher requirements of weight-adjusted antibiotic dosing.¹³ Body mass index (BMI) of 40 kg/m² or more (morbid obesity) and BMI over 50 kg/m² have been associated with 9 times and 21.3 times increased risk of PJI, respectively.^13,14 Delaying surgery with dietary consultation has been suggested,^33,34 and bariatric surgery before TKA may decrease infection rates by 3.5 times.³⁵

Nutritional markers are considered before arthroplasty. According to most laboratories, a serum transferrin level under 200 mg/dL, albumin level under 3.5 g/dL, and total lymphocyte count under 1500 cells/mm³ indicate malnourishment, which can increase the incidence of wound complications by 5 to 7 times.³⁶ Patients should also have sufficient protein, vitamin, and mineral supplementation, particularly vitamins A and C, zinc, and copper.³⁷Smokers who cease smoking at least 4 to 6 weeks before surgery lower their wound complication rate by up to 26%.^38,39 When nicotine leaves the bloodstream, vasodilation occurs, oxygenation improves, and the immune system recovers.³⁹ Studies have found more SSIs in patients who abuse alcohol,40 and numerous authors have confirmed this finding in the arthroplasty population.^24,41,42 Alcohol inhibits platelet function and may predispose to a postoperative hematoma. In contrast to smoking cessation evidence, evidence regarding alcohol interventions in preventing postoperative infections is less conclusive.^43,44

MRSA Colonization

Methicillin-resistant Staphylococcus aureus (MRSA) is a particularly difficult bacterium to eradicate in PJI. As the mean cost of treating a single case of MRSA-related prosthetic infection is $107,264 vs $68,053 for susceptible strains,45,46 many infection-containment strategies focus on addressing benign MRSA colonization before surgery.

MRSA is present in the nares of 25 million people in the United States. Nasal colonization increases the risk of bacteremia 4-fold⁴⁷ and SSI 2- to 9-fold.^48,49 Nasal swabs are analyzed with either a rapid polymerase chain reaction (PCR) test, which provides results in 2 hours, or a bacterial culture, which provides results in 1 to 4 days. The PCR test is more expensive.

Eradication of MRSA colonization is increasingly prevalent. Several Scandinavian countries have instituted strict practices by which patients are denied elective surgery until negative nasal swabs are obtained.⁴⁹ Nasal decontamination is one method of colonization reduction. Topical mupirocin, which yields eradication in 91% of nasal carriers immediately after treatment and in 87% after 4 weeks,⁵⁰ is effective in reducing SSI rates only when used in conjunction with a body wash, which is used to clean the axilla and groin.⁵¹ There is no consensus on optimal timing, but Bode and colleagues⁵² found a significant decrease in deep SSIs when decontamination occurred just 24 hours before surgery.

Povidone-iodine showers went out of favor with the realization that chlorhexidine gluconate acts longer on the skin surface.^53,54 Preoperative showers involve rinsing with liquid chlorhexidine soap 24 to 48 hours before surgery. However, chlorhexidine binds preferentially to the cotton in washcloths instead of the skin. Edmiston and colleagues^54,55 found that 4% chlorhexidine liquid soaps achieve much lower skin chlorhexidine concentrations than 2% polyester cloths do. Use of these “chlorhexidine wipes” the night before and the day of surgery has decreased PJI after TKA from 2.2% to 0.6%.^56,57

Intraoperative Risk Prevention

Preparation

Which preoperative antibiotic to use is one of the first operative considerations in PJI prophylaxis (Table 2). Cefazolin is recommended as a first-line agent for its excellent soft-tissue penetration, long half-life, and activity against gram-positive bacteria such as skin flora.⁵⁸ Clindamycin may be considered for patients allergic to β-lactam antibiotics. Vancomycin may be considered for adjunctive use with cephalosporins in cases of known MRSA colonization. Vancomycin infusion should be started earlier than infusion with other antibiotics, as vancomycin must be infused slowly and takes longer to become therapeutic.

Antibiotic dosing should be based on local antibiograms, adjusted dosing weight, or BMI.⁵⁹ For revision arthroplasty, preoperative prophylaxis should not be stopped out of fear of affecting operative cultures.⁶⁰ Some surgeons pause antibiotic use if a preoperative joint aspirate has not been obtained. Infusion within 1 hour of incision is part of the pay-for-performance guidelines established by the US Centers for Medicare & Medicaid Services.⁶¹ An antibiotic should be redosed if the operation will take longer than 2 half-lives of the drug.⁵⁹ Surgeons should consider administering a dose every 4 hours or whenever blood loss exceeds 1000 mL.⁶² Engesæter and colleagues⁶³ found that antibiotic prophylaxis was most effective given 4 times perioperatively (1 time before surgery, 3 times after surgery). Postoperative antibiotics should not be administered longer than 24 hours, as prolonged dosing confers no benefit.⁵⁸ Operating room conditions must be optimized for prophylaxis. More people and operating room traffic in nonsterile corridors increase contamination of instruments open to air.⁶⁴ Laminar airflow systems are commonly used. Although there is little dispute that laminar flow decreases the bacterial load of air, there are mixed results regarding its benefit in preventing PJI.^65-68 Skin preparation may address patient risk factors. Hair clipping is preferred to shaving, which may cause microabrasions and increased susceptibility to skin flora.69 Patients should be prepared with antiseptic solution. One randomized controlled trial found that 2% chlorhexidine gluconate mixed with 70% isopropyl alcohol was superior to 10% povidone-iodine in preventing SSIs.⁷⁰ However, a recent cohort study showed a lower rate of superficial wound infections when 1% povidone-iodine (vs 0.5% chlorhexidine) was used with alcohol.⁷¹ This finding may indicate the need for alcohol preparation, higher concentrations of chlorhexidine, or both.

Proper scrubbing and protective gear are needed to reduce surgeon risk factors. Hand washing is a routine part of any surgery. Alcohol-based hand scrubs are as effective as hand scrubbing.65 They reduce local skin flora by 95% immediately and by 99% with repeated applications.⁷² Lidwell and colleagues⁷³ found a 75% reduction in infection when body exhaust suits were used in combination with laminar flow in a multicenter randomized controlled trial of 8052 patients. Sterile draping with impermeable drapes should be done over properly prepared skin. Ioban drapes (3M) are often used as a protective barrier. Interestingly, a Cochrane review found no benefit in using plastic adhesives impregnated with iodine over sterilely prepared skin.⁷⁴

Operative Considerations

Surgical gloves become contaminated in almost one third of cases, half the time during draping.⁷⁵ For this reason, many surgeons change gloves after draping. In addition, double gloving prevents a breech of aseptic technique should the outer glove become perforated.⁷⁶ Demircay and colleagues⁷⁷ assessed double latex gloving in arthroplasty and found the outer and inner gloves perforated in 18.4% and 8.4% of cases, respectively. Punctures are most common along the nondominant index finger, and then the dominant thumb.^77,78 Perforation is more common when 2 latex gloves are worn—vs 1 latex glove plus an outer cloth glove—and the chance of perforation increases with surgery duration. The inner glove may become punctured in up to 100% of operations that last over 3 hours.⁷⁹ Although Dodds and colleagues⁸⁰ found no change in bacterial counts on surgeons’ hands or gloves after perforation, precautions are still recommended. Al-Maiyah and colleagues⁸¹ went as far as to recommend glove changes at 20-minute intervals and before cementation.

Surgical instruments can be sources of contamination. Some authors change the suction tip every hour to minimize the risk of deep wound infection.^82-85 Others change it before femoral canal preparation and prosthesis insertion during THA.⁸⁶ The splash basin is frequently contaminated, and instruments placed in it should not be returned to the operative field.⁸⁷ Hargrove and colleagues⁸⁸ suggested pulsatile lavage decreases PJI more than bulb syringe irrigation does, whereas others argued that high-pressure lavage allows bacteria to penetrate more deeply, which could lead to retention of more bacteria.⁸⁹ Minimizing operating room time was found by Kurtz and colleagues⁹⁰ and Peersman and colleagues⁹¹ to decrease PJI incidence. Carroll and colleagues⁷¹ correlated longer tourniquet use with a higher rate of infection after TKA; proposed mechanisms include local tissue hypoxia and lowered concentrations of prophylactic antibiotics.

Similarly, minimizing blood loss and transfusion needs is another strategy for preventing infection. Allogenic transfusion may increase the risk of PJI 2 times.^23,71,92 The mechanism seems to be immune system modulation by allogenic blood, which impairs microcirculation and oxygen delivery at the surgical site.^23,75 Transfusions should be approached with caution, and consideration given to preoperative optimization and autologous blood donation. Cherian and colleagues⁹³ reviewed different blood management strategies and found preoperative iron therapy, intravenous erythropoietin, and autologous blood donation to be equally effective in reducing the need for allogenic transfusions. Numerous studies of tranexamic acid, thrombin-based hemostatic matrix (Floseal; Baxter Inc), and bipolar sealer with radiofrequency ablation (Aquamantys; Medtronic Inc) have found no alterations in infection rates, but most have used calculated blood loss, not PJI, as the primary endpoint.^94-105 Antibiotic cement also can be used to block infection.^63,106-110 Although liquid gentamicin may weaken bone cement,¹¹¹ most antibiotics, including powdered tobramycin and vancomycin, do not weaken its fatigue strength.^111-114 A recent meta-analysis by Parvizi and colleagues¹¹⁵ revealed that deep infection rates dropped from 2.3% to 1.2% with use of antibiotic cement for primary THAs. Cummins and colleagues,¹¹⁶ however, reported the limited cost-effectiveness of antibiotic cement in primary arthroplasty. Performing povidone-iodine lavage at the end of the case may be a more inexpensive alternative. Brown and colleagues¹¹⁷ found that rinsing with dilute povidone-iodine (.35%) for 3 minutes significantly decreased the incidence of PJI.

Closure techniques and sutures have been a focus of much of the recent literature. Winiarsky and colleagues³⁴ advocated using a longer incision for obese patients and augmenting closure in fattier areas with vertical mattress retention sutures, which are removed after 5 days. A barbed monofilament suture (Quill; Angiotech Inc) is gaining in popularity. Laboratory research has shown that bacteria adhere less to barbed monofilament sutures than to braided sutures.¹¹⁸ Smith and colleagues¹¹⁹ found a statistically nonsignificant higher rate of wound complications with barbed monofilament sutures, whereas Ting and colleagues120 found no difference in complications. These studies were powered to detect differences in time and cost, not postoperative complications. Skin adhesive (Dermabond; Ethicon Inc), also used in closure, may be superior to staples in avoiding superficial skin abscesses.¹²¹ Although expensive, silver-impregnated dressing has antimicrobial activity that reduces PJI incidence by up to 74%.¹²² One brand of this dressing (Aquacel; ConvaTec Inc) has a polyurethane waterproof barrier that allows it to be worn for 7 days.

Three factors commonly mentioned in PJI prevention show little supporting evidence. Drains, which are often used, may create a passage for postoperative infection and are associated with increased transfusion needs.^123,124 Adding antibiotics to irrigation solution¹²⁵ and routinely changing scalpel blades^126-129 also have little supporting evidence. In 2014, the utility of changing scalpel blades after incision was studied by Lee and colleagues,¹³⁰ who reported persistence of Propionibacterium acnes in the dermal layer after skin preparation. Their study, however, was isolated to the upper back region, not the hip or knee.

Postoperative Risk Prevention

Most arthroplasty patients receive anticoagulation after surgery, but it must be used with caution. Large hematomas can predispose to wound complications. Parvizi and colleagues¹³¹ associated wound drainage, hematoma, and subsequent PJI with an INR above 1.5 in the early postoperative period. Therefore, balanced anticoagulation is crucial. Postoperative glucose control is also essential, particularly for patients with diabetes. Although preoperative blood glucose levels may or may not affect PJI risk,^15,17,132 postoperative blood glucose levels of 126 mg/dL or higher are strongly associated with joint infections.¹³³ Even nondiabetic patients with postoperative morning levels over 140 mg/dL are 3 times more likely to develop an infection.¹⁷

Efforts should be made to discharge patients as soon as it is safe to do so. With longer hospital stays, patients are more exposed to nosocomial organisms and increased antibiotic resistance.^5,23,134 Outpatient antibiotics should be considered for dental, gastrointestinal, and genitourinary procedures. Oral antibiotic prophylaxis is controversial, as there is some evidence that dental procedures increase the risk of PJI only minimally.^10,135-138

Conclusion

PJI is a potentially devastating complication of TJA. For this reason, much research has been devoted to proper diagnosis and treatment. Although the literature on PJI prophylaxis is abundant, there is relatively little consensus on appropriate PJI precautions. Preoperative considerations should include medical comorbidities, use of immunocompromising medications, obesity, nutritional factors, smoking, alcohol use, and MRSA colonization. Surgeons must have a consistent intraoperative method of antibiotic administration, skin preparation, scrubbing, draping, gloving, instrument exchange, blood loss management, cementing, and closure. In addition, monitoring of postoperative anticoagulation and blood glucose management is important. Having a thorough understanding of PJI risk factors may help reduce the incidence of this devastating complication.

Although elbow arthroscopy was first described in the 1930s, it has become increasingly popular in the last 30 years.¹ While initially considered as a tool for diagnosis and loose body removal, indications have expanded to include treatment of osteochondritis dissecans (OCD), treatment of lateral epicondylitis, fixation of fractures, and others.^2-5 Miyake and colleagues⁶ found a significant improvement in range of motion, both flexion and extension, and outcome scores when elbow arthroscopy was used to remove impinging osteophytes. Babaqi and colleagues⁷ found significant improvement in pain, satisfaction, and outcome scores in 31 patients who underwent elbow arthroscopy for lateral epicondylitis refractory to nonsurgical management. The technical difficulty of the procedure, lower frequency of pathology amenable to arthroscopic intervention, and potential neurovascular complications make the elbow less frequently evaluated with the arthroscope vs other joints, such as the knee and shoulder.^2,8,9

Geographic distribution of subjects undergoing elbow arthroscopy, the indications used, surgical techniques being performed, and their associated clinical outcomes have received little to no recognition in the peer-reviewed literature.10 Differences in the elbow arthroscopy literature include characteristics related to the patient (age, gender, hand dominance, duration of symptoms), study (level of evidence, number of subjects, number of participating centers, design), indication (lateral epicondylitis, loose bodies, olecranon osteophytes, OCD), surgical technique, and outcome. Evidence-based medicine and clinical practice guidelines direct surgeons in clinical decision-making. Payers investigate the cost of surgical interventions and the value that surgery may provide, while following trends in different surgical techniques. Regulatory agencies and associations emphasize subjective patient-reported outcomes as the primary outcome measured in high-quality trials. Thus, in discussion of complex surgical interventions such as elbow arthroscopy, it is important to characterize the studies, subjects, and surgeries across the world to understand the geographic similarities and differences to optimize care in this clinical situation.

The goal of this study was to perform a systematic review and meta-analysis of elbow arthroscopy literature to identify and compare the characteristics of the studies published, the subjects analyzed, and surgical techniques performed across continents and countries to answer these questions: “Across the world, what demographic of patients are undergoing elbow arthroscopy, what are the most common indications for elbow arthroscopy, and how good is the evidence?” The authors hypothesized that patients who undergo elbow arthroscopy will be largely age <40 years, the most common indication for elbow arthroscopy will be a release/débridement, and the evidence for elbow arthroscopy will be poor. Also, no significant differences will exist in elbow arthroscopy publications, subjects, outcomes, and techniques based on continent/country of publication.

Methods

A systematic review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines using a PRISMA checklist.¹¹ Systematic review registration was performed using the International Prospective Register of Ongoing Systematic Reviews (PROSPERO; registration number, CRD42014010580; registration date, July 15, 2014).¹² Two study authors independently conducted the search on June 23, 2014 using the following databases: Medline, Cochrane Central Register of Controlled Trials, SportDiscus, and CINAHL. The electronic search citation algorithm used was: (elbow) AND arthroscopy) NOT shoulder) NOT knee) NOT ankle) NOT wrist) NOT hip) NOT dog) NOT cadaver). English language Level I-IV evidence (2012 update by the Oxford Centre for Evidence-Based Medicine¹³) clinical studies were eligible for inclusion into this study. Abstracts were ineligible for inclusion. All references in selected studies were cross-referenced for inclusion if they were missed during the initial search. Duplicate subject publications within separate unique studies were not reported twice. The study with longer duration follow-up, higher level of evidence, greater number of subjects, or more detailed subject, surgical technique, or outcome reporting was retained for inclusion. Level V evidence reviews, expert opinion articles, letters to the editor, basic science, biomechanical studies, open elbow surgery, imaging, surgical technique, and classification studies were excluded.

All included patients underwent elbow arthroscopy for either intra- or extra-articular elbow pathology (ulnotrochlear osteoarthritis, lateral epicondylitis, rheumatoid arthritis, post-traumatic contracture, osteonecrosis of the capitellum or radial head, osteoid osteoma, and others). There was no minimum follow-up duration or rehabilitation requirement. The study and subject demographic parameters that we analyzed included year of publication, years of subject enrollment, presence of study financial conflict of interest, number of subjects and elbows, elbow dominance, gender, age, body mass index, diagnoses treated, type of anesthesia (block or general), and surgical positioning. Postoperative splint application and pain management, and whether a continuous passive motion machine was used and whether a drain was placed were recorded. Clinical outcome scores were DASH (Disability of the Arm, Shoulder, and Hand), Morrey score, MEPS (Mayo Elbow Performance Score), Andrews-Carson score, Timmerman-Andrews score, LES (Liverpool Elbow Score), Tegner score, HSS (Hospital for Special Surgery Score), VAS (Visual Analog Scale), EFA (Elbow Functional Assessment), Short Form-12 (SF-12), Short Form-36 (SF-36), Kerlan-Jobe Orthopaedic Clinic (KJOC) Shoulder and Elbow Questionnaire, and MAESS (Modified Andrews Elbow Scoring System). Radiographs, computed tomography (CT), computed tomography arthrography (CTA), magnetic resonance imaging (MRI), and magnetic resonance arthrography (MRA) data were extracted when available. Range of motion (flexion, extension, supination, and pronation) and grip strength data, both preoperative and postoperative, were extracted when available. Study methodological quality was evaluated using the Modified Coleman Methodology Score (MCMS).¹⁴

Statistical Analysis

Study descriptive statistics were calculated. Continuous variable data were reported as weighted means ± weighted standard deviations. Categorical variable data were reported as frequencies with percentages. For all statistical analysis either measured and calculated from study data extraction or directly reported from the individual studies, P < .05 was considered statistically significant. Study, subject, and surgical outcomes data were compared using 1-way analysis of variance (ANOVA) tests. Where applicable, study, subject, and surgical outcomes data were also compared using 2-sample and 2-proportion Z-test calculators with α .05 because of the difference in sample sizes between compared groups. To examine trends over time, Pearson’s correlation coefficients were calculated. For the purposes of analysis, the indications of “osteoarthritis,” “arthrofibrosis,” “loose body removal,” “ulnotrochlear osteoarthritis causing stiffness,” “post-traumatic contracture/stiffness,” and “post-operative elbow contracture” were combined into the indication “release and débridement.” For the 3 most common indications for arthroscopy (OCD, lateral epicondylitis, and release and débridement) data were combined into 5-year increments to overcome the smaller sample size within each of these categories, and Pearson’s correlation coefficients were calculated to determine if number of reported cases covaried with year period. Within these 3 diagnoses, ANOVA analyses were performed to determine whether the number of cases differed between continents and countries.

Results

A total of 353 studies were located, and, after implementation of the exclusion criteria, 112 studies were included in the final analysis (Figure 1; 3093 subjects; 3168 elbows; 64% male; mean age, 34.9 ± 14.68 years). There was a mean of 33.4 ± 26.02 months of follow-up, and 75% of surgeries involved the dominant elbow (Table 1). Most studies were level IV evidence (94.6%), had a low MCMS (mean 28.1 ± 8.06; poor rating), and were single-center investigations (94.6%). Most studies did not report financial conflicts of interest (56.3%) (Tables 1 and 2). From 1985 through 2014, the number of publications significantly increased with time (P = .004) among all continents. The MCMS was unchanged over time (P = .247) (Figure 2A), as was the level of evidence (P = .094) (Figure 2B). Conflicts of interest significantly increased with time (P = .025) (Figure 3).

Among continents, North America published the largest number of studies (54), and had the largest number of patients (1395) and elbow surgeries (1425) (Table 1). The United States published the largest number of studies (43%). There were no significant differences between age (P = .331), length of follow-up (P = .403), MCMS (P = .123), and level of evidence (P = .288) between continents. Of the 32 studies that reported the use of preoperative MRI, studies from Asia reported significantly more MRI scans than those from other continents (P = .040); there were no other significant differences between continents in reference to preoperative imaging studies or other demographic information.

The most common surgical indications were OCD (Figure 4), lateral epicondylitis (Figure 5), and release and débridement (Figure 6, Table 3; all studies listed indications). The number of reported cases for these 3 indications significantly increased over time (OCD P = .005, lateral epicondylitis P = .044, release and débridement P = .042) but did not significantly differ between regions (P > .05 in all cases).

Thirty-two (28.6%) studies reported the use of outcome measures (16 different outcome scores were used by the included studies). Asia reported outcome measures in 9 of 23 studies (39%), Europe in 12 of 35 studies (34%) and North America in 11 of 54 (20%) of studies. The MEPS was the most frequently used outcome score in 9.8% of studies, followed by VAS for pain in 5.3% of cases. North American studies reported a significantly higher increase in extension after elbow arthroscopy than Asia (P = .0432) (Figure 7), with no differences in flexion (P = .699), pronation (P = .376), or supination (P = .408). No significant differences were observed between continents in the type of anesthesia chosen (general anesthesia [P = .94] or regional anesthesia [P = .85]). Asia and Europe performed elbow arthroscopy most frequently in the lateral decubitus position, while North American studies most often used the supine position (Table 4).

Twenty (17.9%) studies reported the use of a postoperative splint, 12 (10.7%) studies reported use of a drain, 2 (1.79%) studies reported use of a hinged elbow brace, 9 (8.03%) studies reported use of a continuous passive motion machine postoperatively, and 3 (2.68%) studies reported use of an indwelling axillary catheter for postoperative pain management. Of 130 reported surgical complications (4.1%), the most frequent complication was transient sensory ulnar nerve palsy (1.5%), followed by persistent wound drainage (.76%), and transient sensory radial nerve palsy (.38%). Other reported complications included infection (.22%), transient sensory palsy of the median nerve (.19%), heterotopic ossification (.13%), complete transection of the ulnar nerve (.10%), loose body formation (.06%), hematoma formation (.06%), transient sensory palsy of the posterior interosseous (.06%), or anterior interosseous nerve (.03%), and complete transection of the radial (.03%), or median nerve (.03%).

Discussion

Elbow arthroscopy is an evolving surgical procedure that is used to treat intra- and extra-articular pathologies of the elbow. Outcomes of elbow arthroscopy for certain conditions have generally been reported as good, with improvements seen in pain, functional scores, and range of motion.^6,15-17 The authors’ hypotheses were mostly confirmed in that the average age of patients undergoing elbow arthroscopy was <40 years, release/débridement was one of the most common indications (along with lateral epicondylitis and OCD), and the general evidence for elbow arthroscopy was poor. Also, there were almost no differences between continents/countries related to patient indications, preoperative imaging, anesthesia choice, indications, postoperative protocols, and outcomes (although the number of studies that reported outcomes was low and could have skewed the results), with the exception of a higher number of preoperative MRI scans in Asia. Some of the notable findings of this study included: 1) the number of studies published on elbow arthroscopy is significantly increasing with time, despite a lack of improvement in the level of evidence; 2) the majority of studies on elbow arthroscopy do not report a surgical outcome score; and 3) the number of reported cases for the 3 most common indications significantly increased over time (OCD, P = .005; lateral epicondylitis, P = .044; release and débridement, P = .042) but did not differ between regions (P > .05 in all cases).

The indications for elbow arthroscopy have grown dramatically in the past 2 decades to include both intra- and extra-articular pathologies.¹⁸ Despite this increase in the number of indications for elbow arthroscopy, the study did not find a significant difference between countries/continents in the indications each used for elbow arthroscopy patients. There was a trend towards an increase in OCD cases in all continents, especially Asia (Figure 4), with time. Interestingly, while not statistically significant, there was variation among countries for surgical indications. In North America, removal of loose bodies accounts for 18% of patients, while in Europe this accounted for only 9% and in Asia for 1%. Post-traumatic stiffness was the indication for elbow arthroscopy in Europe in 19% of patients vs 7% in North America and 10% in Asia. In Asia, OCD accounts for 40% of arthroscopies, 7% in Europe, and 14% in North America (Figure 4) (Table 3).

This study demonstrated that the mean increase in elbow extension gained after surgery in North America was significantly greater when compared with studies from Asia, but the gain in flexion, pronation, and supination was similar across continents. The underlying cause of this difference in improvement in elbow extension between nations is unclear, although differences in diagnosis could account for some variation. This study did not examine differences in rehabilitation protocols, and certainly, it is plausible that protocol variations by country could account for some discrepancy. Furthermore, differences in functional needs may vary by continent and could have driven this result.

This study found no routine reporting of outcome scores by elbow arthroscopy studies from any continent, and that when outcome scores are reported, there is substantial inconsistency with regard to the actual scoring system used. No continent reported outcome scores in more than 40% of the studies published from that area, and the variation of outcome scores used, even from a single region, was large. This makes comparing clinical outcomes between studies difficult, even when performing identical procedures for identical indications, because there is no standardized method of reporting outcomes. To allow comparison of studies and generalizability of the results to different populations, a more standardized approach to outcome reporting needs to be instituted in the elbow arthroscopy literature. To date, there is no standardized score that has been validated for reporting clinical outcomes after elbow arthroscopy.19 Hence, it is not surprising that there were 16 different outcome scores reported throughout the 112 studies analyzed in this review, with the most frequent score, the MEPS, reported in a total of 10 studies. As medicine moves towards pay scales that are based on patient outcomes, it will become more important to define a clear outcome score that can be used to assess these patients, and reliably report scores. This will allow comparison of patients across nations to determine the best surgical treatment for different clinical problems. A validation study comparing these outcome scores to determine which score best summarizes the patient’s level of pain and function after surgery would be beneficial, because this could identify 1 score that could be standardized to allow comparison among reported outcomes.

Limitations

This study had several limitations. Despite having 2 authors search independently for studies, some studies could have been missed during the search process, introducing possible selection bias. Including only published studies could have introduced publication bias. Numerous studies did not report all the variables the authors examined. This could have skewed some results, and had additional variables been reported, could have altered the data to show significant differences in some measured variables. Because this study did not compare outcome measures for varying pathologies, conclusions cannot be drawn on the best treatment options for different indications. Case reports could have lowered the MCMS score and the average in studies reporting outcomes. Furthermore, the poor quality of the underlying data used in this study could limit the validity/generalizability of the results because this is a systematic review, and its level of evidence is only as high as the studies it includes. Because the primary aim was to report on demographics, this study did not examine concomitant pathology at the time of surgery or rehabilitation protocols.

Conclusion

The quantity, but not the quality, of arthroscopic elbow publications has significantly increased over time. Most patients undergo elbow arthroscopy for lateral epicondylitis, OCD, and release and débridement. Pathology and indications do not appear to differ geographically with more men undergoing elbow arthroscopy than women.

Although elbow arthroscopy was first described in the 1930s, it has become increasingly popular in the last 30 years.¹ While initially considered as a tool for diagnosis and loose body removal, indications have expanded to include treatment of osteochondritis dissecans (OCD), treatment of lateral epicondylitis, fixation of fractures, and others.^2-5 Miyake and colleagues⁶ found a significant improvement in range of motion, both flexion and extension, and outcome scores when elbow arthroscopy was used to remove impinging osteophytes. Babaqi and colleagues⁷ found significant improvement in pain, satisfaction, and outcome scores in 31 patients who underwent elbow arthroscopy for lateral epicondylitis refractory to nonsurgical management. The technical difficulty of the procedure, lower frequency of pathology amenable to arthroscopic intervention, and potential neurovascular complications make the elbow less frequently evaluated with the arthroscope vs other joints, such as the knee and shoulder.^2,8,9

Geographic distribution of subjects undergoing elbow arthroscopy, the indications used, surgical techniques being performed, and their associated clinical outcomes have received little to no recognition in the peer-reviewed literature.10 Differences in the elbow arthroscopy literature include characteristics related to the patient (age, gender, hand dominance, duration of symptoms), study (level of evidence, number of subjects, number of participating centers, design), indication (lateral epicondylitis, loose bodies, olecranon osteophytes, OCD), surgical technique, and outcome. Evidence-based medicine and clinical practice guidelines direct surgeons in clinical decision-making. Payers investigate the cost of surgical interventions and the value that surgery may provide, while following trends in different surgical techniques. Regulatory agencies and associations emphasize subjective patient-reported outcomes as the primary outcome measured in high-quality trials. Thus, in discussion of complex surgical interventions such as elbow arthroscopy, it is important to characterize the studies, subjects, and surgeries across the world to understand the geographic similarities and differences to optimize care in this clinical situation.

The goal of this study was to perform a systematic review and meta-analysis of elbow arthroscopy literature to identify and compare the characteristics of the studies published, the subjects analyzed, and surgical techniques performed across continents and countries to answer these questions: “Across the world, what demographic of patients are undergoing elbow arthroscopy, what are the most common indications for elbow arthroscopy, and how good is the evidence?” The authors hypothesized that patients who undergo elbow arthroscopy will be largely age <40 years, the most common indication for elbow arthroscopy will be a release/débridement, and the evidence for elbow arthroscopy will be poor. Also, no significant differences will exist in elbow arthroscopy publications, subjects, outcomes, and techniques based on continent/country of publication.

Methods

A systematic review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines using a PRISMA checklist.¹¹ Systematic review registration was performed using the International Prospective Register of Ongoing Systematic Reviews (PROSPERO; registration number, CRD42014010580; registration date, July 15, 2014).¹² Two study authors independently conducted the search on June 23, 2014 using the following databases: Medline, Cochrane Central Register of Controlled Trials, SportDiscus, and CINAHL. The electronic search citation algorithm used was: (elbow) AND arthroscopy) NOT shoulder) NOT knee) NOT ankle) NOT wrist) NOT hip) NOT dog) NOT cadaver). English language Level I-IV evidence (2012 update by the Oxford Centre for Evidence-Based Medicine¹³) clinical studies were eligible for inclusion into this study. Abstracts were ineligible for inclusion. All references in selected studies were cross-referenced for inclusion if they were missed during the initial search. Duplicate subject publications within separate unique studies were not reported twice. The study with longer duration follow-up, higher level of evidence, greater number of subjects, or more detailed subject, surgical technique, or outcome reporting was retained for inclusion. Level V evidence reviews, expert opinion articles, letters to the editor, basic science, biomechanical studies, open elbow surgery, imaging, surgical technique, and classification studies were excluded.

All included patients underwent elbow arthroscopy for either intra- or extra-articular elbow pathology (ulnotrochlear osteoarthritis, lateral epicondylitis, rheumatoid arthritis, post-traumatic contracture, osteonecrosis of the capitellum or radial head, osteoid osteoma, and others). There was no minimum follow-up duration or rehabilitation requirement. The study and subject demographic parameters that we analyzed included year of publication, years of subject enrollment, presence of study financial conflict of interest, number of subjects and elbows, elbow dominance, gender, age, body mass index, diagnoses treated, type of anesthesia (block or general), and surgical positioning. Postoperative splint application and pain management, and whether a continuous passive motion machine was used and whether a drain was placed were recorded. Clinical outcome scores were DASH (Disability of the Arm, Shoulder, and Hand), Morrey score, MEPS (Mayo Elbow Performance Score), Andrews-Carson score, Timmerman-Andrews score, LES (Liverpool Elbow Score), Tegner score, HSS (Hospital for Special Surgery Score), VAS (Visual Analog Scale), EFA (Elbow Functional Assessment), Short Form-12 (SF-12), Short Form-36 (SF-36), Kerlan-Jobe Orthopaedic Clinic (KJOC) Shoulder and Elbow Questionnaire, and MAESS (Modified Andrews Elbow Scoring System). Radiographs, computed tomography (CT), computed tomography arthrography (CTA), magnetic resonance imaging (MRI), and magnetic resonance arthrography (MRA) data were extracted when available. Range of motion (flexion, extension, supination, and pronation) and grip strength data, both preoperative and postoperative, were extracted when available. Study methodological quality was evaluated using the Modified Coleman Methodology Score (MCMS).¹⁴

Statistical Analysis

Study descriptive statistics were calculated. Continuous variable data were reported as weighted means ± weighted standard deviations. Categorical variable data were reported as frequencies with percentages. For all statistical analysis either measured and calculated from study data extraction or directly reported from the individual studies, P < .05 was considered statistically significant. Study, subject, and surgical outcomes data were compared using 1-way analysis of variance (ANOVA) tests. Where applicable, study, subject, and surgical outcomes data were also compared using 2-sample and 2-proportion Z-test calculators with α .05 because of the difference in sample sizes between compared groups. To examine trends over time, Pearson’s correlation coefficients were calculated. For the purposes of analysis, the indications of “osteoarthritis,” “arthrofibrosis,” “loose body removal,” “ulnotrochlear osteoarthritis causing stiffness,” “post-traumatic contracture/stiffness,” and “post-operative elbow contracture” were combined into the indication “release and débridement.” For the 3 most common indications for arthroscopy (OCD, lateral epicondylitis, and release and débridement) data were combined into 5-year increments to overcome the smaller sample size within each of these categories, and Pearson’s correlation coefficients were calculated to determine if number of reported cases covaried with year period. Within these 3 diagnoses, ANOVA analyses were performed to determine whether the number of cases differed between continents and countries.

Results

A total of 353 studies were located, and, after implementation of the exclusion criteria, 112 studies were included in the final analysis (Figure 1; 3093 subjects; 3168 elbows; 64% male; mean age, 34.9 ± 14.68 years). There was a mean of 33.4 ± 26.02 months of follow-up, and 75% of surgeries involved the dominant elbow (Table 1). Most studies were level IV evidence (94.6%), had a low MCMS (mean 28.1 ± 8.06; poor rating), and were single-center investigations (94.6%). Most studies did not report financial conflicts of interest (56.3%) (Tables 1 and 2). From 1985 through 2014, the number of publications significantly increased with time (P = .004) among all continents. The MCMS was unchanged over time (P = .247) (Figure 2A), as was the level of evidence (P = .094) (Figure 2B). Conflicts of interest significantly increased with time (P = .025) (Figure 3).

Among continents, North America published the largest number of studies (54), and had the largest number of patients (1395) and elbow surgeries (1425) (Table 1). The United States published the largest number of studies (43%). There were no significant differences between age (P = .331), length of follow-up (P = .403), MCMS (P = .123), and level of evidence (P = .288) between continents. Of the 32 studies that reported the use of preoperative MRI, studies from Asia reported significantly more MRI scans than those from other continents (P = .040); there were no other significant differences between continents in reference to preoperative imaging studies or other demographic information.

The most common surgical indications were OCD (Figure 4), lateral epicondylitis (Figure 5), and release and débridement (Figure 6, Table 3; all studies listed indications). The number of reported cases for these 3 indications significantly increased over time (OCD P = .005, lateral epicondylitis P = .044, release and débridement P = .042) but did not significantly differ between regions (P > .05 in all cases).

Thirty-two (28.6%) studies reported the use of outcome measures (16 different outcome scores were used by the included studies). Asia reported outcome measures in 9 of 23 studies (39%), Europe in 12 of 35 studies (34%) and North America in 11 of 54 (20%) of studies. The MEPS was the most frequently used outcome score in 9.8% of studies, followed by VAS for pain in 5.3% of cases. North American studies reported a significantly higher increase in extension after elbow arthroscopy than Asia (P = .0432) (Figure 7), with no differences in flexion (P = .699), pronation (P = .376), or supination (P = .408). No significant differences were observed between continents in the type of anesthesia chosen (general anesthesia [P = .94] or regional anesthesia [P = .85]). Asia and Europe performed elbow arthroscopy most frequently in the lateral decubitus position, while North American studies most often used the supine position (Table 4).

Twenty (17.9%) studies reported the use of a postoperative splint, 12 (10.7%) studies reported use of a drain, 2 (1.79%) studies reported use of a hinged elbow brace, 9 (8.03%) studies reported use of a continuous passive motion machine postoperatively, and 3 (2.68%) studies reported use of an indwelling axillary catheter for postoperative pain management. Of 130 reported surgical complications (4.1%), the most frequent complication was transient sensory ulnar nerve palsy (1.5%), followed by persistent wound drainage (.76%), and transient sensory radial nerve palsy (.38%). Other reported complications included infection (.22%), transient sensory palsy of the median nerve (.19%), heterotopic ossification (.13%), complete transection of the ulnar nerve (.10%), loose body formation (.06%), hematoma formation (.06%), transient sensory palsy of the posterior interosseous (.06%), or anterior interosseous nerve (.03%), and complete transection of the radial (.03%), or median nerve (.03%).

Discussion

Elbow arthroscopy is an evolving surgical procedure that is used to treat intra- and extra-articular pathologies of the elbow. Outcomes of elbow arthroscopy for certain conditions have generally been reported as good, with improvements seen in pain, functional scores, and range of motion.^6,15-17 The authors’ hypotheses were mostly confirmed in that the average age of patients undergoing elbow arthroscopy was <40 years, release/débridement was one of the most common indications (along with lateral epicondylitis and OCD), and the general evidence for elbow arthroscopy was poor. Also, there were almost no differences between continents/countries related to patient indications, preoperative imaging, anesthesia choice, indications, postoperative protocols, and outcomes (although the number of studies that reported outcomes was low and could have skewed the results), with the exception of a higher number of preoperative MRI scans in Asia. Some of the notable findings of this study included: 1) the number of studies published on elbow arthroscopy is significantly increasing with time, despite a lack of improvement in the level of evidence; 2) the majority of studies on elbow arthroscopy do not report a surgical outcome score; and 3) the number of reported cases for the 3 most common indications significantly increased over time (OCD, P = .005; lateral epicondylitis, P = .044; release and débridement, P = .042) but did not differ between regions (P > .05 in all cases).

The indications for elbow arthroscopy have grown dramatically in the past 2 decades to include both intra- and extra-articular pathologies.¹⁸ Despite this increase in the number of indications for elbow arthroscopy, the study did not find a significant difference between countries/continents in the indications each used for elbow arthroscopy patients. There was a trend towards an increase in OCD cases in all continents, especially Asia (Figure 4), with time. Interestingly, while not statistically significant, there was variation among countries for surgical indications. In North America, removal of loose bodies accounts for 18% of patients, while in Europe this accounted for only 9% and in Asia for 1%. Post-traumatic stiffness was the indication for elbow arthroscopy in Europe in 19% of patients vs 7% in North America and 10% in Asia. In Asia, OCD accounts for 40% of arthroscopies, 7% in Europe, and 14% in North America (Figure 4) (Table 3).

This study demonstrated that the mean increase in elbow extension gained after surgery in North America was significantly greater when compared with studies from Asia, but the gain in flexion, pronation, and supination was similar across continents. The underlying cause of this difference in improvement in elbow extension between nations is unclear, although differences in diagnosis could account for some variation. This study did not examine differences in rehabilitation protocols, and certainly, it is plausible that protocol variations by country could account for some discrepancy. Furthermore, differences in functional needs may vary by continent and could have driven this result.

This study found no routine reporting of outcome scores by elbow arthroscopy studies from any continent, and that when outcome scores are reported, there is substantial inconsistency with regard to the actual scoring system used. No continent reported outcome scores in more than 40% of the studies published from that area, and the variation of outcome scores used, even from a single region, was large. This makes comparing clinical outcomes between studies difficult, even when performing identical procedures for identical indications, because there is no standardized method of reporting outcomes. To allow comparison of studies and generalizability of the results to different populations, a more standardized approach to outcome reporting needs to be instituted in the elbow arthroscopy literature. To date, there is no standardized score that has been validated for reporting clinical outcomes after elbow arthroscopy.19 Hence, it is not surprising that there were 16 different outcome scores reported throughout the 112 studies analyzed in this review, with the most frequent score, the MEPS, reported in a total of 10 studies. As medicine moves towards pay scales that are based on patient outcomes, it will become more important to define a clear outcome score that can be used to assess these patients, and reliably report scores. This will allow comparison of patients across nations to determine the best surgical treatment for different clinical problems. A validation study comparing these outcome scores to determine which score best summarizes the patient’s level of pain and function after surgery would be beneficial, because this could identify 1 score that could be standardized to allow comparison among reported outcomes.

Limitations

This study had several limitations. Despite having 2 authors search independently for studies, some studies could have been missed during the search process, introducing possible selection bias. Including only published studies could have introduced publication bias. Numerous studies did not report all the variables the authors examined. This could have skewed some results, and had additional variables been reported, could have altered the data to show significant differences in some measured variables. Because this study did not compare outcome measures for varying pathologies, conclusions cannot be drawn on the best treatment options for different indications. Case reports could have lowered the MCMS score and the average in studies reporting outcomes. Furthermore, the poor quality of the underlying data used in this study could limit the validity/generalizability of the results because this is a systematic review, and its level of evidence is only as high as the studies it includes. Because the primary aim was to report on demographics, this study did not examine concomitant pathology at the time of surgery or rehabilitation protocols.

Conclusion

The quantity, but not the quality, of arthroscopic elbow publications has significantly increased over time. Most patients undergo elbow arthroscopy for lateral epicondylitis, OCD, and release and débridement. Pathology and indications do not appear to differ geographically with more men undergoing elbow arthroscopy than women.

Although elbow arthroscopy was first described in the 1930s, it has become increasingly popular in the last 30 years.¹ While initially considered as a tool for diagnosis and loose body removal, indications have expanded to include treatment of osteochondritis dissecans (OCD), treatment of lateral epicondylitis, fixation of fractures, and others.^2-5 Miyake and colleagues⁶ found a significant improvement in range of motion, both flexion and extension, and outcome scores when elbow arthroscopy was used to remove impinging osteophytes. Babaqi and colleagues⁷ found significant improvement in pain, satisfaction, and outcome scores in 31 patients who underwent elbow arthroscopy for lateral epicondylitis refractory to nonsurgical management. The technical difficulty of the procedure, lower frequency of pathology amenable to arthroscopic intervention, and potential neurovascular complications make the elbow less frequently evaluated with the arthroscope vs other joints, such as the knee and shoulder.^2,8,9

Geographic distribution of subjects undergoing elbow arthroscopy, the indications used, surgical techniques being performed, and their associated clinical outcomes have received little to no recognition in the peer-reviewed literature.10 Differences in the elbow arthroscopy literature include characteristics related to the patient (age, gender, hand dominance, duration of symptoms), study (level of evidence, number of subjects, number of participating centers, design), indication (lateral epicondylitis, loose bodies, olecranon osteophytes, OCD), surgical technique, and outcome. Evidence-based medicine and clinical practice guidelines direct surgeons in clinical decision-making. Payers investigate the cost of surgical interventions and the value that surgery may provide, while following trends in different surgical techniques. Regulatory agencies and associations emphasize subjective patient-reported outcomes as the primary outcome measured in high-quality trials. Thus, in discussion of complex surgical interventions such as elbow arthroscopy, it is important to characterize the studies, subjects, and surgeries across the world to understand the geographic similarities and differences to optimize care in this clinical situation.

The goal of this study was to perform a systematic review and meta-analysis of elbow arthroscopy literature to identify and compare the characteristics of the studies published, the subjects analyzed, and surgical techniques performed across continents and countries to answer these questions: “Across the world, what demographic of patients are undergoing elbow arthroscopy, what are the most common indications for elbow arthroscopy, and how good is the evidence?” The authors hypothesized that patients who undergo elbow arthroscopy will be largely age <40 years, the most common indication for elbow arthroscopy will be a release/débridement, and the evidence for elbow arthroscopy will be poor. Also, no significant differences will exist in elbow arthroscopy publications, subjects, outcomes, and techniques based on continent/country of publication.

Methods

A systematic review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines using a PRISMA checklist.¹¹ Systematic review registration was performed using the International Prospective Register of Ongoing Systematic Reviews (PROSPERO; registration number, CRD42014010580; registration date, July 15, 2014).¹² Two study authors independently conducted the search on June 23, 2014 using the following databases: Medline, Cochrane Central Register of Controlled Trials, SportDiscus, and CINAHL. The electronic search citation algorithm used was: (elbow) AND arthroscopy) NOT shoulder) NOT knee) NOT ankle) NOT wrist) NOT hip) NOT dog) NOT cadaver). English language Level I-IV evidence (2012 update by the Oxford Centre for Evidence-Based Medicine¹³) clinical studies were eligible for inclusion into this study. Abstracts were ineligible for inclusion. All references in selected studies were cross-referenced for inclusion if they were missed during the initial search. Duplicate subject publications within separate unique studies were not reported twice. The study with longer duration follow-up, higher level of evidence, greater number of subjects, or more detailed subject, surgical technique, or outcome reporting was retained for inclusion. Level V evidence reviews, expert opinion articles, letters to the editor, basic science, biomechanical studies, open elbow surgery, imaging, surgical technique, and classification studies were excluded.

All included patients underwent elbow arthroscopy for either intra- or extra-articular elbow pathology (ulnotrochlear osteoarthritis, lateral epicondylitis, rheumatoid arthritis, post-traumatic contracture, osteonecrosis of the capitellum or radial head, osteoid osteoma, and others). There was no minimum follow-up duration or rehabilitation requirement. The study and subject demographic parameters that we analyzed included year of publication, years of subject enrollment, presence of study financial conflict of interest, number of subjects and elbows, elbow dominance, gender, age, body mass index, diagnoses treated, type of anesthesia (block or general), and surgical positioning. Postoperative splint application and pain management, and whether a continuous passive motion machine was used and whether a drain was placed were recorded. Clinical outcome scores were DASH (Disability of the Arm, Shoulder, and Hand), Morrey score, MEPS (Mayo Elbow Performance Score), Andrews-Carson score, Timmerman-Andrews score, LES (Liverpool Elbow Score), Tegner score, HSS (Hospital for Special Surgery Score), VAS (Visual Analog Scale), EFA (Elbow Functional Assessment), Short Form-12 (SF-12), Short Form-36 (SF-36), Kerlan-Jobe Orthopaedic Clinic (KJOC) Shoulder and Elbow Questionnaire, and MAESS (Modified Andrews Elbow Scoring System). Radiographs, computed tomography (CT), computed tomography arthrography (CTA), magnetic resonance imaging (MRI), and magnetic resonance arthrography (MRA) data were extracted when available. Range of motion (flexion, extension, supination, and pronation) and grip strength data, both preoperative and postoperative, were extracted when available. Study methodological quality was evaluated using the Modified Coleman Methodology Score (MCMS).¹⁴

Statistical Analysis

Study descriptive statistics were calculated. Continuous variable data were reported as weighted means ± weighted standard deviations. Categorical variable data were reported as frequencies with percentages. For all statistical analysis either measured and calculated from study data extraction or directly reported from the individual studies, P < .05 was considered statistically significant. Study, subject, and surgical outcomes data were compared using 1-way analysis of variance (ANOVA) tests. Where applicable, study, subject, and surgical outcomes data were also compared using 2-sample and 2-proportion Z-test calculators with α .05 because of the difference in sample sizes between compared groups. To examine trends over time, Pearson’s correlation coefficients were calculated. For the purposes of analysis, the indications of “osteoarthritis,” “arthrofibrosis,” “loose body removal,” “ulnotrochlear osteoarthritis causing stiffness,” “post-traumatic contracture/stiffness,” and “post-operative elbow contracture” were combined into the indication “release and débridement.” For the 3 most common indications for arthroscopy (OCD, lateral epicondylitis, and release and débridement) data were combined into 5-year increments to overcome the smaller sample size within each of these categories, and Pearson’s correlation coefficients were calculated to determine if number of reported cases covaried with year period. Within these 3 diagnoses, ANOVA analyses were performed to determine whether the number of cases differed between continents and countries.

Results

A total of 353 studies were located, and, after implementation of the exclusion criteria, 112 studies were included in the final analysis (Figure 1; 3093 subjects; 3168 elbows; 64% male; mean age, 34.9 ± 14.68 years). There was a mean of 33.4 ± 26.02 months of follow-up, and 75% of surgeries involved the dominant elbow (Table 1). Most studies were level IV evidence (94.6%), had a low MCMS (mean 28.1 ± 8.06; poor rating), and were single-center investigations (94.6%). Most studies did not report financial conflicts of interest (56.3%) (Tables 1 and 2). From 1985 through 2014, the number of publications significantly increased with time (P = .004) among all continents. The MCMS was unchanged over time (P = .247) (Figure 2A), as was the level of evidence (P = .094) (Figure 2B). Conflicts of interest significantly increased with time (P = .025) (Figure 3).

Among continents, North America published the largest number of studies (54), and had the largest number of patients (1395) and elbow surgeries (1425) (Table 1). The United States published the largest number of studies (43%). There were no significant differences between age (P = .331), length of follow-up (P = .403), MCMS (P = .123), and level of evidence (P = .288) between continents. Of the 32 studies that reported the use of preoperative MRI, studies from Asia reported significantly more MRI scans than those from other continents (P = .040); there were no other significant differences between continents in reference to preoperative imaging studies or other demographic information.

The most common surgical indications were OCD (Figure 4), lateral epicondylitis (Figure 5), and release and débridement (Figure 6, Table 3; all studies listed indications). The number of reported cases for these 3 indications significantly increased over time (OCD P = .005, lateral epicondylitis P = .044, release and débridement P = .042) but did not significantly differ between regions (P > .05 in all cases).

Thirty-two (28.6%) studies reported the use of outcome measures (16 different outcome scores were used by the included studies). Asia reported outcome measures in 9 of 23 studies (39%), Europe in 12 of 35 studies (34%) and North America in 11 of 54 (20%) of studies. The MEPS was the most frequently used outcome score in 9.8% of studies, followed by VAS for pain in 5.3% of cases. North American studies reported a significantly higher increase in extension after elbow arthroscopy than Asia (P = .0432) (Figure 7), with no differences in flexion (P = .699), pronation (P = .376), or supination (P = .408). No significant differences were observed between continents in the type of anesthesia chosen (general anesthesia [P = .94] or regional anesthesia [P = .85]). Asia and Europe performed elbow arthroscopy most frequently in the lateral decubitus position, while North American studies most often used the supine position (Table 4).

Twenty (17.9%) studies reported the use of a postoperative splint, 12 (10.7%) studies reported use of a drain, 2 (1.79%) studies reported use of a hinged elbow brace, 9 (8.03%) studies reported use of a continuous passive motion machine postoperatively, and 3 (2.68%) studies reported use of an indwelling axillary catheter for postoperative pain management. Of 130 reported surgical complications (4.1%), the most frequent complication was transient sensory ulnar nerve palsy (1.5%), followed by persistent wound drainage (.76%), and transient sensory radial nerve palsy (.38%). Other reported complications included infection (.22%), transient sensory palsy of the median nerve (.19%), heterotopic ossification (.13%), complete transection of the ulnar nerve (.10%), loose body formation (.06%), hematoma formation (.06%), transient sensory palsy of the posterior interosseous (.06%), or anterior interosseous nerve (.03%), and complete transection of the radial (.03%), or median nerve (.03%).

Discussion

Elbow arthroscopy is an evolving surgical procedure that is used to treat intra- and extra-articular pathologies of the elbow. Outcomes of elbow arthroscopy for certain conditions have generally been reported as good, with improvements seen in pain, functional scores, and range of motion.^6,15-17 The authors’ hypotheses were mostly confirmed in that the average age of patients undergoing elbow arthroscopy was <40 years, release/débridement was one of the most common indications (along with lateral epicondylitis and OCD), and the general evidence for elbow arthroscopy was poor. Also, there were almost no differences between continents/countries related to patient indications, preoperative imaging, anesthesia choice, indications, postoperative protocols, and outcomes (although the number of studies that reported outcomes was low and could have skewed the results), with the exception of a higher number of preoperative MRI scans in Asia. Some of the notable findings of this study included: 1) the number of studies published on elbow arthroscopy is significantly increasing with time, despite a lack of improvement in the level of evidence; 2) the majority of studies on elbow arthroscopy do not report a surgical outcome score; and 3) the number of reported cases for the 3 most common indications significantly increased over time (OCD, P = .005; lateral epicondylitis, P = .044; release and débridement, P = .042) but did not differ between regions (P > .05 in all cases).

The indications for elbow arthroscopy have grown dramatically in the past 2 decades to include both intra- and extra-articular pathologies.¹⁸ Despite this increase in the number of indications for elbow arthroscopy, the study did not find a significant difference between countries/continents in the indications each used for elbow arthroscopy patients. There was a trend towards an increase in OCD cases in all continents, especially Asia (Figure 4), with time. Interestingly, while not statistically significant, there was variation among countries for surgical indications. In North America, removal of loose bodies accounts for 18% of patients, while in Europe this accounted for only 9% and in Asia for 1%. Post-traumatic stiffness was the indication for elbow arthroscopy in Europe in 19% of patients vs 7% in North America and 10% in Asia. In Asia, OCD accounts for 40% of arthroscopies, 7% in Europe, and 14% in North America (Figure 4) (Table 3).

This study demonstrated that the mean increase in elbow extension gained after surgery in North America was significantly greater when compared with studies from Asia, but the gain in flexion, pronation, and supination was similar across continents. The underlying cause of this difference in improvement in elbow extension between nations is unclear, although differences in diagnosis could account for some variation. This study did not examine differences in rehabilitation protocols, and certainly, it is plausible that protocol variations by country could account for some discrepancy. Furthermore, differences in functional needs may vary by continent and could have driven this result.

This study found no routine reporting of outcome scores by elbow arthroscopy studies from any continent, and that when outcome scores are reported, there is substantial inconsistency with regard to the actual scoring system used. No continent reported outcome scores in more than 40% of the studies published from that area, and the variation of outcome scores used, even from a single region, was large. This makes comparing clinical outcomes between studies difficult, even when performing identical procedures for identical indications, because there is no standardized method of reporting outcomes. To allow comparison of studies and generalizability of the results to different populations, a more standardized approach to outcome reporting needs to be instituted in the elbow arthroscopy literature. To date, there is no standardized score that has been validated for reporting clinical outcomes after elbow arthroscopy.19 Hence, it is not surprising that there were 16 different outcome scores reported throughout the 112 studies analyzed in this review, with the most frequent score, the MEPS, reported in a total of 10 studies. As medicine moves towards pay scales that are based on patient outcomes, it will become more important to define a clear outcome score that can be used to assess these patients, and reliably report scores. This will allow comparison of patients across nations to determine the best surgical treatment for different clinical problems. A validation study comparing these outcome scores to determine which score best summarizes the patient’s level of pain and function after surgery would be beneficial, because this could identify 1 score that could be standardized to allow comparison among reported outcomes.

Limitations

This study had several limitations. Despite having 2 authors search independently for studies, some studies could have been missed during the search process, introducing possible selection bias. Including only published studies could have introduced publication bias. Numerous studies did not report all the variables the authors examined. This could have skewed some results, and had additional variables been reported, could have altered the data to show significant differences in some measured variables. Because this study did not compare outcome measures for varying pathologies, conclusions cannot be drawn on the best treatment options for different indications. Case reports could have lowered the MCMS score and the average in studies reporting outcomes. Furthermore, the poor quality of the underlying data used in this study could limit the validity/generalizability of the results because this is a systematic review, and its level of evidence is only as high as the studies it includes. Because the primary aim was to report on demographics, this study did not examine concomitant pathology at the time of surgery or rehabilitation protocols.

Conclusion

The quantity, but not the quality, of arthroscopic elbow publications has significantly increased over time. Most patients undergo elbow arthroscopy for lateral epicondylitis, OCD, and release and débridement. Pathology and indications do not appear to differ geographically with more men undergoing elbow arthroscopy than women.

Stand Up To Cancer is calling for proposals to investigate additional uses for nivolumab, ipilimumab, elotuzumab, and urelumab, as part of a new researcher-industry collaborative program.

As many as four projects will be funded by Bristol-Myers Squibb, maker of the four agents, in the range of $1 million to $3 million each, according to a written statement from the American Association for Cancer Research (AACR).

The company will provide access to the three drugs already approved for the treatement of various cancers –nivolumab, ipilimumab, and elotuzumab– and to urelumab, an investigational agent that is currently in early clinical trials.

Proposals can include the study of one or more of the products, alone or in combination with other treatments, and may include products from other companies, as well as explore potential new uses for the drug(s), AACR said in the statement.

Nivolumab (Opdivo) is currently approved to treat advanced melanoma, non-small cell lung cancer, renal cell carcinoma, and classical Hodgkin lymphoma; Ipilimumab (Yervoy) is approved to treat melanoma; and elotuzumab (Empliciti) is approved to treat multiple myeloma, in conjunction with other drugs. Urelumab is being evaluated as a treatment for a range of cancers, including some hematological cancers, advanced colorectal cancer, and head and neck cancers.

The Stand Up To Cancer (SU2C) Catalyst program was launched in April to “use funding and materials from the pharmaceutical, biotechnology, diagnostic, and medical devices industries to accelerate research on cancer prevention, detection, and treatment,” according to a written statement from SU2C. Founding collaborators in addition to Bristol-Myers Squibb include Merck and Genentech.

The Catalyst projects must follow the SU2C model be carried out by a collaborative team, and be designed to accelerate the clinical use of therapeutic agents within the 3-year term of the grant, and to deliver near-term patient benefit.

The Request for Proposal for the Bristol-Myers Squibb agents is available at proposalCENTRAL, with proposals due by noon ET Monday, Aug. 15.

[email protected]

On Twitter @NikolaidesLaura

Stand Up To Cancer is calling for proposals to investigate additional uses for nivolumab, ipilimumab, elotuzumab, and urelumab, as part of a new researcher-industry collaborative program.

As many as four projects will be funded by Bristol-Myers Squibb, maker of the four agents, in the range of $1 million to $3 million each, according to a written statement from the American Association for Cancer Research (AACR).

The company will provide access to the three drugs already approved for the treatement of various cancers –nivolumab, ipilimumab, and elotuzumab– and to urelumab, an investigational agent that is currently in early clinical trials.

Proposals can include the study of one or more of the products, alone or in combination with other treatments, and may include products from other companies, as well as explore potential new uses for the drug(s), AACR said in the statement.

Nivolumab (Opdivo) is currently approved to treat advanced melanoma, non-small cell lung cancer, renal cell carcinoma, and classical Hodgkin lymphoma; Ipilimumab (Yervoy) is approved to treat melanoma; and elotuzumab (Empliciti) is approved to treat multiple myeloma, in conjunction with other drugs. Urelumab is being evaluated as a treatment for a range of cancers, including some hematological cancers, advanced colorectal cancer, and head and neck cancers.

The Stand Up To Cancer (SU2C) Catalyst program was launched in April to “use funding and materials from the pharmaceutical, biotechnology, diagnostic, and medical devices industries to accelerate research on cancer prevention, detection, and treatment,” according to a written statement from SU2C. Founding collaborators in addition to Bristol-Myers Squibb include Merck and Genentech.

The Catalyst projects must follow the SU2C model be carried out by a collaborative team, and be designed to accelerate the clinical use of therapeutic agents within the 3-year term of the grant, and to deliver near-term patient benefit.

The Request for Proposal for the Bristol-Myers Squibb agents is available at proposalCENTRAL, with proposals due by noon ET Monday, Aug. 15.

[email protected]

On Twitter @NikolaidesLaura

Stand Up To Cancer is calling for proposals to investigate additional uses for nivolumab, ipilimumab, elotuzumab, and urelumab, as part of a new researcher-industry collaborative program.

As many as four projects will be funded by Bristol-Myers Squibb, maker of the four agents, in the range of $1 million to $3 million each, according to a written statement from the American Association for Cancer Research (AACR).

The company will provide access to the three drugs already approved for the treatement of various cancers –nivolumab, ipilimumab, and elotuzumab– and to urelumab, an investigational agent that is currently in early clinical trials.

Proposals can include the study of one or more of the products, alone or in combination with other treatments, and may include products from other companies, as well as explore potential new uses for the drug(s), AACR said in the statement.

Nivolumab (Opdivo) is currently approved to treat advanced melanoma, non-small cell lung cancer, renal cell carcinoma, and classical Hodgkin lymphoma; Ipilimumab (Yervoy) is approved to treat melanoma; and elotuzumab (Empliciti) is approved to treat multiple myeloma, in conjunction with other drugs. Urelumab is being evaluated as a treatment for a range of cancers, including some hematological cancers, advanced colorectal cancer, and head and neck cancers.

The Stand Up To Cancer (SU2C) Catalyst program was launched in April to “use funding and materials from the pharmaceutical, biotechnology, diagnostic, and medical devices industries to accelerate research on cancer prevention, detection, and treatment,” according to a written statement from SU2C. Founding collaborators in addition to Bristol-Myers Squibb include Merck and Genentech.

The Catalyst projects must follow the SU2C model be carried out by a collaborative team, and be designed to accelerate the clinical use of therapeutic agents within the 3-year term of the grant, and to deliver near-term patient benefit.

The Request for Proposal for the Bristol-Myers Squibb agents is available at proposalCENTRAL, with proposals due by noon ET Monday, Aug. 15.

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