Background: FTR is a quality measure defined as death after a serious, potentially preventable complication. Frailty incorporates different domains including physical performance, gait, mobility, nutritional status, mental health, and cognition. Although there are some studies linking frailty and FTR and postoperative morbidity, the degree and association with low-risk procedures is unclear.

Frailty assessment should be considered a part of the routine perioperative evaluation and should stimulate preoperative interventions aimed at reducing risk for postoperative complications.

Bottom line: This large retrospective study found an association between increasing frailty and both the number of complications and FTR for both low-risk and high-risk surgical procedures.

Citation: Shah R et al. Association of frailty with failure to rescue after low-risk and high-risk inpatient surgery. JAMA Surg. 2018 Mar 21;153(5):e180214.

Dr. Canepa is a hospitalist in the division of hospital medicine at the University of Kentucky, Lexington.

Background: FTR is a quality measure defined as death after a serious, potentially preventable complication. Frailty incorporates different domains including physical performance, gait, mobility, nutritional status, mental health, and cognition. Although there are some studies linking frailty and FTR and postoperative morbidity, the degree and association with low-risk procedures is unclear.

Frailty assessment should be considered a part of the routine perioperative evaluation and should stimulate preoperative interventions aimed at reducing risk for postoperative complications.

Bottom line: This large retrospective study found an association between increasing frailty and both the number of complications and FTR for both low-risk and high-risk surgical procedures.

Citation: Shah R et al. Association of frailty with failure to rescue after low-risk and high-risk inpatient surgery. JAMA Surg. 2018 Mar 21;153(5):e180214.

Dr. Canepa is a hospitalist in the division of hospital medicine at the University of Kentucky, Lexington.

Background: FTR is a quality measure defined as death after a serious, potentially preventable complication. Frailty incorporates different domains including physical performance, gait, mobility, nutritional status, mental health, and cognition. Although there are some studies linking frailty and FTR and postoperative morbidity, the degree and association with low-risk procedures is unclear.

Frailty assessment should be considered a part of the routine perioperative evaluation and should stimulate preoperative interventions aimed at reducing risk for postoperative complications.

Bottom line: This large retrospective study found an association between increasing frailty and both the number of complications and FTR for both low-risk and high-risk surgical procedures.

Citation: Shah R et al. Association of frailty with failure to rescue after low-risk and high-risk inpatient surgery. JAMA Surg. 2018 Mar 21;153(5):e180214.

Dr. Canepa is a hospitalist in the division of hospital medicine at the University of Kentucky, Lexington.

The U.S. Preventive Services Task Force has issued draft recommendations counseling interventions for women at increased risk for perinatal depression.

KatarzynaBialasiewicz/Thinkstock

It has given this draft recommendation a B grade, which means that there is moderate certainty of at least moderate net benefit. This is the first time the USPSTF has reviewed this topic.

It’s estimated that one in seven women are affected by perinatal depression, which can have negative effects on both the mothers affected and their children. In its review of evidence, the USPSTF found convincing evidence that counseling, particularly cognitive-behavioral and interpersonal therapies, can prevent perinatal depression.

The draft recommendation affects women who are pregnant or 1 year post partum; specifically, these women will not have a current diagnosis of depression but are at increased risk for it nonetheless. At this time, there is no accurate screening tool available to determine whether women have perinatal depression or are at increased risk. However, certain risk factors have been associated with it, including current stressful life events, personal or family history of depression, history of physical or sexual abuse, pregestational or gestational diabetes, complications during pregnancy such as hyperemesis or premature contractions, adolescent pregnancy, lack of social or financial support, and low socioeconomic status.

The USPSTF reviewed 50 trials considered to be of good or fair quality, with a mean participant age of 29 years; 26 included pregnant women, 22 included women post partum, and 2 included both. Counseling interventions were the most widely studied and “reduced the likelihood of the onset of perinatal depression by 39%” for a pooled risk ratio of 0.61 (95% confidence interval, 0.47-0.78), compared with control conditions. Two kinds of therapies stood out as especially effective: cognitive-behavioral and interpersonal. Cognitive-behavioral therapy focuses on negative thoughts, moods, behaviors, and attitudes and seeks to increase positive events and activities. Interpersonal therapy focuses on how interpersonal interactions and patterns can contribute to the development and maintenance of psychological issues and distress.

The comment period for these draft recommendations will continue through Sept. 24 at www.uspreventiveservicestaskforce.org/tfcomment.htm.

This article was updated 8/28/18.

[email protected]

The U.S. Preventive Services Task Force has issued draft recommendations counseling interventions for women at increased risk for perinatal depression.

KatarzynaBialasiewicz/Thinkstock

It has given this draft recommendation a B grade, which means that there is moderate certainty of at least moderate net benefit. This is the first time the USPSTF has reviewed this topic.

It’s estimated that one in seven women are affected by perinatal depression, which can have negative effects on both the mothers affected and their children. In its review of evidence, the USPSTF found convincing evidence that counseling, particularly cognitive-behavioral and interpersonal therapies, can prevent perinatal depression.

The draft recommendation affects women who are pregnant or 1 year post partum; specifically, these women will not have a current diagnosis of depression but are at increased risk for it nonetheless. At this time, there is no accurate screening tool available to determine whether women have perinatal depression or are at increased risk. However, certain risk factors have been associated with it, including current stressful life events, personal or family history of depression, history of physical or sexual abuse, pregestational or gestational diabetes, complications during pregnancy such as hyperemesis or premature contractions, adolescent pregnancy, lack of social or financial support, and low socioeconomic status.

The USPSTF reviewed 50 trials considered to be of good or fair quality, with a mean participant age of 29 years; 26 included pregnant women, 22 included women post partum, and 2 included both. Counseling interventions were the most widely studied and “reduced the likelihood of the onset of perinatal depression by 39%” for a pooled risk ratio of 0.61 (95% confidence interval, 0.47-0.78), compared with control conditions. Two kinds of therapies stood out as especially effective: cognitive-behavioral and interpersonal. Cognitive-behavioral therapy focuses on negative thoughts, moods, behaviors, and attitudes and seeks to increase positive events and activities. Interpersonal therapy focuses on how interpersonal interactions and patterns can contribute to the development and maintenance of psychological issues and distress.

The comment period for these draft recommendations will continue through Sept. 24 at www.uspreventiveservicestaskforce.org/tfcomment.htm.

This article was updated 8/28/18.

[email protected]

The U.S. Preventive Services Task Force has issued draft recommendations counseling interventions for women at increased risk for perinatal depression.

KatarzynaBialasiewicz/Thinkstock

It has given this draft recommendation a B grade, which means that there is moderate certainty of at least moderate net benefit. This is the first time the USPSTF has reviewed this topic.

It’s estimated that one in seven women are affected by perinatal depression, which can have negative effects on both the mothers affected and their children. In its review of evidence, the USPSTF found convincing evidence that counseling, particularly cognitive-behavioral and interpersonal therapies, can prevent perinatal depression.

The draft recommendation affects women who are pregnant or 1 year post partum; specifically, these women will not have a current diagnosis of depression but are at increased risk for it nonetheless. At this time, there is no accurate screening tool available to determine whether women have perinatal depression or are at increased risk. However, certain risk factors have been associated with it, including current stressful life events, personal or family history of depression, history of physical or sexual abuse, pregestational or gestational diabetes, complications during pregnancy such as hyperemesis or premature contractions, adolescent pregnancy, lack of social or financial support, and low socioeconomic status.

The USPSTF reviewed 50 trials considered to be of good or fair quality, with a mean participant age of 29 years; 26 included pregnant women, 22 included women post partum, and 2 included both. Counseling interventions were the most widely studied and “reduced the likelihood of the onset of perinatal depression by 39%” for a pooled risk ratio of 0.61 (95% confidence interval, 0.47-0.78), compared with control conditions. Two kinds of therapies stood out as especially effective: cognitive-behavioral and interpersonal. Cognitive-behavioral therapy focuses on negative thoughts, moods, behaviors, and attitudes and seeks to increase positive events and activities. Interpersonal therapy focuses on how interpersonal interactions and patterns can contribute to the development and maintenance of psychological issues and distress.

The comment period for these draft recommendations will continue through Sept. 24 at www.uspreventiveservicestaskforce.org/tfcomment.htm.

This article was updated 8/28/18.

[email protected]

The itchy patch of skin on this 60-year-old man’s forearm, beneath his watch, has troubled him intermittently for a year. It is unresponsive to topical medications, including tolnaftate cream and 1% hydrocortisone cream; the latter seemed to improve the condition initially, but with time, the patch grew larger and itchier.

The patient’s primary care provider believed the rash might be precancerous and prescribed 5-fluorouracil cream, which showed no benefit. The patient was then referred to a dermatologist, who performed a KOH examination. No fungal elements were found.

At that point, the patient decided to simply ignore the problem. That resolve ended when the itchiness increased—leading to his presentation today. He is in decent health but has had a kidney transplant and is taking the standard immunosuppressant (anti-rejection) medications.

EXAMINATION
A faintly pink, scaly rash is located on the patient’s forearm. It is unimpressive in appearance but very bothersome to the patient.

Despite the patient’s history, fungal origin remains a possibility, as does psoriasis. A punch biopsy is performed.

What is the diagnosis?

Normally, dermatophytes (the organisms that cause superficial fungal infections) are incapable of invading deeper tissues, making KOH exam a simple diagnostic method. But with immune suppression, the infection is able to invade deeper structures, making it more difficult to diagnose and treat. In this patient’s case, the use of steroid creams under occlusion (ie, the watch) had suppressed the body’s immune response to the infection.

The terminology used to describe this phenomenon varies according to the severity of infection. Tinea incognito might be used to describe this patient’s case, in which the steroid rendered the condition almost impossible to diagnose visually. With continued use of stronger topical steroids, the degree of inflammation might have been worse, involving deeper, larger nodules instead of faint pink scaling. In such cases, the term Majocchi fungal granuloma is used.

This patient moved his watch to the other arm temporarily and was successfully treated with twice-daily application of topical econazole cream and a two-week course of oral terbinafine (250 mg/d).

TAKE-HOME LEARNING POINTS

• Immunosuppression can make fungal infections more difficult to diagnose and treat.
• Dermatophytes don’t normally invade deeper structures and can usually be detected with a KOH exam of surface skin cells.
• If the patient is immunocompromised, a fungal diagnosis is best confirmed with a punch biopsy, and treatment achieved with a combination of oral and topical antifungal products.
• Mild cases of this kind are termed tinea incognito, while more severe cases are called Majocchi fungal granuloma.

The itchy patch of skin on this 60-year-old man’s forearm, beneath his watch, has troubled him intermittently for a year. It is unresponsive to topical medications, including tolnaftate cream and 1% hydrocortisone cream; the latter seemed to improve the condition initially, but with time, the patch grew larger and itchier.

The patient’s primary care provider believed the rash might be precancerous and prescribed 5-fluorouracil cream, which showed no benefit. The patient was then referred to a dermatologist, who performed a KOH examination. No fungal elements were found.

At that point, the patient decided to simply ignore the problem. That resolve ended when the itchiness increased—leading to his presentation today. He is in decent health but has had a kidney transplant and is taking the standard immunosuppressant (anti-rejection) medications.

EXAMINATION
A faintly pink, scaly rash is located on the patient’s forearm. It is unimpressive in appearance but very bothersome to the patient.

Despite the patient’s history, fungal origin remains a possibility, as does psoriasis. A punch biopsy is performed.

What is the diagnosis?

Normally, dermatophytes (the organisms that cause superficial fungal infections) are incapable of invading deeper tissues, making KOH exam a simple diagnostic method. But with immune suppression, the infection is able to invade deeper structures, making it more difficult to diagnose and treat. In this patient’s case, the use of steroid creams under occlusion (ie, the watch) had suppressed the body’s immune response to the infection.

The terminology used to describe this phenomenon varies according to the severity of infection. Tinea incognito might be used to describe this patient’s case, in which the steroid rendered the condition almost impossible to diagnose visually. With continued use of stronger topical steroids, the degree of inflammation might have been worse, involving deeper, larger nodules instead of faint pink scaling. In such cases, the term Majocchi fungal granuloma is used.

This patient moved his watch to the other arm temporarily and was successfully treated with twice-daily application of topical econazole cream and a two-week course of oral terbinafine (250 mg/d).

TAKE-HOME LEARNING POINTS

• Immunosuppression can make fungal infections more difficult to diagnose and treat.
• Dermatophytes don’t normally invade deeper structures and can usually be detected with a KOH exam of surface skin cells.
• If the patient is immunocompromised, a fungal diagnosis is best confirmed with a punch biopsy, and treatment achieved with a combination of oral and topical antifungal products.
• Mild cases of this kind are termed tinea incognito, while more severe cases are called Majocchi fungal granuloma.

The itchy patch of skin on this 60-year-old man’s forearm, beneath his watch, has troubled him intermittently for a year. It is unresponsive to topical medications, including tolnaftate cream and 1% hydrocortisone cream; the latter seemed to improve the condition initially, but with time, the patch grew larger and itchier.

The patient’s primary care provider believed the rash might be precancerous and prescribed 5-fluorouracil cream, which showed no benefit. The patient was then referred to a dermatologist, who performed a KOH examination. No fungal elements were found.

At that point, the patient decided to simply ignore the problem. That resolve ended when the itchiness increased—leading to his presentation today. He is in decent health but has had a kidney transplant and is taking the standard immunosuppressant (anti-rejection) medications.

EXAMINATION
A faintly pink, scaly rash is located on the patient’s forearm. It is unimpressive in appearance but very bothersome to the patient.

Despite the patient’s history, fungal origin remains a possibility, as does psoriasis. A punch biopsy is performed.

What is the diagnosis?

Normally, dermatophytes (the organisms that cause superficial fungal infections) are incapable of invading deeper tissues, making KOH exam a simple diagnostic method. But with immune suppression, the infection is able to invade deeper structures, making it more difficult to diagnose and treat. In this patient’s case, the use of steroid creams under occlusion (ie, the watch) had suppressed the body’s immune response to the infection.

The terminology used to describe this phenomenon varies according to the severity of infection. Tinea incognito might be used to describe this patient’s case, in which the steroid rendered the condition almost impossible to diagnose visually. With continued use of stronger topical steroids, the degree of inflammation might have been worse, involving deeper, larger nodules instead of faint pink scaling. In such cases, the term Majocchi fungal granuloma is used.

This patient moved his watch to the other arm temporarily and was successfully treated with twice-daily application of topical econazole cream and a two-week course of oral terbinafine (250 mg/d).

TAKE-HOME LEARNING POINTS

• Immunosuppression can make fungal infections more difficult to diagnose and treat.
• Dermatophytes don’t normally invade deeper structures and can usually be detected with a KOH exam of surface skin cells.
• If the patient is immunocompromised, a fungal diagnosis is best confirmed with a punch biopsy, and treatment achieved with a combination of oral and topical antifungal products.
• Mild cases of this kind are termed tinea incognito, while more severe cases are called Majocchi fungal granuloma.

The European Commission (EC) has granted approval for tisagenlecleucel (Kymriah) and axicabtagene ciloleucel (Yescarta), two chimeric antigen receptor (CAR) T-cell therapies.

Tisagenlecleucel is now approved for use in pediatric and young adult patients up to 25 years of age with B-cell acute lymphoblastic leukemia (ALL) that is refractory, in relapse post transplant, or in second or later relapse.

Tisagenlecleucel is also approved to treat adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who have received two or more lines of systemic therapy.

Axicabtagene ciloleucel is approved for adults with relapsed/refractory DLBCL and primary mediastinal large B-cell lymphoma (PMBCL) after two or more lines of systemic therapy. The treatment is marketed by Kite, a Gilead company.

The axicabtagene ciloleucel approval is based on results from the single arm, ZUMA-1 trial. During the study of 101 patients who received a single infusion, 72% responded to therapy and 51% achieved a complete response. At 1 year, median overall survival had not been reached.

Novartis expects to launch tisagenlecleucel initially for pediatric ALL. The company said timing for tisagenlecleucel availability in each country will depend on multiple factors, including the onboarding of qualified treatment centers for the appropriate indications, as well as the completion of national reimbursement procedures.

The EC’s approval of tisagenlecleucel is based on results from the phase 2 JULIET and ELIANA trials.

Updated results from JULIET were presented at the annual congress of the European Hematology Association in June 2018. The trial enrolled 165 adults with relapsed/refractory DLBCL, and 111 of them received a single infusion of tisagenlecleucel. Most of the patients who discontinued before dosing did so because of disease progression or clinical deterioration.

The median time from infusion to data cutoff was 13.9 months.

The overall response rate was 52%, and the complete response (CR) rate was 40%. At the time of data cutoff, none of the responders had gone on to receive a stem cell transplant.

Updated results from ELIANA were published in New England Journal of Medicine (2018;378:439-48).

The trial included 75 children and young adults with relapsed/refractory ALL. The overall remission rate was 81% (61/75), with 60% of patients (n = 45) achieving a complete remission (CR) and 21% (n = 16) achieving a CR with incomplete hematologic recovery (CRi).

All patients whose best response was CR/CRi were negative for minimal residual disease. The median duration of response was not met.

[email protected]

The European Commission (EC) has granted approval for tisagenlecleucel (Kymriah) and axicabtagene ciloleucel (Yescarta), two chimeric antigen receptor (CAR) T-cell therapies.

Tisagenlecleucel is now approved for use in pediatric and young adult patients up to 25 years of age with B-cell acute lymphoblastic leukemia (ALL) that is refractory, in relapse post transplant, or in second or later relapse.

Tisagenlecleucel is also approved to treat adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who have received two or more lines of systemic therapy.

Axicabtagene ciloleucel is approved for adults with relapsed/refractory DLBCL and primary mediastinal large B-cell lymphoma (PMBCL) after two or more lines of systemic therapy. The treatment is marketed by Kite, a Gilead company.

The axicabtagene ciloleucel approval is based on results from the single arm, ZUMA-1 trial. During the study of 101 patients who received a single infusion, 72% responded to therapy and 51% achieved a complete response. At 1 year, median overall survival had not been reached.

Novartis expects to launch tisagenlecleucel initially for pediatric ALL. The company said timing for tisagenlecleucel availability in each country will depend on multiple factors, including the onboarding of qualified treatment centers for the appropriate indications, as well as the completion of national reimbursement procedures.

The EC’s approval of tisagenlecleucel is based on results from the phase 2 JULIET and ELIANA trials.

Updated results from JULIET were presented at the annual congress of the European Hematology Association in June 2018. The trial enrolled 165 adults with relapsed/refractory DLBCL, and 111 of them received a single infusion of tisagenlecleucel. Most of the patients who discontinued before dosing did so because of disease progression or clinical deterioration.

The median time from infusion to data cutoff was 13.9 months.

The overall response rate was 52%, and the complete response (CR) rate was 40%. At the time of data cutoff, none of the responders had gone on to receive a stem cell transplant.

Updated results from ELIANA were published in New England Journal of Medicine (2018;378:439-48).

The trial included 75 children and young adults with relapsed/refractory ALL. The overall remission rate was 81% (61/75), with 60% of patients (n = 45) achieving a complete remission (CR) and 21% (n = 16) achieving a CR with incomplete hematologic recovery (CRi).

All patients whose best response was CR/CRi were negative for minimal residual disease. The median duration of response was not met.

[email protected]

The European Commission (EC) has granted approval for tisagenlecleucel (Kymriah) and axicabtagene ciloleucel (Yescarta), two chimeric antigen receptor (CAR) T-cell therapies.

Tisagenlecleucel is now approved for use in pediatric and young adult patients up to 25 years of age with B-cell acute lymphoblastic leukemia (ALL) that is refractory, in relapse post transplant, or in second or later relapse.

Tisagenlecleucel is also approved to treat adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who have received two or more lines of systemic therapy.

Axicabtagene ciloleucel is approved for adults with relapsed/refractory DLBCL and primary mediastinal large B-cell lymphoma (PMBCL) after two or more lines of systemic therapy. The treatment is marketed by Kite, a Gilead company.

The axicabtagene ciloleucel approval is based on results from the single arm, ZUMA-1 trial. During the study of 101 patients who received a single infusion, 72% responded to therapy and 51% achieved a complete response. At 1 year, median overall survival had not been reached.

Novartis expects to launch tisagenlecleucel initially for pediatric ALL. The company said timing for tisagenlecleucel availability in each country will depend on multiple factors, including the onboarding of qualified treatment centers for the appropriate indications, as well as the completion of national reimbursement procedures.

The EC’s approval of tisagenlecleucel is based on results from the phase 2 JULIET and ELIANA trials.

Updated results from JULIET were presented at the annual congress of the European Hematology Association in June 2018. The trial enrolled 165 adults with relapsed/refractory DLBCL, and 111 of them received a single infusion of tisagenlecleucel. Most of the patients who discontinued before dosing did so because of disease progression or clinical deterioration.

The median time from infusion to data cutoff was 13.9 months.

The overall response rate was 52%, and the complete response (CR) rate was 40%. At the time of data cutoff, none of the responders had gone on to receive a stem cell transplant.

Updated results from ELIANA were published in New England Journal of Medicine (2018;378:439-48).

The trial included 75 children and young adults with relapsed/refractory ALL. The overall remission rate was 81% (61/75), with 60% of patients (n = 45) achieving a complete remission (CR) and 21% (n = 16) achieving a CR with incomplete hematologic recovery (CRi).

All patients whose best response was CR/CRi were negative for minimal residual disease. The median duration of response was not met.

[email protected]

The Diagnosis: Eruptive Blue Nevus

All biopsies demonstrated similar histologic features, including an intradermal proliferation of heavily pigmented, spindle-shaped dendritic melanocytes (Figure). The dermal pigment was most pronounced in the grossly darker papules, and there was not a substantial amount of background pigmentation at the stratum basale. Cytologic atypia, foci of necrosis, and mitotic activity were absent from all sections. There was no definitive junctional component identified, no multinucleated giant cells, and there was no overlying epidermal aberration. With some background pigmentation seen histologically, nevus spilus was considered, but because this acute eruption occurred in a young adult without appreciable gross background hyperpigmentation, the clinical context led to a diagnosis of eruptive blue nevus. After communicating the findings to the patient, he declined further treatment.

Eruptive blue nevus is an exceptionally rare subtype of blue nevus with few cases reported since the 1940s.^1-9 Generally, each case report found a triggering event that could possibly have precipitated the acute proliferation and evolution of nevi. Triggering events can include bullous processes such as erythema multiforme² and Stevens-Johnson syndrome,³ severe sunburn,⁴ trauma,⁵ immunosuppression,⁶ and a variety of endocrinopathies. No such history could be identified in our patient, except the biopsy.

Common blue nevi are benign, usually congenital, well-circumscribed, solitary, blue-gray macules or papules. Half of blue nevi cases are found on the dorsal aspects of the hands and feet but can present anywhere (eg, face, scalp, wrists, sacrum, buttocks). The blue-gray color appreciated clinically is attributed to the Tyndall effect, which occurs when long-wavelength light--red, orange, and yellow--is absorbed by the melanin deep in the dermis, while short-wavelength visible light--blue, violet, and indigo--is reflected with backscattering. On polarized dermoscopy, a homogeneous blue-gray hue is appreciated, but lighter segments may be present when collagen deposition is robust. Histopathologic findings confirm spindle-shaped dendritic melanocytes in the dermis without epidermal involvement. It generally is accepted that the etiology of these benign nevi is a failed migration of neural crest cells to the epidermis.^10,11 Although the common blue nevus may be simple to diagnose, several subtypes have been described in the literature, including combined blue nevus, desmoplastic blue nevus, hypomelanotic/amelanotic blue nevus, and epithelioid blue nevus of Carney complex, and excluding a malignant process is of monumental importance.^7,12

Biopsy is recommended for common blue nevi in the evaluation of newly acquired lesions, expansion of previously stable nevi, or for nevi larger than 10 mm in diameter. The nature of eruptive blue nevi warrants a biopsy to exclude melanoma or another malignant process. While the Becker nevus may manifest in adolescent males, it is clinically distinct from an eruptive blue nevus due to the size, relative homogeneity, and presence of hair within the lesion. Cutaneous amyloidosis may appear clinically similar to an eruptive blue nevus, but globular or amorphous material was not present in the papillary dermis of biopsied lesions in our patient. Since there was no cellular atypia or mitotic activity, melanoma and other malignancies were ruled out. Lastly, NAME syndrome by definition must include atrial myxomas, myxoid neurofibromas, and ephelides in addition to the nevi; however, our patient had only nevi and few ephelides. Once the diagnosis is established and benign nature confirmed, treatment is not necessarily required. If the patient elects to remove the lesion for aesthetic reasons, an excision into the subcutaneous fat is required to ensure complete removal of deep dermal melanocytes. Prior excisions of eruptive blue nevi have had no recurrence after more than 10 months.^8,9

The Diagnosis: Eruptive Blue Nevus

All biopsies demonstrated similar histologic features, including an intradermal proliferation of heavily pigmented, spindle-shaped dendritic melanocytes (Figure). The dermal pigment was most pronounced in the grossly darker papules, and there was not a substantial amount of background pigmentation at the stratum basale. Cytologic atypia, foci of necrosis, and mitotic activity were absent from all sections. There was no definitive junctional component identified, no multinucleated giant cells, and there was no overlying epidermal aberration. With some background pigmentation seen histologically, nevus spilus was considered, but because this acute eruption occurred in a young adult without appreciable gross background hyperpigmentation, the clinical context led to a diagnosis of eruptive blue nevus. After communicating the findings to the patient, he declined further treatment.

Eruptive blue nevus is an exceptionally rare subtype of blue nevus with few cases reported since the 1940s.^1-9 Generally, each case report found a triggering event that could possibly have precipitated the acute proliferation and evolution of nevi. Triggering events can include bullous processes such as erythema multiforme² and Stevens-Johnson syndrome,³ severe sunburn,⁴ trauma,⁵ immunosuppression,⁶ and a variety of endocrinopathies. No such history could be identified in our patient, except the biopsy.

Common blue nevi are benign, usually congenital, well-circumscribed, solitary, blue-gray macules or papules. Half of blue nevi cases are found on the dorsal aspects of the hands and feet but can present anywhere (eg, face, scalp, wrists, sacrum, buttocks). The blue-gray color appreciated clinically is attributed to the Tyndall effect, which occurs when long-wavelength light--red, orange, and yellow--is absorbed by the melanin deep in the dermis, while short-wavelength visible light--blue, violet, and indigo--is reflected with backscattering. On polarized dermoscopy, a homogeneous blue-gray hue is appreciated, but lighter segments may be present when collagen deposition is robust. Histopathologic findings confirm spindle-shaped dendritic melanocytes in the dermis without epidermal involvement. It generally is accepted that the etiology of these benign nevi is a failed migration of neural crest cells to the epidermis.^10,11 Although the common blue nevus may be simple to diagnose, several subtypes have been described in the literature, including combined blue nevus, desmoplastic blue nevus, hypomelanotic/amelanotic blue nevus, and epithelioid blue nevus of Carney complex, and excluding a malignant process is of monumental importance.^7,12

Biopsy is recommended for common blue nevi in the evaluation of newly acquired lesions, expansion of previously stable nevi, or for nevi larger than 10 mm in diameter. The nature of eruptive blue nevi warrants a biopsy to exclude melanoma or another malignant process. While the Becker nevus may manifest in adolescent males, it is clinically distinct from an eruptive blue nevus due to the size, relative homogeneity, and presence of hair within the lesion. Cutaneous amyloidosis may appear clinically similar to an eruptive blue nevus, but globular or amorphous material was not present in the papillary dermis of biopsied lesions in our patient. Since there was no cellular atypia or mitotic activity, melanoma and other malignancies were ruled out. Lastly, NAME syndrome by definition must include atrial myxomas, myxoid neurofibromas, and ephelides in addition to the nevi; however, our patient had only nevi and few ephelides. Once the diagnosis is established and benign nature confirmed, treatment is not necessarily required. If the patient elects to remove the lesion for aesthetic reasons, an excision into the subcutaneous fat is required to ensure complete removal of deep dermal melanocytes. Prior excisions of eruptive blue nevi have had no recurrence after more than 10 months.^8,9

The Diagnosis: Eruptive Blue Nevus

All biopsies demonstrated similar histologic features, including an intradermal proliferation of heavily pigmented, spindle-shaped dendritic melanocytes (Figure). The dermal pigment was most pronounced in the grossly darker papules, and there was not a substantial amount of background pigmentation at the stratum basale. Cytologic atypia, foci of necrosis, and mitotic activity were absent from all sections. There was no definitive junctional component identified, no multinucleated giant cells, and there was no overlying epidermal aberration. With some background pigmentation seen histologically, nevus spilus was considered, but because this acute eruption occurred in a young adult without appreciable gross background hyperpigmentation, the clinical context led to a diagnosis of eruptive blue nevus. After communicating the findings to the patient, he declined further treatment.

Eruptive blue nevus is an exceptionally rare subtype of blue nevus with few cases reported since the 1940s.^1-9 Generally, each case report found a triggering event that could possibly have precipitated the acute proliferation and evolution of nevi. Triggering events can include bullous processes such as erythema multiforme² and Stevens-Johnson syndrome,³ severe sunburn,⁴ trauma,⁵ immunosuppression,⁶ and a variety of endocrinopathies. No such history could be identified in our patient, except the biopsy.

Common blue nevi are benign, usually congenital, well-circumscribed, solitary, blue-gray macules or papules. Half of blue nevi cases are found on the dorsal aspects of the hands and feet but can present anywhere (eg, face, scalp, wrists, sacrum, buttocks). The blue-gray color appreciated clinically is attributed to the Tyndall effect, which occurs when long-wavelength light--red, orange, and yellow--is absorbed by the melanin deep in the dermis, while short-wavelength visible light--blue, violet, and indigo--is reflected with backscattering. On polarized dermoscopy, a homogeneous blue-gray hue is appreciated, but lighter segments may be present when collagen deposition is robust. Histopathologic findings confirm spindle-shaped dendritic melanocytes in the dermis without epidermal involvement. It generally is accepted that the etiology of these benign nevi is a failed migration of neural crest cells to the epidermis.^10,11 Although the common blue nevus may be simple to diagnose, several subtypes have been described in the literature, including combined blue nevus, desmoplastic blue nevus, hypomelanotic/amelanotic blue nevus, and epithelioid blue nevus of Carney complex, and excluding a malignant process is of monumental importance.^7,12

Biopsy is recommended for common blue nevi in the evaluation of newly acquired lesions, expansion of previously stable nevi, or for nevi larger than 10 mm in diameter. The nature of eruptive blue nevi warrants a biopsy to exclude melanoma or another malignant process. While the Becker nevus may manifest in adolescent males, it is clinically distinct from an eruptive blue nevus due to the size, relative homogeneity, and presence of hair within the lesion. Cutaneous amyloidosis may appear clinically similar to an eruptive blue nevus, but globular or amorphous material was not present in the papillary dermis of biopsied lesions in our patient. Since there was no cellular atypia or mitotic activity, melanoma and other malignancies were ruled out. Lastly, NAME syndrome by definition must include atrial myxomas, myxoid neurofibromas, and ephelides in addition to the nevi; however, our patient had only nevi and few ephelides. Once the diagnosis is established and benign nature confirmed, treatment is not necessarily required. If the patient elects to remove the lesion for aesthetic reasons, an excision into the subcutaneous fat is required to ensure complete removal of deep dermal melanocytes. Prior excisions of eruptive blue nevi have had no recurrence after more than 10 months.^8,9

MUNICH – The worldwide cardiology community’s newly revised universal definition of an MI refines the way that cardiologists distinguish between myocardial infarction and myocardial injury, said Joseph S. Alpert, MD, one of the two chairs of the definition-writing panel.

“We had three previous definitions, but there is still a lot of confusion [about distinguishing] between injury and infarction. We definitely hope that this fourth definition will further help people distinguish the two and help people determine whether or not a patient has an MI,” said Dr. Alpert following a session at the annual congress of the European Society of Cardiology that introduced some of the key elements of the new revision.

Days before the ESC congress, a task force formed by the European Society of Cardiology, the American College of Cardiology, the American Heart Association, and the World Heart Federation released the Fourth Universal Definition of Myocardial Infarction (2018) (J Am Coll Cardiol. 2018 Aug 24. doi: 10.1016/j.jacc.2018.08.1038), which follows the series of three prior MI definitions that these groups have issued since the first iteration came out in 2007 (J Am Coll Cardiol. 2007;50[22]:2173-95).

The new revision includes 5 “new concepts,” 14 updated concepts, and 6 new sections since the third universal definition from 2012. The change that topped Dr. Alpert’s list of key messages was the need to determine whether a rise in cardiac troponin, a key biomarker of cardiac damage, resulted from infarction or injury.

These two alternative diagnoses mean “a very different outlook for patients. Treatment is different, and their prognosis is different. It’s important to make the distinction,” said Dr. Alpert, professor of medicine at the University of Arizona in Tucson.

The new changes to making an MI diagnosis will likely help drive a couple of important changes in the way U.S. patients with suspected myocardial injury or infarction get assessed, he said in an interview. The first change will be wide uptake of high sensitivity cardiac troponin (hscTn) assays over the next 5 years or so, as the ability to measure this key diagnostic biomarker progresses from its initial Food and Drug Administration approval for the U.S. market in 2017 to “close to 100% of U.S. hospitals using it,” he predicted. A big issue that is currently slowing even quicker adoption of hscTn is that many hospitals, including the one where Dr. Alpert practices, still have laboratory contracts in place that tether them to older troponin-testing technologies and make it economically unfeasible to change until their contracts expire. The contract in place where Dr. Alpert practices runs out in 2019, and soon after that happens he expects to gain the ability to order a hscTn test.

The new, fourth definition says that hscTn is “recommended for routine clinical use,” but routine U.S. use “won’t be immediate because many hospitals will put in hscTn only when their old contract runs out,” he said.

Another practice-changing impact from the fourth definition may be expanded U.S. availability and use of MR imaging, which the fourth definition identified as the most informative and versatile of the several imaging options used to confirm or rule out an MI.

Cardiac MR “provides both functional and tissue characterization. It’s the technique with the most potential,” able to noninvasively identify “both the nature and extent of myocardial damage,” explained Chiara Bucciarelli-Ducci, MD, a cardiologist and imaging specialist at the Bristol (England) Heart Institute. A single cardiac MR scan “gives many answers,” said Dr. Bucciarelli-Ducci, who also served on the fourth definition task force and spoke at the session about the document’s revised imaging recommendations.

Mitchel L. Zoler/MDedge News

“In the setting of acute MI, cardiac MR can also be used to assess the presence and extent of myocardium at risk (myocardial edema), myocardial salvage, microvascular obstruction, intramyocardial hemorrhage, and infarct size, all markers of myocardial injury that have prognostic value,” according to the fourth definition. “In patients with possible acute MI but unobstructed coronary arteries, cardiac MR can help to diagnose alternative conditions such as myocarditis, Takotsubo syndrome, embolic infarction, or MI with spontaneous recanalization.”

“What’s turning out is that, a large number of patients with chest pain have an infection and not an MI, and cardiac MR can distinguish inflammation and myocarditis from infarction. We’re now doing a lot more MRs,” Dr. Alpert said. Although MR capability is not as widely available today as other imaging methods, like echocardiography and CT, over the next 5 years that will likely change, he said. But Dr. Alpert cautioned that not every patient with a suspected MI needs MR assessment. It’s best focused for selected patients with an uncertain diagnosis based on the core indicators of disease: history, ECG, changes in hscTn levels over time, and a chest x-ray. “MR is for when there are questions,” he said. When patients present with classic MI signs and symptoms the diagnosis can depend just on the basics, perhaps supplemented with a more widely available imaging method like echocardiography to look for wall motion abnormalities, he said. “If echo shows good left ventricular function you probably don’t need MR.” he said.

CT coronary angiography (CTCA) is another useful diagnostic tool, and right now is more widely available than MR. CTCA “may be used to diagnose coronary artery disease in patients with an acute coronary syndrome event in the emergency department or chest pain unit, particularly in low- to intermediate-risk patients with normal hscTn at presentation,” said the fourth definition. But Dr. Alpert cited the radiation dose from CT as a limiting factor. “We have patients who get repeat CT scans, and we know that increases their cancer risk. There is no such thing as a totally safe dose of radiation.” Lack of radiation exposure is another feature that makes MR imaging attractive.

Dr. Alpert had no disclosures. Dr. Bucciarelli-Ducci has had a financial relationship with Circle Cardiovascular Imaging.

[email protected]


 

MUNICH – The worldwide cardiology community’s newly revised universal definition of an MI refines the way that cardiologists distinguish between myocardial infarction and myocardial injury, said Joseph S. Alpert, MD, one of the two chairs of the definition-writing panel.

“We had three previous definitions, but there is still a lot of confusion [about distinguishing] between injury and infarction. We definitely hope that this fourth definition will further help people distinguish the two and help people determine whether or not a patient has an MI,” said Dr. Alpert following a session at the annual congress of the European Society of Cardiology that introduced some of the key elements of the new revision.

Days before the ESC congress, a task force formed by the European Society of Cardiology, the American College of Cardiology, the American Heart Association, and the World Heart Federation released the Fourth Universal Definition of Myocardial Infarction (2018) (J Am Coll Cardiol. 2018 Aug 24. doi: 10.1016/j.jacc.2018.08.1038), which follows the series of three prior MI definitions that these groups have issued since the first iteration came out in 2007 (J Am Coll Cardiol. 2007;50[22]:2173-95).

The new revision includes 5 “new concepts,” 14 updated concepts, and 6 new sections since the third universal definition from 2012. The change that topped Dr. Alpert’s list of key messages was the need to determine whether a rise in cardiac troponin, a key biomarker of cardiac damage, resulted from infarction or injury.

These two alternative diagnoses mean “a very different outlook for patients. Treatment is different, and their prognosis is different. It’s important to make the distinction,” said Dr. Alpert, professor of medicine at the University of Arizona in Tucson.

The new changes to making an MI diagnosis will likely help drive a couple of important changes in the way U.S. patients with suspected myocardial injury or infarction get assessed, he said in an interview. The first change will be wide uptake of high sensitivity cardiac troponin (hscTn) assays over the next 5 years or so, as the ability to measure this key diagnostic biomarker progresses from its initial Food and Drug Administration approval for the U.S. market in 2017 to “close to 100% of U.S. hospitals using it,” he predicted. A big issue that is currently slowing even quicker adoption of hscTn is that many hospitals, including the one where Dr. Alpert practices, still have laboratory contracts in place that tether them to older troponin-testing technologies and make it economically unfeasible to change until their contracts expire. The contract in place where Dr. Alpert practices runs out in 2019, and soon after that happens he expects to gain the ability to order a hscTn test.

The new, fourth definition says that hscTn is “recommended for routine clinical use,” but routine U.S. use “won’t be immediate because many hospitals will put in hscTn only when their old contract runs out,” he said.

Another practice-changing impact from the fourth definition may be expanded U.S. availability and use of MR imaging, which the fourth definition identified as the most informative and versatile of the several imaging options used to confirm or rule out an MI.

Cardiac MR “provides both functional and tissue characterization. It’s the technique with the most potential,” able to noninvasively identify “both the nature and extent of myocardial damage,” explained Chiara Bucciarelli-Ducci, MD, a cardiologist and imaging specialist at the Bristol (England) Heart Institute. A single cardiac MR scan “gives many answers,” said Dr. Bucciarelli-Ducci, who also served on the fourth definition task force and spoke at the session about the document’s revised imaging recommendations.

Mitchel L. Zoler/MDedge News

“In the setting of acute MI, cardiac MR can also be used to assess the presence and extent of myocardium at risk (myocardial edema), myocardial salvage, microvascular obstruction, intramyocardial hemorrhage, and infarct size, all markers of myocardial injury that have prognostic value,” according to the fourth definition. “In patients with possible acute MI but unobstructed coronary arteries, cardiac MR can help to diagnose alternative conditions such as myocarditis, Takotsubo syndrome, embolic infarction, or MI with spontaneous recanalization.”

“What’s turning out is that, a large number of patients with chest pain have an infection and not an MI, and cardiac MR can distinguish inflammation and myocarditis from infarction. We’re now doing a lot more MRs,” Dr. Alpert said. Although MR capability is not as widely available today as other imaging methods, like echocardiography and CT, over the next 5 years that will likely change, he said. But Dr. Alpert cautioned that not every patient with a suspected MI needs MR assessment. It’s best focused for selected patients with an uncertain diagnosis based on the core indicators of disease: history, ECG, changes in hscTn levels over time, and a chest x-ray. “MR is for when there are questions,” he said. When patients present with classic MI signs and symptoms the diagnosis can depend just on the basics, perhaps supplemented with a more widely available imaging method like echocardiography to look for wall motion abnormalities, he said. “If echo shows good left ventricular function you probably don’t need MR.” he said.

CT coronary angiography (CTCA) is another useful diagnostic tool, and right now is more widely available than MR. CTCA “may be used to diagnose coronary artery disease in patients with an acute coronary syndrome event in the emergency department or chest pain unit, particularly in low- to intermediate-risk patients with normal hscTn at presentation,” said the fourth definition. But Dr. Alpert cited the radiation dose from CT as a limiting factor. “We have patients who get repeat CT scans, and we know that increases their cancer risk. There is no such thing as a totally safe dose of radiation.” Lack of radiation exposure is another feature that makes MR imaging attractive.

Dr. Alpert had no disclosures. Dr. Bucciarelli-Ducci has had a financial relationship with Circle Cardiovascular Imaging.

[email protected]


 

MUNICH – The worldwide cardiology community’s newly revised universal definition of an MI refines the way that cardiologists distinguish between myocardial infarction and myocardial injury, said Joseph S. Alpert, MD, one of the two chairs of the definition-writing panel.

“We had three previous definitions, but there is still a lot of confusion [about distinguishing] between injury and infarction. We definitely hope that this fourth definition will further help people distinguish the two and help people determine whether or not a patient has an MI,” said Dr. Alpert following a session at the annual congress of the European Society of Cardiology that introduced some of the key elements of the new revision.

Days before the ESC congress, a task force formed by the European Society of Cardiology, the American College of Cardiology, the American Heart Association, and the World Heart Federation released the Fourth Universal Definition of Myocardial Infarction (2018) (J Am Coll Cardiol. 2018 Aug 24. doi: 10.1016/j.jacc.2018.08.1038), which follows the series of three prior MI definitions that these groups have issued since the first iteration came out in 2007 (J Am Coll Cardiol. 2007;50[22]:2173-95).

The new revision includes 5 “new concepts,” 14 updated concepts, and 6 new sections since the third universal definition from 2012. The change that topped Dr. Alpert’s list of key messages was the need to determine whether a rise in cardiac troponin, a key biomarker of cardiac damage, resulted from infarction or injury.

These two alternative diagnoses mean “a very different outlook for patients. Treatment is different, and their prognosis is different. It’s important to make the distinction,” said Dr. Alpert, professor of medicine at the University of Arizona in Tucson.

The new changes to making an MI diagnosis will likely help drive a couple of important changes in the way U.S. patients with suspected myocardial injury or infarction get assessed, he said in an interview. The first change will be wide uptake of high sensitivity cardiac troponin (hscTn) assays over the next 5 years or so, as the ability to measure this key diagnostic biomarker progresses from its initial Food and Drug Administration approval for the U.S. market in 2017 to “close to 100% of U.S. hospitals using it,” he predicted. A big issue that is currently slowing even quicker adoption of hscTn is that many hospitals, including the one where Dr. Alpert practices, still have laboratory contracts in place that tether them to older troponin-testing technologies and make it economically unfeasible to change until their contracts expire. The contract in place where Dr. Alpert practices runs out in 2019, and soon after that happens he expects to gain the ability to order a hscTn test.

The new, fourth definition says that hscTn is “recommended for routine clinical use,” but routine U.S. use “won’t be immediate because many hospitals will put in hscTn only when their old contract runs out,” he said.

Another practice-changing impact from the fourth definition may be expanded U.S. availability and use of MR imaging, which the fourth definition identified as the most informative and versatile of the several imaging options used to confirm or rule out an MI.

Cardiac MR “provides both functional and tissue characterization. It’s the technique with the most potential,” able to noninvasively identify “both the nature and extent of myocardial damage,” explained Chiara Bucciarelli-Ducci, MD, a cardiologist and imaging specialist at the Bristol (England) Heart Institute. A single cardiac MR scan “gives many answers,” said Dr. Bucciarelli-Ducci, who also served on the fourth definition task force and spoke at the session about the document’s revised imaging recommendations.

Mitchel L. Zoler/MDedge News

“In the setting of acute MI, cardiac MR can also be used to assess the presence and extent of myocardium at risk (myocardial edema), myocardial salvage, microvascular obstruction, intramyocardial hemorrhage, and infarct size, all markers of myocardial injury that have prognostic value,” according to the fourth definition. “In patients with possible acute MI but unobstructed coronary arteries, cardiac MR can help to diagnose alternative conditions such as myocarditis, Takotsubo syndrome, embolic infarction, or MI with spontaneous recanalization.”

“What’s turning out is that, a large number of patients with chest pain have an infection and not an MI, and cardiac MR can distinguish inflammation and myocarditis from infarction. We’re now doing a lot more MRs,” Dr. Alpert said. Although MR capability is not as widely available today as other imaging methods, like echocardiography and CT, over the next 5 years that will likely change, he said. But Dr. Alpert cautioned that not every patient with a suspected MI needs MR assessment. It’s best focused for selected patients with an uncertain diagnosis based on the core indicators of disease: history, ECG, changes in hscTn levels over time, and a chest x-ray. “MR is for when there are questions,” he said. When patients present with classic MI signs and symptoms the diagnosis can depend just on the basics, perhaps supplemented with a more widely available imaging method like echocardiography to look for wall motion abnormalities, he said. “If echo shows good left ventricular function you probably don’t need MR.” he said.

CT coronary angiography (CTCA) is another useful diagnostic tool, and right now is more widely available than MR. CTCA “may be used to diagnose coronary artery disease in patients with an acute coronary syndrome event in the emergency department or chest pain unit, particularly in low- to intermediate-risk patients with normal hscTn at presentation,” said the fourth definition. But Dr. Alpert cited the radiation dose from CT as a limiting factor. “We have patients who get repeat CT scans, and we know that increases their cancer risk. There is no such thing as a totally safe dose of radiation.” Lack of radiation exposure is another feature that makes MR imaging attractive.

Dr. Alpert had no disclosures. Dr. Bucciarelli-Ducci has had a financial relationship with Circle Cardiovascular Imaging.

[email protected]


 

LOS ANGELES – Serum neurofilament light chain shows promise as a biomarker for disease severity and response to treatment with autologous bone marrow transplant in patients with multiple sclerosis, according to findings from an analysis of paired samples.

solitude72/iStockphoto

Serum neurofilament light chain (Nf-L) levels were found to be significantly elevated in both the serum and cerebrospinal fluid (CSF) of 23 patients with aggressive multiple sclerosis (MS), compared with samples from 5 controls with noninflammatory neurologic conditions such as chronic fatigue syndrome or migraine. The levels in the patients with MS were significantly reduced following autologous bone marrow transplant (BMT), Simon Thebault, MD, reported in a poster at the annual meeting of the American Academy of Neurology.

Nf-L has been shown to be a biomarker for neuronal damage and to have potential for denoting disease severity and treatment response in MS; for this analysis, samples from patients were collected at baseline and annually for 3 years after transplant. Samples from controls were obtained for comparison.

“Our objective, really, was [to determine if we could] detect a treatment response in neurofilament light chain, and secondly, did the degree of neurofilament light chain being high at baseline predict anything about subsequent disease outcome?” Dr. Thebault, a third-year resident at the University of Ottawa, reported in the poster.

Indeed, a treatment response was detected; baseline levels were high, and levels in both serum and CSF were down significantly (P = .05) at both 1 and 3 years following bone marrow transplant, and they stayed down. “In fact, they were so low, they were not significantly different from [the levels] in noninflammatory controls,” he said, noting that serum and CSF NfL levels were highly correlated (r = .833; P less than .001).

Study subjects were patients with aggressive MS, characterized by early disease onset, rapid progression, frequent relapses, and poor treatment responses. Such patients who have received autologous BMT represent an interesting group for examining treatment responses, he said.

At baseline, these patients presumably have a high burden of tissue injury, which would be representative of high levels of Nf-L; good, prospective data show these patients have no evidence of ongoing inflammatory disease following an intensive regimen that includes chemoablation and reinfusion of autologous stem cells, which is representative of a significant reduction of neurofilament levels, he explained.

Importantly, serum and CSF levels were correlated in this study, he said, noting that most prior work has involved CSF, but “the real clinical utility in neurofilament light chain is probably in the serum, because patients don’t like having lumbar punctures too often.”

With respect to the second question pertaining to disease outcomes, the study did show that patients with baseline Nf-L levels above the median for the group had worse T1 lesion volumes at baseline and after transplant (P = .0021 at 36 months), and also had worsening brain atrophy even after transplant (P = .0389 at 60 months).

The curves appeared to be diverging, suggesting that, in the absence of inflammatory disease activity, patients with high Nf-L levels at baseline continue to have ongoing atrophy at a differential rate, compared with those with low baseline levels, Dr. Thebault said.

Other findings included better Expanded Disability Status Scale outcomes after transplant in patients with lower baseline Nf-L, and a trend toward worsening outcomes among those with higher baseline Nf-L levels, although the study may have been underpowered for this. Additionally, lower baseline Nf-L predicted significantly lower T1 and T2 lesion volume, number of gadolinium-enhancing lesions, and a reduction in brain atrophy, whereas higher baseline Nf-L predicted the opposite, he noted, adding that N-acetylaspartate-to-creatinine ratios also tended to vary inversely with Nf-L levels.

The most important findings of the study are “the sustained reduction in Nf-L levels after BMT, and that higher baseline levels predicted worse MRI outcomes,” Dr. Thebault noted. “Together these data add to a growing body of evidence that suggests that serum Nf-L has a role in monitoring treatment responses and even a predictive value in determining disease severity.”

This study was supported by Quanterix, which provided Nf-L assay kits. Dr. Thebault reported having no disclosures.

[email protected]

SOURCE: Thebault S et al. Neurology. 2018 Apr;90(15 Suppl.):P5.036.

LOS ANGELES – Serum neurofilament light chain shows promise as a biomarker for disease severity and response to treatment with autologous bone marrow transplant in patients with multiple sclerosis, according to findings from an analysis of paired samples.

solitude72/iStockphoto

Serum neurofilament light chain (Nf-L) levels were found to be significantly elevated in both the serum and cerebrospinal fluid (CSF) of 23 patients with aggressive multiple sclerosis (MS), compared with samples from 5 controls with noninflammatory neurologic conditions such as chronic fatigue syndrome or migraine. The levels in the patients with MS were significantly reduced following autologous bone marrow transplant (BMT), Simon Thebault, MD, reported in a poster at the annual meeting of the American Academy of Neurology.

Nf-L has been shown to be a biomarker for neuronal damage and to have potential for denoting disease severity and treatment response in MS; for this analysis, samples from patients were collected at baseline and annually for 3 years after transplant. Samples from controls were obtained for comparison.

“Our objective, really, was [to determine if we could] detect a treatment response in neurofilament light chain, and secondly, did the degree of neurofilament light chain being high at baseline predict anything about subsequent disease outcome?” Dr. Thebault, a third-year resident at the University of Ottawa, reported in the poster.

Indeed, a treatment response was detected; baseline levels were high, and levels in both serum and CSF were down significantly (P = .05) at both 1 and 3 years following bone marrow transplant, and they stayed down. “In fact, they were so low, they were not significantly different from [the levels] in noninflammatory controls,” he said, noting that serum and CSF NfL levels were highly correlated (r = .833; P less than .001).

Study subjects were patients with aggressive MS, characterized by early disease onset, rapid progression, frequent relapses, and poor treatment responses. Such patients who have received autologous BMT represent an interesting group for examining treatment responses, he said.

At baseline, these patients presumably have a high burden of tissue injury, which would be representative of high levels of Nf-L; good, prospective data show these patients have no evidence of ongoing inflammatory disease following an intensive regimen that includes chemoablation and reinfusion of autologous stem cells, which is representative of a significant reduction of neurofilament levels, he explained.

Importantly, serum and CSF levels were correlated in this study, he said, noting that most prior work has involved CSF, but “the real clinical utility in neurofilament light chain is probably in the serum, because patients don’t like having lumbar punctures too often.”

With respect to the second question pertaining to disease outcomes, the study did show that patients with baseline Nf-L levels above the median for the group had worse T1 lesion volumes at baseline and after transplant (P = .0021 at 36 months), and also had worsening brain atrophy even after transplant (P = .0389 at 60 months).

The curves appeared to be diverging, suggesting that, in the absence of inflammatory disease activity, patients with high Nf-L levels at baseline continue to have ongoing atrophy at a differential rate, compared with those with low baseline levels, Dr. Thebault said.

Other findings included better Expanded Disability Status Scale outcomes after transplant in patients with lower baseline Nf-L, and a trend toward worsening outcomes among those with higher baseline Nf-L levels, although the study may have been underpowered for this. Additionally, lower baseline Nf-L predicted significantly lower T1 and T2 lesion volume, number of gadolinium-enhancing lesions, and a reduction in brain atrophy, whereas higher baseline Nf-L predicted the opposite, he noted, adding that N-acetylaspartate-to-creatinine ratios also tended to vary inversely with Nf-L levels.

The most important findings of the study are “the sustained reduction in Nf-L levels after BMT, and that higher baseline levels predicted worse MRI outcomes,” Dr. Thebault noted. “Together these data add to a growing body of evidence that suggests that serum Nf-L has a role in monitoring treatment responses and even a predictive value in determining disease severity.”

This study was supported by Quanterix, which provided Nf-L assay kits. Dr. Thebault reported having no disclosures.

[email protected]

SOURCE: Thebault S et al. Neurology. 2018 Apr;90(15 Suppl.):P5.036.

LOS ANGELES – Serum neurofilament light chain shows promise as a biomarker for disease severity and response to treatment with autologous bone marrow transplant in patients with multiple sclerosis, according to findings from an analysis of paired samples.

solitude72/iStockphoto

Serum neurofilament light chain (Nf-L) levels were found to be significantly elevated in both the serum and cerebrospinal fluid (CSF) of 23 patients with aggressive multiple sclerosis (MS), compared with samples from 5 controls with noninflammatory neurologic conditions such as chronic fatigue syndrome or migraine. The levels in the patients with MS were significantly reduced following autologous bone marrow transplant (BMT), Simon Thebault, MD, reported in a poster at the annual meeting of the American Academy of Neurology.

Nf-L has been shown to be a biomarker for neuronal damage and to have potential for denoting disease severity and treatment response in MS; for this analysis, samples from patients were collected at baseline and annually for 3 years after transplant. Samples from controls were obtained for comparison.

“Our objective, really, was [to determine if we could] detect a treatment response in neurofilament light chain, and secondly, did the degree of neurofilament light chain being high at baseline predict anything about subsequent disease outcome?” Dr. Thebault, a third-year resident at the University of Ottawa, reported in the poster.

Indeed, a treatment response was detected; baseline levels were high, and levels in both serum and CSF were down significantly (P = .05) at both 1 and 3 years following bone marrow transplant, and they stayed down. “In fact, they were so low, they were not significantly different from [the levels] in noninflammatory controls,” he said, noting that serum and CSF NfL levels were highly correlated (r = .833; P less than .001).

Study subjects were patients with aggressive MS, characterized by early disease onset, rapid progression, frequent relapses, and poor treatment responses. Such patients who have received autologous BMT represent an interesting group for examining treatment responses, he said.

At baseline, these patients presumably have a high burden of tissue injury, which would be representative of high levels of Nf-L; good, prospective data show these patients have no evidence of ongoing inflammatory disease following an intensive regimen that includes chemoablation and reinfusion of autologous stem cells, which is representative of a significant reduction of neurofilament levels, he explained.

Importantly, serum and CSF levels were correlated in this study, he said, noting that most prior work has involved CSF, but “the real clinical utility in neurofilament light chain is probably in the serum, because patients don’t like having lumbar punctures too often.”

With respect to the second question pertaining to disease outcomes, the study did show that patients with baseline Nf-L levels above the median for the group had worse T1 lesion volumes at baseline and after transplant (P = .0021 at 36 months), and also had worsening brain atrophy even after transplant (P = .0389 at 60 months).

The curves appeared to be diverging, suggesting that, in the absence of inflammatory disease activity, patients with high Nf-L levels at baseline continue to have ongoing atrophy at a differential rate, compared with those with low baseline levels, Dr. Thebault said.

Other findings included better Expanded Disability Status Scale outcomes after transplant in patients with lower baseline Nf-L, and a trend toward worsening outcomes among those with higher baseline Nf-L levels, although the study may have been underpowered for this. Additionally, lower baseline Nf-L predicted significantly lower T1 and T2 lesion volume, number of gadolinium-enhancing lesions, and a reduction in brain atrophy, whereas higher baseline Nf-L predicted the opposite, he noted, adding that N-acetylaspartate-to-creatinine ratios also tended to vary inversely with Nf-L levels.

The most important findings of the study are “the sustained reduction in Nf-L levels after BMT, and that higher baseline levels predicted worse MRI outcomes,” Dr. Thebault noted. “Together these data add to a growing body of evidence that suggests that serum Nf-L has a role in monitoring treatment responses and even a predictive value in determining disease severity.”

This study was supported by Quanterix, which provided Nf-L assay kits. Dr. Thebault reported having no disclosures.

[email protected]

SOURCE: Thebault S et al. Neurology. 2018 Apr;90(15 Suppl.):P5.036.

Adherents of the Abrahamic faiths or students of the Bible as literature will easily recall the circumstances of this famous quotation from the Hebrew Scriptures. Cain has killed his brother Abel, earning the disrepute of committing the first murder in biblical history. Scholars of ethics have answered Cain’s sardonic question in the affirmative: avowing that while the individual is primarily responsible for his conduct and its consequences, the community also bears a responsibility.¹

Many of you will have seen news clips of yet another Department of Veteran Affairs (VA) scandal: This one involving an impaired pathologist. I have purposely not used the pathologist’s name to emphasize that our shared obligation to protect patients from impaired members of the profession goes far beyond this single outrage. Although we might believe we could never be that individual; none of us are immune from depression, dementia, or physical disabilities that diminish our ability to care for patients. Although it is worth noting that having read or watched everything I could find on the story, the “facts” are few and far between, which I will argue later only underscores the problems with professional accountability especially in a large bureaucratic organization.

This column is not meant to impugn or exculpate anyone but to encourage us to reflect on our ethical awareness and response to hints that there might be an impaired practitioner among us. The Fayetteville VA Medical Center (VAMC) in North Carolina—ground zero for this incident—held several town halls in which anxious and angry veterans demanded an explanation for how an impaired pathologist could have placed in harm’s way nearly 19,000 patients.² Of this cohort, 5,250 patients have died since 2005. The VA leadership, including the VISN 16 network director and the interim medical director of the Fayetteville VAMC indicated that out of 911 pathology reports that had undergone expert peer review, an incorrect diagnosis was identified in at least 7 with 1 possible associated death.³

The VA officials estimate that the entire review may involve more than 30,000 cases. The allegations are that the pathologist was impaired due to a substance use disorder, in this case alcohol. In interviews, the physician has admitted the alcohol problem and receiving treatment for it but denied he was ever impaired on duty.⁴ This denial directly contradicts the VA reports that he was intoxicated on duty at least twice.

We do know that the physician in question was enrolled in the Mississippi Physician Health Program (PHP). The Federation of State Physician Health Programs (FSPHP), of which the Mississippi program is a member, provides confidential initial evaluation, ongoing treatment, and monitoring for state licensed health care practitioners with a substance use or other mental health disorder or other condition that could potentially impair their fitness for duty. The PHPs have been career saving for many physicians and other health care professionals. The incentives to return to the practice of medicine are powerful, leading to a higher recovery rate than that of the general population.⁵

According to FSPHP, “While both PHPs and state licensing boards are engaged in patient safety efforts, PHPs primary focus is on improving the health of the physician, and the licensing board’s primary duty is to protect the public.”⁶ This potential conflict of interest has been criticized recently.⁷ News reports suggest that the ambiguity of this relationship between PHP and licensing board may have left a “who’s minding the store” mentality. But here are the facts of this particular case.

In March 2016, an employee reported that the pathologist was intoxicated on duty, and he was immediately removed from service. Of the many elephants in the room, the biggest moral pachyderm is why, given the chronic and progressive nature of substance use disorders did it take 11 years for a formal report leading to action?

Having been in circles of leadership, I know well that often there is much discussed that cannot be disclosed, which frequently contributes to staff demoralization. Dozens of medical center employees over decades must have seen behaviors; some of those employees likely reported their observations. The news reports are silent on this point except for attributing it to “fear of retaliation.” In our current VA climate this is a major intimidator of staff trying to tell the truth and leaders seeking to do what is right. Yet research has identified myriad other motives for not reporting impaired colleagues, including loyalty, collusion, denial, indifference, scarcity of resources, and overwork.⁸

In October 2017, the pathologist was again found intoxicated on the job, attributing it to a migraine headache. The hospital investigated, but the pathologist may have continued working in some capacity. Finally, after the pathologist was arrested for driving while intoxicated March 1 of this year, the interim VAMC director contacted the Mississippi licensing board, declaring that the pathologist “had failed to meet standards of practice” and indicted that he “constituted an imminent threat to patient welfare.” The Arkansas Medical Foundation then rescinded its support of the pathologist, citing the pathologist’s failure to adhere to monitoring and reporting requirements. The Mississippi program followed suit on June 20, and the medical board rescinded his license.

All employees at whatever level are owed due process and respect for their rights, but Congress recently saw fit to legislate further limits on federal employee protections. Most health care administrators still standing in the chaos of today’s VA would tell you that survival is all about when did you know and what did you do about it? But it is not just administrators, the code of ethics of almost every health care profession includes an obligation to report impaired practitioners. Principle II of the American Medical Association Code of Ethics states, “A physician shall uphold the standards of professionalism, be honest in all professional interactions, and strive to report physicians deficient in character or competence, or engaging in fraud or deception, to appropriate entities.”⁹

If one is in private practice in a small town, it is easier to pull your friend aside on the golf course and say you seem to be having a problem, counsel your friend to get help, often through a PHP. Then if the gentler approach fails, take the harder action of reporting to the medical board or other authority. To report takes moral courage. It takes seeing that the practitioner is not betraying the “white line” of health care professions but honoring the highest commitment of professionalism to the patient.

The last thing we need in our current suspicious and fearful environment is to turn VAMCs and clinics into a dystopia.Yet reporting in a large organization with rules and red tape can seem terrifying, overwhelming, and confusing. A fair, safe, transparent, clear, and consistent means for staff to discharge their ethical obligations is sorely needed. Or else we will be reading about another tragic scandal and asking each other, “How could this have happened?”

Adherents of the Abrahamic faiths or students of the Bible as literature will easily recall the circumstances of this famous quotation from the Hebrew Scriptures. Cain has killed his brother Abel, earning the disrepute of committing the first murder in biblical history. Scholars of ethics have answered Cain’s sardonic question in the affirmative: avowing that while the individual is primarily responsible for his conduct and its consequences, the community also bears a responsibility.¹

Many of you will have seen news clips of yet another Department of Veteran Affairs (VA) scandal: This one involving an impaired pathologist. I have purposely not used the pathologist’s name to emphasize that our shared obligation to protect patients from impaired members of the profession goes far beyond this single outrage. Although we might believe we could never be that individual; none of us are immune from depression, dementia, or physical disabilities that diminish our ability to care for patients. Although it is worth noting that having read or watched everything I could find on the story, the “facts” are few and far between, which I will argue later only underscores the problems with professional accountability especially in a large bureaucratic organization.

This column is not meant to impugn or exculpate anyone but to encourage us to reflect on our ethical awareness and response to hints that there might be an impaired practitioner among us. The Fayetteville VA Medical Center (VAMC) in North Carolina—ground zero for this incident—held several town halls in which anxious and angry veterans demanded an explanation for how an impaired pathologist could have placed in harm’s way nearly 19,000 patients.² Of this cohort, 5,250 patients have died since 2005. The VA leadership, including the VISN 16 network director and the interim medical director of the Fayetteville VAMC indicated that out of 911 pathology reports that had undergone expert peer review, an incorrect diagnosis was identified in at least 7 with 1 possible associated death.³

The VA officials estimate that the entire review may involve more than 30,000 cases. The allegations are that the pathologist was impaired due to a substance use disorder, in this case alcohol. In interviews, the physician has admitted the alcohol problem and receiving treatment for it but denied he was ever impaired on duty.⁴ This denial directly contradicts the VA reports that he was intoxicated on duty at least twice.

We do know that the physician in question was enrolled in the Mississippi Physician Health Program (PHP). The Federation of State Physician Health Programs (FSPHP), of which the Mississippi program is a member, provides confidential initial evaluation, ongoing treatment, and monitoring for state licensed health care practitioners with a substance use or other mental health disorder or other condition that could potentially impair their fitness for duty. The PHPs have been career saving for many physicians and other health care professionals. The incentives to return to the practice of medicine are powerful, leading to a higher recovery rate than that of the general population.⁵

According to FSPHP, “While both PHPs and state licensing boards are engaged in patient safety efforts, PHPs primary focus is on improving the health of the physician, and the licensing board’s primary duty is to protect the public.”⁶ This potential conflict of interest has been criticized recently.⁷ News reports suggest that the ambiguity of this relationship between PHP and licensing board may have left a “who’s minding the store” mentality. But here are the facts of this particular case.

In March 2016, an employee reported that the pathologist was intoxicated on duty, and he was immediately removed from service. Of the many elephants in the room, the biggest moral pachyderm is why, given the chronic and progressive nature of substance use disorders did it take 11 years for a formal report leading to action?

Having been in circles of leadership, I know well that often there is much discussed that cannot be disclosed, which frequently contributes to staff demoralization. Dozens of medical center employees over decades must have seen behaviors; some of those employees likely reported their observations. The news reports are silent on this point except for attributing it to “fear of retaliation.” In our current VA climate this is a major intimidator of staff trying to tell the truth and leaders seeking to do what is right. Yet research has identified myriad other motives for not reporting impaired colleagues, including loyalty, collusion, denial, indifference, scarcity of resources, and overwork.⁸

In October 2017, the pathologist was again found intoxicated on the job, attributing it to a migraine headache. The hospital investigated, but the pathologist may have continued working in some capacity. Finally, after the pathologist was arrested for driving while intoxicated March 1 of this year, the interim VAMC director contacted the Mississippi licensing board, declaring that the pathologist “had failed to meet standards of practice” and indicted that he “constituted an imminent threat to patient welfare.” The Arkansas Medical Foundation then rescinded its support of the pathologist, citing the pathologist’s failure to adhere to monitoring and reporting requirements. The Mississippi program followed suit on June 20, and the medical board rescinded his license.

All employees at whatever level are owed due process and respect for their rights, but Congress recently saw fit to legislate further limits on federal employee protections. Most health care administrators still standing in the chaos of today’s VA would tell you that survival is all about when did you know and what did you do about it? But it is not just administrators, the code of ethics of almost every health care profession includes an obligation to report impaired practitioners. Principle II of the American Medical Association Code of Ethics states, “A physician shall uphold the standards of professionalism, be honest in all professional interactions, and strive to report physicians deficient in character or competence, or engaging in fraud or deception, to appropriate entities.”⁹

If one is in private practice in a small town, it is easier to pull your friend aside on the golf course and say you seem to be having a problem, counsel your friend to get help, often through a PHP. Then if the gentler approach fails, take the harder action of reporting to the medical board or other authority. To report takes moral courage. It takes seeing that the practitioner is not betraying the “white line” of health care professions but honoring the highest commitment of professionalism to the patient.

The last thing we need in our current suspicious and fearful environment is to turn VAMCs and clinics into a dystopia.Yet reporting in a large organization with rules and red tape can seem terrifying, overwhelming, and confusing. A fair, safe, transparent, clear, and consistent means for staff to discharge their ethical obligations is sorely needed. Or else we will be reading about another tragic scandal and asking each other, “How could this have happened?”

Adherents of the Abrahamic faiths or students of the Bible as literature will easily recall the circumstances of this famous quotation from the Hebrew Scriptures. Cain has killed his brother Abel, earning the disrepute of committing the first murder in biblical history. Scholars of ethics have answered Cain’s sardonic question in the affirmative: avowing that while the individual is primarily responsible for his conduct and its consequences, the community also bears a responsibility.¹

Many of you will have seen news clips of yet another Department of Veteran Affairs (VA) scandal: This one involving an impaired pathologist. I have purposely not used the pathologist’s name to emphasize that our shared obligation to protect patients from impaired members of the profession goes far beyond this single outrage. Although we might believe we could never be that individual; none of us are immune from depression, dementia, or physical disabilities that diminish our ability to care for patients. Although it is worth noting that having read or watched everything I could find on the story, the “facts” are few and far between, which I will argue later only underscores the problems with professional accountability especially in a large bureaucratic organization.

This column is not meant to impugn or exculpate anyone but to encourage us to reflect on our ethical awareness and response to hints that there might be an impaired practitioner among us. The Fayetteville VA Medical Center (VAMC) in North Carolina—ground zero for this incident—held several town halls in which anxious and angry veterans demanded an explanation for how an impaired pathologist could have placed in harm’s way nearly 19,000 patients.² Of this cohort, 5,250 patients have died since 2005. The VA leadership, including the VISN 16 network director and the interim medical director of the Fayetteville VAMC indicated that out of 911 pathology reports that had undergone expert peer review, an incorrect diagnosis was identified in at least 7 with 1 possible associated death.³

The VA officials estimate that the entire review may involve more than 30,000 cases. The allegations are that the pathologist was impaired due to a substance use disorder, in this case alcohol. In interviews, the physician has admitted the alcohol problem and receiving treatment for it but denied he was ever impaired on duty.⁴ This denial directly contradicts the VA reports that he was intoxicated on duty at least twice.

We do know that the physician in question was enrolled in the Mississippi Physician Health Program (PHP). The Federation of State Physician Health Programs (FSPHP), of which the Mississippi program is a member, provides confidential initial evaluation, ongoing treatment, and monitoring for state licensed health care practitioners with a substance use or other mental health disorder or other condition that could potentially impair their fitness for duty. The PHPs have been career saving for many physicians and other health care professionals. The incentives to return to the practice of medicine are powerful, leading to a higher recovery rate than that of the general population.⁵

According to FSPHP, “While both PHPs and state licensing boards are engaged in patient safety efforts, PHPs primary focus is on improving the health of the physician, and the licensing board’s primary duty is to protect the public.”⁶ This potential conflict of interest has been criticized recently.⁷ News reports suggest that the ambiguity of this relationship between PHP and licensing board may have left a “who’s minding the store” mentality. But here are the facts of this particular case.

In March 2016, an employee reported that the pathologist was intoxicated on duty, and he was immediately removed from service. Of the many elephants in the room, the biggest moral pachyderm is why, given the chronic and progressive nature of substance use disorders did it take 11 years for a formal report leading to action?

Having been in circles of leadership, I know well that often there is much discussed that cannot be disclosed, which frequently contributes to staff demoralization. Dozens of medical center employees over decades must have seen behaviors; some of those employees likely reported their observations. The news reports are silent on this point except for attributing it to “fear of retaliation.” In our current VA climate this is a major intimidator of staff trying to tell the truth and leaders seeking to do what is right. Yet research has identified myriad other motives for not reporting impaired colleagues, including loyalty, collusion, denial, indifference, scarcity of resources, and overwork.⁸

In October 2017, the pathologist was again found intoxicated on the job, attributing it to a migraine headache. The hospital investigated, but the pathologist may have continued working in some capacity. Finally, after the pathologist was arrested for driving while intoxicated March 1 of this year, the interim VAMC director contacted the Mississippi licensing board, declaring that the pathologist “had failed to meet standards of practice” and indicted that he “constituted an imminent threat to patient welfare.” The Arkansas Medical Foundation then rescinded its support of the pathologist, citing the pathologist’s failure to adhere to monitoring and reporting requirements. The Mississippi program followed suit on June 20, and the medical board rescinded his license.

All employees at whatever level are owed due process and respect for their rights, but Congress recently saw fit to legislate further limits on federal employee protections. Most health care administrators still standing in the chaos of today’s VA would tell you that survival is all about when did you know and what did you do about it? But it is not just administrators, the code of ethics of almost every health care profession includes an obligation to report impaired practitioners. Principle II of the American Medical Association Code of Ethics states, “A physician shall uphold the standards of professionalism, be honest in all professional interactions, and strive to report physicians deficient in character or competence, or engaging in fraud or deception, to appropriate entities.”⁹

If one is in private practice in a small town, it is easier to pull your friend aside on the golf course and say you seem to be having a problem, counsel your friend to get help, often through a PHP. Then if the gentler approach fails, take the harder action of reporting to the medical board or other authority. To report takes moral courage. It takes seeing that the practitioner is not betraying the “white line” of health care professions but honoring the highest commitment of professionalism to the patient.

The last thing we need in our current suspicious and fearful environment is to turn VAMCs and clinics into a dystopia.Yet reporting in a large organization with rules and red tape can seem terrifying, overwhelming, and confusing. A fair, safe, transparent, clear, and consistent means for staff to discharge their ethical obligations is sorely needed. Or else we will be reading about another tragic scandal and asking each other, “How could this have happened?”

As patients with HIV, hepatitis B (HBV), and hepatitis C (HCV) live longer, more active lives with the help of antiviral treatments, they are now more often having joint replacement surgeries. But HIV, HBV, and HCV can increase the risk of postoperative complications, say researchers from Duke University in North Carolina.

The researchers studied 16,338 patients in 4 cohorts: those with HIV, HBV, HCV, and HIV plus HBV or HCV. They evaluated the patients at 30 days, 90 days, and 2 years after total joint arthroplasty (TJA), comparing their progress with that of a control group.

Patients with HBV and HCV were at risk of both acute and long-term medical and surgical complications. At 90 days and 2 years, the participants had increased risk of pneumonia, sepsis, joint infection, and revision surgery. They also had a greater risk of complications than did patients with HIV, especially for infection, within the first 90 days postsurgery.

Notably, after TJA, patients with HCV had increased risk of acute kidney injury, sepsis, and transfusion at 30 and 90 days. After hip replacement, patients with HBV had a higher risk of acute kidney injury, pneumonia, and transfusion at 30 and 90 days.

Only 364 patients in the study had both HIV and HBV or HBC, but they did have a greater risk of transfusion at 30 and 90 days following both knee and hip surgery.

Following total hip arthroplasty, patients with HIV were more at risk for deep vein thrombosis and transfusion rather than infection. The lower incidence of infection is likely to be related to effective  highly active antiretroviral therapy, the researchers say. HIV patients also were more likely to have mechanical complications, such as loosening, periprosthetic fracture, and revision at 90 days, but not at 2 years. Patients with HIV who underwent total knee arthroplasty (TKA) had a higher risk of death at 30 days and medical complications at 90 days. At 2 years, they had a higher risk of periprosthetic joint infection, irrigation and debridement, and revision. The researchers say the higher incidence of mechanical complications can be explained by the younger, more active, and healthy HIV patients in the cohort—the majority were aged younger than 65 years. They also emphasize that the only risk of infection following TJA in their study was 2 years after TKA.

The researchers suggest that their findings could help prompt future guidelines supporting routine screening prior to elective TJA.

Source:
Kildow BJ, Politzer CS, DiLallo M, Bolognesi MP, Seyler TM. J Arthroplasty. 2018;33(suppl 7):S86-S92.
doi: 10.1016/j.arth.2017.10.061.

As patients with HIV, hepatitis B (HBV), and hepatitis C (HCV) live longer, more active lives with the help of antiviral treatments, they are now more often having joint replacement surgeries. But HIV, HBV, and HCV can increase the risk of postoperative complications, say researchers from Duke University in North Carolina.

The researchers studied 16,338 patients in 4 cohorts: those with HIV, HBV, HCV, and HIV plus HBV or HCV. They evaluated the patients at 30 days, 90 days, and 2 years after total joint arthroplasty (TJA), comparing their progress with that of a control group.

Patients with HBV and HCV were at risk of both acute and long-term medical and surgical complications. At 90 days and 2 years, the participants had increased risk of pneumonia, sepsis, joint infection, and revision surgery. They also had a greater risk of complications than did patients with HIV, especially for infection, within the first 90 days postsurgery.

Notably, after TJA, patients with HCV had increased risk of acute kidney injury, sepsis, and transfusion at 30 and 90 days. After hip replacement, patients with HBV had a higher risk of acute kidney injury, pneumonia, and transfusion at 30 and 90 days.

Only 364 patients in the study had both HIV and HBV or HBC, but they did have a greater risk of transfusion at 30 and 90 days following both knee and hip surgery.

Following total hip arthroplasty, patients with HIV were more at risk for deep vein thrombosis and transfusion rather than infection. The lower incidence of infection is likely to be related to effective  highly active antiretroviral therapy, the researchers say. HIV patients also were more likely to have mechanical complications, such as loosening, periprosthetic fracture, and revision at 90 days, but not at 2 years. Patients with HIV who underwent total knee arthroplasty (TKA) had a higher risk of death at 30 days and medical complications at 90 days. At 2 years, they had a higher risk of periprosthetic joint infection, irrigation and debridement, and revision. The researchers say the higher incidence of mechanical complications can be explained by the younger, more active, and healthy HIV patients in the cohort—the majority were aged younger than 65 years. They also emphasize that the only risk of infection following TJA in their study was 2 years after TKA.

The researchers suggest that their findings could help prompt future guidelines supporting routine screening prior to elective TJA.

Source:
Kildow BJ, Politzer CS, DiLallo M, Bolognesi MP, Seyler TM. J Arthroplasty. 2018;33(suppl 7):S86-S92.
doi: 10.1016/j.arth.2017.10.061.

As patients with HIV, hepatitis B (HBV), and hepatitis C (HCV) live longer, more active lives with the help of antiviral treatments, they are now more often having joint replacement surgeries. But HIV, HBV, and HCV can increase the risk of postoperative complications, say researchers from Duke University in North Carolina.

The researchers studied 16,338 patients in 4 cohorts: those with HIV, HBV, HCV, and HIV plus HBV or HCV. They evaluated the patients at 30 days, 90 days, and 2 years after total joint arthroplasty (TJA), comparing their progress with that of a control group.

Patients with HBV and HCV were at risk of both acute and long-term medical and surgical complications. At 90 days and 2 years, the participants had increased risk of pneumonia, sepsis, joint infection, and revision surgery. They also had a greater risk of complications than did patients with HIV, especially for infection, within the first 90 days postsurgery.

Notably, after TJA, patients with HCV had increased risk of acute kidney injury, sepsis, and transfusion at 30 and 90 days. After hip replacement, patients with HBV had a higher risk of acute kidney injury, pneumonia, and transfusion at 30 and 90 days.

Only 364 patients in the study had both HIV and HBV or HBC, but they did have a greater risk of transfusion at 30 and 90 days following both knee and hip surgery.

Following total hip arthroplasty, patients with HIV were more at risk for deep vein thrombosis and transfusion rather than infection. The lower incidence of infection is likely to be related to effective  highly active antiretroviral therapy, the researchers say. HIV patients also were more likely to have mechanical complications, such as loosening, periprosthetic fracture, and revision at 90 days, but not at 2 years. Patients with HIV who underwent total knee arthroplasty (TKA) had a higher risk of death at 30 days and medical complications at 90 days. At 2 years, they had a higher risk of periprosthetic joint infection, irrigation and debridement, and revision. The researchers say the higher incidence of mechanical complications can be explained by the younger, more active, and healthy HIV patients in the cohort—the majority were aged younger than 65 years. They also emphasize that the only risk of infection following TJA in their study was 2 years after TKA.

The researchers suggest that their findings could help prompt future guidelines supporting routine screening prior to elective TJA.

Source:
Kildow BJ, Politzer CS, DiLallo M, Bolognesi MP, Seyler TM. J Arthroplasty. 2018;33(suppl 7):S86-S92.
doi: 10.1016/j.arth.2017.10.061.

Micrograph showing DLBCL

The European Commission (EC) has approved the chimeric antigen receptor (CAR) T-cell therapy axicabtagene ciloleucel (Yescarta®) to treat two types of lymphoma.

Axicabtagene ciloleucel is now approved to treat adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) and primary mediastinal large B-cell lymphoma (PMBCL) after two or more lines of systemic therapy.

The approval extends to all member countries of the European Union, as well as Norway, Iceland, and Liechtenstein.

The EC’s approval of axicabtagene ciloleucel is supported by data from the ZUMA-1 trial.

Results from this phase 2 trial were presented at the 2017 ASH Annual Meeting and published simultaneously in NEJM.

The trial enrolled 111 patients with relapsed/refractory B-cell lymphomas. There were 101 patients who received axicabtagene ciloleucel—77 with DLBCL, 8 with PMBCL, and 16 with transformed follicular lymphoma (TFL).

Patients received conditioning with low-dose cyclophosphamide and fludarabine, followed by axicabtagene ciloleucel.

The objective response rate (ORR) was 82% (n=83), and the complete response (CR) rate was 54% (n=55).

Among the DLBCL patients, the ORR was 82% (63/77), and the CR rate was 49% (38/77). In the patients with PMBCL or TFL, the ORR was 83% (20/24), and the CR rate was 71% (17/24).

With a median follow-up of 15.4 months, 42% of patients retained their response, and 40% retained a CR.

At 18 months, the overall survival rate was 52%. Most deaths were due to disease progression.

However, 2 patients died of adverse events related to axicabtagene ciloleucel, both cytokine release syndrome.

The most common grade 3 or higher adverse events were neutropenia (78%), anemia (43%), thrombocytopenia (38%), and febrile neutropenia (31%).

Grade 3 or higher cytokine release syndrome occurred in 13% of patients, and grade 3 or higher neurologic events occurred in 28%.

Micrograph showing DLBCL

The European Commission (EC) has approved the chimeric antigen receptor (CAR) T-cell therapy axicabtagene ciloleucel (Yescarta®) to treat two types of lymphoma.

Axicabtagene ciloleucel is now approved to treat adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) and primary mediastinal large B-cell lymphoma (PMBCL) after two or more lines of systemic therapy.

The approval extends to all member countries of the European Union, as well as Norway, Iceland, and Liechtenstein.

The EC’s approval of axicabtagene ciloleucel is supported by data from the ZUMA-1 trial.

Results from this phase 2 trial were presented at the 2017 ASH Annual Meeting and published simultaneously in NEJM.

The trial enrolled 111 patients with relapsed/refractory B-cell lymphomas. There were 101 patients who received axicabtagene ciloleucel—77 with DLBCL, 8 with PMBCL, and 16 with transformed follicular lymphoma (TFL).

Patients received conditioning with low-dose cyclophosphamide and fludarabine, followed by axicabtagene ciloleucel.

The objective response rate (ORR) was 82% (n=83), and the complete response (CR) rate was 54% (n=55).

Among the DLBCL patients, the ORR was 82% (63/77), and the CR rate was 49% (38/77). In the patients with PMBCL or TFL, the ORR was 83% (20/24), and the CR rate was 71% (17/24).

With a median follow-up of 15.4 months, 42% of patients retained their response, and 40% retained a CR.

At 18 months, the overall survival rate was 52%. Most deaths were due to disease progression.

However, 2 patients died of adverse events related to axicabtagene ciloleucel, both cytokine release syndrome.

The most common grade 3 or higher adverse events were neutropenia (78%), anemia (43%), thrombocytopenia (38%), and febrile neutropenia (31%).

Grade 3 or higher cytokine release syndrome occurred in 13% of patients, and grade 3 or higher neurologic events occurred in 28%.

Micrograph showing DLBCL

The European Commission (EC) has approved the chimeric antigen receptor (CAR) T-cell therapy axicabtagene ciloleucel (Yescarta®) to treat two types of lymphoma.

Axicabtagene ciloleucel is now approved to treat adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) and primary mediastinal large B-cell lymphoma (PMBCL) after two or more lines of systemic therapy.

The approval extends to all member countries of the European Union, as well as Norway, Iceland, and Liechtenstein.

The EC’s approval of axicabtagene ciloleucel is supported by data from the ZUMA-1 trial.

Results from this phase 2 trial were presented at the 2017 ASH Annual Meeting and published simultaneously in NEJM.

The trial enrolled 111 patients with relapsed/refractory B-cell lymphomas. There were 101 patients who received axicabtagene ciloleucel—77 with DLBCL, 8 with PMBCL, and 16 with transformed follicular lymphoma (TFL).

Patients received conditioning with low-dose cyclophosphamide and fludarabine, followed by axicabtagene ciloleucel.

The objective response rate (ORR) was 82% (n=83), and the complete response (CR) rate was 54% (n=55).

Among the DLBCL patients, the ORR was 82% (63/77), and the CR rate was 49% (38/77). In the patients with PMBCL or TFL, the ORR was 83% (20/24), and the CR rate was 71% (17/24).

With a median follow-up of 15.4 months, 42% of patients retained their response, and 40% retained a CR.

At 18 months, the overall survival rate was 52%. Most deaths were due to disease progression.

However, 2 patients died of adverse events related to axicabtagene ciloleucel, both cytokine release syndrome.

The most common grade 3 or higher adverse events were neutropenia (78%), anemia (43%), thrombocytopenia (38%), and febrile neutropenia (31%).

Grade 3 or higher cytokine release syndrome occurred in 13% of patients, and grade 3 or higher neurologic events occurred in 28%.