A punch biopsy from one of the lesions on the feet showed subtle basal vacuolar interface inflammation on the epidermis and rare apoptotic keratinocytes. There was an underlying dermal lymphocytic inflammatory infiltrate around the vascular plexus. Dermal mucin appeared slightly increased. The histologic findings are consistent with pernio. He had a negative direct immunofluorescence study.

Laboratory work-up showed an elevated antinuclear antibody (ANA) of 1:620; positive anticardiolipin IgM was at 15.2. A complete blood count showed no anemia or lymphopenia, he had normal complement C3 and C4 levels, normal urinalysis, negative cryoglobulins and cold agglutinins, and a normal protein electrophoresis.

Given the chronicity of his lesions, the lack of improvement with weather changes, the histopathologic findings of a vacuolar interface dermatitis and the positive ANA titer he was diagnosed with chilblain lupus.

Chilblain lupus erythematosus (CLE) is an uncommon form of chronic cutaneous lupus erythematosus that presents with tender pink to violaceous macules, papules, and/or nodules that sometimes can ulcerate and are present on the fingers, toes, and sometimes the nose and ears. The lesions are usually triggered by cold exposure.¹ These patients also have clinical and laboratory findings consistent with lupus erythematosus.

Even though more studies are needed to clarify the clinical and histopathologic features of chilblain lupus, compared with idiopathic pernio, some authors suggest several characteristics: CLE lesions tend to persist in summer months, as occurred in our patient, and histopathologic evaluation usually shows vacuolar and interface inflammation on the basal cell layer and may also have a positive lupus band on direct immunofluorescence.² About 20% of patient with CLE may later develop systemic lupus erythematosus.³

There is also a familial form of CLE which is usually inherited as an autosomal-dominant trait. Mutations in TREX1, SAMHD1, and STING have been described in these patients.⁴ Affected children present with skin lesions at a young age and those with TREX1 mutations are at a higher risk to develop systemic lupus erythematosus.

The differential diagnosis of chilblain lupus includes idiopathic pernio or pernio secondary to other conditions. Other conditions that are thought to be associated with pernio, besides lupus erythematosus, include infectious causes (hepatitis B, COVID-19 infection),⁵ autoimmune conditions, malignancy and hematologic disorders (paraproteinemia).⁶ In histopathology, pernio lesions present with dermal edema and superficial and deep lymphocytic infiltrate.

The pathogenesis of pernio is not fully understood but is thought be related to vasospasm with secondary poor perfusion and ischemia and type I interferon (INF1) immune response. A recent review of the published studies trying to explain the causality between COVID 19 and pernio-like lesions, from January 2020 to December 2020, speculate several possible mechanisms: an increase in the vasoconstrictive, prothrombotic, and proinflammatory effects of the angiotensin II pathway through activation of the ACE2 by the virus; COVID-19 triggers a robust INF1 immune response in predisposed patients; pernio as a sign of mild disease, may be explained by genetic and hormonal differences in the patients affected.⁷

Another condition that can be confused with CLE is Raynaud phenomenon, were patients present with white to purple to red patches on the fingers and toes after exposure to cold, but in comparison with pernio, the lesions improve within minutes to hours after rewarming. Secondary Raynaud phenomenon can be seen in patients with systemic lupus erythematosus and in patients with other connective tissue disorders. The skin lesions in our patient were persistent and were not triggered by cold exposure, making Raynaud phenomenon less likely. Children with vasculitis can present with painful red, violaceous, or necrotic lesions on the extremities, which can mimic pernio. Vasculitis lesions tend to be more purpuric and angulated, compared with pernio lesions, though in severe cases of pernio with ulceration it may be difficult to distinguish between the two entities and a skin biopsy may be needed.

Sweet syndrome, also known as acute febrile neutrophilic dermatosis, is a rare skin condition in which children present with edematous tender nodules on the hands and with less frequency in other parts of the body with associated fever, malaise, conjunctivitis, or joint pain and it is usually associated with infection or malignancy. Our patient denied any systemic symptoms and had no conjunctivitis nor arthritis.

Most patients with idiopathic pernio do not require a biopsy or further laboratory evaluation unless the lesions are atypical, chronic, or there is a suspected associated condition. The workup for patients with prolonged or atypical pernio-like lesions include a skin biopsy with direct immunofluorescence, ANA, complete blood count, complement levels, antiphospholipid antibodies, cold agglutinins, and cryoglobulins.

Treatment of mild CLE is with moderate- to high-potency topical corticosteroids. In those patients not responding to topical measures and keeping the extremities warm, the use of hydroxychloroquine has been reported to be beneficial in some patients as well as the use of calcium-channel blockers.

Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego.

References

1. Su WP et al. Cutis. 1994 Dec;54(6):395-9.

2. Boada A et al. Am J Dermatopathol. 2010 Feb;32(1):19-23.

3. Patel et al. SBMJ Case Rep. 2013;2013:bcr2013201165.

4. Genes Yi et al. BMC. 2020 Apr 15;18(1):32.

5. Battesti G et al. J Am Acad Dermatol. 2020;83(4):1219-22.

6. Cappel JA et al. Mayo Clin Proc. 2014 Feb;89(2):207-15.

7. Cappel MA et al. Mayo Clin Proc. 2021;96(4):989-1005.

A punch biopsy from one of the lesions on the feet showed subtle basal vacuolar interface inflammation on the epidermis and rare apoptotic keratinocytes. There was an underlying dermal lymphocytic inflammatory infiltrate around the vascular plexus. Dermal mucin appeared slightly increased. The histologic findings are consistent with pernio. He had a negative direct immunofluorescence study.

Laboratory work-up showed an elevated antinuclear antibody (ANA) of 1:620; positive anticardiolipin IgM was at 15.2. A complete blood count showed no anemia or lymphopenia, he had normal complement C3 and C4 levels, normal urinalysis, negative cryoglobulins and cold agglutinins, and a normal protein electrophoresis.

Given the chronicity of his lesions, the lack of improvement with weather changes, the histopathologic findings of a vacuolar interface dermatitis and the positive ANA titer he was diagnosed with chilblain lupus.

Chilblain lupus erythematosus (CLE) is an uncommon form of chronic cutaneous lupus erythematosus that presents with tender pink to violaceous macules, papules, and/or nodules that sometimes can ulcerate and are present on the fingers, toes, and sometimes the nose and ears. The lesions are usually triggered by cold exposure.¹ These patients also have clinical and laboratory findings consistent with lupus erythematosus.

Even though more studies are needed to clarify the clinical and histopathologic features of chilblain lupus, compared with idiopathic pernio, some authors suggest several characteristics: CLE lesions tend to persist in summer months, as occurred in our patient, and histopathologic evaluation usually shows vacuolar and interface inflammation on the basal cell layer and may also have a positive lupus band on direct immunofluorescence.² About 20% of patient with CLE may later develop systemic lupus erythematosus.³

There is also a familial form of CLE which is usually inherited as an autosomal-dominant trait. Mutations in TREX1, SAMHD1, and STING have been described in these patients.⁴ Affected children present with skin lesions at a young age and those with TREX1 mutations are at a higher risk to develop systemic lupus erythematosus.

The differential diagnosis of chilblain lupus includes idiopathic pernio or pernio secondary to other conditions. Other conditions that are thought to be associated with pernio, besides lupus erythematosus, include infectious causes (hepatitis B, COVID-19 infection),⁵ autoimmune conditions, malignancy and hematologic disorders (paraproteinemia).⁶ In histopathology, pernio lesions present with dermal edema and superficial and deep lymphocytic infiltrate.

The pathogenesis of pernio is not fully understood but is thought be related to vasospasm with secondary poor perfusion and ischemia and type I interferon (INF1) immune response. A recent review of the published studies trying to explain the causality between COVID 19 and pernio-like lesions, from January 2020 to December 2020, speculate several possible mechanisms: an increase in the vasoconstrictive, prothrombotic, and proinflammatory effects of the angiotensin II pathway through activation of the ACE2 by the virus; COVID-19 triggers a robust INF1 immune response in predisposed patients; pernio as a sign of mild disease, may be explained by genetic and hormonal differences in the patients affected.⁷

Another condition that can be confused with CLE is Raynaud phenomenon, were patients present with white to purple to red patches on the fingers and toes after exposure to cold, but in comparison with pernio, the lesions improve within minutes to hours after rewarming. Secondary Raynaud phenomenon can be seen in patients with systemic lupus erythematosus and in patients with other connective tissue disorders. The skin lesions in our patient were persistent and were not triggered by cold exposure, making Raynaud phenomenon less likely. Children with vasculitis can present with painful red, violaceous, or necrotic lesions on the extremities, which can mimic pernio. Vasculitis lesions tend to be more purpuric and angulated, compared with pernio lesions, though in severe cases of pernio with ulceration it may be difficult to distinguish between the two entities and a skin biopsy may be needed.

Sweet syndrome, also known as acute febrile neutrophilic dermatosis, is a rare skin condition in which children present with edematous tender nodules on the hands and with less frequency in other parts of the body with associated fever, malaise, conjunctivitis, or joint pain and it is usually associated with infection or malignancy. Our patient denied any systemic symptoms and had no conjunctivitis nor arthritis.

Most patients with idiopathic pernio do not require a biopsy or further laboratory evaluation unless the lesions are atypical, chronic, or there is a suspected associated condition. The workup for patients with prolonged or atypical pernio-like lesions include a skin biopsy with direct immunofluorescence, ANA, complete blood count, complement levels, antiphospholipid antibodies, cold agglutinins, and cryoglobulins.

Treatment of mild CLE is with moderate- to high-potency topical corticosteroids. In those patients not responding to topical measures and keeping the extremities warm, the use of hydroxychloroquine has been reported to be beneficial in some patients as well as the use of calcium-channel blockers.

Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego.

References

1. Su WP et al. Cutis. 1994 Dec;54(6):395-9.

2. Boada A et al. Am J Dermatopathol. 2010 Feb;32(1):19-23.

3. Patel et al. SBMJ Case Rep. 2013;2013:bcr2013201165.

4. Genes Yi et al. BMC. 2020 Apr 15;18(1):32.

5. Battesti G et al. J Am Acad Dermatol. 2020;83(4):1219-22.

6. Cappel JA et al. Mayo Clin Proc. 2014 Feb;89(2):207-15.

7. Cappel MA et al. Mayo Clin Proc. 2021;96(4):989-1005.

A punch biopsy from one of the lesions on the feet showed subtle basal vacuolar interface inflammation on the epidermis and rare apoptotic keratinocytes. There was an underlying dermal lymphocytic inflammatory infiltrate around the vascular plexus. Dermal mucin appeared slightly increased. The histologic findings are consistent with pernio. He had a negative direct immunofluorescence study.

Laboratory work-up showed an elevated antinuclear antibody (ANA) of 1:620; positive anticardiolipin IgM was at 15.2. A complete blood count showed no anemia or lymphopenia, he had normal complement C3 and C4 levels, normal urinalysis, negative cryoglobulins and cold agglutinins, and a normal protein electrophoresis.

Given the chronicity of his lesions, the lack of improvement with weather changes, the histopathologic findings of a vacuolar interface dermatitis and the positive ANA titer he was diagnosed with chilblain lupus.

Chilblain lupus erythematosus (CLE) is an uncommon form of chronic cutaneous lupus erythematosus that presents with tender pink to violaceous macules, papules, and/or nodules that sometimes can ulcerate and are present on the fingers, toes, and sometimes the nose and ears. The lesions are usually triggered by cold exposure.¹ These patients also have clinical and laboratory findings consistent with lupus erythematosus.

Even though more studies are needed to clarify the clinical and histopathologic features of chilblain lupus, compared with idiopathic pernio, some authors suggest several characteristics: CLE lesions tend to persist in summer months, as occurred in our patient, and histopathologic evaluation usually shows vacuolar and interface inflammation on the basal cell layer and may also have a positive lupus band on direct immunofluorescence.² About 20% of patient with CLE may later develop systemic lupus erythematosus.³

There is also a familial form of CLE which is usually inherited as an autosomal-dominant trait. Mutations in TREX1, SAMHD1, and STING have been described in these patients.⁴ Affected children present with skin lesions at a young age and those with TREX1 mutations are at a higher risk to develop systemic lupus erythematosus.

The differential diagnosis of chilblain lupus includes idiopathic pernio or pernio secondary to other conditions. Other conditions that are thought to be associated with pernio, besides lupus erythematosus, include infectious causes (hepatitis B, COVID-19 infection),⁵ autoimmune conditions, malignancy and hematologic disorders (paraproteinemia).⁶ In histopathology, pernio lesions present with dermal edema and superficial and deep lymphocytic infiltrate.

The pathogenesis of pernio is not fully understood but is thought be related to vasospasm with secondary poor perfusion and ischemia and type I interferon (INF1) immune response. A recent review of the published studies trying to explain the causality between COVID 19 and pernio-like lesions, from January 2020 to December 2020, speculate several possible mechanisms: an increase in the vasoconstrictive, prothrombotic, and proinflammatory effects of the angiotensin II pathway through activation of the ACE2 by the virus; COVID-19 triggers a robust INF1 immune response in predisposed patients; pernio as a sign of mild disease, may be explained by genetic and hormonal differences in the patients affected.⁷

Another condition that can be confused with CLE is Raynaud phenomenon, were patients present with white to purple to red patches on the fingers and toes after exposure to cold, but in comparison with pernio, the lesions improve within minutes to hours after rewarming. Secondary Raynaud phenomenon can be seen in patients with systemic lupus erythematosus and in patients with other connective tissue disorders. The skin lesions in our patient were persistent and were not triggered by cold exposure, making Raynaud phenomenon less likely. Children with vasculitis can present with painful red, violaceous, or necrotic lesions on the extremities, which can mimic pernio. Vasculitis lesions tend to be more purpuric and angulated, compared with pernio lesions, though in severe cases of pernio with ulceration it may be difficult to distinguish between the two entities and a skin biopsy may be needed.

Sweet syndrome, also known as acute febrile neutrophilic dermatosis, is a rare skin condition in which children present with edematous tender nodules on the hands and with less frequency in other parts of the body with associated fever, malaise, conjunctivitis, or joint pain and it is usually associated with infection or malignancy. Our patient denied any systemic symptoms and had no conjunctivitis nor arthritis.

Most patients with idiopathic pernio do not require a biopsy or further laboratory evaluation unless the lesions are atypical, chronic, or there is a suspected associated condition. The workup for patients with prolonged or atypical pernio-like lesions include a skin biopsy with direct immunofluorescence, ANA, complete blood count, complement levels, antiphospholipid antibodies, cold agglutinins, and cryoglobulins.

Treatment of mild CLE is with moderate- to high-potency topical corticosteroids. In those patients not responding to topical measures and keeping the extremities warm, the use of hydroxychloroquine has been reported to be beneficial in some patients as well as the use of calcium-channel blockers.

Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego.

References

1. Su WP et al. Cutis. 1994 Dec;54(6):395-9.

2. Boada A et al. Am J Dermatopathol. 2010 Feb;32(1):19-23.

3. Patel et al. SBMJ Case Rep. 2013;2013:bcr2013201165.

4. Genes Yi et al. BMC. 2020 Apr 15;18(1):32.

5. Battesti G et al. J Am Acad Dermatol. 2020;83(4):1219-22.

6. Cappel JA et al. Mayo Clin Proc. 2014 Feb;89(2):207-15.

7. Cappel MA et al. Mayo Clin Proc. 2021;96(4):989-1005.

Necrobiosis lipoidica, or Necrobiosis lipoidica diabeticorum (NLD), is an uncommon dermatologic condition that presents as plaques on the skin. Women are often more affected than men. Patients often present in their 30s and 40s. The cause of NLD is unknown. Twenty percent of patients with NLD will have glucose intolerance or a family history of diabetes.¹ The percentage of patients with NLD who have diabetes varies in reports from 11% to 65%.² NLD may progress despite the diabetes treatment. Only 0.03% of patient with diabetes will have NLD.³

Lesions most commonly occur on the extremities, with shins being affected in most cases. They vary from asymptomatic to painful. Typically, lesions begin as small, firm erythematous papules that evolve into shiny, well-defined plaques. In older plaques, the center will often appear yellow, depressed, and atrophic, with telangiectasias. The periphery appears pink to violaceous to brown. Ulceration may be present, particularly after trauma, and there may be decreased sensation in the plaques. NLD is clinically distinct from diabetic dermopathy, which appear as brown macules, often in older patients with diabetes.

Ideally, biopsy should be taken at the edge of a lesion. Histologically, the epidermis appears normal or atrophic. A diffuse palisaded and interstitial granulomatous dermatitis consisting of histiocytes, multinucleated giant cells, lymphocytes, and plasma cells is seen in the dermis. Granulomas are often oriented parallel to the epidermis. There is no mucin at the center of the granulomas (as seen in granuloma annulare). Inflammation may extend into the subcutaneous fat. Asteroid bodies (as seen in sarcoid) are absent.

Unfortunately, treatment of NLD is often unsuccessful. Treatment includes potent topical corticosteroids for early lesions and intralesional triamcinolone to the leading edge of lesions. Care should be taken to avoid injecting centrally where atrophy and ulceration may result. Systemic steroids may be helpful in some cases, but can elevate glucose levels. Other reported medical treatments include pentoxifylline, cyclosporine, and niacinamide. Some lesions may spontaneously resolve. Ulcerations may require surgical excision with grafting.

This case and photo are provided by Dr. Bilu Martin, who is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].

References

1. James WD et al. Andrews’ Diseases of the Skin: Clinical Dermatology. Philadelphia: Saunders Elsevier, 2006.

2. Hashemi D et al. JAMA Dermatol. 2019 Apr 1;155(4):455-9.

3. Bolognia JL et al. Dermatology. St. Louis, Mo.: Mosby Elsevier, 2008.

Necrobiosis lipoidica, or Necrobiosis lipoidica diabeticorum (NLD), is an uncommon dermatologic condition that presents as plaques on the skin. Women are often more affected than men. Patients often present in their 30s and 40s. The cause of NLD is unknown. Twenty percent of patients with NLD will have glucose intolerance or a family history of diabetes.¹ The percentage of patients with NLD who have diabetes varies in reports from 11% to 65%.² NLD may progress despite the diabetes treatment. Only 0.03% of patient with diabetes will have NLD.³

Lesions most commonly occur on the extremities, with shins being affected in most cases. They vary from asymptomatic to painful. Typically, lesions begin as small, firm erythematous papules that evolve into shiny, well-defined plaques. In older plaques, the center will often appear yellow, depressed, and atrophic, with telangiectasias. The periphery appears pink to violaceous to brown. Ulceration may be present, particularly after trauma, and there may be decreased sensation in the plaques. NLD is clinically distinct from diabetic dermopathy, which appear as brown macules, often in older patients with diabetes.

Ideally, biopsy should be taken at the edge of a lesion. Histologically, the epidermis appears normal or atrophic. A diffuse palisaded and interstitial granulomatous dermatitis consisting of histiocytes, multinucleated giant cells, lymphocytes, and plasma cells is seen in the dermis. Granulomas are often oriented parallel to the epidermis. There is no mucin at the center of the granulomas (as seen in granuloma annulare). Inflammation may extend into the subcutaneous fat. Asteroid bodies (as seen in sarcoid) are absent.

Unfortunately, treatment of NLD is often unsuccessful. Treatment includes potent topical corticosteroids for early lesions and intralesional triamcinolone to the leading edge of lesions. Care should be taken to avoid injecting centrally where atrophy and ulceration may result. Systemic steroids may be helpful in some cases, but can elevate glucose levels. Other reported medical treatments include pentoxifylline, cyclosporine, and niacinamide. Some lesions may spontaneously resolve. Ulcerations may require surgical excision with grafting.

This case and photo are provided by Dr. Bilu Martin, who is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].

References

1. James WD et al. Andrews’ Diseases of the Skin: Clinical Dermatology. Philadelphia: Saunders Elsevier, 2006.

2. Hashemi D et al. JAMA Dermatol. 2019 Apr 1;155(4):455-9.

3. Bolognia JL et al. Dermatology. St. Louis, Mo.: Mosby Elsevier, 2008.

Necrobiosis lipoidica, or Necrobiosis lipoidica diabeticorum (NLD), is an uncommon dermatologic condition that presents as plaques on the skin. Women are often more affected than men. Patients often present in their 30s and 40s. The cause of NLD is unknown. Twenty percent of patients with NLD will have glucose intolerance or a family history of diabetes.¹ The percentage of patients with NLD who have diabetes varies in reports from 11% to 65%.² NLD may progress despite the diabetes treatment. Only 0.03% of patient with diabetes will have NLD.³

Lesions most commonly occur on the extremities, with shins being affected in most cases. They vary from asymptomatic to painful. Typically, lesions begin as small, firm erythematous papules that evolve into shiny, well-defined plaques. In older plaques, the center will often appear yellow, depressed, and atrophic, with telangiectasias. The periphery appears pink to violaceous to brown. Ulceration may be present, particularly after trauma, and there may be decreased sensation in the plaques. NLD is clinically distinct from diabetic dermopathy, which appear as brown macules, often in older patients with diabetes.

Ideally, biopsy should be taken at the edge of a lesion. Histologically, the epidermis appears normal or atrophic. A diffuse palisaded and interstitial granulomatous dermatitis consisting of histiocytes, multinucleated giant cells, lymphocytes, and plasma cells is seen in the dermis. Granulomas are often oriented parallel to the epidermis. There is no mucin at the center of the granulomas (as seen in granuloma annulare). Inflammation may extend into the subcutaneous fat. Asteroid bodies (as seen in sarcoid) are absent.

Unfortunately, treatment of NLD is often unsuccessful. Treatment includes potent topical corticosteroids for early lesions and intralesional triamcinolone to the leading edge of lesions. Care should be taken to avoid injecting centrally where atrophy and ulceration may result. Systemic steroids may be helpful in some cases, but can elevate glucose levels. Other reported medical treatments include pentoxifylline, cyclosporine, and niacinamide. Some lesions may spontaneously resolve. Ulcerations may require surgical excision with grafting.

This case and photo are provided by Dr. Bilu Martin, who is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].

References

1. James WD et al. Andrews’ Diseases of the Skin: Clinical Dermatology. Philadelphia: Saunders Elsevier, 2006.

2. Hashemi D et al. JAMA Dermatol. 2019 Apr 1;155(4):455-9.

3. Bolognia JL et al. Dermatology. St. Louis, Mo.: Mosby Elsevier, 2008.

First-line tebentafusp significantly improved overall survival (OS) when compared with immunotherapy or chemotherapy in patients with metastatic uveal melanoma in a phase 3 trial.

Tebentafusp is the first investigational therapy in a phase 3 trial to improve OS in metastatic uveal melanoma, said Jessica Hassel, MD, of University Hospital Heidelberg in Germany, when presenting the results at the American Association for Cancer Research Annual Meeting 2021: Week 1 (Abstract CT002).

Dr. Hassel explained that tebentafusp is a bispecific fusion protein designed to target gp100 through a high affinity T-cell receptor binding domain and an anti-CD3 T-cell engaging domain, which redirects T cells to kill gp100-expressing tumor cells. Because the T-cell receptor binding domain only recognizes a specific gp100-derived peptide presented on HLA-A*02:01, tebentafusp can only be used to treat patients with this HLA type.

In the phase 3 trial, investigators enrolled 378 treatment-naive HLA-A*02:01-positive patients with metastatic uveal melanoma. Their median age was 65 years, and 50% were men.

Patients were assigned 2:1 to receive tebentafusp (n = 252) or investigator’s choice of pembrolizumab (n = 103), ipilimumab (n = 16), or dacarbazine (n = 7).
 

Prolonged OS despite low response rate

At a median follow-up of 14.1 months, patients receiving tebentafusp had significantly longer OS than that of patients in the investigator’s choice arm – 21.7 months and 16.0 months, respectively. The estimated 1-year OS rate was 73.2% in the tebentafusp arm and 58.5% in the standard therapy arm (hazard ratio, 0.51; 95% confidence interval, 0.37-0.71; P < .0001). The OS benefit was consistent across subgroups, Dr. Hassel said.

At a median follow-up of 11.4 months, the median progression-free survival was 3.3 months in the tebentafusp arm and 2.9 months in the investigator’s choice arm (HR, 0.73; 95% CI, 0.58-0.94; P = .0139).

The objective response rate was 9% in the tebentafusp arm and 5% in the investigator’s choice arm. There was only one complete response, and it was in the tebentafusp arm.

The disease control rate, defined as response or stable disease for 12 or more weeks, was 46% in the tebentafusp arm and 27% in the investigator’s choice arm. Rates of progressive disease were 52% and 62%, respectively.

Dr. Hassel pointed out that a landmark analysis of OS in patients with a best response of progressive disease, with patients continuing to receive treatment after progression, showed a hazard ratio of 0.4 (95% CI, 0.248-0.642) for those receiving tebentafusp vs. investigator’s choice. The OS benefit, despite low response rates, suggests that patients progress but are then stabilized with tebentafusp treatment.

“So this drug is slowing down developing disease,” she said.
 

‘Manageable’ adverse events

Target-mediated or cytokine-mediated adverse events were the most common side effects with tebentafusp. These included pyrexia (76%), pruritus (69%), and rash (83%), which decreased in frequency and severity after the first three to four doses.

While cytokine release syndrome was common (89%), the rate of grade 3-4 cytokine release syndrome was very low (1%). Adverse events were generally manageable with standard interventions, Dr. Hassel said.

The discontinuation rate was lower in the tebentafusp arm than in the investigator’s choice arm – 2% and 4.5%, respectively. There were no tebentafusp-related deaths.
 

‘Practice-changing’ results

“This is the first randomized controlled trial to be positive for overall survival in uveal melanoma. These are seminal and practice-changing results,” said AACR discussant Caroline Robert, MD, PhD, of Gustave Roussy and Paris-Saclay University in France.

She observed that the biology of uveal melanoma is distinct from that of cutaneous melanoma, and future research will have to address why tebentafusp doesn’t work as well in cutaneous melanoma. Tebentafusp will be evaluated in combination with immune checkpoint inhibitors as well, she added.

The major limitation of tebentafusp, Dr. Hassel observed, is that it can be used only in HLA-A*02:01-positive patients. “There still remains an unmet need for patients who do not have this particular surface protein,” she said.

The study was sponsored by Immunocore. Dr. Hassel disclosed relationships with Immunocore and other companies. Dr. Robert disclosed relationships with Bristol Myers Squibb, Pierre Fabre, Novartis, and other companies.

First-line tebentafusp significantly improved overall survival (OS) when compared with immunotherapy or chemotherapy in patients with metastatic uveal melanoma in a phase 3 trial.

Tebentafusp is the first investigational therapy in a phase 3 trial to improve OS in metastatic uveal melanoma, said Jessica Hassel, MD, of University Hospital Heidelberg in Germany, when presenting the results at the American Association for Cancer Research Annual Meeting 2021: Week 1 (Abstract CT002).

Dr. Hassel explained that tebentafusp is a bispecific fusion protein designed to target gp100 through a high affinity T-cell receptor binding domain and an anti-CD3 T-cell engaging domain, which redirects T cells to kill gp100-expressing tumor cells. Because the T-cell receptor binding domain only recognizes a specific gp100-derived peptide presented on HLA-A*02:01, tebentafusp can only be used to treat patients with this HLA type.

In the phase 3 trial, investigators enrolled 378 treatment-naive HLA-A*02:01-positive patients with metastatic uveal melanoma. Their median age was 65 years, and 50% were men.

Patients were assigned 2:1 to receive tebentafusp (n = 252) or investigator’s choice of pembrolizumab (n = 103), ipilimumab (n = 16), or dacarbazine (n = 7).
 

Prolonged OS despite low response rate

At a median follow-up of 14.1 months, patients receiving tebentafusp had significantly longer OS than that of patients in the investigator’s choice arm – 21.7 months and 16.0 months, respectively. The estimated 1-year OS rate was 73.2% in the tebentafusp arm and 58.5% in the standard therapy arm (hazard ratio, 0.51; 95% confidence interval, 0.37-0.71; P < .0001). The OS benefit was consistent across subgroups, Dr. Hassel said.

At a median follow-up of 11.4 months, the median progression-free survival was 3.3 months in the tebentafusp arm and 2.9 months in the investigator’s choice arm (HR, 0.73; 95% CI, 0.58-0.94; P = .0139).

The objective response rate was 9% in the tebentafusp arm and 5% in the investigator’s choice arm. There was only one complete response, and it was in the tebentafusp arm.

The disease control rate, defined as response or stable disease for 12 or more weeks, was 46% in the tebentafusp arm and 27% in the investigator’s choice arm. Rates of progressive disease were 52% and 62%, respectively.

Dr. Hassel pointed out that a landmark analysis of OS in patients with a best response of progressive disease, with patients continuing to receive treatment after progression, showed a hazard ratio of 0.4 (95% CI, 0.248-0.642) for those receiving tebentafusp vs. investigator’s choice. The OS benefit, despite low response rates, suggests that patients progress but are then stabilized with tebentafusp treatment.

“So this drug is slowing down developing disease,” she said.
 

‘Manageable’ adverse events

Target-mediated or cytokine-mediated adverse events were the most common side effects with tebentafusp. These included pyrexia (76%), pruritus (69%), and rash (83%), which decreased in frequency and severity after the first three to four doses.

While cytokine release syndrome was common (89%), the rate of grade 3-4 cytokine release syndrome was very low (1%). Adverse events were generally manageable with standard interventions, Dr. Hassel said.

The discontinuation rate was lower in the tebentafusp arm than in the investigator’s choice arm – 2% and 4.5%, respectively. There were no tebentafusp-related deaths.
 

‘Practice-changing’ results

“This is the first randomized controlled trial to be positive for overall survival in uveal melanoma. These are seminal and practice-changing results,” said AACR discussant Caroline Robert, MD, PhD, of Gustave Roussy and Paris-Saclay University in France.

She observed that the biology of uveal melanoma is distinct from that of cutaneous melanoma, and future research will have to address why tebentafusp doesn’t work as well in cutaneous melanoma. Tebentafusp will be evaluated in combination with immune checkpoint inhibitors as well, she added.

The major limitation of tebentafusp, Dr. Hassel observed, is that it can be used only in HLA-A*02:01-positive patients. “There still remains an unmet need for patients who do not have this particular surface protein,” she said.

The study was sponsored by Immunocore. Dr. Hassel disclosed relationships with Immunocore and other companies. Dr. Robert disclosed relationships with Bristol Myers Squibb, Pierre Fabre, Novartis, and other companies.

First-line tebentafusp significantly improved overall survival (OS) when compared with immunotherapy or chemotherapy in patients with metastatic uveal melanoma in a phase 3 trial.

Tebentafusp is the first investigational therapy in a phase 3 trial to improve OS in metastatic uveal melanoma, said Jessica Hassel, MD, of University Hospital Heidelberg in Germany, when presenting the results at the American Association for Cancer Research Annual Meeting 2021: Week 1 (Abstract CT002).

Dr. Hassel explained that tebentafusp is a bispecific fusion protein designed to target gp100 through a high affinity T-cell receptor binding domain and an anti-CD3 T-cell engaging domain, which redirects T cells to kill gp100-expressing tumor cells. Because the T-cell receptor binding domain only recognizes a specific gp100-derived peptide presented on HLA-A*02:01, tebentafusp can only be used to treat patients with this HLA type.

In the phase 3 trial, investigators enrolled 378 treatment-naive HLA-A*02:01-positive patients with metastatic uveal melanoma. Their median age was 65 years, and 50% were men.

Patients were assigned 2:1 to receive tebentafusp (n = 252) or investigator’s choice of pembrolizumab (n = 103), ipilimumab (n = 16), or dacarbazine (n = 7).
 

Prolonged OS despite low response rate

At a median follow-up of 14.1 months, patients receiving tebentafusp had significantly longer OS than that of patients in the investigator’s choice arm – 21.7 months and 16.0 months, respectively. The estimated 1-year OS rate was 73.2% in the tebentafusp arm and 58.5% in the standard therapy arm (hazard ratio, 0.51; 95% confidence interval, 0.37-0.71; P < .0001). The OS benefit was consistent across subgroups, Dr. Hassel said.

At a median follow-up of 11.4 months, the median progression-free survival was 3.3 months in the tebentafusp arm and 2.9 months in the investigator’s choice arm (HR, 0.73; 95% CI, 0.58-0.94; P = .0139).

The objective response rate was 9% in the tebentafusp arm and 5% in the investigator’s choice arm. There was only one complete response, and it was in the tebentafusp arm.

The disease control rate, defined as response or stable disease for 12 or more weeks, was 46% in the tebentafusp arm and 27% in the investigator’s choice arm. Rates of progressive disease were 52% and 62%, respectively.

Dr. Hassel pointed out that a landmark analysis of OS in patients with a best response of progressive disease, with patients continuing to receive treatment after progression, showed a hazard ratio of 0.4 (95% CI, 0.248-0.642) for those receiving tebentafusp vs. investigator’s choice. The OS benefit, despite low response rates, suggests that patients progress but are then stabilized with tebentafusp treatment.

“So this drug is slowing down developing disease,” she said.
 

‘Manageable’ adverse events

Target-mediated or cytokine-mediated adverse events were the most common side effects with tebentafusp. These included pyrexia (76%), pruritus (69%), and rash (83%), which decreased in frequency and severity after the first three to four doses.

While cytokine release syndrome was common (89%), the rate of grade 3-4 cytokine release syndrome was very low (1%). Adverse events were generally manageable with standard interventions, Dr. Hassel said.

The discontinuation rate was lower in the tebentafusp arm than in the investigator’s choice arm – 2% and 4.5%, respectively. There were no tebentafusp-related deaths.
 

‘Practice-changing’ results

“This is the first randomized controlled trial to be positive for overall survival in uveal melanoma. These are seminal and practice-changing results,” said AACR discussant Caroline Robert, MD, PhD, of Gustave Roussy and Paris-Saclay University in France.

She observed that the biology of uveal melanoma is distinct from that of cutaneous melanoma, and future research will have to address why tebentafusp doesn’t work as well in cutaneous melanoma. Tebentafusp will be evaluated in combination with immune checkpoint inhibitors as well, she added.

The major limitation of tebentafusp, Dr. Hassel observed, is that it can be used only in HLA-A*02:01-positive patients. “There still remains an unmet need for patients who do not have this particular surface protein,” she said.

The study was sponsored by Immunocore. Dr. Hassel disclosed relationships with Immunocore and other companies. Dr. Robert disclosed relationships with Bristol Myers Squibb, Pierre Fabre, Novartis, and other companies.

Black patients diagnosed by dermatologists with cutaneous sarcoidosis were significantly more likely to have unrecognized systemic organ involvement than were non-Black patients, according to a retrospective chart review of patients seen at Massachusetts General Hospital and Brigham and Women’s Hospital, both in Boston.

Black patients were also significantly more likely to have two or more organs involved and have higher rates of cardiac involvement, the latter of which is associated with worse prognosis. “Our data suggest there may be substantial variations in organ involvement between racial groups of patients presenting with cutaneous sarcoidosis,” said medical student Kylee Kus, a medical student at Oakland University, Auburn Hills, Mich., who presented the findings with Bina Kassamali, a medical student at Harvard University, Boston, at the annual Skin of Color Society scientific symposium.

Sotonye Imadojemu, MD, MBE; Avery LeChance, MD, MPH; and Ruth Anne Vleugels, MD, MPH, MBA; of Brigham and Women’s Hospital, are cosenior authors of the abstract.

The researchers identified 111 patients who were diagnosed with cutaneous sarcoidosis over a 20-year period (January 2000–December 2019), 50 of whom presented without established extracutaneous disease. They examined the charts of these 50 patients for whether subsequent work-up revealed systemic disease.

Of the 50 patients, 9 were Black. Seven of these nine patients (77.8%), were found to have systemic involvement, compared with 14 of 41 (46.3%) non-Black patients – a 31.5% higher probability (P < .05). One-third of the nine Black patients were found to have disease in one organ, and 44.4% in two or more organs. In non-Black patients, these rates were 12.2% and 34.1%, respectively.

Cardiovascular involvement was not found in any of the non-Black patients who had extracutaneous disease, but was found in 29% of the Black patients with extracutaneous disease, a statistically significant difference.

Black patients are known to be at higher risk for sarcoidosis than non-Black patients, and because “there is an association between cardiac sarcoid involvement and poor prognosis largely due to manifestations such as heart block, arrhythmias, and heart failure ... the study helps demonstrate how this organ involvement can disproportionately affect the Black population,” Ms. Kassamali said in an interview after the meeting.

A separate, recently published analysis of data from the same patient population examined the work-ups that patients received after a dermatologist’s diagnosis of sarcoidosis and found that patients with no previous systemic work-up were subsequently assessed for cardiac involvement in only 58.3% of cases. Assessment for pulmonary and ocular disease was completed more than 90% of the time.

“Crucial testing for cardiac involvement fell short,” Dr. Imadojemu, of the department of dermatology, Brigham and Women’s Hospital, and coinvestigators wrote in the research letter.

“Because the cutaneous manifestations of sarcoidosis often present at disease onset, dermatologists may be the first physicians to diagnose a patient with sarcoidosis,” they wrote. “As such, dermatologists are often responsible for initiating the appropriate evaluation of patients with sarcoidosis.”

Pulmonary involvement occurs in nearly all cases of sarcoidosis, while ocular and cardiac disease develop in approximately 25% and 10% of patients, respectively. Cardiac sarcoidosis is usually asymptomatic and accounts for 13%-25% of sarcoidosis-related deaths in the United States, they wrote.

An electrocardiogram is the appropriate initial screening tool and “is warranted in all patients with sarcoidosis,” they advised.

Black patients diagnosed by dermatologists with cutaneous sarcoidosis were significantly more likely to have unrecognized systemic organ involvement than were non-Black patients, according to a retrospective chart review of patients seen at Massachusetts General Hospital and Brigham and Women’s Hospital, both in Boston.

Black patients were also significantly more likely to have two or more organs involved and have higher rates of cardiac involvement, the latter of which is associated with worse prognosis. “Our data suggest there may be substantial variations in organ involvement between racial groups of patients presenting with cutaneous sarcoidosis,” said medical student Kylee Kus, a medical student at Oakland University, Auburn Hills, Mich., who presented the findings with Bina Kassamali, a medical student at Harvard University, Boston, at the annual Skin of Color Society scientific symposium.

Sotonye Imadojemu, MD, MBE; Avery LeChance, MD, MPH; and Ruth Anne Vleugels, MD, MPH, MBA; of Brigham and Women’s Hospital, are cosenior authors of the abstract.

The researchers identified 111 patients who were diagnosed with cutaneous sarcoidosis over a 20-year period (January 2000–December 2019), 50 of whom presented without established extracutaneous disease. They examined the charts of these 50 patients for whether subsequent work-up revealed systemic disease.

Of the 50 patients, 9 were Black. Seven of these nine patients (77.8%), were found to have systemic involvement, compared with 14 of 41 (46.3%) non-Black patients – a 31.5% higher probability (P < .05). One-third of the nine Black patients were found to have disease in one organ, and 44.4% in two or more organs. In non-Black patients, these rates were 12.2% and 34.1%, respectively.

Cardiovascular involvement was not found in any of the non-Black patients who had extracutaneous disease, but was found in 29% of the Black patients with extracutaneous disease, a statistically significant difference.

Black patients are known to be at higher risk for sarcoidosis than non-Black patients, and because “there is an association between cardiac sarcoid involvement and poor prognosis largely due to manifestations such as heart block, arrhythmias, and heart failure ... the study helps demonstrate how this organ involvement can disproportionately affect the Black population,” Ms. Kassamali said in an interview after the meeting.

A separate, recently published analysis of data from the same patient population examined the work-ups that patients received after a dermatologist’s diagnosis of sarcoidosis and found that patients with no previous systemic work-up were subsequently assessed for cardiac involvement in only 58.3% of cases. Assessment for pulmonary and ocular disease was completed more than 90% of the time.

“Crucial testing for cardiac involvement fell short,” Dr. Imadojemu, of the department of dermatology, Brigham and Women’s Hospital, and coinvestigators wrote in the research letter.

“Because the cutaneous manifestations of sarcoidosis often present at disease onset, dermatologists may be the first physicians to diagnose a patient with sarcoidosis,” they wrote. “As such, dermatologists are often responsible for initiating the appropriate evaluation of patients with sarcoidosis.”

Pulmonary involvement occurs in nearly all cases of sarcoidosis, while ocular and cardiac disease develop in approximately 25% and 10% of patients, respectively. Cardiac sarcoidosis is usually asymptomatic and accounts for 13%-25% of sarcoidosis-related deaths in the United States, they wrote.

An electrocardiogram is the appropriate initial screening tool and “is warranted in all patients with sarcoidosis,” they advised.

Black patients diagnosed by dermatologists with cutaneous sarcoidosis were significantly more likely to have unrecognized systemic organ involvement than were non-Black patients, according to a retrospective chart review of patients seen at Massachusetts General Hospital and Brigham and Women’s Hospital, both in Boston.

Black patients were also significantly more likely to have two or more organs involved and have higher rates of cardiac involvement, the latter of which is associated with worse prognosis. “Our data suggest there may be substantial variations in organ involvement between racial groups of patients presenting with cutaneous sarcoidosis,” said medical student Kylee Kus, a medical student at Oakland University, Auburn Hills, Mich., who presented the findings with Bina Kassamali, a medical student at Harvard University, Boston, at the annual Skin of Color Society scientific symposium.

Sotonye Imadojemu, MD, MBE; Avery LeChance, MD, MPH; and Ruth Anne Vleugels, MD, MPH, MBA; of Brigham and Women’s Hospital, are cosenior authors of the abstract.

The researchers identified 111 patients who were diagnosed with cutaneous sarcoidosis over a 20-year period (January 2000–December 2019), 50 of whom presented without established extracutaneous disease. They examined the charts of these 50 patients for whether subsequent work-up revealed systemic disease.

Of the 50 patients, 9 were Black. Seven of these nine patients (77.8%), were found to have systemic involvement, compared with 14 of 41 (46.3%) non-Black patients – a 31.5% higher probability (P < .05). One-third of the nine Black patients were found to have disease in one organ, and 44.4% in two or more organs. In non-Black patients, these rates were 12.2% and 34.1%, respectively.

Cardiovascular involvement was not found in any of the non-Black patients who had extracutaneous disease, but was found in 29% of the Black patients with extracutaneous disease, a statistically significant difference.

Black patients are known to be at higher risk for sarcoidosis than non-Black patients, and because “there is an association between cardiac sarcoid involvement and poor prognosis largely due to manifestations such as heart block, arrhythmias, and heart failure ... the study helps demonstrate how this organ involvement can disproportionately affect the Black population,” Ms. Kassamali said in an interview after the meeting.

A separate, recently published analysis of data from the same patient population examined the work-ups that patients received after a dermatologist’s diagnosis of sarcoidosis and found that patients with no previous systemic work-up were subsequently assessed for cardiac involvement in only 58.3% of cases. Assessment for pulmonary and ocular disease was completed more than 90% of the time.

“Crucial testing for cardiac involvement fell short,” Dr. Imadojemu, of the department of dermatology, Brigham and Women’s Hospital, and coinvestigators wrote in the research letter.

“Because the cutaneous manifestations of sarcoidosis often present at disease onset, dermatologists may be the first physicians to diagnose a patient with sarcoidosis,” they wrote. “As such, dermatologists are often responsible for initiating the appropriate evaluation of patients with sarcoidosis.”

Pulmonary involvement occurs in nearly all cases of sarcoidosis, while ocular and cardiac disease develop in approximately 25% and 10% of patients, respectively. Cardiac sarcoidosis is usually asymptomatic and accounts for 13%-25% of sarcoidosis-related deaths in the United States, they wrote.

An electrocardiogram is the appropriate initial screening tool and “is warranted in all patients with sarcoidosis,” they advised.

In a study by Trembely et al. sponsored by Pfizer, an indirect comparison of both studies was performed using a simulated treatment comparison to account for differences in patient characteristics. As expected, the overall response rates were higher in the venetoclax study compared to the glasdegib study (48% vs. 24%), but overall survival was similar (hazard ratio 0.75 vs. HR 0.46). This study demonstrates again that CR/CRi cannot be used as a surrogate endpoint for survival in AML. In addition, with the negative study of V-LDAC vs. LDAC and the improved overall survival of the combination of azacytidine + venetoclax (Aza-ven) vs. azacitdine, the current standard of care of newly diagnosed patients with AML unbale to tolerate intensive chemotherapy is Aza-ven and V-LDAC is rarely used.

The success of Aza-ven is not without side effects. This was demonstrated recently in a retrospective study by Feld et al. In that study 72 patients with newly diagnosed AML (26), relapsed refractory AML (39) and MDS (7) received azacitdine + venetoclax. The main side effect was myelosuppression with only 15% of patients who were transfusion dependent become transfusion independent. In addition, 46% of patients had a neutropenic fever and 43.7% of patients requiring admission. Most patients (54.9%) required treatment interruption and 35.2% stopped venetoclax for toxicity.

This study highlighted that the optimal dose and frequency of venetoclax remains unclear. A shorted duration or lower dose of venetoclax maybe more ideal, however that may lead to less efficacy. In addition, bone marrow evaluation to assess for cellularity on D21 to D28 of the first cycle may help guide dose adjustments. Finally with the high CR/CRi rates in AML and short duration of response further studies are ongoing to further define molecular abnormalities that may refine prognosis or guide therapy. Two of those studies recently reported identified a prognostic and possible therapeutic role for both EZH2 and the PI3 kinase mTOR pathway.

In a study by Trembely et al. sponsored by Pfizer, an indirect comparison of both studies was performed using a simulated treatment comparison to account for differences in patient characteristics. As expected, the overall response rates were higher in the venetoclax study compared to the glasdegib study (48% vs. 24%), but overall survival was similar (hazard ratio 0.75 vs. HR 0.46). This study demonstrates again that CR/CRi cannot be used as a surrogate endpoint for survival in AML. In addition, with the negative study of V-LDAC vs. LDAC and the improved overall survival of the combination of azacytidine + venetoclax (Aza-ven) vs. azacitdine, the current standard of care of newly diagnosed patients with AML unbale to tolerate intensive chemotherapy is Aza-ven and V-LDAC is rarely used.

The success of Aza-ven is not without side effects. This was demonstrated recently in a retrospective study by Feld et al. In that study 72 patients with newly diagnosed AML (26), relapsed refractory AML (39) and MDS (7) received azacitdine + venetoclax. The main side effect was myelosuppression with only 15% of patients who were transfusion dependent become transfusion independent. In addition, 46% of patients had a neutropenic fever and 43.7% of patients requiring admission. Most patients (54.9%) required treatment interruption and 35.2% stopped venetoclax for toxicity.

This study highlighted that the optimal dose and frequency of venetoclax remains unclear. A shorted duration or lower dose of venetoclax maybe more ideal, however that may lead to less efficacy. In addition, bone marrow evaluation to assess for cellularity on D21 to D28 of the first cycle may help guide dose adjustments. Finally with the high CR/CRi rates in AML and short duration of response further studies are ongoing to further define molecular abnormalities that may refine prognosis or guide therapy. Two of those studies recently reported identified a prognostic and possible therapeutic role for both EZH2 and the PI3 kinase mTOR pathway.

In a study by Trembely et al. sponsored by Pfizer, an indirect comparison of both studies was performed using a simulated treatment comparison to account for differences in patient characteristics. As expected, the overall response rates were higher in the venetoclax study compared to the glasdegib study (48% vs. 24%), but overall survival was similar (hazard ratio 0.75 vs. HR 0.46). This study demonstrates again that CR/CRi cannot be used as a surrogate endpoint for survival in AML. In addition, with the negative study of V-LDAC vs. LDAC and the improved overall survival of the combination of azacytidine + venetoclax (Aza-ven) vs. azacitdine, the current standard of care of newly diagnosed patients with AML unbale to tolerate intensive chemotherapy is Aza-ven and V-LDAC is rarely used.

The success of Aza-ven is not without side effects. This was demonstrated recently in a retrospective study by Feld et al. In that study 72 patients with newly diagnosed AML (26), relapsed refractory AML (39) and MDS (7) received azacitdine + venetoclax. The main side effect was myelosuppression with only 15% of patients who were transfusion dependent become transfusion independent. In addition, 46% of patients had a neutropenic fever and 43.7% of patients requiring admission. Most patients (54.9%) required treatment interruption and 35.2% stopped venetoclax for toxicity.

This study highlighted that the optimal dose and frequency of venetoclax remains unclear. A shorted duration or lower dose of venetoclax maybe more ideal, however that may lead to less efficacy. In addition, bone marrow evaluation to assess for cellularity on D21 to D28 of the first cycle may help guide dose adjustments. Finally with the high CR/CRi rates in AML and short duration of response further studies are ongoing to further define molecular abnormalities that may refine prognosis or guide therapy. Two of those studies recently reported identified a prognostic and possible therapeutic role for both EZH2 and the PI3 kinase mTOR pathway.

Welcome to our national obsession: Vaccines! You may have noticed – it’s all talk, all the time, with short breaks to discuss what we’re watching on Netflix.

Geber86/Getty Images

For months, every session with almost every patient includes a commentary on someone they know who has gotten “the shot.” Before our state expanded eligibility to all adults, the discussion might include thoughts about who deserves to go first, who “cut the line,” how they did it, what vaccine is best, and worries about side effects.

And it’s not just my patients: With every friend, with every acquaintance, and even just walking by strangers who are conversing, the topic of discussion is vaccines. The narratives are similar; people want to talk about who has gotten vaccinated, why they qualified, where they went, which one they got, and what side effects they experienced. This is followed by a discussion about what they are now doing that they weren’t doing before being vaccinated, if anything. Some have returned to indoor restaurant dining, others only dine outdoors, still others continue to avoid public settings. There are the fully vaccinated, the partially vaccinated, and those scheduled for the first shot. In the unvaccinated/unregistered group there are the vaccine-hesitants and vaccine-refusers, with their concerns about everything from the safety of the agent to whether the government is using this as a way to insert tracker chips into all of us. There is enthusiasm, trepidation, anxiety, fear, excitement, relief, and absolute joy.

Recently I opened two emails from old friends I have not communicated with in a long time. Both emails began with, “I am fully vaccinated.” I know that the Uber driver who took me to the airport recently received his first dose the Saturday before. And yes, I heard the status of his wife and two children. In the course of one work day, I received distressed text messages from two patients about vaccines – one was anxious about having received the Janssen vaccine that was paused that morning, another was worried about getting a second dose of the Pfizer vaccine later in the week because he was having a symptom that could be indicative of COVID-19. I suggested that his primary care physician might be a better resource for this, but then added that he should probably get tested and delay having the second dose if positive. It seems I did have thoughts about a course of action after all.

Some psychiatrists have wondered how to handle patient questions about their own vaccination status. I have taken the stance that we are physicians, and that patients who may be seeing us – now or in the future – for in-person appointments are entitled to know if we pose a risk to their health, and so I have chosen to answer, without further exploration, when patients ask if I’ve received that coronavirus vaccine. Some psychiatrists feel it is our responsibility to share this information with our patients as a way of modeling safe behavior, and I have had one patient who said she would not be getting vaccinated until I told her that I thought she should.

“Did you get it?” she asked.

“I did,” I responded.

“Okay, if you got it, I will.” She soon discovered that vaccinations were hard to come by and that in her social group, being vaccinated was something of a status symbol. In addition to the worry about contracting a potentially fatal virus, her hesitancy yielded to “vaccine FOMO” or fear of missing out.

Some psychiatrists have felt uneasy with a question that pertains to their personal health, or have used the question as a springboard for exploration. Nicole Leistikow, MD (fully vaccinated, Moderna), is a psychiatrist in private practice in Baltimore. She notes, “Recently, I was discussing vaccination with a patient who wasn’t sure what information to believe or how much to trust the U.S. government. My careful exploration comparing different risks was not very helpful. I mentioned that I was vaccinated and that if he got vaccinated, he could come for a low-risk, in-person appointment after a year of telephone visits. This proved to be a winning argument and he called back later that day to say he had already had his first shot from leftover vaccine at his pharmacy.”

I grew up in a world that did not question vaccines. You got them and they were good things. No one asked which pharmaceutical company manufactured the vaccine. We trusted the system and our physicians. Schools asked for proof of vaccination, and it never occurred to me not to be vaccinated. Life has grown more complicated in the last 30 years, and the groups of people who are opposed to being vaccinated are more diverse. Those opposed to getting a COVID-19 vaccine are not necessarily the same as the broader group of anti-vaxxers that spawned from the fear that childhood vaccines cause autism. For some, it’s a personal issue related to their own health and risk perception, for others it’s a polarized political issue, and for another group there is the question of where their trust lies.

What lies ahead in our postvaccine world? This will be our next national conversation, and just as we negotiated our own levels of comfort with regard to working and socializing during the pandemic, I imagine the postvaccine world will have the same adjustment. There already are cases of COVID-19 in those who have been fully vaccinated, as well as the rare hospitalizations and deaths – we simply cannot expect a vaccine that did so well in controlled studies of tens of thousands of study subjects to do as well when given to tens of millions of uncontrolled citizens. One of the first deaths in a fully vaccinated person in late March was an older psychologist, and it remains unclear how effective the vaccine is for immunocompromised patients. Some people will play it very safe, eschewing all activities that entail risk, while others will choose to adhere to either their own intuition about what is safe, or to the recommendations of Anthony S. Fauci, MD, and the Centers for Disease Control and Prevention.

I’ll end with a final thought from the Twitter feed of Ashish K. Jha, MD, dean of the School of Public Health at Brown University, Providence, R.I. Dr. Jha tweeted, “Once you get fully vaccinated, it absolutely changes what you can do safely.” It seems our national conversation is not slated to change anytime soon.

Dr. Miller is a coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University Press, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins, both in Baltimore.

Welcome to our national obsession: Vaccines! You may have noticed – it’s all talk, all the time, with short breaks to discuss what we’re watching on Netflix.

Geber86/Getty Images

For months, every session with almost every patient includes a commentary on someone they know who has gotten “the shot.” Before our state expanded eligibility to all adults, the discussion might include thoughts about who deserves to go first, who “cut the line,” how they did it, what vaccine is best, and worries about side effects.

And it’s not just my patients: With every friend, with every acquaintance, and even just walking by strangers who are conversing, the topic of discussion is vaccines. The narratives are similar; people want to talk about who has gotten vaccinated, why they qualified, where they went, which one they got, and what side effects they experienced. This is followed by a discussion about what they are now doing that they weren’t doing before being vaccinated, if anything. Some have returned to indoor restaurant dining, others only dine outdoors, still others continue to avoid public settings. There are the fully vaccinated, the partially vaccinated, and those scheduled for the first shot. In the unvaccinated/unregistered group there are the vaccine-hesitants and vaccine-refusers, with their concerns about everything from the safety of the agent to whether the government is using this as a way to insert tracker chips into all of us. There is enthusiasm, trepidation, anxiety, fear, excitement, relief, and absolute joy.

Recently I opened two emails from old friends I have not communicated with in a long time. Both emails began with, “I am fully vaccinated.” I know that the Uber driver who took me to the airport recently received his first dose the Saturday before. And yes, I heard the status of his wife and two children. In the course of one work day, I received distressed text messages from two patients about vaccines – one was anxious about having received the Janssen vaccine that was paused that morning, another was worried about getting a second dose of the Pfizer vaccine later in the week because he was having a symptom that could be indicative of COVID-19. I suggested that his primary care physician might be a better resource for this, but then added that he should probably get tested and delay having the second dose if positive. It seems I did have thoughts about a course of action after all.

Some psychiatrists have wondered how to handle patient questions about their own vaccination status. I have taken the stance that we are physicians, and that patients who may be seeing us – now or in the future – for in-person appointments are entitled to know if we pose a risk to their health, and so I have chosen to answer, without further exploration, when patients ask if I’ve received that coronavirus vaccine. Some psychiatrists feel it is our responsibility to share this information with our patients as a way of modeling safe behavior, and I have had one patient who said she would not be getting vaccinated until I told her that I thought she should.

“Did you get it?” she asked.

“I did,” I responded.

“Okay, if you got it, I will.” She soon discovered that vaccinations were hard to come by and that in her social group, being vaccinated was something of a status symbol. In addition to the worry about contracting a potentially fatal virus, her hesitancy yielded to “vaccine FOMO” or fear of missing out.

Some psychiatrists have felt uneasy with a question that pertains to their personal health, or have used the question as a springboard for exploration. Nicole Leistikow, MD (fully vaccinated, Moderna), is a psychiatrist in private practice in Baltimore. She notes, “Recently, I was discussing vaccination with a patient who wasn’t sure what information to believe or how much to trust the U.S. government. My careful exploration comparing different risks was not very helpful. I mentioned that I was vaccinated and that if he got vaccinated, he could come for a low-risk, in-person appointment after a year of telephone visits. This proved to be a winning argument and he called back later that day to say he had already had his first shot from leftover vaccine at his pharmacy.”

I grew up in a world that did not question vaccines. You got them and they were good things. No one asked which pharmaceutical company manufactured the vaccine. We trusted the system and our physicians. Schools asked for proof of vaccination, and it never occurred to me not to be vaccinated. Life has grown more complicated in the last 30 years, and the groups of people who are opposed to being vaccinated are more diverse. Those opposed to getting a COVID-19 vaccine are not necessarily the same as the broader group of anti-vaxxers that spawned from the fear that childhood vaccines cause autism. For some, it’s a personal issue related to their own health and risk perception, for others it’s a polarized political issue, and for another group there is the question of where their trust lies.

What lies ahead in our postvaccine world? This will be our next national conversation, and just as we negotiated our own levels of comfort with regard to working and socializing during the pandemic, I imagine the postvaccine world will have the same adjustment. There already are cases of COVID-19 in those who have been fully vaccinated, as well as the rare hospitalizations and deaths – we simply cannot expect a vaccine that did so well in controlled studies of tens of thousands of study subjects to do as well when given to tens of millions of uncontrolled citizens. One of the first deaths in a fully vaccinated person in late March was an older psychologist, and it remains unclear how effective the vaccine is for immunocompromised patients. Some people will play it very safe, eschewing all activities that entail risk, while others will choose to adhere to either their own intuition about what is safe, or to the recommendations of Anthony S. Fauci, MD, and the Centers for Disease Control and Prevention.

I’ll end with a final thought from the Twitter feed of Ashish K. Jha, MD, dean of the School of Public Health at Brown University, Providence, R.I. Dr. Jha tweeted, “Once you get fully vaccinated, it absolutely changes what you can do safely.” It seems our national conversation is not slated to change anytime soon.

Dr. Miller is a coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University Press, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins, both in Baltimore.

Welcome to our national obsession: Vaccines! You may have noticed – it’s all talk, all the time, with short breaks to discuss what we’re watching on Netflix.

Geber86/Getty Images

For months, every session with almost every patient includes a commentary on someone they know who has gotten “the shot.” Before our state expanded eligibility to all adults, the discussion might include thoughts about who deserves to go first, who “cut the line,” how they did it, what vaccine is best, and worries about side effects.

And it’s not just my patients: With every friend, with every acquaintance, and even just walking by strangers who are conversing, the topic of discussion is vaccines. The narratives are similar; people want to talk about who has gotten vaccinated, why they qualified, where they went, which one they got, and what side effects they experienced. This is followed by a discussion about what they are now doing that they weren’t doing before being vaccinated, if anything. Some have returned to indoor restaurant dining, others only dine outdoors, still others continue to avoid public settings. There are the fully vaccinated, the partially vaccinated, and those scheduled for the first shot. In the unvaccinated/unregistered group there are the vaccine-hesitants and vaccine-refusers, with their concerns about everything from the safety of the agent to whether the government is using this as a way to insert tracker chips into all of us. There is enthusiasm, trepidation, anxiety, fear, excitement, relief, and absolute joy.

Recently I opened two emails from old friends I have not communicated with in a long time. Both emails began with, “I am fully vaccinated.” I know that the Uber driver who took me to the airport recently received his first dose the Saturday before. And yes, I heard the status of his wife and two children. In the course of one work day, I received distressed text messages from two patients about vaccines – one was anxious about having received the Janssen vaccine that was paused that morning, another was worried about getting a second dose of the Pfizer vaccine later in the week because he was having a symptom that could be indicative of COVID-19. I suggested that his primary care physician might be a better resource for this, but then added that he should probably get tested and delay having the second dose if positive. It seems I did have thoughts about a course of action after all.

Some psychiatrists have wondered how to handle patient questions about their own vaccination status. I have taken the stance that we are physicians, and that patients who may be seeing us – now or in the future – for in-person appointments are entitled to know if we pose a risk to their health, and so I have chosen to answer, without further exploration, when patients ask if I’ve received that coronavirus vaccine. Some psychiatrists feel it is our responsibility to share this information with our patients as a way of modeling safe behavior, and I have had one patient who said she would not be getting vaccinated until I told her that I thought she should.

“Did you get it?” she asked.

“I did,” I responded.

“Okay, if you got it, I will.” She soon discovered that vaccinations were hard to come by and that in her social group, being vaccinated was something of a status symbol. In addition to the worry about contracting a potentially fatal virus, her hesitancy yielded to “vaccine FOMO” or fear of missing out.

Some psychiatrists have felt uneasy with a question that pertains to their personal health, or have used the question as a springboard for exploration. Nicole Leistikow, MD (fully vaccinated, Moderna), is a psychiatrist in private practice in Baltimore. She notes, “Recently, I was discussing vaccination with a patient who wasn’t sure what information to believe or how much to trust the U.S. government. My careful exploration comparing different risks was not very helpful. I mentioned that I was vaccinated and that if he got vaccinated, he could come for a low-risk, in-person appointment after a year of telephone visits. This proved to be a winning argument and he called back later that day to say he had already had his first shot from leftover vaccine at his pharmacy.”

I grew up in a world that did not question vaccines. You got them and they were good things. No one asked which pharmaceutical company manufactured the vaccine. We trusted the system and our physicians. Schools asked for proof of vaccination, and it never occurred to me not to be vaccinated. Life has grown more complicated in the last 30 years, and the groups of people who are opposed to being vaccinated are more diverse. Those opposed to getting a COVID-19 vaccine are not necessarily the same as the broader group of anti-vaxxers that spawned from the fear that childhood vaccines cause autism. For some, it’s a personal issue related to their own health and risk perception, for others it’s a polarized political issue, and for another group there is the question of where their trust lies.

What lies ahead in our postvaccine world? This will be our next national conversation, and just as we negotiated our own levels of comfort with regard to working and socializing during the pandemic, I imagine the postvaccine world will have the same adjustment. There already are cases of COVID-19 in those who have been fully vaccinated, as well as the rare hospitalizations and deaths – we simply cannot expect a vaccine that did so well in controlled studies of tens of thousands of study subjects to do as well when given to tens of millions of uncontrolled citizens. One of the first deaths in a fully vaccinated person in late March was an older psychologist, and it remains unclear how effective the vaccine is for immunocompromised patients. Some people will play it very safe, eschewing all activities that entail risk, while others will choose to adhere to either their own intuition about what is safe, or to the recommendations of Anthony S. Fauci, MD, and the Centers for Disease Control and Prevention.

I’ll end with a final thought from the Twitter feed of Ashish K. Jha, MD, dean of the School of Public Health at Brown University, Providence, R.I. Dr. Jha tweeted, “Once you get fully vaccinated, it absolutely changes what you can do safely.” It seems our national conversation is not slated to change anytime soon.

Dr. Miller is a coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University Press, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins, both in Baltimore.

For intrapartum fetal surveillance, the old way may be the best way, according to a meta-analysis involving more than 118,000 patients.

Intermittent auscultation with a Pinard stethoscope and handheld Doppler was associated with a significantly lower risk of emergency cesarean deliveries than newer monitoring techniques without jeopardizing maternal or neonatal outcomes, reported lead author Bassel H. Al Wattar, MD, PhD, of University of Warwick, Coventry, England, and University College London Hospitals, and colleagues.

“Over the last 50 years, several newer surveillance methods have been evaluated, with varied uptake in practice,” the investigators wrote in the Canadian Medical Association Journal, noting that cardiotocography (CTG) is the most common method for high-risk pregnancies, typically coupled with at least one other modality, such as fetal scalp pH analysis (FBS), fetal pulse oximetry (FPO), or fetal heart electrocardiogram (STAN).

“Despite extensive investment in clinical research, the overall effectiveness of such methods in improving maternal and neonatal outcomes remains debatable as stillbirth rates have plateaued worldwide, while cesarean delivery rates continue to rise,” the investigators wrote. Previous meta-analyses have relied upon head-to-head comparisons of monitoring techniques and did not take into account effects on maternal and neonatal outcomes.

To address this knowledge gap, Dr. Al Wattar and colleagues conducted the present systematic review and meta-analysis, ultimately including 33 trials with 118,863 women who underwent intrapartum fetal surveillance, dating back to 1976. Ten surveillance types were evaluated, including intermittent auscultation with Pinard stethoscope and handheld Doppler, CTG with or without computer-aided decision models (cCTG), and CTG or cCTG combined with one or two other techniques, such as FBS, FPO, and STAN.

This revealed that intermittent auscultation outperformed all other techniques in terms of emergency cesarean deliveries and emergency cesarean deliveries because of fetal distress.

Specifically, intermittent auscultation significantly reduced risk of emergency cesarean deliveries, compared with CTG (relative risk, 0.83; 95% confidence interval, 0.72-0.97), CTG-FBS (RR, 0.71; 95% CI, 0.63-0.80), CTG-lactate (RR, 0.77; 95% CI, 0.64-0.92), and FPO-CTG-FBS (RR, 0.81; 95% CI, 0.67-0.99). Conversely, compared with IA, STAN-CTG-FBS and cCTG-FBS raised risk of emergency cesarean deliveries by 17% and 21%, respectively.

Compared with other modalities, the superiority of intermittent auscultation was even more pronounced in terms of emergency cesarean deliveries because of fetal distress. Intermittent auscultation reduced risk by 43%, compared with CTG, 66% compared with CTG-FBS, 58%, compared with FPO-CTG, and 17%, compared with FPO-CTG-FBS. Conversely, compared with intermittent auscultation, STAN-CTG and cCTG-FBS increased risk of emergency cesarean deliveries because of fetal distress by 39% and 80%, respectively.

Further analysis showed that all types of surveillance had similar effects on neonatal outcomes, such as admission to neonatal unit and neonatal acidemia. Although a combination of STAN or FPO with CTG-FBS “seemed to improve the likelihood of reducing adverse neonatal outcomes,” the investigators noted that these differences were not significant in network meta­-analysis.

“New fetal surveillance methods did not improve neonatal outcomes or reduce unnecessary maternal interventions,” Dr. Al Wattar and colleagues concluded. “Further evidence is needed to evaluate the effects of fetal pulse oximetry and fetal heart electrocardiography in labor.”

Courtney Rhoades, DO, MBA, FACOG, medical director of labor and delivery and assistant professor of obstetrics and gynecology at the University of Florida, Jacksonville, suggested that the meta-analysis supports the safety of intermittent auscultation, but the results may not be entirely applicable to real-world practice.

“It is hard, in practice, to draw the same conclusion that they do in the study that the newer methods may cause too many emergency C-sections because our fetal monitoring equipment, methodology for interpretation, ability to do emergency C-sections and maternal risk factors have changed in the last 50 years,” Dr. Rhoades said. “Continuous fetal monitoring gives more data points during labor, and with more data points, there are more opportunities to interpret and act – either correctly or incorrectly. As they state in the study, the decision to do a C-section is multifactorial.”

Dr. Rhoades, who recently authored a textbook chapter on intrapartum monitoring and fetal assessment, recommended that intermittent auscultation be reserved for low-risk patients.

“The American College of Obstetricians and Gynecologists has endorsed intermittent auscultation for low-risk pregnancies and this study affirms their support,” Dr. Rhoades said. “Women with a low-risk pregnancy can benefit from intermittent auscultation because it allows them more autonomy and movement during labor so it should be offered to our low-risk patients.”

Dr. Al Wattar reported a personal Academic Clinical Lectureship from the U.K. National Health Institute of Research. Dr. Khan disclosed funding from the Beatriz Galindo Program Grant given to the University of Granada by the Ministry of Science, Innovation, and Universities of the Spanish Government.

For intrapartum fetal surveillance, the old way may be the best way, according to a meta-analysis involving more than 118,000 patients.

Intermittent auscultation with a Pinard stethoscope and handheld Doppler was associated with a significantly lower risk of emergency cesarean deliveries than newer monitoring techniques without jeopardizing maternal or neonatal outcomes, reported lead author Bassel H. Al Wattar, MD, PhD, of University of Warwick, Coventry, England, and University College London Hospitals, and colleagues.

“Over the last 50 years, several newer surveillance methods have been evaluated, with varied uptake in practice,” the investigators wrote in the Canadian Medical Association Journal, noting that cardiotocography (CTG) is the most common method for high-risk pregnancies, typically coupled with at least one other modality, such as fetal scalp pH analysis (FBS), fetal pulse oximetry (FPO), or fetal heart electrocardiogram (STAN).

“Despite extensive investment in clinical research, the overall effectiveness of such methods in improving maternal and neonatal outcomes remains debatable as stillbirth rates have plateaued worldwide, while cesarean delivery rates continue to rise,” the investigators wrote. Previous meta-analyses have relied upon head-to-head comparisons of monitoring techniques and did not take into account effects on maternal and neonatal outcomes.

To address this knowledge gap, Dr. Al Wattar and colleagues conducted the present systematic review and meta-analysis, ultimately including 33 trials with 118,863 women who underwent intrapartum fetal surveillance, dating back to 1976. Ten surveillance types were evaluated, including intermittent auscultation with Pinard stethoscope and handheld Doppler, CTG with or without computer-aided decision models (cCTG), and CTG or cCTG combined with one or two other techniques, such as FBS, FPO, and STAN.

This revealed that intermittent auscultation outperformed all other techniques in terms of emergency cesarean deliveries and emergency cesarean deliveries because of fetal distress.

Specifically, intermittent auscultation significantly reduced risk of emergency cesarean deliveries, compared with CTG (relative risk, 0.83; 95% confidence interval, 0.72-0.97), CTG-FBS (RR, 0.71; 95% CI, 0.63-0.80), CTG-lactate (RR, 0.77; 95% CI, 0.64-0.92), and FPO-CTG-FBS (RR, 0.81; 95% CI, 0.67-0.99). Conversely, compared with IA, STAN-CTG-FBS and cCTG-FBS raised risk of emergency cesarean deliveries by 17% and 21%, respectively.

Compared with other modalities, the superiority of intermittent auscultation was even more pronounced in terms of emergency cesarean deliveries because of fetal distress. Intermittent auscultation reduced risk by 43%, compared with CTG, 66% compared with CTG-FBS, 58%, compared with FPO-CTG, and 17%, compared with FPO-CTG-FBS. Conversely, compared with intermittent auscultation, STAN-CTG and cCTG-FBS increased risk of emergency cesarean deliveries because of fetal distress by 39% and 80%, respectively.

Further analysis showed that all types of surveillance had similar effects on neonatal outcomes, such as admission to neonatal unit and neonatal acidemia. Although a combination of STAN or FPO with CTG-FBS “seemed to improve the likelihood of reducing adverse neonatal outcomes,” the investigators noted that these differences were not significant in network meta­-analysis.

“New fetal surveillance methods did not improve neonatal outcomes or reduce unnecessary maternal interventions,” Dr. Al Wattar and colleagues concluded. “Further evidence is needed to evaluate the effects of fetal pulse oximetry and fetal heart electrocardiography in labor.”

Courtney Rhoades, DO, MBA, FACOG, medical director of labor and delivery and assistant professor of obstetrics and gynecology at the University of Florida, Jacksonville, suggested that the meta-analysis supports the safety of intermittent auscultation, but the results may not be entirely applicable to real-world practice.

“It is hard, in practice, to draw the same conclusion that they do in the study that the newer methods may cause too many emergency C-sections because our fetal monitoring equipment, methodology for interpretation, ability to do emergency C-sections and maternal risk factors have changed in the last 50 years,” Dr. Rhoades said. “Continuous fetal monitoring gives more data points during labor, and with more data points, there are more opportunities to interpret and act – either correctly or incorrectly. As they state in the study, the decision to do a C-section is multifactorial.”

Dr. Rhoades, who recently authored a textbook chapter on intrapartum monitoring and fetal assessment, recommended that intermittent auscultation be reserved for low-risk patients.

“The American College of Obstetricians and Gynecologists has endorsed intermittent auscultation for low-risk pregnancies and this study affirms their support,” Dr. Rhoades said. “Women with a low-risk pregnancy can benefit from intermittent auscultation because it allows them more autonomy and movement during labor so it should be offered to our low-risk patients.”

Dr. Al Wattar reported a personal Academic Clinical Lectureship from the U.K. National Health Institute of Research. Dr. Khan disclosed funding from the Beatriz Galindo Program Grant given to the University of Granada by the Ministry of Science, Innovation, and Universities of the Spanish Government.

For intrapartum fetal surveillance, the old way may be the best way, according to a meta-analysis involving more than 118,000 patients.

Intermittent auscultation with a Pinard stethoscope and handheld Doppler was associated with a significantly lower risk of emergency cesarean deliveries than newer monitoring techniques without jeopardizing maternal or neonatal outcomes, reported lead author Bassel H. Al Wattar, MD, PhD, of University of Warwick, Coventry, England, and University College London Hospitals, and colleagues.

“Over the last 50 years, several newer surveillance methods have been evaluated, with varied uptake in practice,” the investigators wrote in the Canadian Medical Association Journal, noting that cardiotocography (CTG) is the most common method for high-risk pregnancies, typically coupled with at least one other modality, such as fetal scalp pH analysis (FBS), fetal pulse oximetry (FPO), or fetal heart electrocardiogram (STAN).

“Despite extensive investment in clinical research, the overall effectiveness of such methods in improving maternal and neonatal outcomes remains debatable as stillbirth rates have plateaued worldwide, while cesarean delivery rates continue to rise,” the investigators wrote. Previous meta-analyses have relied upon head-to-head comparisons of monitoring techniques and did not take into account effects on maternal and neonatal outcomes.

To address this knowledge gap, Dr. Al Wattar and colleagues conducted the present systematic review and meta-analysis, ultimately including 33 trials with 118,863 women who underwent intrapartum fetal surveillance, dating back to 1976. Ten surveillance types were evaluated, including intermittent auscultation with Pinard stethoscope and handheld Doppler, CTG with or without computer-aided decision models (cCTG), and CTG or cCTG combined with one or two other techniques, such as FBS, FPO, and STAN.

This revealed that intermittent auscultation outperformed all other techniques in terms of emergency cesarean deliveries and emergency cesarean deliveries because of fetal distress.

Specifically, intermittent auscultation significantly reduced risk of emergency cesarean deliveries, compared with CTG (relative risk, 0.83; 95% confidence interval, 0.72-0.97), CTG-FBS (RR, 0.71; 95% CI, 0.63-0.80), CTG-lactate (RR, 0.77; 95% CI, 0.64-0.92), and FPO-CTG-FBS (RR, 0.81; 95% CI, 0.67-0.99). Conversely, compared with IA, STAN-CTG-FBS and cCTG-FBS raised risk of emergency cesarean deliveries by 17% and 21%, respectively.

Compared with other modalities, the superiority of intermittent auscultation was even more pronounced in terms of emergency cesarean deliveries because of fetal distress. Intermittent auscultation reduced risk by 43%, compared with CTG, 66% compared with CTG-FBS, 58%, compared with FPO-CTG, and 17%, compared with FPO-CTG-FBS. Conversely, compared with intermittent auscultation, STAN-CTG and cCTG-FBS increased risk of emergency cesarean deliveries because of fetal distress by 39% and 80%, respectively.

Further analysis showed that all types of surveillance had similar effects on neonatal outcomes, such as admission to neonatal unit and neonatal acidemia. Although a combination of STAN or FPO with CTG-FBS “seemed to improve the likelihood of reducing adverse neonatal outcomes,” the investigators noted that these differences were not significant in network meta­-analysis.

“New fetal surveillance methods did not improve neonatal outcomes or reduce unnecessary maternal interventions,” Dr. Al Wattar and colleagues concluded. “Further evidence is needed to evaluate the effects of fetal pulse oximetry and fetal heart electrocardiography in labor.”

Courtney Rhoades, DO, MBA, FACOG, medical director of labor and delivery and assistant professor of obstetrics and gynecology at the University of Florida, Jacksonville, suggested that the meta-analysis supports the safety of intermittent auscultation, but the results may not be entirely applicable to real-world practice.

“It is hard, in practice, to draw the same conclusion that they do in the study that the newer methods may cause too many emergency C-sections because our fetal monitoring equipment, methodology for interpretation, ability to do emergency C-sections and maternal risk factors have changed in the last 50 years,” Dr. Rhoades said. “Continuous fetal monitoring gives more data points during labor, and with more data points, there are more opportunities to interpret and act – either correctly or incorrectly. As they state in the study, the decision to do a C-section is multifactorial.”

Dr. Rhoades, who recently authored a textbook chapter on intrapartum monitoring and fetal assessment, recommended that intermittent auscultation be reserved for low-risk patients.

“The American College of Obstetricians and Gynecologists has endorsed intermittent auscultation for low-risk pregnancies and this study affirms their support,” Dr. Rhoades said. “Women with a low-risk pregnancy can benefit from intermittent auscultation because it allows them more autonomy and movement during labor so it should be offered to our low-risk patients.”

Dr. Al Wattar reported a personal Academic Clinical Lectureship from the U.K. National Health Institute of Research. Dr. Khan disclosed funding from the Beatriz Galindo Program Grant given to the University of Granada by the Ministry of Science, Innovation, and Universities of the Spanish Government.

Updated data continue to show significant clinical benefits for patients with unresectable hepatocellular carcinoma (HCC) with the combination of the immune checkpoint inhibitor atezolizumab and the angiogenesis inhibitor bevacizumab.

The new analysis shows benefit even in patients with high-risk disease.

The findings come from the practice-changing IMBRave150 trial, and the new data are from a median follow-up of 15.6 months. They show that median overall survival in the intention-to-treat (ITT) population, which included both high-risk and non–high-risk patients, was 19.2 months for patients randomized to atezolizumab-bevacizumab vs. 13.4 months for patients on sorafenib (P = .0009).

Jennifer J. Knox, MD, of Princess Margaret Cancer Centre at the University of Toronto, said that the updated data confirm her first impressions of the atezolizumab-bevacizumab combination.

“As a clinician who treats HCC, I can’t tell you how exciting it was to see these [survival] curves, now published in The New England Journal of Medicine, where you can see the superiority of the atezolizumab-bevacizumab combination over sorafenib, with early separation of the curves that last in both overall survival and progression-free survival,” she said.

Dr. Knox was acting as a discussant for the presentation, where the new data were reported by Richard S. Finn, MD, of Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, at the American Association for Cancer Research Annual Meeting 2021: Week 1 (Abstract CT009).
 

Benefit seen also in high-risk group

At the meeting, Dr. Finn reported results from a subgroup of 101 patients who had high-risk disease (from 501 patients in the ITT population).

High-risk disease included tumor invasion of the main trunk of the portal vein of the liver and/or the portal vein branch contralateral to the primarily involved lobe (Vp4), and/or bile duct invasion, and/or tumor occupancy of at least 50% of the liver. Many of these patients would have been excluded from contemporary trials in HCC, Dr. Finn noted. 

In this subgroup of patients with high-risk disease, the median overall survival with atezolizumab-bevacizumab was 7.6 months, compared with 5.5 months with sorafenib. This difference translated into a hazard ratio (HR) for death of 0.62 for the combination, although the upper limit of the 95% confidence was 1.00, and therefore statistically not significant.

The overall survival benefit for high-risk patients was similar to that in the non–high-risk population of 400 patients (HR, 0.68; 95% CI 0.51 - 0.91), Dr. Finn said. 

Median progression-free survival (PFS) among high-risk patients was 5.4 months vs. 2.8 months with sorafenib, although this difference too was not significant, possibly because of the relatively small sample size.

“The data in this high-risk group is generally consistent with what we saw in the intent-to-treat population, and that is to say that atezo-bev has improved overall survival and PFS as compared to sorafenib, and a very similar objective response rate in this high-risk group as in the intent-to-treat population,” he said.

However, there were five fatal upper gastrointestinal bleeding events among high-risk patients treated with the combination, compared with none in the sorafenib arm. None of the deaths were considered by investigators to be treatment related, Dr. Finn said. All five patients who died had microvascular invasion, suggesting that patients with these features are at especially elevated risk for adverse events, he noted.

Overall, there were 23 on-study deaths among patients who received the combination (10 high-risk and 13 non–high-risk patients), compared with 9 patients treated with sorafenib (3 high-risk and 6 non–high-risk). Six of the deaths in the combination arm were attributed to treatment vs. one in the sorafenib arm.

Treatment-related adverse events of any grade, and grade 3 or 4 adverse events, occurred more frequently with sorafenib than with the combination in both high-risk and non–high-risk patients.

In both treatment groups, however, the incidence of serious adverse events was higher with the combination. Dr. Finn noted that the duration of therapy was longer with atezolizumab-bevacizumab than with sorafenib, which could account for the higher incidence of serious adverse events with the combination.
 

What’s next?

In her discussion, Dr. Knox noted that several other combinations are currently being explored for first-line treatment of HCC, including two trials with dual checkpoint inhibitors, and two comparing a tyrosine kinase inhibitor plus checkpoint inhibitor with tyrosine kinase inhibitors alone.

“There’s a lot of excitement about seeing these results, and I think when they read out in the next year or two, there will be a lot of cross-trial comparisons with patient groups and outcomes with the IMBRave150 data, which will be informative in choosing treatments for our patients,” she said.

“This abstract has shown that there is real benefit across both the high- and the lower-risk patients, and that clinicians need to be careful about the risk of hemorrhage in portal vein thrombosis,” Dr. Knox summarized.

The IMBRave150 trial is sponsored by F. Hoffmann–La Roche. Dr. Finn disclosed consulting activities for F. Hoffmann–La Roche, and institutional grant/research support from Roche and others. Dr. Knox disclosed grant/research support from F. Hoffmann–La Roche and others, and consulting for Merck, Pfizer, and Esai.

A version of this article first appeared on Medscape.com.

Updated data continue to show significant clinical benefits for patients with unresectable hepatocellular carcinoma (HCC) with the combination of the immune checkpoint inhibitor atezolizumab and the angiogenesis inhibitor bevacizumab.

The new analysis shows benefit even in patients with high-risk disease.

The findings come from the practice-changing IMBRave150 trial, and the new data are from a median follow-up of 15.6 months. They show that median overall survival in the intention-to-treat (ITT) population, which included both high-risk and non–high-risk patients, was 19.2 months for patients randomized to atezolizumab-bevacizumab vs. 13.4 months for patients on sorafenib (P = .0009).

Jennifer J. Knox, MD, of Princess Margaret Cancer Centre at the University of Toronto, said that the updated data confirm her first impressions of the atezolizumab-bevacizumab combination.

“As a clinician who treats HCC, I can’t tell you how exciting it was to see these [survival] curves, now published in The New England Journal of Medicine, where you can see the superiority of the atezolizumab-bevacizumab combination over sorafenib, with early separation of the curves that last in both overall survival and progression-free survival,” she said.

Dr. Knox was acting as a discussant for the presentation, where the new data were reported by Richard S. Finn, MD, of Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, at the American Association for Cancer Research Annual Meeting 2021: Week 1 (Abstract CT009).
 

Benefit seen also in high-risk group

At the meeting, Dr. Finn reported results from a subgroup of 101 patients who had high-risk disease (from 501 patients in the ITT population).

High-risk disease included tumor invasion of the main trunk of the portal vein of the liver and/or the portal vein branch contralateral to the primarily involved lobe (Vp4), and/or bile duct invasion, and/or tumor occupancy of at least 50% of the liver. Many of these patients would have been excluded from contemporary trials in HCC, Dr. Finn noted. 

In this subgroup of patients with high-risk disease, the median overall survival with atezolizumab-bevacizumab was 7.6 months, compared with 5.5 months with sorafenib. This difference translated into a hazard ratio (HR) for death of 0.62 for the combination, although the upper limit of the 95% confidence was 1.00, and therefore statistically not significant.

The overall survival benefit for high-risk patients was similar to that in the non–high-risk population of 400 patients (HR, 0.68; 95% CI 0.51 - 0.91), Dr. Finn said. 

Median progression-free survival (PFS) among high-risk patients was 5.4 months vs. 2.8 months with sorafenib, although this difference too was not significant, possibly because of the relatively small sample size.

“The data in this high-risk group is generally consistent with what we saw in the intent-to-treat population, and that is to say that atezo-bev has improved overall survival and PFS as compared to sorafenib, and a very similar objective response rate in this high-risk group as in the intent-to-treat population,” he said.

However, there were five fatal upper gastrointestinal bleeding events among high-risk patients treated with the combination, compared with none in the sorafenib arm. None of the deaths were considered by investigators to be treatment related, Dr. Finn said. All five patients who died had microvascular invasion, suggesting that patients with these features are at especially elevated risk for adverse events, he noted.

Overall, there were 23 on-study deaths among patients who received the combination (10 high-risk and 13 non–high-risk patients), compared with 9 patients treated with sorafenib (3 high-risk and 6 non–high-risk). Six of the deaths in the combination arm were attributed to treatment vs. one in the sorafenib arm.

Treatment-related adverse events of any grade, and grade 3 or 4 adverse events, occurred more frequently with sorafenib than with the combination in both high-risk and non–high-risk patients.

In both treatment groups, however, the incidence of serious adverse events was higher with the combination. Dr. Finn noted that the duration of therapy was longer with atezolizumab-bevacizumab than with sorafenib, which could account for the higher incidence of serious adverse events with the combination.
 

What’s next?

In her discussion, Dr. Knox noted that several other combinations are currently being explored for first-line treatment of HCC, including two trials with dual checkpoint inhibitors, and two comparing a tyrosine kinase inhibitor plus checkpoint inhibitor with tyrosine kinase inhibitors alone.

“There’s a lot of excitement about seeing these results, and I think when they read out in the next year or two, there will be a lot of cross-trial comparisons with patient groups and outcomes with the IMBRave150 data, which will be informative in choosing treatments for our patients,” she said.

“This abstract has shown that there is real benefit across both the high- and the lower-risk patients, and that clinicians need to be careful about the risk of hemorrhage in portal vein thrombosis,” Dr. Knox summarized.

The IMBRave150 trial is sponsored by F. Hoffmann–La Roche. Dr. Finn disclosed consulting activities for F. Hoffmann–La Roche, and institutional grant/research support from Roche and others. Dr. Knox disclosed grant/research support from F. Hoffmann–La Roche and others, and consulting for Merck, Pfizer, and Esai.

A version of this article first appeared on Medscape.com.

Updated data continue to show significant clinical benefits for patients with unresectable hepatocellular carcinoma (HCC) with the combination of the immune checkpoint inhibitor atezolizumab and the angiogenesis inhibitor bevacizumab.

The new analysis shows benefit even in patients with high-risk disease.

The findings come from the practice-changing IMBRave150 trial, and the new data are from a median follow-up of 15.6 months. They show that median overall survival in the intention-to-treat (ITT) population, which included both high-risk and non–high-risk patients, was 19.2 months for patients randomized to atezolizumab-bevacizumab vs. 13.4 months for patients on sorafenib (P = .0009).

Jennifer J. Knox, MD, of Princess Margaret Cancer Centre at the University of Toronto, said that the updated data confirm her first impressions of the atezolizumab-bevacizumab combination.

“As a clinician who treats HCC, I can’t tell you how exciting it was to see these [survival] curves, now published in The New England Journal of Medicine, where you can see the superiority of the atezolizumab-bevacizumab combination over sorafenib, with early separation of the curves that last in both overall survival and progression-free survival,” she said.

Dr. Knox was acting as a discussant for the presentation, where the new data were reported by Richard S. Finn, MD, of Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, at the American Association for Cancer Research Annual Meeting 2021: Week 1 (Abstract CT009).
 

Benefit seen also in high-risk group

At the meeting, Dr. Finn reported results from a subgroup of 101 patients who had high-risk disease (from 501 patients in the ITT population).

High-risk disease included tumor invasion of the main trunk of the portal vein of the liver and/or the portal vein branch contralateral to the primarily involved lobe (Vp4), and/or bile duct invasion, and/or tumor occupancy of at least 50% of the liver. Many of these patients would have been excluded from contemporary trials in HCC, Dr. Finn noted. 

In this subgroup of patients with high-risk disease, the median overall survival with atezolizumab-bevacizumab was 7.6 months, compared with 5.5 months with sorafenib. This difference translated into a hazard ratio (HR) for death of 0.62 for the combination, although the upper limit of the 95% confidence was 1.00, and therefore statistically not significant.

The overall survival benefit for high-risk patients was similar to that in the non–high-risk population of 400 patients (HR, 0.68; 95% CI 0.51 - 0.91), Dr. Finn said. 

Median progression-free survival (PFS) among high-risk patients was 5.4 months vs. 2.8 months with sorafenib, although this difference too was not significant, possibly because of the relatively small sample size.

“The data in this high-risk group is generally consistent with what we saw in the intent-to-treat population, and that is to say that atezo-bev has improved overall survival and PFS as compared to sorafenib, and a very similar objective response rate in this high-risk group as in the intent-to-treat population,” he said.

However, there were five fatal upper gastrointestinal bleeding events among high-risk patients treated with the combination, compared with none in the sorafenib arm. None of the deaths were considered by investigators to be treatment related, Dr. Finn said. All five patients who died had microvascular invasion, suggesting that patients with these features are at especially elevated risk for adverse events, he noted.

Overall, there were 23 on-study deaths among patients who received the combination (10 high-risk and 13 non–high-risk patients), compared with 9 patients treated with sorafenib (3 high-risk and 6 non–high-risk). Six of the deaths in the combination arm were attributed to treatment vs. one in the sorafenib arm.

Treatment-related adverse events of any grade, and grade 3 or 4 adverse events, occurred more frequently with sorafenib than with the combination in both high-risk and non–high-risk patients.

In both treatment groups, however, the incidence of serious adverse events was higher with the combination. Dr. Finn noted that the duration of therapy was longer with atezolizumab-bevacizumab than with sorafenib, which could account for the higher incidence of serious adverse events with the combination.
 

What’s next?

In her discussion, Dr. Knox noted that several other combinations are currently being explored for first-line treatment of HCC, including two trials with dual checkpoint inhibitors, and two comparing a tyrosine kinase inhibitor plus checkpoint inhibitor with tyrosine kinase inhibitors alone.

“There’s a lot of excitement about seeing these results, and I think when they read out in the next year or two, there will be a lot of cross-trial comparisons with patient groups and outcomes with the IMBRave150 data, which will be informative in choosing treatments for our patients,” she said.

“This abstract has shown that there is real benefit across both the high- and the lower-risk patients, and that clinicians need to be careful about the risk of hemorrhage in portal vein thrombosis,” Dr. Knox summarized.

The IMBRave150 trial is sponsored by F. Hoffmann–La Roche. Dr. Finn disclosed consulting activities for F. Hoffmann–La Roche, and institutional grant/research support from Roche and others. Dr. Knox disclosed grant/research support from F. Hoffmann–La Roche and others, and consulting for Merck, Pfizer, and Esai.

A version of this article first appeared on Medscape.com.

During the early months of the COVID-19 pandemic, hospital groups and systems scrambled to create protocols and models to respond to the novel coronavirus. In the pre-pandemic world, hospital groups have traditionally focused on standardizing clinical protocols and care models that rely on evidence-based medical practices or extended experience.

During COVID-19, however, our team at Dell Medical School needed to rapidly and iteratively standardize care based on evolving science, effectively communicate that approach across rotating hospital medicine physicians and residents, and update care models, workflows, and technology every few days. In this article, we review our initial experiences, describe the strategies we employed to respond to these challenges, and reflect on the lessons learned and our proposed strategy moving forward.
 

Early pandemic challenges

Our initial inpatient strategies focused on containment, infection prevention, and bracing ourselves rather than creating a COVID Center of Excellence (COE). In fact, our hospital network’s initial strategy was to have COVID-19 patients transferred to a different hospital within our network. However, as March progressed, we became the designated COVID-19 hospital in our area’s network because of the increasing volume of patients we saw.

Patients from the surrounding regional hospitals were transferring their COVID-19 patients to us and we quickly saw the wide spectrum of illness, ranging from mild pneumonia to severe disease requiring mechanical ventilation upon admission. All frontline providers felt the stress of needing to find treatment options quickly for our sickest patients. We realized that to provide safe, effective, and high-quality care to COVID-19 patients, we needed to create a sustainable and standardized interdisciplinary approach.

COVID-19 testing was a major challenge when the pandemic hit as testing kits and personal protective equipment were in limited supply. How would we choose who to test or empirically place in COVID-19 isolation? In addition, we faced questions surrounding safe discharge practices, especially for patients who could not self-isolate in their home (if they even had one).

In March, emergency use authorization (EUA) for hydroxychloroquine was granted by the U.S. FDA despite limited data. This resulted in pressure from the public to use this drug in our patients. At the same time, we saw that some patients quickly got better on their own with supportive care. As clinicians striving to practice evidence-based medicine, we certainly did not want to give patients an unproven therapy that could do more harm than good. We also felt the need to respond with statements about what we could do that worked – rather than negotiate about withholding certain treatments featured in the news. Clearly, a “one-size-fits-all” approach to therapeutics was not going to work in treating patients with COVID-19.

We realized we were going to have to learn and adapt together – quickly. It became apparent that we needed to create structures to rapidly adjudicate and integrate emerging science into standardized clinical care delivery.
 

Solutions in the form of better structures

In response to these challenges, we created early morning meetings or “huddles” among COVID-19 care teams and hospital administration. A designated “COVID ID” physician from Infectious Diseases would meet with hospitalist and critical care teams each morning in our daily huddles to review all newly admitted patients, current hospitalized patients, and patients with pending COVID-19 tests or suspected initial false-negative tests.

Together, and via the newly developed Therapeutics and Informatics Committee, we created early treatment recommendations based upon available evidence, treatment availability, and the patient’s severity of illness. Within the first ten days of admitting our first patient, it had become standard practice to review eligible patients soon after admission for therapies such as convalescent plasma, and, later, remdesivir and steroids.

We codified these consensus recommendations and processes in our Dell Med COVID Manual, a living document that was frequently updated and disseminated to our group. It created a single ‘true north’ of standardized workflows for triage, diagnosis, management, discharge coordination, and end-of-life care. The document allowed for continuous and asynchronous multi-person collaboration and extremely rapid cycles of improvement. Between March and December 2020, this 100-page handbook went through more than 130 iterations.
 

Strategy for the future

This approach – communicating frequently, adapting on a daily to weekly basis, and continuously scanning the science for opportunities to improve our care delivery – became the foundation of our approach and the Therapeutics and Informatics Committee. Just as importantly, this created a culture of engagement, collaboration, and shared problem-solving that helped us stay organized, keep up to date with the latest science, and innovate rather than panic when faced with ongoing unpredictability and chaos in the early days of the pandemic.

As the pandemic enters into its 13th month, we carry this foundation and our strategies forward. The infrastructure and systems of communication that we have set in place will allow us to be nimble in our response as COVID-19 numbers surge in our region.
 

Dr. Gandhi is an assistant professor in the department of internal medicine at Dell Medical School, University of Texas, Austin. Dr. Mondy is chief of the division of infectious disease and associate professor in the department of internal medicine at Dell Medical School. Dr. Busch and Dr. Brode are assistant professors in the department of internal medicine at Dell Medical School. This article is part of a series originally published in The Hospital Leader, the official blog of SHM.

During the early months of the COVID-19 pandemic, hospital groups and systems scrambled to create protocols and models to respond to the novel coronavirus. In the pre-pandemic world, hospital groups have traditionally focused on standardizing clinical protocols and care models that rely on evidence-based medical practices or extended experience.

During COVID-19, however, our team at Dell Medical School needed to rapidly and iteratively standardize care based on evolving science, effectively communicate that approach across rotating hospital medicine physicians and residents, and update care models, workflows, and technology every few days. In this article, we review our initial experiences, describe the strategies we employed to respond to these challenges, and reflect on the lessons learned and our proposed strategy moving forward.
 

Early pandemic challenges

Our initial inpatient strategies focused on containment, infection prevention, and bracing ourselves rather than creating a COVID Center of Excellence (COE). In fact, our hospital network’s initial strategy was to have COVID-19 patients transferred to a different hospital within our network. However, as March progressed, we became the designated COVID-19 hospital in our area’s network because of the increasing volume of patients we saw.

Patients from the surrounding regional hospitals were transferring their COVID-19 patients to us and we quickly saw the wide spectrum of illness, ranging from mild pneumonia to severe disease requiring mechanical ventilation upon admission. All frontline providers felt the stress of needing to find treatment options quickly for our sickest patients. We realized that to provide safe, effective, and high-quality care to COVID-19 patients, we needed to create a sustainable and standardized interdisciplinary approach.

COVID-19 testing was a major challenge when the pandemic hit as testing kits and personal protective equipment were in limited supply. How would we choose who to test or empirically place in COVID-19 isolation? In addition, we faced questions surrounding safe discharge practices, especially for patients who could not self-isolate in their home (if they even had one).

In March, emergency use authorization (EUA) for hydroxychloroquine was granted by the U.S. FDA despite limited data. This resulted in pressure from the public to use this drug in our patients. At the same time, we saw that some patients quickly got better on their own with supportive care. As clinicians striving to practice evidence-based medicine, we certainly did not want to give patients an unproven therapy that could do more harm than good. We also felt the need to respond with statements about what we could do that worked – rather than negotiate about withholding certain treatments featured in the news. Clearly, a “one-size-fits-all” approach to therapeutics was not going to work in treating patients with COVID-19.

We realized we were going to have to learn and adapt together – quickly. It became apparent that we needed to create structures to rapidly adjudicate and integrate emerging science into standardized clinical care delivery.
 

Solutions in the form of better structures

In response to these challenges, we created early morning meetings or “huddles” among COVID-19 care teams and hospital administration. A designated “COVID ID” physician from Infectious Diseases would meet with hospitalist and critical care teams each morning in our daily huddles to review all newly admitted patients, current hospitalized patients, and patients with pending COVID-19 tests or suspected initial false-negative tests.

Together, and via the newly developed Therapeutics and Informatics Committee, we created early treatment recommendations based upon available evidence, treatment availability, and the patient’s severity of illness. Within the first ten days of admitting our first patient, it had become standard practice to review eligible patients soon after admission for therapies such as convalescent plasma, and, later, remdesivir and steroids.

We codified these consensus recommendations and processes in our Dell Med COVID Manual, a living document that was frequently updated and disseminated to our group. It created a single ‘true north’ of standardized workflows for triage, diagnosis, management, discharge coordination, and end-of-life care. The document allowed for continuous and asynchronous multi-person collaboration and extremely rapid cycles of improvement. Between March and December 2020, this 100-page handbook went through more than 130 iterations.
 

Strategy for the future

This approach – communicating frequently, adapting on a daily to weekly basis, and continuously scanning the science for opportunities to improve our care delivery – became the foundation of our approach and the Therapeutics and Informatics Committee. Just as importantly, this created a culture of engagement, collaboration, and shared problem-solving that helped us stay organized, keep up to date with the latest science, and innovate rather than panic when faced with ongoing unpredictability and chaos in the early days of the pandemic.

As the pandemic enters into its 13th month, we carry this foundation and our strategies forward. The infrastructure and systems of communication that we have set in place will allow us to be nimble in our response as COVID-19 numbers surge in our region.
 

Dr. Gandhi is an assistant professor in the department of internal medicine at Dell Medical School, University of Texas, Austin. Dr. Mondy is chief of the division of infectious disease and associate professor in the department of internal medicine at Dell Medical School. Dr. Busch and Dr. Brode are assistant professors in the department of internal medicine at Dell Medical School. This article is part of a series originally published in The Hospital Leader, the official blog of SHM.

During the early months of the COVID-19 pandemic, hospital groups and systems scrambled to create protocols and models to respond to the novel coronavirus. In the pre-pandemic world, hospital groups have traditionally focused on standardizing clinical protocols and care models that rely on evidence-based medical practices or extended experience.

During COVID-19, however, our team at Dell Medical School needed to rapidly and iteratively standardize care based on evolving science, effectively communicate that approach across rotating hospital medicine physicians and residents, and update care models, workflows, and technology every few days. In this article, we review our initial experiences, describe the strategies we employed to respond to these challenges, and reflect on the lessons learned and our proposed strategy moving forward.
 

Early pandemic challenges

Our initial inpatient strategies focused on containment, infection prevention, and bracing ourselves rather than creating a COVID Center of Excellence (COE). In fact, our hospital network’s initial strategy was to have COVID-19 patients transferred to a different hospital within our network. However, as March progressed, we became the designated COVID-19 hospital in our area’s network because of the increasing volume of patients we saw.

Patients from the surrounding regional hospitals were transferring their COVID-19 patients to us and we quickly saw the wide spectrum of illness, ranging from mild pneumonia to severe disease requiring mechanical ventilation upon admission. All frontline providers felt the stress of needing to find treatment options quickly for our sickest patients. We realized that to provide safe, effective, and high-quality care to COVID-19 patients, we needed to create a sustainable and standardized interdisciplinary approach.

COVID-19 testing was a major challenge when the pandemic hit as testing kits and personal protective equipment were in limited supply. How would we choose who to test or empirically place in COVID-19 isolation? In addition, we faced questions surrounding safe discharge practices, especially for patients who could not self-isolate in their home (if they even had one).

In March, emergency use authorization (EUA) for hydroxychloroquine was granted by the U.S. FDA despite limited data. This resulted in pressure from the public to use this drug in our patients. At the same time, we saw that some patients quickly got better on their own with supportive care. As clinicians striving to practice evidence-based medicine, we certainly did not want to give patients an unproven therapy that could do more harm than good. We also felt the need to respond with statements about what we could do that worked – rather than negotiate about withholding certain treatments featured in the news. Clearly, a “one-size-fits-all” approach to therapeutics was not going to work in treating patients with COVID-19.

We realized we were going to have to learn and adapt together – quickly. It became apparent that we needed to create structures to rapidly adjudicate and integrate emerging science into standardized clinical care delivery.
 

Solutions in the form of better structures

In response to these challenges, we created early morning meetings or “huddles” among COVID-19 care teams and hospital administration. A designated “COVID ID” physician from Infectious Diseases would meet with hospitalist and critical care teams each morning in our daily huddles to review all newly admitted patients, current hospitalized patients, and patients with pending COVID-19 tests or suspected initial false-negative tests.

Together, and via the newly developed Therapeutics and Informatics Committee, we created early treatment recommendations based upon available evidence, treatment availability, and the patient’s severity of illness. Within the first ten days of admitting our first patient, it had become standard practice to review eligible patients soon after admission for therapies such as convalescent plasma, and, later, remdesivir and steroids.

We codified these consensus recommendations and processes in our Dell Med COVID Manual, a living document that was frequently updated and disseminated to our group. It created a single ‘true north’ of standardized workflows for triage, diagnosis, management, discharge coordination, and end-of-life care. The document allowed for continuous and asynchronous multi-person collaboration and extremely rapid cycles of improvement. Between March and December 2020, this 100-page handbook went through more than 130 iterations.
 

Strategy for the future

This approach – communicating frequently, adapting on a daily to weekly basis, and continuously scanning the science for opportunities to improve our care delivery – became the foundation of our approach and the Therapeutics and Informatics Committee. Just as importantly, this created a culture of engagement, collaboration, and shared problem-solving that helped us stay organized, keep up to date with the latest science, and innovate rather than panic when faced with ongoing unpredictability and chaos in the early days of the pandemic.

As the pandemic enters into its 13th month, we carry this foundation and our strategies forward. The infrastructure and systems of communication that we have set in place will allow us to be nimble in our response as COVID-19 numbers surge in our region.
 

Dr. Gandhi is an assistant professor in the department of internal medicine at Dell Medical School, University of Texas, Austin. Dr. Mondy is chief of the division of infectious disease and associate professor in the department of internal medicine at Dell Medical School. Dr. Busch and Dr. Brode are assistant professors in the department of internal medicine at Dell Medical School. This article is part of a series originally published in The Hospital Leader, the official blog of SHM.

The development of unusual movements after COVID-19 vaccination may be a result of functional neurologic disorder rather than being a direct adverse effect of the vaccine, it has been suggested.

Writing in an article published online in JAMA Neurology on April 9, 2021, two neurologists and a psychiatrist report the recent circulation of videos on social media about major neurologic adverse events, including continuous movements of the trunk and limbs or walking difficulties after administration of the COVID-19 vaccine. Some of these videos have been viewed millions of times by the public, they noted.

While these videos may be unsubstantiated, and it is not definitively known if the COVID-19 vaccine was administered in these cases, it was reported in the news that at least one patient was told by their physician that the diagnosis was conversion disorder, also known as functional neurological disorder (FND), the authors noted.

In addition, the Functional Neurological Disorder Society released a statement in January 2021 pointing out that the conditions described in these videos are seemingly consistent with FND, they added.

“We thought it would be useful to explain more about what functional neurological disorder is, as many people are not familiar with it,” lead author David Kim, MD, said in an interview. “We wanted to provide some contextual information about the condition, as these reports may not necessarily mean the vaccine is unsafe.”

Dr. Kim, who is part of the division of cognitive behavioral neurology at Massachusetts General Hospital, Boston, explained that, in FND, physical symptoms can be brought about after events such as head injury, surgery, vaccination, other medical procedures, or life events such as loss of employment.

“Many different factors can bring these symptoms on, and while there are definitely cases associated with stressful events, it is not necessarily stress induced,” he said. “However, the event itself does not cause the condition, rather it is the reaction of the patient to the event.”

FND is now viewed as a true brain-based disorder, Dr. Kim noted. “While in the past it has been described as psychosomatic, we are now moving away from that terminology, toward the idea of a neurological disorder that affects function. It is a neuropsychiatric disorder on the borderline between neurology and psychiatry.”

The authors believed that some of these cases of unusual movements reported after COVID vaccination are likely to be FND.

“In these cases, it is not the substance in the vaccine that is causing the condition, but the common side effects that can occur after vaccination such as aches and chills bring the attention of the patient to their bodily functions and this reaction can become maladaptive, triggering FND,” Dr. Kim said.

“We believe that health care professionals should be more aware of FND at the current time. They need to know that the general public are aware that some people are experiencing movement disorders after COVID vaccination, and that this conversation is happening on social media,” he commented. “If they see patients with these symptoms, they could consider FND to be one possibility.”

The authors emphasized that, because they have not seen the individual patients, they cannot comment on any specific cases.

“But as some of these videos circulating can be consistent with the condition being FND, and especially with news reports indicating that at least one patient was given that diagnosis, we wanted to raise awareness of this condition among health professionals,” Dr. Kim added.  

He explained that, in the past, FND has been a diagnosis of exclusion but now it is diagnosed with a clinical history and physical examination, looking for appropriate rule-in signs. Ancillary testing such as neuroimaging, electrophysiological studies, and blood tests are often used to rule out other conditions.

“Neurologists have a lot of training in this condition, as it is the second most common reason for a patient to visit a neurologist after headache,” Dr. Kim noted.

It is managed with education, counseling, physical rehabilitation and cognitive behavioral therapy. “A key part of the therapeutic process is working with the patient to explain the diagnosis. If they understand the condition, they do better. Patients can learn distraction techniques to allow more fluid movements,” he reported.

“As neurologists, and health care professionals more broadly, we must explain transparently and nonjudgmentally the nature of FND, including that these symptoms are real but not the direct result of toxic vaccine effects,” the authors wrote.

“Transparency and effective communication are needed in our society more than ever, and a condition as prevalent and potentially debilitating as FND can no longer remain marginalized and in the shadows. Effective communication will help educate the public and reduce fears so that patients can make informed decisions for themselves on receiving the vaccine to reduce the risk of COVID-19,” they concluded.

A version of this article first appeared on Medscape.com.

The development of unusual movements after COVID-19 vaccination may be a result of functional neurologic disorder rather than being a direct adverse effect of the vaccine, it has been suggested.

Writing in an article published online in JAMA Neurology on April 9, 2021, two neurologists and a psychiatrist report the recent circulation of videos on social media about major neurologic adverse events, including continuous movements of the trunk and limbs or walking difficulties after administration of the COVID-19 vaccine. Some of these videos have been viewed millions of times by the public, they noted.

While these videos may be unsubstantiated, and it is not definitively known if the COVID-19 vaccine was administered in these cases, it was reported in the news that at least one patient was told by their physician that the diagnosis was conversion disorder, also known as functional neurological disorder (FND), the authors noted.

In addition, the Functional Neurological Disorder Society released a statement in January 2021 pointing out that the conditions described in these videos are seemingly consistent with FND, they added.

“We thought it would be useful to explain more about what functional neurological disorder is, as many people are not familiar with it,” lead author David Kim, MD, said in an interview. “We wanted to provide some contextual information about the condition, as these reports may not necessarily mean the vaccine is unsafe.”

Dr. Kim, who is part of the division of cognitive behavioral neurology at Massachusetts General Hospital, Boston, explained that, in FND, physical symptoms can be brought about after events such as head injury, surgery, vaccination, other medical procedures, or life events such as loss of employment.

“Many different factors can bring these symptoms on, and while there are definitely cases associated with stressful events, it is not necessarily stress induced,” he said. “However, the event itself does not cause the condition, rather it is the reaction of the patient to the event.”

FND is now viewed as a true brain-based disorder, Dr. Kim noted. “While in the past it has been described as psychosomatic, we are now moving away from that terminology, toward the idea of a neurological disorder that affects function. It is a neuropsychiatric disorder on the borderline between neurology and psychiatry.”

The authors believed that some of these cases of unusual movements reported after COVID vaccination are likely to be FND.

“In these cases, it is not the substance in the vaccine that is causing the condition, but the common side effects that can occur after vaccination such as aches and chills bring the attention of the patient to their bodily functions and this reaction can become maladaptive, triggering FND,” Dr. Kim said.

“We believe that health care professionals should be more aware of FND at the current time. They need to know that the general public are aware that some people are experiencing movement disorders after COVID vaccination, and that this conversation is happening on social media,” he commented. “If they see patients with these symptoms, they could consider FND to be one possibility.”

The authors emphasized that, because they have not seen the individual patients, they cannot comment on any specific cases.

“But as some of these videos circulating can be consistent with the condition being FND, and especially with news reports indicating that at least one patient was given that diagnosis, we wanted to raise awareness of this condition among health professionals,” Dr. Kim added.  

He explained that, in the past, FND has been a diagnosis of exclusion but now it is diagnosed with a clinical history and physical examination, looking for appropriate rule-in signs. Ancillary testing such as neuroimaging, electrophysiological studies, and blood tests are often used to rule out other conditions.

“Neurologists have a lot of training in this condition, as it is the second most common reason for a patient to visit a neurologist after headache,” Dr. Kim noted.

It is managed with education, counseling, physical rehabilitation and cognitive behavioral therapy. “A key part of the therapeutic process is working with the patient to explain the diagnosis. If they understand the condition, they do better. Patients can learn distraction techniques to allow more fluid movements,” he reported.

“As neurologists, and health care professionals more broadly, we must explain transparently and nonjudgmentally the nature of FND, including that these symptoms are real but not the direct result of toxic vaccine effects,” the authors wrote.

“Transparency and effective communication are needed in our society more than ever, and a condition as prevalent and potentially debilitating as FND can no longer remain marginalized and in the shadows. Effective communication will help educate the public and reduce fears so that patients can make informed decisions for themselves on receiving the vaccine to reduce the risk of COVID-19,” they concluded.

A version of this article first appeared on Medscape.com.

The development of unusual movements after COVID-19 vaccination may be a result of functional neurologic disorder rather than being a direct adverse effect of the vaccine, it has been suggested.

Writing in an article published online in JAMA Neurology on April 9, 2021, two neurologists and a psychiatrist report the recent circulation of videos on social media about major neurologic adverse events, including continuous movements of the trunk and limbs or walking difficulties after administration of the COVID-19 vaccine. Some of these videos have been viewed millions of times by the public, they noted.

While these videos may be unsubstantiated, and it is not definitively known if the COVID-19 vaccine was administered in these cases, it was reported in the news that at least one patient was told by their physician that the diagnosis was conversion disorder, also known as functional neurological disorder (FND), the authors noted.

In addition, the Functional Neurological Disorder Society released a statement in January 2021 pointing out that the conditions described in these videos are seemingly consistent with FND, they added.

“We thought it would be useful to explain more about what functional neurological disorder is, as many people are not familiar with it,” lead author David Kim, MD, said in an interview. “We wanted to provide some contextual information about the condition, as these reports may not necessarily mean the vaccine is unsafe.”

Dr. Kim, who is part of the division of cognitive behavioral neurology at Massachusetts General Hospital, Boston, explained that, in FND, physical symptoms can be brought about after events such as head injury, surgery, vaccination, other medical procedures, or life events such as loss of employment.

“Many different factors can bring these symptoms on, and while there are definitely cases associated with stressful events, it is not necessarily stress induced,” he said. “However, the event itself does not cause the condition, rather it is the reaction of the patient to the event.”

FND is now viewed as a true brain-based disorder, Dr. Kim noted. “While in the past it has been described as psychosomatic, we are now moving away from that terminology, toward the idea of a neurological disorder that affects function. It is a neuropsychiatric disorder on the borderline between neurology and psychiatry.”

The authors believed that some of these cases of unusual movements reported after COVID vaccination are likely to be FND.

“In these cases, it is not the substance in the vaccine that is causing the condition, but the common side effects that can occur after vaccination such as aches and chills bring the attention of the patient to their bodily functions and this reaction can become maladaptive, triggering FND,” Dr. Kim said.

“We believe that health care professionals should be more aware of FND at the current time. They need to know that the general public are aware that some people are experiencing movement disorders after COVID vaccination, and that this conversation is happening on social media,” he commented. “If they see patients with these symptoms, they could consider FND to be one possibility.”

The authors emphasized that, because they have not seen the individual patients, they cannot comment on any specific cases.

“But as some of these videos circulating can be consistent with the condition being FND, and especially with news reports indicating that at least one patient was given that diagnosis, we wanted to raise awareness of this condition among health professionals,” Dr. Kim added.  

He explained that, in the past, FND has been a diagnosis of exclusion but now it is diagnosed with a clinical history and physical examination, looking for appropriate rule-in signs. Ancillary testing such as neuroimaging, electrophysiological studies, and blood tests are often used to rule out other conditions.

“Neurologists have a lot of training in this condition, as it is the second most common reason for a patient to visit a neurologist after headache,” Dr. Kim noted.

It is managed with education, counseling, physical rehabilitation and cognitive behavioral therapy. “A key part of the therapeutic process is working with the patient to explain the diagnosis. If they understand the condition, they do better. Patients can learn distraction techniques to allow more fluid movements,” he reported.

“As neurologists, and health care professionals more broadly, we must explain transparently and nonjudgmentally the nature of FND, including that these symptoms are real but not the direct result of toxic vaccine effects,” the authors wrote.

“Transparency and effective communication are needed in our society more than ever, and a condition as prevalent and potentially debilitating as FND can no longer remain marginalized and in the shadows. Effective communication will help educate the public and reduce fears so that patients can make informed decisions for themselves on receiving the vaccine to reduce the risk of COVID-19,” they concluded.

A version of this article first appeared on Medscape.com.