The Impact of Surgical Delay in Primary Cutaneous Melanoma: A Systematic Review.

BACKGROUND AND OBJECTIVES: The prognosis of patients diagnosed with melanoma is highly dependent on staging, early detection, and early intervention. In this systematic review, the authors aimed to investigate the impact of surgical delay (time between diagnostic biopsy and definitive surgical excision) on melanoma-specific outcomes. MATERIAL AND METHODS: A systematic review was conducted from Embase (1974-present), MEDLINE (1946-present), Cochrane Central Register of Controlled Trials (2005-present), Scopus, and Web of Science. A total of 977 studies were included for review after removal of duplicates. A total of 10 studies were included for final analysis. RESULTS: In total, 70% (7/10) of the studies found that longer wait times between initial biopsy and surgical intervention are correlated with lower overall survival. Among the 9 studies that reported overall survival as a percentage, the median and SD overall survival was 82% ± 5.87. CONCLUSION: There is evidence that prolonged surgical delay in patients diagnosed with Stage I cutaneous melanoma is associated with worsened overall mortality, whereas the effect of surgical delay on overall mortality in Stages II and III melanomas is uncertain. Future prospective studies and randomized clinical trials are needed to better define the appropriate surgical wait times between biopsy and surgical treatment.

Targeted testing of bone marrow specimens with cytoplasmic vacuolization to identify previously undiagnosed cases of VEXAS syndrome.

OBJECTIVE: To retrospectively identify patients with VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic syndrome) among male patients with bone marrow vacuolization using a clinically applicable, targeted-screening approach. METHODS: Bone marrow reports from 1 May 2014 through 18 February 2022 were reviewed for documentation of cytoplasmic vacuolization. Patients with acute leukaemia, lymphoma, metastatic solid tumour, amyloidosis or POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes) syndrome were excluded, as were those without clinical records available for direct chart review. Cases were rated for suspicion of VEXAS syndrome using a 5-point scale based on the presence of laboratory findings, clinical features and treatment response. Patients with available DNA material and moderate (three patients) or high (four to five patients) suspicion were tested for somatic UBA1 variants associated with VEXAS syndrome. RESULTS: A total of 315 reports from 292 unique patients included documentation of vacuolization. Following exclusion criteria, 64 patients underwent direct medical chart review to assess likelihood of VEXAS syndrome, for which 21 patients met moderate to high suspicion. Available DNA was present in eight patients, seven (87.5%) of whom had a pathogenic somatic UBA1 variant consistent with VEXAS syndrome. The distribution of cytoplasmic vacuolization in the bone marrow biopsy reports among patients with VEXAS syndrome were erythroid and myeloid precursors (6/7), erythroid precursors only (1/7) and myeloid precursors only (0/7). CONCLUSION: In this study, the utilization of a clinically applicable targeted-screening approach to test bone marrow specimens (with vacuolization) for the presence of previously undiagnosed VEXAS syndrome resulted in a positive detection rate of 87.5%.

Pulmonary manifestations in VEXAS syndrome.

BACKGROUND: Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is a recently recognized multisystem disorder caused by somatic mutations in the UBA1 gene. METHODS: A retrospective cohort study was conducted on all patients with VEXAS syndrome evaluated at our institution from June 2020 through May 2022. Medical records and chest imaging studies were reviewed. RESULTS: We identified 45 subjects with median age of 68 years (range, 57-89), all men. Prior to VEXAS diagnosis, most patients had been diagnosed with various hematologic, rheumatologic, and dermatologic disorders. Most patients (84%) demonstrated canonical UBA1 methionine-41 (p.Met41) somatic mutations in hematopoietic cells. Fever (82%), skin lesions (91%), and respiratory symptoms (93%) were common presenting features. Chest CT manifested abnormalities in 91% of patients including parenchymal opacities in 25 (74%), most commonly ground-glass opacities (47%), along with mediastinal lymphadenopathy (29%), airway abnormalities (29%), and pleural effusion (24%). Pulmonary function test results available in 18 (40%) patients demonstrated mild restrictive impairment or normal results. Bronchoalveolar lavage and lung biopsy performed in a minority of patients demonstrated neutrophilic alveolitis and parenchymal inflammation, respectively. All patients received glucocorticoid therapy with at least partial response, but relapses were common and other immunosuppressive agents were employed in most patients. Pulmonary involvement appeared to improve in patients who received tocilizumab and JAK inhibitors. CONCLUSION: The pulmonary manifestations in VEXAS are relatively nonspecific and nonsevere, occur in the context of systemic inflammation and are responsive to escalation in glucocorticoid dosing.

Cutaneous involvement in VEXAS syndrome: clinical and histopathologic findings.

BACKGROUND: VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is an autoinflammatory disease with frequent cutaneous manifestations. METHODS: We conducted a retrospective study of all patients with genetically confirmed VEXAS syndrome seen at our institution. Available clinical photographs and skin biopsy slides were reviewed. RESULTS: Cutaneous manifestations developed in 22/25 (88%) patients with VEXAS syndrome. From this group, 10/22 (45%) developed skin involvement before or at the time of other clinical features of VEXAS. Twenty distinct dermatologic presentations of VEXAS from 14 patients were reviewed, and histopathologic patterns were classified as follows: neutrophilic urticarial dermatosis (n = 5, 25%), leukocytoclastic/urticarial vasculitis (n = 4, 20%), urticarial tissue reaction (n = 4, 20%), neutrophilic dermatosis (n = 3, 15%), neutrophilic panniculitis (n = 2, 10%), and nonspecific chronic septal panniculitis (n = 2, 10%). Common systemic findings included macrocytic anemia (96%), fever (88%), thrombocytopenia (76%), weight loss (76%), ocular inflammation (64%), pulmonary infiltrates (56%), deep venous thrombosis or pulmonary embolism (52%), and inflammatory arthritis (52%). CONCLUSIONS: Cutaneous involvement is a common feature of VEXAS syndrome, and histopathologic findings exist on a spectrum of neutrophilic inflammatory dermatoses.

Retrospective analysis of 450 emergency department dermatology consultations: An analysis of in-person and teledermatology consultations from 2015 to 2019.

INTRODUCTION: Dermatologic complaints are a common reason for emergency department visits. METHODS: Retrospective chart review from 1 January 2015 to 31 December 2019. Patients in the Mayo Clinic Emergency Department receiving dermatology consultation were included. RESULTS: Dermatitis (24.7%, n = 113), infection (20.4%, n = 93), and drug reaction (10.3%, n = 47) accounted for the majority of diagnoses. Emergency department providers often provide no diagnosis (38%) or a differential diagnosis (22%), and dermatology consultation frequently alters diagnosis (46%) and treatment (83%). Patients receiving in-person consultations are admitted more frequently than those receiving teledermatology consultations (40% vs. 16%, p < 0.001). Primary diagnostic concordance with subsequent dermatology evaluation is high for in-person (94%) and teledermatology (88%) consultations. DISCUSSION: This is the largest study of emergency department dermatology consultations in the United States and the first to compare in-person and teledermatology emergency department consultation utilization in clinical practice. These modalities are utilized in a complementary fashion at our institution, with severe dermatologic diagnoses seen in-person. The valuable role of emergency department dermatologists is highlighted by frequent changes to diagnosis and treatment plans that result from dermatology consultation. Furthermore, our data suggest that teledermatology is an effective modality with the potential to expand access to dermatologic expertise in the emergency department setting.

Liver transplantation for acute liver failure in a SARS-CoV-2 PCR-positive patient.

Current guidelines recommend deferring liver transplantation (LT) in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection until clinical improvement occurs and two PCR tests collected at least 24 hours apart are negative. We report a case of an 18-year-old, previously healthy African-American woman diagnosed with COVID-19, who presents with acute liver failure (ALF) requiring urgent LT in the context of SARS-CoV-2 polymerase chain reaction (PCR) positivity. The patient was thought to have acute Wilsonian crisis on the basis of hemolytic anemia, alkaline phosphatase:bilirubin ratio <4, AST:ALT ratio >2.2, elevated serum copper, and low uric acid, although an unusual presentation of COVID-19 causing ALF could not be excluded. After meeting criteria for status 1a listing, the patient underwent successful LT, despite ongoing SARS-CoV-2 PCR positivity. Remdesivir was given immediately posttransplant, and mycophenolate mofetil was withheld initially and the SARS-CoV-2 PCR test eventually became negative. Three months following transplantation, the patient has made a near-complete recovery. This case highlights that COVID-19 with SARS-CoV-2 PCR positivity may not be an absolute contraindication for transplantation in ALF. Criteria for patient selection and timing of LT amid the COVID-19 pandemic need to be validated in future studies.