Local Recurrence Rates After Excision of Desmoplastic Melanoma: A Systematic Review and Meta-Analysis.

BACKGROUND: Few prospective studies have evaluated local recurrence rates (LRR) after excision of desmoplastic melanoma (DM); however, several retrospective studies have reported high LRR. OBJECTIVE: To determine LRR after excision of DM and evaluate factors affecting LRR. MATERIALS AND METHODS: Systematic review of the PubMed, Embase, and Web of Science databases was performed to identify studies reporting local recurrence after excision of DM with conventional wide local excision (WLE), Mohs micrographic surgery (MMS), or staged excision (SE). Meta-analysis was performed to calculate summary LRR and pooled risk ratios (RR). RESULTS: Literature search identified 4 studies evaluating MMS or SE (total n = 61 DM). 53 studies assessed WLE ( n = 3,080) and were analyzed quantitatively. The overall LRR after WLE of DM was 21% (95% CI, 0.16-0.28; n = 2,308). Local recurrence rate was higher with positive/unknown histologic excision margins (49%, 95% CI, 0.25-0.74; n = 91) versus negative histologic margins (11%, 95% CI, 0.07-0.17; n = 1,075; [ p < .01]). Neurotropism was also associated with increased LRR (RR, 1.79; 95% CI, 1.34-2.38, p < .01; n = 644). CONCLUSION: DM has high LRR after WLE. Local recurrence risk was greatest with positive excision margins, indicating the importance of achieving negative microscopic margins. Greater study of MMS and SE for DM is required.

Single-Cell Analysis Suggests that Ongoing Affinity Maturation Drives the Emergence of Pemphigus Vulgaris Autoimmune Disease.

Pemphigus vulgaris (PV) is an autoimmune disease characterized by blistering sores on skin and mucosal membranes, caused by autoantibodies primarily targeting the cellular adhesion protein, desmoglein-3 (Dsg3). To better understand how Dsg3-specific autoantibodies develop and cause disease in humans, we performed a cross-sectional study of PV patients before and after treatment to track relevant cellular responses underlying disease pathogenesis, and we provide an in-depth analysis of two patients by generating a panel of mAbs from single Dsg3-specific memory B cells (MBCs). Additionally, we analyzed a paired sample from one patient collected 15-months prior to disease diagnosis. We find that Dsg3-specific MBCs have an activated phenotype and show signs of ongoing affinity maturation and clonal selection. Monoclonal antibodies (mAbs) with pathogenic activity primarily target epitopes in the extracellular domains EC1 and EC2 of Dsg3, though they can also bind to the EC4 domain. Combining antibodies targeting different epitopes synergistically enhances in vitro pathogenicity.

Continuous Glucose Monitoring for Hypoglycemia Avoidance and Glucose Counterregulation in Long-Standing Type 1 Diabetes.

Context: Patients with long-standing type 1 diabetes (T1D) are at increased risk for severe hypoglycemia because of defects in glucose counterregulation and recognition of hypoglycemia symptoms, in part mediated through exposure to hypoglycemia. Objective: To determine whether implementation of real-time continuous glucose monitoring (CGM) as a strategy for hypoglycemia avoidance could improve glucose counterregulation in patients with long-standing T1D and hypoglycemia unawareness. Design, Setting, Participants, and Intervention: Eleven patients with T1D disease duration of ∼31 years were studied longitudinally in the Clinical & Translational Research Center of the University of Pennsylvania before and 6 and 18 months after initiation of CGM and were compared with 12 nondiabetic control participants. Main Outcome Measure: Endogenous glucose production response derived from paired hyperinsulinemic stepped-hypoglycemic and euglycemic clamps with infusion of 6,6-2H2-glucose. Results: In patients with T1D, hypoglycemia awareness (Clarke score) and severity (HYPO score and severe events) improved (P < 0.01 for all) without change in hemoglobin A1c (baseline, 7.2% ± 0.2%). In response to insulin-induced hypoglycemia, endogenous glucose production did not change from before to 6 months (0.42 ± 0.08 vs 0.54 ± 0.07 mg·kg-1·min-1) but improved after 18 months (0.84 ± 0.15 mg·kg-1·min-1; P < 0.05 vs before CGM), albeit remaining less than in controls (1.39 ± 0.11 mg·kg-1·min-1; P ≤ 0.01 vs all). Conclusions: Real-time CGM can improve awareness and reduce the burden of problematic hypoglycemia in patients with long-standing T1D, but with only modest improvement in the endogenous glucose production response that is required to prevent or correct low blood glucose.

Rituximab therapy in pemphigus and other autoantibody-mediated diseases.

Rituximab, a monoclonal antibody targeting the B cell marker CD20, was initially approved in 1997 by the United States Food and Drug Administration (FDA) for the treatment of non-Hodgkin lymphoma. Since that time, rituximab has been FDA-approved for rheumatoid arthritis and vasculitides, such as granulomatosis with polyangiitis and microscopic polyangiitis. Additionally, rituximab has been used off-label in the treatment of numerous other autoimmune diseases, with notable success in pemphigus, an autoantibody-mediated skin blistering disease. The efficacy of rituximab therapy in pemphigus has spurred interest in its potential to treat other autoantibody-mediated diseases. This review summarizes the efficacy of rituximab in pemphigus and examines its off-label use in other select autoantibody-mediated diseases.

Patient Perspectives on Biosimilar Insulin.

Given that a new wave of biosimilar insulins will likely enter the market in coming years, it is important to understand patient perspectives on these biosimilars. A survey (N = 3214) conducted by the market research company dQ&A, which maintains a 10 000-patient panel of people with type 1 or type 2 diabetes in roughly equal measure, investigated these perspectives. The survey asked whether patients would switch to a hypothetical less expensive biosimilar insulin that was approved by their provider. Approximately 66% of respondents reported that they would "definitely" or "likely" use a biosimilar insulin, while 17% reported that they were "unlikely" to use or would "definitely not use" such a product. Type 2 diabetes patients demonstrated slightly more willingness to use biosimilars than type 1 diabetes patients. Common patient concerns included whether biosimilars would be as effective as reference products (~650 respondents), whether side effect profiles would deviate from those of reference products (~220 respondents), and the design of the delivery device (~50 respondents). While cost savings associated with biosimilar insulins could increase patient uptake, especially among patients without health insurance (some recent estimates suggest that biosimilars will come at a substantial discount), patients may still need assurance that a cheaper price tag is not necessarily associated with substandard quality. Overall, the dQ&A survey indicates that the majority of patients are willing to consider biosimilar insulins, but manufacturers will need to work proactively to address and assuage patient concerns regarding efficacy, safety, drug administration, and other factors.