Commensal bacteria protect against food allergen sensitization.

Environmentally induced alterations in the commensal microbiota have been implicated in the increasing prevalence of food allergy. We show here that sensitization to a food allergen is increased in mice that have been treated with antibiotics or are devoid of a commensal microbiota. By selectively colonizing gnotobiotic mice, we demonstrate that the allergy-protective capacity is conferred by a Clostridia-containing microbiota. Microarray analysis of intestinal epithelial cells from gnotobiotic mice revealed a previously unidentified mechanism by which Clostridia regulate innate lymphoid cell function and intestinal epithelial permeability to protect against allergen sensitization. Our findings will inform the development of novel approaches to prevent or treat food allergy based on modulating the composition of the intestinal microbiota.

A national cross-sectional analysis of dermatology away rotations using the Visiting Student Application Service database.

The highly competitive nature of the dermatology match requires applicants to undertake a variety of measures in the hopes of securing a residency position. Among the opportunities available to applicants is the chance to participate in away or "audition" rotations during their final year of undergraduate medical education. Away rotations are now performed by a majority of medical students applying into dermatology, but littleresearch has been done to describe the nature of this opportunity for interested applicants. An analysis of all dermatology electives offered in the Visiting Student Application Service (VSAS) database wasperformed. Results indicate that students have the option to pursue electives in a variety of subjects offered by 100 sponsoring institutions spread across a wide geographic distribution. Although manyopportunities exist, this analysis sheds light on several areas for improving the quality of this experience for interested applicants, including providing more electives in advanced subject matter, permitting more flexibility in scheduling, and promoting wider participation in VSAS.

Evaluating Live Virtual Chalk Talks as a Teaching Tool for Medical Students on a Dermatology Clerkship.

The COVID-19 pandemic has highlighted a continued need for innovative virtual teaching methods. Chalk talks, or brief illustrated interactive talks, are easily made virtual with an online whiteboard. We evaluated the efficacy of a live virtual chalk talk curriculum for medical students on their dermatology clerkship. A curriculum of one to three 1-h chalk talks was designed on the following topics: papulosquamous diseases, erythroderma, and immunobullous diseases. Talks were delivered monthly via Zoom to dermatology clerkship students. Pre- and post-talk surveys were administered to assess knowledge, confidence, and satisfaction. Compared with pre-talk, students (n = 18) achieved a greater percentage of possible points on knowledge assessment questions after the talks (41.0 ± 27.7% versus 90.4 ± 18.4%, p < 0.001). As assessed on a Likert scale (1 = not at all confident, 5 = extremely confident), students became more confident in differentiating conditions within each disease group and working up the conditions (2.02 ± 0.53 versus 3.53 ± 0.55, p < 0.001, and 2.09 ± 0.44 versus 3.76 ± 0.89, p < 0.001, respectively). Qualitative responses showed that students appreciated the student-teacher interactions. In conclusion, we found that live chalk talks are an effective and engaging way to teach dermatology to medical students in the virtual setting. Supplementary Information: The online version contains supplementary material available at 10.1007/s40670-023-01781-4.

Clinical Outcomes of Lung Transplantation in the Presence of Donor-Specific Antibodies.

Rationale: There is significant variation in approach to pre-lung transplant donor-specific antibodies (DSA), with some centers declining to cross any DSA. We implemented a protocol for transplantation for candidates with pretransplant DSA so long as a prospective complement-dependent cytotoxicity crossmatch was negative, regardless of number, specificity, class, or mean fluorescence intensity.Objectives: To compare post-transplant outcomes including overall survival, chronic lung allograft dysfunction-free survival, antibody-mediated rejection, and acute cellular rejection in lung transplant recipients where pretransplant DSA was and was not present.Methods: This was a single-center retrospective cohort study. For recipients with pretransplant DSA, if the prospective complement-dependent cytotoxicity crossmatch was negative, the donor offer was accepted and plasmapheresis was performed within 24 hours of transplantation and continued until retrospective crossmatch results returned. Immunosuppression and post-transplant management were not otherwise modified.Results: Of the 203 included recipients, 18 (8.9%) had pretransplant DSA. The median DSA mean fluorescence intensity was 4,000 (interquartile range, 2,975-5,625; total range, 2,100-17,000). The median number of DSA present per patient was one (interquartile range, 1-2). The presence of pretransplant DSA was not associated with increased mortality (hazard ratio, 1.2; 95% confidence interval [CI], 0.4-3.4) or decreased chronic lung allograft dysfunction-free survival (hazard ratio, 1.1; 95% CI, 0.6-2.1). Recipients with pretransplant DSA were more likely to require prolonged mechanical ventilation (adjusted odds ratio, 7.0; 95% CI, 2.3-21.6) and to have antibody-mediated rejection requiring treatment (adjusted odds ratio, 7.5; 95% CI, 1.0-55.8).Conclusions: A protocol of accepting donor offers for lung transplant candidates with preformed, complement-dependent cytotoxicity crossmatch-negative DSA is associated with increased need for prolonged mechanical ventilation and antibody-mediated rejection without affecting short-term overall or chronic lung allograft dysfunction-free survival.

Opioid Prescribing Patterns and Complications in the Dermatology Medicare Population.

Importance: The ongoing opioid epidemic in the United States has been fueled by prescription opioids. Increases in opioid-related deaths and complications mandate clinicians in all fields to scrutinize their prescribing patterns. Objective: To characterize the current status and potential complications of opioid prescribing practices among dermatologists for Medicare beneficiaries. Design, Setting, and Participants: A cross-sectional study used Medicare Part D prescriber data to evaluate opioid prescriptions by dermatologists from January 1 to December 31, 2014. The number of prescribers, opioid claims, beneficiaries, and days supplied as well as the type of opioid and geographic location of prescribers were extracted and analyzed. The top 1% of dermatologists prescribing opioids were identified and compared with a random sample of the same size among the remaining dermatologists based on sex, geographic location, type of practice, and time in practice. A systematic literature review was conducted to estimate the outcome of opioid prescribing practices on the exposed population. Main Outcome and Measures: Practice characteristics, epidemiologic factors, and consequences of opioids prescribed by dermatologists. Results: Of the 12 537 dermatologists in the study, 5305 (42.3%) prescribed no opioid claims, 5408 (43.1%) prescribed 1 to 10 opioid claims, and 1824 (14.5%) prescribed more than 10 opioid claims. Among dermatologists prescribing at least 10 opioid claims, a mean of 1.0 opioid claims was given to each beneficiary, with a supply lasting a mean of 4.4 days. A total of 108 dermatologists (93.9%) in the top 1% of opioid prescribers (n = 115) work in a surgical practice. Estimates suggest that opioids prescribed by dermatologists could annually lead to 3877 to 7602 beneficiaries continuing to use opioids at 1 year and 1825 to 4209 continuing to use opioids at 3 years. A total of 9882 to 22 806 beneficiaries could experience gastrointestinal tract or central nervous system adverse effects and 588 to 999 could experience fractures. Conclusions and Relevance: Opioid prescribing among dermatologists is limited and concentrated in the surgical setting, but it may be associated with a substantial number of adverse events that serve as a reminder to emphasize nonopioid pain medications in the postoperative setting.

Anaplastic Lymphoma Kinase in Cutaneous Malignancies.

Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase that has been implicated in the pathogenesis of a variety of neoplasms. As suggested by its name, ALK was first described as part of a translocation product in cases of anaplastic large-cell lymphoma, with other genetic and cytogenetic ALK mutations subsequently coming to attention in the development of many other hematologic and solid organ malignancies. ALK has now been shown to play a role in the pathogenesis of several cutaneous malignancies, including secondary cutaneous systemic anaplastic large-cell lymphoma (ALCL) and primary cutaneous ALCL, melanoma, spitzoid tumors, epithelioid fibrous histiocytoma, Merkel cell carcinoma, and basal cell carcinoma. The characterization of ALK-positivity in these cutaneous malignancies presents exciting opportunities for utilizing ALK-targeted inhibitors in the treatment of these diseases.

A 65-Year-Old Male with Primary Central Nervous System Diffuse Large B-Cell Lymphoma on Nivolumab with Oral Mucositis and Targetoid Plaques.

BACKGROUND/AIMS: The development of programmed cell death-1 (PD-1) inhibitors has greatly improved patient outcomes in the treatment of a variety of advanced malignancies. These novel immunotherapies are not without adverse effects, the most common of which are dermatologic. METHODS: We report our experience with an atypical erythema multiforme-like eruption in a patient with primary central nervous system diffuse large B-cell lymphoma treated with nivolumab. RESULTS: The patient presented with oral mucositis and scattered erythematous papules which progressed to targetoid purpuric plaques with hyperkeratotic centers. Histopathology demonstrated interface dermatitis with dyskeratotic keratinocytes and pigment incontinence. The patient experienced improvement of the eruption with discontinuation of nivolumab and on systemic and topical glucocorticoids. CONCLUSION: As PD-1 inhibitors become more widely used in the treatment of advanced malignancies, the early recognition and treatment of rare dermatologic toxicities remain of great importance.

The Microbiome Activates CD4 T-cell-mediated Immunity to Compensate for Increased Intestinal Permeability.

BACKGROUND & AIMS: Despite a prominent association, chronic intestinal barrier loss is insufficient to induce disease in human subjects or experimental animals. We hypothesized that compensatory mucosal immune activation might protect individuals with increased intestinal permeability from disease. We used a model in which intestinal barrier loss is triggered by intestinal epithelial-specific expression of constitutively active myosin light chain kinase (CA-MLCK). Here we asked whether constitutive tight junction barrier loss impacts susceptibility to enteric pathogens. METHODS: Acute or chronic Toxoplasma gondii or Salmonella typhimurium infection was assessed in CA-MLCK transgenic or wild-type mice. Germ-free mice or those lacking specific immune cell populations were used to investigate the effect of microbial-activated immunity on pathogen translocation in the context of increased intestinal permeability. RESULTS: Acute T gondii and S typhimurium translocation across the epithelial barrier was reduced in CA-MLCK mice. This protection was due to enhanced mucosal immune activation that required CD4+ T cells and interleukin 17A but not immunoglobulin A. The protective mucosal immune activation in CA-MLCK mice depended on segmented filamentous bacteria (SFB), because protection against early S typhimurium invasion was lost in germ-free CA-MLCK mice but could be restored by conventionalization with SFB-containing, not SFB-deficient, microbiota. In contrast, chronic S typhimurium infection was more severe in CA-MLCK mice, suggesting that despite activation of protective mucosal immunity, barrier defects ultimately result in enhanced disease progression. CONCLUSIONS: Increased epithelial tight junction permeability synergizes with commensal bacteria to promote intestinal CD4+ T-cell expansion and interleukin 17A production that limits enteric pathogen invasion.

The role of commensal bacteria in the regulation of sensitization to food allergens.

The prevalence of life-threatening anaphylactic responses to food is rising at an alarming rate. The emerging role of the gut microbiota in regulating food allergen sensitization may help explain this trend. The mechanisms by which commensal bacteria influence sensitization to dietary antigens are only beginning to be explored. We have found that a population of mucosa-associated commensal anaerobes prevents food allergen sensitization by promoting an IL-22-dependent barrier protective immune response that limits the access of food allergens to the systemic circulation. This early response is followed by an adaptive immune response mediated in part by an expansion of Foxp3(+) Tregs that fortifies the tolerogenic milieu needed to maintain non-responsiveness to food. Bacterial metabolites, such as short-chain fatty acids, may contribute to the process through their ability to promote Foxp3(+) Treg differentiation. This work suggests that environmentally induced alterations of the gut microbiota offset the regulatory signals conferred by protective bacterial species to promote aberrant responses to food. Our research presents exciting new possibilities for preventing and treating food allergies based on interventions that modulate the composition of the gut microbiota.