Background A new trend includes taking a dedicated year away from medical school to complete a research fellowship. There is minimal data on the benefit of a gap year. We aimed to identify if a gap year makes a dermatology applicant more successful in The Match.Methods Dermatology applicants who applied to Mayo Clinic Arizona for the 2018-2019 application cycle and Mayo Clinic Rochester, Arizona, and Florida for the 2019-2020 application cycle were surveyed. Results In total, 291 dermatology applicants completed the initial survey, and 236 completed the follow-up survey. Ninety applicants took a gap year, 198 applicants did not.There was no significant difference in match rates. When comparing match rates at top dermatology residency programs, 40.6% of gap-year applicants matched to these residencies versus 19.0% of no gap-year applicants (P < 0.01). ConclusionApplicants should weigh the opportunity costs before pursuing research gap years as they may not be universally helpful. Applicants who want to match at a top dermatology program may benefit from a research gap year. This data may have limited generalizability outside of the United States.
Background The pathogenesis of pityriasis rubra pilaris (PRP) is not completely understood, but interleukin (IL)‐17 has been shown to play a critical role. There are no reliable immunomodulatory agents to treat PRP. We conducted an open‐label, single‐arm clinical trial of secukinumab, a monoclonal antibody that inhibits IL‐17A, for the treatment of PRP. Objectives To evaluate the clinical efficacy of secukinumab and define the transcriptomic landscape of PRP and its response to IL‐17A blockade. Methods Twelve patients with PRP were recruited for an open‐label trial of secukinumab. Patients received a 24‐week course of secukinumab. The primary endpoint was a ≥ 75% reduction in Psoriasis Area and Severity Index (PASI 75) from baseline to week 28. Secondary endpoints included PASI 90, change in Physician’s Global Assessment (PGA), and change in Dermatology Life Quality Index (DLQI). RNA sequencing was performed on lesional and nonlesional skin biopsies obtained at baseline and week 2. Sample groups were compared to identify differential gene expression and pathway enrichment. This trial was registered with http://clinicaltrials.gov: ‘Cosentyx (secukinumab) for the treatment of adult onset pityriasis rubra pilaris’ – NCT03342573. Results At week 28, six of 11 patients (55%) achieved PASI 75, and three patients (27%) achieved PASI 90. PGA (P = 0.008) and DLQI scores (P = 0.010) showed significant improvement with treatment. No serious treatment‐related adverse events were encountered. Treatment with secukinumab normalized transcriptional differences between lesional and nonlesional skin. Transcriptomic data from nonresponsive patients suggest that overactivity of innate immune pathways may be driving resistance to secukinumab. Conclusions Secukinumab appears to be an effective treatment for PRP and warrants further investigation. PRP is a transcriptionally heterogeneous disease, reflecting its variable response to therapy. Agents targeting other IL‐17 isoforms and innate immune mediators should be considered for future clinical trials. What is already known about this topic? The pathogenesis of pityriasis rubra pilaris is incompletely understood. Successful treatment has been reported with a variety of immunomodulatory agents, but disease is often refractory to therapy. Interleukin (IL)‐17 is thought to drive keratinocyte proliferation and vascular dysfunction in this disease. A previous trial demonstrated efficacy of the anti‐IL‐17A drug ixekizumab for pityriasis rubra pilaris. What does this study add? Herein we describe the findings of a clinical trial of secukinumab, an anti‐IL‐17A monoclonal antibody, for the treatment of pityriasis rubra pilaris. Secukinumab was effective in treating pityriasis rubra pilaris. Our transcriptomic data give new insight into the expressional changes that occur in response to secukinumab and suggest mechanisms of treatment resistance.
Cell-based mathematical models have previously been developed to simulate the immune system in response to pathogens. Mathematical modeling papers which study the human immune response to pathogens have predicted concentrations of a variety of cells, including activated and resting macrophages, plasma cells, and antibodies. This study aims to create a comprehensive mathematical model that can predict cytokine levels in response to a gram-positive bacterium, S. aureus by coupling previous models. To accomplish this, the cytokines Tumor Necrosis Factor Alpha (TNF-α), Interleukin 6 (IL-6), Interleukin 8 (IL-8), and Interleukin 10 (IL-10) are included to quantify the relationship between cytokine release from macrophages and the concentration of the pathogen, S. aureus, ex vivo. Partial differential equations (PDEs) are used to model cellular response and ordinary differential equations (ODEs) are used to model cytokine response, and interactions between both components produce a more robust and more complete systems-level understanding of immune activation. In the coupled cellular and cytokine model outlined in this paper, a low concentration of S. aureus is used to stimulate the measured cellular response and cytokine expression. Results show that our cellular activation and cytokine expression model characterizing septic conditions can predict ex vivo mechanisms in response to gram-negative and gram-positive bacteria. Our simulations provide new insights into how the human immune system responds to infections from different pathogens. Novel applications of these insights help in the development of more powerful tools and protocols in infection biology.
Emergency physician empathy and communication is increasingly important and influences patient satisfaction. This study investigated if there is a need for improvement in provider empathy and communication in our emergency department and what areas could be targeted for future improvement. Patients cared for by emergency physicians with the lowest satisfaction scores were surveyed within 1 week of discharge. Patients rated their emergency provider’s empathy and communication and provided feedback on the patient–provider interaction. Compared to survey responses nationally, our providers fell between the 10th and 25th percentiles for all questions, except question 5 (making a plan of action with [the patient]) which was between the 5th and 10th percentile. Areas most frequently cited for improvement were “wanting to know why” (N = 30), “time is short” (N = 15), and “listen to the patient” (N = 13). Survey percentiles and open-ended suggestions demonstrate a need for providers to give thorough explanations, spend more time with the patient, and demonstrate active listening. These themes can be used to strengthen the provider–patient relationship.
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