Sex-dependent niche responses modulate steady-state and regenerative hematopoiesis.

Hematopoietic stem cells (HSCs) adapt to organismal blood production needs by balancing self-renewal and differentiation, adjusting to physiological demands and external stimuli. Although sex differences have been implicated in differential hematopoietic function in males versus females, the mediators responsible for these effects require further study. Here, we characterized hematopoiesis at a steady state and during regeneration following hematopoietic stem cell transplantation (HST). RNA sequencing of lineage(-) bone marrow cells from C57/Bl6 mice revealed a broad transcriptional similarity between the sexes. However, we identified distinct sex differences in key biological pathways, with female cells showing reduced expression of signatures involved in inflammation and enrichment of genes related to glycolysis, hypoxia, and cell cycle regulation, suggesting a more quiescent and less inflammatory profile compared with male cells. To determine the functional impacts of the observed transcriptomic differences, we performed sex-matched and mismatched transplantation studies of lineage(-) donor cells. During short-term 56-day HST recovery, we found a male donor cell proliferative advantage, coinciding with elevated serum TNF-α, and a male recipient engraftment advantage, coinciding with increased serum CXCL12. Together, we show that sex-specific cell responses, marked by differing expression of pathways regulating metabolism, hypoxia, and inflammation, shape normal and regenerative hematopoiesis, with implications for the clinical understanding of hematopoietic function.

Retrospective Analysis of Onychomycosis Risk Factors Using the 2003-2014 National Inpatient Sample.

INTRODUCTION: Onychomycosis, a fungal nail infection, is associated with significant morbidity and negative impact on quality of life. Therefore, understanding associated risk factors may inform onychomycosis screening guidelines. OBJECTIVES: This retrospective study investigated common demographic and comorbidity risk factors among hospitalized patients using the National Inpatient Sample. METHODS: The 2003-2014 National Inpatient Sample (NIS) database was used to identify onychomycosis cases and age and sex matched controls in a 1:2 ratio. Chi-square tests and T-tests for independent samples were utilized to compare categorical and continuous patient factors. Demographic and comorbidity variables significant (P < 0.05) on univariate analysis were analyzed via a multivariate regression model with Bonferroni correction (P < 0.0029). RESULTS: 119,662 onychomycosis cases and 239,324 controls were identified. Compared to controls, onychomycosis patients frequently were White (69.0% versus 68.0%; P < 0.001), Black (17.9% versus 5.8%; P < 0.0001), and insured by Medicare or Medicaid (80.1% versus 71.1%; P < 0.0001). Patients had greater hospital stays (9.69 versus 5.39 days; P < 0.0001) and costs ($39,925 versus $36,720; P < 0.001) compared to controls. On multivariate analysis, onychomycosis was commonly associated with tinea pedis (odds ratio [OR]: 111.993; P < 0.0001), human immunodeficiency virus (OR: 4.372; P < 0.001), venous insufficiency (OR: 6.916; P < 0.0001), and psoriasis (OR: 3.668; P < 0.001). CONCLUSIONS: Onychomycosis patients had longer hospital stays and greater costs compared to controls. Black patients were disproportionately represented among cases compared to controls. Onychomycosis was associated with tinea pedis, venous insufficiency, human immunodeficiency virus, psoriasis, obesity (body mass index [BMI] ≥ 30 kg/m2), peripheral vascular disease, and diabetes with chronic complications, suggesting that inpatients with onychomycosis should be screened for these conditions.

Smoking impacts outcomes in transcervical Zenker's diverticulectomy.

PURPOSE: There is sparse literature discussing the impact of smoking on postoperative outcomes following surgical treatment of Zenker's diverticulum. In this study, we seek to characterize differences in the management and outcomes of open Zenker's diverticulectomy based on patient smoking status. METHODS AND MATERIALS: This paper is a retrospective cohort review. The 2005-2018 American College of Surgeons National Surgical Quality Improvement (ACS-NSQIP) database was queried for patients undergoing open Zenker's diverticulectomy. Chi-square and multivariable logistic regression were performed to determine statistical associations between postoperative outcomes and smoking status. RESULTS: Of the 715 identified patients, 70 (9.8 %) were smokers and 645 (91.2 %) were non-smokers. Smokers were younger than non-smokers (mean 63.9 vs. 71.7 years, p < 0.001) and more likely to have a prolonged operative time (20.0 % vs. 11.6 %, p = 0.044). On multivariable regression analysis controlling for demographics and comorbidities, smokers had greater odds than non-smokers for developing overall postoperative complications (OR: 2.776, p = 0.013), surgical infections (OR: 3.194, p = 0.039), medical complications (OR: 3.563, p = 0.011), and medical infections (OR: 1.247, p = 0.016). Smokers also had greater odds for requiring ventilation/intubation (OR: 8.508, p = 0.025) and having a prolonged postoperative stay (OR: 2.425, p = 0.030). CONCLUSION: In a cohort of patients undergoing transcervical Zenker's diverticulectomy, smokers are at increased risk for overall complications, medical complications, medical infections, surgical infections, prolonged postoperative stay, and ventilation/intubation.

Analysis of Utilization, Cost, and Prescription Trends of Common Immunosuppressive Medications Among Medicare Patients 2013 to 2019.

Immunosuppressive medications are commonly used to manage dermatological conditions, including atopic dermatitis, psoriasis, and bullous diseases. However, cost and adverse effect profile, including increased risk of infections, are important considerations.

Targeting the chromatin binding of exportin-1 disrupts NFAT and T cell activation.

Exportin-1 (XPO1/CRM1) plays a central role in the nuclear-to-cytoplasmic transport of hundreds of proteins and contributes to other cellular processes, such as centrosome duplication. Small molecules targeting XPO1 induce cytotoxicity, and selinexor was approved by the Food and Drug Administration in 2019 as a cancer chemotherapy for relapsed multiple myeloma. Here, we describe a cell-type-dependent chromatin-binding function for XPO1 that is essential for the chromatin occupancy of NFAT transcription factors and thus the appropriate activation of T cells. Additionally, we establish a class of XPO1-targeting small molecules capable of disrupting the chromatin binding of XPO1 without perturbing nuclear export or inducing cytotoxicity. This work defines a broad transcription regulatory role for XPO1 that is essential for T cell activation as well as a new class of XPO1 modulators to enable therapeutic targeting of XPO1 beyond oncology including in T cell-driven autoimmune disorders.

Increased Interest in Oral Minoxidil for Hair Loss Treatment Following Publication of August 2022 New York Times Article: A Google Trends Analysis.

Introduction: Androgenetic alopecia (AGA) is the most common form of hair loss, with negative impact on patient quality of life. Oral minoxidil is used off-label for AGA treatment. We hypothesized increased public interest in oral minoxidil for hair loss treatment following the New York Times (NYT) Article on oral minoxidil: "An Old Medicine Grows New Hair for Pennies a Day, Doctors Say." The objective of this study was to quantify interest in oral minoxidil for hair loss treatment before and after the NYT article and help inform dermatologists about treatments of interest to their patients. Method: We performed a cross-sectional analysis of Google Trends evaluating relative prevalence of "oral minoxidil," "minoxidil," "hair loss," and "Rogaine®" 2/2022-5/2023. t tests compared mean search volume and linear regression analysis quantified changes in public interest over time. Results: Oral minoxidil and minoxidil search volumes increased from 0.86 to 3.00 and 22.43 to 32.60, respectively, before and after the NYT article (both p < 0.05). Minoxidil searches continually increased by 500,000 searches per month (p < 0.001). Conclusions: There was a significant and sustained increase in Google searches for oral minoxidil after publication of the NYT article, indicating increased patient interest. Larger clinical trials are needed to provide evidence-based care to AGA patients.

Home Is Where the Match Is: Mentorship and Dermatology Residency Match Trends Before and During the COVID-19 Pandemic.

Dermatology is one of the most competitive residencies for matching among medical school applicants. A strong connection with a residency program through research or clinical rotations may distinguish between similarly qualified applicants. Our previous study of research-mentor relationships among matched dermatology applicants corroborated the importance of program connections.1 However, the 2020-2021 residency match cycle was uniquely affected by the COVID-19 pandemic, which prevented applicants from fostering connections with faculty at outside institutions. Our study objectives were to evaluate research-mentor relationships among matched dermatology applicants in the 2020-2021 pandemic match cycle with comparisons to pre-pandemic match cycles.

Adult Burn Inpatients Have Increased Burn Severity and Mortality Compared to Children in Retrospective Analysis of National Inpatient Sample 2017.

INTRODUCTION: Socioeconomic status and comorbidities are associated with increased mortality in patients with external surface burn patients, however differences between pediatric and adult burn populations have not been adequately studied. OBJECTIVES: Our objectives were to explore the presentation, management, and outcomes of external surface burns across age groups. METHODS: The 2017 National Inpatient Sample (NIS) was queried for patients with any diagnosis of external body surface burns. Demographics, comorbidities, complications, total charges, length of stay (LOS), number of procedures undergone (NPU), and time from admission to first procedure (TFP) were identified. Univariate and multivariable analyses were used to identify statistical associations with age. RESULTS: 52,335 inpatients were identified with burns, with the majority male (63.6%) and adults (81.8%). Mean age was 50.5 (standard error [SE] 0.1) and 5.5 (SE 0.1) years for adults and children, respectively. Adults had higher prevalence of hypertensive disease (43.5% versus. 1.4%), diabetes mellitus (24.1% versus 0.3%), and obesity (11.7% versus 1.6%) than children (P < 0.001). Adults versus children had higher odds for mortality (odds ratio [OR] 4.26, 95% confidence interval [CI] 3.08-5.89), sepsis (OR 5.16, 95% CI 4.10-6.48), and pneumonia (OR 4.26, 95% CI 3.30-5.50). CONCLUSIONS: In this national cohort of inpatients with external surface burns, comorbidities, and odds for mortality and complications varied by age. Pediatric patients more often had lower household incomes; however, adults had significantly higher odds for mortality suggesting that age and comorbidity status are more impactful on burn outcomes than socioeconomic status.