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Known disparities exist amongst HPV-related cancer outcomes in urban versus;rural populations, including squamous cell carcinoma (SCC) of the penis.; Appalachia as a whole, and West Virginia specifically, present a unique opportunity for analysis of penile cancer in underserved areas with few tertiary care centers and large distances and travel time;between centers.; The majority of patients in the state seek urologic oncology care at two tertiary centers.; This study seeks;to examine;differences in penile cancer presentation (including TNM stage,;grade, pertinent risk factors,;presenting symptoms and duration), treatment, and outcomes;between rural and urban populations in West Virginia.; Identification of disparities is crucial in detecting disease;to provide earlier intervention and improve outcomes in a traditionally underserved population. Following approval from institutional review boards, 89;patients with biopsy-proven SCC of the penis treated at Charleston Area Medical Center (CAMC) and West Virginia University over a fourteen-year period (2007-2022) were studied via retrospective chart review.; Distance and travel time from the respective tertiary care centers were collected based on zip code, and patients were stratified into urban and rural groups according to county based on the US Census Burea defition of Census Places >10,000.; T-stage, clinical node positivity, grade, risk factors (circumcision, smoking), primary tumor size and location, and treatment modality (chemotherapy, radiation, local therapy vs. partial penectomy vs. radical penectomy) and timing (symptom duration and time from presentation to surgery);were analyzed.; Patients were also followed post-operatively to assess the endpoints of death from penile cancer and local/nodal/distant recurrence.; Appropriate statistical tests were performed using SPSS. Patients;further from;tertiary care centers;(travel time) were more likely to undergo radical penectomy as primary therapy;(p=0.03), although advanced stage;(pT2 or greater) and clinical nodal status at diagnosis;did not increase;with travel time.; Those living;in counties classified as "urban";had higher BMI on average (p=0.004) and were more likely to present with a lesion on the penile shaft (p=0.06).; No significant;difference exists in stage or grade at diagnosis, other risk factors;(smoking status, circumcision), primary tumor size,;clinically palpable lymph nodes, radiation and chemotherapy use, symptom duration, or timing of therapy based on distance or travel time or when stratified based on rural/urban county of residence.; Patients were followed for a mean 32.8 months post-operatively and 30% exhibited local/nodal recurrence and 42% mortality.; Disease burden and stage appears greater in West Virginia when compared nationally. Penile cancer patients in West Virginia fare poorly when compared to allcomers in the US in terms of both disease at presentation, recurrence, and mortality.; Patients further from tertiary care center (travel time) are more likely to undergo radical penectomy as definitive therapy. This did not occur due to higher risk disease based on pT stage statistically, although anecdotally there does appear to be more disease >pT1b in rural populations. When stratified based on census definitions, rural patients had lower BMI and presented less often with disease of the penile shaft, suggesting they may opt for a definitive radical penectomy due to difficulties with healthcare access. [ABSTRACT FROM AUTHOR]

Background: Differences in male vs. female immune responses are well-documented and have significant clinical implications. While the immunomodulatory effects of sex hormones are well established, the contributions of sex chromosome complement (XX vs. XY) and gut microbiome diversity on immune sexual dimorphisms have only recently become appreciated. Here we investigate the individual and collaborative influences of sex chromosome complements and gut microbiota on humoral immune activation. Methods: Male and female Four Core Genotype (FCG) mice were immunized with heat-killed Streptococcus pneumoniae (HKSP). Humoral immune responses were assessed, and X-linked immune-related gene expression was evaluated to explain the identified XX-dependent phenotype. The functional role of Kdm6a, an X-linked epigenetic regulatory gene of interest, was evaluated ex vivo using mitogen stimulation of B cells. Additional influences of the gut microbiome on sex chromosome-dependent B cell activation was also evaluated by antibiotically depleting gut microbiota prior to HKSP immunization. Reconstitution of the depleted microbiome with short-chain fatty acid (SCFA)-producing bacteria tested the impact of SCFAs on XX-dependent immune activation. Results: XX mice exhibited higher HKSP-specific IgM-secreting B cells and plasma cell frequencies than XY mice, regardless of gonadal sex. Although Kdm6a was identified as an X-linked gene overexpressed in XX B cells, inhibition of its enzymatic activity did not affect mitogen-induced plasma cell differentiation or antibody production in a sex chromosome-dependent manner ex vivo. Enhanced humoral responses in XX vs. XY immunized FCG mice were eliminated after microbiome depletion, indicating that the microbiome contributes to the identified XX-dependent immune enhancement. Reconstituting microbiota-depleted mice with select SCFA-producing bacteria enhanced fecal SCFA concentrations and increased humoral responses in XX, but not XY, FCG mice. However, exposure to the SCFA propionate alone did not enhance mitogenic B cell stimulation in ex vivo studies. Conclusions: FCG mice have been used to assess sex hormone and sex chromosome complement influences on various sexually dimorphic traits. The current study indicates that the gut microbiome impacts humoral responses in an XX-dependent manner, suggesting that the collaborative influence of gut bacteria and other sex-specific factors should be considered when interpreting data aimed at delineating the mechanisms that promote sexual dimorphism. Highlights: Humoral immune responses against HKSP immunization are influenced by the possession of an XX vs. XY sex chromosome complement. While gonadal sex differentially influenced the number of antigen-specific IgM-secreting cells, the overall percentage of CD138 + plasma cells generated in response to HKSP immunization was not influenced by gonadal sex. Kdm6a is overexpressed in XX vs. XY B cells and splenocytes of HKSP-immunized mice and is demonstrated to be biallelically expressed in a subset of B cells. Ex vivo inhibition of KDM6a enzymatic activity promotes plasma cell differentiation in response to mitogenic stimulation. However, this effect was not sex chromosome-dependent. KDM6a inhibition did not impact total IgM concentrations in culture supernatants following mitogenic stimulation. XX-dependent immune enhancement is microbiome-dependent. Reconstitution of the antibiotic-depleted gut microbiome with select SCFA-producing bacteria rescued the XX-dependent immune phenotype observed in XX, but not XY, FCG mice. Plain language summary: Male and female immune systems differ in their ability to respond to infectious challenge. While males tend to be more susceptible to infection and produce lower amounts of antibodies in response to vaccination, females are more prone to develop autoimmune and inflammatory diseases. Key contributors to these differences include sex hormones, sex chromosome complement (XX in females vs. XY in males), and distinct gut microbial communities capable of regulating immune activation. While each factor has been studied individually, this research underscores the potential for these factors to collaboratively impact immune activation. Here, possession of an XX vs. XY sex chromosome complement was demonstrated to enhance antibody responses to heat-killed Streptococcuspneumoniae vaccination. While attempting to determine the underlying cause of this immune enhancement, the gut microbiome was identified to play a critical role. In the absence of an intact gut microbiome, XX immune activation was reduced to levels similar to those seen in XY sex chromosome complement-possessing mice. Replacement of the depleted gut microbiomes with select SCFA-producing bacterial species enhanced SCFA levels in antibiotic-treated mice and rescued the XX-dependent immune enhancement, suggesting a SCFA-mediated contribution. Further studies are needed to determine exactly how these select bacteria impact immune activation in a sex chromosome complement-dependent manner. Our findings highlight the need to consider the collaborative effects of individual sex-specific factors when attempting to understand immune sex biases, as a better understanding of these interactions will likely pave the way for improving therapeutics and vaccines tailored to both sexes. [ABSTRACT FROM AUTHOR]

Central line–associated bloodstream infection is a complication with serious consequences and biofilm development is thought to play a role. This study evaluated the impact of sterilization technique on central venous catheter (CVC) biofilm formation. This pilot study was conducted in the surgical intensive care unit of a tertiary care facility. All CVCs were inserted with chlorhexidine preparation (CHG). CHG-only CVCs were compared to the use of CHG with chlorhexidine gluconate–impregnated sponge (CHGIS). After removal, a punch biopsy of the CVC was taken at the noted skin level. Scanning electron microscopy identified the stage of biofilm. Confocal laser scanning microscopy with SYPRO stain confirmed the presence of glycocalyx and a volumetric analysis was completed. Twenty four CVCs were collected. Indications for line placement were similar, with 42% placed for sepsis in the CHGIS group and 33% in the CHG group. There were no positive line cultures or bacteremia and 2/12 CHGIS patients had candidemia. CHGIS lines were in place for a mean of 91 h, compared to 60 h with CHG alone (P = 0.19). The interior of CVCs had lower stage biofilms than the exterior and lacked stage 4 biofilms. Stage 4 biofilms were present externally on 50% of CVCs (8/12 CHG and 4/12 CHGIS). Stage 3 biofilms were present on 7/12 CHG and 6/12 CHGIS interior samples. Volume analysis found an increase in biofilm and glycocalyx in CHGIS compared to CHG samples. This study identified biofilms on both surfaces of CVCs. No significant difference in biofilm formation was found based on a sterilization technique. [ABSTRACT FROM AUTHOR]