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Abstract Background Immunosuppression is a recognized risk factor for severe and disseminated coccidioidomycosis; however, data describing outcomes in patients with inflammatory bowel disease (IBD) receiving advanced therapy, including biologics and small molecules, remain limited. We aim to describe the prevalence, clinical presentation, treatment patterns, and outcomes of coccidioidomycosis in IBD patients receiving advanced therapy at an endemic tertiary care center. Methods We performed a retrospective observational study of adult patients with IBD at Mayo Clinic Arizona diagnosed with coccidioidomycosis between 2023 and 2026. Patients were included if IBD diagnosis preceded coccidioidomycosis diagnosis and advanced therapy had been active for at least 4 weeks before infection. Cases were classified as proven, probable, or possible based on microbiologic, clinical, radiographic, and serologic criteria. Clinical outcomes included antifungal treatment duration, hospitalization related to coccidioidomycosis or IBD, IBD treatment modification after diagnosis, re-emergence of coccidioidomycosis symptoms, and IBD-related surgery. Results A total of 48 patients met inclusion criteria. Among 1083 tested IBD patients receiving advanced therapy, coccidioidomycosis positivity prevalence was 4.4% when including all serologically positive patients and 1.9% when restricted to proven or probable cases. The median age at coccidioidomycosis diagnosis was 40 years (range 19-87 years), and 30 (62.5%) of 48 had Crohn’s disease. Proven or probable infection was identified in 21 (43.8%) of 48 patients, while 14 (29.2%) of 48 patients were classified as possible. Antifungal therapy was prescribed in 32 (66.7%) of 48 patients, including all proven cases, 15 (88.2%) of 17 probable cases, 9 (64.3%) of 14 possible cases, and 3 (25.0%) of 12 nondiagnostic cases. Among proven/probable/possible cases, the median antifungal treatment duration was 174 days (range 8-831 days). Advanced IBD therapy was continued in 3 (75.0%) of 4 proven cases, 9 (52.9%) of 17 probable cases, 12 (85.7%) of 14 possible cases, and all nondiagnostic cases. Hospitalization occurred in 6 (12.5%) of 48 of the cohort, all of which were proven/probable cases. Most patients remained on advanced therapy after diagnosis, although tumor necrosis factor α inhibitors were the most interrupted or discontinued agents. Conclusions In this endemic tertiary care cohort, management decisions varied according to diagnostic certainty. Patients with proven or probable coccidioidomycosis were more likely to receive antifungal therapy and undergo advanced IBD therapy modification, whereas most patients with possible or nondiagnostic serologic findings remained on advanced therapy without major IBD-related complications. Prolonged antifungal treatment was common, highlighting the complexity of managing coccidioidomycosis in immunosuppressed patients with IBD.

Background: Given aspirin’s biologic plausibility for antifibrotic and antineoplastic effects, we conducted a systematic review and meta-analysis to examine the association between aspirin use and major liver-related outcomes in metabolic dysfunction-associated steatotic liver disease (MASLD). To our knowledge, this is the first systematic review and meta-analysis restricted exclusively to patients with biopsy- or registry-confirmed MASLD. Methods: A comprehensive search of Ovid MEDLINE, Ovid EMBASE, Scopus, and Web of Science was performed in October 2025. Studies enrolling adults with a confirmed MASLD diagnosis were included; those with viral hepatitis or alcohol-related liver disease were excluded. Outcomes assessed included hepatocellular carcinoma (HCC), fibrosis progression, cirrhosis, all-cause and liver-related mortality, gastrointestinal (GI) bleeding, hemorrhagic stroke, and liver disease progression. Hazard ratios (HRs) with 95% CIs were pooled using random-effects models. Heterogeneity was assessed using I2 statistics. Results: Seven studies met the eligibility criteria, with approximately 720,000 individuals included. Pooled analysis showed that aspirin use was associated with a significantly lower HCC risk (HR 0.59; 95% CI 0.43–0.81; I2 = 83%). No statistically significant association was found between aspirin use and cirrhosis incidence (HR 0.55; 95% CI 0.13–2.37; I2 = 83.4%) or GI bleeding (HR 1.11; 95% CI 0.74–1.66; I2 = 98.9%). Among the two studies that explored all-cause mortality, aspirin was associated with a modest but statistically significant reduction in all-cause mortality (HR 0.86; 95% CI 0.78–0.95; I2 = 0%). Conclusions: Aspirin use is associated with a reduced risk of HCC and all-cause mortality in MASLD without significantly increasing GI bleeding or hemorrhagic strokes. These associations may reflect aspirin’s anti-inflammatory properties in liver disease. Further RCTs are needed to verify the causal role of aspirin in MASLD management.

Background: Perianal fistulizing Crohn’s disease (CD) is associated with significant morbidity and remains difficult to treat. Although advanced medical therapies are widely used, much of the available evidence derives from heterogeneous fistula populations or luminal CD trials, with limited perianal-specific synthesis and inconsistent outcome definitions. We conducted a systematic review focusing exclusively on perianal-specific clinical, radiologic, and composite outcomes in adults with perianal fistula (PAF) CD. Methods: We performed a systematic review in accordance with PRISMA 2020. Electronic databases were searched from inception through November 2025. We included randomized controlled trials and cohort studies enrolling adults with CD reporting outcomes specific to PAF. Interventions included biologics and small-molecule therapies, compared with placebo or other therapies. Due to substantial heterogeneity in outcome definitions and study designs, a meta-analysis was not performed. Risk of bias was assessed using Risk of Bias 2 (RoB 2) for randomized trials and the Newcastle–Ottawa Scale for observational studies. Results: Seven studies including >1200 participants with PAF-CD met inclusion criteria. Follow-up ranged from 24 weeks to 5 years. Across studies, outcome definitions and assessment modalities varied. Upadacitinib demonstrated significantly higher clinical fistula closure compared with placebo across multiple dose regimens at 52 weeks. In observational comparisons, ustekinumab and vedolizumab were associated with higher clinical closure rates than anti-TNF therapies. However, infliximab demonstrated higher closure rates than adalimumab as a first-line treatment. The definition for radiologic remission was less consistent across studies and often did not parallel clinical outcomes. Composite clinical–radiologic remission and response were reported in a limited number of studies, with filgotinib showing higher composite outcomes in comparison to placebo in a phase 2 trial. Surgical interventions, relapse outcomes, biomarkers [C-reactive protein (CRP)/fecal calprotectin (FCP)], and patient-reported outcomes were variably reported and not consistently significant across comparisons. Conclusions: Evidence for advanced therapies in PAF CD remains limited by heterogeneity in endpoint definitions, subjectivity in clinical observation, inconsistent radiologic reporting, and reliance on subgroup or observational comparisons. While anti-TNF therapy remains the most established option in guidelines, emerging data suggest significant benefits with ustekinumab, vedolizumab, and JAK inhibitors in selected patients. There is a need for PAF-specific, adequately powered randomized trials using standardized composite clinical and radiologic endpoints.

Abstract Introduction Hypertrophic cardiomyopathy (HCM) is an autosomal dominant disorder with a pathogenic mutation identified in approximately 50% of cases. The MYH7 and MYBPC3 genes account for over half of these cases, while dozens of other genes can be pathogenic(1). Genetic test results are not independently used to determine which people with HCM benefit from implanted cardiac defibrillators (ICDs)(2, 3). Little is known about the additive role of genetic testing results to existing indications for ICD insertion. Purpose This study aims to examine the interaction between genetic testing results and existing ICD indications and imaging results on defibrillator discharge rates in HCM. Methods Patients who underwent an ICD for HCM, who underwent a cardiac magnetic resonance (CMR) study and who underwent genetic testing were included across 3 sites. The outcome was the incidence rate of appropriate ICD discharges, calculated using cox regression controlling for current age and primary vs secondary prevention. Interaction analysis between genetic risk factors and existing ICD indications, and with CMR quantification of LGE and septal thickness, was performed, and stratum specific estimates calculated using linear computation. Results 177 patients were included in the study, of whom 70 (39.55%) had a pathogenic mutation, 5 (2.82%) had a variant likely pathogenic (VLP), 44 (24.86%) had a variant of undetermined significance (VUS) and 58 (39.55%) had no identifiable mutation. The event rate was 3.32 {2.28 to 4.84) per 100 person years. There was no association between genetic variables and ICD discharge rate. There was an 80% reduction in ICD discharge rate in people who underwent ICD insertion exclusively for family history of sudden cardiac death or for syncope who had no pathogenic or likely pathogenic mutation, however this change was not statistically significant (table 2). Conclusion There is no strong association between genetic characteristics and ICD discharge rates among people with hypertrophic cardiomyopathy with an existing ICD indication. There is a nonsignificant trend towards fewer ICD discharges among people who underwent ICD insertion for family history alone or for a history of syncope and did not have a pathologic variant.Table 1 Table 2

Abstract IntroductionPatients with interstitial lung disease (ILD) who are admitted to the intensive care unit (ICU) face significant challenges, with high rates of morbidity and mortality. Despite the severity of outcomes in this population, the potential impact of gender disparities on ICU outcomes in ILD has not been well studied.MethodsWe analyzed data from the NIS spanning 2016 to 2018, focusing on adults (≥18 years) hospitalized with ILD (J84), and defined ICU stays using ICD codes for central line placement and mechanical ventilation. The NIS, part of the Healthcare Cost and Utilization Project, provides a weighted, nationally representative sample of U.S. hospitalizations. Demographic, clinical, and hospital characteristics were collected, with race/ethnicity categorized per NIS classifications. Multivariable logistic and linear regression models adjusted for potential confounders to evaluate gender differences in outcomes.ResultsOur study identified 810,295 adult hospitalizations with ILD, of which 42,080 required ICU-level care. Of these, 46.7% were female. Female ICU patients were younger (mean age 66.9 ± 13.8 vs. 69.1 ± 12.7, p<0.001), more likely to be African American (17.0% vs. 10.9%, p<0.001), and less likely to be Caucasian (63.7% vs. 69.2%, p<0.001). Females were more often from lower-income ZIP codes (33.2% vs. 38.3%, p<0.001) and had lower rates of tobacco use disorder (35.0% vs. 43.9%, p<0.001). Mortality was significantly lower in females (40.5% vs. 48.1%, p<0.001). After adjusting for confounders, female gender was independently associated with reduced mortality risk (adjusted odds ratio 0.77, 95% CI 0.70-0.84, p<0.001) and a shorter length of hospital stay (adjusted difference 1.15 days, 95% CI 0.54-1.77).ConclusionOur study highlights notable gender differences in outcomes for patients with ILD admitted to the ICU. Female patients had a significantly lower risk of mortality and shorter hospital stays than male patients, even after adjusting for key clinical and socioeconomic confounders. These findings are consistent with emerging evidence that biological sex and gender-related factors play a critical role in disease expression and outcomes in ILD.Several mechanisms may explain these gender disparities. Sex hormones, such as estrogen, have been shown to exert protective effects in pulmonary fibrosis models, potentially influencing the disease course in women. Incorporating these considerations into clinical practice and future research will be vital for advancing individualized, patient-centered medicine in ILD.

Abstract Introduction:Hemophagocytic lymphohistiocytosis (HLH) is a severe hyperinflammatory syndrome characterized by excessive immune activation and cytokine release, leading to multi-organ failure and mortality. Despite guideline management to include chemotherapy and transplantation, the characteristics and predictors of critical outcomes in post-transplant-associated hemophagocytic lymphohistiocytosis (PT-HLH) remain poorly understood. Methods:This study is a retrospective cohort analysis of patients admitted to acute care hospitals in the U.S. with HLH between 2016 and 2018. We utilized the National Inpatient Sample, identifying HLH patients using International Classification of Diseases, Tenth Revision-Clinical Modification (ICD-10-CM) codes D76.1, D76.2, and D76.3. Patient demographics, such as age, gender, race, ethnicity, zip code, and insurance status, were obtained from the NIS, while hospital-level characteristics, location and teaching vs. non-teaching status, were considered in the study amongst others. We examined the baseline epidemiology of transplant status, including ICU-related outcomes and resource utilization in patients with and without transplants. Data were analyzed using STATA weighted function, with logistic regression for categorical outcomes. Results:Out of 8,330 adult HLH hospitalizations, 520 (6.2%) were transplant recipients. Among these, 350 (67%) had bone marrow transplants, 90 (17%) had kidney transplants, and 30 (5.8%) had liver transplants. The mean age of HLH patients was 50 ± 19 years; transplant patients were younger (mean age 46 ± 17 years) compared to non-transplant patients (50 ± 18 years), p<0.05. Transplant patients were more likely to be male (72.1% vs. 50.1%, p<0.05), have CMV infection (14.4% vs. 4.1%, p<0.05), be Hispanic (20.8% vs. 14.7%, p<0.05), come from higher median household income areas (38.8% vs. 24.5%, p<0.05), and be treated in teaching hospitals (96.1% vs. 85.8%, p<0.05). Among HLH patients who died in the hospital, 130 (25%) were transplant recipients, compared to 1,180 (15.1%) non-transplant recipients, p<0.05. After adjusting for potential confounders, transplant status was associated with a higher risk of mortality (adjusted odds ratio 1.77, 95% CI 1.11-2.83) and sepsis (adjusted odds ratio o1.78, 95% CI 1.08-2.92). Discussion:In examining a national cohort of PT-HLH cases, our findings review potential risk factors for critical care-related outcomes in post-transplant associated HLH care. PT-HLH patients in our cohort presented with distinct characteristics compared to non-transplant HLH cases. ICU-related outcomes showed statistically significant differences between transplant and non-transplant HLH patients. Specifically, transplant status remained independently associated with a higher risk of mortality and sepsis. Our findings underscore the importance of tailoring treatment plans to each patient's specific risk profile.

Background: Cardiopulmonary Exercise Testing (CPET) analyzes physiologic information with gas exchange during exercise. Peak oxygen volume consumption (absolute peak VO2 and percent predicted peak VO2), minute ventilation divided by carbon dioxide volume (VE/VCO2 slope) and heart rate reduction after 1 minute of recovery (heart rate recovery, HRR) all have well-established prognostic cardiovascular implications. Aim: Given the wider use of echocardiography, we aimed to see if important CPET data could be determined from resting transthoracic echocardiography (TTE). Methods: In this retrospective study, cardiology patients above 18 years who underwent both resting TTE and a max-effort CPET within 3 months of each other (2017-2022) were included. Patients with a history of coronary artery bypass grafting, valve surgery, pacemakers, congenital heart disease, severe valve dysfunction and pulmonary hypertension were excluded before analysis. Univariate analysis with Spearman correlations was used to assess the relationship between 4 CPET measurements {absolute peak VO2 per kg, percent predicted peak VO2/kg (adjusted for age, sex and body surface area), HRR, and VE/VCO2}; and 22 quantitative TTE parameters. Bonferroni correction was applied within each set of correlations, with significance set at p-values <0.025. Multivariate linear regression models were built for all the related TTE measurements to assess relationship with the 4 CPET parameters, adjusting for age and sex. Results: Table 1 shows, out of 1909 patients analyzed, our regression model is strongest for absolute peak VO2/kg (R-squared=0.57), with 3 significantly associated TTE parameters. For percent-predicted peak VO2 per kg, 4 TTE variables were significantly associated. For heart rate recovery, only LV stroke-volume index was correlated. No TTE parameters were associated with VE/VCO2. Conclusion: Notably, echocardiographic stroke volume and tricuspid valve regurgitation peak velocity exhibited a strong correlation with absolute peak VO2/kg and percent predicted peak VO2/kg. LV stroke volume index was correlated with heart rate recovery. VE/VCO2 was not associated with any resting echocardiographic parameters, suggesting this parameter is truly exercise-dependent.

Introduction: Metabolic equivalents (METs), a measure of energy use during a specified exercise intensity, and volume of oxygen consumed (VO2) are key measurements in cardiopulmonary exercise tests (CPETs). METs are traditionally converted to VO2 via multiplying METs by 3.5 ml/kg/min when VO2 data is not available, due to the fact that the latter requires more-expensive, accurate measurements of volume of inspired and expired oxygen and CO2. However, it is unclear which populations have significant variation between peak METs and peak VO2. Research Question: In a general cardiology population, do older women have a weaker relationship between peak METs and peak VO2? Methods: We present a retrospective study analyzing the relationship of peak METs and peak VO2 achieved on a CPET. Patients presenting to the cardiology clinic who received a CPET from 2017-2022 were included. Patients with severe valvular dysfunction, congenital heart disease, prior coronary artery bypass grafting, or ejection fraction < 50% were removed to limit confounding. A Spearman correlation coefficient was calculated for the whole sample comparing peak METs and peak VO2. Subsequently, a subgroup of women age 65 or greater were compared to the general sample by a fisher’s z transformation. Results: 1907 patients were included. There was a strong positive correlation between peak VO2 and peak METs in the whole sample (r(1860) = 0.914), p<0,001), shown in Figure 1. Women age 65 or greater had a weaker correlation (r(190)=0.808, p<0.0001) compared to the those who were not (r(1668) = 0.915, p<0.0001; z = -5.656, p<0.001), shown in Figure 2. Conclusions: Peak METs and peak VO2 have an extremely strong positive correlation in a general cardiology population. However, these relationships weaken for women age 65 or greater. METs are an accurate, cost-effective proxy measurement of VO2 in a general population, however may lack reliability for certain demographics.

Introduction: As today’s healthcare model moves toward more streamlined and corporate industrialism, it is our responsibility, as doctors, to ensure the integrity of medicine’s foundation in professionalism. The erosion of professional values not only creates a climate of animosity, but reverberates negatively to impact the development of students, who model their behaviour after those they most respect. This hazard has spurred an evaluation of medical school curricula, with a new emphasis on professionalism in the philosophy of medical education. Courses such as Gross Anatomy that, in the past, offered “pure content,” are now being used to teach and evaluate professionalism. The goal of this study was to determine if peer evaluation and self-evaluation used in conjunction and implemented early in the medical curriculum, can serve as useful tools to assess and provide feedback regarding professional behaviour in first-year medical students. Materials and Methods: From 1999 to 2003, students at Mayo Clinic College of Medicine evaluated themselves and their peers during the Gross and Developmental Anatomy Course. Numerical evaluations and written comments were statistically analysed within established categories of professionalism and correlated with academic performance, gender, and peer rating and self-rating. Results: The majority of written comments pertained to inter-professional respect, responsibility, and excellence. Students who gave higher peer evaluation and selfevaluation scores provided more positive comments, and students performing well in the course provided more positive comments about their peers and themselves than did those struggling academically. Students consistently rated their peers higher than themselves, and male students rated themselves higher than did female students. Conclusions: Implementing peer evaluation and self-evaluation early in the medical curriculum is a valuable exercise in teaching first-year medical students assessment skills when evaluating their behaviour, as well as the behaviour of their colleagues.