Citations

Our study identified chronic obstructive pulmonary disease (COPD)-associated differences in the lung extracellular matrix (ECM) composition. We highlight the compartmental differences in the ECM landscape in different subtypes of COPD. The most prominent differences were observed for severe-early onset COPD. Moreover, we identified unique ECM signatures that describe airway walls and parenchyma providing insight into the intertwined nature and complexity of ECM changes in COPD that together drive ECM remodeling and may contribute to disease pathogenesis.

<sec><b>Objective</b>This paper sought to evaluate the impact of a year-long Health Equity Curriculum (HEC) on the knowledge of health disparities, cross-cultural humility, and empathy among physicians, trainees, and research staff.</sec><sec><b>Background</b>There has been an increase in the inclusion of equity, cultural humility, and the social determinants of health into medical education at various levels. However, the frequency of this education is low and not well quantified or defined. The authors report the results of an education program, namely the HEC, on the knowledge of health disparities, cross-cultural humility, and empathy.</sec><sec><b>Materials and methods</b>The HEC was delivered between March 2020 and May 2021. It included the following four modules: the social determinants of health, cultural humility, health literacy, and unconscious bias. The participants attended lectures and reviewed articles/videos using online modules and reflection assignments. The Jefferson Scale of Empathy (JSE) and the Cross-Cultural Competence Instrument for Health Care Professionals (CCCHP) were administered pre- and post-HEC. The results were statistically analyzed.</sec><sec><b>Results</b>Of the 102 enrolled participants, 46 completed the entire course. The JSE showed a statistically significant improvement in the empathy scores from pre-HEC to post-HEC (p &lt; 0.01). The CCCHP showed a significant improvement from pre-HEC to post-HEC total scores and in subcomponent scores of Motivation/Curiosity, Attitude, and Knowledge (p &lt; 0.05). There were no significant differences in scores for the Skills and Emotions/Empathy subcomponents.</sec><sec><b>Conclusions</b>Enrollment and completion in the HEC were associated with statistically significant improvements in the validated measures of cultural competence and empathy. Scaling this type of content and curriculum can educate professionals on equity and serving diverse communities. A further study is warranted.</sec>

Background. Chronic systemic inflammation is associated with mortality in patients with chronic kidney disease, cardiovascular disease, and diabetes. The goal of this study was to examine the relationship between pretransplant inflammatory biomarkers (growth differentiation factor-15 [GDF-15], interleukin-6 [IL-6], soluble tumor necrosis factor receptor-1, monokine induced by gamma interferon/chemokine [C-X-C motif] ligand 9 [MIG/CXCL9], monocyte chemoattractant protein-1, soluble FAS, tumor necrosis factor-α, interleukin-15, and interleukin-1β) and death with function (DWF) after kidney transplantation (KT). Methods. We retrospectively measured inflammatory biomarker levels in serum collected up to 1 y before KT (time from blood draw to KT was 130 ± 110 d) in recipients transplanted between January 2006 and December 2018. Kaplan-Meier estimation, Cox regression, and Gradient Boosting Machine modeling were used to examine the relationship between inflammatory biomarkers and DWF. Results. Our cohort consisted of 1595 KT recipients, of whom 62.9% were male and 83.2% were non-Hispanic White. Over a mean follow-up of 7.4 ± 3.9 y, 21.2% of patients (n = 338) experienced DWF. Patients with the highest quartile levels of GDF-15 (>4766 pg/mL), IL-6 (>6.11 pg/mL), and MIG/CXCL9 (> 5835 pg/mL) had increased rates of DWF, and each predicted mortality independently of the others. When adjusted for clinical factors (age, diabetes, etc), the highest quartile levels of GDF-15 and IL-6 remained independently associated with DWF. Adding inflammatory markers to a clinical Cox model improved the C-statistic for DWF from 0.727 to 0.762 using a Gradient Boosting Machine modeling approach. Conclusions. These findings suggest that pre-KT serum concentrations of GDF-15, IL-6, and MIG/CXCL9 may help to risk stratify and manage patients undergoing KT and suggests that chronic inflammation may play a role in mortality in KT recipients.

Abstract Background Few antiviral therapies have been studied in patients with coronavirus disease 2019 (COVID-19) and kidney impairment. Herein, the efficacy, safety, and pharmacokinetics of remdesivir, its metabolites, and sulfobutylether-β-cyclodextrin excipient were evaluated in hospitalized patients with COVID-19 and severe kidney impairment. Methods In REDPINE, a phase 3, randomized, double-blind, placebo-controlled study, participants aged ≥12 years hospitalized for COVID-19 pneumonia with acute kidney injury, chronic kidney disease, or kidney failure were randomized 2:1 to receive intravenous remdesivir (200 mg on day 1; 100 mg daily up to day 5) or placebo (enrollment from March 2021 to March 2022). The primary efficacy end point was the composite of the all-cause mortality rate or invasive mechanical ventilation rate through day 29. Safety was evaluated through day 60. Results Although enrollment concluded early, 243 participants were enrolled and treated (remdesivir, n = 163; placebo, n = 80). At baseline, 90 participants (37.0%) had acute kidney injury (remdesivir, n = 60; placebo, n = 30), 64 (26.3%) had chronic kidney disease (remdesivir, n = 44; placebo, n = 20), and 89 (36.6%) had kidney failure (remdesivir, n = 59; placebo, n = 30); and 31 (12.8%) were vaccinated against COVID-19. Composite all-cause mortality or invasive mechanical ventilation rates through day 29 were 29.4% and 32.5% in the remdesivir and placebo group, respectively (P = .61). Treatment-emergent adverse events were reported in 80.4% for remdesivir versus 77.5% for placebo, and serious adverse events in 50.3% versus 50.0%, respectively. Pharmacokinetic plasma exposure to remdesivir was not affected by kidney function. Conclusions Although the study was underpowered, no significant difference in efficacy was observed between treatment groups. REDPINE demonstrated that remdesivir is safe in patients with COVID-19 and severe kidney impairment. Clinical Trials Registration EudraCT 2020-005416-22; Clinical Trials.gov NCT04745351.

We report a rare and intricate case of nesidioblastosis, marked by hyperinsulinemic hypoglycemia, in a patient with diabetes and chronic kidney disease (CKD). PET-CT imaging and histopathology confirmed the condition, culminating in a comprehensive treatment strategy comprising subtotal pancreatectomy and pharmacotherapy. This case marks the first documented occurrence of nesidioblastosis in a patient with CKD and diabetes. The presence of CKD further complicated the clinical picture, influencing hypoglycemic risk, drug efficacy, insulin clearance, and counter-regulatory mechanisms.

ABSTRACT Over 2.5 million prosthetic joint implantation surgeries occur annually in the United States. Periprosthetic joint infections (PJIs), though occurring in only 1–2% of patients receiving replacement joints, are challenging to diagnose and treat and are associated with significant morbidity. The Gram-positive bacterium Enterococcus faecalis , which can be highly antibiotic-resistant and is a robust biofilm producer on indwelling medical devices, accounts for 2–11% of PJIs. E. faecalis PJIs are understudied compared to those caused by other pathogens, such as Staphylococcus aureus . This motivates the need to generate a comprehensive understanding of E. faecalis PJIs to guide future treatments for these infections. To address this, we describe a panel of E. faecalis strains isolated from the surface of prosthetic joints in a cohort of individuals treated at the Mayo Clinic in Rochester, MN. Here, we present the first complete genome assemblage of E. faecalis PJI isolates. Comparative genomics shows differences in genome size, virulence factors, antimicrobial resistance genes, plasmids, and prophages, underscoring the genetic diversity of these strains. These isolates have strain-specific differences in in vitro biofilm biomass, biofilm burden, and biofilm morphology. We measured robust changes in biofilm architecture and aggregation for all isolates when grown in simulated synovial fluid (SSF). Finally, we evaluated the antibiotic efficacy of these isolates and found strain-specific changes across all strains when grown in SSF. Results of this study highlight the existence of genetic and phenotypic heterogeneity among E. faecalis PJI isolates which will provide valuable insight and resources for future E. faecalis PJI research. IMPORTANCE Periprosthetic joint infections (PJIs) affect ~1–2% of those who undergo joint replacement surgery. Enterococcus faecalis is a Gram-positive opportunistic pathogen that causes ~10% of PJIs in the United States each year, but our understanding of how and why E. faecalis causes PJIs is limited. E. faecalis infections are typically biofilm-associated and can be difficult to clear with antibiotic therapy. Here, we provide complete genomes for four E. faecalis PJI isolates from the Mayo Clinic. These isolates have strain-specific differences in biofilm formation, aggregation, and antibiotic susceptibility in simulated synovial fluid. These results provide important insight into the genomic and phenotypic features of E. faecalis isolates from PJI.