Citations

Although the etiology of rheumatoid arthritis (RA) is unknown, a strong genetic predisposition and the presence of preclinical antibodies before the onset of symptoms is documented. An expansion of Eggerthella lenta is associated with severe disease in RA. Here, using a humanized mouse model of collagen-induced arthritis, we determined the impact of E. lenta abundance on RA severity. Naïve mice gavaged with E. lenta produce preclinical rheumatoid factor and, when induced for arthritis, develop severe disease. The augmented antibody response was much higher in female mice, and among patients with RA, women had higher average load of E. lenta . Expansion of E. lenta increased CXCL5 and CD4 T cells, and both interleukin-17– and interferon-γ–producing B cells. Further, E. lenta gavage caused gut dysbiosis and decline in amino acids and nicotinamide adenine dinucleotide with an increase in microbe-dependent bile acids and succinyl carnitine causing systemic senescent-like inflammation.

Background: In smaller studies, allograft-prosthetic composite (APC) has been used for proximal humerus bone loss with some success, although with notable complication risk. This systematic review and meta-analysis sought to describe outcomes and complications after proximal humerus APC and how major APC complications are defined in the literature. Methods: A systematic review was performed per Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed/MEDLINE, EMBASE, Web of Science, and Cochrane were queried for articles on APC for proximal humeral bone loss secondary to tumor, fracture, or failed arthroplasty. Primary outcomes included postoperative range of motion, outcome scores (Musculoskeletal Tumor Society [MSTS], Simple Shoulder Test [SST], American Shoulder and Elbow Surgeons [ASES], Constant, visual analog scale [VAS], and subjective shoulder value [SSV]), and complication incidence. We also described individual study definitions of APC malunion/nonunion, methods of postoperative evaluation, malunion/nonunion rates, allograft fracture/fragmentation rates, and mean union time, when available. Secondarily, we compared hemiarthroplasty and reverse total shoulder arthroplasty. Results: Sixteen articles including 375 shoulders were evaluated (average age: 49 years, follow-up: 54 months). Fifty-seven percent of procedures were performed for tumors, 1% for proximal humerus trauma sequelae, and 42% for revision arthroplasty. Average postoperative forward elevation was 82° (69-94°), abduction 60° (30-90°), and external rotation 23° (17-28°). Average MSTS score was 82% (77%-87%), SST score 5.3 (4.5-6.1), ASES score 64 (54-74), Constant score 44 (38-50), VAS score 2.2 (1.7-2.7), and SSV 51 (45-58). There was a 51% complication rate with an 18% nonallograft surgical complication rate, 26% APC nonunion/malunion/resorption rate, and 10% APC fracture/fragmentation rate. Fifteen percent of nonunited APCs underwent secondary bone grafting; 3% required a new allograft; and overall revision rate was 12%. APC nonunion/malunion was defined in 2 of 16, malunion/nonunion rates in 14 of 16, fracture/fragmentation rates in 6 of 16, and mean union time (7 months) in 4 of 16 studies. Conclusion: APC reconstruction of the proximal humerus remains a treatment option, albeit with substantial complication rates. In addition, there is a need for APC literature to report institutional definitions of nonunion/malunion, postoperative evaluation, and time to union for a more standardized evaluation. Level of Evidence: Level IV ; systematic review. See Instructions for Authors for a complete description of levels of evidence.

ImportanceRespiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections (LRTIs) and infant hospitalization worldwide.ObjectiveTo evaluate the characteristics and outcomes of RSV-related critical illness in US infants during peak 2022 RSV transmission.Design, Setting, and ParticipantsThis cross-sectional study used a public health prospective surveillance registry in 39 pediatric hospitals across 27 US states. Participants were infants admitted for 24 or more hours between October 17 and December 16, 2022, to a unit providing intensive care due to laboratory-confirmed RSV infection.ExposureRespiratory syncytial virus.Main Outcomes and MeasuresData were captured on demographics, clinical characteristics, signs and symptoms, laboratory values, severity measures, and clinical outcomes, including receipt of noninvasive respiratory support, invasive mechanical ventilation, vasopressors or extracorporeal membrane oxygenation, and death. Mixed-effects multivariable log-binomial regression models were used to assess associations between intubation status and demographic factors, gestational age, and underlying conditions, including hospital as a random effect to account for between-site heterogeneity.ResultsThe first 15 to 20 consecutive eligible infants from each site were included for a target sample size of 600. Among the 600 infants, the median (IQR) age was 2.6 (1.4-6.0) months; 361 (60.2%) were male, 169 (28.9%) were born prematurely, and 487 (81.2%) had no underlying medical conditions. Primary reasons for admission included LRTI (594 infants [99.0%]) and apnea or bradycardia (77 infants [12.8%]). Overall, 143 infants (23.8%) received invasive mechanical ventilation (median [IQR], 6.0 [4.0-10.0] days). The highest level of respiratory support for nonintubated infants was high-flow nasal cannula (243 infants [40.5%]), followed by bilevel positive airway pressure (150 infants [25.0%]) and continuous positive airway pressure (52 infants [8.7%]). Infants younger than 3 months, those born prematurely (gestational age <37 weeks), or those publicly insured were at higher risk for intubation. Four infants (0.7%) received extracorporeal membrane oxygenation, and 2 died. The median (IQR) length of hospitalization for survivors was 5 (4-10) days.Conclusions and RelevanceIn this cross-sectional study, most US infants who required intensive care for RSV LRTIs were young, healthy, and born at term. These findings highlight the need for RSV preventive interventions targeting all infants to reduce the burden of severe RSV illness.

In response to the social inequities that exist in health care, the NIH-funded Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR) recently formed a diversity committee to examine systemic racism and implicit bias in the care and research of eosinophilic gastrointestinal diseases (EGIDs). Herein, we describe our process, highlighting milestones and issues addressed since the committee’s inception, which we hope will inspire other researchers to enhance diversity, equity, inclusion, and accessibility (DEIA) in their fields. Our journey began by establishing mission and vision statements to define the purpose of the committee. Regular discussion of diversity-related topics was incorporated into existing meetings and web-based materials were shared. This was followed by educational initiatives, including establishing a library of relevant publications and a speaker series to address DEIA topics. We then established a research agenda focused on the following actionable items: (1) to define what is known about the demographics of EGIDs by systematic review of population-based studies; (2) to develop a practical tool for reporting participant demographics to reduce bias in EGID literature; (3) to examine health disparities in the care of individuals with eosinophilic esophagitis who present to the emergency department with an esophageal food impaction; (4) to examine how access to a gastroenterologist affects the conclusions of published research examining the prevalence of pediatric eosinophilic esophagitis; and (5) to develop a model for examining the dimensions of diversity, and provide a framework for CEGIR’s ongoing projects and data capture. In addition to promoting consciousness of DEIA, this initiative has fostered inclusivity among CEGIR members and will continue to inspire positive changes in EGID care and research.

Background: HER2 amplification (HER2+) occurs in approximately 3% of patients with metastatic colorectal cancer (mCRC). Despite the recent addition of HER2-directed therapies to treatment recommendations in the NCCN Guidelines, until more recently there were no FDA-approved treatments. This study examined real-world treatment patterns in patients with HER2+ mCRC in the United States before and after the emerging awareness of HER2-directed therapies in 2018. Methods: This was a retrospective observational study of patients with HER2+ mCRC from the GuardantINFORM database, which contains claims data for patients with Guardant360 genomic testing results. Patients were aged ≥18 years, were diagnosed with mCRC between January 2014 and September 2020, and had confirmed ERBB2 amplification via the blood-based Guardant360 test. Treatment patterns and real-world time to next treatment (rwTTNT) were evaluated. Results: This study included 142 patients with a median age of 59 years; 31 (21.8%) patients with ERBB2 amplifications also had ERBB2 mutations. Treatment patterns were heterogeneous and evolved over time; before 2018, the most common regimen prescribed after detection of ERBB2 amplification was anti-VEGF therapy with or without chemotherapy (31.6%; n=25), and after 2018, HER2-directed therapies were the most commonly prescribed (36.5%; n=23). Median rwTTNT among the overall cohort was 8.4 months (95% CI, 6.5–10.0); rwTTNT was numerically longer in patients who received HER2-directed therapy compared with those who received non–HER2-directed therapies (11.0 months [95% CI, 6.3–12.3] vs 7.2 months [95% CI, 5.8–9.6]). Conclusions: This real-world study of the largest clinically annotated dataset of patients with HER2+ mCRC showed that many patients do not receive HER2-directed therapy despite its inclusion in NCCN Guidelines, with heterogeneous treatment patterns suggesting that standard of care remains undefined and targeted therapy remains underutilized. Greater awareness of the unmet need in this patient population, together with new effective therapies, will facilitate strategies for improved, targeted treatment approaches.

Electrophysiology is the study of the electrical properties of biological tissues, which involves the movement of ions across cell membranes. The analysis of the movement of electrical charges through the body has a wide range of biomedical applications, such as diagnosing and planning treatment in cardiovascular, nervous systems, muscular, and gastrointestinal disorders. The dielectric properties of biological tissues change according to the water content in the tissue and are measured as permittivity and conductivity relative to the frequency of the electrical field. This principle has been applied in diagnostics and therapeutics using microwave energysuch as imaging and ablation, etc. This review article summarizes the potential use of measuring dielectric properties using microwave imaging and how it can augment electrophysiological studies in medicine.

Abstract Background Engineering students encounter high levels of stress, which may negatively impact their mental health. Nevertheless, engineering students who experience mental health distress are less likely than their peers to seek professional help, even when controlling for gender and race/ethnicity. Purpose We examined beliefs that undergraduate engineering students have about barriers and facilitators to seeking professional help for their mental health. We also sought to identify cultural and systemic factors within and beyond engineering that might affect help‐seeking. Together, these beliefs influence students' sense of personal agency around seeking mental health care. Method We implemented a pragmatic qualitative design that incorporated the integrated behavioral model to investigate engineering students' ( N = 33) professional mental health help‐seeking beliefs. We used thematic analysis to analyze help‐seeking beliefs and perceived barriers and facilitators that students described during interviews. Results We identified four themes: Navigating the system impacts personal agency; sacrifices associated with help‐seeking act as a barrier; engineering culture acts as a barrier to help‐seeking; and student confidence in help‐seeking varies significantly. These themes portray the effect of perceived barriers and facilitators on students' personal agency for accessing mental health care. Our findings have implications for engineering departments and university counseling centers that want to minimize barriers to help‐seeking. Conclusions Engineering stakeholders must improve access to professional help for engineering students. Implementing changes to normalize help‐seeking behaviors, enhance personal agency, and facilitate engagement with mental health resources will create better conditions for engineers. Further research is necessary to understand how other beliefs (e.g., attitudes, perceived norms) inform the relationships between student mental health, professional help seeking, and engineering culture.