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Background: Peripheral arterial disease (PAD) is a manifestation of systemic atherosclerosis characterized by chronic inflammation and immune dysregulation. Single-cell RNA sequencing (scRNA-seq) studies of human atherosclerotic plaques have identified distinct transcriptional programs within plaque-associated immune cells. We sought to determine whether transcriptional features described within these plaque-resident cells can be identified in peripheral blood mononuclear cells (PBMCs). Methods: PBMCs from patients with PAD (n = 4) and healthy controls (HC) (n = 5) were profiled using scRNA-seq using the Parse Biosciences platform, yielding approximately 135,000 high-quality cells. Data analysis was conducted in R, using Seurat for quality control, dimensionality reduction and clustering. Cell-type annotation was performed using Azimuth reference-based mapping. Plaque-associated inflammatory and metabolic gene programs were curated from published human plaque single-cell atlases. Results: Gene expression differences between HC and PAD cells were visualized using UMAP plots. CD14+ mononuclear phagocytes (MNPs) exhibited the most prominent and consistent transcriptional differences between HC and PAD samples (Figure 1). Within CD14+ MNPs, genes involved in lipid handling and macrophage metabolic function demonstrated a higher median percentage of expressing cells in PAD compared with HC (Figure 2). Further analysis of AQP9 and CD36, genes implicated in macrophage metabolic activation and lipid uptake in atherosclerotic plaques, with z-score normalization and subject-level averaging revealed modest but consistent increases in relative expression in PAD across subjects. These findings support the relevance of these circulating transcriptional shifts to PAD pathophysiology. Conclusions: Circulating CD14+ MNPs in PAD have detectable transcriptional features consistent with potential engagement of plaque-associated myeloid activation programs. In PAD, increased expression of CD36, which encodes the immune cell scavenger receptor for oxidized LDL, and AQP9, associated with unstable plaques and the endothelial-to-mesenchymal transition, suggest altered immunometabolism states in circulating MNPs. Although effect sizes are modest, they are consistent across subjects and statistically robust. These findings highlight PBMC scRNA-seq as a minimally invasive approach to interrogate systemic immune programs relevant to PAD pathobiology.

As artificial intelligence (AI) integrates within the intersecting domains of healthcare and computational biology, developing interpretable models tailored to medical contexts is met with significant challenges. Explainable AI (XAI) is vital for fostering trust and enabling effective use of AI in healthcare, particularly in image-based specialties such as pathology and radiology where adjunctive AI solutions for diagnostic image analysis are increasingly utilized. Overcoming these challenges necessitates interdisciplinary collaboration, essential for advancing XAI to enhance patient care. This commentary underscores the critical role of interdisciplinary conferences in promoting the necessary cross-disciplinary exchange for XAI innovation. A literature review was conducted to identify key challenges, best practices, and case studies related to interdisciplinary collaboration for XAI in healthcare. The distinctive contributions of specialized conferences in fostering dialogue, driving innovation, and influencing research directions were scrutinized. Best practices and recommendations for fostering collaboration, organizing conferences, and achieving targeted XAI solutions were adapted from the literature. By enabling crucial collaborative junctures that drive XAI progress, interdisciplinary conferences integrate diverse insights to produce new ideas, identify knowledge gaps, crystallize solutions, and spur long-term partnerships that generate high-impact research. Thoughtful structuring of these events, such as including sessions focused on theoretical foundations, real-world applications, and standardized evaluation, along with ample networking opportunities, is key to directing varied expertise toward overcoming core challenges. Successful collaborations depend on building mutual understanding and respect, clear communication, defined roles, and a shared commitment to the ethical development of robust, interpretable models. Specialized conferences are essential to shape the future of explainable AI and computational biology, contributing to improved patient outcomes and healthcare innovations. Recognizing the catalytic power of this collaborative model is key to accelerating the innovation and implementation of interpretable AI in medicine.

RATIONALE: New evidence is available examining the use of corticosteroids in sepsis, acute respiratory distress syndrome (ARDS) and community-acquired pneumonia (CAP), warranting a focused update of the 2017 guideline on critical illness-related corticosteroid insufficiency. OBJECTIVES: To develop evidence-based recommendations for use of corticosteroids in hospitalized adults and children with sepsis, ARDS, and CAP. PANEL DESIGN: The 22-member panel included diverse representation from medicine, including adult and pediatric intensivists, pulmonologists, endocrinologists, nurses, pharmacists, and clinician-methodologists with expertise in developing evidence-based Clinical Practice Guidelines. We followed Society of Critical Care Medicine conflict of interest policies in all phases of the guideline development, including task force selection and voting. METHODS: After development of five focused Population, Intervention, Control, and Outcomes (PICO) questions, we conducted systematic reviews to identify the best available evidence addressing each question. We evaluated the certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach and formulated recommendations using the evidence-to-decision framework. RESULTS: In response to the five PICOs, the panel issued four recommendations addressing the use of corticosteroids in patients with sepsis, ARDS, and CAP. These included a conditional recommendation to administer corticosteroids for patients with septic shock and critically ill patients with ARDS and a strong recommendation for use in hospitalized patients with severe CAP. The panel also recommended against high dose/short duration administration of corticosteroids for septic shock. In response to the final PICO regarding type of corticosteroid molecule in ARDS, the panel was unable to provide specific recommendations addressing corticosteroid molecule, dose, and duration of therapy, based on currently available evidence. CONCLUSIONS: The panel provided updated recommendations based on current evidence to inform clinicians, patients, and other stakeholders on the use of corticosteroids for sepsis, ARDS, and CAP.

AbstractPurposeThe term “pectoralis minor syndrome” refers to this constellation of symptoms that can occur when the pectoralis minor (Pm) is shortened and contracted. Release of the tendon of the Pm from the coracoid has been reported to provide substantial clinical improvement to patients presenting with pectoralis minor syndrome. The purpose of this study was (1) to describe the technique for endoscopic release of pectoralis minor tendon at the subdeltoid space, (2) to classify the pectoralis minor syndrome according to its severity and (3) and to report the short‐term outcomes of this procedure in a consecutive series of patients diagnosed with pectoralis minor syndrome.MethodsEndoscopic release of the pectoralis minor tendon was performed in a series of 10 patients presenting with pectoralis minor syndrome. There were six females and four males with a median age at the time of surgery of 42 (range from 20 to 58) years. Four shoulders were categorized as grade I (scapular dyskinesis), and six as grade II (intermittent brachial plexopathy). Shoulders were evaluated for pain, motion, satisfaction, subjective shoulder value (SSV), quick‐DASH, ASES score, and complications. The mean follow‐up time was 19 (range, 6 to 49) months.ResultsArthroscopic release of the tendon of the Pm led to substantial resolution of pectoralis minor syndrome symptoms in all but one shoulder, which was considered a failure. Preoperatively, the median VAS for pain was 8.5 (range, 7–10) and the mean SSV was 20% (range, 10% ‐ 50%). At most recent follow‐up the mean VAS for pain was 1 (range, 0–6) and the mean SSV 80% (range, 50% ‐ 90%). Before surgery, mean ASES and quick‐DASH scores were 19.1 (range, 10–41.6) and 83.1 (range, 71 and 95.5) points respectively. At most recent follow‐up, mean ASES and quick‐DASH scores were 80.1 (range, 40–100) and 19.3 (range, 2.3–68) points respectively. No surgical complications occurred in any of the shoulder included in this study.ConclusionsEndoscopic release of the tendon of the pectoralis minor from the coracoid improves pain, function and patient reported outcomes in the majority of patients presenting with the diagnosis of isolated pectoralis minor syndrome.

Abstract Virtual care, introduced previously as a replacement for in-person visits, is now being integrated into clinical care delivery models to complement in-person visits. The COVID-19 pandemic sped up this process. The rapid uptake of virtual care at the start of the pandemic prevented educators from taking deliberate steps to design the foundational elements of the related learning environment, including workflow, competencies, and assessment methods. Educators must now pursue an informed and purposeful approach to design a curriculum and implement virtual care in the learning environment. Engaging learners in virtual care offers opportunities for novel ways to teach and assess their performance and to effectively integrate technology such that it is accessible and equitable. It also offers opportunities for learners to demonstrate professionalism in a virtual environment, to obtain a patient’s history incorporating interpersonal and communication skills, to interact with multiple parties during a patient encounter (patient, caregiver, translator, telepresenter, faculty member), to enhance physical examination techniques via videoconferencing, and ideally to optimize demonstrations of empathy through “webside manner.” Feedback and assessment, important features of training in any setting, must be timely, specific, and actionable in the new virtual care environment. Recognizing the importance of integrating virtual care into education, leaders from across the United States convened on September 10, 2020, for a symposium titled, “Crossing the Virtual Chasm: Rethinking Curriculum, Competency, and Culture in the Virtual Care Era.” In this article, the authors share recommendations that came out of this symposium for the implementation of educational tools in the evolving virtual care environment. They present core competencies, assessment tools, precepting workflows, and technology to optimize the delivery of high-quality virtual care that is safe, timely, effective, efficient, equitable, and patient-centered.

Abstract Background With a reported incidence of up to 12%, periprosthetic joint infection (PJI) is a frequent complication of total elbow arthroplasty (TEA). Its microbiologic diagnosis is usually based on periprosthetic tissue culture (hereafter referred to as tissue culture), despite the poor sensitivity of this technique. Although implant sonication cultures have been shown to be superior to tissue cultures for hip and knee PJI diagnosis, only a single small study (including fewer than 10 infected implants) has assessed sonication of elbow arthroplasties. Methods We retrospectively analysed 116 sonicate fluid cultures from patients who underwent revision of a TEA at our Institution between 2007 and 2019, comparing results to tissue cultures. Nine elbows who had fewer than 2 tissue samples obtained during surgery were excluded. Using the IDSA guidelines to define PJI, there were 46 infected cases and 61 aseptic failures. We reviewed clinical characteristics and calculated the sensitivity and specificity of periprosthetic tissue culture compared to culture of samples obtained by implant sonication. In addition, we compared the sensitivity of tissue culture to the combination of tissue and sonicate fluid culture. Results A total of 107 elbows were included. Median ages in the aseptic failure and PJI groups were 60 and 67 years, respectively. Gender distribution was similar for both groups (PJI group 62% females; aseptic group 65% females). The most common pathogens were coagulase negative Staphylococcus species (66%), followed by Staphylococcus aureus (18%). The sensitivity of tissue culture was 63% and the sensitivity of sonicate fluid culture was 76% (p=0.14). The specificity of tissue culture was 86% and the specificity of sonicate fluid culture was 100%. Sensitivity of sonicate fluid culture in combination with tissue culture was 91% (p=0.045). Table. Comparison of tests for microbiologic diagnosis of PJI Conclusion The combination of sonicate fluid culture and tissue culture had a greater sensitivity than tissue culture alone for microbiologic diagnosis of elbow TEA infection. Disclosures Joachin Sanchez-Sotelo, M.D, PhD, Elsevier (Other Financial or Material Support, Publishing Royalties)Exactech (Consultant)Oxford Univerity Press (Other Financial or Material Support, Publishing Royalties)Stryker (Grant/Research Support)Wright (Consultant) Robin Patel, MD, Accelerate Diagnostics (Grant/Research Support)CD Diagnostics (Grant/Research Support)Contrafect (Grant/Research Support)Curetis (Consultant)GenMark Diagnostics (Consultant)Heraeus Medical (Consultant)Hutchison Biofilm Medical Solutions (Grant/Research Support)Merck (Grant/Research Support)Next Gen Diagnostics (Consultant)PathoQuest (Consultant)Qvella (Consultant)Samsung (Other Financial or Material Support, Dr. Patel has a patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic, and a patent on an anti-biofilm substance issued.)Selux Dx (Consultant)Shionogi (Grant/Research Support)Specific Technologies (Consultant)

BackgroundStudies examining one‐year mortality respecting component blood transfusion are sparse. We hypothesize that component blood product transfusions are negatively associated with 90‐day and 1‐year survival for all patients requiring veno‐arterial (VA) or veno‐venous (VV) ECMO.Study Design and MethodsThis was an IRB‐approved retrospective cohort analysis of 676 consecutive patients requiring ECMO at the University of Pittsburgh between 2005 and 2016. Patients were analysed both as an entire cohort and as two subsets with respect to ECMO modality (VA vs. VV). Additional data collected and analysed included patient characteristics, laboratory values and blood product transfusion.ResultsMultivariable analysis revealed that platelet transfusion was associated with 90‐day mortality (OR: 1·05, P = 0·037) and one‐year mortality for the entire cohort (OR = 1·05, P = 0·046,). Platelet transfusion volume was also associated with mortality in the VA‐ECMO subset of patients at both 90 days (OR = 1·08, P = 0·03) and one year (OR: 1·11, P = 0·014). Age, peak International Normalized Raton ECMO, nadir haemoglobin (on ECMO) and final haemoglobin (after ECMO) were significantly associated with mortality for patients requiring VA‐ECMO. For VV‐ECMO patients, age, INR and peak creatinine on ECMO were associated with mortality. No individual component blood product was associated with one‐year mortality for patients requiring VV‐ECMO.ConclusionPlatelet transfusion was associated with increased 90‐day and 1‐year mortality for patients requiring VA‐ECMO.