Citations

Background: Long COVID, the chronic sequela of SARS-CoV-2 infection, has affected millions of people worldwide. However, its pathogenesis and treatment remain unknown. To address this critical gap, the National Institutes of Health (NIH) developed the Researching COVID to Enhance Recovery (RECOVER) Initiative that included the Viral Persistence and Reactivation, and Immune Dysregulation (RECOVER-VITAL) study as one of the first of five NIH-sponsored, integrated platform protocols to support the rigorous and rapid investigation of potential interventions for Long COVID. Methods: Experts across academia, the NIH, and the community of patients and caregivers were brought together to design the RECOVER-VITAL protocol. We present the challenges and rationale underpinning critical components of this protocol and provide evidence for use of the platform for efficient execution of current and future Long COVID clinical trials. Facets of the RECOVER-VITAL protocol, including inclusion criteria, intervention groups, study procedures, investigation of biomarkers, and endpoints, were carefully crafted to advance the current and future science and operations of Long COVID clinical trials, particularly in the absence of existing data. The initial trial within the RECOVER-VITAL platform evaluated two durations of an antiviral drug, nirmatrelvir/ritonavir, to test the proposed etiology of viral persistence on the Long COVID symptom clusters of autonomic dysfunction, cognitive dysfunction, and exercise intolerance. The primary outcome measures were patient-reported, and secondary outcomes included performance-based measures for each of the symptom clusters of interest. Conclusions: The RECOVER-VITAL platform protocol has substantial implications for the design and conduct of future Long COVID clinical trials.

Asthma is a heterogeneous chronic respiratory disease driven by diverse inflammatory pathways that vary across patients. The recognition of distinct molecular endotypes has led to the development of targeted biologic therapies that have transformed the management of moderate-to-severe asthma. However, selecting the most appropriate biologic therapy for each patient remains challenging. Health providers often rely on trial-and-error approaches that may delay disease control, increase costs, and expose patients to unnecessary side effects. Biomarkers are key to precision asthma care, as they provide objective measures of underlying disease mechanisms. Established biomarkers such as blood eosinophil count, fractional exhaled nitric oxide, and serum total immunoglobulin E are important for identifying type 2-high asthma. Sputum biomarkers offer direct insight into airway inflammation, but their use is limited by technical complexity and availability across centers. Emerging biomarkers, including proteomic, transcriptomic, metabolomic, and genomic biomarkers, show promise in further refining biologic therapy selection. In addition, digital biomarkers derived from electronic health records, wearable devices, and artificial intelligence-based algorithms offer new opportunities to capture real-world changes in disease and treatment response. Non-medical drivers of health, particularly socioeconomic factors, are increasingly recognized as modifiers of biologic effectiveness and may also be helpful in selecting biologic therapies. This review summarizes the existing evidence on established and emerging biomarkers used to guide biologic therapy selection in asthma. Integrating multiple biomarkers will be essential to improve biological selection, monitor response, and ultimately achieve the goal of remission in asthma.

Abstract The transition from internship to residency represents an important period for trainees. However, little is known about self-assessed preparedness among physiatry trainees. This national cross-sectional exploratory survey of United States postgraduate year 2–4 physiatry residents aimed to examine self-reported preparedness at the start of postgraduate year 2. A total of 109 postgraduate year 2–4 residents completed this survey, with 57.8% (63/109) reporting feeling prepared to assume patient care responsibilities at the start of postgraduate year 2 and 42.2% (46/109) reporting feeling unprepared to do so. Specific internship experiences (e.g., developing comfort handling overnight calls and rapid responses), but not type of intern year (e.g., transitional year, preliminary internal medicine or surgery year, intern year included in a categorical physiatry residency program) may be associated with self-reported clinical preparedness. Further research is warranted to explore in more detail factors identified as potentially associated with self-assessed clinical preparedness, as well as opportunities to identify and address physiatry trainee needs.

It is well established that many tumor types possess defective autophagic pathways. Several studies have reported that the transmembrane, autophagic lipid scramblase ATG9B is altered in multiple cancers, suggesting that this dysregulation could contribute to oncogenesis. Therefore, the goal of this study was to define the cellular distribution of ATG9B in two different tumor cell types and to provide insights into its cellular function. Surprisingly, we found that ATG9B shows a modest association with autophagic structures and exhibits a unique and prominent localization to mitochondria, in contrast to its related form ATG9A. Upon expression of tagged ATG9B forms, this mitochondrial distribution was accompanied by aberrant changes in mitochondrial morphology as well as a reduction in the mitochondrial membrane potential and the release of mtDNA. Few indicators for ATG9B-dependent mitophagy were noted. Instead, ATG9B overexpression led to pronounced apoptotic cell death as assessed by a variety of indicators. Further, we find that the N-terminal sequence of ATG9B acts as a mitochondrial targeting domain and that expression of this peptide alone can induce apoptotic cell death. These findings provide new insights into a putative cellular localization and function for ATG9B.

Background: Acute traumatic patellar dislocations may cause intra-articular derangements of the knee in the setting of acute and chronic instability which may not always be appropriately identified on magnetic resonance imaging (MRI). Purpose: To determine the rates of coexisting intra-articular pathology in patients with patellar instability requiring medial patellofemoral ligament (MPFL) reconstruction and to report discrepancies between preoperative magnetic resonance imaging (MRI) findings and diagnostic arthroscopy results. Study Design: Cohort study (Diagnosis); Level of evidence, 3. Methods: Patients who underwent MPFL reconstruction at a single institution between 2010 and 2023 were identified. Operative reports and preoperative MRIs were reviewed. Records without full MRI reports as read by a radiologist or cases in which a diagnostic arthroscopy was not conducted were excluded. Intra-articular pathologies noted on MRI and confirmed by arthroscopy were documented. MRI findings were considered to be discordant from arthroscopic findings if a lesion was identified on diagnostic arthroscopy that was not present in the full MRI report and that lesion resulted in additional surgical procedures. Results: There were 331 arthroscopic procedures conducted within the study population of 508 patients who underwent diagnostic arthroscopy at the time of their patellar stabilization procedures. These procedures included 180 loose body removals, 95 osteochondral lesions treated via a variety of interventions including open reduction and internal fixation (26 cases), particulated allograft chondral grafting (30 cases), osteochondral allograft transplantation (9 cases), and microfracture (30 cases), and 39 meniscal tears resulting in 33 partial meniscectomies and 6 meniscal repairs. Among these 508 patients, 105 (21%) demonstrated discordance of preoperative MRI and arthroscopic findings that necessitated additional procedures. This discordance was responsible for a total of 109 (33%) of the 331 arthroscopic procedures. These included 75 loose body removals, 2 osteochondral fracture fixation procedures, 2 microfractures for full-thickness cartilage loss, 16 partial meniscectomies, and 2 meniscal repairs, among others. Conclusion: Among patients undergoing patellar stabilization, 21% had intra-articular lesions not identified on preoperative MRI detected at the time of diagnostic arthroscopy that resulted in surgical intervention. This study, representing the largest cohort to date of patellar stabilization surgeries with both MRI and arthroscopy findings, underscores the importance of diagnostic arthroscopy for improving diagnostic accuracy and addressing associated intra-articular pathology.

Introduction: The Revised Cardiac Risk Index (RCRI) and the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) are well-recognized tools to predict 30-day postoperative cardiac events in noncardiac surgeries. However, their predictive accuracy is yet to be assessed in minimally invasive transurethral prostate surgery. We compared the RCRI- and NSQIP-predicted postoperative cardiac outcomes with the actual incidence of cardiac events after transurethral prostate surgery. Methods: We conducted a retrospective review of patients who underwent transurethral prostate surgery between July and December of 2022. We assessed for postoperative cardiac events within 30 days, as defined by the seminal cardiac VISION study. The RCRI and NSQIP cardiac event predictions were calculated. Fisher’s exact test was used for analysis. Results: We included 185 patients with an average age of 73 ± 8.4 (standard deviation) years, 86 of whom (46%) had transurethral resection of the prostate, and 99 underwent Holmium Laser Enucleation of the Prostate (54%). Myocardial injury after noncardiac surgery surveillance was needed for 34 patients (18.4%) as per standard practice. No patient had any intraoperative cardiac events. One patient experienced a nonfatal postoperative cardiac event (asystole) within hours of surgery. The 30-day cardiac event prediction by the RCRI was 4.8% of the patient cohort ( n ≈ 9), significantly higher than the observed incidence of 0.5% ( p = 0.0198). NSQIP predicted that 0.54% of the patient cohort ( n = 1) will have a cardiac complication within 30 days, which is not significantly different from the observed cardiac event incidence ( p = 1). Conclusion: The RCRI significantly overestimated the 30-day cardiac risk after transurethral prostate surgery, whereas NSQIP predictions and the observed rate of cardiac events were similar. Utilizing more representative predictive tools helps improve risk stratification and will allow patients and surgeons to make better-informed decisions.

Key Points Both sodium zirconium cyclosilicate and patiromer effectively lower serum potassium and provide clinical benefits. Sodium zirconium cyclosilicate is associated with higher risk of edema. Patiromer is associated with the increased risk of constipation and hypokalemia. Background Sodium zirconium cyclosilicate (SZC) and patiromer have recently been approved for the treatment of hyperkalemia. However, their efficacy in lowering serum potassium according to the phase of intervention, safety profile, and impact clinical outcomes remains to be fully defined. This study aims to assess their efficacy and tolerability in the management of hyperkalemia. Methods A comprehensive search of PubMed, Scopus, and Cochrane Central Register of Controlled Trials was conducted up to June 6, 2025. Eligible studies included randomized controlled trials reporting the effects of SZC and patiromer on laboratory parameters, clinical outcomes, and safety profiles. Meta-analyses were synthesized using a random-effects model, with results presented as weighted mean differences (WMD) or relative risks (RR), along with 95% confidence intervals (CI). Results Nineteen randomized controlled trials involving 3627 patients (1911 on SZC; 1716 on patiromer) were analyzed. During the initial 48–72 hours, only SZC significantly reduced serum potassium levels (WMD, −0.45 mEq/L; 95% CI, –0.61 to –0.29). At the end of treatment, both agents effectively lowered serum potassium (SZC: WMD, –0.50 mEq/L; 95% CI, –0.63 to –0.38; patiromer: WMD, –0.36 mEq/L; 95% CI, –0.51 to –0.21). SZC significantly normalized serum potassium and reduced hyperkalemia incidence, while patiromer enabled renin-angiotensin-aldosterone system inhibitor optimization by supporting target dosing and reducing discontinuation due to hyperkalemia. However, SZC was associated with a higher incidence of edema (RR, 2.92; 95% CI, 1.08 to 7.90) and patiromer with increased rates of constipation (RR, 2.96; 95% CI, 1.21 to 7.22) and hypokalemia (RR, 1.46; 95% CI, 1.05 to 2.03). Conclusions Both SZC and patiromer effectively lower serum potassium and provide clinical benefits, with distinct safety considerations. Therapy selection should be guided by treatment goals and the patient's individual risk profile.

Background: Overweight and obesity are rising globally. During perimenopause years, declining estrogen and changes in body composition increase visceral fat and insulin resistance, increasing cardiometabolic risk. Objective: To estimate trends in overweight and obesity among U.S. women aged 40–64 years, examine variations by age and state, and project prevalence to 2050. Design: Secondary analysis of publicly available body mass index (BMI) data accessed through the Global Burden of Disease (GBD) Health Data Exchange, using pooled cross-sectional estimates and hierarchical logistic growth modeling.This sub‑study is not part of the official GBD analysis. Methods: Harmonized data from the GBD Health Data Exchange integrated National Health Interview Survey, National Health and Nutrition Examination Survey (NHANES), and Behavioral Risk Factor Surveillance System microdata (1990–2021) for nonpregnant women aged 40–64 years, with calibration of self-reported BMI to measured NHANES data. BMI categories followed WHO cutoffs. Weighted estimates were age-standardized, and hierarchical logistic models projected state-specific trends to 2050. The pooled sample included 150,842 women, representing about 90 million weighted person-years. All data were de-identified and publicly available; ethics approval and consent were not required. Results: Combined overweight/obesity prevalence increased from 49.2% (95% uncertainty interval (UI) 45.8–52.2; 17.7 million (95% UI 16.5–18.8 million)) in 1990 to 74.2% (95% UI 68.8–79.1; 33.4 million (95% UI 31.0–35.6 million)) in 2021, and projected to reach 83.4% (95% UI 75.5–88.3; 41.7 million (95% UI 37.8–44.2 million)). In 2021, rates ranged from 68.3% in Colorado to 82.8% in Mississippi. Conclusion: Overweight and obesity among midlife women have increased sharply with a continuing shift from overweight to obesity. Menopause-specific preventive strategies and policies promoting physical activity and healthy diet are critical to slow future increases.