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Recurrent myocardial infarction identified by centralized troponin review: Insights from the MINT trial.

BACKGROUND: The utility of routine troponin testing to identify recurrent myocardial infarction (MI) after an incident MI is unclear. We assessed the incidence and prognosis of recurrent MIs identified from centralized troponin review in patients from the Myocardial Ischemia and Transfusion (MINT) trial. METHODS: The MINT trial randomized patients with acute MI and anemia to a liberal vs restrictive red blood cell transfusion strategy. Suspected recurrent MIs were identified through both site-report and centralized review of troponin levels collected for 3 days following randomization. Differences in cardiac, noncardiac, and all-cause death at 30 and 180 days were compared across patients with any site-reported MI, only centrally identified MI, and no recurrent MI. RESULTS: Among 3,504 patients, 275 (7.8%) had a recurrent MI within 30 days; 119 (43.3%) by site-report, and 156 (56.7%) by central troponin review only. Rates of cardiac and all-cause death at 30 and 180 days were highest for patients with site-reported MI, intermediate for centrally identified MI, and lowest for no recurrent MI; rates of noncardiac death did not vary. Patients with only centrally identified recurrent MI had an increased risk of cardiac death at 30 days (RR 1.9, 95% CI 1.0-3.4) and 180 days (RR 1.7, 95% CI 1.1-2.7) compared to those without recurrent MI. CONCLUSIONS: In patients with acute MI and anemia, centralized troponin review identified more than half of all recurrent MI events. Patients with centrally identified MI had a higher risk of cardiac death than those with no recurrent MI. TRIAL REGISTRATION: ClinicalTrials.gov NCT02981407 https://clinicaltrials.gov/study/NCT02619136.

Humans

Reducing state anxiety with alpha-frequency transcranial alternating current stimulation.

BACKGROUND: Anxiety reactivity to acute stress is a transdiagnostic vulnerability factor. We tested whether a single session of alpha-frequency transcranial alternating current stimulation (tACS) targeting the frontoparietal control network reduces stress-evoked state anxiety in healthy adults. METHODS: In a randomized, blinded, sham-controlled study, 42 participants (mean age 58.9 years) completed an acute stress task before and after stimulation. The task was an adapted moving-circles paradigm in which circle collisions triggered a brief aversive event (mild electric shock plus unpleasant noise and a white flash). Active stimulation consisted of 20 min of 10-Hz tACS (2.0 mA/channel; 30-s ramp up/down) delivered via electrodes at F3, P3, Cz, and T7 (0° phase at F3/P3; 180° at Cz/T7). Sham stimulation used the same montage and ramp periods but no sustained current. RESULTS: State anxiety showed a significant Time × Protocol interaction (F(1,35) = 4.22, p = .047): STAI-S decreased after active tACS (Δ = -3.16) but increased slightly after sham (Δ = +1.17). Perceived stress appraisal (SAAS) did not change. Resting-state alpha power at F3/P3 showed no reliable pre-post effects. During the task, left-frontal relative alpha differed by protocol and showed a trend toward larger increases following active tACS. Electrodermal and pupil indices changed across sessions in both groups, with no differential stimulation effects. CONCLUSIONS: A single alpha-tACS session produced a modest, selective reduction in stress-evoked state anxiety, supporting oscillatory neuromodulation as a scalable approach to dampen anxiety reactivity.

Humans

Cost-Effectiveness and the Economics of Genomic Testing and Molecularly Matched Therapies.

Cost-effectiveness analysis of precision oncology can help guide value-driven care. Next-generation sequencing is increasingly cost-efficient over single gene testing because diagnostic algorithms require multiple individual gene tests to determine biomarker status. Matched targeted therapy is often not cost-effective due to the high cost associated with drug treatment. However, genomic profiling can promote cost-effective care by identifying patients who are unlikely to benefit from therapy. Additional applications of genomic profiling such as universal testing for hereditary cancer syndromes and germline testing in patients with cancer may represent cost-effective approaches compared with traditional history-based diagnostic methods.

Humans

The effects of nitrate and nitrite supplementation on mitochondrial respiration in permeabilized muscle fibres in young healthy adults.

Nitric oxide (NO) is a direct regulator of mitochondrial respiration. Nitrate (NO3-) and nitrite (NO2-) are good sources of NO, but whether their effects on mitochondrial respiration differ between in vivo and in vitro administration remains unclear. In Study 1, 8 participants consumed NO3- -rich beetroot juice (BR) (∼12.8 mmol NO3-) and NO3- -depleted placebo beetroot juice (PL) (∼0.08 mmol NO3-) acutely and chronically for 2 weeks in a randomised, double-blind, crossover design. A substrate-uncoupler-inhibitor titration (SUIT) protocol was used to assess mitochondrial respiration using high-resolution respirometry (oxygen tension: ∼200-450 μM) in permeabilized muscle fibres. In Study 2, skeletal muscle samples were collected from 11 participants. In a randomised, crossover design, different doses (0, 1.5, and 3.0 μM) of sodium nitrite (NaNO2) were administered to permeabilized muscle fibres. Mitochondrial respiration was measured using the same SUIT protocol under lower oxygen tension (∼50-200 μM). Although muscle NO3- concentration significantly increased after both acute and chronic BR supplementation, mitochondrial respiration and exercise performance did not differ between PL and BR in either condition. Similarly, absolute oxygen flux across different respiratory states were not different between different doses of NaNO2. However, the leak control ratio, reflecting the degree of uncoupling of mitochondrial respiration, was significantly higher with 3.0 μM NaNO2 administration (0.12 ± 0.05) compared to 0 μM NaNO2 administration (0.09 ± 0.04, P = 0.03). These findings, involving both in vivo and in vitro administration approaches, albeit in the presence of relatively high oxygen concentrations, suggest that neither NO3- nor NO2- improves mitochondrial respiration, at least in young healthy adults.

Humans

Integrated Telehealth Rehabilitation and Quality of Life in Mechanically Ventilated Adults: A Randomized Clinical Trial.

IMPORTANCE: Whether integrated rehabilitation strategies spanning intensive care unit (ICU), hospital, and postdischarge phases improve quality of life after acute respiratory failure is uncertain. OBJECTIVE: To evaluate the effect of an integrated multicomponent telehealth-based rehabilitation intervention on health-related quality of life at 90 days after hospital discharge among adults with acute hypoxemic respiratory failure requiring invasive mechanical ventilation. DESIGN, SETTING, AND PARTICIPANTS: This stepped-wedge cluster randomized clinical trial in ICUs of 20 public hospitals in Brazil enrolled adults with acute hypoxemic respiratory failure requiring invasive mechanical ventilation between June 2024 and May 2025, with follow-up through September 2025. INTERVENTIONS: A multicomponent telehealth-based rehabilitation program integrating an ICU telehealth-based rehabilitation intervention focused on ventilator liberation; a ward telehealth-based rehabilitation intervention targeting risk stratification and initiation of individualized rehabilitation plans; and a postdischarge telehealth-based rehabilitation intervention consisting of a 2-month personalized centralized telerehabilitation program. MAIN OUTCOMES AND MEASURES: Health-related quality of life at 90 days after hospital discharge, measured using the EuroQol 5-Dimension 3-Level (EQ-5D-3L) utility score (range, -0.17 [worse than death] to 1 [best health state], with 0 representing death). RESULTS: Among 1916 enrolled patients (mean [SD] age, 60.6 [17.3] years; 43.6% female), 1063 were assigned to the intervention and 853 to usual care per local protocols. At 90 days after hospital discharge, mean (SD) EQ-5D-3L utility scores were higher in the intervention group than in the usual care group (0.16 [0.31] vs 0.12 [0.28]; adjusted difference, 0.049; 95% CI, 0.0002 to 0.098; P&#x2009;=&#x2009;.04) but did not differ among survivors (0.60 [0.32] vs 0.59 [0.32]; adjusted difference, -0.045; 95% CI, -0.138 to 0.045; P&#x2009;=&#x2009;.34). Compared with usual care, the intervention resulted in lower 90-day all-cause mortality (71.8% [676 of 941] vs 78.3% [584 of 746]; adjusted difference, -7.6%; 95% CI, -14.7% to -0.6%; P&#x2009;=&#x2009;.03) and shorter mean (SD) mechanical ventilation duration (9.9 [10.3] vs 15.5 [15.9] days; adjusted difference, -6.2 days; 95% CI, -8.5 to -3.9; P&#x2009;<&#x2009;.001). CONCLUSIONS AND RELEVANCE: In this study, an integrated telehealth-based rehabilitation strategy delivered across ICU, hospital, and postdischarge phases improved 90-day health-related quality of life, potentially influenced by reduced mortality. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06343545.

Humans

Transcriptomic insights into thermal stress reveal physiological trade-off between thermal stress adaptation and reproductive investment in Spodoptera litura.

Spodoptera litura, a highly polyphagous lepidopteran pest, poses a major threat to agricultural productivity due to its remarkable adaptability to diverse environmental conditions. Although heat stress is known to trigger transcriptional reprogramming in insects, the molecular mechanisms underlying thermal stress responses in S. litura remain poorly understood. In the present study, fourth-instar larvae were exposed to acute heat stress (44&#xa0;&#xb0;C) and compared with control conditions (27&#xa0;&#xb1;&#xa0;1&#xa0;&#xb0;C) to investigate heat-induced transcriptional alterations affecting physiology and reproduction. High-quality RNA-Seq data achieved more than 80% mapping efficiency, with a total of 15,782 transcripts were identified. Transcriptome analysis of S. litura larvae showed 323 differentially expressed genes (DEGs), of which 262 genes were significantly upregulated and 61 were downregulated in heat-stressed larvae compared to the control group. The DEGs were associated with stress response, reproduction, signalling, proteostasis, detoxification, oxidative stress, metabolism, development, and chromatin regulation. Heat shock proteins genes, including HSP70, HSP90, and HSP27, together with co-chaperones such as TRET-1, STIP1, and Starvin, were strongly upregulated, indicating enhanced cellular protection against protein damage and oxidative stress under heat stress. Conversely, key reproductive and cell cycle-related genes, including BARR, CAPD2, FEO, CDK2 and MORULA, were significantly downregulated, suggesting reproductive impairment and developmental arrest. RT-qPCR validation corroborated the RNA-Seq findings, demonstrating a heat-induced physiological trade-off that prioritizes survival over reproduction. Consistent with these molecular responses, heat-stressed insects exhibited marked reproductive impairment, including significant reductions in gonadosomatic index, eupyrene sperm bundle count, mating frequency, mating success, female calling behaviour, copulation duration, fecundity, and egg fertility. Collectively, these findings provide comprehensive insights into the molecular basis of thermal adaptation in S. litura and demonstrate that acute heat stress compromises reproductive fitness while activating conserved stress-response pathways that promote short-term survival.

Animals

Optimizing physical activity bouts to interrupt sedentary behaviour for cardiometabolic health: a systematic review and meta-analyses of randomized controlled trials.

AIMS: Chronic diseases such as type 2 diabetes mellitus and cardiovascular diseases are leading causes of mortality worldwide, with sedentary behaviour (SB) and physical inactivity recognized as major interrelated risk factors. Prolonged SB, particularly when combined with insufficient physical activity, adversely affects cardiometabolic health. This systematic review aimed to evaluate which characteristics of physical activity (PA) bouts, in terms of frequency, duration, and intensity, are associated with improvements in cardiometabolic outcomes. METHODS AND RESULTS: Studies assessing physical activity interventions compared with sedentary control conditions were included. Eligible studies involved adults aged 18-65 years, with or without cardiometabolic conditions. PubMed, Cochrane Central, Embase, and Web of Science were searched to February 2025. Random-effects models were used to calculate pooled standardized mean differences (SMD) with 95% confidence interval (CI). Subgroup and meta-regression analyses explored potential moderators. A total of 144 studies (247 intervention arms; 2216 participants) were included. Frequent PA bouts reduced blood glucose [SMD -0.22 (95% CI -0.27 to -0.16)]. Longer and/or more intense PA bouts decreased triglycerides [SMD -0.27 (-0.34 to -0.19)], with significant duration &#xd7; intensity interactions for glucose (P = 0.032) and triglycerides (P < 0.001). Moderate-to-vigorous PA bouts improved endothelial function [flow-mediated dilation SMD 0.88 (0.47-2.24); shear rate SMD 0.54 (0.31-0.78)]. PA bouts also lowered insulin [SMD -0.26 (-0.32 to -0.19)], systolic BP [SMD -0.29 (-0.39 to -0.19)], and diastolic BP [SMD -0.16 (-0.26 to -0.05)]. CONCLUSION: In acute experimental settings, glucose regulation appears to benefit more from frequent PA bouts, while triglyceride responses are more closely related to greater duration and/or intensity. Blood pressure shows favourable acute responses across PA types, whereas higher PA intensity is associated with improved endothelial function. Tailoring strategies to interrupt SB with PA bouts may help inform approaches to improve cardiometabolic health.

Humans

Effect of adding umbilical cord blood derived stem cells to haploidentical stem cell transplant (haplo-cord) on post-transplant survival and graft-versus-host disease in patients with hematological malignancies: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: Haploidentical stem cell transplantation (haplo-SCT) carries a substantial risk of graft-versus-host disease (GvHD), whereas umbilical cord blood (UCB) transplantation offers lower GvHD risk but slower engraftment. The haplo-cord approach combines both graft sources, aiming to mitigate GvHD while ensuring timely engraftment. This meta-analysis compares haplo-cord transplantation with haplo-SCT alone for the treatment of hematological malignancies. METHODS: Four electronic databases and two clinical trial registries were systematically searched. Effect sizes from eligible studies were pooled using odds ratios (ORs) for dichotomous outcomes and hazard ratios (HRs) for time-to-event outcomes. RESULTS: Twelve studies met the inclusion criteria. Haplo-cord was associated with a statistically significant reduction in chronic GvHD (OR&#xa0;=&#xa0;0.62, 95%-CI: 0.42-0.93), while no significant difference was observed for grade II-IV acute GvHD (OR&#xa0;=&#xa0;0.75, 95%-CI: 0.52-1.09). Survival outcomes favored haplo-cord, with lower HRs for overall survival (HR&#xa0;=&#xa0;0.68, 95%-CI: 0.53-0.86) and event-free survival (HR&#xa0;=&#xa0;0.61, 95%-CI: 0.52-0.72), while non-relapse mortality was not significant. Relapse at 3&#xa0;years was significantly lower with haplo-cord (OR&#xa0;=&#xa0;0.54, 95%-CI: 0.35-0.82). Haplo-cord also demonstrated higher day-30 engraftment, along with lower relapse-related and GvHD-related mortality, while CMV and EBV viremia showed no difference between groups. CD34 selection in the haplo graft significantly influenced effect sizes and heterogeneity in both subgroup analyses and meta-regression for acute GvHD. CONCLUSION: Haplo-cord transplantation improves GvHD outcomes, survival, and relapse risk compared with haplo-SCT alone. However, whether protocol optimization, possibly via CD34 selection, confers additional benefit remains uncertain and requires confirmation in future studies.

Humans

Effects of antidepressant administration on physical performance and perceived exertion in athletes: systematic review and meta-analysis.

INTRODUCTION: Antidepressants are commonly prescribed in athletes with depressive disorders, yet their potential effects on physical performance and perceived exertion remain unclear, and existing evidence is limited and inconsistent. AIM: This systematic review and meta-analysis aimed to evaluate the effects of antidepressant use on objective physical performance and perceived exertion in athletes. METHOD: A systematic literature search was conducted in PubMed, the Cochrane Library, Web of Science, and SPORTDiscus through March 2025. Eligible studies were randomised controlled trials (RCTs) published in English that enrolled elite, competitive, or recreational athletes; compared antidepressant administration with placebo or no treatment; and reported at least one objective or subjective performance-related outcome. Meta-analyses were performed using random-effects models, and pooled mean differences with 95% confidence intervals (CI) were calculated. This systematic review and meta-analysis was registered in PROSPERO (CRD420251123740). RESULTS: Ten crossover RCTs involving 99 male athletes were included. Interventions included a norepinephrine reuptake inhibitor (reboxetine), a norepinephrine-dopamine reuptake inhibitor (bupropion), and selective serotonin reuptake inhibitors (fluoxetine or paroxetine). Acute antidepressant administration was associated with a small increase in rating of perceived exertion (RPE; mean difference 0.52 points on the Borg 6-20 scale, 95% CI 0.01-1.04; p&#x2009;<&#x2009;0.05). No significant overall effects were observed for time-trial performance, mean power output, heart rate or blood lactate. However, subgroup analyses showed that reboxetine significantly impaired time-trial performance (mean difference 3.62&#xa0;min, 95% CI 0.18-7.06; p&#x2009;<&#x2009;0.05) and reduced mean power output (mean difference&#x2009;-&#x2009;19.97 W, 95% CI&#x2009;-&#x2009;36.87 to&#x2009;-&#x2009;3.06; p&#x2009;<&#x2009;0.05). CONCLUSION: Short-term antidepressant administration in athletes was associated with a small increase in perceived exertion, without consistent impairment in objective physical performance. As the current evidence derives exclusively from male athletes and acute exposure, further research should clarify its relevance to female athletes and to longer-term antidepressant treatment in athletes with depressive disorders.

Humans

Efficacy and Safety of Rivaroxaban in Patients with Peripheral Artery Disease: A GRADE-assessed Systematic Review and Meta-Analysis.

BACKGROUND: Peripheral artery disease (PAD) is a common atherosclerotic disorder characterized by progressive arterial narrowing in the limbs. This study aims to determine the efficacy and safety of rivaroxaban, focusing on major cardiovascular events, limb outcomes, and bleeding risks. METHODS: PubMed, Cochrane, and EMBASE were searched for randomized controlled trials (RCTs) and nonrandomized comparative studies that compared rivaroxaban, either alone or in combination with aspirin, to placebo or standard care such as antiplatelet therapy. Risk ratios and hazard ratios with 95% confidence intervals were pooled using R v4.5.1 with an appropriate random-effects model applied. Subgroup analyses were performed according to rivaroxaban plus aspirin versus rivaroxaban alone. RESULTS: A total of 39,991 participants across 6 studies were included. Compared with control, use of rivaroxaban was linked to a significant reduction in composite efficacy outcomes (relative risk [RR] = 0.84, 95% confidence interval [CI] 0.78-0.91, P < 0.001), risk of acute limb ischemia (RR = 0.65, 95% CI 0.55-0.78, P < 0.001), and thromboembolism (RR = 0.60, 95% CI 0.38-0.97, P = 0.037). Although rivaroxaban plus aspirin failed to show a significant reduction in the risk of amputation, rivaroxaban alone reported a significant risk reduction (RR = 0.50, 95% CI 0.30-0.85, P = 0.003). However, its use was associated with a significantly higher risk of major bleeding (hazard ratio [HR] = 1.54, 95% CI 1.38-1.72, P < 0.001) and International Society on Thrombosis and Hemostasis-defined bleeding (RR = 1.45, 95% CI 1.19-1.76, P < 0.001). No significant differences were observed for stroke, myocardial infarction, major adverse limb events, fatal bleeding, mortality, or cardiovascular mortality. CONCLUSION: Rivaroxaban-based therapy reduced the trial-defined composite efficacy outcome, acute limb ischemia, and thromboembolism in patients with PAD, but increased the risk of major bleeding. These findings support individualized use of rivaroxaban-based therapy in carefully selected patients, balancing ischemic and limb-protective benefits against bleeding risk.

Humans

Prophylactic Surgical Left Atrial Appendage Closure in Bioprosthetic Aortic Valve Replacement: Short-Term Outcomes of Randomized Controlled LAA-CLOSURE Trial.

BACKGROUND: Surgical closure of the left atrial appendage (LAA) reduces stroke risk in patients with atrial fibrillation (AF) undergoing cardiac surgery. We evaluated the safety and efficacy of prophylactic LAA closure during bioprosthetic surgical aortic valve replacement in patients without prior AF. METHODS: In this investigator-initiated, academic, randomized, open-label, multicenter LAA-CLOSURE (Left Atrial Appendage CLOSURE for the Prevention of Thromboembolisms in Patients Undergoing Aortic Bioprosthesis Surgery) trial, 921 patients without prior AF undergoing bioprosthetic surgical aortic valve replacement with or without concomitant surgery were randomized and 904 patients included in the modified intention-to-treat analysis (prophylactic LAA closure, n=445; or usual care, n=459). Median age was 73&#x2009;years (interquartile range, 69-76), 34.8% were women, and 49% had concomitant coronary artery disease. The primary end point was a composite of cardiovascular death, stroke, or systemic embolism at 30&#x2009;days. RESULTS: The primary end point occurred in 10 of 434 (2.2%) patients in the LAA closure group and 14 of 452 (3.1%) patients in the control group; however, the treatment effect changed direction at &#x2248;7&#x2009;days. In the time-split Cox regression model, hazard ratios were 2.4 (95% CI, 0.62-9.4; P=0.20) between 0 and 7&#x2009;days and 0.29 (95% CI, 0.080-1.0; P=0.056) between 7 and 30&#x2009;days. No closure-related serious complications or differences in bleeding were observed. Postoperative AF occurred in 205 of 445 (46.1%) versus 184 of 459 (40.1%) patients (relative risk, 1.1 [95% CI, 0.99-1.3]; P=0.07), and AF at discharge in 40 of 445 (9.2%) versus 34 of 459 (7.7%) patients (relative risk, 1.2 [95% CI, 0.77-1.8]; P=0.44), in the closure and control groups, respectively. CONCLUSIONS: Prophylactic LAA closure during bioprosthetic surgical aortic valve replacement was safe and did not increase bleeding. REGISTRATION: URL: clinicaltrials.gov; Unique Identifier: NCT02321137.

Aged

Feasibility and acceptability of skills training in affective recovery (STAR) video and TextSTAR text message program for recent sexual assault survivors.

Background: Sexual assault (SA) affects more than 50% of women in the United States and is associated with elevated risk for impairing posttraumatic stress symptoms and substance, particularly opioid, misuse. Intervening following SA exposure could attenuate these risks.Objective: This study examined the acceptability and feasibility of a 17-minute video, Skills Training in Affective Recovery (STAR) and a 21-day text message program (TextSTAR), that were delivered in the acute post-SA period to prevent the onset or escalation of posttraumatic stress symptoms and substance misuse. The interventions provide psychoeducation about trauma, strategies to reduce fear and avoidance, suggestions to increase social support, and coping strategies for substance use.Method: Participants were 50 women age 18 or older who presented for a Sexual Assault Medical Forensic Exam (SAMFE) within seven days of a SA. Using a Sequential Multiple Assignment Randomized Controlled Trial (SMART) design, participants were randomized to receive the STAR video (n&#x2009;=&#x2009;25) or no video (n&#x2009;=&#x2009;25) at the SAMFE. Those who received the video answered questions about video acceptability immediately after viewing the video. At 1-week post-SAMFE, participants completed online questionnaires about substance use and posttraumatic stress; those above threshold on acute stress or opioid use (n&#x2009;=&#x2009;36) were randomized to TextSTAR (n&#x2009;=&#x2009;18) or no-text program (n&#x2009;=&#x2009;18). Participants completed weekly online surveys 2-4 weeks post-SAMFE about symptoms and text program acceptability.Results: Participants found STAR and TextSTAR at least moderately acceptable; 80% who received STAR found it extremely acceptable while 60-90% (depending on timepoint) who received TextSTAR found it at least moderately acceptable. Our ability to enroll 50 participants and retain 94% at 1 week and 90% at 4 weeks suggests the intervention trial is feasible.Conclusions: STAR and TextSTAR are acceptable and feasible brief interventions for recent sexual assault survivors.Trial registration: ClinicalTrials.gov identifier: NCT06456190.

Humans

Higher Rates of PASS and SCB After Arthroscopic Subspine Decompression Are Associated With a Positive Diagnostic AIIS Injection: A Propensity Score-Matched Cohort Study.

BACKGROUND: Hip arthroscopy effectively treats femoroacetabular impingement syndrome (FAIS), but persistent pain may be related to concomitant extra-articular pathology such as subspine impingement syndrome (SSI). Standard diagnosis of SSI often relies on 3-dimensional computed tomography (3D-CT) morphology (Hetsroni type II/III), although this morphology is common in individuals who are asymptomatic and correlates poorly with symptoms. PURPOSE: To compare minimum 2-year clinical outcomes after arthroscopic subspine decompression in patients with concurrent FAIS and type II/III anterior inferior iliac spine (AIIS) morphology, stratified by diagnostic method: 3D-CT morphology alone versus 3D-CT morphology plus a positive ultrasound-guided diagnostic injection. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: This study included patients aged 18 to 55 years with type II/III AIIS morphology who underwent primary hip arthroscopy for FAIS and SSI between January 2021 and November 2023 and had minimum 2-year follow-up. Patients diagnosed by CT morphology alone (CT classification group) were propensity score matched 1:1 to patients with a positive ultrasound-guided AIIS injection (injection group), with 57 patients per group. Matching variables were age, sex, body mass index, lateral center-edge angle, alpha angle, T&#xf6;nnis grade, and Beighton score. All patients underwent arthroscopic subspine decompression. Patient-reported outcomes and rates of achieving the minimal clinically important difference, Patient Acceptable Symptom State (PASS), and substantial clinical benefit (SCB) were compared. RESULTS: Preoperative patient-reported outcome scores were similar between groups (all P > .05). At minimum 2-year follow-up, the injection group had significantly better scores on the modified Harris Hip Score (90.8 vs 84.2), Hip Outcome Score-Activities of Daily Living (88.4 vs 82.4), Hip Outcome Score-Sports Subscale (71.9 vs 64.1), 12-item International Hip Outcome Tool (83.9 vs 76.1), and visual analog scale for pain (1.2 vs 2.0) (all P < .001). Minimal clinically important difference rates were high in both groups, with higher rates in the injection group for modified Harris Hip Score (93% vs 77%; P = .033) and Hip Outcome Score-Activities of Daily Living (91% vs 75%; P = .042). PASS and SCB rates were significantly higher in the injection group across all patient-reported outcome measures (all P < .05). Revision and complication rates were low and did not differ significantly between groups. CONCLUSION: Both groups improved significantly after arthroscopic subspine decompression. However, patients with a positive ultrasound-guided diagnostic AIIS injection achieved higher PASS and SCB rates than those selected by CT morphology alone, suggesting that injection-confirmed SSI may improve patient selection for subspine decompression.

Humans

Histoplasmosis in children: emerging insights and evolving guidelines.

PURPOSE OF REVIEW: This review provides an update on the epidemiology, risk factors, clinical presentation, diagnosis, and management recommendations incorporating recommendations from recent publications including the Infectious Disease Society of America guidelines for the management of pulmonary and disseminated histoplasmosis. RECENT FINDINGS: Updates to the epidemiology of histoplasmosis indicate a broader geographic range than historically defined. Updated guidelines do not recommend routine treatment for asymptomatic, mild and moderate pulmonary histoplasmosis although itraconazole can be offered for immunocompromised children or for prolonged or worsening symptoms. Liposomal amphotericin B is recommended as initial treatment for severe histoplasmosis syndromes (severe pulmonary and disseminated histoplasmosis). Fibrosing mediastinitis, a late complication of histoplasmosis is treated with stenting of vessels and bronchi. Recent studies demonstrate that rituximab (anti-CD20 monoclonal antibody) may stop progression or lead to regression of progressive fibrosis. SUMMARY: Histoplasmosis has manifold manifestations, many of which are self-limited and do not require treatment. Severe histoplasmosis and its complications should be treated with liposomal amphotericin B followed by itraconazole. Clinical trials are needed to assess the efficacy of rituximab for the treatment of fibrosing mediastinitis.

Humans

Cardiovascular risks in psychiatric disorders and psychiatric risks in cardiovascular disorders: implications for prevention and clinical management - a large-scale umbrella review encompassing 76 meta-analyses.

OBJECTIVE: Psychiatric and cardiovascular disorders often co-occur, complicating their assessment and management. No umbrella review(UR) has summarized the meta-analytic evidence on the co-occurrence of psychiatric and cardiovascular disorders and assessed its credibility. METHODS: Meta-analytic systematic reviews of observational studies documenting the prevalence, risk factors, and outcomes associated with the co-occurrence of cardiovascular and psychiatric disorders, indexed from inception through March.16.2026, and meeting established diagnostic criteria, were included. Meta-analytic association and prevalence estimates were recalculated and graded based on established or adapted criteria. The AMSTAR-2 assessed the quality of the meta-analyses, while several subgroup analyses and meta-regressions aimed to explain the heterogeneity. RESULTS: We included 76 meta-analyses yielding 131 meta-analytic estimates. Based on pre-existing meta-analytic evidence, 22/24 prevalence estimates (91.7%) met moderate/strong credibility criteria. Strong credibility emerged for: orthostatic hypotension in Lewy body(58%;95%C.I.&#xa0;=&#xa0;50-66%) and Alzheimer's dementias(28.0%&#xa0;=&#xa0;95%C.I.&#xa0;=&#xa0;17.0-40.0%); pericardial effusion in anorexia nervosa(25.0%;95%C.I.&#xa0;=&#xa0;17.0-34.0%); in heart failure(HF): major depressive disorder(MDD)(41.9%;95%C.I.&#xa0;=&#xa0;36.7-47.1%), mild cognitive impairment(MCI)(41.4%;95%C.I.&#xa0;=&#xa0;38.3-45.6%), anxiety(32.0%;95%C.I.&#xa0;=&#xa0;26.5-37.6%), MDD&#xa0;+&#xa0;anxiety(24.7%;95%C.I.&#xa0;=&#xa0;17.9-34.3%), and dementia(19.8%;95%C.I.&#xa0;=&#xa0;12.9-27.8%); in atrial fibrillation(AF): MCI(26.0%;95%C.I.&#xa0;=&#xa0;21.0-30.0%), anxiety in patients undergoing pulmonary vein isolation(PVI)(25.0%;95%C.I.&#xa0;=&#xa0;12.0-46.0%), MDD in PVI patients (20.0%;95%C.I.&#xa0;=&#xa0;13.0-29.0%); in coronary artery disease: MDD&#xa0;+&#xa0;anxiety(19.8%;95%C.I.&#xa0;=&#xa0;16.0-24.6%): in schizophrenia spectrum disorders: clozapine-associated-cardiomyopathy(0.6%;95%C.I.&#xa0;=&#xa0;0.2-2.3%); clozapine-associated-cardiomyopathy absolute death rates (0.0003;95%C.I.&#xa0;=&#xa0;0.0001-0.0012); clozapine-associated-cardiomyopathy case fatality rate (0.078;95%C.I.&#xa0;=&#xa0;0.018-0.285). Several additional disorders were multimorbid in>5% of people, yet with a lower credibility rating. No re-pooled risk factors/outcomes reached strong credibility criteria. CONCLUSIONS: The present study provides an atlas of cardiovascular and psychiatric multimorbidity across varying levels of credibility, reinforcing the need for an integrated, multidisciplinary approach to patient care and for more research on actionable risk/protective factors and outcomes.

Humans

Effects of transcutaneous electrical acupoint stimulation versus acupressure on the trajectories of multidimensional adverse reactions to chemotherapy in breast cancer patients: a secondary analysis of a randomized controlled trial.

BACKGROUND: Chemotherapy for breast cancer often induces multidimensional adverse reactions such as nausea and vomiting, anxiety, depression, and sleep disturbances. These symptoms are interrelated and may evolve dynamically, impacting patients' treatment outcomes and quality of life. As non-pharmacological interventions, transcutaneous electrical acupoint stimulation (TEAS) and self-acupressure (SA) have shown potential in alleviating symptoms. However, their long-term effects on the joint developmental trajectories of these multidimensional symptoms (nausea and vomiting, anxiety, depression, and sleep disturbances) remain unclear. OBJECTIVE: This study aimed to identify potential trajectory class of multidimensional adverse reactions in breast cancer patients undergoing chemotherapy and to explore the differential effects of TEAS and SA on different trajectory subgroups. METHODS: This was a secondary analysis of a randomized controlled trial. A total of 189 breast cancer patients receiving chemotherapy were included. The Group-Based Multi-Trajectory Model (GBMTM) was employed to identify joint developmental trajectories of acute/delayed chemotherapy-induced nausea and vomiting (CINV), anxiety, depression, and sleep quality during chemotherapy. Subsequently, causal forest was used to analyze the average treatment effects (ATE) of TEAS (vs. control group) and SA (vs. control group) on patients' symptom trajectory. RESULTS: Multidimensional adverse reactions were classified into two heterogeneous trajectories: a "High Symptom Burden-Persistent (HSBP)" type (n&#x2009;=&#x2009;101) and a "Low Symptom Burden-Relieving (LSBR)" type (n&#x2009;=&#x2009;88). The persistent high incidence of acute CINV contrasted sharply with the comprehensive relief of other symptoms in the latter group. Causal forest suggested that both TEAS and SA significantly increased the probability of patients being classified into the "LSBR" trajectory. The ATE was 0.147 (95% CI: 0.143, 0.151) for TEAS, slightly lower (P&#x2009;<&#x2009;0.05) than 0.176 (95% CI: 0.162, 0.190) for SA.&#xa0; CONCLUSION: Multidimensional adverse reactions in breast cancer patients undergoing chemotherapy exhibit heterogeneity in their trajectories. Both TEAS and SA were associated with a higher probability of patients being classified into a more favorable symptom trajectory-LSBR. The multidimensional trajectory identification with treatment effect estimation may serve as a useful analytical strategy for future longitudinal research in cancer chemotherapy-induced adverse reactions symptom management. CLINICAL TRIAL REGISTRATION: ChiCTR2300077667 (Chinese Clinical Trial Registry, https://www.chictr.org.cn/ ), Registered 15 November 2023.

Humans

Design, rationale, and baseline patient characteristics for the Sickle Cell Disease and CardiovAscular Risk-Red cell Exchange (SCD-CARRE) trial.

BACKGROUND: Despite wide utilization of automated red blood cell exchange (RBCX) transfusion in adult patients with sickle cell disease (SCD), no consensus or quality efficacy data exist on its use. The Sickle Cell Disease and CardiovAscular Risk- Red cell Exchange (SCD-CARRE) trial tests the hypothesis that an automated chronic RBCX transfusion strategy reduces acute health care encounters and death while improving quality of life and end-organ function (cardiac, pulmonary and renal) in participants with SCD that are at high risk of death. METHODS: Adult patients with SCD with elevated tricuspid regurgitant jet velocity (TRV) and/or chronic kidney disease were considered to be at high risk of death and were randomly assigned to RBCX plus standard of care vs standard of care alone. Participants assigned to RBCX received 12 months of exchange transfusions to maintain target pretransfusion hemoglobin S% < 30%, post-transfusion hemoglobin S% < 20%, and post-transfusion hemoglobin concentration &#x2265;10 g/dL. All study participants were managed according to NHLBI/ASH/ATS Expert Panel guidelines. The primary endpoint was the number of SCD acute health care encounters or death over 13 months. Secondary endpoints included measures of cardiovascular and renal function, exercise capacity, patient reported outcomes (all collected at baseline, and months 4, 8, and 12), and transfusion-related adverse events (collected monthly). RESULTS: Between 2020 and 2025, the SCD-CARRE trial randomized 173 participants at 23 sites across 3 countries. Enrolled participants had mean (SD) age of 45.8 (11.8) years and 54% were female. At baseline, participants had average TRV of 2.8 (0.5) m/s such that 45.9% had a TRV between 2.5 to 2.9 m/sec and 28.1% had a TRV &#x2265; 3.0 m/sec. The median (Q1, Q3) eGFR in this cohort was 60 (36, 110) mL/min/1.73 m2. The median (Q1, Q3) 6-minute walk test distance was 375 meters (309, 439), the median daily steps were 3,728 (2,187, 5,821), and participants experienced a median (Q1, Q3) of 2 (1, 5) pain episodes in the year prior to randomization. The trial results are pending. CONCLUSIONS: The SCD-CARRE trial successfully enrolled a cohort of n = 173 adults with SCD. This study highlights a rationale to evaluate the effect of automated chronic RBCX transfusion strategy plus standard of care as compared to standard of care alone in SCD patients at high risk of death with a focus on patient centered outcomes, preservation of cardiovascular function, end-organ complications and death. TRIAL REGISTRATION: ClinicalTrials.gov, Identifier: NCT04084080, https://clinicaltrials.gov/study/NCT04084080.

Adult

Unraveling a Diagnostic Enigma: A TECPR2 Case Solved Through Multi-Omic Genomics.

TECPR2 is a key regulator of autophagy, encoded by the TECPR2 gene. Pathogenic variants in this gene have been linked to a rare hereditary sensory and autonomic neuropathy with intellectual disability (HSAN9). We report a teenage female with a syndromic intellectual disability disorder associated with neuromuscular abnormalities. Multi-omics analysis including genomics, transcriptomics, and proteomics, together with muscle biopsy from the affected individual, were used in this clinical case. Through trio exome sequencing we identified two heterozygous variants in the TECPR2 gene, NM_014844.4: c.480G>A; p.(Gln160=) and c.2846C>A; p.(Ala949Glu). Both were classified as variants of uncertain significance due to the lack of supporting evidence for pathogenicity. Subsequent long-read sequencing phased the variants and confirmed they were in trans. Additional functional studies using RNAseq and proteomics analyses verified the pathogenicity of the variants. This case study demonstrated the value of a multi-omics assisted analysis, which complemented the traditional phenotype-first approach in reaching a definitive clinical diagnosis.

Humans