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PubMed2026

Effects of testosterone-augmented multimodal exercise intervention in spinal cord injury: a randomized controlled trial.

CONTEXT: Spinal cord injury (SCI) leads to profound muscle atrophy, aerobic deconditioning, and metabolic dysfunction. Exercise-based interventions alone produce modest benefits. Whether testosterone can augment physiologic responses to exercise in this population remains untested. OBJECTIVE: To evaluate efficacy and safety of home-based intervention combining functional electrical stimulation-assisted leg cycling (FES-LC), arm ergometry (AE), and testosterone compared with FES-LC, AE plus placebo in adults with SCI. METHODS: This randomized, placebo-controlled, double-blind trial enrolled 84 adults (76 males and 8 females) aged 19-70 years with SCI (neurologic levels C4-T12; AIS grades A-D). Participants were randomized to multimodality intervention (home-based FES-LC, AE and intramuscular testosterone undecanoate) (n = 38) or control intervention (FES-LC, AE plus placebo) (n = 46) for 16 weeks. The primary outcome was change in aerobic capacity (peak VO2) during AE cardiopulmonary exercise testing. Secondary outcomes included lean mass, hemoglobin, cardiometabolic markers, and safety. RESULTS: Mean (SD) age was 44 (13) years and time since injury was 13.9 (13) years). Between-group changes in peak VO2 were not statistically significant. Within-group improvements were larger in multimodality (∼19% increase; 0.10 L/min; 95% CI, 0.02-0.18 L/min) compared to controls (∼6% increase; 0.06 L/min; 95% CI, -0.01-0.13). The multimodality group gained significantly more lean mass (whole-body:1.84 kg, 95% CI: 0.52-3.16, P = .007; lower extremity 0.92 kg, 95% CI: 0.38-1.45, P = .001), and anemia was corrected in a greater proportion of participants. Adverse event rates were similar between groups. CONCLUSION: A home-based multimodality intervention combining FES-LC, AE, and testosterone was safe and associated with greater improvements in lean mass and hemoglobin. Although between-group differences in aerobic capacity were not statistically significant, greater within-group increases were observed in the multimodality group. These findings may inform future studies of testosterone-augmented exercise interventions for individuals living with SCI.

Humans↗

PubMed2026

Respiratory effects of recruitment maneuvers according to lung recruitability assessed by electrical impedance tomography in patients with acute respiratory distress syndrome.

Recruitment maneuvers (RM) can improve oxygenation in patients with acute respiratory distress syndrome (ARDS), but their physiological effects depend on lung recruitability. This secondary analysis of a randomized controlled trial (RCT) evaluated oxygenation, respiratory mechanics, regional ventilation, and cardiorespiratory adverse events responses to a RM followed by electrical impedance tomography (EIT)-guided PEEP titration, using EIT to assess lung recruitability. In this study, fifty patients with moderate-to-severe ARDS underwent a stepwise RM followed by individualized PEEP titration guided by EIT. Lung recruitability was determined using the collapse index at PEEP 6 cmH₂O (CLPEEP6), defined as the proportion of collapsed lung at this PEEP level. Patients were classified into high- and low-recruitability groups based on median CLPEEP6 values. Oxygenation (PaO₂/FiO₂), static compliance (Cstat), driving pressure (Pdriv), regional ventilation distribution, and cardiorespiratory adverse events were compared before and after RM, during subsequent individualized EIT-guided PEEP titration. In patients with high recruitability (CLPEEP6 > 12.5), the PaO₂/FiO₂ ratio and Cstat increased significantly after RM (PaO₂/FiO₂: 100.8 ± 30.3 vs. 125.4 ± 38.3 mmHg, p < 0.05; Cstat: 21.5 ± 5.8 vs. 28.0 ± 7.0 mL/cmH₂O, p < 0.001), Pdriv decreased (19.1 ± 3.5 vs. 15.6 ± 3.2 cmH₂O, p < 0.001). EIT demonstrated a posterior redistribution of ventilation after RM. In contrast, patients with low recruitability (CLPEEP6 ≤ 12.5) showed no significant mechanical or oxygenation improvement and transient hypotension, arrhythmia, and desaturation appeared numerically more common in this group. No barotrauma or cardiac arrest occurred, and ICU mortality was similar between groups. A strategy combining a RM with subsequent individualized EIT-guided PEEP titration was associated with improved oxygenation and lung mechanics in patients with high lung recruitability, whereas patients with low recruitability showed limited physiological benefit, with cardiorespiratory adverse events appearing numerically more frequent. The EIT-derived CLPEEP6 index represents a feasible and clinically applicable https://clinicaltrials.gov/study/NCT06733168.

Humans↗

PubMed2026

Intravenous lidocaine reduces the propofol EC50 for loss of consciousness and intraoperative anesthetic consumption in gynecological laparoscopy: A randomized controlled trial.

BACKGROUND: Intravenous lidocaine reduces propofol requirements and procedure-related adverse events. OBJECTIVES: The study aimed to test whether intravenous lidocaine would reduce the effect-site concentration of propofol required to achieve loss of consciousness and decrease propofol consumption during total intravenous anesthesia in gynecological laparoscopy. METHODS: This was a prospective, randomized, double-blind, placebo-controlled trial. Sixty patients were randomly allocated to receive either intravenous lidocaine (1.5 mg·kg-¹ bolus) followed by continuous infusion or an equal volume of saline. Propofol was administered via target-controlled infusion starting at an effect-site concentration of 3.5 μg/mL. The concentration was then adjusted in steps of 0.5 μg/mLaccording to Dixon's up-and-down sequential method: decreased if loss of consciousness was achieved, or increased if not. Loss of consciousness was defined as loss of response to verbal commands. The median effective concentration (EC50) of propofol for inducing loss of consciousness was calculated using the Dixon's up-and-down method. General anesthesia was maintained with propofol and remifentanil, guided by state entropy (target 40-60) and surgical pleth index (target 20-50). Drug consumption was normalized to anesthesia duration and body weight. RESULTS: The estimated EC50 of propofol for inducing loss of consciousness was significantly lower in the lidocaine group than in the saline group (3.32 μg/mL, 95% Confidence Interval (CI): 3.04-3.59 vs. 3.89 μg/mL, 95% CI: 3.50-4.28). Under the study protocol, the lidocaine group also required less propofol (8.62 mg·kg-1·h-1, 95% CI: 8.10-9.15 vs. 9.89 mg·kg-1·h-1, 95% CI: 9.05-10.73) and less remifentanil (0.23 μg·kg-1·min-1, 95% CI: 0.21-0.24 vs. 0.27 μg·kg-1·min-1, 95% CI: 0.24-0.30) compared with the saline group. CONCLUSION: Intravenous lidocaine reduced the propofol EC50 for Loss of Consciousness (LOC) and decreased intraoperative propofol and remifentanil consumptions in patients undergoing gynecological laparoscopy. These findings suggest a propofol- and opioid-sparing effect of intravenous lidocaine in this setting, although confirmation in larger multicenter trials is needed.

Humans↗

PubMed2026

Corneal Epithelial Alterations Associated With Cyclin-Dependent Kinase 4/6 Inhibitor Therapy in Hormone Receptor-Positive Breast Cancer.

IMPORTANCE: Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors are standard therapy for hormone receptor-positive (HR+), HER2-negative breast cancer. By blocking the G1/S cell-cycle transition, these agents may impair renewal of the corneal epithelium. No controlled study has systematically evaluated corneal epithelial changes in patients receiving CDK4/6 inhibitors. OBJECTIVE: To determine whether CDK4/6 inhibitor-based therapy is associated with cornealepithelial alterations independent of aromatase inhibitor exposure and tear film dysfunction. DESIGN, SETTING, AND PARTICIPANTS: Retrospective comparative cross-sectional study at a tertiary ophthalmology center. A total of 132 women were enrolled: 45 receiving a CDK4/6 inhibitor plus an aromatase inhibitor (CDKAI group), 44 receiving aromatase inhibitor monotherapy (AI group), and 43 age-matched postmenopausal controls without systemic oncologic therapy. EXPOSURES: CDK4/6 inhibitor (ribociclib, palbociclib, or abemaciclib) combined with an aromatase inhibitor; aromatase inhibitor alone; or no systemic oncologic therapy. MAIN OUTCOMES AND MEASURES: Prevalence and severity of punctate epitheliopathy and vortex keratopathy, assessed by a masked ophthalmologist. Secondary outcomes included Schirmer I test, tear film break-up time, and Ocular Surface Disease Index (OSDI). RESULTS: PE was present in 44.4% of eyes in the CDKAI group vs 4.7% in the AI group and 2.3% in controls (χ² = 34.31; P < .001). All moderate (13.3%) and severe/complicated (8.9%) PE cases occurred exclusively in the CDKAI group. Vortex keratopathy was observed in 13.3% of CDKAI patients and in none of the other groups (P = .025). Schirmer values, tear film break-up time, and OSDI scores did not differ among groups (all P > .05). Within the CDKAI group, PE was not associated with treatment duration (P = .963) or tear film parameters. CONCLUSIONS AND RELEVANCE: In this comparative study, CDK4/6 inhibitor-based therapy was associated with significantly higher prevalence and severity of PE and vortex keratopathy, independent of aromatase inhibitor exposure and in the absence of measurable tear film dysfunction. These findings suggest a direct cytostatic effect on the corneal epithelium. Symptom scores were low, although OSDI interpretation was limited by incomplete responses. Proactive corneal surface evaluation with fluorescein staining may be warranted during CDK4/6 inhibitor treatment.

Humans↗

PubMed2026

Characteristics of post-exercise responders versus non-responders following aerobic or isometric exercise in physically inactive adults of African and South Asian descent with high-normal blood pressure or grade I hypertension.

OBJECTIVE: To investigate interindividual variability in post-exercise hypotension (PEH) and to characterise cardiovascular and autonomic differences between responders and non-responders following aerobic and isometric exercise in adults of African and South Asian descent with elevated blood pressure (BP). METHODS: Physically inactive adults of African and South Asian descent living in Suriname (18-65 years) with high-normal BP or grade I hypertension participated in a randomised controlled crossover trial. In this randomised cross-over trial, 47 adults (50.1 ± 10.8 years; 38% male) with high-normal blood pressure or grade I hypertension completed three conditions: aerobic exercise (30 min at 40-60% heart rate reserve), isometric handgrip exercise, and a non-exercise control. Ambulatory BP was assessed over 24 h. PEH was defined as the net effect: (post-exercise - pre-exercise) - (post-control - pre-control). Participants were classified as responders if daytime BP decreased ≥5 mmHg. Arterial stiffness, cardiac, and autonomic parameters were assessed. RESULTS: Following aerobic exercise, 46% of participants were classified as systolic responders compared with 28% after isometric exercise. No baseline differences were observed in demographic or clinical characteristics between responders and non-responders, suggesting that PEH variability may reflect underlying physiological rather than clinical differences. Aerobic responders demonstrated greater reductions in aortic augmentation index (-19.4% vs. -10.9%, p = 0.05), larger increases in stroke volume (+8.1 vs. -5.3 mL, p = 0.05) and cardiac output (+1.54 ± 1.89 vs. +0.58 ± 1.60 L/min, p = 0.009), and more favourable autonomic recovery. Among all variables, only the change in cardiac output was associated with PEH magnitude (r = -0.46, p = 0.006). No consistent physiological differences were observed following isometric exercise. CONCLUSION: PEH following aerobic exercise is characterised by a distinct responder phenotype associated with greater reductions in aortic augmentation index and favourable cardiac adaptations. These findings highlight substantial interindividual variability in BP responses and support the need for individualised exercise strategies in hypertension management.

Adolescent↗

PubMed2026

Changes in heroin-related ambulance attendances following the introduction of a medically supervised injecting room in Victoria, Australia.

BACKGROUND: Injecting drug use contributes significantly to morbidity, mortality and broader social harms globally. Supervised Injecting Facilities (SIFs) are harm reduction interventions that reduce overdose risk and facilitate access to health services for marginalised individuals. While international evidence supports the effectiveness of SIFs, Australian population-level surveillance data quantifying their impact on emergency medical service utilisation remain limited. METHODS: Using data from the National Ambulance Surveillance System, we conducted a retrospective, interrupted time series analysis of heroin-related ambulance attendances within the local catchment of the Medically Supervised Injecting Room (MSIR) between January 2015 and December 2023. Supplementary analysis included comparisons with central Melbourne suburbs and the broader state of Victoria. Key intervention timepoints, including the opening of the MSIR on 30 June 2018, expansion of its operating hours in July 2019, and the COVID-19 pandemic from April 2020 to October 2021, were examined to assess changes in heroin-related attendances over time. Segmented regression models were used to assess changes in heroin-related ambulance attendance trends over time. RESULTS: At the time the MSIR opened, the model-predicted heroin-related ambulance attendance rate within the MSIR catchment was 123 per 100,000 population per month, equivalent to approximately 48 heroin-related ambulance attendances per month. Prior to implementation, the attendance rate was increasing by an estimated 0.74 per 100,000 population per month. Following the opening of the MSIR, the previously increasing trajectory reversed, with ambulance attendance rates declining by approximately 2.3 per 100,000 population per month relative to the pre-intervention trend. By the end of the study period (December 2023), the predicted monthly heroin-related ambulance attendance rate had declined to 36 per 100,000 population (approximately 14 attendances per month), representing an overall reduction of 70.7% from the time of MSIR implementation. These reductions persisted throughout the COVID-19 lockdown period and were sustained after restrictions lifted. Supplementary analysis showed no comparable reductions in the central Melbourne region or the remainder of Victoria. CONCLUSIONS: The introduction of the MSIR in Richmond was associated with a sustained reduction in heroin-related ambulance attendances within its catchment area. These findings provide strong population-level evidence that SIFs reduce acute heroin-related harms requiring emergency ambulance response, reinforcing their role as an effective harm reduction strategy within the Australian context.

Humans↗

PubMed2026

Sacral Neuromodulation in the Management of Refractory Pediatric Lower Urinary Tract Dysfunction.

INTRODUCTION: Sacral neuromodulation is currently used in the pediatric patient population for refractory lower urinary tract dysfunction (LUTD). Evidence, however, is currently limited for institutional experiences of long-term outcomes for sacral neuromodulation in the pediatric patient population. OBJECTIVE: The objective of this study is to perform a retrospective review of a large multi-institutional cohort of pediatric patients that underwent sacral neuromodulation (SNM) for refractory LUTD, focused on rates of symptom improvement, quality of life, and bowel-bladder dysfunction measures following device implantation. Secondary objectives included assessing device complication rates and device removals due to failure or successful resolution of symptoms. METHODS: We performed a retrospective cohort study of pediatric patients at three children's hospitals that underwent SNM device implantation for refractory LUTD. Patients 4-18 years of age who were diagnosed with refractory LUTD and managed at a participating institution with follow-up were included. Outcomes were evaluated at baseline and post-operatively after two-stage device implantation at initial follow-up and annually until device removal or final follow-up. RESULTS: From 2010 to 2022, a total of 205 children underwent SNM procedures at three pediatric hospital centers. 204 patients completed the two-stage procedure for permanent device implantation with a median follow-up of 3.4 years (1.3, 4.9). One hundred seventy-eight patients reported partial (25%) or complete (54%) device response/symptom improvement by final follow-up. Comparison of patient-reported validated questionnaires completed at baseline and by final follow-up visit revealed significant improvement in median Pediatric Quality of Life Inventory (PedsQL) (p = 0.004) and Vancouver Nonneurogenic Lower Urinary Tract Dysfunction/Dysfunctional Elimination Syndrome bowel-bladder dysfunction (BBD) scores (p < 0.001). Of those with any device complication (n = 43;21%), 19 patients required device revision, and 20 required complete device removal. Separately, twenty-eight patients (13%) underwent device removal due to resolution of symptoms or treatment success at a median period of 5 years (4,7). CONCLUSION: SNM use demonstrated a majority of patients reporting at least partial subjective symptom improvement following device implantation across multiple institutions by final follow-up. SNM is a viable treatment option for refractory LUTD in the pediatric patient if willing to undergo an invasive procedure and in which thorough counseling of risks and benefits has occurred.

Humans↗

PubMed2026

Weight-bearing locomotion mitigates the progression of post-traumatic knee osteoarthritis in male rodents: A systematic review and meta-analysis.

OBJECTIVE: Although knee post-traumatic osteoarthritis (PTOA) has been associated with altered loading, how weight-bearing (WB) activities should be modulated post-injury to preserve knee health remains unknown. This systematic review and meta-analysis examined the effects of WB locomotion on knee PTOA in rodents to provide insight into potential clinical implications. DESIGN: Studies published in PubMed, Cochrane Library, Embase, and CINAHL through 02/2025 and meeting the following criteria were included: 1) rodents with knee PTOA, 2) compared locomotor exercises (treadmill/wheel) to no exercise, 3) outcome measures of PTOA (OARSI/Mankin OA scores, bone quality, osteophyte condition, cartilage quality/morphology). If significant heterogeneity across studies was observed, locomotion speed, time/number of intervention sessions, frequency and duration of intervention, exercise initiation, follow-up time, animal species, PTOA model were analyzed as potential moderator variables that may influence findings. RESULTS: Twenty-two studies met the criteria, resulting in a total of 156 effect sizes (ESs) for meta-analysis (all males). A positive ES denotes less PTOA. Based on the CAMARADES checklist, 5 studies were ranked low risk of bias and 14 studies were ranked moderate risk of bias. Locomotion significantly reduced PTOA severity evaluated using OARSI/Mankin scores (ES=0.927, 95% CI: [0.590, 1.264]) and improved bone quality (ES=0.379, 95% CI: [-0.023, 0.780]) with substantial heterogeneity across studies. Follow-up analyses indicated that greater ESs for reducing OA scores were associated with a shorter duration of each training session, more training sessions, longer intervention duration, and longer follow-up time (all P≤0.004). Greater ESs for improving bone quality were associated with a longer follow-up time and later exercise initiation post-injury (both P≤0.014). Locomotion resulted in small to moderate but non-significant positive effects for isolated measures assessing osteophyte condition (ES=0.379, 95% CI: [-0.023, 0.780]), cartilage quality (ES=0.430, 95% CI: [-0.034, 0.893]), and cartilage morphology (ES=0.464, 95% CI: [-0.006, 0.934]). CONCLUSION: WB locomotion reduced the overall degree of knee PTOA in male rodents. Composite knee OA scores may be more responsive to exercise interventions than isolated cartilage/osteophyte measures. The benefits of locomotion may be more prominent with a longer follow-up time or with exercise protocols consisting of shorter but more individual sessions and longer overall intervention durations.

Animals↗

PubMed2026

HPV circulating tumor DNA as a potential prognostic and predictive biomarker in head and neck squamous cell carcinoma: a systematic review.

PURPOSE: Human papillomavirus circulating tumor DNA (HPVctDNA) has emerged as a promising prognostic biomarker in HPV-related head and neck squamous cell carcinoma (HNSCC). This systematic review aimed to synthesize current evidence on the diagnostic accuracy and prognostic value of HPVctDNA in HNSCC management. MATERIAL/METHODS: We systematically reviewed a PubMed-indexed database of studies published between January 2012 and September 2025. Eligible studies were assessed for design, primary tumor site and stage, treatment modality, HPVctDNA detection method, diagnostic accuracy (sensitivity and specificity), and reported clinical endpoints. Descriptive syntheses were performed; sensitivity and specificity were standardized to proportions and summarized as median values per group. RESULTS: A total of 60 studies, including 8,234 patients were analyzed, of which 41 (68.3%) focused exclusively on oropharyngeal squamous cell carcinoma (OPSCC) and 17 (28.3%) included mixed HPV-related HNSCC subsites and HPV-positive cancers of unknown primary. The median follow-up across the included studies was 23 months. Among the included studies, 19 were retrospective (31.7%) and 33 were prospective (55.0%), with a small proportion of cross-sectional and randomized clinical trials. Overall, 40 (66.7%) evaluated the role of HPVctDNA in a curative setting. Plasma was the most common sample type, analyzed in 55 studies (91.7%), while 5 studies also included saliva. Detection methods varied: 40 employed droplet digital PCR (ddPCR), 16 used quantitative PCR (qPCR) and 4 applied NGS-based assays. Most of these studies (38, 63.3%) evaluated the prognostic utility of HPVctDNA, while only 4 (6.7%) assessed HPVctDNA in a screening or diagnostic setting. Regarding diagnostic accuracy, the median sensitivity across evaluable studies was 91.1%, while the median specificity was 99.4%. In OPSCC-only cohorts, the median sensitivity and specificity were 89.4% and 99.4%, respectively. Dynamic changes in HPVctDNA levels during or after treatment were consistently associated with outcomes: clearance or sustained negativity correlated with higher response rates, improved progression-free survival and overall survival, while persistent positivity or increasing levels predicted disease progression and recurrence. CONCLUSIONS: HPVctDNA demonstrates high diagnostic and prognostic accuracy in HPV-related HNSCC, especially OPSCC, supporting its use for prognosis, treatment monitoring and early detection of recurrence. However, prospective interventional studies are still required to demonstrate that HPVctDNA-guided treatment decisions improve clinical outcomes before routine implementation.

Humans↗

PubMed2026

Comparative Evaluation of Virtual Reality versus Standard Nursing Care in Managing Pain and Fear during Lumbar Puncture Procedures: A Randomised Controlled Trial.

BACKGROUND: Meningitis is a serious infectious disease that can cause significant morbidity and long-term neurological problems. Although a lumbar puncture is a necessary diagnostic procedure, it is often accompanied by discomfort, anxiety, and fear, which can severely impact the patient's experience. Although there is few data on its application prior to lumbar puncture in adult patients with meningitis, immersive virtual reality (VR) has become a promising non-pharmacological technique for lowering procedural distress. Thus, among individuals undergoing lumbar punctures, this randomized controlled research assessed how well pre-procedural VR reduced pain, anxiety, and fear while enhancing patient satisfaction. OBJECTIVE: This study aims to evaluate the effectiveness of virtual reality (VR) in reducing pain and fear among adults undergoing lumbar puncture (LP) compared with standard care protocol. METHODS: A randomised clinical trial was conducted from May to October 2025, using a single-blind, true experimental design. A total of 85 patients were randomly assigned to either the VR intervention group ( n = 41) or the control group receiving standard care ( n = 44). Pain levels were assessed using a visual analogue scale. Fear was assessed using the Multidimensional Fear-of-Injection Scale. Data were analysed using SPSS version 26. RESULTS: According to the study, the findings revealed a significant reduction in pain levels among the study group following the VR intervention, with mean pain scores dropping from 7.54 ± 1.925 to 2.49 ± 0.675. In contrast, the control group showed increased pain intensity, with mean scores rising from 6.84 ± 1.842 to 8.36 ± 1.348. The VR group showed a significant reduction in fear scores across all domains, whereas no significant changes were observed in the control group. Direct fear decreased from 20.12 ± 1.71 to 9.44 ± 2.00, indirect fear from 17.24 ± 1.46 to 8.66 ± 2.24, physiological response improved from 0.34 ± 0.66 to 3.00 ± 1.00 and avoidance behaviour decreased from 16.71 ± 1.49 to 7.80 ± 1.85. CONCLUSIONS: The research shows that the use of VR prior to LP significantly reduces level of pain and fear compared to standard care. These results support VR as a non-pharmacological intervention for fear and pain to improve patient experience during invasive procedures. In contrast, the control group experienced no improvement.Trial Registration: The IRCT code for the trial was IRCT ID 20250803066743N1.

Humans↗

PubMed2026

Characterisation of HIV-1 Gag Cytotoxic T-Lymphocyte Epitopes in the Southern African Region-A Systematic Review.

During early HIV-1 infection, robust Cytotoxic T-lymphocyte (CTL) responses are mostly targeted at immunodominant Gag p24 epitopes to reduce HIV-1 viraemia to a set-point. The aim of this study was to review the current body of knowledge on HIV-1 Gag CTL epitopes in the southern African region where subtype C is prevalent. Peer-reviewed records were obtained from three databases: PubMed Central, Web of Science Core Collection, and Scopus, using the following search terms: HIV subtype C Gag epitopes, and HIV clade C Gag epitopes. The search results were restricted to countries within the southern African region, and only data published in English and between the years 2000-2025 were considered for this review. The search from the three databases produced a total of 2103 peer-reviewed records, and 49 records were included in the review. The majority of studies (58.44%) were conducted in South Africa, followed by Botswana (15.58%), Zambia (10.39%), Malawi (7.79%), Zimbabwe (6.49%) and Angola (1.30%). There were no studies identified from other southern African countries. A total of 60 Gag CTL epitopes were identified, of which 17 (28.33%) were located within the matrix protein (p17), 33 (55.00%) within the capsid protein (p24), and 4 (6.67%) within the Gag polyprotein (p2p7p1p6). The commonly detected immunodominant epitopes were mostly located within the Gag p24 protein; and included TPQDLNTML (TL9, Gag p24 48-56) and TSTLQEQIGW (TW10, Gag p24 108-117) present at 16.00% and 13.3%, respectively. The proportion of HLA-A, B and C allotypes in this systematic review were 18%, 78%, and 4%, respectively. The more common HLA-B allotypes that restrict immunodominant Gag epitopes and facilitate better control of HIV-1 were HLA-B*57, -B*58:01, -B*42:01 and -B*81:01. This systematic review has provided important insights into the description of immunodominant Gag epitopes and HLA-I alleles that contribute to the control of HIV-1 viraemia in the southern African region. It has also exposed that some CTL epitopes identified in the southern African studies are not reported on the Los Alamos HIV database (LANL HIV database). This highlights a need to have this database updated with this information as it is used as a reference for epitopes. This review could provide insights into the design of an epitope-based HIV-1 vaccine that would also be effective in the southern African region.

Humans↗

PubMed2026

Deucravacitinib 5-Year Safety and Efficacy Results in Plaque Psoriasis: A Phase 3 Open-Label Extension of Randomized Clinical Trials.

BACKGROUND: Deucravacitinib, an oral, selective, tyrosine kinase 2 inhibitor, is approved for adults with moderate to severe plaque psoriasis who are candidates for systemic therapy and for adults with active psoriatic arthritis. OBJECTIVE: We evaluated deucravacitinib safety and efficacy over 5 years in the phase 3 POETYK PSO-1, PSO-2, and long-term extension (LTE) trials in patients with moderate to severe plaque psoriasis. METHODS: PSO-1 and PSO-2 (parent trials) randomized patients 1:2:1 to oral placebo, deucravacitinib 6 mg once daily, or apremilast 30 mg twice daily. At 52 weeks, patients enrolled in the LTE trial received open-label deucravacitinib. Safety was reported as exposure-adjusted incidence rates (EAIRs) per 100 person-years (PY). Clinician- and patient-reported outcomes were analyzed using modified nonresponder imputation in patients receiving continuous deucravacitinib from day 1 (PSO-1/PSO-2) through 5 years. RESULTS: Overall, 1519 patients received one or more deucravacitinib dose; total exposure was 5046.7 PY through data cutoff (September 2, 2024). EAIRs/100 PY were comparable or decreased from the 1-year to 5-year cumulative period for adverse events (AEs) (229.23, 127.40, respectively), serious AEs (5.68, 5.06), discontinuation due to AEs (4.38, 2.09), deaths (0.20, 0.22), serious infections excluding coronavirus disease 2019 (COVID-19) (1.53, 0.94), malignancies (1.02, 0.92), major adverse cardiovascular events (0.30, 0.34), and venous thromboembolism (0.20, 0.06). Clinical outcomes were well-maintained in patients receiving continuous deucravacitinib (n = 513) from 1 through 5 years, including achievement of a ≥ 75% reduction from baseline in the Psoriasis Area and Severity Index (1 year, 72.1% [95% CI 68.2-76.1]; 5 years, 67.3% [62.0-72.6]) and a static Physician Global Assessment score of 0 (clear) or 1 (almost clear) (1 year, 57.5% [53.1-61.9]; 5 years, 52.6% [47.0-58.1]). Dermatology Life Quality Index 0 or 1 was well-maintained from 1 year (52.5% [48.0-57.1]) through 5 years (45.4% [40.0-50.8]). CONCLUSIONS: These findings demonstrate a consistent safety profile with no new safety signals and durable clinical response through 5 years of treatment with deucravacitinib. CLINICAL TRIAL REGISTRATION: NCT03624127, NCT03611751, NCT04036435.

Humans↗

PubMed2026

Adverse Experiences in Brief Meditation Practices: Randomized Controlled Trial.

BACKGROUND: Meditation has become increasingly popular in recent decades. However, relatively little remains known about the prevalence of and risk factors for adverse experiences related to a single meditation practice. OBJECTIVE: The objective of our study was to examine adverse experiences associated with 3 brief, digitally delivered meditation practices (mindfulness, self-compassion, and gratitude) relative to using the internet as usual, as well as to investigate whether preintervention characteristics could predict such outcomes. METHODS: In a secondary analysis of a randomized controlled trial using samples that were representative of the US and UK adult populations with regard to ethnicity, sex, and age, we examined adverse experiences associated with 3 brief (ie, 5 or 10 minutes) meditation practices (ie, mindfulness, self-compassion, and gratitude) relative to using the internet as usual. We also investigated the potential of using preintervention characteristics to predict such outcomes. RESULTS: A total of 5049 participants completed all preintervention measures and were randomly assigned to meditation or control conditions. Across the sample, 4.1% (204/4925) of participants reported having a distressing experience during the intervention, and 7.1% (348/4908) of participants experienced an increase in negative affect from before to after the intervention. The results showed that participants who were randomized to a brief meditation intervention were no more likely to report a distressing experience than those who were randomized to use the internet as usual (odds ratio [OR] 1.05, 95% CI 0.76-1.47; P=.76). The results also showed that participants who were randomized to a brief meditation intervention were less likely to report clinically relevant increases in negative affect relative to using the internet as usual (OR 0.63, 95% CI 0.50-0.80; P<.001). Notably, participants in the 10-minute condition had a significantly higher likelihood of reporting a distressing experience than those in the 5-minute condition (OR 1.42, 95% CI 1.07-1.89; P=.02). Preintervention characteristics showed acceptable discrimination ability to predict a distressing experience (area under the curve=0.73) and slightly lower ability to predict increased negative affect (area under the curve=0.67). CONCLUSIONS: Taken together, we found that the brief, digitally delivered meditation practices tested in this study carry risks of adverse experiences that are comparable to or lower than those of typical activities on the internet; 10-minute condition was more likely to result in distressing experiences than 5-minute condition; and adverse responses to a brief meditation practice can, at least to a certain degree, be predicted using preintervention characteristics. TRIAL REGISTRATION: Open Science Framework 94HKS; https://osf.io/94hks/overview.

Humans↗

PubMed2026

Occlusion site and outcomes in intra-arterial tenecteplase after successful endovascular therapy: a secondary analysis of the ANGEL-TNK trial.

BACKGROUND: Endovascular thrombectomy achieves macroreperfusion in large vessel occlusion (LVO) stroke, but only one-quarter of patients had excellent functional outcome. Adjunct intra-arterial (IA) tenecteplase could further improve the treatment effect, yet its efficacy across internal carotid artery (ICA) versus middle cerebral artery (MCA) M1/M2 occlusion remains unclear. OBJECTIVE: To evaluate whether IA tenecteplase improves 90-day functional outcomes in LVO patients stratified by occlusion site (ICA, MCA M1, MCA M2). METHODS: Prespecified secondary analysis of the ANGEL-TNK trial (multicenter, randomized, open-label, blinded endpoint) in 19 Chinese stroke centers. Participants were enrolled who had anterior circulation LVO, 4.5-24 hours from symptom onset, and CT angiography (CTA)/magnetic resonance angiography (MRA)-proven ICA, M1, or M2 occlusion. INTERVENTION: Randomization (1:1) to IA tenecteplase (0.125 mg/kg) or standard medical management after expanded Thrombolysis in Cerebral Infarction (eTICI) 2b50-3 reperfusion. MAIN OUTCOME MEASURE: The primary outcome was the rate of 90-day modified Rankin Scale (mRS) 0-1. RESULTS: There were 256 patients in the trial, including 71 (27.7%) ICA, 122 (47.6%) MCA M1, and 62 (24.2%) MCA M2. ICA occlusion patients treated with IA tenecteplase had higher rates of 90-day mRS 0-1 (39.4% vs 13.2%; relative risk (RR) 2.99; 95% CI 1.51 to 5.96; p=0.002) and mRS 0-3 (54.5% vs 42.1%; RR 1.30; p=0.048) versus controls, with a significant shift toward better mRS scores (median 3 (IQR 1-4) vs 4 (2-6); odds ratio (OR) 2.26; p<0.001). Post hoc analysis showed higher eTICI progression in ICA patients (51.5%) versus MCA M1 (37.9%) and M2 (25.7%). IA tenecteplase had a lower any intracranial hemorrhage within 48 hours in ICA patients (15.2% vs 39.5%; RR 0.38; p<0.001) compared with standard medical management. No significant benefits were observed in the MCA M1/M2 subgroups, and interaction effects were significant between ICA and MCA segments for functional outcomes and safety. CONCLUSIONS AND RELEVANCE: IA tenecteplase had a better functional outcome and lower hemorrhage risk in ICA occlusion compared with standard medical management but not in MCA M1/M2. Occlusion site is a critical determinant of response to IA tenecteplase. A pooled analysis of IA tenecteplase stratified by occlusion site strata is warranted.

Humans↗

PubMed2026

Effects of semaglutide and empagliflozin on markers of endothelial function in persons with type 2 diabetes: A post hoc analysis of a randomized clinical trial.

AIMS: The endothelium maintains vascular health by regulating blood flow and protecting against inflammatory damage. In type 2 diabetes (T2DM), however, hyperglycemia, hypertension, and hyperlipidemia place a significant burden on the endothelium, potentially leading to atherosclerosis and cardiovascular disease (CVD). While semaglutide and empagliflozin have been shown to reduce CVD risk in T2DM, it remains unclear whether these benefits are mediated by improved endothelial function. This post-hoc analysis explores the effects of these agents on markers of endothelial function, i.e. the reactive hyperaemic index (RHI) and the endothelial-derived cell adhesion molecules (CAMs) E-Selectin, ICAM-1, P-Selectin, and VCAM-1. METHODS: This was a post-hoc analysis of a 32-week randomized trial evaluating the separate and combined effects of semaglutide and empagliflozin on cardio-renal organ damage. One hundred and twenty participants with type 2 diabetes, age ≥ 50 were randomized to four groups (semaglutide, empagliflozin, the combination or placebo). An increase in RHI and/or a decrease in CAMs were considered beneficial. RESULTS: RHI increased compared to baseline (0.11, 95%CI [0.008;0.21], p = 0.03) but not compared to placebo in the semaglutide group (0.11, 95%CI [-0.04;0.24], p = 0.16). There was no effect on RHI in the empagliflozin group. Compared to placebo, E-Selectin decreased significantly in the semaglutide and combination groups (-9, 95%CI [-14.1;-5.1] p < 0.01 and - 9, 95%CI [-14.3; -5.2] p < 0.01, respectively). VCAM-1 increased in the same groups, compared to placebo (12.3, 95%CI[2.8;20.8] p = 0.01 and 16.2, 95%CI [7.2;24.3], p < 0.01, respectively).P-Selectin and ICAM-1 was not significantly affected in any of the groups, compared to placebo (p ≥ 0.11 and p ≥ 0.09, respectively). CONCLUSION: Semaglutide improved endothelial function compared to baseline, but not significantly versus placebo, which likely is due to limited power. CAM responses were heterogeneous, suggesting distinct roles in endothelial dysfunction and atherosclerosis. ClinicalTrialsRegister.eu: EudraCT 2019-000781-38.

Aged↗

PubMed2026

Quality of life and gender identity in females with congenital adrenal hyperplasia after genital restoration surgery: A single-center experience.

BACKGROUND: Legislation restricting surgical interventions in children with differences of sex development (DSD) has intensified debate about female genital restoration surgery (FGRS) in patients with congenital adrenal hyperplasia (CAH). Long-term patient-reported outcomes are needed regarding the optimal timing of surgery. OBJECTIVE: We aimed to assess health-related quality of life (HRQoL), gender identity, and family satisfaction regarding surgical timing and outcome in females with CAH following genital restoration surgery. STUDY DESIGN: Cross-sectional survey of CAH patients who underwent surgery between January 2007 to December 2016 at our institution. Validated instruments (KINDL questionnaire for HRQoL, Utrecht Gender Dysphoria Scale, UGDS) and structured telephone interviews were employed. RESULTS: Data on HRQoL was available for 25 patients (self- and/or parent-reported) out of 56 eligible patients (45% response rate). Median age at first surgery was 6 months (range: 3-137 months). Patients' age at time of participation ranged from 2 to 28 years. All had 21-hydroxylase deficiency (92% salt-wasting form) with Prader grades ranging from II-V. Wound dehiscence requiring secondary suturing occurred in 15% of patients with primary surgery at our center, while only one (4%) patient developed vaginal stenosis after early primary vaginoplasty. Two additional patients (8%) with prior outside surgery required vaginal revision after FGRS at age 12. HRQoL scores were comparable to healthy reference populations across most age groups. Children aged 3-6 and adolescents and young adults showed no significant difference from reference values, while children aged 7-13 showed a slight elevation. None of five patients ≥14 years demonstrated gender dysphoria (all UGDS scores <40, threshold ≥40). 14 patients and families were also interviewed by telephone. All preferred early surgical timing. No family expressed regret about the decision or preferred delayed surgery. DISCUSSION: This study provides validated intermediate-term patient- and parent-reported outcomes after FGRS in CAH. Key limitations include the small sample size, single-center design, and young age of most patients. Selection bias may exist, though participating families included those who underwent revision surgery. The absence of a non-operated comparison group reflects current clinical reality, as nearly all CAH patients with urogenital sinus underwent surgical correction. CONCLUSIONS: Females with CAH reported normal HRQoL and a comfortable female gender identity after early FGRS. The patients and their families expressed a preference for early surgery. However, there is need for longer-term follow-up to assess sexual function and reproductive outcomes as well comparison of outcomes with a non-operated group.

Humans↗

PubMed2026

Combined Effects of Nicorandil and Enhanced External Counterpulsation on Coronary Microcirculation and Exercise Capacity in Patients With Coronary Slow Flow Phenomenon: A Randomized, Controlled, 3-Arm Trial.

PURPOSE: To evaluate the combined efficacy and safety of combined nicorandil and enhanced external counterpulsation (EECP) therapy compared with respective monotherapies in patients with coronary slow flow phenomenon (CSFP). METHODS: In this prospective, randomized, 3-arm clinical trial, 309 patients with angiographically defined CSFP based on corrected TIMI frame count were assigned (1:1:1) to the Nicorandil group (N group, n = 103), the EECP group (E group, n = 103), or the Combined therapy group (N+E group, n = 103). The trial was prospectively registered at ClinicalTrials.gov (NCT07534410). IMR and CFR were measured to characterize coronary microvascular physiological status and treatment response. The primary endpoint was corrected TFC at 6 months. Key secondary endpoints included invasive physiological indices (IMR and CFR), Seattle Angina Questionnaire scores, 6-minute walk test (6MWT) distance, peak oxygen uptake via cardiopulmonary exercise testing, and the 12-month rate of re-hospitalization due to recurrent angina. FINDINGS: At 6 months, the N+E group demonstrated superior improvement in coronary hemodynamics compared to the N and E monotherapy groups, with significantly lower TFC (30.4 ± 3.5 vs 38.2 ± 3.8 and 37.5 ± 4.0, respectively; P < 0.001) and IMR (21.2 ± 2.8 vs 28.4 ± 3.2 and 27.6 ± 3.5, respectively; P < 0.001). Clinical symptoms and functional capacity showed the most substantial gains in the N+E group, with significantly higher Seattle Angina Questionnaire angina frequency scores (87.5 ± 8.8) and 6MWT distances (506.8 ± 41.8 m) compared to monotherapy groups (all P < 0.001). Furthermore, peak oxygen uptake in the N+E group increased to 23.5 ± 2.6 mL/kg/min, significantly outperforming the N and E groups (P < 0.001). During the 12-month follow-up, the observed rate of re-hospitalization due to recurrent angina was lower in the N+E group (5.8%) than in the N group (17.5%, P = 0.017), although this clinical outcome should be interpreted cautiously because the trial was powered primarily for physiological endpoints. No significant differences were observed in the incidence of adverse reactions among the 3 groups (P = 0.954). IMPLICATIONS: For patients with CSFP, the combination of Nicorandil and EECP improved coronary microvascular function, anginal symptoms, and objective exercise tolerance more effectively than either active monotherapy. The lower observed rate of angina-related re-hospitalization suggests a potential clinical benefit, but this finding should be considered exploratory and requires confirmation in trials adequately powered for clinical outcomes.

Humans↗

PubMed2026

Exploring Professional Experiences in Caring for Vulnerable Migrants in an Italian Rural Reception Centre: A Qualitative Study Using Multidimensional Textual Analysis-Professional Experiences in Rural Migrant Care.

AIM: This study aims to explore the experiences, strengths, challenges, and potential improvements for professionals in managing the complex needs of vulnerable migrants (VM) in an Italian rural reception centre. METHODS: A qualitative study using semi-structured interviews was conducted in April 2024. Data were analysed using the Automatic Analysis of Textual Data, based on Fraire's seven-step model for Exploratory Multidimensional Data Analysis. DATA SOURCES: Data were collected from 16 professionals working in a rural reception centre in southern Italy. Interviews were conducted and analysed using AATD in April 2024. FINDINGS: The analysis identified two main dimensions of professionals' roles: balancing systemic responsibilities with personal engagement and managing immediate needs versus long-term integration goals. Professionals face significant challenges, such as resource scarcity, bureaucratic inefficiencies, and emotional fatigue, which impact their well-being and the quality of care provided to migrants. Resilience, adaptability, and multidisciplinary collaboration were identified as key strengths. CONCLUSION: The study highlights the dual nature of professionals' work in reception centres, requiring them to balance operational tasks with emotional involvement in migrant care. Targeted interventions and systemic reforms are necessary to support professionals and enhance the quality of care for vulnerable migrants, particularly in resource-constrained rural settings. IMPLICATIONS FOR PRACTICE AND/OR PATIENT CARE: This study underscores the importance of providing targeted support to professionals working in reception centres, including training in intercultural competence, stress management, and coping strategies. Policies should address systemic challenges and provide resources to enhance healthcare delivery and social integration programs. REPORTING METHOD: This study adhered to the EQUATOR guidelines for reporting qualitative research (COREQ). The findings were reported in compliance with these guidelines, ensuring methodological rigour and transparency. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: This study highlights the critical need for targeted support and training for professionals working in reception centres, particularly in rural settings. To improve care for vulnerable migrants, professionals should receive training in intercultural competence, stress management, and coping strategies to better navigate the complex challenges they face. Furthermore, systemic changes are necessary to alleviate the pressures on reception centres, such as streamlining bureaucratic processes and enhancing healthcare infrastructure, particularly in rural areas where resources are limited. By addressing these needs, we can improve the well-being of both the professionals and the migrants they serve, fostering more effective support systems and better care outcomes. Additionally, fostering multidisciplinary collaboration and community engagement can contribute to more comprehensive and sustainable care models. PROTOCOL REGISTRATION: The Ethics Committee of the University of Rome Tor Vergata approved this study on 07/07/2021 (protocol registration number 160.21).

Humans↗