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PubMed2026

Non-motor symptoms and healthcare utilization before diagnosis of myasthenia gravis: a nationwide cohort study.

BACKGROUND: Non-motor symptoms have been reported prior to myasthenia gravis (MG) diagnosis. However, the temporal patterns of non-motor symptoms and healthcare utilization before MG diagnosis remain unclear. METHODS: We conducted a retrospective, population-based cohort study using the Korean National Health Insurance Service (KNHIS) database from 2011 to 2021. Incident MG cases were identified using the International Classification of Diseases, Tenth and Rare Intractable Disease codes. Individuals younger than 20  years or with missing health screening data were excluded. Each MG case was matched 1:10 by age, sex, and index date to controls. Non-motor symptoms and healthcare utilization were defined using operational criteria derived from KNHIS claims data. Rate ratios (RRs) and 95 % confidence intervals (CIs) were estimated across four prespecified intervals (0-1, 1-2, 2-5, and 5-10  years) before MG diagnosis. RESULTS: We included 8,355 MG patients and 83,550 controls (mean age, 53.7  years; male, 44 %). MG patients had higher rates of any non-motor symptoms over 10  years(RR 1.34; 95 % CI 1.30-1.39), with the sharpest increase in the year before diagnosis. Depression, anxiety, migraine, constipation, and insomnia consistently showed higher RRs across all intervals. Hospitalizations (RR 1.66; 95 % CI 1.61-1.71) and outpatient clinic visits (RR 1.10; 95 % CI 1.04-1.17) were consistently higher across 10  years, peaking during the 0-1 year before MG diagnosis. CONCLUSION: Non-motor symptoms and healthcare utilization increased years before MG diagnosis. Earlier recognition of these symptom patterns may facilitate timelier evaluation for MG and improve diagnostic pathways.

Humans↗

PubMed2026

Efficacy of high-intensity laser therapy versus ultrasound therapy in patients with knee osteoarthritis: a randomized controlled trial.

PURPOSE: High-intensity laser therapy (HILT) and ultrasound (US) are widely used for knee osteoarthritis (KOA), but comparative efficacy data remain scarce. This study compared HILT and US as exercise adjuncts in patients with KOA. METHODS: In this single-center, assessor-blinded RCT, 66 adults with KOA were randomized 1:1 to HILT or US twice weekly for 6 weeks as exercise adjuncts. The primary outcome was WOMAC total score change from baseline to 12 weeks post-treatment (minimum important change [MIC] = 10 points, applied as an approximation). Secondary outcomes included VAS, OKS, KOOS, and EQ-5D-5L. RESULTS: In ITT analysis (N = 66), the HILT group achieved a mean WOMAC reduction of 40.0 vs 8.2 points (adjusted between-group difference: -27.7 points, 95% CI: - 39.0 to - 16.5; p < 0.001, partial η2 = 0.277). At 12 weeks post-treatment, greater improvements across all secondary outcomes were observed in exploratory analyses (p ≤ 0.012). Furthermore, HILT maintained therapeutic effects up to 12 weeks post-treatment, whereas the US group experienced a gradual loss of post-treatment gains. CONCLUSION: HILT combined with exercise produced greater short-term improvements in WOMAC total score than US in patients with KOA, with exploratory findings suggesting consistent benefits in pain, function, and quality of life, and with benefits maintained up to 12 weeks after the last treatment session.

Humans↗

PubMed2026

A phase I clinical study of the safety, tolerability, pharmacokinetics and pharmacodynamics of SHR-2106, an anti-CD40 antibody, following single intravenous or subcutaneous administration in healthy participants.

BACKGROUND: SHR-2106 is a humanized IgG1 monoclonal antibody that blocks CD40-CD40L interactions and has demonstrated immunosuppressive activity and graft-prolonging effects in preclinical studies. This first-in-human Phase I study evaluated the safety, pharmacokinetics, pharmacodynamics, and immunogenicity of single intravenous or subcutaneous doses of SHR-2106 in healthy adults. METHODS: This randomized, double-blind, placebo-controlled Phase I study enrolled healthy participants. Fifty-one participants were enrolled in seven cohorts and received five intravenous doses (50-1200 mg) or two subcutaneous doses (300 and 600 mg). Safety, serum pharmacokinetics, CD40 occupancy on B cells, and anti-drug antibodies were assessed using standard clinical and bioanalytical methods. RESULTS: SHR-2106 demonstrated a favorable safety and tolerability profile, and most treatment-emergent adverse events were mild to moderate laboratory abnormalities with incidence rates comparable to placebo. SHR-2106 exhibited nonlinear pharmacokinetics consistent with target-mediated drug disposition, with a dose-dependent increase in geometric mean terminal half-life following intravenous administration (1.83-10.7 days). Absolute bioavailability after subcutaneous administration was approximately 60%. CD40 occupancy exceeded 80% within 24 h at all doses, with saturation duration increasing from 7 to 70 days across the intravenous dose range and remaining comparable between routes at matched doses. Anti-drug antibody incidence decreased with increasing intravenous dose and did not significantly affect pharmacokinetics or pharmacodynamics. CONCLUSION: SHR-2106 was well tolerated and achieved rapid and sustained CD40 engagement, supporting dose and route selection for Phase II studies.

Humans↗

PubMed2026

Excimer laser angioplasty for acute coronary occlusion: a stratified meta-analysis of efficacy against aspiration thrombectomy and conventional PCI.

Primary percutaneous coronary intervention (PCI) achieves epicardial reperfusion in most STEMI patients, yet microvascular obstruction persists in up to 60% of patients. Excimer laser coronary angioplasty (ELCA) vaporizes thrombus in situ and may reduce distal embolization, but the evidence base has not been systematically synthesized. This systematic review and meta-analysis (PROSPERO CRD420261422463) included comparative studies of adjunctive ELCA versus aspiration thrombectomy (Stratum A) or PCI alone (Stratum B) in acute coronary occlusion. Primary outcomes were final TIMI-3 flow and myocardial blush grade (MBG) 3; secondary outcomes were short-term mortality, MACCE, and slow-flow/no-reflow. A random-effects model with Hartung-Knapp-Sidik-Jonkman confidence intervals was applied to all outcomes. Certainty was assessed with GRADE. Ten studies (1 RCT, 9 observational) were included, from a total enrolled population exceeding 3,500. In Stratum A, no outcome reached significance: MBG-3 (OR 3.57, 95% CI 0.07-185.10), mortality (OR 0.31, 0.02-4.04), MACCE (OR 0.22, 0.04-1.26), TIMI-3 flow (OR 1.58, 0.67-3.75) and slow-flow/no-reflow (OR 0.78, 0.22-2.78). In Stratum B, using each study's propensity-matched data, no outcome differed significantly (TIMI-3 OR 0.88, 0.38-2.03; MBG-3 OR 1.06, 0.13-8.43; slow-flow/no-reflow OR 0.93, 0.29-3.02; mortality OR 0.44, 0.05-3.80). Composite endpoints were not pooled across incompatible follow-up horizons, and all outcomes were of very low certainty. Adjunctive ELCA-containing strategies during primary PCI were not associated with improved angiographic or short-term clinical outcomes against either comparator. Multicenter randomized trials are required before recommending clinical adoption.

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PubMed2026

Insulin, Semaglutide and Dapagliflozin in Adults With Type 1 Diabetes: Design and Methods of Triple Therapy for Type 1 Diabetes (TTT1)-An International Phase 3 Clinical Trial.

AIMS: Attaining target glycaemia can be a challenge in Type 1 Diabetes (T1D) due to insulin-induced weight gain. Adjunct therapy with modern glucose-lowering agents developed for type 2 diabetes (T2D) has great potential but may be insufficiently efficacious and carries risks of hypoglycaemia and ketosis. We designed the first Phase 3 clinical trial to assess the efficacy and safety of adding a Glucagon-Like Peptide 1 receptor agonist (GLP-1RA) and a Sodium-Glucose Co-transporter (SGLT2) Inhibitor to insulin therapy in overweight and obese adults with T1D and glycaemia above target (HbA1c 7.5%-11.0% inclusive) (NCT03899402). MATERIALS AND METHODS: In Period 1, participants are randomized 2:1 (open label) for 26 weeks to semaglutide and insulin (uptitrated to 1.0 mg weekly) or standard insulin therapy. In Period 2, those randomized to semaglutide and insulin in Period 1 are further randomized (double-blind) for 26 weeks to dapagliflozin (10 mg daily) or placebo, in addition to semaglutide. The primary objective is to compare change in HbA1c on 'triple therapy' (dapagliflozin, semaglutide and insulin) with 'dual therapy' (placebo, semaglutide and insulin). Secondary objectives include comparisons of triple therapy with standard insulin therapy and dual therapy (semaglutide and insulin) with standard insulin therapy. Safety outcomes include hypoglycaemia and ketosis. A sample size recalculation during the trial based on analysis of masked data revised the original recruitment target from 114 to 82 participants. CONCLUSION: The TTT1 trial will provide clinically useful information on combination adjunct therapy in the treatment of T1D.

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PubMed2026

Stretched penile length in boys with hypospadias: Population-based analysis using validated nomogram.

BACKGROUND: Hypospadias affects 1 in 200-300 male births. Parents are often concerned about penile adequacy beyond the urethral defect itself, yet few studies have systematically compared stretched penile length (SPL) in hypospadias against population-based reference standards. OBJECTIVE: To evaluate SPL distribution patterns in boys with Types I and II hypospadias and compare them with established normative data. METHODS: The authors studied 876 consecutive boys aged 1-14 years with unoperated Types I (distal) and II (mid-shaft) hypospadias. Two observers independently measured SPL using the validated SPLINT technique. The SPL measurements were compared against age-matched normative data from 1276 Indian children. Exact binomial probability tests were used for percentile distributions, chi-square tests for subtype comparisons and t-tests for mean deviations. RESULTS: The cohort included 479 Type I and 397 Type II cases. SPL distribution showed a marked leftward shift: 71% fell below the 50th percentile (expected 50%, p < 0.001) and 41.5% below the 25th percentile. Lower percentiles were overrepresented, 20.7% were below the 10th percentile and 20.8% in the 10th-25th range. Upper percentiles were depleted: only 7.4% in the 75th-90th range and 1.7% above the 90th percentile (all p < 0.001). Mean SPL was reduced by 6.8% (95% CI: -8.18 to -5.42%) in Type I and 7.5% (95% CI: -9.05 to -5.92%) in Type II. The two subtypes showed no significant distributional difference (χ2 = 6.22, p = 0.18), suggesting that meatal position does not predict SPL reduction. CONCLUSIONS: Boys with distal and mid-shaft hypospadias show clinically meaningful SPL reduction that follows a continuous distribution rather than an all-or-none pattern. SPL reduction appears independent of meatal position. These findings support routine SPL assessment using population-specific references and can guide preoperative counselling.

Humans↗

PubMed2026

Understanding FDA's reasons for nonapproval: A systematic review of complete response letters in cell and gene therapy.

BACKGROUND AIMS: Cell and gene therapy products face unique regulatory challenges due to their biological complexity and the stringent expectations for manufacturing control, analytical testing, and clinical assessment. As the pipeline grows, understanding the drivers of FDA non‑approval is increasingly important for improving first‑cycle success and reducing development delays. In this study, we aimed to characterize the frequency and impact of refuse‑to‑file actions, major amendments, and complete response letters issued for biologics licensing applications; and to identify recurring patterns of deficiencies contributing to delayed approval. METHODS: Publicly available documents were extracted from the FDA website. Data from each approved cell and gene therapy product's regulatory history-including complete responses, major amendments, inspection timing, and cited deficiencies-were compiled and categorized across clinical, quality, and labeling domains. RESULTS: Analysis showed that informational deficiencies were common across modalities. Major amendments occurred in roughly half of applications, and complete responses had the most significant impact. Quality deficiencies appeared in all complete responses and were the predominant barrier, while clinical and labeling issues were less frequent but meaningful when present. CONCLUSION: Overall, these findings highlight the need for proactive FDA engagement, comprehensive readiness, and early inspection preparation to reduce regulatory risk and improve first cycle approval outcomes.

Humans↗

PubMed2026

Effects of Cognitive Behavioral Couple Therapy With Integrated Mindfulness on Mindful Attention, Depressive Symptoms, and Dyadic Adjustment in Low-Income Couples: A Pilot Randomized Clinical Trial.

Psychosocial distress can exacerbate marital conflict, maladjustment, and mental health vulnerability. This pilot randomized clinical trial examined cognitive-behavioral couple therapy (CBCT) integrated with mindfulness in low-income Brazilian couples (per-capita household income up to one minimum wage). Thirty-four participants (17 heterosexual couples) were randomized (independent computer-generated sequence) to an experimental (n = 16) or waitlist control group (n = 18). We assessed dyadic adjustment, mindful attention, marital social skills, and depressive symptoms (R-DAS, MAAS, IHSC, BDI-II) at baseline, post-treatment, and 3-month follow-up. The intervention was eight 80-min conjoint sessions plus daily home exercises. Time × group effects favored the experimental group for dyadic adjustment, mindful attention, and depressive symptoms (all p < 0.001, = 0.20-0.37), but not marital social skills (p = 0.14). Because two outcomes differed at baseline, effects were confirmed with baseline- and dependence-adjusted sensitivity analyses. These findings provide preliminary evidence that CBCT with mindfulness may benefit disadvantaged couples.

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PubMed2026

Relationship between menopausal hormone therapy and incidence risk of breast cancer: systematic review and meta-analysis.

BACKGROUND: Menopausal hormone therapy (MHT) is widely prescribed for alleviating menopausal symptoms. Prior studies have mainly focused on individual hormone therapy formulations. This meta-analysis comprehensively synthesized evidence across various regimens to systematically evaluate the association between MHT and breast cancer risk. MATERIALS AND METHODS: We systematically searched CNKI, Wanfang, PubMed, and Web of Science from inception through August 2024. Eligible studies examining breast cancer risk following MHT were independently screened and assessed by two reviewers. The review and meta-analysis followed PRISMA guidelines. RESULTS: Thirty-four studies were included. The random-effects model showed a significant but heterogeneous overall association (OR = 1.15, 95% CI: 1.09-1.22; I² = 92.4%). Subgroup analysis identified hormone type, use status, and region as key determinants (P for interaction < 0.001). Stratification by hormone type resolved much of the heterogeneity, revealing risk confined to estrogen-progestin therapy (EPT; OR = 1.44, 95% CI: 1.26-1.64), while estrogen-only therapy (ET) showed no overall association (OR = 1.00, 95% CI: 0.91-1.10). Study type, region, and sample size were significant effect modifiers. For ET, randomized controlled trials demonstrated a protective effect (OR = 0.78, 95% CI: 0.70-0.87), contrasting with neutral findings from observational studies. CONCLUSIONS: MHT is associated with a modest but significant increase in breast cancer risk, primarily driven by EPT. This risk was not observed with ET in observational studies, though trials suggested a protective effect. Crucially, the association shows marked geographical heterogeneity, indicating risk is modified by regimen and regional factors.

Humans↗

PubMed2026

Effectiveness of psychologically informed physical therapy, tendon-specific exercise program and routine physical therapy in prolonged unilateral shoulder pain and symptom correlations with imaging: a single-center, randomized, parallel-group, three-arm study (RESPECT).

BACKGROUND: Shoulder complaints are one of the most common musculoskeletal ailments. Patient-specific characteristics such as obesity, depression and physical labor are established risk factors, whereas imaging findings are common and associations between specific imaging findings and symptomatology is limited. General exercises are considered useful in treatment whereas evidence for specific tendon exercises is lacking. Biopsychosocial model is also recommended, but has not been extensively studied concerning shoulder symptoms. This article describes the study protocol designed to evaluate the effectiveness and the cost-effectiveness of routine and specific physical therapy (PT) interventions. Imaging is performed for descriptive, longitudinal and imaging-symptom correlation studies. METHODS: The Rehabilitation of Shoulder Pain: Evaluation and Clinical Trial (RESPECT) is a randomized three-arm parallel-group study involving 300 participants aged 20 to 60 years with prolonged unilateral shoulder pain. Participants will receive either routine PT, physiotherapist-guided tendon-specific exercise program or psychologically informed PT. Bilateral shoulder radiographs, ultrasound and magnetic resonance imaging will be done at the baseline and at 12 and 36 months. Electronic surveys will be completed at the baseline and at 3, 6, 12 and 36 months. The primary outcome will be patient-specific functional scale (PSFS) at 12 months, analyzed using analysis of covariance (ANCOVA), adjusted for baseline PSFS. DISCUSSION: RESPECT will provide systematic and controlled data regarding different PT interventions in prolonged shoulder symptoms, which is currently limited. Being one of the most common sources of musculoskeletal pain, improved management could reduce symptom-related burden and prolonged functional impairment at individual and population level. CLINICALTRIALS: gov; Registration number NCT07235969; Registered November 18th, 2025; Version: 1.0.

Humans↗

PubMed2026

Treatment of Hot Flashes in Men With Prostate Cancer Undergoing Androgen Deprivation Therapy.

BACKGROUND: Hot flashes are common and often debilitating side effects of castration therapy; a cornerstone in the treatment of metastatic prostate cancer (PCa) as well as in localized or locally advanced PCa when combined with radiotherapy. The evidence for relieving vasomotor symptoms is limited. This systematic review presents both pharmacological and non-pharmacological interventions for treating hot flashes in men with PCa undergoing castration therapy, primarily androgen deprivation therapy (ADT). METHODS: a systematic literature search was conducted in PubMed using ("hot flash*" OR "hot flush*" OR "vasomotor*") AND ("prostate") as keywords. Studies with intervention for hot flashes due to castration therapy, estimation of treatment response (e.g., reduction in frequency or impact on quality of life) and patients with PCa (any stage) were eligible. RESULTS: Of 469 papers, 35 were included in the review. The included studies evaluated cyproterone acetate, estrogen or estrogen derivatives, progesterone derivatives, selective serotonin reuptake inhibitors (SSRIs), gabapentin, oxybutynin, and clonidine, as well as non-pharmacological interventions such as acupuncture, cognitive behavioral therapy (CBT), and dietary supplements (e.g., Dong Quai/Angelica Sinensis, Serelys Homme, soy protein, and Salvia officinalis). Across all blinded pharmacological interventions, the relative reduction in hot flash frequency ranged from -21% to -84%, and the placebo effect was between -19% and -30%. CONCLUSION: Hormonal agents such as cyproterone acetate and estrogen appear to be the most effective treatments, although they are associated with side effects. Non-pharmacological options like acupuncture and CBT may offer some benefit, while dietary supplements seem to be ineffective. Future studies are needed also to evaluate newer treatments, such as fezolinetant, in this patient population.

Humans↗

PubMed2026

A translational framework for early-phase inner-ear gene therapy: clinical trial design, regulatory strategy, and ethical considerations.

PURPOSE OF REVIEW: Hereditary hearing loss has historically been approached as a diagnostic category rather than a therapeutically modifiable disease. Recent advances in molecular genetics, cochlear gene delivery, and first-in-human clinical trials are changing that. This review summarizes contemporary progress in the genetics of hearing loss, with emphasis on emerging gene-based therapies, clinical trial design, regulatory and ethical considerations, and practical implications for otolaryngologists as biologic treatment enters clinical practice. RECENT FINDINGS: Early clinical trials targeting OTOF -related DFNB9 deafness have demonstrated satisfactory safety profiles and meaningful auditory recovery, establishing the first proof-of-concept for cochlear gene therapy in humans, culminating in the April 2026 FDA approval of Otarmeni. Genetic diagnoses are increasingly informing prognosis, cochlear implant counseling, and therapeutic candidacy. Preclinical research continues to expand toward recessive, dominant, and syndromic hearing loss using gene replacement, antisense, RNA interference, and genome-editing strategies. Substantial challenges remain, including heterogeneous outcome measures, uncertain long-term efficacy, regulatory complexity, and inequitable global access. SUMMARY: The genetics of hearing loss is transitioning from a diagnostic modality to an interventional one. Widespread clinical impact will require advances in vector engineering, equitable implementation, multidisciplinary counseling, and integration with established rehabilitation pathways. For otolaryngologists, genetic literacy is becoming essential to contemporary hearing care.

Humans↗

PubMed2026

The effect of combining visuo-vestibular exercises with manual therapy and exercise on sensorimotor function in chronic neck pain: A randomized controlled trial.

OBJECTIVE: To investigate whether adding visuo-vestibular exercises to standard manual therapy and exercise produces superior improvements in sensorimotor function, pain, balance, and functional disability in adults with chronic neck pain. METHODS: This prospective, randomized controlled trial enrolled 58 adults with chronic neck pain (≥3 months) allocated to a manual therapy and exercise group (MtE; n = 29) or MtE plus visuo-vestibular exercises (MtE-VVE; n = 29). Both groups completed 12 supervised sessions over six weeks with a daily home exercise programme. Outcomes were assessed at baseline, 6 weeks, and 12 weeks, and included pain intensity (Visual Analog Scale [VAS]), upper extremity reaction time, computerized posturography, the Neck Disability Index (NDI), and cervical muscle endurance. RESULTS: Fifty-four participants (27 per group) completed the study. Both groups improved significantly across all outcomes (p < 0.001). At 12-week follow-up, the MtE-VVE group demonstrated superior outcomes: activity-related pain was reduced by an additional 2.00 cm (95% CI: 0.75-3.25; p = 0.005), bilateral reaction time improved by 1.70 s (p = 0.001), eyes-open mediolateral sway decreased by 0.50 mm (p < 0.001), NDI score was 6.30 points lower (95% CI: 3.42-9.18; p < 0.001), and cervical flexion and extension endurance improved by 12.00 s and 27.70 s, respectively (p ≤ 0.020). CONCLUSION: Adding visuo-vestibular exercises to standard manual therapy and exercise produces clinically meaningful and sustained improvements in activity-related pain, sensorimotor function, postural control, and functional disability in adults with chronic neck pain, and may be recommended as an effective adjunctive intervention.

Humans↗

PubMed2026

Effects of automated massage chair therapy on mental health and physical health: A comprehensive study.

BACKGROUND AND OBJECTIVE: Automated massage chair therapy is a non-pharmacological intervention widely believed to enhance wellness, yet evidence regarding its effects remains limited. This 3-part study evaluated the effects of automated massage chair therapy on mental and physical health. METHODS: In Part 1, 20 moderately stressed students were randomized to receive a 20-minute automated massage chair therapy session followed by a 20-minute control session, or vice versa, with a 48-hour washout period. Blood pressure (BP), heart rate (HR), electroencephalogram (EEG), State-Trait Anxiety Inventory (STAI), and Visual Analog Scale (VAS) were measured. In Part 2, 20 hypertensive hospital staff received three 20-minute automated massage chair therapy sessions on alternate days. BP, HR, and skin blood flow (SBF) were measured. In Part 3, 20 hospital staff with chronic low back pain received three 20-minute automated massage chair therapy sessions on alternate days. Electromyogram (EMG) and VAS were measured. RESULTS: Automated massage chair therapy significantly reduced diastolic blood pressure (DBP), HR, stress, and anxiety among moderately stressed students. In hospital staff with hypertension, SBF did not change significantly, whereas BP and HR decreased significantly after automated massage chair therapy. In hospital staff with chronic low back pain, low back function improved, and pain was significantly reduced after automated massage chair therapy. CONCLUSION: These findings indicate that automated massage chair therapy may help reduce stress, lower blood pressure, and alleviate low back pain.

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PubMed2026

Identifying biomarkers of accelerated ageing in cancer patients from routine clinical data.

INTRODUCTION: Cancer and ageing have a bidirectional relationship: age is the strongest risk factor for cancer, and cancer and treatments can accelerate ageing. Therefore, biological age can differ from chronological age; biomarkers are needed to stratify interventions to minimise accelerated ageing. METHODS: PhenoAge was calculated from routine blood test results of patients attending a Geriatric Oncology clinic. PhenoAgeAccel was the residual from a regression of PhenoAge against age. RESULTS: Data were available for 173 patients (62% male). Mean PhenoAge was higher than age (84.3 (12.6) vs 76.2 (7.24), p < 0.001), though the two were correlated (r = 0.579, p < 0.001). Unlike age, PhenoAge and PhenoAgeAccel were associated with one-year mortality (PhenoAge OR=1.083, 95% CI: 1.038-1.136; PhenoAgeAccel OR=1.096, 95% CI: 1.047-1.155). PhenoAge correlated with Clinical Frailty Score and Timed Up and Go (CFS: Rs=0.31, p < 0.001; TUG: Rs=0.25, p < 0.005); there were no correlations with age. PhenoAgeAccel correlated with the number of CGA interventions made (Rs=0.17, p < 0.05), unlike age and PhenoAge. Patients with diabetes mellitus had a higher PhenoAgeAccel compared to those without (3.40 vs -1.71, p = 0.002). In patients receiving systemic anti-cancer treatment, patients with PhenoAgeAccel calculated pre-treatment had less age acceleration than those with PhenoAgeAccel calculated post-treatment, both overall (2.18 vs -2.87; p = 0.048) and in matched samples (n = 21, 7.76 vs -2.87, p < 0.001). CONCLUSIONS: PhenoAgeAccel is a greater predictor of risk than chronological age in older people with cancer. This makes it a promising biomarker to stratify patients for holistic geriatric assessment, dose reductions, or future geroprotective measures which could be integrated within electronic healthcare record systems.

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PubMed2026

Acute Performance, Mechanical and Thermal Effects of Isometric Conditioning Versus Standardized Volleyball Pre-Training Activation in Highly Trained Male Players.

This study compared acute performance, neuromuscular, and thermal responses to a maximal isometric conditioning activity (ICA) versus a standardized volleyball pre-training activation (VPA) in highly trained male volleyball players, and to explore putative mechanisms underpinning post-activation performance enhancement (PAPE) considering training load. In a randomized crossover, 14 men (27 ± 3 y) completed two sessions: VPA (mobility/plyometric drills; 9 min), and ICA comprising 3×5×3-s maximal isometric back-squat contractions (knee angle 120°; 3-min inter-set rest). Countermovement jump (CMJ) height (primary), relative peak power (PP), RSImod, and contraction time (CT) were recorded pre and 3, 6, 9, and 12 min post. Rectus femoris muscle viscoelastic properties and skin surface temperature (SST) were assessed at matched time points. Analyses used repeated-measures ANOVA, responder analysis, correlations, and regression. Period×Sequence interactions favored ICA for CMJ and PP when delivered in Period 2 (lower training volume): ∆CMJ was higher under ICA versus VPA (p = 0.005, d = 1.20); PP likewise greater (p = 0.026, ηp2 = 0.35). ICA yielded more beneficial responders than VPA (9/14 vs 1/14; McNemar exact p = 0.021). In Period 2, reductions in rectus femoris muscle stiffness independently predicted CMJ gains (β_std = -0.495, p = 0.005), whereas SST changes did not (p = 0.974). RSImod and CT showed no differences. A brief, high-effort isometric squat protocol was associated with superior acute improvements in jump performance compared with a standard volleyball warm-up, but this advantage emerged specifically when the preceding training volume was reduced (Period 2), suggesting that residual fatigue from training may reduce the effects of PAPE. Gains align with neuro-mechanical rather than thermal mechanisms, supporting ICA as a practical, equipment-minimal priming strategy for elite volleyball.

Humans↗

PubMed2026

Animal-assisted therapy in pediatric urodynamics.

INTRODUCTION/BACKGROUND: Urodynamics (UDS) is associated with high levels of patient anxiety/discomfort. Children are often unable to complete UDS, with anesthesia needed to place catheters. Animal-assisted therapy (AAT) has been used in a variety of settings, but it has not been studied for UDS before. OBJECTIVE: To determine if AAT can increase success of completing UDS testing without anesthesia in children who were previously unable to perform UDS, along with decreasing distress levels. STUDY DESIGN: We performed a pilot case series of 7 patients (2 female, 5 male) aged 4-16 (mean 9.7) years who previously were unable to complete UDS awake, with AAT prior to and during the UDS procedure. A visual analog scale (VAS) was used to measure patient stress levels before and after AAT. RESULTS: We were able to successfully complete UDS testing with AAT in 6 of the 7 patients (85.7%) without the need for anesthesia. VAS scores decreased from before to after AAT (5.4-3.6, p = 0.020) but with discrepancy when compared to UDS success. DISCUSSION: Our study was the first to describe AAT during UDS. Our preliminary data found AAT to be feasible in UDS. Subjective distress may not correlate with procedural success. AAT in UDS may be more beneficial in certain populations, such as anxious children who previously were unable to tolerate UDS, and not in others such as severe neurodevelopmental conditions. Our study was limited by the small sample size, a single provider, single center, single therapy dog, inclusion of a specific population of patients, and no control group due to this being a pilot study. CONCLUSION: AAT for certain children undergoing UDS testing could help improve the ability to complete the testing without anesthesia. Further studies are needed to fully demonstrate its usefulness in UDS.

Humans↗

PubMed2026

Adeno-Associated Virus Gene Therapy Translation: Lessons from Early Regulatory Meetings.

The Platform Vector-Gene Therapy (PaVe-GT) program is a National Institutes of Health (NIH) initiative that aims to develop adeno-associated virus (AAV) gene therapies for four monogenic rare diseases, two organic acidemias and two congenital myasthenic syndromes. PaVe-GT's platform-based approach identifies and diminishes redundancies and applies efficiencies in preclinical, clinical, and regulatory activities. The program's hypothesis is that implementing these efficiencies can accelerate clinical trial initiation. Based on its platform-centric experience and public-serving mission, the PaVe-GT program actively shares its scientific and regulatory learnings with the public to benefit the development of similar gene therapy products for rare diseases. PaVe-GT's first investigational AAV gene therapy candidate is AAV serotype 9 human propionyl-CoA carboxylase alpha subunit (AAV9-hPCCA) for propionic acidemia caused by PCCA deficiency, which received initial feedback from the Food and Drug Administration (FDA) in an INitial Targeted Engagement for Regulatory Advice on CBER/Center for Drug Evaluation and Research (CDER) ProducTs (INTERACT) meeting. Upon further product development that took into consideration the FDA's initial advice, the program obtained the Agency's feedback in pre-investigational new drug (IND) (Type B) and Type C meetings. Here, we share our experience from these meetings, including strategy, preparation, pre- and post-meeting feedback from the FDA, and lessons learned during the AAV9-hPCCA regulatory process, which the program plans to apply across the PaVe-GT platform. Topics discussed in the regulatory meetings included animal model and efficacy studies, toxicology study plans, manufacturing of the investigational AAV product, and clinical trial design. The main lessons learned from the pre-IND and Type C meetings for AAV9-hPCCA are: (1) Pharmacology/Toxicology studies in a single rodent species are sufficient for filing an initial IND; (2) FDA feedback guides product quality improvements and early development of a quantitative potency assay; (3) use of biomarkers as potential surrogate endpoints in a future efficacy trial benefits from collection of data in the natural history study and the first-in-human Phase 1/2 study; and (4) evidence from the Phase 1/2 clinical trial could be leveraged to support a license application. Lightly redacted regulatory documents and comprehensive templates developed by the PaVe-GT team are available on the PaVe-GT website.

Dependovirus↗