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PubMed2026

Repeated scoring with the adult appendicitis score improves the sensitivity and the specificity of appendicitis diagnosis in patients with early equivocal signs of appendicitis: a secondary analysis.

PURPOSE: The utilization of computed tomography in the early stage of acute appendicitis may result in overdiagnosis and unnecessarily expose patients to ionising radiation. The Adult Appendicitis Score (AAS) can be used to select patients for imaging. Observation and re-scoring in the DIAMOND trial reduced the need for imaging. Now, we wanted to determine if the change in AAS (∆AAS) can serve as a diagnostic tool to select patients for imaging even more precisely. METHODS: Eighty-eight patients with early equivocal appendicitis participated in the observation arm of the DIAMOND trial. The data for these patients were reanalysed, and ∆AAS during the observation was calculated. The baseline AAS, final AAS, and the change in C-reactive protein (∆CRP) were selected as reference standards. RESULTS: Eighty-three patients with complete data were included in the analysis. The AUROC (Area Under the Receiver Operating Characteristic) values are as follows: ∆AAS, 0.932 (95% CI 0.868-0.996); baseline AAS, 0.629 (95% CI 0.498-0.760); final AAS, 0.936 (95% CI 0.886-0.987); and ∆CRP, 0.796 (95% CI 0.696-0.897). Using receiver operating characteristic curves, we established the thresholds for low (AAS ≤ -2), intermediate (AAS -1 to 0), and high (AAS ≥ 1) probability of appendicitis. The negative predictive value for the low-probability group and the positive predictive value for the high-probability group concerning acute appendicitis were 97% and 94%, respectively. CONCLUSION: Patients with equivocal signs of appendicitis may benefit from short observation and the calculation of ∆AAS to reduce overdiagnosis and exposure to excessive imaging. REGISTRATION: The DIAMOND trial was officially registered on ClinicalTrials.gov (NCT02742402) on April 13, 2016.

Adult↗

PubMed2026

The efficacy of non-invasive brain stimulation interventions in obsessive-compulsive disorder management: A network meta-analysis of randomized controlled trials.

Non-invasive brain stimulation (NIBS) has been widely used as an alternative treatment for obsessive compulsive disorder (OCD). However, the most effective NIBS parameters are unclear. To compare the efficacy of NIBS in OCD. We conducted a systematic review and network meta-analyses (NMA) to combine direct and indirect comparisons of NIBS.Systematic searches were conducted in Cochrane CENTRAL, EMBASE, PubMed, and Web of Science from inception to June 20, 2025. Forty-two randomized sham-controlled trials (n = 1456) were included. All statistical analyses were conducted with R statistical software. Bayesian NMAs mainly using the BUGSnet package and gemtc package. Five NIBS protocols produced statistically significant reductions in Yale-Brown Obsessive Compulsive Scale (Y-BOCS) scores compared with sham stimulation: high-frequency rTMS over the FzFCz (Hf-rTMS-FzFCz; MD -11.77, 95% CrI -20.62 to -3.09), low-frequency rTMS over F3F4 (Lf-rTMS-F3F4; MD -9.93, 95% CrI -18.07 to -1.65), low-frequency rTMS over FCz (Lf-rTMS-FCz; MD -3.25, 95% CrI -6.06 to -0.40), high-frequency deep TMS over FzFC (Hf-dTMS-FzFC; MD -6.48, 95% CrI -12.32 to -0.50), and 2 mA anodal tDCS over F3 with cathodal over Fp2 (MD -9.34, 95% CrI -16.01 to -3.03).For secondary outcomes, high-frequency deep rTMS over FzFCz produced the largest reduction both in depressive symptoms (SMD -1.24, 95% CrI -1.92 to -0.55) and anxiety scores (SMD -1.88, 95% CrI -2.62 to -1.11), but had no effect on Clinical Global Impression-Severity (CGI-S) scores.Specific NIBS protocols are safe and effective adjunctive treatments for OCD, with promising yet inconclusive improvements in comorbid depressive symptoms. Further high-quality, head-to-head trials are needed.

Humans↗

PubMed2026

Secretory Phospholipase A2 in Patients With Sickle Cell Disease Hospitalized for Vaso-Occlusive Pain Episodes.

BACKGROUND: Secretory phospholipase A2 (sPLA2) is an inflammatory mediator linked to acute chest syndrome (ACS) in sickle cell disease (SCD), a serious complication that can develop during an acute vaso-occlusive pain episode (VOE). Plasma sPLA2 levels have been proposed as a potential biomarker for predicting ACS onset. OBJECTIVE: To assess serial plasma sPLA2 levels in 105 pediatric patients hospitalized for SCD-VOE and determine the effects of arginine therapy compared to placebo. PROCEDURES: This is a pharmacokinetics/pharmacodynamics and randomized controlled trial of intravenous arginine therapy. Statistical methods included t-tests, chi-square, and correlation analyses. RESULTS: Mean age was 12.7 ± 3.7 years, 48% were male, 67% had Hb-SS, and 70% were prescribed hydroxyurea. Using a previously established SCD-specific cutoff of 48 ng/mL, presenting sPLA2 levels were elevated in 33% of patients (mean sPLA2 level 85.7 ± 32.9 ng/mL). SPLA2 elevation in the emergency department was more common in patients with ACS compared to those without ACS (64% vs. 30%; p = 0.02; negative predictive value of 94%). Peak sPLA2 levels were significantly higher in febrile (n = 34) versus afebrile patients (n = 71;101.0 ± 45.3 vs. 48.7 ± 35.4 ng/mL; p < 0.0001). Among subjects with elevated baseline sPLA2, arginine therapy resulted in a significant reduction in sPLA2 levels by discharge compared to placebo (-27.8 ± 38.1 ng/mL; p = 0.002; n = 23 vs. -15.0 ± 41.2 ng/mL; p = 0.23; n = 12). CONCLUSIONS: SPLA2 is an underutilized biomarker of ACS given accumulating evidence of its role. In particular, low levels may identify patients at low risk for ACS. Arginine therapy may modulate inflammation in patients with SCD during VOE and/or ACS. TRIAL REGISTRATION: ClinicalTrials.gov identifiers: NCT02447874; NCT02536170.

Humans↗

PubMed2026

Mortality of Individuals With PRNP Variants Associated With Prion Disease in the United States, 1998-2024.

BACKGROUND AND OBJECTIVES: To characterize the survival of individuals with pathogenic PRNP variants-including to estimate annual hazards, to judge the accuracy of previously reported survival data, and to evaluate the utility of public record searches in determining vital status. METHODS: In this single-center cohort study, we gathered data on individuals who received positive antemortem PRNP genetic tests at the US National Prion Disease Pathology Surveillance Center (NPDPSC), including both diagnostic tests in symptomatic individuals, and predictive tests in asymptomatic individuals. Genetic test and autopsy results were queried from the NPDPSC database, and public record searches were conducted using online tools. RESULTS: Four hundred four individuals received positive genetic test results. Of 206 cases symptomatic at the time of genetic testing, 188 are likely now deceased based on typical disease duration for their genetic variants. Combined autopsy and public record searches in combination confirmed 174 of these deaths, for an estimated 92.6% sensitivity. We evaluated the age-dependent penetrance of the reportedly highly penetrance variants D178N and E200K and the reportedly low-penetrance variant V210I. Among 99 initially asymptomatic individuals with the pathogenic E200K variant, more than 936 person-years of follow-up, 18 deaths were observed, significantly fewer than 27.4 expected according to life tables based on retrospective data. The age-dependent penetrance of E200K calculated from these longitudinal data was significantly lower than that from retrospective data, with 69% penetrance by age 80 and a median age at death of 75. For the pathogenic D178N variant, the median age at death was 57, which was numerically later, but not significantly different from, that seen in retrospective data. For V210I, just 2 deaths occurred, both after age 90, consistent with minimal penetrance. DISCUSSION: Our data support high penetrance of PRNP D178N and E200K variants and low penetrance of V210I. For E200K, the age at onset distribution appears to be shifted slightly later, and lifetime risk slightly lower, than previously reported. Autopsy data and public death records in combination were sensitive and concordant for determining long-term outcomes, but additional prospective data should be gathered to support future preventive trials.

Journal Article↗

PubMed2026

Direct Oral Anticoagulants as Primary or Secondary Treatment for Heparin-Induced Thrombocytopenia (HIT) and Associated Thromboembolism (HITT)-A Meta-Analysis.

INTRODUCTION: Heparin-induced thrombocytopenia (HIT) is associated with a high risk for thrombosis. The role of direct oral anticoagulants (DOACs) is still emerging and data are limited considering efficacy and safety among patients with HIT. The aim of this review is to evaluate current data on DOACs as primary or secondary treatment among patients with HIT. METHODS: This is a systematic review utilising Pubmed, Scopus and Embase online databases. Eligible studies were published up to December 2024 evaluating DOACs as primary or secondary treatment among patients with HIT and/or associated thrombosis (HITT). Primary outcomes included thrombosis rate (TR) and bleeding rate (BR) during follow-up. RESULTS: A total of 44 publications were included (29 case reports, 5 case studies and 10 cohort studies [n > 10 patients]). Regarding treatment, 19 articles evaluated only rivaroxaban, 7 articles only apixaban, 11 articles only dabigatran and 7 articles more than one regimen. A total of 352 patients were included. Overall, 190 patients (53.8%) were given DOAC as primary treatment whereas 162 patients were given a parenteral treatment first and continued with a DOAC. Mean nadir platelet count at diagnosis was 63 000/μL. HITT rate was 190/352 (53.9%; 8% had arterial thrombosis). Mean follow-up was 7.6 months. TR was 20/352 (Pooled proportion = 0.064 [95% CI = 0.042-0.092]) (30% of them were new thromboses without initial thrombosis), and BR was 9/352 (Pooled proportion = 0.039 [95% CI = 0.022-0.062]). Finally, there was no difference found regarding TR and BR between primary or secondary treatment, and among different regimens. CONCLUSIONS: DOACs are associated with low rates of thrombosis and major bleeding among patients treated for HIT or HITT, either as primary or secondary treatment. However, the certainty of evidence is very low because of the quality and limitations of the available studies.

Humans↗

PubMed2026

Impact of estimated total blood volume on NT-proBNP response to angiotensin receptor-neprilysin inhibition in acute heart failure: Insights from the PREMIER study.

BACKGROUND: Sacubitril/valsartan (Sac/Val) reduces N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels in acute heart failure (AHF), particularly in patients with reduced ejection fraction. However, whether estimated total blood volume (TBV), calculated using anthropometric equations, is associated with heterogeneity in biomarker response remains uncertain. METHODS: This post hoc exploratory sub-analysis of the PREMIER randomized trial evaluated whether baseline estimated TBV was associated with heterogeneity in NT-proBNP reduction after Sac/Val compared with angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB) therapy. Estimated TBV was calculated using validated anthropometric equations and dichotomized at the median (4.05 L). Patients were further stratified by left ventricular ejection fraction (LVEF <40% vs ≥40%). The primary endpoint was the proportional change in NT-proBNP from baseline to Week 8. RESULTS: Among 376 patients, 372 with baseline estimated TBV data were analyzed. In the high TBV group, Sac/Val was associated with greater NT-proBNP reduction than ACEI/ARB (-56% vs -32%; ratio of change, 0.67; 95% confidence interval, 0.53-0.84; P = .001), whereas no significant difference was observed in the low TBV group (P for heterogeneity = 0.063). In patients with LVEF <40%, Sac/Val was associated with greater NT-proBNP reduction in both TBV groups. In patients with LVEF ≥40%, Sac/Val was associated with greater NT-proBNP reduction in the high TBV group, whereas the point estimate in the low TBV group numerically favored ACEI/ARB. CONCLUSIONS: In this exploratory post hoc analysis, higher estimated TBV was associated with greater NT-proBNP reduction after Sac/Val, particularly among patients with LVEF ≥40%. These findings are hypothesis-generating and require external validation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05164653; Japan Registry of Clinical Trials, jRCTs021210046.

Humans↗

PubMed2026

Skeletal Muscles Do Not Compete for Growth: Activating Additional Muscle Mass Does Not Compromise Changes in Muscle Size.

Kataoka, R, Yamada, Y, Hammert, WB, Sallberg, RW, Kang, A, Song, JS, Kassiano, W, Metcalf, EE, and Loenneke, JP. Skeletal muscles do not compete for growth: Activating additional muscle mass does not compromise changes in muscle size. J Strength Cond Res 40(9): 1043-1049, 2026-This study investigated whether the magnitude of muscle size and strength differed based on the amount of muscle recruited during training sessions. One hundred five untrained individuals were randomly assigned to 1 of 3 groups: low-load unilateral elbow flexion exercise (a) to failure (LL-Failure, n = 36), (b) to failure and low-load knee extension exercise to failure (LL-Failure + Legs, n = 33), or (c) a time-matched nonexercise control (CON, n = 36). Training groups completed 18 supervised sessions over 6 weeks (2 sets at 30% 1 repetition maximum [1RM] to failure). LL-Failure + Legs group performed 4 additional sets of knee extension exercise in each leg (20-30 RM). Muscle thickness on the anterior upper arm (60 and 70% sites) and elbow flexor 1RM strength of the trained arm were measured at pretesting and posttesting. Changes were compared using the ANCOVA function of Bayes Factors for Informative Hypotheses (prevalues as the covariate). Specific hypotheses were evaluated by comparing Bayes factors and the posterior probabilities between models. Six weeks of training led to increases in muscle size and strength. However, performing additional leg exercise did not attenuate the muscle growth in the anterior upper arm (0.19 cm) compared with performing only arm exercise to failure (0.18 cm). Changes in 1RM strength also did not differ between training groups (0.32 and 0.25 kg for LL-Failure and LL-Failure + Legs, respectively). Overall, there was no evidence for competition of adaptations in muscle size and strength under uncontrolled nutritional conditions. Whether greater training volume or limited nutrient intake induces a competition for resources warrants further investigation.

Humans↗

PubMed2026

Imaging-based surgical stratification of parasagittal meningiomas involving the superior sagittal sinus: a case analysis of 62 patients.

OBJECTIVE: The objective was to evaluate the Superior Sagittal Sinus Involvement Grading (SSIG) system as an imaging-based surgical stratification framework for parasagittal meningiomas adjacent to the superior sagittal sinus (SSS) and to assess its relationship with established sinus invasion grading, venous sinus patency, and operative strategy. METHODS: In this single-center retrospective cohort study, the authors included 62 consecutive parasagittal meningioma resections performed by a single surgeon. SSIG grade was assigned primarily on contrast-enhanced coronal MRI, with CT/MR venography used when available to evaluate sinus patency and collateral venous drainage. Operative variables, resection strategy, and clinicopathological factors were compared across SSIG and Sindou grades, and postoperative complications were compared between low- and high-involvement SSIG groups. RESULTS: SSIG correlated significantly with Sindou grade (rs = 0.790, τb = 0.702, both p < 0.001), and among patients with available venous imaging, it also correlated with the venous sinus involvement grade (rs = 0.742, τb = 0.665, both p < 0.001). With increasing SSIG grade, operative time, intraoperative blood loss, and intraoperative fluid administration increased (p = 0.012, p = 0.008, and p = 0.007, respectively). Compared with the low-involvement group (SSIG grades 1, 2, and 4a), the high-involvement group (SSIG grades 3, 4b, and 5) was less likely to achieve Simpson grade I resection and more likely to adopt Simpson grades II-III strategies (66.7% vs 13.6%, p < 0.001; OR 12.667). Surgery-related complication rates did not differ significantly between groups. The mean follow-up was 13.3 ± 7.9 months, with no radiographic recurrence or progression at last follow-up. CONCLUSIONS: SSIG characterizes parasagittal meningiomas by integrating sinus invasion, venous patency, falcine extension, and parasagittal convexity involvement on preoperative imaging. This surgically oriented framework may help anticipate operative exposure, sinus handling, and resection strategy. Its predictive value for complications and long-term oncological outcomes requires validation in larger cohorts with longer follow-up.

Humans↗

PubMed2026

Machine learning vs. traditional methods for predicting postoperative cardiac complications after non-cardiac surgery: a systematic review and Bayesian network meta-analysis.

INTRODUCTION: Accurate prediction of peri-operative cardiac complications is critical to optimise pre-operative decision-making. Traditional risk prediction scores, such as the Revised Cardiac Risk Index, show only modest discrimination. Machine learning can model complex, non-linear relationships but their predictive performance compared with traditional scores remains unclear. METHODS: We performed a systematic review and Bayesian network meta-analysis. The primary outcome was postoperative adverse cardiac events following non-cardiac surgery. Prediction models were assessed relative to the Revised Cardiac Risk Index. As many studies evaluated multiple versions of each model type, the highest performing ('best version') and lowest performing ('worst version') results were analysed. Models were ranked using the surface under the cumulative ranking curve (SUCRA). RESULTS: Thirteen studies evaluating 54 models and 927,113 patients were included. Machine learning approaches generally outperformed traditional risk scores. Automated machine learning ranked highest (SUCRA 96.6) showed the greatest improvement in the best version analysis (mean difference (MD) 0.28 (95%CrI 0.16-0.40)) and remained superior in the sensitivity analysis (MD 0.30 (95%CrI 0.14-0.45)). Gradient boosting models showed superior performance over the Revised Cardiac Risk Index across analysis (best version: MD 0.20 (95%CrI 0.14-0.26), worst version: MD 0.18 (95%CrI 0.12-0.25), SUCRA 82.4). The Gupta Perioperative Risk for Myocardial Infarction or Cardiac Arrest score outperformed the Revised Cardiac Risk Index in the best version analysis (MD 0.16 (95%CrI 0.01-0.32)). Between-study heterogeneity was low. None of the included studies externally validated their machine learning models and only six were judged to be at low risk of bias. DISCUSSION: Most machine learning models showed better discrimination than traditional risk scores, with automated machine learning and gradient boosting models ranking highest. However, study quality, calibration reporting and absence of external validation limit immediate clinical adoption. Prospective, multicentre evaluation is required before integration of these models into peri-operative practice.

Humans↗

PubMed2026

PGR expression as a pharmacogenomic companion biomarker to GENE70-derived genomic risk in ER-positive/HER2-negative breast cancer.

BACKGROUND: The biology of the estrogen receptor-positive (ER+) and human epidermal growth factor receptor 2-negative (HER2-) breast cancers is heterogeneous even when they are categorized by their risk via genomics. Transcriptomic PGR expression reflects endocrine pathway activity and may provide complementary biological information within established GENE70-derived genomic-risk categories. Whether this molecular marker improves the biological interpretation of genomic-risk stratification beyond conventional clinicopathological assessment remains uncertain. OBJECTIVES: The aim of this study was to determine whether transcriptomic PGR expression provides complementary biological and prognostic information within reconstructed GENE70-derived genomic-risk categories and refines the characterization of endocrine-related tumour biology in ER-positive/HER2-negative breast cancer. METHODS: This study analysed publicly available transcriptomic and clinical data from three cohorts: METABRIC (discovery cohort), GSE96058/SCAN-B cohort (validation cohort) and TCGA-BRCA cohort (molecular validation cohort). The GENE70-derived genomic-risk score was reconstructed for each cohort using matched genes. Cox regression, Kaplan-Meier analysis and subgroup comparisons were used to assess relationships between PGR expression, clinicopathologic variables, molecular features and survival outcomes. RESULTS: Across the three independent cohorts, low transcriptomic PGR expression was consistently associated with higher GENE70-derived genomic risk, increased MKI67 expression, reduced ESR1 expression and enrichment of the Luminal B subtype. Survival findings differed between cohorts. In the discovery METABRIC cohort, transcriptomic PGR expression showed heterogeneous associations with survival, particularly within GENE70-derived high-risk subgroups, whereas the external GSE96058/SCAN-B validation cohort demonstrated consistent associations between low PGR expression and poorer overall survival in both the overall ER-positive/HER2-negative population and GENE70-derived high-risk subgroups. CONCLUSION: These findings suggest that transcriptomic PGR provides complementary biological and prognostic information within GENE70-derived genomic-risk categories. However, because treatment response was not evaluated in the present study, the findings should not be interpreted as evidence of predictive or pharmacogenomic utility and prospective studies incorporating treatment-response analyses are required before such applications can be established.

Humans↗

PubMed2026

Antibody-drug conjugates against multidrug-resistant cancers: Biomarker-guided patient selection, payload engineering, linker chemistry, and bystander effects.

Antibody-drug conjugates (ADCs) are one of the most significant advancements in modern cancer therapeutics. Combining the target selectivity of monoclonal antibodies with the cytotoxic potential of payloads, ADCs effectively kill cancer cells and offer hope to patients with even refractory cancer types. Beyond simply increasing the number of therapeutic options available for cancer patients, ADCs have become a powerful frontline agent in overcoming multidrug resistance (MDR). As one of the most challenging obstacles to effective cancer care, MDR is mediated by ATP-binding cassette (ABC) transporter-mediated drug efflux, target-based mutations, and dysregulated apoptosis. The clinical success of ADCs specifically engineered to overcome MDR, including in heterogeneous tumors and cancer cells that exhibit bypass signaling, is well established. This is especially evident with trastuzumab deruxtecan (T-DXd) in HER2-low, HER2-positive, and HER2-mutant cancers; sacituzumab govitecan (SG) in TROP2-expressing triple-negative breast cancer (TNBC) and urothelial carcinoma; and enfortumab vedotin in Nectin-4-positive bladder cancer. By overcoming MDR, ADCs have enabled more effective treatment algorithms across multiple malignancies. Most importantly, the clinical application of ADCs has become inextricably linked to cancer genomics. HER2 testing has evolved from a two-tiered system to a continuous spectrum including HER2-ultralow, HER2-low, HER2-positive, and ERBB2-mutant categories. Each of these categories exhibits different eligibility guidelines for ADC patient selection. As cancer cells continue to evolve and develop resistance to even ADCs through mutations and variants, researchers and clinicians have used pharmacogenomics to predict ADC response and resistance. To define the genomic architecture of ADC-resistant tumor subpopulations, single-cell transcriptomic studies and liquid biopsy approaches are being used to enable real-time examination of the tumor genome during ADC therapy, thereby optimizing treatment and circumventing resistance driven by emerging mutations and variants. This review provides a comprehensive analysis of the molecular structure of ADCs, the pharmacological principles underlying their potent cytotoxic activity against MDR cancer cells, the genomic and transcriptomic biomarkers that guide ADC patient selection, and the emerging resistance mechanisms that will shape the next generation of promising ADC development.

Humans↗

PubMed2026

Safety, tolerability, pharmacokinetics, and pharmacodynamics of oral JMKX003002 in Chinese healthy participants: a randomized, double-blind, placebo-controlled, single- and multiple-ascending dose, and food-effect phase I clinical trial.

OBJECTIVE: To evaluate the safety, tolerability, pharmacokinetics (PK), and pharma-codynamics (PD) of the sodium-hydrogen exchanger 3 (NHE3) inhibitor JMKX003002 in Chinese healthy participants. PATIENTS AND METHODS: This phase I, randomized, double-blind, placebo-controlled study included a single-ascending dose (SAD) study with seven cohorts (1 mg [n = 4] and 5, 20, 50, 75, 100, or 125 mg [n = 8]), a food-effect (FE) study with six sequence groups (25 mg twice daily, n = 4), and a multiple-ascending dose (MAD) study with two cohorts (10 mg or 20 mg twice daily, n = 10). RESULTS: JMKX003002 was well-tolerated, with mostly mild treatment-related adverse events. One Grade 3 diarrhoea occurred in each of the 50 mg and 125 mg groups. No serious adverse events were reported, and no participants discontinued or withdrew due to treatment-emergent adverse events. Most plasma samples were below the limit of quantification (0.2 ng/mL), with only transient detection of low concentrations, indicating low systemic exposure. JMKX003002 was primarily excreted in stool (79.9% recovered) and was undetectable in urine. The PD results consistently showed decreased urinary sodium and phosphorus, along with increased stool sodium and phosphorus, compared to baseline across all three studies. One day after discontinuation, stool sodium and phosphorus remained elevated relative to baseline in the MAD study. Mixed-effects model analysis in the FE study demonstrated significant food effect on stool sodium and phosphorus excretion. CONCLUSION: JMKX003002 exhibited favorable safety and tolerability with minimal systemic exposure. It effectively increased sodium and phosphorus excretion in stool. These promising findings warrant further investigation of JMKX003002 to evaluate its clinical benefits. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2300070473). Registered on April 13, 2023; prospectively registered.

Adult↗

PubMed2026

Intraocular Pressure Changes Following Intraluminal Stent Removal From the Paul Glaucoma Implant: A Systematic Review and Meta-Analysis.

PURPOSE: This study aims to systematically review and perform a single-arm meta-analysis to comprehensively evaluate the effect of removal of intraluminal stent from the Paul glaucoma implant (PGI) on intraocular pressure (IOP) changes and to summarize its long-term efficacy and safety. CLINICAL RELEVANCE: Glaucoma remains one of the leading global causes of irreversible vision loss, necessitating effective surgical management for refractory cases. Glaucoma drainage devices are critical for these complex forms, and intraluminal stent removal from the PGI serves as a key strategy to titrate aqueous outflow and optimize long-term IOP control. METHODS: A systematic review was conducted by searching EMBASE, Medline, and CENTRAL. The meta-analysis ultimately included 5 observational studies. The Risk of Bias in Nonrandomized Studies of Interventions (ROBINS-I) tool was used to assess the quality of the included studies. Continuous outcomes (eg, postremoval stent IOP reduction) were analyzed using the mean difference (MD) with 95% confidence intervals (CI); dichotomous outcomes (eg, hypotony incidence) were evaluated using pooled proportion with 95% CI. All meta-analyses employed a random-effects model. RESULTS: Our meta-analysis included 5 studies, involving a total of 283 eyes. The meta-analysis revealed that removal of the stent leads to a significant and immediate IOP reduction. The IOP reduction (immediate postremoval stent IOP minus preremoval stent IOP) was significant, with a pooled MD of -9.09 mm Hg IOP (MD = 9.09; 95% CI = [-11.77, -6.41]). In the preremoval stent high-IOP (>21 mm Hg) subgroup, the IOP reduction is -11.82 (95% CI = [-10.14, -13.51]). This reduction was significantly greater than the preremoval stent low-IOP (<21 mm Hg) subgroup, whose reduction is -6.66 mm Hg (95% CI = [-5.55, -7.77]). Regarding safety, the pooled proportion of clinically hypotony was low and highly consistent (I² = 0.00%) at only 0.03 (95% CI = [0.00, 0.15]). CONCLUSIONS: Intraluminal stent removal from the PGI is an effective and safe IOP-lowering intervention. Its IOP reduction effect is significantly more pronounced in patients with preremoval stent high IOP, providing crucial clinical guidance for managing persistently high IOP after PGI implantation.

Humans↗

PubMed2026

The Effects of Intermittent Hypoxic Training Strategies on Maximal Oxygen Uptake in Healthy Humans: A Meta-analysis with Meta-regression.

BACKGROUND: Intermittent hypoxic training aims to enhance exercise performance and health, commonly assessed through maximal oxygen uptake (VO2max). Currently applied methods are live-high train-low (LHTL), live-low train-high (LLTH) and passive hypoxic conditioning (PHC). However, within these methods, numerous modes of application exist, and effectiveness is debated. OBJECTIVE: To determine the effect of LHTL, LLTH and PHC on VO2max in healthy participants, and identify factors associated with the amplitude of change in VO2max. METHODS: We conducted a systematic review with random-effects meta-analysis and meta-regression. Studies were identified through PubMed, EMBASE and Web of Science. We included controlled studies, calculating between-group standardised mean differences. Athlete and non-athlete populations were analysed separately. RoB2 was used to assess study quality and publication bias was investigated with funnel plots and the Egger's test. RESULTS: Of the 5244 identified studies, 62 were included for analysis, resulting in a sample size of 1332 participants (610 athletes, 722 non-athletes). LHTL increased VO2max significantly more than control in athletes (mean difference [MD] = 2.17; 95% CI = 0.77, 3.56) but not in non-athletes (MD = 3.1; 95% CI =  - 0.23, 6.43). LLTH did not increase VO2max significantly more than control in athletes (MD = 0.89; 95% CI =  - 0.27, 2.05) but it did in non-athletes (MD = 1.70; 95% CI = 0.85, 2.54). PHC did not increase VO2max significantly more than control in athletes (MD =  - 1.07; 95% CI =  - 3.51, 1.37) but it did in non-athletes (MD = 2.26; 95% CI = 1.00, 3.52). Multivariate meta-regressions identified the severity, duration, and frequency of hypoxic exposure to be significantly associated with the change in VO2max. CONCLUSIONS: LHTL showed a significant effect on VO2max in athletic populations while LLTH and PHC showed a significant effect on VO2max in non-athletic populations only. Future studies should target investigating which characteristics (e.g. severity, duration) of the hypoxic exposure are most beneficial.

Journal Article↗

PubMed2026

Efficacy and safety of thulium fiber laser versus conventional holmium:YAG laser in anatomical endoscopic enucleation of the prostate: a systematic review and pairwise meta-analysis.

PURPOSE: Anatomical endoscopic enucleation is an established treatment for benign prostatic obstruction. Whether thulium fiber laser enucleation (ThuFLEP) improves outcomes over conventional holmium:YAG laser enucleation (HoLEP) remains uncertain. We compared the efficacy and safety of ThuFLEP versus non-MOSES-modulated HoLEP. METHODS: We performed a PRISMA-compliant systematic review and pairwise meta-analysis of randomised and comparative cohort studies comparing ThuFLEP and conventional HoLEP in adult men. Six databases were searched. Outcomes included International Prostate Symptom Score (IPSS), IPSS quality-of-life score, maximum urinary flow rate (Qmax), post-void residual volume, hospital stay, and complications. Risk of bias and certainty of evidence were assessed with RoB 2/ROBINS-I and GRADE. RESULTS: Seven non-overlapping comparative populations in eight publications included 3,509 patients. ThuFLEP was associated with a small statistically significant reduction in IPSS at 3 months (mean difference [MD] -1.04 points, 95% confidence interval [CI] -1.81 to -0.28) of uncertain clinical relevance. Qmax differences were small and directionally inconsistent across follow-up (favouring HoLEP at 3 months and ThuFLEP at 6 and 12 months) and derived mainly from retrospective cohorts, with neutral randomised subgroups. Stress and urge urinary incontinence were less frequent overall (RR 0.75, 95% CI 0.58 to 0.96, and RR 0.39, 95% CI 0.22 to 0.68), but both estimates depended on one large registry cohort and were not robust to its exclusion. Most other complications and hospital stay showed no clear between-group difference. Limitations include few studies per outcome, heterogeneity, sparse safety events, inconsistent prostate-specific antigen reporting, and mostly low/very low certainty evidence. CONCLUSION: ThuFLEP and conventional HoLEP are clinically comparable with no definitive superiority of either laser. Platform selection should be individualised according to surgeon expertise, institutional resources, and patient characteristics. Future trials should standardise cost-effectiveness outcomes and investigate whether the distinct laser-tissue interactions impact adenoma clearance, PSA reduction, enucleation completeness, and long-term durability.

Humans↗

PubMed2026

Efficacy and safety of deucravacitinib, an oral, selective tyrosine kinase 2 inhibitor, in patients with active psoriatic arthritis: 52-week results from the randomised, double-blind, placebo-controlled phase 3 POETYK PsA-1 trial.

OBJECTIVES: The randomised, double-blind, placebo-controlled, phase 3 Program fOr Evaluation of TYK2 inhibitor Psoriatic Arthritis-1 (POETYK PsA-1) trial evaluated the efficacy, safety, and tolerability of deucravacitinib, an oral, selective tyrosine kinase 2 inhibitor, in patients with PsA naïve to biologic disease-modifying antirheumatic drugs. METHODS: Adults with active PsA, high-sensitivity C-reactive protein concentration ≥ 3 mg/L, and ≥ 1 PsA-related hand and/or foot erosion detectable via radiograph were randomised 1:1 to oral deucravacitinib 6 mg once daily or placebo through week (W) 16. At W16, patients continued receiving deucravacitinib or switched from placebo to deucravacitinib through W52. The primary endpoint was American College of Rheumatology 20% improvement in response (ACR20) at W16. Nonresponder imputation was used for missing data. Efficacy and safety were evaluated through W52. Post hoc rank analysis of covariance was used to evaluate structural damage with no missing data imputation. RESULTS: In 670 patients, a significantly greater proportion of those receiving deucravacitinib vs placebo achieved ACR20 at W16 (54.2% vs 34.1%, P < .001). Responses with deucravacitinib were increased at W52. Patients who switched from placebo to deucravacitinib achieved improvements similar to those in patients who received continuous deucravacitinib. Inhibition of structural damage was observed at W16 and W52. At W16, incidences of serious adverse events (AEs) (deucravacitinib, 1.8%; placebo, 2.4%) and discontinuations due to AEs (2.4%; 1.8%) were low and remained low through W52, without imbalances in cardiovascular events, malignancies, or opportunistic infections. No new safety signals were detected; no deaths occurred. CONCLUSIONS: Deucravacitinib demonstrated superiority vs placebo for clinical responses, patient-reported outcomes, and structural damage inhibition in patients with PsA, with favourable tolerability and safety.

Humans↗

PubMed2026

Sex modifies the association of high-altitude hypoxia with poor sleep quality and depression in school-age children and adolescents.

BACKGROUND: While chronic exposure to high-altitude hypoxia is known to impair sleep and mental health, whether these effects are sex-dependent remains unclear. This study addresses a critical gap by investigating how sex modifies the association between high-altitude hypoxia and risks of poor sleep quality, depressive symptoms, and their co-occurrence in children and adolescents. METHODS: In this cross-sectional study (March-May 2024), we enrolled 1,345 long-term residents of the Shannan Tibet Autonomous Prefecture (altitude: 3,650-4,800 m) and 2,909 age-matched controls from low-altitude plains (Anhui Province, China). Sleep quality and depression were assessed using the Pittsburgh Sleep Quality Index (PSQI) and Montgomery-Asberg Depression Rating Scale (MADRS), respectively. Sex-stratified analyses and interaction metrics (RERI/AP/SI) were employed to evaluate additive and multiplicative effects. RESULTS: High-altitude residents exhibited significantly higher prevalence of poor sleep (24.2% vs. 18.7%, P < 0.001), depression (23.6% vs. 15.3%, P < 0.001), and their co-occurrence (12.6% vs. 8.6%, P < 0.001) compared to low-altitude controls. A significant negative additive interaction (RERI = - 0.78, 95% CI: -1.35 to - 0.3; P < 0.001) indicated that sex modifies the altitude-outcome association. Specifically: (1) high-altitude residence significantly increased poor sleep risk in males (OR = 1.60, 95% CI: 1.26-2.03) but not in females (OR = 1.39, 95% CI: 1.07-1.79); and (2) the expected female predominance in poor sleep observed in the plain region (OR = 1.452, 95% CI: 1.191-1.769) disappeared in the plateau region (OR = 0.865, 95% CI: 0.667-1.121). Similar patterns were independently replicated for depressive symptoms. These findings confirm that high-altitude exposure differentially increases risk in males rather than protecting females. CONCLUSION: Males show marked vulnerability to high-altitude-associated sleep and mood impairments, while females demonstrate resilience. Sex-tailored interventions for high-altitude populations, particularly targeting male adolescents, are urgently needed.

Humans↗

PubMed2026

Access to palliative care in rural settings: A mixed-methods systematic review.

BACKGROUND: Rural populations experience persistent inequities in access to palliative care. Existing evidence often describes individual barriers separately, with less attention to how access breaks down across the care pathway or how different service configurations shape access. OBJECTIVES: To synthesise evidence on access to palliative care in rural settings and examine how access barriers, service models, and implementation conditions interact across the care pathway. METHODS: A mixed-methods systematic review using a convergent integrated approach searched nine databases (PubMed, Embase, CINAHL, Web of Science, Scopus, PsycINFO, CNKI, WanFang, SinoMed) from inception to 15 March 2026, supplemented by hand-searching. Eligible studies were primary qualitative, quantitative, and mixed-methods studies on access to palliative care for adults in rural or non-urban settings. Two reviewers independently screened studies, extracted data, and assessed quality using the Mixed Methods Appraisal Tool. Findings were mapped to the Levesque access framework, analysed using the updated Consolidated Framework for Implementation Research, and integrated through mixed-methods synthesis, with additional coding of service models. RESULTS: Thirty-four studies were included, of which 26 were conducted in high-income countries and eight in low- and middle-income countries. Service configurations included specialist or hospice-oriented care, generalist or primary-care-oriented care, mixed specialist-generalist models, home-based and caregiver-centred care, nurse-coordinated services, telehealth-supported care, and community or implementation-oriented approaches. Access broke down cumulatively across four interdependent stages: recognition, entry, reach, and use and continuity, with affordability constraining every stage. Recognition was limited by low awareness, poor service visibility, and delayed identification of need. Entry was shaped by stigma, trust, family expectations, and unclear referral processes. Reach was constrained by distance, transport, workforce shortages, limited specialist capacity, and weak infrastructure. Use and continuity were affected by fragmented coordination, weak transitions, unstable follow-up, and reliance on family caregivers. Access problems varied across service configurations. Evidence on service innovations was methodologically less certain, and the overall evidence base remained concentrated in high-income countries. CONCLUSIONS: Access to palliative care in rural settings is best understood as a pathway and service-configuration problem rather than simply a deficit in service availability. Improving access requires earlier recognition, clearer referral routes, stronger specialist-generalist and nursing links, better support for family caregivers, and greater attention to affordability, continuity, and rural settings with limited resources. REGISTRATION: International Prospective Register of Systematic Reviews: CRD420261340783.

Health Services Accessibility↗