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PubMed2026

Targeting depression before it starts: An updated systematic review and meta-analysis of preventive interventions in young adults from randomized controlled trials.

INTRODUCTION: Young adulthood is a high-risk period for major depressive disorder (MDD) onset yet is underrepresented in prevention research. This systematic review and meta-analysis examined the effectiveness of psychosocial preventive interventions in adults aged 18-25 years, focusing on symptom reduction, medium- and long-term effects, and MDD onset. METHODS: We conducted a PRISMA-compliant systematic review and meta-analysis (PROSPERO: CRD42024625481) of randomized controlled trials (RCTs) of psychosocial preventive interventions for depression in young adults (18-25) published up to April 15, 2025. Between-group symptom reduction was quantified using Hedges' g and pooled with random-effects models. Outcomes were analyzed at post-intervention, 6-, and 12-month follow-up. Effects on MDD onset were assessed via risk ratio (RR). Risk of bias was assessed with the RoB-2 tool. RESULTS: We included 65 interventions from 58 RCTs (N = 11,333; mean age 20.4; 61.6% female), with 92.8% rated high risk of bias. Interventions at post-test reduced depressive symptoms vs. controls (k = 65; g = -0.52; 95%CI:-0.70;-0.33; p < 0.01), with significant heterogeneity (I2 = 93.0%). Indicated, guided, and face-to-face interventions outperformed universal, selective, self-guided, and online interventions. Effects on symptomatology were highly heterogeneous and non-significant at 6- (k = 8) and 12-month (k = 4) follow-up. Four RCTs were identified evaluating MDD onset risk; pooled effects suggested a reduction in MDD onset (RR = 0.77; 95%CI:0.61;0.97; p < 0.01) though risk of bias was high and samples were highly selective. INTERPRETATION: Psychosocial preventive interventions modestly reduce depressive symptoms at post-test and may lower onset risk in highly selective populations. However, findings remain limited by high risk of bias, scarce data on the long-term sustainability of effects, and unclear mechanisms.

Adolescent↗

PubMed2026

A systematic review and meta-analysis of OCT-based ophthalmic changes in amyotrophic lateral sclerosis.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease marked by motor decline and respiratory failure. Optical coherence tomography (OCT), a non-invasive imaging technique, has been explored for detecting retinal structural changes that may reflect neurodegeneration in ALS. While some studies report thinning of retinal layers, findings remain inconsistent. Therefore, a meta-analysis is needed to clarify the extent of retinal involvement and the potential of OCT as a biomarker in ALS. METHODS: A systematic literature search was conducted across PubMed, EMBASE, and Cochrane databases for studies published between 2010 and May 2025. Study quality was assessed using the Newcastle-Ottawa Scale (NOS), and publication bias was evaluated through funnel plot asymmetry and Egger's test. Pooled effect sizes were calculated using random-effects models to account for between-study heterogeneity, and differences in OCT parameters between ALS patients and healthy controls were expressed as standardized mean differences (SMD) with 95% confidence intervals (CI). Statistical heterogeneity was quantified using the I2 statistic. RESULTS: A total of 17 studies were included in the present meta-analysis. The primary unadjusted global model demonstrated significant reduction of retinal nerve fibre layer (RNFL) thickness in ALS patients compared to controls (unadjusted SMD = -0.295, 95% CI: -0.522, -0.068). Upon applying a Design Effect variance inflation model to address fellow-eye non-independence, the pooled estimate remained robustly significant across a conservative range of intraclass correlations (SMD ranged from -0.256 to -0.249). Subgroup analyses revealed that RNFL thinning was particularly pronounced in spinal-onset ALS (SMD = -0.54, 95% CI: (-0.98, -0.10). When studies were stratified by the region of conduct, RNFL and macular thinning reached statistical significance only within the non-Asian subgroup, though the formal test for subgroup differences was not significant. CONCLUSION: This meta-analysis demonstrates significant bilateral RNFL thinning in ALS, with relative preservation of the Inner Nuclear Layer and Ganglion Cell Layer - Inner Plexiform Layer, supporting retinal neurodegeneration as a feature of this multisystem disorder. SYSTEMATIC REVIEW REGISTRATION: PROSPERO identifier CRD420251076035.

Humans↗

PubMed2026

Effects of Transcranial Direct Current Stimulation and Individualized Physical Therapy on Pain and Function in Individuals With Chronic Knee Pain: A Pilot Study.

BACKGROUND AND PURPOSE: Noninvasive brain stimulation is a promising neuromodulatory intervention for chronic pain. This study aimed to determine the impact that transcranial direct current stimulation (tDCS) in combination with individualized physical therapy (PT) has on pain and function in individuals with chronic knee pain. METHODS: This study was a preliminary pragmatic, triple-blinded, randomized, and sham-controlled clinical trial performed in an outpatient orthopedic physical therapy clinic. Participants participated in 5 sessions of active or sham tDCS followed by individualized PT intervention. Pain outcomes included the Numeric Pain Rating Scale, Movement-Evoked Pain, pressure pain thresholds (PPT), and the Central Sensitization Inventory. Functional outcomes included the 2-minute walk test, 5-time sit-to-stand test, quadriceps strength, knee range of motion, Patient Specific Functional Scale, and the Lower Extremity Functional Scale. RESULTS: Thirty participants with chronic knee pain completed the study. There were no significant differences observed for primary patient-centered pain and functional outcomes. For secondary outcomes, the active tDCS group had a significant effect (p < 0.05) on percent change in lateral joint line PPT and a significant multivariate effect of group on PPT change scores for 3-site and 5-site clusters (p < 0.05). Exploratory responder analyses demonstrated that the active tDCS group was 12.8 times more likely to achieve the minimum detectable change in quadriceps strength improvement compared with the sham tDCS group (p < 0.05). DISCUSSION: There were no significant between-group differences for primary pain and functional outcomes. However, the active tDCS group showed improvements in pain sensitivity, as measured by PPT, and quadriceps strength, which were superior to those seen in the sham tDCS group. These preliminary findings provide insight into possible mechanisms of tDCS in addressing pain as opposed to efficacy. Given that there were no clear between-group differences in patient-centered outcomes, there is insufficient evidence for routine tDCS use for chronic knee pain. TRIAL REGISTRATION: NCT06132412.

Humans↗

PubMed2026

From prediction to mechanism: Explainable AI uncovers plasma and CSF proteomic signatures of Alzheimer's disease.

Alzheimer's disease (AD) plasma and cerebrospinal fluid (CSF) proteomics can distinguish AD from cognitively normal controls, but the generalizability of machine learning performance and the recurrence of biological signals across datasets require cautious interpretation. We developed an explainable artificial intelligence framework spanning two fluids and four ADNI proteomic datasets, covering 2082 modality specific samples, all analysed internally within ADNI. Phase 1 analysed plasma using a 119 analyte NULISA and targeted UPENN panel (n = 727; 216 CE, 511 controls). Phase 2 extended the analysis to CSF using SOMAscan7k, TMT-MS and targeted SET2, with Elecsys Aβ42, Aβ40, total tau and p-tau181 as anchor biomarkers. Only SOMAscan was subject-independent relative to Phase 1 plasma; TMT-MS and SET2 overlapped with Phase 1 for 96.0% and 97.7% of subjects and therefore are not independent replication cohorts. Under subject-level splits with fold internal preprocessing, we compared Elastic Net, Explainable Boosting Machines and gradient boosted trees with SHAP-based explanations. Among the candidate pipelines, we selected the pipeline with the highest held-out test ROC AUC for each platform; the selected values were 0.927 in plasma and 0.954-0.973 across the three CSF datasets. Because the same held out test performance was used for pipeline selection and headline reporting, these are optimistically selected single-holdout estimates, not unbiased estimates of generalizable or clinical performance. Explanations identified five recurring biological axes within ADNI: cholinergic (ACHE), tau/14-3-3 (YWHAG, YWHAZ, YWHAB, YWHAE), neuro-axonal (NEFL, NEFH), microglial/complement (CHIT1, SMOC1, CHI3L1, C7, CFH) and synaptic (NPTXR, NPTX2, DLG4, SYT5, VSNL1, ELAVL2). CSF analyses showed synaptic vesicle-cycle enrichment (q = 2 × 10-6), and CSF YWHAG correlated strongly with total tau (ρ = 0.87). Cross-fluid directional concordance was modest overall (54-57%) but increased to 73-80% among mapped analyte/protein rows reaching q < 0.05 in CSF. These findings provide hypothesis-generating, internally supported evidence within ADNI. Independent external cohorts with locked pipelines are required to evaluate generalizable performance and biological reproducibility; the overlapping TMT-MS and SET2 analyses should not be interpreted as independent replication.

Alzheimer Disease↗

PubMed2026

The voice clone intelligibility benefit in noise in middle-aged listeners.

Research with younger adults showed that cloned voices are more intelligible than human voices in noise, with a benefit of 13.4%. This study tested whether this benefit extends to 40 middle-aged listeners (45-65 years), as this population may show emerging difficulties with speech-in-noise. Participants recognised sentences by ten human voices and ten voice clones in four noise levels. Cloned voices were 11.8% more intelligible, with benefits enhanced at the two most severe noise levels (15.9% at -6 dB and 17.5% at -3 dB), suggesting cloned speech enhanced perception in middle-aged listeners, potentially by reducing listening effort and compensating for emerging age-related auditory-cognitive decline.

Humans↗

PubMed2026

Prognostic value of the Island sign for hematoma expansion and functional outcome after intracerebral hemorrhage: a systematic review and meta-analysis.

PURPOSE: The Island Sign (IS) is a radiological finding observed in patients with intracerebral hemorrhage (ICH). This meta-analysis aimed to evaluate the association between IS and both hematoma expansion (HE) and functional outcomes by comparing ICH patients with and without IS. METHODS: We searched PubMed, Embase and Cochrane Library for studies of intracerebral hemorrhage reporting the IS. The primary outcomes were functional status and hematoma expansion, secondary outcome was mortality. Statistical analysis was performed using RStudio, effect sizes were calculated as odds ratios (ORs) with 95% confidence interval (95% CIs), and heterogeneity was assessed with I2 statistics. In addition, meta-regression and sensitivity analyses were performed, and publication bias was assessed through funnel plots and Egger's regression test. RESULTS: We included 21 observational studies with a total of 9,459 patients with spontaneous ICH, 1,769 of them had IS, while 7,690 did not. The mean age was 63.5 ± 13.2 and 5,835 (61.7%) were male. Poor functional outcomes (OR 2.77, 95% CI: 2.14-3.58, p < 0.0001, I2 = 4.9%) and hematoma expansion (OR 2.75, 95% CI: 1.87-4.03, p < 0.0001, I2 = 77.4%) were substantially higher in patients with IS, as well as the overall mortality rate (OR 2.54, 95% CI: 1.55-4.17, p = 0.0002, I2 = 0%). Meta-regression analysis showed no statistically significant association between imaging-related timing variables and hematoma expansion. Furthermore, the leave-one-out sensitivity analyses showed that no single study exerted a disproportionate influence on the overall effect for the examined outcomes, and Egger's linear regression tests were not statistically significant for both outcomes. CONCLUSION: Patients with the Island Sign are associated with higher rates of poor functional outcomes and hematoma expansion. Thus, IS is a relevant radiological finding with potential to support early risk stratification and optimize patient management and treatment selection.

Humans↗

PubMed2026

The role of the external genitalia score (EGS) in evaluation of disorders of sex development.

OBJECTIVE: To investigate the utility of the External Genitalia Score (EGS) in the diagnosis of disorders of sex development (DSD) and decision-making regarding gender assignment in affected patients. METHODS: A retrospective cohort study was conducted, enrolling 114 DSD patients aged <2 years (88 reared as males, 26 reared as females) treated at our hospital between April 2005 and June 2023, alongside 40 hypospadias patients aged <2 years who underwent surgery at our institution from January to July 2023. Demographic data (age) and EGS assessments of external genitalia were collected for all participants. Statistical analyses included independent samples t-tests, Mann-Whitney U tests and Receiver Operating Characteristic (ROC) curve analysis. Specifically, EGS scores were compared between the hypospadias group and the male-reared subgroup of the DSD cohort; additionally, EGS scores were contrasted between male-reared and female-reared DSD subgroups. RESULTS: The mean age was 20.3 months in the hypospadias group, 17.9 months in the male-reared DSD group, and 18.8 months in the female-reared DSD group. EGS ranged from 5.5 to 11.5 (median 10.5) in the hypospadias group and from 1 to 12 (median 4.75) in the DSD group. ROC curve analysis was performed to compare EGS scores between the hypospadias group and the male-reared DSD subgroup. The optimal diagnostic threshold was determined by maximizing the Youden index (sensitivity + specificity - 1), which balances sensitivity and specificity. A cut-off value of ≤8.50 was identified as indicative of DSD; clinically, patients with an EGS score <9 should be prioritized for DSD screening. Further comparison between male-reared and female-reared DSD subgroups yielded a threshold of 4.00. Clinically, an EGS score ≤4 may suggest a preference for female gender assignment. DISCUSSION: The EGS scale is a reliable, valid, and clinically feasible tool for characterizing external genitalia in DSD patients. An EGS score of 9 can serve as an indicator for initiating detailed sex development evaluation in hypospadias patients. While gender assignment in DSD is a complex, multifactorial process, EGS scores showed a significant association with the sex of rearing in our cohort. In settings where major determinants are balanced, EGS may serve as an adjunctive descriptive parameter rather than a standalone decision-making tool.

Humans↗

PubMed2026

Cine-derived mitral annular relaxation velocity for detection of preclinical left ventricular diastolic dysfunction.

OBJECTIVES: Imaging diastolic dysfunction in pre-clinical heart failure (HF) is challenging. We evaluated a novel cardiac MRI (CMR) biomarker, CMR e-prime (CMR-MARV), in patients at risk of HF. METHODS: In this substudy of the PARABLE trial (NCT04687111), 236 patients (71.6 ± 7.7 years, 61.6% male) fulfilling trial-defined ALVDD citeria underwent CMR with measurement of mitral annular relaxation velocity (CMR-MARV) at four mitral annular anchor points. Diastolic strain rates from FT were also assessed. Twenty-five age- and sex-matched controls were included (73.8 ± 3.1 years, 52% male). Group differences were tested with t-tests, diagnostic accuracy with ROC analysis, and predictors of diastolic dysfunction with adjusted logistic regression. RESULTS: Compared with controls, patients had significantly higher indexed maximal left atrial volume (LAVimax), LV end-diastolic and end-systolic volumes, and LV mass (all p < 0.001). Of FT variables, only peak diastolic longitudinal velocity differed between groups (p < 0.001). In multivariate models, CMR-MARV correlated with radial, circumferential, and longitudinal diastolic strain rates, radial and longitudinal diastolic velocities (all p < 0.001), echocardiographic e' (r = 0.20, p = 0.007), LV mass (r = -0.18, p = 0.008), LAVimax (r = -0.18, p = 0.008), and NT-proBNP (r = -0.30, p < 0.0001). LAVimax and CMR-MARV were strongly independently associated with ALVDD (AUC 0.89 and 0.76, respectively; p < 0.0001). A combined model (LAVimax + CMR-MARV) achieved excellent discrimination (AUC 0.91, 95% CI 0.86-0.97, p < 0.0001). Independent predictors included LAVimax, CMR-MARV, and peak diastolic longitudinal velocity (all p < 0.001). CONCLUSION: CMR-MARV provides a simple cine-derived measure of longitudinal relaxation that correlates with established structural and biochemical markers of diastolic burden. Within an at-risk population, it offers incremental functional information beyond conventional parameters and may support multiparametric CMR phenotyping of preclinical diastolic dysfunction.

Aged↗

PubMed2026

Effects of an internet-based combined exercise and cognitive-behavioral therapy intervention on endocannabinoid system biomarkers and physical fitness in adults with mild-to-moderate depression: a SONRIE randomized controlled trial.

BACKGROUND: This SONRIE randomized controlled trial (NCT05849792) examined the effects of a 12-week combined physical exercise and internet-based cognitive-behavioral therapy (iCBT) intervention on endocannabinoid system (ES) biomarkers and physical fitness in adults with mild-to-moderate depression. METHODS: Eighty adults were randomly assigned 1:1 to an intervention (IG) or control (CG) group. Outcomes included nine ES biomarkers (2-arachidonoylglycerol, 2-AG; anandamide, AEA; seven analogues) and physical fitness, including cardiorespiratory fitness (CRF; 6-minute walking test) and muscular strength. Measurements were taken at baseline, post-intervention and 8-week follow-up. Primary analysis performed 2 × 3 repeated-measures ANOVA on completers; mixed-effects intention-to-treat model as sensitivity analysis. RESULTS: No significant time × group interaction was detected for any ES biomarker, including 2-AG (F(2,88) = 0.17, p = 0.844) and AEA (F(2,88) = 1.20, p = 0.306); both groups showed comparable within-group decreases in 2-AG, 2-LG and 2-OG. The intervention significantly improved CRF [between-group difference + 81.6 m at 12 weeks (F(2,78) = 7.88, p = 0.001)], exceeding the established minimal clinically important difference. None of the exploratory muscular fitness outcomes reached statistical significance; the arm curl test showed a borderline non-significant interaction (F(2,78) = 2.83, p = 0.065). CONCLUSION: A 12-week internet-based combined exercise and iCBT intervention significantly improved CRF in adults with mild-to-moderate depression. We did not find evidence of an intervention-specific effect on plasma ES biomarkers. These findings support the inclusion of internet-delivered exercise and psychological interventions in comprehensive treatment strategies for depression. TRIAL REGISTRATION: ClinicalTrials.gov NCT05849792 (registered 6 May 2023).

Humans↗

PubMed2026

Comparison of short-term clinical outcomes and patient satisfaction between intraoral scanning and conventional impressions for complete-arch implant prostheses: a pilot RCT.

OBJECTIVE: To compare framework passive fit, subjective evaluations, and short-term clinical outcomes between conventional impressions (CI) and intraoral scanning (IOS) for complete-arch implant-supported fixed dental prostheses (CIFDPs). METHODS: In this randomized controlled trial, 22 patients were allocated to the CI or IOS groups. All participants received a definitive one-piece CIFDP. The primary outcome was framework passive fit, assessed using the Vision and Tactile Score (V&T score), which included framework lift-off, the single-screw test, the full-screw test, smoothness of screw insertion, and radiographic gap assessment. Secondary outcomes included operator evaluation, patient satisfaction using a visual analog scale (VAS), early implant survival, marginal bone loss (MBL), modified Plaque Index (mPII), and complications at the 6-month follow-up. RESULTS: Twenty-two patients were enrolled (CI: n = 11; IOS: n = 11), and one patient in the CI group was lost to follow-up. No statistically significant difference in the V&T score was observed between the CI and IOS groups (4.66 ± 0.17 vs. 4.65 ± 0.28; P = 0.93). The operator reported greater nervousness during the CI procedure than during IOS (21.82 ± 15.69 vs. 8.64 ± 7.47; P < 0.05). Patients in the CI group reported significantly greater discomfort, including nausea and anxiety, than those in the IOS group (P < 0.05). At the 6-month follow-up, the early implant survival rate was 100% in both groups. No significant differences were found between the groups in MBL (0.09 ± 0.09 vs. 0.06 ± 0.10 mm; P = 0.43) or mPII (0.10 ± 0.12 vs. 0.10 ± 0.28; P = 0.99). CONCLUSION: IOS and CI achieved comparable short-term clinical outcomes in patients who met the predefined inclusion criteria, including controlled implant number, spacing, and angulation. IOS provided a more favorable experience for both operators and patients. CLINICAL SIGNIFICANCE: In complete-arch implant restorations, intraoral scanning may provide clinical outcomes comparable to those of conventional impressions while improving patient comfort.

Humans↗

PubMed2026

Effects of Photobiomodulation Therapy in Lateral Luxation of Anterior Permanent Teeth: A Randomized, Double-Blind Clinical Trial.

BACKGROUND: Among the traumatic dental injuries (TDIs), lateral luxation may present poor prognosis due to frequent root resorption and consequent tooth loss. Photobiomodulation therapy (PBMT) modulates cellular activities (proliferation, differentiation, growth factor secretion) and may improve outcomes. OBJECTIVE: This randomized, double-blind, placebo-controlled trial evaluated PBMT (660 vs. 808 nm) for post-operative pain and pulp sensitivity recovery in lateral luxation of permanent anterior teeth. METHODS: Initially, 41 patients were included, with a total of 63 teeth traumatized by lateral luxation and were allocated to G1 (n = 21): Splinting + sham PBM (placebo), G2 (n = 21): Splinting + 808 nm infrared PBM and G3 (n = 21): Splinting + 660 nm red PBM. Four weekly sessions (3 J/point, 3 points) were administered. Pain (by numeric rating scale) and pulp sensitivity (by cold test) were assessed weekly. Pain was analyzed using the Kruskal-Wallis test, followed by multiple comparisons using Dunn's method with Bonferroni correction, and pulp sensitivity by a logistic regression model (p < 0.05). RESULTS: Three participants (total of 5 teeth) were excluded due to loss to follow-up. Fifty-eight teeth were analyzed (G1 = 21, G2 = 17, G3 = 20). Pain: All groups showed a significant reduction in pain over time (p < 0.001). Both G2 and G3 demonstrated a significantly greater reduction in pain compared to G1 (p < 0.001 and p = 0.026, respectively). No significant difference in pain reduction was observed between G2 and G3. Pulp sensitivity: G2 showed a significant improvement over time (p < 0.001), despite starting from a more unfavorable baseline. In contrast, no significant change in pulp sensitivity was observed for G1 or G3 between the initial and final assessments. CONCLUSION: Within the limitations of this clinical study, all intervention groups were effective in reducing pain in lateral luxation of permanent anterior teeth, with superior results for laser groups compared to the placebo. However, only the 808 nm laser irradiation protocol demonstrated a significant improvement in pulp sensitivity, suggesting it may offer a more complete therapeutic response.

Humans↗

PubMed2026

The Impact of Chatbot Type and Normative Messaging on Chatbot Usage Intention Based on the Health Technology Acceptance Model: Randomized Controlled Trial.

BACKGROUND: Digital health tools, such as health chatbots, may improve access to scalable health support, but adoption remains inconsistent. Existing models do not fully integrate technology acceptance factors with health motivation factors relevant to digital health use. OBJECTIVE: This study proposed and tested the health technology acceptance model and examined whether normative message framing and chatbot type were associated with health motivation, technology acceptance, and intention to use a health chatbot. METHODS: In October 2025, we conducted a 4 × 2 between-participants online experiment with 1000 US adults recruited from a nationally representative YouGov panel. Participants were randomized to 1 of 8 conditions varying norm message type (self-oriented, peer-oriented, expert-oriented, or family-oriented) and chatbot type (AI-powered or rule-based) in a cancer prevention and genetic risk information scenario. Outcomes included descriptive norms, injunctive norms, perceived susceptibility, perceived severity, perceived benefits, self-efficacy, perceived ease of use, trust, privacy concerns, and usage intention. Data were analyzed using a multivariate ANOVA with Bonferroni-adjusted post hoc tests and multiple linear regression. RESULTS: Peer-oriented and family-oriented messages produced higher usage intention than expert-oriented messages, and peer-oriented messages also increased descriptive norms, injunctive norms, self-efficacy, and trust. AI-powered chatbots were associated with higher usage intention (P=.02) and greater trust (P=.008) than rule-based chatbots. In regression analyses, the model explained 50.8% of the variance in usage intention. Usage intention was positively associated with descriptive norms (β=0.087; P=.003), injunctive norms (β=0.078; P=.009), perceived susceptibility (β=0.051; P=.03), perceived benefits (β=0.253; P<.001), and trust (β=0.33; P<.001), and negatively associated with perceived severity (β=-0.047; P=.049) and privacy concerns (β=-0.11; P<.001). Perceived ease of use and self-efficacy were not significant predictors. CONCLUSIONS: The health technology acceptance model was a useful framework for explaining the intention to use a health chatbot by combining technology acceptance and health motivation constructs. Both social design features and chatbot design features shaped adoption-related beliefs, with peer-oriented and family-oriented framing and AI-powered chatbots showing particular promise. Trust and privacy concerns remained central determinants of intended use.

Humans↗

PubMed2026

Chinese herbal medicine Xiangsu Hewei Granules in treating non-erosive gastroesophageal reflux disease with liver stomach stagnation heat syndrome: A multicentre, randomized, double-blind, placebo-controlled trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Xiangsu Hewei Granules are an herbal preparation that has shown potential for controlling symptoms of nonerosive gastroesophageal reflux disease (NERD) in preliminary studies. However, high-quality randomized controlled evidence for its use in NERD remains lacking. AIM: To verify the efficacy and safety of Xiangsu Hewei Granules in treating NERD with liver stomach stagnation heat syndrome. MATERIALS AND METHODS: This randomized, double-blind, placebo-controlled, multicentre phase III trial included 480 patients (aged 18-65 years) with confirmed NERD (GerdQ≥8; negative H. pylori) and traditional Chinese medicine (TCM) liver stomach stagnation heat syndrome. Patients were randomized 3:1 to receive either Xiangsu Hewei Granules or placebo, thrice daily for 8 weeks. The primary outcomes were the effective rate of the response based on visual analog scale (VAS) scores for heartburn and acid regurgitation at week 8. The secondary outcomes included reductions in the TCM syndrome score, etc. RESULTS: 479 participants (mean age 48.5 years, SD10.2; 54.3% female) entered the full analysis set and safety set (360 tests group; 119 control group, 1 participant in the control group withdrawing before medication). At week 8, compared with the control group, the test group demonstrated significantly better effective rate of VAS score response for heartburn(76.39% vs 21.01%, 95% CI 55.38 (45.98, 62.94) %, p < 0.01),acid regurgitation (79.72% vs 23.53%, 95% CI56.39 (46.90, 64.12) %, p < 0.01), and TCM syndrome score (69.23% vs 30.13%, p < 0.01) at week 8. CONCLUSION: In this selected population of NERD patients with liver-stomach stagnation heat syndrome (e.g., negative H. pylori, no pH-impedance phenotype, and low anxiety/depression scores), Xiangsu Hewei Granules demonstrated efficacy and safety in improving heartburn, acid regurgitation, and TCM syndrome scores. However, generalizability to the broader NERD population and its comparative effectiveness against standard proton pump inhibitor therapy require further investigation.

Humans↗

PubMed2026

Bypassing the emergency department for testicular torsion.

BACKGROUND: Testicular torsion is a time-sensitive urologic emergency that can result in testicular ischemia, atrophy, and loss if detorsion is delayed. Patients transferred from outside hospitals oftentimes experience prolonged ischemia due to repetitive assessments in the receiving emergency department (ED) and lengthy interhospital transfers. To address these delays, our institution created a pathway allowing patients with a confirmed diagnosis of testicular torsion to bypass the ED and proceed directly to the OR. OBJECTIVE: To evaluate the efficacy of an emergency department bypass pathway on time to surgical intervention and testicular salvage rates for patients transferred from outside hospitals with confirmed testicular torsion. STUDY DESIGN: Following one year of pathway implementation and institutional review board approval, a retrospective chart review was performed. Patients aged 12-18 years that were transferred from outside hospitals for confirmed testicular torsion were included in the pathway. A pre-pathway cohort (January 2022-December 2022) of patients with ED management was compared to a post-pathway cohort (August 2023-September 2024) of patients managed via direct OR transfer. Comparisons included patient age, mean time from ED registration to surgery start, orchiectomy rates, testicular atrophy rates at follow-up, and overall length of follow-up. T-tests and Fisher's exact tests were used for statistical analysis. RESULTS: 71 patients were included. Mean time from registration to OR start was significantly shortened in the post-pathway cohort compared to the pre-pathway cohort (70 min vs. 23 min, p < 0.0001). This represents a 67% decrease in time to surgery. Post-pathway patients were significantly older than pre-pathway patients (15 years vs. 13 years, p = 0.0025). Orchiectomy rates did not significantly differ between the two groups (14% post-pathway and 28% pre-pathway, p = 0.2454). Similarly, no significant difference was observed for testicular atrophy at follow-up (17% post-pathway and 15% pre-pathway, p = 1.0). Mean length of follow-up was insignificant (90 days for post-pathway and 76 days for pre-pathway, p = 0.6605). DISCUSSION: Direct transfer to the OR with ED bypass significantly reduced time to surgical detorsion. Other variables such as orchiectomy and testicular atrophy rates were not significantly impacted. Patient-limited factors may have influenced outcomes, such as delays in symptom recognition and time to initial care. CONCLUSION: An ED bypass pathway for transferred patients with testicular torsion was highly effective at reducing time to surgical intervention. Although testicular salvage rates were not significantly affected, reducing ischemia time is clinically important and encourages pathway refinement and broader use.

Humans↗

PubMed2026

A standardised risk-stratified approach to the urological management of children with spina bifida.

BACKGROUND: The establishment of a multidisciplinary spina bifida (SB) clinic in 2006 resulted in a review of the literature and an audit of renal outcomes based on then management practices. The audit showed 17% new onset renal scarring over a mean 5.8-year follow-up period. This prompted the development of a local protocol based on risk stratification combining serial ultrasound and non-invasive bladder function assessments, with invasive urodynamic studies reserved for high-risk patients. OBJECTIVE: This study sought to assess the impact of a risk stratified protocol on renal scarring and continence outcomes in children with SB. METHODS: A single centre, retrospective case review of SB patients treated after the introduction of the protocol was conducted. Electronic medical records were used to access patient demographics, continence status and the results of investigations and adherence to the local management protocol. Management that deviated from the protocol was deemed non-adherence. Renal scarring was determined by the presence of scarring on DMSA renogram. Continence was defined as having no urinary incontinence or no more than a single episode of incontinence in a month in patients above the age of 5. For statistical analysis, descriptive statistics in percentages were used, for comparisons of dichotomous variables the Students t-test was performed and to calculate statistical significance a Fisher exact test was done. RESULTS: 167 SB patients were identified with a mean follow up of 56 months. 141 patients were considered adherent to the protocol, 26 were non-adherent. In the protocol adherent group 5 patients (3.5%) developed renal scarring compared with 6 patients (23%) managed out of protocol (p = 0.002). Overall, 49/108 patients were continent either self-voiding 8/108 (7%), with urethral CIC 19/108 (20%) and 22/108 (45%) of them required bladder augmentation. Urinary continence improved with age with 26% continence at age 10, 64% continence by age 15 and 90% continent above 15 years of age. CONCLUSION: A management approach based on risk stratification resulted in incidence of renal scarring that is better than historical controls and comparable to published outcomes. Social continence was achieved in 90% of SB patients by 15 years of age. Hostile bladder changes can be readily identified using non-invasive assessment methods. An expectant treatment approach based on risk stratification is associated with good long term renal outcome and utilises invasive urodynamic resources for SB patients at high risk of renal injury or to address urinary continence in the older child.

Humans↗

PubMed2026

Obinutuzumab or Tacrolimus in Primary Membranous Nephropathy.

BACKGROUND: Studies of obinutuzumab, a type II anti-CD20 antibody, have shown efficacy in the treatment of hematologic cancers and autoimmune diseases. An evaluation of the efficacy and safety of obinutuzumab in patients with primary membranous nephropathy is needed. METHODS: In a phase 3 trial, we randomly assigned adults with primary membranous nephropathy in a 1:1 ratio to receive intravenous obinutuzumab or oral tacrolimus. The primary end point was complete remission (defined as a urinary protein-to-creatinine ratio of 0.3 or lower and a stable estimated glomerular filtration rate [eGFR]) at week 104. Key secondary end points were complete or partial remission at week 104, complete remission at week 76, a sustained reduction in the eGFR of at least 30%, duration of complete remission, and change in the Patient-Reported Outcomes Measurement Information System Fatigue T score from baseline to week 104. Fixed-sequence hierarchical testing was performed. Safety was assessed. RESULTS: A total of 142 patients underwent randomization. At week 104, complete remission was observed in 26 of 71 patients in the obinutuzumab group and in 4 of 70 patients in the tacrolimus group (37% vs. 6% with multiple imputation for missing data; adjusted difference, 31 percentage points; 95% CI, 18 to 44; P<0.001). The analyses of complete or partial remission at week 104 and complete remission at week 76 also showed a significant treatment effect. The analysis of a sustained eGFR reduction did not show a significant treatment effect; thus, subsequent end points in the hierarchy were not formally tested for significance. Adverse events of grade 3 or higher were reported in 16 patients (22%) in the obinutuzumab group and in 13 patients (19%) in the tacrolimus group; serious adverse events occurred in 12 (17%) and 10 (14%), respectively. There were 61 and 57 infections per 100 patient-years in the obinutuzumab and tacrolimus groups, respectively; 3 and 4 serious infections per 100 patient-years; and 11 and 14 serious adverse events per 100 patient-years. Adverse drug reactions with obinutuzumab included infusion-related reactions, respiratory tract infections, and neutropenia. One patient in each group died during escape therapy. CONCLUSIONS: Obinutuzumab was superior to tacrolimus in inducing complete remission in patients with primary membranous nephropathy. (Funded by F. Hoffmann-La Roche; MAJESTY ClinicalTrials.gov number, NCT04629248.).

Adult↗

PubMed2026

Maternal anemia and the risk of preterm birth: a meta-analysis.

BACKGROUND: Globally, preterm birth continues to be a primary contributor to neonatal complications and fatalities. Anemia among the most common nutritional disorders in pregnancy has been proposed as a potential contributor to early delivery. Although extensively studied, the available evidence does not yet provide a clear consensus. This study aimed to conduct a meta-analysis to quantitatively assess the relationship between maternal anemia and the risk of preterm birth. METHODS: This meta-analysis was conducted and reported in accordance with the PRISMA guidelines and the MOOSE checklist. A systematic and exhaustive search was performed across multiple electronic databases PubMed, Scopus, Web of Science, Embase, and the Cochrane Library to identify relevant studies published from inception to 1 January 2025. Effect sizes were combined using a random-effects meta-analysis. RESULTS: A total of 45 articles, reporting 60 independent study populations comprising 2,119,392 pregnant individuals were included. Considerable heterogeneity was found across the included studies (I2 = 95.54%, p < 0.001), which justified the application of a random-effects model for pooling effect sizes. Maternal anemia was significantly associated with an increased risk of preterm birth (pooled odds ratio[OR] = 1.28, 95% confidence interval [CI]: 1.20-1.36, p < 0.001). Despite substantial heterogeneity, sensitivity analyses confirmed the robustness of this association. The relationship was strongest in studies conducted in Asia (OR = 1.30, 95% CI: 1.22-1.40; p < 0.001) and the Europe (OR = 1.24, 95% CI: 1.08-1.41; p = 0.001) and reached statistical significance when anemia was assessed during the first trimester (OR = 1.12, 95% CI: 1.03-1.51; p = 0.007) and the third trimester (OR = 1.65, 95% CI: 1.42-1.91; p < 0.001), while no significant associations were found in the second trimesters (OR = 1.10, 95% CI: 0.99-1.22; p = 0.05). Funnel plot asymmetry and a significant Egger's test (p = 0.001) indicated potential publication bias, although Begg's test was not significant (p = 0.425). CONCLUSIONS: The current evidence suggests that maternal anemia, particularly in the third trimester, is significantly associated with an increased risk of preterm birth. These findings emphasize the clinical imperative for comprehensive and timely anemia screening during the third trimester. Integrating targeted interventions such as iron and micronutrient supplementation, is essential to mitigate the risk of preterm delivery and improve neonatal outcomes.

Humans↗

PubMed2026

The identification of growth-promoting lncRNAs in oral cavity squamous cell carcinoma.

Oral Cavity Squamous Cell Carcinoma (OCSCC) is an aggressive tumor that develops within the mouth of patients. Tumor-suppressor gene loss and genomic arrangements fuel tumorigenesis and transcriptional reprogramming. Understanding how these alterations contribute to OCSCC growth and cell survival may identify new therapeutic vulnerabilities or biomarkers. We profiled the role of long non-coding RNAs (lncRNAs) in the growth of three OCSCC cell lines using a CRISPRi-screen and identified 19 lncRNAs that contribute to OCSCC proliferation. By comparing these lncRNAs to other screens, we find that these lncRNAs are uniquely required in OCSCC and not other malignancies. We show that these lncRNAs are abundantly expressed in OCSCC cells and tumors. Independent testing of candidate lncRNAs confirms their role in supporting OCSCC growth. Our results show that a novel subset of lncRNAs are required for the growth of OCSCC cancer cells and that these lncRNAs are cell lineage specific.

CRISPRi↗