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PubMed2026

Reduced FOXP3 expression and its association with genetic ancestry in neuromyelitis Optica spectrum disorder: a Colombian cohort.

BACKGROUND: Autoimmune disorders are characterized by impaired immune tolerance, largely mediated by CD4⁺ regulatory T cells (Tregs), whose function depends on the transcription factor FOXP3. OBJECTIVES: To compare FOXP3 expression levels between patients with neuromyelitis optica spectrum disorder (NMOSD) and healthy controls from Bogotá, Colombia, and to explore their association with genetic ancestry. METHODS: FOXP3 expression was quantified from peripheral blood mononuclear cells using RNA-based analysis. Genomic ancestry proportions were estimated using ancestry-informative markers. RESULTS: FOXP3 mRNA expression was significantly reduced in NMOSD patients compared with controls (∼2.4-fold decrease in median expression; p = 0.027). Lower FOXP3 mRNA expression was associated with optic neuritis (p = 0.0059), but not with historical or current AQP4-IgG seropositivity. In a sensitivity analysis restricted to patients with documented historical AQP4-IgG seropositivity, the direction of reduced FOXP3 mRNA expression was preserved but did not reach statistical significance. In pre-specified exploratory ancestry-related analyses, African (p = 0.035) and Amerindian ancestry (p = 0.012) were associated with FOXP3 mRNA expression levels. CONCLUSIONS: Reduced FOXP3 mRNA expression in Peripheral Blood Mononuclear Cells (PBMCs) suggests an altered immune regulatory profile in NMOSD, potentially involving mechanisms beyond antibody-mediated immunity. The association between genetic ancestry and FOXP3 mRNA expression suggests that population-specific genetic background may influence immune regulatory pathways. These findings should be interpreted as exploratory and require validation in larger, clinically homogeneous cohorts.

Adolescent↗

PubMed2026

Endoscopic submucosal dissection for locally recurrent gastric neoplasia following endoscopic resection: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Endoscopic submucosal dissection (ESD) for locally recurrent gastric neoplasia following endoscopic resection (ER) is technically challenging because of scar-related submucosal fibrosis. We performed a systematic review and meta-analysis to evaluate the efficacy and safety of salvage ESD in this setting. METHODS: Multiple databases were searched through December 2025 for studies reporting ESD outcomes for locally recurrent gastric lesions at or contiguous with a prior ER scar. Primary outcome was curative resection and need for surgery. Secondary outcomes were en bloc and R0 resection, local recurrence, delayed bleeding, and perforation. Meta-analyses were performed using a random effects model. Heterogeneity was assessed using I2. RESULTS: Seven studies (259 patients; 265 ESDs) were included. Across 5 studies and 243 ESDs, pooled curative resection rate was 69.7% (95% CI, 60.6-78.1; I2 = 38%), while 8.2% (95% CI, 3.3-14.6; I2 = 38.4%) required surgery. En bloc resection rate was 92.3% (95% CI, 79.1-99.7; I2 = 83.7%) across 6 studies, and pooled R0 resection rate was 87.5% (95% CI, 82.1-92.2; I2 = 0%) across 4 studies. Over a mean follow-up of 42 months, pooled local recurrence was 2.0% (95% CI, 0.0-9.7; I2 = 54.1%) across 6 studies. Delayed bleeding was 4.1% (95% CI, 0.8-9.0; I2 = 40.8%) and perforation was 4.1% (95% CI, 1.6-7.3; I2 = 0%). CONCLUSIONS: ESD for locally recurrent gastric neoplasia after ER achieves acceptable curative resection, high en bloc/R0 resection, and low local recurrence and morbidity. It is a viable organ-preserving option for appropriately selected patients, ideally performed at expert centers with close surveillance.

Humans↗

PubMed2026

Pancreatic fat and the risk of future dysglycemia: a systematic review and meta-analysis.

CONTEXT: Pancreatic fat has emerged as a metabolically relevant ectopic fat depot, but its longitudinal association with future dysglycemic outcomes remains incompletely defined. OBJECTIVE: This study aims to evaluate the longitudinal association of pancreatic fat with incident type 2 diabetes (T2D) and glycemic progression, with exploratory narrative synthesis of evidence in lean populations. DATA SOURCES: PubMed, Embase, Web of Science, and the Cochrane Library were searched from inception to March 1, 2026. STUDY SELECTION: Longitudinal observational studies assessing pancreatic fat at baseline and reporting subsequent incident T2D, glycemic progression, or both were included. DATA EXTRACTION: Two reviewers independently screened studies and extracted data. Methodological quality was assessed using the Newcastle-Ottawa Scale. DATA SYNTHESIS: Ten studies were included. In the primary binary meta-analysis (5 studies), higher pancreatic fat burden was associated with incident T2D (pooled effect estimate, 2.56; 95% CI, 1.27-5.14; I2 = 93.3%). Exclusion of 1 influential ultrasound-based study attenuated heterogeneity while preserving the association (pooled effect estimate, 1.45; 95% CI, 1.23-1.73; I2 = 10.2%). A separate continuous analysis (3 studies) also supported an association with incident T2D (1.17; 95% CI, 1.04-1.32; I2 = 79.2%), although exposure scales were not directly comparable. Pancreatic fat was also associated with glycemic progression (2 studies; 1.96; 95% CI, 1.10-3.48; I2 = 73.2%). Exploratory lean-population evidence was limited to 2 analytical contexts, synthesized narratively, and directionally consistent with the overall findings. CONCLUSION: Pancreatic fat was associated with adverse future glycemic outcomes across multiple analytical contexts. These findings support pancreatic fat as a potentially meaningful imaging-derived marker of future dysglycemia, while suggesting that heterogeneity is partly explained by differences in exposure ascertainment.

Humans↗

PubMed2026

Intramuscular patient-derived xenografts achieve high engraftment rates in gastric cancer: implications for pharmacodynamic testing and genomic biomarker discovery.

BACKGROUND: Gastric cancer (GC) exhibits marked inter-patient heterogeneity, limiting empirical chemotherapy efficacy. Patient-derived xenograft (PDX) models preserve the molecular features of parental tumors and can serve as pharmacodynamic surrogates, but conventional subcutaneous PDX suffers from low engraftment rates. This study evaluated an optimized intramuscular PDX platform for individualized drug testing in GC and applied whole exome sequencing (WES) for biomarker identification (Clinical trial registry: ChiCTR-OOC-17012731). MATERIALS AND METHODS: Ninety-eight treatment-naive GC patients were enrolled between April 2018 and December 2020. Fresh tumor tissues were engrafted into NCG mice by intramuscular transplantation. Drug efficacy was evaluated using tumor cell necrosis rate and Ki-67 expression. WES was performed on 32 engrafted tumorgrafts to characterize driver mutations in fast- and slow-growing subgroups. RESULTS: An engraftment rate of 71.7% (43/60) was achieved, substantially exceeding rates reported in prior studies. Clinical characteristics were independent of engraftment success and outgrowth time (all p > 0.05). Fast- and slow-growing tumorgrafts diverged in frequently altered genes: KMT2C, APOB, CDK12 and MSH2 predominated in fast-growing grafts, whereas TP53, CHD3 and TET2 were enriched in slow-growing grafts. Slow-growing tumorgrafts correlated with longer progression-free survival (p = 0.02). PDX-guided treatment was associated with improved prognosis. CONCLUSIONS: Intramuscular transplantation into NCG mice yields high engraftment rates for GC PDX. PDX-guided chemotherapy selection is associated with favorable outcomes. Driver mutation divergence between fast- and slow-growing tumorgrafts provides candidate prognostic biomarkers.

Animals↗

PubMed2026

Splenic hilum nodal involvement in resected left-sided pancreatic cancer: meta-analysis.

BACKGROUND: Splenectomy is standard of care during left pancreatectomy for pancreatic ductal adenocarcinoma (PDAC) to obtain adequate lymphadenectomy. However, evidence supporting this approach is lacking. Splenic preservation would reduce short-term morbidity and is essential for emerging oncological adjunctive therapies, including immunotherapy and personalized cancer vaccines. This study reviewed the incidence of splenic hilum nodal involvement (SHNI) in left-sided PDAC. METHODS: A systematic review of the PubMed, Embase, and Cochrane databases was performed, identifying studies published from inception to July 2026. Outcomes of interest were the rate of SHNI (station 10), overall survival, and the rate of splenic artery nodal involvement (SANI; station 11). Meta-analyses were conducted using random-effects models. Subgroup analyses for SHNI were performed per tumour localization (pancreatic neck, body, tail). RESULTS: Among 2776 screened studies, 22 with 2260 patients undergoing left pancreatectomy for PDAC were included. The pooled prevalence of SHNI was 3.7% (95% confidence interval (c.i.) 2.2% to 6.2%); 1.1% for pancreatic body PDAC (95% c.i. 0.3% to 4.3%) and 9.7% for pancreatic tail PDAC (95% c.i. 3.5% to 24.0%). SHNI was not significantly associated with survival (pooled hazard ratio 2.05; 95% c.i. 0.89% to 4.72; P = 0.072). The pooled prevalence of SANI was 39.1% (95% c.i. 25.1% to 55.1%). CONCLUSION: In patients undergoing left pancreatectomy for PDAC, the presence of SHNI is rare, particularly in pancreatic body cancer (1.1%). These findings suggest that the relevance of routine splenectomy remains unclear, especially for pancreatic body PDAC. However, because the quality of current evidence is low, further investigation in prospective studies is required.

Humans↗

PubMed2026

Comparison of VCV and PCV-VG modes on diaphragmatic function in diabetic patients undergoing laparoscopic colorectal surgery: a prospective randomized controlled study.

BACKGROUND: Diabetic patients are prone to induce diaphragmatic weakness, which can lead to postoperative pulmonary complications (PPCs). The optimal mechanical ventilation mode may potentially improve postoperative diaphragmatic function. This study evaluates the effects of two ventilation modes under driving pressure-guided ventilation strategy on diaphragmatic function, as assessed by diaphragm thickening fraction (DTF) and diaphragm excursion (DE), in diabetic patients following laparoscopic colorectal surgery. METHODS: Eighty patients diagnosed with Type II diabetes scheduled for elective laparoscopic colorectal surgery, were randomly allocated to either the pressure-controlled volume-guaranteed ventilation (PCV-VG) group (Group P) or the volume-controlled ventilation (VCV) group (Group V) during surgery. The primary outcome was diaphragmatic function assessed during both tidal breathing and maximal inspiratory effort after surgery. Secondary outcomes included intraoperative mechanical power, PPCs, and other complications. RESULTS: A total of eighty patients were included in the final analysis. The averaged area under the curve (AUC) for mechanical power during ventilation was significantly lower in Group P than in Group V (p = 0.002). PCV-VG significantly improved both DE and DTF within the first two days post-surgery (AUCDEtidal: p = 0.088, AUCDTFtidal: p = 0.004, AUCDEmax: p = 0.029, AUCDTFmax: p = 0.017). Postoperative diaphragmatic weakness was less frequent in Group P than in Group V (p = 0.019). However, there was no difference in the incidence of PPCs between the two groups (p = 0.155). CONCLUSION: PCV-VG mode can reduce intraoperative mechanical power, better preserve postoperative diaphragmatic function. However, these improvements did not translate into clinical benefits, as evidenced by the lack of reduction in the incidence of PPCs.

Humans↗

PubMed2026

Feasibility and efficacy of left bundle branch area pacing guided by modified chest lead 1.

BACKGROUND: Left bundle branch area pacing (LBBAP) typically requires 12‑lead electrocardiogram (ECG) measurements using an electrophysiology (EP) recording system. However, a simplified approach using modified chest lead 1 (MCL1) is potentially feasible. This study aimed to compare the success rate and pacing outcomes of LBBAP guided by MCL1 with those guided by the 12‑lead ECG using an EP recording system. METHODS: This retrospective, single-center study included patients with preserved left ventricular ejection fraction who underwent LBBAP for bradyarrhythmia. LBBAP was either guided by 12‑lead ECG using an EP recording system or by MCL1. In the MCL1 group, a follow-up examination with a 12‑lead ECG using an EP recording system was conducted within one week postoperatively. RESULTS: A total of 65 patients underwent LBBAP (EP recording system group: n = 35; MCL1 group: n = 30). The overall success rate of LBBAP was 84.6%, with no significant difference between groups (88.5% vs. 80.0%, p = 0.49). No significant differences were observed in the paced QRS duration (140.4 ± 8.0 vs. 141.9 ± 13.1 ms, p = 0.54), V6-V1 interpeak interval (39.7 ± 16.5 vs. 38.3 ± 15.6 ms, p = 0.79), or V6 R-wave peak time (69.8 ± 12.3 vs. 71.5 ± 12.1 ms, p = 0.68). CONCLUSIONS: MCL1-guided LBBAP was feasible and achieved a high success rate, with outcomes comparable to those of conventional EP recording system-guided implantation. This simplified approach may reduce procedural complexity and may allow LBBAP implantation without the routine use of an EP recording system.

Humans↗

PubMed2026

Impact of neoprene wetsuits on lung volumes and work of breathing: implications for military diver safety and performance.

INTRODUCTION: Neoprene wetsuits may impose mechanical constraints on the chest wall, potentially altering respiratory function. This study investigated the impact of neoprene wetsuits on lung volumes, airway mechanics, and work of breathing (WOB) in healthy male divers. METHODS: A randomised crossover trial was conducted with 31 male divers at the Royal Netherlands Navy Diving Medical Centre. Participants underwent pulmonary function testing, including spirometry, body plethysmography, the forced oscillation technique (FOT), and diffusion capacity measurements, both with and without a hoodless standardised 5 mm neoprene full body wetsuit with a neoprene neck seal. Primary outcomes included changes in forced vital capacity (FVC), functional residual capacity (FRC), airway resistance (Raw), reactance (Xrs), and WOB. RESULTS: Wearing a neoprene wetsuit led to statistically significant reductions in FVC (2.8%, P < 0.05), forced expiration in one second (2.9%, P < 0.05), FRC (4.0%, P < 0.05), and expiratory reserve volume (10.9%, P < 0.05), alongside increases in inspiratory capacity and tidal volume. Raw increased significantly (P < 0.05), while the FOT revealed altered airway mechanics, evidenced by increased Xrs at multiple frequencies (P < 0.05). Diffusion capacity remained unchanged, suggesting preserved alveolar-capillary function. CONCLUSIONS: Neoprene wetsuits induce mechanically restrictive effects on the chest wall, reducing static and dynamic lung volumes and increasing WOB. While these changes may not be clinically relevant at rest, their impact needs to be determined during strenuous or prolonged dives, particularly when combined with other equipment that limits thorax excursions. Future research should explore the effects of the military 5 mm wetsuit under immersed conditions to better understand their operational impact on diver performance and safety.

Male↗

PubMed2026

Therapeutic Exercise Protocol During Hospitalization in Pediatric Oncohematological Patients: Randomized Clinical Trial.

BACKGROUND: Leukemias, lymphomas, and central nervous system tumors are among the most common pediatric cancers and may lead to motor deficits, impaired balance, reduced muscle strength, fatigue, and decreased functional capacity. Early physiotherapy during hospitalization may help prevent inactivity and support functional preservation in this population. OBJECTIVE: To evaluate the effects of a therapeutic exercise program on quality of life, muscle strength, fatigue, and functional capacity in hospitalized pediatric oncohematological patients. METHODS: Thirty participants aged 8-17 years with oncohematological diseases were randomized to an intervention group (IG) or a minimal active physiotherapy comparator group (CG). Assessments included the 6-min walk test, handgrip dynamometry, the PedsQL Multidimensional Fatigue Scale, and the PedsQL Cancer Module at admission and discharge. The IG performed daily 25-min supervised sessions including aerobic, resistance, and breathing exercises with ambulation guidance, whereas the CG received breathing exercises and ambulation guidance. RESULTS: No significant group × time interactions were observed for total fatigue or its domains, overall quality of life or its assessed domains, handgrip strength, or six-minute walk test distance. Time-related changes were observed for some outcomes, but these occurred without evidence of differential change between groups and were not interpreted as effects of the structured exercise protocol. No intervention-related adverse events requiring permanent protocol discontinuation were recorded. CONCLUSION: The structured in-hospital therapeutic exercise protocol could be delivered under close clinical supervision without recorded intervention-related adverse events requiring permanent discontinuation. However, the structured protocol did not demonstrate superiority over the minimal active physiotherapy comparator for fatigue, quality of life, muscle strength, or functional capacity. These findings should be interpreted cautiously because of the small sample size, clinical heterogeneity, variable intervention exposure, and limited intervention-fidelity data. TRIAL REGISTRATION: Brazilian Registry of Clinical Trials (ReBEC), RBR-8sxnfyd.

Humans↗

PubMed2026

Vertical distribution of accessory canals in different tooth types: A systematic review and meta-analysis.

OBJECTIVE: To systematically analyze the vertical distribution of accessory canals and propose potential root-end resection levels in different tooth types. DATA: Proportional distribution of accessory canals (PD-AC) in 1 mm intervals, cumulative proportions within 2 mm and 3 mm (CP-AC0-2 and CP-AC0-3), mean distance from accessory foramen to root apex or main foramen (MD-AF), and prevalence of accessory canals in 2D cross-sections (PR-AC-2D). SOURCES: A systematic search of electronic databases was conducted through December 25, 2025. The review was registered in PROSPERO (CRD420251107855). STUDY SELECTION: Two reviewers independently performed study selection, data extraction, and risk of bias assessment using the AQUA tool. Nineteen studies were included for qualitative synthesis, of which eleven provided sufficient data for meta-analysis. A random-effects model was used, and subgroup analyses were stratified by tooth type, accessory canal type, and country. Within 0-1 mm, 1-2 mm, 2-3 mm, and 3-4 mm from the apex, 41.5%, 34.3%, 9.9%, and 4.4% of accessory canals were located, respectively. Molars had significantly higher proportions than anterior teeth both within 2 mm (90.0% vs. 72.4%) and 3 mm (96.9% vs. 87.5%). Of apical ramifications, 86.4% were within 2 mm. The pooled MD-AF was 1.472 mm. PR-AC-2D decreased from 29.3% at 1 mm to 1.3% at 5 mm. All studies presented moderate to high risk of bias. CONCLUSIONS: A 2 mm root-end resection level may be sufficient for molars, whereas anterior teeth may require a higher level. Further randomized controlled trials are needed. CLINICAL SIGNIFICANCE: A 2 mm resection may adequately expose or remove most accessory canals in molars, potentially preserving more root length while maintaining treatment efficacy. In anterior teeth, a traditional 3 mm resection remains advisable until further evidence becomes available.

Humans↗

PubMed2026

A child and young person focused systematic review of scrotal ultrasound with Mitigants to identify missed torsion.

BACKGROUND: Diagnostic accuracy of ultrasound for adults is stated as excellent. Paediatric and adult acute scrotal diseases are different. Findings in adults may not apply in children. The authors have seen overconfidence and interpretation with adult disease in mind in children with scrotal pain and have seen testicular loss as a result. OBJECTIVES: To interrogate the literature methodologically to report diagnostic accuracy of ultrasound (US) for the acute scrotum specifically in CYP with a follow-up methodology which allows identification of missed torsion. STUDY DESIGN: We performed systematic review and meta-analysis of studies reporting true diagnostic accuracy of ultrasound for testicular torsion (TT). PubMed, MEDLINE, Scopus, and Web of Science databases were searched from platform start until September 2023 using MeSH terms with protocol as detailed on PROSPERO. Multiple author search was undertaken. Two authors extracted data for included studies. Study quality was reported through QUADAS-2 methodology. Surgical findings or 12 months follow up in non-operative cases would be the gold standard to identify late atrophy due to missed torsion. Studies with methodology to identify missed torsion outwith the initial consult were included for meta-analysis. RESULTS: A total of 6790 cases were reported from the 38 papers identified. Studies were often flawed with poor definition of outcomes and short follow-up duration. Meta-analysis of the 10 high-quality studies revealed pooled sensitivity and specificity of 0.93 and 0.99. Doppler US by trained individuals demonstrated excellent diagnostic accuracy. Nonetheless, on extrapolation of the data, especially where flow was preserved, 5.6% of torsions were missed. DISCUSSION/CONCLUSION: Our review confirms a high diagnostic accuracy of US for TT in CYP. However, a 5.6% missed torsion rate was found if flow alone was considered diagnostic. The authors suggest US should be used as an adjunct in ambiguous cases, ensuring that clinically obvious torsion goes to theatre immediately and is not delayed by ultrasound. TRIAL REGISTRATION: PROSPERO: CRD42023412619.

Humans↗

PubMed2026

Diagnostic performance of machine learning models versus established risk stratification for intracranial aneurysm rupture: a systematic review and bivariate meta-analysis.

BACKGROUND: Machine learning (ML) models have been proposed to improve the discrimination of intracranial aneurysm rupture status beyond established clinical risk stratification tools. However, reported performance is heterogeneous and the relative contribution of model architecture and feature dominance remains unclear. METHODS: We performed a Preferred Reporting Items for Systematic Reviews and Meta-Analyses-diagnostic test accuracy systematic review and diagnostic meta-analysis of studies evaluating ML models for intracranial aneurysm rupture discrimination. PubMed, Embase and CENTRAL were searched to February 2026. Sensitivity and specificity were pooled using a bivariate random-effects model, with summary receiver operating characteristic curves generated across training, internal testing and external validation datasets. Models were compared with regression-based approaches and Population, Hypertension, Age, Size of aneurysm, Earlier subarachnoid haemorrhage, Site of aneurysm (PHASES) scores. Subgroup and meta-regression analyses explored associations between algorithm family and feature domain. RESULTS: Sixty-two retrospective cohorts (29 709 patients 209 models) met the inclusion criteria. In training datasets, pooled sensitivity and specificity for ML were 0.81 (95% CI 0.75 to 0.85) and 0.83 (0.80-0.86), with an area under the curve (AUC) of 0.878, exceeding PHASES (AUC 0.667). In testing datasets, ML retained higher discrimination (AUC 0.837) than regression models (0.806) and PHASES (0.646). In external validation, sensitivity was preserved (0.82), but specificity declined (0.66). Deep learning demonstrated the highest AUCs (training and testing). Incorporation of haemodynamic or radiomic features improved pooled discrimination relative to morphology alone. Evidence of small-study effects and mostly unclear Prediction Model Risk Of Bias Assessment Tool ratings were observed. CONCLUSIONS: ML approaches demonstrate higher pooled discrimination for aneurysm rupture status than conventional risk scores in retrospective datasets, but reduced external validation specificity and heterogeneity limit confidence for clinical translation. Prospective, externally validated, calibrated models are required before integration into routine cerebrovascular risk stratification.

Humans↗

PubMed2026

Choice of Anesthesia in Microelectrode Recording-guided Deep Brain Stimulation Surgery for Parkinson's Disease (CHAMPION): A Noninferiority Randomized Controlled Trial.

BACKGROUND: Deep brain stimulation for Parkinson's disease is often performed under conscious sedation or general anesthesia. However, anesthetic agents may influence intraoperative microelectrode recording, and the optimal anesthesia method for microelectrode recording remains unclear. This study compared general anesthesia and conscious sedation in preserving microelectrode recording signal intensity during deep brain stimulation. METHODS: In this prospective, noninferiority randomized controlled trial, patients with Parkinson's disease (United Kingdom Brain Bank criteria) undergoing elective bilateral surgery were randomized 1:1 to the conscious sedation or the general anesthesia group. During surgery, a desflurane anesthetic titrated against the quality of the electrophysiologic signal was applied in the general anesthesia group, whereas patients in the conscious sedation group received dexmedetomidine anesthesia. The primary outcome was the proportion of patients with high-quality microelectrode recording (normalized root mean square greater than 2.0), assessed postoperatively off-line. Secondary outcomes included operation and recording duration, 6-month clinical efficacy, and complication rates. RESULTS: Of 188 randomized patients (94 general anesthesia, 93 conscious sedation), desflurane anesthesia was noninferior for high normalized root mean square proportion (89.4% vs . 90.3%; difference, -0.96%; 95% CI, -9.62 to 7.70). The general anesthesia group had shorter operative time (difference, -9.07 min; 95% CI, -13.99 to -4.14; P < 0.001). At 6 months, changes in Unified Parkinson's Disease Rating Scale score (difference, -2.50; 95% CI, -7.20 to 2.20; P = 0.297), levodopa equivalent daily dose (difference, -58.4 mg; 95% CI, -133.56 to 16.75; P = 0.128), and complication rates (general anesthesia: 10.9% vs . conscious sedation: 8.9%; P = 0.655) were comparable between the groups. CONCLUSIONS: General anesthesia is noninferior to conscious sedation for microelectrode-guided subthalamic nucleus deep brain stimulation, providing equivalent signal intensity and clinical outcomes while improving procedural efficiency, supporting its use as a valid clinical option.

Humans↗

PubMed2026

Lung function after randomization to metformin, lifestyle intervention or placebo in the Diabetes Prevention Program Outcomes Study (DPPOS).

INTRODUCTION: Metformin and physical activity have been suggested as beneficial for chronic lung disease; however, there are no prior randomized trials. METHODS: The Diabetes Prevention Program (DPP) was a 3-year trial that randomized 3234 individuals at risk for diabetes to metformin, lifestyle intervention or placebo. After the DPP, 88% of participants enrolled in the DPP Outcomes Study that offered lifestyle intervention to all and open-label continuation of metformin. Spirometry was performed at approximately 19 and 22 years post-randomization. Lung function measures were compared in an intention-to-treat (ITT) analysis by original randomization group. Models were unadjusted and adjusted for demographics, body size, smoking and sitting/standing at spirometry. Additional analyses tested prevalence of obstruction (FEV1/FVC <70%), restrictive pattern (FVC < LLN and FEV1/FVC ≥70%), preserved ratio impaired spirometry (PRISm: FEV1 <80% predicted, FEV1/FVC ≥70%) and symptoms (COPD Assessment Test [CAT] score ≥10). RESULTS: The 1888 participants with spirometry were a mean (±SD) age of 68.2 ± 9.3 years, 70% female and 6% currently smoked and 33% had previously smoked cigarettes. Mean follow-up time was 19.0 ± 0.8 years. The mean FEV1 was 2.14 ± 0.60 L, FVC 2.74 ± 0.74 L, FEV1/FVC 78.4 ± 6.4%, mean BMI was 32.4 ± 6.7 kg/m2 and 58% had diabetes. In both unadjusted and adjusted ITT analyses, randomization group was not associated with FEV1, FVC or FEV1/FVC. Likewise, rates of obstruction, restrictive pattern, PRISm or symptoms did not differ by randomization group. CONCLUSIONS: In this long-term follow-up after a randomized trial, we found no significant associations between randomization to metformin or lifestyle intervention and lung function or respiratory symptoms.

Humans↗

PubMed2026

Finerenone and quality of life in heart failure: component-level analyses and clinical relevance of the Kansas City cardiomyopathy questionnaire.

AIMS: Finerenone was shown to improve overall health status, as measured by the aggregate 23-item Kansas City Cardiomyopathy Questionnaire (KCCQ) score, in heart failure with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF). This study aimed to contextualize KCCQ changes in a manner that is relevant to patients and clinicians, thereby improving understanding of this metric in HFmrEF/HFpEF. METHODS AND RESULTS: In this prespecified analysis of FINEARTS-HF, a double-blind, randomized, placebo-controlled trial of finerenone in HFmrEF/HFpEF, we performed exploratory assessments of treatment effects on mean score changes from baseline to 12 months for each of the 23 KCCQ components (scaled from 0 [worst] to 100 [best]) using multivariable linear regression. We further compared the impact of finerenone on the KCCQ-overall summary score (KCCQ-OSS) at 12 months with the expected decline per year. Of 6001 participants in FINEARTS-HF, 5006 completed the KCCQ both at baseline and 12 months (age: 72 ± 10 years, women: 45%, baseline KCCQ-OSS: 63.9 ± 22.0). Finerenone, compared with placebo, numerically improved all but one KCCQ component, with the greatest nominal improvement observed in lower limb oedema frequency (+2.5, 95% CI: 0.9-4.1), fatigue burden (+2.2, 95% CI: 0.9-3.5), fatigue frequency (+2.1, 95% CI: 0.7-3.6), and lower limb oedema burden (+1.8, 95% CI: 0.6-2.9). KCCQ-OSS at 12 months was inversely related to age, with finerenone shifting the age-KCCQ-OSS relationship by 4.7 (95% CI: 0.4-9.1) years. CONCLUSIONS: In FINEARTS-HF, finerenone was associated with modest improvements in health status-most notably lower limb oedema and fatigue-in patients with HFmrEF/HFpEF.

Humans↗

PubMed2026

Comparison of deep and nondeep hypothermia in thoracic and thoracoabdominal aortic surgery: A systematic review and meta-analysis.

OBJECTIVE: Deep hypothermic circulatory arrest (DHCA) remains a cornerstone technique for neuroprotection and end-organ preservation during ascending aorta and arch surgeries. However, its benefits and risks compared with non-DHCA strategies in thoracic and thoracoabdominal aortic aneurysm (TAAA) repair are uncertain owing to conflicting evidence and variable institutional practices. METHODS: A systematic review and meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis and Cochrane guidelines. PubMed, Embase, and Cochrane Library were searched for comparative studies evaluating DHCA and non-DHCA techniques for open thoracic and TAAA repair. Random-effects models were applied to calculate pooled effect estimates. Effect sizes were risk ratio (RR) for binary end points and mean difference for continuous end points, both with 95% confidence intervals. Statistical significance was set at P < .05. Between-study heterogeneity was estimated using the I2 statistic. Metaregression analyses were used to explore the sources of heterogeneity. RESULTS: Nine observational studies, including 1041 patients, were analyzed. DHCA use was associated with a significantly lower risk of spinal cord injury (RR, 0.44; P = .012) compared with non-DHCA. However, DHCA was also associated with prolonged postoperative ventilation time (RR, 1.34; P = .003). No significant differences were observed in overall mortality, length of hospital and intensive care unit stay, stroke, or renal complications. Metaregression identified patient age as a moderator of length of stay variability, with older cohorts demonstrating longer recovery periods. CONCLUSIONS: DHCA is associated with a lower risk of spinal cord injury during TAAA repair without increasing mortality or stroke risk, although it is associated with longer ventilation times.

Humans↗

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

Robust error-minimization in the genetic code across physicochemical metrics and variant codes: A graph-theoretic analysis in GF(2)6.

The standard genetic code reduces the impact of point mutations, but the robustness of this property across physicochemical metrics, naturally occurring variant codes, and codon-reassignment mechanisms remains incompletely quantified. Embedding the 64 codons in GF(2)6 represents the hypercube Q6 as a coordinate-dependent subgraph of the encoding-independent single-nucleotide mutation graph H(3,4), and enables continuous ρ-interpolation between the two. Under a quartet-pattern shuffle null (n=10,000), the standard code is significantly low-cost across four established, code-independent physicochemical distance metrics with partially overlapping content (Grant ham p=0.0062; Miyata p<0.001; Woese polar requirement p=0.003; Kyte-Doolittle hydropathy p=0.001), and the signal strengthens monotonically as ρ moves Q6→H(3,4). A structure-aware sensitivity analysis under the alignment-derived ProtSub matrix (Jia & Jernigan 2021) yields the most extreme percentile of any measure tested (p=0.0004; all five p-values pass Bonferroni at α=0.05). Across the 27 NCBI translation tables, near-optimality is preserved: 11 of 12 informative-distance variants retain top-5% placement after BH-FDR correction. Natural codon reassignments avoid disrupting codon-family connectivity: under the encoding-independent H(3,4) adjacency, observed events are topology-breaking at relative risk 0.32 versus the candidate landscape (permutation p≤10-4). The H(3,4) result is stable by construction; the Q6 decomposition is representation-specific and fails to show depletion under 8 of 24 base-to-bit encodings, so we report H(3,4) as the primary test and Q6 as a sensitivity. Event-level conditional-logit modelling shows that topology avoidance and local physicochemical cost provide complementary, only weakly correlated signal (rs=0.15), and that topology adds explanatory value beyond physicochemistry under both Q6 and encoding-independent H(3,4) adjacency. Retrospective reanalysis of nine genome-recoding datasets is consistent with codon-family topology operating as an evolutionary-trajectory constraint distinct from acute engineering fitness. The contribution is the second axis: code evolution is jointly constrained by physicochemical smoothness and codon-family topological integrity, and these two constraints are partly independent.

Codon reassignment↗