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Preoperative Proximal Migration of the Radial Head as an Independent Predictor of Suboptimal Outcomes After Osteochondral Autograft Transplantation for Capitellar Osteochondritis Dissecans: A Retrospective Cohort Study.

BACKGROUND: Osteochondral autograft transplantation (OAT) is widely performed for capitellar osteochondritis dissecans (OCD). However, preoperative predictors of suboptimal postoperative outcomes remain unclear. PURPOSE/HYPOTHESIS: The authors aimed to evaluate clinical outcomes after OAT for capitellar OCD and identify preoperative risk factors associated with suboptimal outcomes. They hypothesized that radiographic indicators of disease severity, including preoperative proximal migration of the radial head, lesion size, and lateral wall disruption, would be associated with suboptimal postoperative clinical outcomes. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: The records of adolescent athletes who underwent OAT for capitellar OCD with a minimum 2-year follow-up were retrospectively reviewed. Clinical outcomes included elbow range of motion (ROM) and Timmerman-Andrews (T-A) score. A suboptimal outcome was defined as a postoperative T-A score <160. Preoperative radiographs were used to measure proximal migration of the radial head relative to the coronoid process, hypertrophy of the radial head, OCD lesion area, and a 5-grade lateral wall disruption classification; measurement reliability was assessed. Multivariate logistic regression analysis was performed to identify independent predictors of a suboptimal outcome, and receiver operating characteristic (ROC) curve analysis was used to determine the optimal cutoff value for proximal migration. RESULTS: A total of 69 elbows (mean age, 13.6 years; mean follow-up, 48 months) were included. ROM and T-A scores improved significantly after OAT, and all athletes returned to any sports. Of these, 50 elbows (72%) achieved good outcomes, whereas 19 (28%) had suboptimal outcomes. Preoperative proximal migration was significantly greater in the suboptimal outcome group compared with the good outcome group (mean, 2.1 &#xb1; 2.3 vs 0.5 &#xb1; 1.7 mm; P = .002), as were lesion area (mean, 70 &#xb1; 16 vs 58 &#xb1; 20 mm2; P = .02) and lateral wall disruption grade (median, 5 vs 3; P = .01). On multivariate analysis, proximal migration of the radial head was the only independent predictor of a suboptimal outcome (adjusted OR, 1.47 per 1-mm increase; 95% CI, 1.03-2.09; P = .033). ROC analysis showed an area under the curve of 0.72 with an optimal cutoff of 2.2 mm (sensitivity, 56%; specificity, 84%). CONCLUSION: OAT resulted in significant clinical improvement in adolescents with capitellar OCD; however, 28% of patients were classified as having suboptimal outcomes. Preoperative proximal migration of the radial head is an independent predictor of a suboptimal postoperative outcome. A value >2.2 mm may indicate advanced radiocapitellar incongruity, a condition in which OAT may be less effective.

Humans

Older adults with resectable gastric cancer undergoing perioperative chemotherapy or preoperative chemoradiotherapy plus perioperative chemotherapy: A secondary analysis of the AGITG TOPGEAR phase III trial.

PURPOSE: To evaluate treatment adherence, adverse events, and survival in older (&#x2265;70 years) adults undergoing perioperative treatment for gastric cancer. METHODS: Patients with resectable gastric/gastro-esophageal junction adenocarcinoma (ECOG 0-1) enrolled in the phase III TOPGEAR trial were randomized to perioperative chemotherapy (ECF/ECX or FLOT) alone or perioperative chemotherapy plus preoperative chemoradiotherapy (45&#x202f;Gy in 25 fractions with concurrent fluoropyrimidine). In this exploratory analysis, treatment completion, grade &#x2265;&#x202f;3 adverse events (CTCAE v3.0), surgical outcomes, overall survival (OS) and progression-free survival (PFS) were compared between older and younger adults. RESULTS: Of the 574 patients enrolled, 135 (24%) were &#x2265;&#x202f;70 years. Older adults more frequently required preoperative chemotherapy dose reductions, omissions, or delays (chemoradiotherapy: 55% vs 35%, p&#x202f;=&#x202f;0.004; chemotherapy: 60% vs 48%, p&#x202f;=&#x202f;0.087). Rates of grade &#x2265;&#x202f;3 adverse events were comparable between older and younger patients (chemoradiotherapy: 66% vs 67%, p&#x202f;=&#x202f;0.874; chemotherapy: 68% vs 59%, p&#x202f;=&#x202f;0.220), but older adults more often had hematologic toxicity and grade &#x2265;&#x202f;3 diarrhea in the chemotherapy group (56% vs 37%, p&#x202f;=&#x202f;0.006; 21% vs 6%, p&#x202f;<&#x202f;0.001). Resection rates, grade 3/4 surgical complications, number of removed lymph nodes, and 30-/90-day mortality were similar by age. OS and PFS were comparable across age groups, with numerically favorable outcomes for older adults (OS: HR 0.86, 95% CI 0.58-1.26 [chemoradiotherapy]; HR 0.75, 95% CI 0.51-1.11 [chemotherapy]; PFS: HR 0.78, 95% CI 0.53-1.15 [chemoradiotherapy]; HR 0.70, 95% CI 0.47-1.03 [chemotherapy]). CONCLUSIONS: Older adults with gastric cancer achieved comparable oncologic outcomes to younger patients, despite more frequent treatment modifications and higher hematologic toxicity.

Humans

Impact of a multimodal prehabilitation program on postoperative cognitive dysfunction: a single-center randomized controlled trial.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is a frequent complication after cardiac surgery. Exercise-based prehabilitation may enhance functional reserve and reduce vulnerability to perioperative cerebral insults. We hypothesized that multimodal prehabilitation reduces POCD 3&#xa0;months after cardiac surgery. METHODS: This prespecified substudy of a single-center randomized controlled trial (NCT03466606) included patients aged &#x2265;50&#xa0;years undergoing elective coronary artery bypass grafting and/or valve surgery. Participants were randomized 1:1 to 4-6&#xa0;weeks of multimodal prehabilitation (exercise training, nutritional support, and psychological support) or standard preoperative care. Cognitive function was assessed at baseline and 3&#xa0;months postoperatively using an age- and education-adjusted neuropsychological battery. POCD was defined as performance &#x2265;1.5 standard deviations below normative values in at least 2 cognitive tests, excluding the Mini-Mental State Examination. Logistic regression analyses were performed to evaluate factors associated with POCD. RESULTS: Of 160 participants screened from the parent trial, 134 met eligibility criteria for the substudy and were randomized; 116 completed 3-month follow-up (prehabilitation n&#xa0;=&#xa0;53; control n&#xa0;=&#xa0;63). POCD occurred in 29 patients (25%), including 15/53 (28%) in the prehabilitation group and 14/63 (22%) in controls (odds ratio [OR] 1.37, 95% confidence interval [CI] 0.54-3.50, P&#xa0;=&#xa0;0.52). In multivariable analysis, preoperative cognitive impairment was independently associated with POCD (OR 13.28, 95% CI 4.06-43.41, P&#xa0;<&#xa0;0.001), whereas prehabilitation was not (OR 1.09, 95% CI 0.35-3.45, P&#xa0;=&#xa0;0.877). Higher physical activity levels at 3&#xa0;months were associated with lower odds of POCD (OR 0.97, 95% CI 0.95-1.00, P&#xa0;=&#xa0;0.047). CONCLUSIONS: In this randomized controlled trial, a 4-6-week multimodal prehabilitation program did not reduce postoperative cognitive dysfunction 3&#xa0;months after cardiac surgery. Although the intervention did not achieve measurable cognitive protection, the observed association between postoperative physical activity levels and postoperative cognitive dysfunction warrants further investigation.

Humans

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&#x2009;>&#x2009;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&#x2009;=&#x2009;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

Tissue origins of the plasma proteomic response to glucose ingestion in humans.

AIMS/HYPOTHESIS: Circulating proteins act as important hormonal signals of nutrient intake. We aimed to systematically characterise the time-resolved proteomic response to glucose ingestion in humans, and to assess its robustness following prolonged complete caloric restriction. METHODS: We conducted oral glucose tolerance tests (OGTTs) in 11 healthy volunteers before and after 7 days of complete caloric restriction and measured the response of >2900 targets through high-resolution plasma protein profiling. RESULTS: We identified a signature of 44 proteins that changed significantly following glucose ingestion, which was reproducible after 7 days without food, and was strongly (20-fold) enriched for 'stomach-specific' proteins. We report that annexin A10 (ANXA10) shows the most significant post-glucose change observed, similar to the trajectories of secreted hormones. We present observational human evidence from multiple sources suggesting that ANXA10 is secreted upon sensing an increase in gastric pH, with the stomach as the major contributing tissue. Despite a profound metabolic shift after 7 days of complete caloric restriction, characterised by delayed insulin secretion and postprandial hyperglycaemia, only four proteins showed robust evidence for a differential trajectory during both OGTTs. This included plasma levels of tryptophanyl-tRNA synthetase&#xa0;1 (WARS), for which we found a genetic association with glucose homeostasis and coronary artery disease. CONCLUSIONS/INTERPRETATION: Our exploratory study identifies the proteomic response to glucose ingestion and demonstrates its reproducibility despite major shifts in glucose homeostasis. We characterise the gastrointestinal origin of these changes, and hypothesise a hitherto under-recognised role for sensing of changes in gastric pH on the plasma proteome.

Humans

Genome-wide characterisation of the myosin light chain gene family in Chinese perch (Siniperca chuatsi) and its expression patterns in muscle fibre types and injury response.

The Class II myosin light chain (myl) genes in Chinese perch (Siniperca chuatsi) have not yet been systematically characterised, and relationships with muscle fibre specification, development, and injury-associated remodelling remain unclear. In this study, fast and slow muscle fibres were initially distinguished using myofibrillar ATPase histochemistry. Subsequently, genome-wide mining identified 16 Class II myl genes, comprising eight essential and eight regulatory light-chain subunits. Their conserved-domain features, chromosomal distribution, phylogenetic relationships and expression profiles were analysed. Transcriptomic profiling showed that summed myl transcript abundance was higher in fast muscle than in slow muscle, accounting for 67.2% of the pooled myl transcript pool across the two muscle types (paired t-test, raw P&#xa0;=&#xa0;0.036). mylpfa, myl1 and mylz3 were the major fast-muscle-associated genes, whereas myl10, myl2b and myl13 were preferentially expressed in slow muscle at the transcript level. These patterns support these genes as candidate fibre-type-associated expression markers. Developmental profiling identified stage-associated myl expression patterns, including a possible expression shift between mylpfb and mylpfa. In the descriptive injury-repair time course (d0-d7), FPKM profiles indicated that fast-muscle-associated genes (mylpfa, mylz3 and myl1) were lower at d1 and recovered by d3, whereas several slow-muscle-associated genes showed biphasic transcript-level increases. The slow-muscle-associated RLC gene mylpfb showed a delayed expression peak at d7. Notably, the embryonic isoform myl6l showed a modest increase from approximately 2 FPKM at d0 to 4-5 FPKM after injury, suggesting a possible injury-associated expression pattern that requires further validation. Together, these findings provide a genome-wide description of the Chinese perch myl gene family and identify candidate fibre-type-associated genes and descriptive injury-associated isoform expression patterns.

Animals

Novelty seeking and rapid symptom improvement across active and sham accelerated iTBS conditions: A pooled individual-patient data analysis.

INTRODUCTION: Major depressive disorder (MDD) is highly prevalent and often treatment-resistant. Accelerated intermittent theta burst stimulation (aiTBS) is a promising intervention for treatment-resistant depression (TRD), though outcomes vary. Personality traits have been examined in relation to rTMS outcomes, yet their role in aiTBS remains underexplored. This pooled individual-patient-data analysis of two randomized, sham-controlled trials examined associations between baseline Temperament and Character Inventory (TCI) traits and one-week symptom change, and whether they differed by condition. METHODS: The left dorsolateral prefrontal cortex was targeted for 20 sessions over 4&#xa0;days. Personality was assessed with the TCI, depression severity with the 17-item Hamilton Depression Rating Scale (HDRS-17). TCI-symptom-change associations were examined with a robust linear mixed-effects model, adjusting for age, gender, repeated measurements, and study membership. RESULTS: 104 participants were included (M/F 45/59; mean age 40.9&#xa0;&#xb1;&#xa0;12.7; active/sham 50/54). The model yielded a Time &#xd7; Novelty Seeking interaction (&#x3b2;&#xa0;=&#xa0;-1.70, p&#xa0;=&#xa0;0.021): higher baseline Novelty Seeking was associated with faster symptom reduction, without a between-arm difference. However, the interaction did not survive Holm correction across 14 trait-interaction tests (adjusted p&#xa0;=&#xa0;0.294) and is therefore exploratory. No other interaction reached the uncorrected threshold. CONCLUSIONS: Higher baseline Novelty Seeking showed a nominal association with faster symptom reduction, without a difference between active and sham conditions. Because it did not survive multiplicity correction and was not reproduced in within-arm analyses, it is preliminary and may reflect contextual or nonspecific processes. Independent replication is required before temperament assessment can be clinically informative.

Humans

Effects of intensive lifestyle interventions with calorie-carbohydrate-restricted diet versus time-restricted eating on appetite and binge eating in type 2 diabetes: A randomized controlled trial.

The impact of intensive lifestyle interventions on appetite regulation and binge eating in individuals with type 2 diabetes (T2D) remains unclear. This study evaluated the effects of combined lifestyle interventions on appetite responses and binge eating in overweight or obese adults with T2D. In a randomized trial, 120 participants with T2D were allocated to three groups (n&#xa0;=&#xa0;40 each): (1) Calorie-carbohydrate restriction (CCR), (2) Time-restricted eating with CCR (TRE&#xa0;+&#xa0;CCR), or (3) Control. Intervention groups received structured exercise and behavioral education based on the Information-Motivation-Behavioral Skills model. Appetite perceptions (hunger, satiety, desire to eat, and prospective food consumption) and binge eating (Binge Eating Scale; BES and objective binge episodes) were evaluated at baseline, week 12, and week 24 using linear mixed models. Both CCR and TRE&#xa0;+&#xa0;CCR significantly improved subjective appetite compared with the control group at 12 and 24 weeks (all p&#xa0;<&#xa0;0.01). At 24 weeks, hunger decreased by -24.1&#x202f;mm (95% CI: -35.8, -12.5) in the CCR group and -32.7&#x202f;mm (95% CI: -44.2, -21.3) in the TRE&#xa0;+&#xa0;CCR group. Satiety also increased by 21.7&#x202f;mm (95% CI: 9.46, 33.9) and 29.4&#x202f;mm (95% CI: 17.4, 41.4), respectively. Significant reductions were observed for desire to eat and prospective food consumption. In contrast, changes in BES and objective binge episodes were not significantly different between groups at any time point. No significant differences were detected between the CCR and the TRE&#xa0;+&#xa0;CCR groups. Intensive lifestyle interventions incorporating CCR or TRE&#xa0;+&#xa0;CCR effectively reduced appetite in adults with T2D but did not significantly affect binge eating. Future research should target individuals with higher baseline BES scores to clarify potential benefits for binge eating behavior.

Humans

Postoperative Curvature Loss in Three-Level Anterior Cervical Discectomy and Fusion With Zero-Profile Device.

PURPOSE: Cervical curvature loss is a frequent complication following 3-level anterior cervical discectomy and fusion (ACDF) using a Zero-Profile device. Consequently, the capacity of this device to maintain cervical sagittal alignment in 3-level ACDF remains highly controversial. This study aimed to identify potential predictors for postoperative curvature loss (PCL) and evaluate its impact on clinical outcomes. METHODS: A total of 113 patients who underwent ACDF for 3-level cervical degenerative disc disease (CDDD) between January 2021 and December 2023 were retrospectively reviewed. Demographic data, radiological parameters, and clinical outcomes were analyzed. Radiographic measures included cervical curvature, T1 slope, C2-7 sagittal vertical axis, and titanium plate and endplate (TPE) distance. Clinical outcomes were assessed using the Visual Analog Scale (VAS), Neck Disability Index (NDI), and Japanese Orthopaedic Association (JOA) scores. Statistical analyses were performed using paired and independent t-tests, as well as Pearson correlation coefficients. RESULTS: The average curvature loss was 6.82&#xb0; from 1&#x2009;week postoperatively to the final follow-up (p&#x2009;<&#x2009;0.001). However, the final curvature (11.65&#xb0;) was maintained, representing a 4.33&#xb0; improvement compared to preoperative values. Significant correlations were observed between PCL and preoperative curvature (r&#x2009;=&#x2009;-0.368, p&#x2009;=&#x2009;0.013), preoperative T1 slope (r&#x2009;=&#x2009;-0.546, p&#x2009;<&#x2009;0.001), &#x2206;T1 slope (r&#x2009;=&#x2009;0.443, p&#x2009;=&#x2009;0.002), and &#x2206;TPE distance (r&#x2009;=&#x2009;0.417, p&#x2009;=&#x2009;0.004). PCL did not correlate with Japanese Orthopaedic Association (JOA) scores or arm VAS scores at the final follow-up. Nevertheless, patients with a PCL&#x2009;&#x2265;&#x2009;6&#xb0; exhibited significantly higher neck VAS (p&#x2009;=&#x2009;0.028) and NDI scores (p&#x2009;=&#x2009;0.041). CONCLUSION: Although contiguous 3-level ACDF with a Zero-Profile device may result in PCL, it preserves an improved cervical lordosis compared to the preoperative baseline. Low preoperative curvature and a low preoperative T1 slope are potentially predictive factors for PCL. Postoperative changes in TPE distance and T1 slope are significantly associated with PCL, suggesting a potential biomechanical link that requires direct validation. Furthermore, PCL may lead to higher neck VAS and NDI scores. Consequently, the Zero-Profile device may require careful consideration in 3-level CDDD patients presenting with low preoperative curvature and a low T1 slope. Importantly, the 6&#xb0; PCL threshold identified is preliminary and requires prospective validation before clinical application.

Humans

Effectiveness of exercise-based prehabilitation on pre and postoperative outcomes of patients undergoing cardiac surgery-An umbrella review of systematic reviews.

AIMS: Individuals undergoing cardiac surgery are becoming older, frailer, and less mobile. Prehabilitation has shown to improve postoperative outcomes by optimizing preoperative physical function. This umbrella review aims to pool the systematic reviews assessing the effectiveness of exercise-based prehabilitation in cardiac surgery. METHODS AND RESULTS: The review followed the PRIOR checklist. PubMed, Embase, CINAHL, Cochrane library, Scopus, Web of science, ProQuest NAHD, ProQuest HMC, Open Grey and MedNar were searched using relevant keywords from inception to 16th December, 2024. Two reviewers screened and extracted data from the included reviews and assessed primary study overlap with the corrected covered area. Methodological quality of the reviews was evaluated with the A MeaSurement Tool to Assess systematic Reviews-2 scale. Certainty of evidence was assessed using a previously developed criteria for overview of reviews. Six systematic reviews with 30 unique trials and 6705 participants were included. The interventions assessed included breathing exercises, inspiratory muscle training, and exercise training. Prehabilitation reduced length of hospital stay, postoperative pulmonary complications, and clinically improved functional capacity with a very low to moderate certainty of evidence. However, there was uncertainty regarding the effects pertaining to adverse events and quality of life. The methodological quality of all reviews was critically low. The primary trials scored poorly in the domains of selection and detection bias. CONCLUSION: Exercise-based prehabilitation might reduce length of hospital stay and postoperative complications, and improve functional capacity. However, the quality of evidence is poor, and individual discretion is required before implementing them into practice. REGISTRATION: PROSPERO: CRD42023480100.

Humans

Weight and metabolic changes in patients with schizophrenia treated with paliperidone palmitate 6-month formulation versus paliperidone palmitate 3-month formulation: a post-hoc analysis.

OBJECTIVE: To determine the effect that paliperidone palmitate 6-month long-acting injectable formulation (PP6M) had on metabolic parameters including body weight (BW), and blood lipid profiles, a post-hoc analysis was conducted to assess changes in BW from baseline to the end of study based on age, body mass index (BMI), and changes in blood lipid profiles during a 12-month, phase 3, double-blind (DB) clinical study. Long term effects of PP6M on BW and BMI were further explored during a 24-month extension study in which participants were treated exclusively with PP6M. METHOD: In the 12-month DB phase, participants were randomized to receive PP6M or paliperidone palmitate 3-month long-acting injectable formulation (PP3M). The mean change in BW and abnormal weight percent change from baseline were calculated at endpoint by age, gender, and BMI. Additionally, treatment-emergent shifts from baseline for the four key lipid parameters (fasting low density lipoprotein [LDL], fasting triglycerides [TG], fasting total cholesterol [TC], and fasting high density lipoprotein [HDL]) during DB were assessed. Following this study, participants were given the opportunity to transition to a 24-month extension study and be treated with PP6M. The mean change and percent change in BW, and the mean change in BMI from DB baseline to the end of the extension study (36&#xa0;months total) were calculated. RESULTS: Participants who were treated with PP6M showed numerically less weight gain, BMI, waist circumference, and more weight decrease compared to PP3M group during 12-month DB phase, though the proportion of participants reporting an abnormal change (&#x2265;7% change) in BW did not significantly differ between PP3M and PP6M. The weight differences were more pronounced in the younger age group (18-25&#xa0;years) and those who were overweight (BMI: 25 to <30&#xa0;kg/m2. Numerical differences in favor of PP6M were found in fasting blood lipids (HDL, LDL, TG, and TC). The changes in BW and BMI over time remained consistent throughout the 24-month extension, favoring PP6M in each instance. CONCLUSIONS: This post-hoc analysis demonstrated that PP6M was comparable to PP3M in terms of metabolic parameters; however, it may have a beneficial effect on weight gain, especially in young patients. TRIAL REGISTRATION: Post-Hoc Analysis of Studies NCT03345342 and NCT04072575 (ClinicalTrials.gov). Significant outcomes The findings from this study have highlighted that participants who were treated with the 6-month long-acting injectable formulation of paliperidone exhibited less weight gain during treatment overall, and significantly less weight gain in adolescents and young adults. Importantly, this trend continued over the course of long-term treatment, regardless of age. Participants treated with the 6-month formulation also had fewer shifts in blood lipids outside of the normal range and had more favorable changes in body mass index and waist circumference. These results suggest that when considering metabolic dysregulation as a factor in choosing a long-acting injectable antipsychotic, the 6-month formulation is a viable alternative to the 3-month formulation, particularly in younger patients with schizophrenia. Limitations Because this is a post hoc analysis and the study was not powered to test weight and metabolic changes, most endpoints were summarized descriptively and the statistical test was limited to the main endpoint (abnormal percent weight gain and loss).

Adult

The impact of prehabilitation on postoperative outcomes in patients undergoing radical prostatectomy for prostate cancer: a systematic review and meta-analysis.

PURPOSE: Preoperative rehabilitation training can optimize functional reserve before radical prostatectomy (RP), thereby improving postoperative outcomes. However, its effects on urinary incontinence, erectile function, and quality of life (QoL) remain controversial. This study systematically evaluated these outcome measures. METHODS: Data from randomized controlled trials (RCTs) were retrieved from the PubMed, Cochrane Library, Embase, and CINAHL databases. The risk of bias was assessed using the RoB-2 tool, and meta-analysis was performed using Stata 18.0 software. Two reviewers independently performed study selection, data extraction, and risk-of-bias assessment. Meta-analyses were conducted using fixed- or random-effects models according to heterogeneity. Outcomes included urinary incontinence incidence, urinary incontinence severity, erectile function, and QoL at different postoperative follow-up time points. RESULTS: 16 randomized controlled trials involving 1,542 participants were included. Prehabilitation significantly reduced the incidence of urinary incontinence at 1&#xa0;month (OR&#x2009;=&#x2009;0.58, 95% CI 0.39-0.84) and 6&#xa0;months (OR&#x2009;=&#x2009;0.52, 95% CI 0.28-0.96) after RP, with a non-significant borderline reduction at 3&#xa0;months, and no significant benefit at 12&#xa0;months. No significant improvement was observed in urinary incontinence severity or erectile function at any follow-up time point. Prehabilitation significantly improved QoL within 3&#xa0;months (SMD&#x2009;=&#x2009;-0.70, 95% CI -1.08 to -0.32) and 6&#xa0;months (SMD&#x2009;=&#x2009;-0.45, 95% CI -0.74 to -0.16) postoperatively. However, within 12&#xa0;months, the effect size attenuated, showing only a marginal trend that did not reach statistical significance (SMD&#x2009;=&#x2009;-0.33, 95% CI -0.66 to 0.00). Risk of bias was generally moderate. CONCLUSION: Prehabilitation reduces early incontinence and improves QoL post-RP, but its effects on severity and erectile function remain unclear. SYSTEMATIC REVIEW REGISTRATION: PROSPERO [CRD420251183407].

Humans

Role of nicotine metabolite ratio in pharmacological interventions on smoking cessation: A systematic review and meta-analyses of randomized controlled trials.

BACKGROUND AND OBJECTIVES: Emerging evidence suggests that the nicotine metabolite ratio (NMR) may influence the efficacy of smoking cessation, yet its role across pharmacotherapies remains unclear. This study aims to investigate how NMR affects cessation outcomes under different medications to guide personalized treatment. METHODS: We searched PubMed, Medline, EMBASE, and the Cochrane Central Register of Controlled Trials (inception to September 30, 2024) for randomized controlled trials on pharmacotherapy for smoking cessation with NMR data. Data were synthesized using random-effects models, with heterogeneity assessment. The primary outcome was verified smoking cessation rate at the end of treatment or the closest time-point. RESULTS: Eleven RCTs with accessible full text were included in the qualitative analyses and nine were included in the quantitative synthesis. For non-titratable nicotine replacement therapy (NRT), normal/fast metabolizers demonstrated lower odds of smoking cessation than slow metabolizers (Odds Ratio, OR=0.81, 95% confidence interval, CI=0.68-0.96; 5 studies, I&#xb2;=62.5%). No significant associations were shown between normal/fast and slow metabolizers using titratable NRT (OR=1.04, 95% CI=0.95-1.14; 2 studies, I&#xb2;=0%), bupropion (OR=0.67, 95% CI=0.38-1.16; 2 studies, I&#xb2;=51.4%), or varenicline (OR=1.17, 95% CI=0.79-1.74; 4 studies, I&#xb2;=59.8%). CONCLUSION: Current evidence demonstrates that NMR moderates' treatment efficacy among those who smoke using non-titratable NRT, with slow metabolizers achieving significantly better cessation outcomes than normal/fast metabolizers. Substantial further research is needed to determine optimal medication hierarchies across metabolic profiles.

Humans

Granger connectivity and graph-theoretical analysis of scalp EEG across the preictal to ictal transition for presurgical evaluation.

OBJECTIVE: To assess the feasibility of estimating lateralization and localization of the epileptogenic zone (EZ) in temporal and extratemporal lobe epilepsy by combining Electric Source Imaging (ESI) with functional connectivity analysis of high-density EEG from the preictal to the ictal phase. METHODS: Adults with drug-resistant focal epilepsy and at least one recorded seizure during 40- or 64 channels EEG monitoring were retrospectively included. Granger causality and hubness centrality were computed over the 10-s preictal interval and the first 5 s of the ictal period, with ictal onset defined as the first EEG change identified by experienced epileptologists. The reference standard for EZ localization was based on resective surgical outcome or stereo-EEG findings. RESULTS: Thirteen patients (7 females; median age 35 years) were included. Connectivity analyses showed higher concordance with clinical findings during the preictal phase than during the ictal phase for both lateralization (91% vs 46%) and localization (73% vs 27%). Performance was highest in temporal (7/7 lateralization; 6/7 localization) and frontal lobe epilepsy (2/2 for both), and lower in parieto-occipital epilepsy (1/2 and 0/2, respectively). In two cases with poor surgical outcome or no surgical indication, connectivity findings were discordant with clinical estimates. CONCLUSIONS: Connectivity analysis across the preictal to ictal transition provides relevant lateralizing and localizing information, particularly in temporal and frontal lobe epilepsy, and may reveal clinically meaningful discordance. SIGNIFICANCE: Integrating high-density EEG, ESI, and functional connectivity during the phase preceding the first EEG change may support non-invasive presurgical evaluation.

Humans

Blood Metabolomic Signatures of 1-Hour Glucose Predict Cardiometabolic Risk.

BACKGROUND: Elevated 1-hour glucose levels during an oral glucose tolerance test strongly predict type 2 diabetes (T2D) and cardiovascular disease. We investigated whether the fasting blood metabolome predicting 1-hour glucose could be a target for improving &#x3b2;-cell function, long-term glycemic trajectories, and reducing the risks of T2D and coronary heart disease. We also investigated whether plasma microRNAs derived from key metabolic organs regulate changes in a metabolomic risk score (MRS) for predicting 1-hour glucose. METHODS: Untargeted blood metabolomics and a frequently sampled 75-g oral glucose tolerance test were performed in participants from the OmniCarb trial (n=162). In an independent weight-loss dietary intervention trial (POUNDS Lost [Preventing Overweight Using Novel Dietary Strategies]), temporal changes in MRS and plasma microRNAs measured by genome-wide sequencing were analyzed. In addition, associations of MRS at baseline and its 10-year changes with long-term risk of incident T2D and coronary heart disease were prospectively investigated in the NHS (Nurses' Health Study). RESULTS: We created a fasting blood MRS for predicting 1-hour glucose (Pearson r=0.8) and found significant associations with half-day (diurnal) postprandial glucose excursions and insulin secretion after 5-week controlled feeding interventions varying in carbohydrate amount and glycemic index. In the POUNDS Lost trial, diet-induced changes in MRSs were related to 2-year trajectories of glucose metabolism; circulating microRNAs regulating cardiometabolic abnormalities were pivotal factors influencing these changes. In the NHS, women in the top 20% of MRS had a multivariate-adjusted relative risk of 3.80 (95% CI, 2.22-6.51) for T2D and 1.48 (95% CI, 1.04-2.12) for coronary heart disease compared with those in the lowest 20%. In addition, 10-year increases in plasma metabolites related to 1-hour glucose were linearly associated with a higher risk of T2D. CONCLUSIONS: Our findings indicate that fasting blood metabolomic signatures predicting elevated 1-hour glucose reflect disease pathophysiology and could be targets for preventing T2D and coronary heart disease.

blood glucose

Exercise prehabilitation in head and neck cancer patients proposed for definitive chemoradiotherapy: The FIT4TREAT randomized controlled trial.

BACKGROUND: Patients with head and neck cancer (HNC) initially scheduled for definitive chemoradiotherapy (CRT) often experience early functional decline and deterioration in health-related quality of life (HRQoL) even before treatment initiation. Evidence for prehabilitation in this non-surgical setting remains limited. This study evaluated whether exercise prehabilitation (EP) initiated before CRT improves functional capacity compared with usual care (UC). METHODS: FIT4TREAT (ClinicalTrials.gov: NCT05418842) was a prospective, single-center, randomized clinical trial. Adults with HNC proposed for definitive CRT were randomly assigned (1:1) to EP or UC. EP consisted of supervised combined aerobic and resistance exercise performed three times per week from baseline until radiotherapy initiation. The primary outcome was the six-minute walk distance (6MWD) at the end of the pre-treatment period. Secondary outcomes included muscle strength, lower-limb functionality, body composition, and HRQoL assessed using the EORTC QLQ-C30 and QLQ-HN43. RESULTS: Between May 2021 and February 2025, 47 patients were enrolled; 40 were included in the primary analysis. After adjustment for baseline 6MWD and the randomization stratification variables, EP resulted in a significantly greater pre-treatment 6MWD than UC (adjusted between-group difference, 28.6&#xa0;m; 95&#xa0;% CI, 4.1-53.1; P&#xa0;=&#xa0;0.023). EP also improved lower-limb functionality (P&#xa0;<&#xa0;0.001) and was associated with better preservation in the QLQ-C30 summary score (P&#xa0;=&#xa0;0.008), social functioning (P&#xa0;=&#xa0;0.038) and body image (P&#xa0;=&#xa0;0.011). CONCLUSION: EP before definitive CRT improves functional capacity and may help preserve HRQoL in patients with HNC, supporting its potential integration into routine oncology care.

Humans

Longitudinal functional trajectory and surgical outcomes after intracranial meningioma resection: implications for surgical decision-making in older patients.

OBJECTIVE: As the population ages, meningiomas are increasingly encountered in older patients, yet longitudinal functional outcomes following surgery across age groups remain incompletely characterized. This study evaluated age-related differences in clinical and tumor characteristics, functional trajectory, and surgical outcomes. METHODS: This was a retrospective cohort study of 396 consecutive patients who underwent surgery for intracranial meningiomas at a single academic center between January 2023 and September 2025. Patients were stratified into 5 age groups (< 65, 65-69, 70-74, 75-79, and &#x2265; 80 years). Neurological deficits and Karnofsky Performance Status (KPS) were assessed preoperatively, at discharge, and at last follow-up. Logistic regression analyses identified predictors of prolonged length of stay (LOS) (> 5 days) and poor functional outcome at discharge (KPS < 80). RESULTS: Older patients presented with greater comorbidity burden, larger tumors, and lower preoperative KPS (all p < 0.05), while gross-total resection was achieved at comparable rates across all age groups (p = 0.504). A clinically meaningful inflection point was observed around age 75 years, with KPS < 80 at discharge rising from 7.4% and 9.7% in the < 65-year and 70- to 74-year subgroups and to 36.2% and 57.1% in the 75- to 79-year and &#x2265; 80-year subgroups (p < 0.001), and median LOS increased from 4 days in the younger groups to 9 and 7 days in the 75- to 79-year and &#x2265; 80-year groups (p < 0.001). However, recovery rates among patients who experienced functional decline at discharge were comparable across age strata. On multivariable analysis, independent predictors of prolonged LOS were age &#x2265; 75 years (OR 2.31, p = 0.019), diabetes mellitus (OR 2.85, p = 0.004), posterior fossa location (OR 2.1, p = 0.008), tumor diameter (OR 1.33, p < 0.001), postoperative edema (OR 2.58, p = 0.015), and neurosurgical complications (OR 3.18, p = 0.002). Independent predictors of poor functional outcome at discharge were age &#x2265; 75 years (OR 5.84, p < 0.001), lower preoperative KPS (OR 2.8, p < 0.001), posterior fossa location (OR 3.72, p = 0.003), neurosurgical complications (OR 3.56, p = 0.008), and recurrent meningioma (OR 2.89, p = 0.025). Among 70 endoscopic endonasal approach patients, higher preoperative deficit burden and subtotal resection rates were observed compared to open craniotomy, though overall functional outcomes were comparable. CONCLUSIONS: Surgical risk in meningioma resection increases from age 75 years onwards, yet recovery capacity following initial functional decline remains similar across all age groups. Preoperative functional status, tumor location, comorbidity burden, and recurrence history should guide surgical decision-making rather than age alone.

Humans

The Impact of Baseline Negative Emotions on Postoperative Quality of Life in Adolescent Idiopathic Scoliosis Patients: A 2-Year Follow-Up Study.

OBJECTIVE: Adolescent idiopathic scoliosis (AIS) is a three-dimensional spinal deformity that develops during puberty without a clear etiology. Beyond physical manifestations, AIS severely impacts adolescents' psychological and social well-being, leading to anxiety, depression, and low self-esteem. While advancements in surgical techniques have enhanced objective outcomes, existing studies on AIS have primarily focused on objective indices, with limited attention to the long-term impact of preoperative negative emotions on patient-reported subjective quality of life. METHODS: This was a retrospective cohort study. A total of 112 eligible AIS patients who underwent posterior spinal correction surgery between April and August 2023 were enrolled. Inclusion criteria included confirmed AIS, completion of 2-year follow-up, and informed consent; exclusion criteria included missing imaging/questionnaire data, comorbid psychiatric/neurological diseases, or prior spinal surgery. Patients were grouped using the Hospital Anxiety and Depression Scale (HADS) administered on admission. Quality of life was assessed preoperatively and 2&#x2009;years postoperatively using the Scoliosis Research Society-22 (SRS-22, evaluating self-image, mental health, pain, function, treatment satisfaction) and Short Form 36 Health Survey (SF-36, assessing 8 physical and mental health dimensions). Statistical analysis was performed via SPSS, using independent t-tests, paired t-tests, Mann-Whitney U test, and chi-square test. p&#x2009;<&#x2009;0.05 was considered significant. RESULTS: There were no significant differences in baseline characteristics (age, gender, BMI, surgical parameters, scoliosis type, preoperative/postoperative Cobb angles) between the two groups (all p&#x2009;>&#x2009;0.05). Preoperatively, SRS-22 and SF-36 scores showed no inter-group differences (all p&#x2009;>&#x2009;0.05). Postoperatively, the Negative Emotion Group had significantly lower scores in SRS-22 mental health (3.9&#x2009;&#xb1;&#x2009;0.3 vs. 4.5&#x2009;&#xb1;&#x2009;0.2) and treatment satisfaction (4.0&#x2009;&#xb1;&#x2009;0.3 vs. 4.6&#x2009;&#xb1;&#x2009;0.7), as well as SF-36 general health (68.6&#x2009;&#xb1;&#x2009;6.4 vs. 79.7&#x2009;&#xb1;&#x2009;13.3), role-emotional (61.3&#x2009;&#xb1;&#x2009;9.3 vs. 70.8&#x2009;&#xb1;&#x2009;9.7), and mental health (61.8&#x2009;&#xb1;&#x2009;14.3 vs. 68.9&#x2009;&#xb1;&#x2009;10.7) (all p&#x2009;<&#x2009;0.05); no inter-group differences were observed in physical function-related dimensions. Both groups showed significant improvements in physical function-related dimensions postoperatively. The Non-Negative Emotion Group also exhibited significant improvements in SRS-22 self-image/pain and SF-36 bodily pain (all p&#x2009;<&#x2009;0.05), while the Negative Emotion Group showed no significant improvements in these dimensions. CONCLUSIONS: Preoperative anxiety and depression do not affect the recovery of physical function in AIS patients after spinal correction surgery but significantly impede improvements in subjective quality of life dimensions, including mental health and treatment satisfaction. These findings highlight the need to integrate psychological assessment and targeted interventions into the perioperative management of AIS. Such a patient-centered approach will help optimize both physical and psychological outcomes, ultimately achieving comprehensive rehabilitation for AIS adolescents.

Humans