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PubMed2026

Association between youth athletes' sports specialization and injuries: a systematic review and meta-analysis.

INTRODUCTION: The purpose of this study was to conduct a systematic review and meta-analysis to examine the specialization-injury relationship, and explore whether the specialization-injury relationship is moderated by study design, sport type, age, sex, and injury measurement type, injury mechanism, and anatomical location. METHODS: We searched eight databases by related keywords and assessed the quality of the included studies using the JBI Critical Appraisal Checklist for Analytical Cross-Sectional Studies and the Newcastle-Ottawa Scale. The Comprehensive Meta-Analysis (CMA) statistical software 3.7 examined heterogeneity, sensitivity, publication bias, overall effect size of specialization-injury relationship, and moderation effects. This review was prospectively registered in PROSPERO (CRD420251233318). Searches were conducted in eight electronic databases from inception to March, 2026. RESULTS: The 15 included studies showed moderate heterogeneity, stable sensitivity analyses, and no publication bias. The overall odds ratio of the sports specialization-injury relationship was 2.00 (95% confidence interval [1.58-2.55], p < .001). Moderation analyses indicated that sport type significantly influenced the specialization-injury relationship, whereas no significant moderation effects were observed for study design, sex, age, injury measurement type, injury mechanism, and injury anatomical location. CONCLUSIONS: The findings indicate a positive association between sport specialization and injury risk among youth athletes, with variation across sport participation contexts. Specifically, athletes in both contact and non-contact sports demonstrated higher pooled odds of injury than those involved in multiple sports. Although the evidence is heterogeneous and should be interpreted with caution, these findings highlight the potential role of diversified sport participation in relation to injury.

Humans↗

PubMed2026

Decoding tumor immune microenvironment heterogeneity by single-cell and spatial multi-omics: From immunotherapy resistance to translational biomarkers.

Immune checkpoint blockade has transformed cancer therapy, yet primary and acquired resistance remain major clinical challenges. Increasing evidence indicates that immunotherapy resistance cannot be fully explained by tumor-intrinsic alterations or conventional biomarkers such as PD-L1 expression, tumor mutational burden, or microsatellite instability. Instead, therapeutic response is shaped by the tumor immune microenvironment (TIME) as a heterogeneous, spatially organized, and dynamically evolving ecosystem. Single-cell omics has revealed diverse immune and stromal cell states, including progenitor and terminally exhausted T cells, suppressive myeloid programs, B-cell/TLS-associated immune-reactive states, and CAF-mediated exclusion phenotypes. Spatial transcriptomics, spatial proteomics, and imaging-based approaches further demonstrate that these cell states assemble into distinct immune niches, including immune-inflamed, T-cell-excluded, myeloid-suppressive, metabolic/hypoxic, and TLS-associated niches. These spatial ecosystems determine whether antitumor immune cells can access malignant cells, receive antigen-presenting support, or become restrained by stromal, vascular, metabolic, and myeloid barriers. In this review, we summarize how single-cell and spatial multi-omics redefine TIME heterogeneity in immunotherapy resistance, highlight ligand-receptor communication networks linking cell states to spatial immune dysfunction, and discuss emerging translational biomarkers for patient stratification. We further propose that future immunotherapy biomarkers should evolve from static single-marker assays toward longitudinal, spatially resolved, and interpretable multi-omics models that guide precision combination immunotherapy.

Humans↗

PubMed2026

Effectiveness of the DASH diet versus alternative dietary interventions for hypertension management: A systematic review and meta-analysis.

BACKGROUND: The Dietary Approaches to Stop Hypertension (DASH) diet is widely recommended for blood pressure control; however, its comparative effectiveness relative to other structured dietary interventions remains uncertain. OBJECTIVE: To evaluate the comparative effectiveness of the DASH diet versus alternative dietary interventions on blood pressure and cardiometabolic outcomes in adults. METHODS: A systematic review and meta-analysis of randomized controlled trials was conducted in accordance with PRISMA guidelines. Multiple databases were searched from inception to February 2026. Eligible studies included adults with elevated blood pressure or hypertension comparing the DASH diet with other dietary interventions or usual care. Continuous outcomes were pooled using random-effects models and expressed as mean differences (MD) or standardized mean differences (SMD). Risk of bias was assessed using the Cochrane RoB 2 tool, and certainty of evidence was evaluated using the GRADE approach. RESULTS: A total of 22 randomized controlled trials were included in the qualitative synthesis, of which 10 were included in the meta-analysis. The DASH diet did not demonstrate a statistically significant advantage over comparator diets in reducing systolic blood pressure (MD = 1.30; 95% CI: -1.54 to 4.14) or diastolic blood pressure (MD = 0.21; 95% CI: -3.72 to 4.14), with substantial heterogeneity observed across studies. Significant effects were identified for selected cardiometabolic outcomes, including reductions in urinary sodium excretion (MD = -32.89; 95% CI: -62.76 to -3.01), LDL cholesterol (MD = -8.59; 95% CI: -14.64 to -2.54), and glycated hemoglobin (HbA1c) (MD = -0.49; 95% CI: -0.52 to -0.46), as well as an increase in urinary potassium excretion (MD = 11.76; 95% CI: 4.08 to 19.44). The certainty of evidence ranged from moderate to very low across outcomes. CONCLUSIONS: The DASH diet was not superior to other dietary interventions in reducing blood pressure; however, it demonstrated consistent benefits in selected cardiometabolic parameters. Given the overall low certainty of evidence and substantial heterogeneity, these findings should be interpreted cautiously. Future research should focus on well-designed trials with standardized outcomes and longer follow-up to clarify comparative effectiveness.

Humans↗

PubMed2026

Is ophthalmology a pain-free career? A systematic review and meta-analysis of musculoskeletal pain among ophthalmologists.

OBJECTIVE: To estimate the pooled prevalence, anatomical distribution, and occupational impact of work-related musculoskeletal (MSK) pain among ophthalmologists, and to identify modifiable ergonomic risk factors. DESIGN: A systematic review and meta-analysis of published data. The protocol was preregistered (PROSPERO CRD42023422368) and reported in accordance with PRISMA. PARTICIPANTS: The participants were 6691 ophthalmologists from 21 studies. METHODS: Electronic databases (MEDLINE, Embase, Cochrane, and PubMed) were searched for peer-reviewed quantitative studies reporting MSK pain prevalence in ophthalmologists. Pooled estimates with 95% CI were calculated using random-effects models; heterogeneity was quantified using I². MAIN OUTCOME MEASURES: Prevalence of overall and site-specific MSK pain; effects on workload and productivity; prevalence of treatment or mitigation strategies. RESULTS: The pooled prevalence of any MSK pain was 70% (95% CI: 65%-75%; I² = 92%); neck (41%; 95% CI: 35%-47%; I² = 95%), lower back (36%; 95% CI: 32%-39%; I² = 87%), and shoulder pain (28%; 95% CI: 22%-35%; I² = 91%) were most common. Pain led to workload modification in up to 44% and contributed to reduced clinical volume, sick leave, or contemplation of early retirement. Forty-six percent (95% CI: 22%-71%) pursued no treatment; 39% (95% CI: 30%-49%) used medical therapy; and 29% (95% CI: 20%-41%) sought physiotherapy. Heterogeneity was high across studies, reflecting differing case definitions and self-reported measures. CONCLUSIONS: MSK pain affects most ophthalmologists, particularly in the cervical and lumbar regions and frequently alters practice patterns. These findings underscore the need for early ergonomic training, structured micro-breaks, and workspace redesign. Prospective intervention trials are required to establish causality and quantify benefit.

Humans↗

PubMed2026

Efficacy and safety of Janus kinase inhibitors in Behçet's disease: A systematic literature review.

INTRODUCTION: Behçet's disease e (BD) is a chronic, relapsing, multisystem inflammatory disorder that if not successfully treated can lead to severe, organ or life-threatening complications. Despite treatment with glucocorticoids, immunosuppressants, and tumor necrosis factor (TNF) inhibitors, some patients still have refractory disease that mandates additional therapeutic options. The pathogenesis of BD involves dysregulated innate and adaptive immune responses with multiple cytokines signaling through the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway. By targeting multiple inflammatory pathways, JAK inhibitors have emerged as a promising therapeutic option. However, current evidence remains limited and heterogeneous. Therefore, we conducted this systematic review to evaluate their efficacy and safety in BD. METHODS: We conducted a systematic literature review in accordance with PRISMA 2020 guidelines (PROSPERO registration: CRD420261381955). PubMed/MEDLINE, Embase, Scopus, and Web of Science were searched from inception to March 2026. Original clinical studies evaluating Janus kinase (JAK) inhibitors in BD were included. Two reviewers independently performed study selection, data extraction, and quality assessment using Joanna Briggs Institute tools. Due to heterogeneity, results were synthesized narratively, focusing on efficacy and safety outcomes. RESULTS: Seventeen studies (99 patients) were included, predominantly case reports and small observational cohorts with overall high methodological quality. All evaluated tofacitinib, baricitinib, or upadacitinib, with no data on other JAK inhibitors. Patients were highly treatment-refractory, with prior failure of conventional and biologic therapies. Upadacitinib was the most frequently studied agent and demonstrated an overall response rate of 85.2% and complete remission in 59.3% in a multi-center study. Efficacy was observed across multiple domains, with the most consistent responses in intestinal disease, including clinical and endoscopic remission, alongside frequent glucocorticoid-sparing effects. Safety findings were consistent with known JAK inhibitor safety profiles, with mainly mild to moderate infections and manageable laboratory abnormalities, and no clear signal for increased thrombotic events, although follow-up was limited. CONCLUSION: JAK inhibitors demonstrate promising efficacy in BD, particularly in refractory and multisystem disease. The most consistent evidence of efficacy was observed in gastrointestinal involvement, whereas data for other disease domains remain limited. Their safety profile appears consistent with existing data, although further follow up and validation is required. High-quality randomized controlled studies are an imminent need to study the potential role of JAK inhibitors in BD.

Humans↗

PubMed2026

Herd-level heterogeneity of antimicrobial resistance in commensal Escherichia coli: A nationwide high-throughput survey of Australian pig herds.

Antimicrobial resistance in commensal Escherichia coli provides a useful indicator for overall antimicrobial resistance burden. We applied this approach to assess antimicrobial resistance within and between commercial pig herds across Australia. A high-throughput robotic workflow was used to isolate 2730 E. coli colonies from rectal contents collected in 2022 from healthy slaughter pigs (n = 300) representing 30 herds (∼70% of national production). Up to 94 isolates per herd underwent antimicrobial susceptibility testing using the Robotic Antimicrobial Susceptibility Platform. Isolate- and herd-level antimicrobial resistance indices were calculated, weighting antimicrobials by their human health importance. Resistance to first-line agents was widespread: ampicillin 77% and tetracycline 79%. By contrast, resistance to critically important antimicrobials was rare (ciprofloxacin 0.11%; extended-spectrum cephalosporins 0.04%), and no clinical resistance to carbapenems or colistin was detected. Overall, 56.9% of isolates were multi-class resistant. Herd-level antimicrobial resistance within indices ranged from 1.51 to 5.76, revealing substantial between-herd heterogeneity. Three herds carried critically important antimicrobials-resistant isolates that would likely have been missed using conventional, lower-density sampling approaches. Whole-genome sequencing identified fluoroquinolone-resistant isolates belonging to ST10 and ST69 (both qnrS1), and ST744 (Quinolone Resistance Determining Region mutations plus blaCTX-M-27). By testing approximately tenfold more isolates than conventional surveys, we uncovered considerable antimicrobial resistance with heterogeneity within and between animals and herds, including farm-specific variability. This expanded sampling also enabled detection of critically important antimicrobial resistance at very low prevalence. In conclusion, high-throughput, high-density testing offers a practical early-warning system and herd-level benchmark to inform surveillance and targeted interventions.

Animals↗

PubMed2026

Clinical outcomes of Epstein-Barr virus infection/reactivation following CAR-T cell therapy: A systematic review.

BACKGROUND: Epstein-Barr virus (EBV) infection or reactivation is an emerging but underrecognized complication following chimeric antigen receptor T-cell (CAR-T) therapy and is likely associated with treatment-induced immune dysregulation. Data regarding its clinical impact remain limited. OBJECTIVE: To evaluate the reported occurrence, clinical manifestations, and outcomes of EBV infection or reactivation in adults undergoing CAR-T therapy. METHODS: A systematic review was conducted in accordance with the PRISMA 2020 guidelines. PubMed, Embase, and Cochrane CENTRAL were searched from inception to March 2025 for studies reporting EBV infection or reactivation after CAR-T therapy in adults. Due to limited and heterogeneous data, results were synthesized descriptively. RESULTS: Five studies comprising 80 patients were included (median age, 55 years; 52.6% male among patients with reported sex data [10/19]). Across the included studies, 11 EBV infection/reactivation events were identified among 80 described CAR-T recipients, representing 13.8% of the reported sample rather than a true incidence estimate. Among events with usable individualized timing data, the median interval from CAR-T infusion to EBV detection/reactivation was 9.8 months (approximate range, 1-44 months). Because EBV surveillance strategies and definitions were inconsistently reported across studies, this proportion should not be interpreted as a true incidence estimate. Four patients (36.4%) developed EBV-associated disease, including three cases of EBV-related lymphoproliferative disorder and one case of EBV-associated diffuse large B-cell lymphoma. Among seven patients with reported post-CAR-T treatment response, four achieved Complete Remission/ Continuous Complete Remission; treatment response should be interpreted separately from final survival status. Confirmed EBV-related mortality occurred in 2/11 patients with reported EBV infection/reactivation and in 2/4 patients with EBV-associated disease; all-cause mortality could not be reliably estimated because patient-level vital status could not be fully attributed to the EBV-reactivated subgroup. Reported toxicities predominantly consisted of low-grade cytokine-release syndrome; however, toxicity data were limited. CONCLUSION: Although infrequently reported, EBV infection or reactivation after CAR-T therapy may be associated with substantial morbidity and mortality among affected patients. However, the available evidence is limited by the small sample size, heterogeneous study designs, and inconsistent EBV surveillance practices.

Humans↗

PubMed2026

Effect of walking training on blood glucose control and metabolic health in patients with type 2 diabetes: A systematic review and meta-analysis.

OBJECTIVE: To systematically evaluate the improvement effect of walking training on blood glucose control and metabolic health indicators in type 2 diabetes patients, and to explore the effect of different intervention program characteristics on the efficacy through subgroup analysis. METHOD: The system searched PubMed, Web of Science, EMBASE, Cochrane Library, and EBSCO databases, with a search period from the establishment of the database to March 15, 2026. Include a randomized controlled trial with the main intervention measures of walking behavior, with an intervention period of ≥8 weeks. Two researchers independently conducted literature screening, data extraction, and bias risk assessment. Meta-analysis was conducted using RevMan 5.4 software, with mean difference (MD) and its 95% confidence interval (CI) as effect measures for continuous variables. Select fixed effects model or random effects model for combined analysis based on heterogeneity size, and conduct subgroup analysis according to intervention program characteristics. RESULTS: Totally 5 randomized controlled trials were included, including 483 patients with type 2 diabetes (241 cases in the intervention group and 242 cases in the control group). Participants had a mean age of 54.2 ± 6.5 years, BMI of 29.1 ± 3.2 kg/m2, and 48.5% were male. The meta-analysis results showed that walking training significantly reduced glycated hemoglobin levels, with a combined effect of -0.48% (95% CI: -0.60 to -0.36, P < 0.00001), There is moderate heterogeneity among the studies (I2 = 67%). Subgroup analysis showed that the "walking + other interventions" subgroup (combined effect size -0.58%, 95% CI: -0.96 to -0.20) and the "clear step target" subgroup (combined effect size -0.52%, 95% CI: -0.65 to -0.39) had larger effect sizes and lower heterogeneity within the subgroups. The bias risk assessment shows that the overall quality of the included research methodology is good. CONCLUSION: Walking training can significantly improve the blood glucose control in patients with type 2 diabetes. Combined with diet or behavioral intervention, setting clear goals for the number of steps may achieve better results. Walking training can be used as an effective auxiliary treatment for the management of type 2 diabetes in clinical promotion. Due to limitations in the number and quality of studies included, the above conclusions still require more high-quality research to validate.

Humans↗

PubMed2026

Prevalence of Claudin 18.2 Expression in Gastric and Gastroesophageal Junction Adenocarcinoma: A Systematic Review and Meta-Analysis.

BACKGROUND: Claudin 18 isoform 2 (CLDN18.2) has emerged as a clinically validated therapeutic target in gastric and gastroesophageal junction (GEJ) adenocarcinoma following the regulatory approval of zolbetuximab in combination with first-line chemotherapy. Accurate prevalence data at the clinically validated immunohistochemical threshold are essential for patient selection, healthcare resource planning, and treatment strategy. Reported prevalence estimates vary widely across studies due to differences in populations, methodologies, and immunohistochemical protocols. This systematic review and meta-analysis aimed to generate a robust pooled prevalence estimate of CLDN18.2 expression at the threshold used in pivotal phase III trials. METHODS: PubMed, Embase, and the Cochrane Library were searched from database inception through March 12th, 2026. Studies reporting CLDN18.2 expression in gastric or gastroesophageal junction adenocarcinoma using the ≥ 75% moderate-to-strong membranous staining threshold were included. Prevalence proportions were pooled using a random-effects model with logit transformation and restricted maximum-likelihood estimation of between-study variance. Heterogeneity was assessed using the I² statistic and Cochran's Q test, and a 95% prediction interval was calculated. Pre-specified subgroup analyses assessed antibody clone and geographic region, with additional exploratory analyses according to disease setting and specimen type. Sensitivity analyses were performed to assess the robustness of the pooled estimate. RESULTS: Twenty-two predominantly retrospective cohort studies comprising 12,173 patients were included. The pooled prevalence of CLDN18.2 positivity using a random-effects model was 33.99% (95% CI: 30.13%-38.07%; 95% prediction interval: approximately 18%-55%), with high between-study heterogeneity (I² = 92.4%). Subgroup analysis by antibody clone showed no statistically significant difference between studies using the 43-14 A clone (32.79%, 95% CI: 28.86%-36.97%) and those using other reported antibody clones (41.74%, 95% CI: 26.76%-58.42%; p = 0.281). One study with an unreported antibody clone was excluded from this subgroup analysis. Geographic subgroup analysis excluding the multinational Shitara et al. cohort demonstrated a non-significant trend toward higher prevalence in non-Asian populations (37.85%, 95% CI: 31.59%-44.54%) compared with Asian populations (32.10%, 95% CI: 27.28%-37.34%; p = 0.169). All three sensitivity analyses confirmed robustness of the pooled estimate. No significant evidence of publication bias was detected (Egger's test p = 0.56). CONCLUSIONS: Approximately one-third of patients with gastric and GEJ adenocarcinoma express CLDN18.2 at the clinically validated ≥ 75% threshold. However, because the included studies encompassed heterogeneous disease settings and were predominantly HER2-unselected, the pooled estimate should not be interpreted directly as the proportion of patients eligible for zolbetuximab. The estimate was robust across sensitivity analyses and provides an evidence base for understanding CLDN18.2 prevalence and biomarker-testing requirements. Standardisation of immunohistochemical assessment methods is warranted to reduce between-study heterogeneity in future research.

Humans↗

PubMed2026

Beyond risk factors: A capacity framework for cancer survivorship research.

Cancer survivorship research has identified numerous biological, behavioral, psychosocial, health care, and structural factors that influence recovery. However, these factors are typically studied as separate determinants rather than interacting influences. This commentary proposes available survivorship capacity as a unifying framework that explains how these diverse determinants collectively shape recovery and survivorship outcomes. Concepts from geroscience, health care delivery, rehabilitation, occupational therapy, and human factors science were synthesized to develop a conceptual framework of available survivorship capacity. The framework conceptualizes recovery as a function of the capacity remaining after competing health care and life demands draw upon survivors' finite physical, cognitive, emotional, social, financial, temporal, and health care resources. It generates testable propositions for measurement, intervention research, health care delivery, and implementation science while positioning available survivorship capacity as a common mechanism linking diverse determinants of recovery and identifying actionable targets for intervention. Available capacity offers a unifying conceptual framework for understanding heterogeneity in survivorship outcomes and intervention effectiveness while generating a research agenda for future survivorship science. Measuring and strengthening survivors' available capacity, while reducing unnecessary demands, may improve engagement in care, health behaviors, and long-term recovery.

Humans↗

PubMed2026

Activity shapes large herbivores' ecological influences.

The ecological effects of large herbivores are shaped by their spatial and temporal patterns of activity (i.e. where, when and how intensely they use specific locations). When large herbivores' ecological influences are perceived to be undesirable, the traditional approach has been to reduce their population size. This numbers-first logic assumes that ecological effects scale primarily with abundance. We argue that this framing provides an incomplete understanding of large herbivores' ecological impacts. Using African elephants (Loxodonta africana) as a well-documented case study, we show that ecological effects on plants, animals and ecosystem processes correlate more with spatio-temporal patterns of activity than with population size. In large, open systems characterized by strong gradients of water availability, forage quality, shade and risk, elephants concentrate into predictable hotspots while relaxing activity elsewhere, generating localized impacts and opportunities for recovery. By contrast, in small, fenced or fragmented landscapes, where movements are constrained, and gradients are weak, spatial self-regulation breaks down, producing homogenized use and widespread ecological effects. We contend that understanding where, when and under what constraints herbivores use space provides a more general and mechanistic basis for interpreting ecological influence than abundance alone, with implications that extend beyond elephants to large herbivores globally.

Animals↗

PubMed2026

Robot-assisted bladder diverticulectomy in adults: a systematic review and pooled analysis of perioperative and functional outcomes.

Robot-assisted bladder diverticulectomy (RABD) is used for symptomatic acquired bladder diverticula, but evidence is dispersed across small single-centre series and the only dedicated systematic review dates from 2010. We reviewed contemporary perioperative and functional outcomes of RABD. Following a protocol registered on the Open Science Framework ( https://doi.org/10.17605/OSF.IO/54CFT ), PubMed, Embase, the Cochrane Library, Scopus and Web of Science were searched from inception to 30 August 2026 (initial search June 2026, re-run and broadened for this version), following PRISMA 2020. Eligible studies were original series of five or more adults undergoing robot-assisted bladder diverticulectomy reporting extractable outcomes. Two reviewers independently screened, extracted data and appraised risk of bias with the Joanna Briggs Institute checklist for case series, with third-reviewer adjudication. Binary outcomes were pooled as proportions with Wilson 95% confidence intervals (CI); continuous outcomes were summarised as patient-number-weighted descriptive values, because mixed median/mean reporting and clinical heterogeneity precluded a formal pooled-effect meta-analysis. Twelve studies (146 patients) were included and all outcomes were extracted from the full-text reports. A transperitoneal route was used throughout. There were no conversions to open surgery (0/129; 95% CI 0-2.9%). Major complications (Clavien-Dindo ≥ III) occurred in 3.0% (4/135; 95% CI 1.2-7.4%). Patient-number-weighted descriptive values (combining study-level medians and means, and therefore not a pooled mean) were: operative time 163 min, blood loss 99 mL, length of stay 3.6 days and catheter duration 7.7 days. Symptom scores and post-void residual improved in every reporting series, significantly in five. The single non-randomised comparison with open surgery reported fewer major complications after RABD (5% [1/20] vs. 50% [3/6], p = 0.007), but the open arm comprised only six patients and this finding should not be regarded as comparative evidence. Across these series, RABD was feasible with low reported short-term morbidity in selected patients: no conversions to open surgery were recorded in the studies reporting conversion status, the major-complication rate was low, and symptom scores and post-void residual improved in every series that measured them. A minority of patients had an incidentally detected intradiverticular tumour; oncological outcomes were not an endpoint of this review. Evidence remains limited by small, heterogeneous, mostly retrospective series, so these findings should be read as descriptive; prospective comparative data are warranted.

Humans↗

PubMed2026

Hormonal contraceptives and women's sleep health: A systematic review.

Sex hormones and hormonal contraceptives influence the regulation of sleep-wake behavior. However, there are very few large-scale studies to date that have comprehensively evaluated how hormonal contraceptives influence women's sleep health. The purpose of this systematic review was to synthesize the existing research on hormonal contraceptive use and sleep in women ages 18-50. The systematic review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement checklist. Nineteen studies were included in this review. Data were extracted and evaluated for risk of bias and heterogeneity. The included studies demonstrated high heterogeneity in terms of objective and/or subjective sleep-related measures and non-sleep primary study outcomes and demonstrated significant risks of bias, underscoring the need for methodological consistency in assessing women's sleep health. Several clinical considerations may be gleaned from this existing research in terms of the behavioral assessment and treatment of sleep difficulties in women using hormonal contraceptives. Additional investigation is needed to identify standardized research and clinical methodology guidelines for assessing and treating women's sleep health.

Humans↗

PubMed2026

Complicated urinary tract infections: evolving definitions, clinical burden, and treatment landscape amid antimicrobial resistance.

INTRODUCTION: Complicated urinary tract infection (cUTI) is a common and heterogeneous infection associated with substantial morbidity, high healthcare utilization, and increasing antimicrobial resistance. Evolving definitions, increasing device use, and changing patient populations have altered its epidemiology and management. Marked variability in diagnostic criteria, clinical trial endpoints within and outside registrational settings, and treatment strategies complicates clinical decision-making and interpretation of therapeutic advances. AREAS COVERED: This review examines contemporary cUTI epidemiology, classification frameworks, and drivers of disease burden. It evaluates resistance trends and their therapeutic implications, alongside stewardship-based management strategies, including empiric antibiotic selection, intravenous-to-oral transition, treatment duration, and source control. Challenges in catheter-associated infection, recurrence, and regulatory endpoint design are discussed, together with the emerging role of novel agents targeting resistant Gram-negative pathogens. EXPERT OPINION: Rising multidrug resistance and limited oral options are reshaping cUTI management, necessitating individualized, stewardship-aligned therapy guided by illness severity and local epidemiology. Current regulatory endpoints inadequately reflect patient-centered outcomes, particularly in the context of asymptomatic bacteriuria. Expanding availability of effective oral agents may enable earlier discharge and outpatient care. Integration of rapid diagnostics and risk stratification will be essential to optimize therapy, limit resistance, and improve outcomes.

Humans↗

PubMed2026

A Multi-omics Regulated Cell Death Framework Defines Immune Phenotypes and Guides Precision Therapy in Colorectal Cancer.

Colorectal cancer (CRC) is molecularly and immunologically heterogeneous, contributing to variable treatment response. Because regulated cell death (RCD) intersects with tumor metabolism, immune regulation, and therapeutic susceptibility, we built an RCD-centered framework for CRC stratification. Multi-cohort transcriptomic data were used to infer RCD subtypes with non-negative matrix factorization (NMF) and non-negative least squares (NNLS). Genomic, bulk RNA-seq, single-cell RNA-seq, and spatial transcriptomic datasets were integrated to characterize subtype-associated biology. Machine-learning models were developed for immunotherapy response and survival-risk estimation. Candidate compounds were screened by GDSC2-based drug-sensitivity modeling and molecular docking, and FSTL3 was functionally assessed in vitro. The framework separated CRC samples into two RCD-related phenotypes resembling immune-hot and immune-cold states. RCD1 showed immune activation and higher mutational burden, whereas RCD2 showed immune-suppressed features, intratumoral heterogeneity, and aggressive biology. RCD-associated signatures showed potential for predicting immunotherapy response and survival risk. Dasatinib was prioritized for immune-cold, high-risk tumors, with preliminary evidence supporting its activity in CRC cells, while functional assays suggested a role for FSTL3 in growth, invasion, epithelial-mesenchymal transition, and apoptosis regulation. These findings suggest that RCD-based multi-omics analysis may refine CRC stratification and help generate therapeutic hypotheses.

Colorectal cancer↗

PubMed2026

Effects of transcutaneous electrical acupoint stimulation versus acupressure on the trajectories of multidimensional adverse reactions to chemotherapy in breast cancer patients: a secondary analysis of a randomized controlled trial.

BACKGROUND: Chemotherapy for breast cancer often induces multidimensional adverse reactions such as nausea and vomiting, anxiety, depression, and sleep disturbances. These symptoms are interrelated and may evolve dynamically, impacting patients' treatment outcomes and quality of life. As non-pharmacological interventions, transcutaneous electrical acupoint stimulation (TEAS) and self-acupressure (SA) have shown potential in alleviating symptoms. However, their long-term effects on the joint developmental trajectories of these multidimensional symptoms (nausea and vomiting, anxiety, depression, and sleep disturbances) remain unclear. OBJECTIVE: This study aimed to identify potential trajectory class of multidimensional adverse reactions in breast cancer patients undergoing chemotherapy and to explore the differential effects of TEAS and SA on different trajectory subgroups. METHODS: This was a secondary analysis of a randomized controlled trial. A total of 189 breast cancer patients receiving chemotherapy were included. The Group-Based Multi-Trajectory Model (GBMTM) was employed to identify joint developmental trajectories of acute/delayed chemotherapy-induced nausea and vomiting (CINV), anxiety, depression, and sleep quality during chemotherapy. Subsequently, causal forest was used to analyze the average treatment effects (ATE) of TEAS (vs. control group) and SA (vs. control group) on patients' symptom trajectory. RESULTS: Multidimensional adverse reactions were classified into two heterogeneous trajectories: a "High Symptom Burden-Persistent (HSBP)" type (n = 101) and a "Low Symptom Burden-Relieving (LSBR)" type (n = 88). The persistent high incidence of acute CINV contrasted sharply with the comprehensive relief of other symptoms in the latter group. Causal forest suggested that both TEAS and SA significantly increased the probability of patients being classified into the "LSBR" trajectory. The ATE was 0.147 (95% CI: 0.143, 0.151) for TEAS, slightly lower (P < 0.05) than 0.176 (95% CI: 0.162, 0.190) for SA.  CONCLUSION: Multidimensional adverse reactions in breast cancer patients undergoing chemotherapy exhibit heterogeneity in their trajectories. Both TEAS and SA were associated with a higher probability of patients being classified into a more favorable symptom trajectory-LSBR. The multidimensional trajectory identification with treatment effect estimation may serve as a useful analytical strategy for future longitudinal research in cancer chemotherapy-induced adverse reactions symptom management. CLINICAL TRIAL REGISTRATION: ChiCTR2300077667 (Chinese Clinical Trial Registry, https://www.chictr.org.cn/ ), Registered 15 November 2023.

Humans↗

PubMed2026

Integrated morphologic, immunophenotypic, and molecular profiling of advanced upper tract urothelial carcinoma across tumor compartments supports biopsy-based testing.

Upper tract urothelial carcinoma (UTUC) is an aggressive malignancy with limited molecular characterization in advanced disease. FGFR3 alterations are well established in low-grade urothelial carcinoma, but their prevalence, stability, and biological significance in locally advanced and metastatic UTUC remain only partially defined. We performed an integrated morphologic, immunohistochemical, and molecular analysis of 24 locally advanced and/or metastatic UTUC from 20 patients. FGFR3 status was assessed by RT-PCR across multiple tumor compartments, including biopsies, primary tumors, lymph-node metastases, and distant metastatic sites. Immunohistochemistry included CK20, CK5, GATA3, p53, and mismatch repair proteins. Targeted next-generation sequencing (NGS) was used to characterize co-occurring genomic alterations and to assess concordance with p53 immunophenotype. FGFR3 alterations were identified in 50% of patients and in 54.2% of analyzed tumors. FGFR3 status showed high intra-patient stability, with concordance between primary tumors and distant metastases in 90% of cases, whereas concordance with lymph node metastases was lower (50%), suggesting site-specific clonal divergence. Despite advanced stage, 92.3% of FGFR3-altered tumors displayed papillary urothelial carcinoma morphology, and most showed a luminal immunophenotype (61.5% by CK20/CK5 and 69.2% by GATA3/CK5). Targeted NGS revealed additional pathogenic alterations in 75% of patients, most frequently involving RTK/RAS/MAPK signaling (70%), cell-cycle regulation (25%), and PI3K/AKT pathway components (10%). TP53 mutations co-occurred with FGFR3 alterations in 60% of FGFR3-mutated patients and showed 90.4% concordance with p53 immunohistochemistry. Finally, a few cases exhibited complex, multi-site FGFR3 mutational patterns, consistent with intratumoral clonal evolutions. In conclusion, FGFR3 alterations are frequent and remarkably stable in advanced UTUC, even in high-grade and metastatic disease. These findings support the reliability of FGFR3 testing on limited diagnostic material and reinforce its relevance for therapeutic stratification. UTUC emerges as a molecularly dynamic disease in which early oncogenic drivers such as FGFR3 continue to shape tumor biology and therapeutic vulnerability at advanced stages.

Humans↗

PubMed2026

How prevalent is fear of cancer recurrence beyond 5 years: a systematic review of validated assessments across tumour types.

PURPOSE: Fear of cancer recurrence (FCR) is an established challenge for cancer survivors. Research however has largely focussed early in treatment, with varying assessments and often single tumour sites. This systematic review set out to determine prevalence of FCR in survivors beyond 5 years across all tumour types. METHOD: We designed a search strategy to identify publications assessing FCR in survivors beyond 5 years with sample size greater than 50, using validated measures. Applying PRISMA methodology and with defined inclusion and exclusion criteria two authors independently assessed the studies for eligibility. Data extraction recorded number of participants, tumour type, study design, FCR tool, time points for assessment and reported prevalence. Risk of bias was assessed to address quality. RESULTS: Ten papers were included, reporting FCR from 5 years to beyond 20 years. Validated tools employed were FCRI-SF and FOP-Q-SF. Sample sizes ranged from 64 to 5983 participants, with a heterogeneous mix of tumour types and age. Only two studies reported longitudinal measurements. Prevalence of FCR above defined threshold ranged from 13 to 33.9% for those studies with acceptable risk of bias reporting distinct cohorts beyond 5 years. CONCLUSION: The limited evidence suggests that clinically relevant FCR persists in some survivors at 5 years. Our review demonstrates the challenge of heterogeneous patient populations in FCR research emphasising the need for improved consensus on measurements and more prospective longitudinal research representing a comprehensive variety of tumour types. We address the clinical implications of persistent FCR and the need to implement effective interventions.

Humans↗