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PubMed2026

Hypoxaemia and mortality in children with lower respiratory infection in low-income and middle-income countries: systematic review and meta-analysis.

BACKGROUND: Hypoxaemic lower respiratory infections (LRIs) are a leading cause of childhood mortality, with the highest burden in low-income and middle-income countries (LMICs). Hypoxaemia-low peripheral capillary oxyhaemoglobin saturation (SpO2)-is a marker of severity, and WHO recommends hospitalisation and oxygen administration for patients with SpO2 <90%. We aimed to update estimates from a 2015 systematic review and meta-analysis examining the association between hypoxaemia and mortality among children with LRIs in LMICs by incorporating studies published over the subsequent decade and evaluating mortality risk across multiple SpO2 thresholds. METHODS: We conducted a systematic review with meta-analysis by searching PubMed, Embase, LILACS, Global Index Medicus, Web of Science, and Scopus for peer-reviewed studies published between Jan 1, 2015, and June 18, 2025, with combined terms related to pneumonia, children, mortality, and LMICs. We also included selected earlier studies through citation checking. Eligible studies reported associations between hypoxaemia and mortality in children younger than 5 years with LRIs in LMICs. We excluded case reports and case series with fewer than five deaths, studies focused exclusively on the neonatal period, and those limited to children with specific comorbidities or to postoperative patients, for consistency with the original review. Two reviewers independently screened studies, extracted data, and assessed quality. Eligible studies were combined with those from the original review and analysed using random-effects models to estimate odds ratios (ORs) by hypoxaemia threshold subgroup. The protocol was registered on PROSPERO (CRD42023433946). FINDINGS: We identified 7734 records; 26 new studies met inclusion criteria and were combined with 18 from the original review. The 44 studies were published between 1993 and 2024 and were primarily from Africa (25 [57%] of 44) or Asia (19 [43%]); some studies spanned multiple locations. Data from 33 studies including 155 633 participants were included in the primary meta-analysis. Hypoxaemia of any threshold was associated with higher odds of LRI mortality (OR 4·36 [95% CI 3·52-5·39]) compared with no hypoxaemia. For SpO2 <90% versus 90-100%, OR for death was 4·75 (95% CI 3·42-6·58). For SpO2 90-94% versus 95-100%, mortality risk was more than twice as high (OR 2·27 [95% CI 1·22-4·25]). Heterogeneity was substantial (I2 64-85% across analyses), and eight (24%) of 33 studies in the primary meta-analysis had a high overall risk of bias; however, a sensitivity analysis restricted to studies with low or moderate risk of bias yielded similar results. INTERPRETATION: SpO2 <90% strongly predicts mortality in children with LRIs in LMICs. Children with SpO2 90-94% also have elevated risk, suggesting that paediatric LRI and pneumonia treatment algorithms should consider management at this hypoxaemia threshold. FUNDING: None.

Journal Article↗

PubMed2026

Direct and spillover hospitalisation patterns during climate hazards across regions of different health-system resilience levels in China: a nationwide retrospective analysis.

BACKGROUND: Health-system resilience serves as a key contributor in mitigating adverse health impacts during climate hazards. However, quantitative insights into resilience-associated health-care utilisation patterns and targeted adaptation policies remain scarce. We aimed to capture the spatiotemporal health impacts in disaster-exposed counties and their neighbouring counties in China during storms, floods, tropical cyclones, and blizzards or winter storms; understand the association between health-system resilience metrics and hazard-attributable hospitalisations; and develop evidence-based adaptation policies towards climate extremes. METHODS: In this retrospective, observational analysis of county-level aggregated hospitalisation data, we used a propensity score matching-difference-in-differences framework to assess the spatiotemporal changes of nine types of disease-specific hospitalisations in both disaster-exposed and neighbouring regions during storms, floods, tropical cyclones, and blizzards in China. We quantified the relative importance and health gains of health-system metrics during such hazards through random forest approach with interpretable partial dependence plots to derive evidence-based adaptation recommendations. FINDINGS: We included hospitalisation data from Jan 1, 2016 to Dec 31, 2023. In this period, 3241 county-hazard event combinations and 41 747 482 hospitalisations were recorded across 955 Chinese counties. The disaster-exposed regions experienced an initial decline in hospitalisation rates, followed by admission surges after disasters. For example, infectious disease admissions decreased by 11·92% (95% CI -10·53 to -13·31) during the flood-active period but increased by 7·68% (6·46-8·91) after 1-2 weeks of floods. Neighbouring zones were also affected through spillover effects, with infectious disease admissions increasing by 3·18% (1·76-4·61) after 1-2 weeks of the floods. Cardiovascular disease, injuries, infectious, respiratory, and mental disorders were more sensitive across all regions. Particularly for disaster-exposed counties, cardiovascular hospitalisations increased by 14·31% (7·34-21·29) during the tropical cyclone-active period. Notably, compared with low-resilience counties, high-resilience counties were associated with 19·48-30·03% smaller hazard-related relative changes in hospitalisation rates during the hazard-active period and 27·07-31·08% smaller hazard-related relative changes in hospitalisation rates in post-hazard periods. For instance, during the storm-active period, the increase in respiratory hospitalisations was 7·21% (0·67-13·75) in high-resilience counties versus 12·13% (5·20-19·05) in low-resilience counties. Health workforce (relative importance 14·58% during the hazard-active period and 13·80% during the post-hazard period) and service delivery (14·10% during the hazard-active period and 14·17% during the post-hazard period) were identified as key contributors of health-system resilience. Empirical synergistic effects were observed when combining interventions during the post-hazard period, with the combined effect of service delivery (individual contribution 8%) and workforce (individual contribution 4%) exceeding the sum of their individual contributions (16% reduction in cumulative excess admissions) by 33%. INTERPRETATION: Climate hazards are associated with substantial changes in hospitalisation rates in both disaster-exposed and neighbouring regions. Health-system resilience is essential in addressing disaster-health challenges. Targeted adaptation interventions should be context-appropriate and threshold-aware, thereby maximising the public health benefits relative to resilience-oriented investments in health systems. FUNDING: Gates Foundation and the National Natural Science Foundation of China.

Journal Article↗

PubMed2026

The impact of artificial intelligence on critical thinking and clinical reasoning in health professions education: A systematic review and meta-analysis.

BACKGROUND: Critical thinking and clinical reasoning underpin healthcare professionals' ability to navigate uncertainties and deliver safe and effective care. With artificial intelligence (AI) advancement and growing adoption, AI-based educational tools are increasingly used to support these cognitive competencies' development. OBJECTIVE: To synthesize randomised and controlled clinical trials on AI-based educational tools in health professions education and examine their effects on critical thinking and clinical reasoning among health professions students. METHODS: Six electronic databases were searched from January 1, 2014 to July 28, 2025 was reviewed: PubMed, Cochrane Central Register of Controlled Trials, CINAHL, Scopus, Embase and Web of Science. Two independent reviewers performed data extraction and quality assessment using standardized JBI checklists. The GRADE approach was used to assess the certainty of evidence. Studies were pooled via random-effects meta-analyses or narrative syntheses. RESULTS: Fourteen randomised controlled trials and seven controlled clinical trials were included (n = 21). Meta-analyses revealed small to medium effect sizes for the surrogate clinical reasoning outcomes of performance-based assessment scores (SMD 0.68; 95% CI [0.38, 0.98], p-value = 0.00; I2 = 38%) and knowledge test scores (SMD 0.39; 95% CI [0.09, 0.69], p-value = 0.01; I2 = 79%). Critical thinking and clinical reasoning skills and dispositions were narratively synthesized, with majority of included studies favouring AI-based interventions but the evidence had low to very low certainty. CONCLUSION: AI-based educational interventions may improve critical thinking and clinical reasoning among health profession students, but the evidence is very uncertain. This review offers preliminary insights but does not allow identification of optimal interventions or discipline-specific recommendations due to small sample sizes and substantial intervention heterogeneity. Further research is required to draw definitive conclusions. PROTOCOL REGISTRATION: CRD42025634074.

Humans↗

PubMed2026

A systematic review and meta-analysis of visuospatial attentional deficits in Parkinson's patients.

Parkinson's disease (PD) is a neurodegenerative condition primarily characterized by motor deficits, yet cognitive impairments are increasingly recognized. While deficits in executive functioning are well documented even in the absence of cognitive decline, evidence of attentional deficits in PD remains inconsistent, and the role of motor symptom lateralization is unclear. In this systematic review and meta-analysis, we examined visual attention in right-handed, cognitively unimpaired idiopathic PD patients, focusing on the canonical attentional domains (sustained, selective, divided) and processes (alerting, endogenous and exogenous orienting, reorienting), as well as visuospatial bias. Four databases were searched for studies comparing PD patients with healthy controls. Meta-analytic estimates were derived using Hedges' g within random-effects models, and studies that could not be quantitatively integrated were summarized narratively. In addition, studies directly comparing patients with left- and right-predominant motor symptoms (LPD vs. RPD) were reviewed qualitatively. Across 51 studies, PD patients exhibited deficits in sustained, selective, and divided attention. Among attentional processes, only exogenous orienting was impaired, whereas alerting, endogenous orienting, and reorienting were preserved. Findings from the few studies examining visuospatial bias indicated small, context-dependent shifts in spatial attention rather than a consistent directional bias. These findings indicate that PD patients show visual-attentional impairments, particularly under high-demand conditions, while basic alertness and voluntary orienting appear preserved. Exogenous orienting deficits and subtle rightward spatial tendencies in LPD suggest disruption of right-hemisphere attentional networks. These results have implications for early cognitive assessment, rehabilitation strategies, and understanding the neural bases of attentional dysfunction in PD.

Humans↗

PubMed2026

Does co-administration of cannabidiol (CBD) influence the plasma availability of delta-9-tetrahydrocannabinol (THC) and its active metabolite in humans? A systematic review and meta-analysis.

BACKGROUND: Research on the pharmacokinetic influence of cannabidiol (CBD) on delta-9-tetrahydrocannabinol (THC) has produced equivocal results. METHODS: We conducted a systematic search following PRISMA guidelines (last search: 24th November 2025, PROSPERO: CRD42023480695). Included studies were acute dosing trials that administered a) a single, fixed dose of THC and b) a matched dose of THC co-administered with CBD. Our objective was to investigate between-group differences in the Cmax, AUCt and AUCinf of circulating THC and its active metabolite, 11-hydroxy-THC (11-OH-THC). Hedges' g and ratio of means (RoM) were pooled from random-effects meta-analyses. The dose-effects of CBD and THC on Hedges' g were explored using meta-regression. Risk of bias was assessed using the Cochrane Collaboration tool RoB 2. RESULTS: 14 studies were included (12 crossover, two parallel group; seven oral administration, five inhalation, one IV, one mixed IV and oral; total participants: 341). In meta-analyses, average AUCt of THC was significantly higher in CBD co-administration study arms versus THC-only (Hedges' g= 0.526, 95%CI= 0.222-0.830), with very low certainty evidence. Both Cmax and AUCt of 11-OH-THC were significantly higher in CBD co-administration study arms (Cmax: g= 0.428, 0.115-0.741; AUCt: g= 0.692, 0.284-1.099), both with medium certainty evidence. In meta-regression analyses, CBD demonstrated dose effects on the Hedges' g of the Cmax and AUCt of 11-OH-THC (P < 0.05), but not THC levels. CONCLUSIONS: Cannabis users and prescribers of cannabinoid-based products should be made aware of the potential for drug-drug pharmacokinetic interactions between CBD and THC.

Humans↗

PubMed2026

Peripheral inflammation and executive function among community samples across the lifespan: A systematic review and meta-analysis.

Higher levels of peripheral inflammatory markers are proposed to disrupt cognitive processes; however, the extent to which this relationship applies to executive functions, specifically, has yet to be systematically evaluated. The current meta-analysis synthesizes all available literature measuring the association between peripheral inflammation and executive functions among community individuals across the lifespan. This systematic review searched Web of Science, PubMed, and PsycINFO for published and unpublished studies, in the English language, that assessed the association between markers of peripheral inflammation and self-report and behavioral measures of executive function. In addition to methodological and demographic information, correlation/beta coefficients were extracted from included studies to quantify the association between inflammation and executive functions. This review included 58 studies, 41 of which were included in the random-effects meta-analysis (N = 255,539). Among community individuals, higher levels of CRP and IL-6 were associated with poorer executive functioning. These results did not differ when models accounted for potential confounding variables. Meta-regressions revealed that the relationship between inflammatory biomarkers and executive function did not differ as a function of age, adiposity, or percentage of the sample who identified as female. Results of the present review indicate that higher levels of specific inflammatory markers are associated with lower performance on executive function measures; however, we observed significant heterogeneity in the study design and measurement of both inflammation and executive functioning, suggesting important considerations for future research.

Humans↗

PubMed2026

Age-related differences in motor unit behaviours and maximal strength: A systematic review and meta-analysis.

Ageing is associated with a decline in strength; however, the neural mechanisms underpinning these changes remain poorly understood. Motor unit discharge rate (MUDR) and recruitment threshold (MURT) regulate the magnitude of motoneuron output through rate coding and orderly recruitment, while discharge rate variability (MUDRV) reflects the steadiness of motoneuron output. Yet, age-related differences in these properties remain inconsistent across the literature. Therefore, this systematic review and meta-analysis quantified age-related differences in motor unit behaviours and their contribution to maximal isometric strength. Electronic databases (Medline, Embase, Scopus, PsycINFO, Ovid Emcare, CENTRAL, and Web of Science) were searched up to May 2025, yielding 1493 records; of these, 48 studies met the inclusion criteria. Standardised mean differences (SMDs) were calculated using random-effects models to compare older and younger adults, and methodological quality was assessed using the AXIS tool. Older adults exhibited markedly lower maximal strength than younger adults (SMD = -1.01; 95% CI -1.22, -0.79). MUDR was lower in older adults across all contraction intensities, with greater reductions at high forces (> 60% maximal voluntary contraction (MVC): SMD = -0.65; 95% CI -0.96, -0.34) compared to low forces (< 30% MVC: SMD = -0.34; 95% CI -0.50, -0.18). Discharge rate variability was greater (SMD = 0.44; 95% CI 0.15, 0.72), whereas recruitment thresholds relative to MVC were lower (SMD = -0.42; 95% CI -0.80, -0.03) in older adults. Collectively, these findings suggest that age-related alterations in motor unit discharge behaviour may contribute, at least in part, to reduced maximal strength in older adults.

Aging↗

PubMed2026

Auditory brainstem response in the identification of cochlear synaptopathy in aged rodents: a systematic review with meta-analysis.

PURPOSE: This systematic review and meta-analysis evaluated the diagnostic performance of auditory brainstem response (ABR) for identifying age-related cochlear synaptopathies in rodents. METHOD: Following PRISMA guidelines, searches were conducted in PubMed/MEDLINE, Cochrane Library, Scopus, Embase, Web of Science, SciELO, LILACS, and gray literature. Studies evaluating CS in naturally aged rodents using short-latency auditory evoked potentials (AEPs) were included. Study selection, data extraction, risk-of-bias (JBI Critical Appraisal Checklist for Analytical Cross-Sectional Studies), and certainty of the evidence (GRADE® system) assessment were conducted independently by two reviewers. Meta-analyses were performed using a random-effects model, with standardized mean differences and 95% confidence intervals. ABR wave I amplitudes were analyzed for click (80 and 90 dB SPL) and tone-burst stimuli stratified by frequency. RESULTS: Among 3,008 identified records, 12 studies were included in the review and five in the meta-analysis. All included studies used ABR measures to investigate CS, with wave I amplitude being the most frequently evaluated biomarker. Meta-analysis demonstrated a significant reduction in ABR wave I amplitude in aged rodents compared with young controls for both click- and tone-burst-evoked responses. Tone-burst ABR showed no significant differences among the evaluated frequencies. These findings should be interpreted with caution due to the limited number of studies and the methodological heterogeneity, which may have reduced statistical power and comparability. CONCLUSIONS: The evidence supports ABR wave I amplitude as a sensitive electrophysiological marker of age-related CS in rodents. Nevertheless, further studies with standardized protocols are needed to strengthen its diagnostic utility and improve comparability across studies.

Animals↗

PubMed2026

Reassessment of the effect of oral l-arginine on blood pressure: A systematic review and meta-analysis based on ambulatory blood pressure monitoring.

OBJECTIVE: This meta-analysis aimed to evaluate the effect of oral l-arginine supplementation on ambulatory blood pressure (ABP). METHODS: A systematic search of PubMed, Cochrane Library, Embase, and Web of Science databases was conducted from their inception through March 1, 2026. Randomized controlled trials (RCTs) assessing the effects of oral l-arginine intervention were included. Outcome measures included 24-h systolic blood pressure (24h SBP), 24-h diastolic blood pressure (24h DBP), daytime systolic blood pressure (dSBP), daytime diastolic blood pressure (dDBP), nighttime systolic blood pressure (nSBP), and nighttime diastolic blood pressure (nDBP). Meta-analysis was performed using Stata 17.0. The weighted mean difference (WMD) was used as the effect size, and the results were pooled with 95% confidence intervals (CIs). RESULTS: A total of 5 RCTs comprising 202 participants were included. Meta-analysis results demonstrated that oral l-arginine significantly reduced 24h SBP (WMD = -4.23 mmHg, 95% CI [-5.87, -2.58]; P < 0.01) and 24h DBP (WMD = -3.04 mmHg, 95% CI [-4.48, -1.59]; P < 0.01). Significant reductions were also observed for dSBP (WMD = -4.16 mmHg, 95% CI [-5.90, -2.41]; P < 0.01) and dDBP (WMD = -4.25 mmHg, 95% CI [-5.85, -2.66]; P < 0.01). Furthermore, oral l-arginine significantly lowered nSBP (WMD = -5.70 mmHg, 95% CI [-7.81, -3.58]; P < 0.01) and nDBP (WMD = -4.18 mmHg, 95% CI [-6.27, -2.09]; P < 0.01). CONCLUSION: Oral l-arginine supplementation significantly reduces ABP. However, the number of included studies was limited, and further validation through additional relevant research is warranted.

Arginine↗

PubMed2026

Construction of precision clinical-proteomics risk model based on machine learning for predicting heart failure in type II diabetes mellitus.

BACKGROUND AND AIMS: Heart failure (HF) is a severe complication in type 2 diabetes mellitus (T2DM), but current risk stratification scores have limited predictive accuracy. We aimed to develop novel prediction tools integrating clinical variables with proteomics to improve risk stratification of hospitalization for HF in T2DM. METHODS AND RESULTS: In this study, we included 2111 UK Biobank participants with T2DM but no prior HF, and profiled 2920 proteins to predict 10-year incident HF hospitalization. Participants were randomly divided into training (70%), tuning (10%), and validation (20%) sets.Three prediction models were developed: a Clinical model based on demographic characteristics, comorbidities, medication use, and laboratory indices; a Protein model based on 40 proteins selected by the Light Gradient Boosting Machine (LGBM); and the Clinical OMics and Protein ASSessment for Heart Failure (COMPASS-HF) model, which integrated both clinical variables and the LGBM-selected proteins. Models were evaluated for area under the curve (AUC), sensitivity, and specificity. During follow-up, 168 participants (7.96%) developed incident HF. The COMPASS-HF model showed better discrimination than the Clinical model, with an AUC of 0.897 (95% CI: 0.850-0.945) versus 0.790 (95% CI: 0.723-0.856). It also demonstrated higher sensitivity (0.882; 95% CI: 0.725-0.967) and consistent performance in subgroups. COMPASS-HF effectively stratified risk of hospitalization for HF, with cumulative incidence rates of 31.9% in the high-risk group and 1.2% in the low-risk group. CONCLUSIONS: By combining clinical and proteomic variables, we developed a high-performance HF prediction model for T2DM, enabling precise risk stratification and informing early intervention strategies.

Humans↗

PubMed2026

Impact of creatine supplementation alone or combined with exercise on inflammatory and clinical outcomes in chronic musculoskeletal pain treated in the rheumatological field: a systematic review.

Creatine supplementation has demonstrated ergogenic and anabolic effects in healthy and clinical populations. However, its potential therapeutic role in individuals with chronic musculoskeletal pain treated in rheumatological contexts remains unclear. The aim was to evaluate the efficacy and safety of creatine supplementation on pain, physical function/disability, quality of life, muscle strength, skeletal muscle mass, and inflammatory markers in people with chronic musculoskeletal pain usually treated from the rheumatological field. A systematic review was conducted following PRISMA guidelines. Searches were performed in MEDLINE, Web of Science, CINAHL, Scopus, and EMBASE up to July 2026. Eligible studies were randomized or nonrandomized clinical trials that provided creatine supplementation alone or in combination with exercise as a treatment compared to a control or placebo group. Eight studies (n = 189) were included, encompassing fibromyalgia, osteoarthritis, rheumatoid arthritis, and juvenile idiopathic arthritis. Creatine dosages varied from chronic low-dose to loading protocols (20 g/d, 2-5 g/d). Combined creatine plus resistance training may improve strength, skeletal muscle mass, and quality of life beyond exercise alone in osteoarthritis. Trials on fibromyalgia suggest an increase in muscle strength, but inconsistent effects on pain. Rheumatoid arthritis studies suggest gains in skeletal muscle mass and, in pilot studies, reduced disease activity. No major adverse events were reported. In conclusion, creatine supplementation alone may be insufficient to obtain clinical benefits, while combined with resistance exercise it could offer potential benefits for muscle strength, skeletal muscle mass and certain aspects of quality of life in these clinical conditions. However, evidence on pain and inflammation remains limited; Furthermore, the response across different clinical conditions is heterogeneous, highlighting the need for larger, high-quality trials.

Humans↗

PubMed2026

Transverse Tibial Transport for Limb Salvage in Ischemic Lower Extremity Disease: Technique, Mechanisms, and Clinical Outcomes-A Systematic Review.

Transverse tibial transport (TTT) is a surgical technique derived from Ilizarov's distraction osteogenesis principles that stimulates angiogenesis and microcirculatory regeneration in the ischemic lower limb without directly manipulating macrovascular anatomy. By creating a proximal tibial cortical bone window and distracting it transversely using an external fixator, TTT triggers converging cascades of growth factor release, endothelial progenitor cell mobilization, and immunomodulation that translate into improved distal limb perfusion and wound healing. Combined TTT plus endovascular therapy improves amputation-free survival versus endovascular therapy alone. Prospective randomized trials and standardized international protocols are needed to consolidate TTT's role in multidisciplinary limb salvage pathways.

Humans↗

PubMed2026

Incidence of retropharyngeal lymph node involvement in oropharyngeal squamous cell carcinoma: a systematic review and meta-analysis.

BACKGROUND: Retropharyngeal lymph node (RPN) involvement in oropharyngeal squamous cell carcinoma (OPSCC) may influence prognosis, staging, radiotherapy target volumes, and treatment strategy. However, its true prevalence and association with clinicopathological factors remain incompletely defined. METHODS: A systematic review and meta-analysis was performed in accordance with the PRISMA 2020 statement. MEDLINE, EMBASE, EMCARE, PubMed, Web of Science, Scopus, and the Cochrane Library were searched from database inception to 15 June 2026. Studies reporting radiological or pathological assessment of retropharyngeal lymph node (RPN) involvement in oropharyngeal squamous cell carcinoma (OPSCC) were included. Pooled prevalence estimates were calculated using a random-effects model, with subgroup analyses according to tumour stage, nodal status, HPV status, and primary tumour subsite. RESULTS: Fourteen studies comprising 8,887 patients were included. The pooled prevalence of RPN involvement was (95% CI 11-16%; 95% PI 6-24%), with substantial heterogeneity. HPV-negative tumours demonstrated higher prevalence than HPV-positive tumours (21% vs 11%). Prevalence increased with advancing T stage, from 2% in T1 to 18% in T4 disease, and was higher in node-positive than node-negative disease (16% vs 1%). Tonsillar primaries showed higher prevalence than base of tongue tumours (14% vs 8%). Among patients with RPN involvement, the pooled distant metastasis rate was 16%. CONCLUSION: RPN metastases were identified in approximately one in eight patients with OPSCC and were more frequent in HPV-negative disease, advanced stage, and tonsillar primaries. These findings support careful evaluation of the retropharyngeal space during staging and may assist risk stratification in selected higher-risk patients.

Humans↗

PubMed2026

Health-Related quality of life (HRQoL) and health state utility values (HSUV) in patients with head and neck Cancer: A systematic review and Meta-Analysis.

BACKGROUND: Head and neck cancer (HNC) and its treatment can substantially impair speech, swallowing, eating, appearance, and social functioning, resulting in persistent reductions in health-related quality of life (HRQoL). Although the EuroQol 5-Dimensions questionnaire (EQ-5D) is widely used to assess generic HRQoL and derive health state utility values (HSUVs), EQ-5D-based evidence in HNC has not been comprehensively synthesized. This study aimed to summarize EQ-5D-based HRQoL and HSUVs in HNC, estimate pooled utility and EQ-VAS scores, explore subgroup differences, and identify predictors of poorer HRQoL. METHODS: A systematic review and meta-analysis was conducted according to PRISMA guidelines and registered in PROSPERO (CRD420261307907). PubMed, EMBASE, Web of Science, Cochrane Library, and Scopus were searched from inception to February 10, 2026. Studies reporting baseline EQ-5D utility values and/or EQ-VAS scores in patients with HNC were included. Random-effects meta-analyses using the DerSimonian-Laird (DL) estimator with the Hartung-Knapp-Sidik-Jonkman (HKSJ) adjustment were performed to pool mean scores. Between-study variance (τ2) and 95 % prediction intervals (PI) were calculated to capture parameter dispersion. Subgroup analyses were conducted across clinical and methodological vectors. RESULTS: Twenty studies involving 7,403 patients were included. The pooled mean EQ-5D utility score was 0.79 (95 % CI: 0.75-0.83; τ2 = 0.0011; 95 % PI: 0.72-0.86). The pooled mean EQ-VAS score was 69.36 (95 % CI: 65.71-73.01; τ2 = 38.4586; 95 % PI: 55.11-83.61). Extreme heterogeneity was observed (I2 = 96.4 % and 97.1 %, respectively). Utility values were significantly higher in studies utilizing the EQ-5D-5 L than the EQ-5D-3 L version (0.82 vs. 0.76). By tumor subsite, nasopharyngeal cancer showed the highest utility value (0.85, exploratory), whereas oral cancer demonstrated the lowest (0.73). Adjusted multivariable models revealed that advanced stage, high treatment intensity, severe pharyngolaryngeal pain, dysphagia, malnutrition, and older age were robust predictors of poorer HRQoL. CONCLUSIONS: Patients with HNC experience substantial and persistent HRQoL impairment, with meaningful variations driven by tumor subsites and instrument versions. In light of the extreme heterogeneity, these pooled findings establish a macro-level, broad reference estimate rather than a fixed target. These parameters directly inform localized survivorship care planning, health technology evaluations, and cost-utility decision-making modeling in head and neck oncology.

Humans↗

PubMed2026

Response-adapted surgical de-escalation following neoadjuvant immunotherapy in resectable mucosal HNSCC A systematic review and meta-analysis.

INTRODUCTION: Recent encouraging outcomes with neoadjuvant immune checkpoint inhibitors (ICIs) in mucosal head and neck squamous cell carcinoma (HNSCC) have generated interest in surgical de-escalation. However, the oncologic safety of response-adapted surgery (RAS) and its ability to achieve survival outcomes comparable to baseline-planned surgery (BPS) remain uncertain. METHODS: A systematic search of the PubMed, EMBASE, Cochrane Library, and the Clinical Trials Registry for studies of neoadjuvant ICIs, with or without chemotherapy, in resectable mucosal HNSCC, that explicitly report surgical extent, between 2020-2025 was performed. Two independent reviewers extracted data following PRISMA guidelines. Main outcomes included major pathologic response (MPR), pathologic complete response (pCR), event-free survival (EFS), and overall survival (OS). Study-level proportions were pooled by random effects models. Heterogeneity was assessed by the I2 statistic. RESULTS: The comparative analysis consisted of 4 RAS studies (involving 202 patients) and 11 BPS studies (403 patients). The pooled overall EFS was 83.3% (76.9-88.2) for the former and 82% (75.2-87.2) for the latter (P=.751), and the respective pooled OS was 92.3% (87.5-95.3) and 91.4% (80.3-96.5) (P=.839). The pooled pCR rate was 41.7% (95% CI 5.4-48.4; I2=.0) for RAS and 19.8% (95%CI 13.3-29.6; I2=.62) for BPS (P=.001), while the MPR was not significantly different (59.6%, versus 48.5%, P=.245). RAS was associated with greater organ preservation and reduced need for mandibulectomy and free-flap reconstruction. CONCLUSIONS: RAS following neoadjuvant ICIs in mucosal HNSCC may enable surgical de-escalation with preserved oncologic outcomes and improved function in selected patients. Larger prospective studies are warranted.

Humans↗

PubMed2026

Positive Margin Rate Following Transoral Surgery in T2-T3 Laryngeal Carcinoma - a Systematic Review and Meta-Analysis.

BACKGROUND: Transoral endoscopic surgery, using either conventional laser techniques or supported by robotic assistance, represents an established treatment modality for selected patients with T2-T3 laryngeal carcinoma. The goal is complete tumor removal, as positive resection margins have been associated with worse oncological outcomes. This systematic review and meta-analysis aimed to determine the positive margin rate following transoral endoscopic surgery for T2-T3 laryngeal carcinoma and to evaluate its impact on oncologic outcomes. METHODS: A systematic search of Medline, Embase, Web of Science, Cochrane CENTRAL, and Google Scholar was performed from inception through March 2025, identifying studies reporting on surgical margin status after transoral resection of T2 and/or T3 laryngeal carcinoma. A random-effects meta-analysis of proportions was used to estimate a pooled positive margin rate. The oncologic impact of margin status is presented descriptively owing to data heterogeneity. RESULTS: Thirty-nine studies comprising 3,281 patients with T2-T3 laryngeal carcinoma met the inclusion criteria. The positive margin rate was 22.0% (95% CI 17.6 - 27.3, I2 = 83.8%) for the total T2-T3 cohort, with stratified rates of 22.4% for T2 and 30.8% for T3 tumors. Among the eight studies assessing the impact of positive margins in T2-T3 stages, three found a significant association with worse oncological outcomes. Conclusion A 22% positive margin rate was identified in T2-T3 laryngeal cancer treated with transoral endoscopic resection. However, the impact of margin status on oncological outcomes remains uncertain, largely due to challenges in sampling and histopathological assessment.

Humans↗

PubMed2026

HPV circulating tumor DNA as a potential prognostic and predictive biomarker in head and neck squamous cell carcinoma: a systematic review.

PURPOSE: Human papillomavirus circulating tumor DNA (HPVctDNA) has emerged as a promising prognostic biomarker in HPV-related head and neck squamous cell carcinoma (HNSCC). This systematic review aimed to synthesize current evidence on the diagnostic accuracy and prognostic value of HPVctDNA in HNSCC management. MATERIAL/METHODS: We systematically reviewed a PubMed-indexed database of studies published between January 2012 and September 2025. Eligible studies were assessed for design, primary tumor site and stage, treatment modality, HPVctDNA detection method, diagnostic accuracy (sensitivity and specificity), and reported clinical endpoints. Descriptive syntheses were performed; sensitivity and specificity were standardized to proportions and summarized as median values per group. RESULTS: A total of 60 studies, including 8,234 patients were analyzed, of which 41 (68.3%) focused exclusively on oropharyngeal squamous cell carcinoma (OPSCC) and 17 (28.3%) included mixed HPV-related HNSCC subsites and HPV-positive cancers of unknown primary. The median follow-up across the included studies was 23 months. Among the included studies, 19 were retrospective (31.7%) and 33 were prospective (55.0%), with a small proportion of cross-sectional and randomized clinical trials. Overall, 40 (66.7%) evaluated the role of HPVctDNA in a curative setting. Plasma was the most common sample type, analyzed in 55 studies (91.7%), while 5 studies also included saliva. Detection methods varied: 40 employed droplet digital PCR (ddPCR), 16 used quantitative PCR (qPCR) and 4 applied NGS-based assays. Most of these studies (38, 63.3%) evaluated the prognostic utility of HPVctDNA, while only 4 (6.7%) assessed HPVctDNA in a screening or diagnostic setting. Regarding diagnostic accuracy, the median sensitivity across evaluable studies was 91.1%, while the median specificity was 99.4%. In OPSCC-only cohorts, the median sensitivity and specificity were 89.4% and 99.4%, respectively. Dynamic changes in HPVctDNA levels during or after treatment were consistently associated with outcomes: clearance or sustained negativity correlated with higher response rates, improved progression-free survival and overall survival, while persistent positivity or increasing levels predicted disease progression and recurrence. CONCLUSIONS: HPVctDNA demonstrates high diagnostic and prognostic accuracy in HPV-related HNSCC, especially OPSCC, supporting its use for prognosis, treatment monitoring and early detection of recurrence. However, prospective interventional studies are still required to demonstrate that HPVctDNA-guided treatment decisions improve clinical outcomes before routine implementation.

Humans↗

PubMed2026

Effect of SGLT2 inhibitor drugs on triglyceride-glucose (TyG) index in adults: A systematic review and meta-analysis.

BACKGROUND: Insulin resistance is a serious public health concern. The triglyceride-glucose (TyG) index is a simple, cheap, and reproducible surrogate of insulin resistance, and sodium-glucose cotransporter-2 (SGLT2) inhibitors have reshaped cardio-metabolic care beyond glycemic control. METHODS: We followed PRISMA and registered the protocol in PROSPERO (CRD420251056341). We searched PubMed, Scopus, Web of Science, EMBASE, and Cochrane from inception to May 31st, 2026, including observational studies and clinical trials reporting baseline and follow-up TyG in adults. Two reviewers screened records, a third resolved disagreements, data were extracted with a standardized form, and quality was assessed with Cochrane RoB 2.0, the Newcastle-Ottawa Scale, and the JBI checklists. The primary outcome was within-group change in TyG pooled with random-effects (Hartung-Knapp); tests were two-sided with a significance threshold of 0.05. RESULTS: Twelve studies comprising thirteen study arms were included, with a total of 1845 participants. Follow-up ranged from 12 weeks to 5 years. Across studies, SGLT2 inhibitor therapy was associated with a significant reduction in TyG index (mean difference = -0.28, 95% confidence interval [-0.41; -0.14], I2 = 99.5%). Egger's test suggested possible small-study effects, whereas Begg's test and trim-and-fill analysis did not show clear evidence of publication bias; leave-one-out analyses showed that no single study materially influenced the pooled estimate. CONCLUSION: Despite heterogeneity in populations, drug choice, and follow-up duration, SGLT2 inhibitors were associated with a significant decrease in TyG, although small-study effects cannot be excluded.

Humans↗