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PubMed2026

"Out of sync and overlooked" - Relationship between social jetlag and anxiety in adolescents: Systematic review and meta-analysis.

Anxiety is the most prevalent mental health difficulty in adolescence, a period characterised by a shift towards an eveningness chronotype that is not aligned with societal demands (i.e., school start times). Experiencing "social jetlag" (SJL), a discrepancy in weekday-weekend sleep timing, is proposed to be associated with increased anxiety. A PRISMA-compliant systematic review and meta-analysis was conducted to investigate the relationship between SJL and anxiety in adolescents (age range: 12-18 years). Systematic searches were conducted in PsycINFO, Web of Science, Embase, PubMed, MEDLINE, and ProQuest Dissertations & Theses Global on 14th November 2024 to retrieve empirical studies analysing the relationship between SJL and anxiety in 12-18-year-olds. A multi-level random-effect meta-analysis was conducted in R to estimate the magnitude of the association between SJL and anxiety. After screening 2,138 records, 18 studies were included in the systematic review, with 12 included in the meta-analysis (235,526 participants in total) and six in a narrative review. A small association was found between increased SJL and more severe anxiety (Fisher's z = 0.0614, 95% CI [0.0268, 0.0961], p = 0.0011). These findings highlight the importance of addressing behavioural strategies targeting healthy regular sleep as a tool to improve mental health in adolescence.

Adolescent↗

PubMed2026

Approaches to observational study designs and analytical options to evaluate the safety of multi-dose vaccines: a systematic review.

INTRODUCTION: Observational studies require careful considerations when evaluating the safety of multidose vaccines. We reviewed design and analytical approaches in observational studies evaluating the safety of multidose vaccines in the post-licensure phase. METHODS: EMBASE, MEDLINE, Web of Science, and Scopus (2018-2022) were searched for hypothesis-testing studies evaluating the safety of multidose vaccines. Key features from frequently used designs were extracted. RESULTS: Among 123 eligible studies, cohort (46%) and self-controlled case series (SCCS)/self-controlled risk interval (SCRI) (40%) followed by case-control (12%) were the most common designs, and 15% of studies used multiple designs. Among cohort studies evaluating multiple doses, vaccination date (36%) and cohort entry with time-updated exposure status (32%) were frequent approaches used to define time zero. Twenty-eight percent of cohort studies did not report time zero; all but one evaluated COVID-19 vaccine effect on post-delivery and fertility-related outcomes. For SCCS/SCRI, 64% of studies accounted for event-dependent exposures, mainly by including pre-exposure periods (53%) and modified SCCS model (48%), while 20% employed multiple correction strategies. Among studies using multiple designs, 68% reached consistent conclusions. CONCLUSIONS: SCCS/SCRI and cohort designs dominate multidose vaccine safety studies. Clear reporting on time zero in pregnancy and fertility-related cohort studies, and on addressing event-dependent exposures in SCCS/SCRI studies is needed, along with guidance on interpreting results from multiple designs.

Humans↗

PubMed2026

Frequency of Human Brucellosis Complications in West Asia: A Systematic Review and Meta-Analysis.

BACKGROUND: Brucellosis is a multi-systemic zoonotic infection. The West Asia/Middle East region is an important global hotspot for brucellosis. This systematic review and meta-analysis aimed to aggregate and synthesize all the available evidence regarding the complications of brucellosis in West Asia/Middle East region. METHODS: PubMed, Embase, Scopus, Web of Science, Google Scholar, and Proquest were searched. Selection of studies, data extraction, and the risk of bias assessment were performed in duplicate. Data extraction was performed for 254 complications. Meta-analysis was performed using a random-effects model with Freeman-Tukey double arcsine transformation. Where applicable small-study effects was assessed using funnel plots and Egger's test. Separate by-country, by-age, and by-publication-decade subgroup analyses were performed if feasible. RESULTS: Out of 9518 results, 240 studies (260 references) were included. The majority of the included studies were conducted in Turkey (n = 177). The reported complications varied and different complication categorization systems were detected. The highest pooled estimate was observed for musculoskeletal involvement (50%, 95%CI: 39%-61%, I2 = 96.63%). The evidences is up-to-date until March 4, 2024. CONCLUSIONS: Some complications such as the complications of the eye were not reported in all the countries. Therefore, it's recommended to determine the relative frequency of those complications in regions without such reports. The pooled estimates of different complications of brucellosis were different. There's a need for the standardization of the reporting of the complications of brucellosis to achieve comparability between studies and across different regions.

Brucellosis↗

PubMed2026

Effectiveness of peer recovery support services for substance use disorders: A systematic review of healthcare utilization, behavioral health, and engagement outcomes.

BACKGROUND: Peer recovery support services (PRS) delivered by individuals with lived experience of substance use, are increasingly incorporated into substance use disorder (SUD) care systems to improve care engagement, reduce acute care use, and support recovery. However, existing systematic reviews have focused on substance use outcomes, with limited attention to healthcare utilization, psychosocial functioning, and outcomes across settings, and populations. METHODS: This systematic review, registered in PROSPERO (CRD42023469279), synthesized peer-reviewed studies from 2003 to 2026 evaluating PRS for individuals with alcohol or drug-related SUD. Using MEDLINE, Embase, PsycINFO, and CINAHL, the review included 53 studies primarily conducted in high-income countries that reported quantitative outcomes across substance use, healthcare utilization, behavioral health, and treatment engagement. Risk of bias was assessed using Cochrane RoB 2, ROBINS-I, and ROBINS-E tools. RESULTS: Overall, evidence was most favorable for selected treatment-linkage and engagement outcomes, whereas findings for substance use, emergency department use, hospitalization, overdose, and mortality were inconsistent. Uncontrolled longitudinal studies frequently reported improvements in depression and anxiety, but no randomized trials evaluated these outcomes, limiting causal inference. Exploratory cross-study patterns suggested that sustained navigation, practical assistance, and repeated peer contact were more often present in programs reporting favorable outcomes; however, these components were not independently evaluated. Substantial heterogeneity, frequent multicomponent interventions, high risk of bias in many nonrandomized studies, and limited long-term and economic data constrain conclusions. CONCLUSIONS: Findings support the promise of PRS while underscoring the need for more rigorous comparative studies, cost-effectiveness data, and further research in low- and middle-income countries.

Humans↗

PubMed2026

Transcutaneous vagus nerve stimulation influences sleep quality and insomnia: A systematic review and meta-analysis.

Impairments in sleep quality, timing, or duration disrupt normal sleep patterns. This systematic review and meta-analysis investigated the effects of transcutaneous vagus nerve stimulation (tVNS) protocols on sleep outcomes. Thirteen randomized controlled trials with parallel or crossover designs that applied tVNS intervention and assessed sleep quality (Pittsburgh Sleep Quality Index) and insomnia severity (Athens Insomnia Scale and Insomnia Severity Index) were included. Effect sizes were calculated by comparing changes between the active tVNS and control groups. Moderator analyses examined whether stimulation of different targeted regions influences sleep outcomes. Meta-regression analyses examined potential relationships between the effects of tVNS protocols on sleep quality and demographic characteristics and multiple tVNS parameters, respectively. The random-effects meta-analysis indicated that tVNS protocols influenced better sleep quality and lower insomnia severity. Moderator variable analysis revealed that tVNS targeting the concha region induced better sleep quality. Meta-regression analysis revealed that better sleep quality was associated with lower ages of participants. These findings suggest that tVNS protocols, particularly those targeting the concha, were associated with favorable changes in sleep quality and insomnia severity, with age potentially moderating the treatment response.

Humans↗

PubMed2026

Assessing the effects of non-invasive transcranial electrical stimulation (tACS and tDCS) on electrophysiological sleep parameters - a systematic review.

Transcranial electrical stimulation (tES), including transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS), is considered a safe method to modulate cortical activity and endogenous brain oscillations. Given the therapeutic potential of tES across various clinical conditions and the central role of sleep in restoration and memory consolidation, numerous studies have investigated its effects on sleep and sleep-related parameters, yielding inconsistent results. This systematic review provides an up-to-date synthesis of 51 studies assessing the impact of tES on objectively measured electrophysiological sleep outcomes in both healthy individuals and clinical populations. The reviewed studies demonstrate heterogeneous effects, reflecting substantial variability in study designs. Nonetheless, consistent trends emerge, including reduced NREM1 and increases in total sleep time, NREM2, and NREM3 following tES. Moreover, slow-oscillatory tES increased slow-wave power during sleep. Here we show that tES, particularly slow-oscillatory tES, may positively influence sleep architecture and continuity by modulating endogenous brain oscillations. However, due to heterogeneous stimulation protocols, inconsistent findings, the limited number of significant effects and substantial risk of bias the current evidence remains inconclusive. Well-designed, large-scale trials targeting specific sleep outcomes are needed to clarify the therapeutic potential of tES.

Humans↗

PubMed2026

Symptom Networks and Core Symptoms in Patients with Solid Tumors Undergoing Chemotherapy: A Systematic Review.

OBJECTIVES: To summarize symptom network characteristics in patients with solid tumors undergoing chemotherapy and synthesize evidence on core symptoms, bridge symptoms, and temporal associations. METHODS: We systematically searched eight databases through October 2025 to identify studies that applied symptom network analysis to adults with solid tumors receiving chemotherapy. Eligible studies assessed symptoms using cross-sectional, longitudinal, or interventional designs. Two reviewers independently screened articles and extracted data on study characteristics, symptom assessment, and network outcomes. Methodological quality was assessed using the National Institutes of Health Study Quality Assessment Tool. RESULTS: Twenty-seven studies involving 13,452 participants were included, yielding 79 symptom networks. Fatigue was the most frequently identified core symptom (10/20, 50%), whereas sadness, lack of appetite, and nausea each occurred in 10% of studies, with variation across cancer types, treatment phases, and latent classes. Bridge symptoms included disturbed sleep, lack of appetite, and dry mouth (2/7, 28.6%). Studies evaluating temporal associations found that symptoms such as sadness, dyspnea, somnolence, and dry mouth predicted subsequent changes in appetite, distress, nausea, and other outcomes. Strength metrics showed acceptable stability (correlation stability coefficients: 0.28-0.83). CONCLUSIONS: Fatigue was frequently identified as a central symptom across studies, largely reflecting evidence from breast cancer studies. Core symptoms varied across cancer types, treatment phases, and latent classes, suggesting heterogeneity. IMPLICATIONS FOR NURSING PRACTICE: These findings highlight the importance of considering relationships among symptoms in clinical care. Focusing on key symptoms such as fatigue, while tailoring management strategies to cancer-specific symptom patterns, may support more effective symptom management.

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

Diet and sleep among college student populations: a systematic review.

College students are at-risk for both poor diet and poor sleep. We aimed to systematically review the evidence regarding associations between diet and sleep health within this population. A comprehensive electronic search was conducted in PubMed, Embase, Scopus, Web of Science, and PsycINFO from the earliest possible date through February 6, 2026. A total of 57 studies representing 44 countries were retained; most were cross-sectional. There were 22 studies that examined dietary patterns in relation to sleep, generally showing that healthier diet patterns, including the Mediterranean Diet, were related to better sleep quality. Among 20 studies that examined individual foods or nutrients, there was evidence that fruits, vegetables, dairy, protein, and lower intake of sugar-sweetened beverages were linked to better sleep health, although some findings were mixed. Finally, 15 studies related meal timing to sleep quality, showing that breakfast skipping and later last meals were associated with poor sleep health. Overall, these studies reveal robust cross-sectional associations between diet and sleep among college students, but more longitudinal studies and randomized controlled trials are needed to evaluate directionality. Moreover, a key direction for future study is consideration of sleep and nutrition situated within the unique contexts of college settings and academic schedules.

Humans↗

PubMed2026

Efficacy and safety of postoperative chewing gum for gastrointestinal recovery in children undergoing surgery: an updated systematic review and meta-analysis.

Chewing gum may stimulate gut motility through a "sham feeding" mechanism, but evidence in children is limited. We performed an updated systematic review and meta-analysis of randomized controlled trials comparing chewing gum plus usual care versus usual care alone in patients younger than 18 years undergoing any surgery. We searched five databases through June 2025. Primary outcomes were the time to first flatus, time to first defecation, and postoperative length of stay (LOS). Certainty was assessed with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Ten studies (n = 649) were included: abdominal surgery (5), spinal fusion (3), and tonsillectomy (2). Chewing gum may result in little to no difference in the time to first flatus (MD - 3.58 h, 95% CI - 8.08 to 0.91) or first defecation (MD - 3.23 h, 95% CI - 6.63 to 0.18), both with low certainty. LOS evidence was very uncertain (MD - 0.18 days, 95% CI - 0.70 to 0.33). Subgroup analyses suggested shorter LOS after abdominal surgery (MD - 0.60 days, 95% CI - 1.99 to 0.79) but not after spinal fusion (MD 0.10 days, 95% CI - 0.29 to 0.50; p for interaction = 0.0362). The benefits of postoperative chewing gum in children remain uncertain, with potential surgery-specific differences in LOS warranting investigation.

Humans↗

PubMed2026

Artificial intelligence in genitourinary oncology: publication trends and systematic review.

OBJECTIVE: To conduct an analysis of publication trends and a systematic review of randomized controlled trials (RCTs) to characterize the current state of artificial intelligence (AI) use in genitourinary (GU) oncology, as AI has emerged as a transformative tool in healthcare with potential applications in diagnostics, treatment planning, and prognostication. METHODS: We searched the Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica dataBASE (EMBASE; Ovid), and Cumulative Index to Nursing and Allied Health Literature (CINAHL) Ultimate for studies related to AI and GU oncology, excluding non-English papers, non-human studies, review articles, and articles using AI solely for manuscript writing. Publication trends were analysed from 2013 to 2023 and categorized by study design and cancer type. RCTs were evaluated through systematic review using Covidence (Veritas Health Innovation Ltd, Melbourne, Victoria, Australia) for screening and data extraction. Two reviewers independently assessed all studies, with risk of bias (RoB) evaluated using the Cochrane RoB 2.0 tool. RESULTS: Of 2409 articles identified, 1220 met inclusion criteria. These included 962 retrospective articles, 175 prospective studies, 79 studies with combined retrospective/prospective methods, and four RCTs. Studies most commonly addressed prostate (n = 923), renal (n = 274), and urothelial (n = 194) cancers. Publications grew from 14 in 2013 to 362 in 2023, with substantial acceleration in 2019. Four RCTs were identified - one in urothelial cancer and three in prostate cancer. Two RCTs evaluated AI-based diagnostics, demonstrating improved performance over conventional methods; the remaining two RCTs evaluated AI in prognostication and treatment planning, showing improved gains in imaging interpretation and operational efficiency. RoB varied across studies, primarily related to randomisation and deviations from intended interventions. CONCLUSIONS: Artificial intelligence research in GU oncology has grown, although high-level evidence from RCTs remains limited. Existing trials underscore AI's promise in diagnostics, prognostication, and treatment planning, and the rapidly evolving nature of this field warrants continued prospective investigation.

Humans↗

PubMed2026

Non-linear predictive modeling and comprehensive meta-analysis of rectal temperature in Santa Inês sheep: a systematic review of thermal challenges and biometerological trends.

A systematic and bibliometric review, combined with a meta-analysis, was used to adjust an equation for estimating the physiological responses of Santa Inês sheep subjected to different thermal challenges. The systematic review compiled data on physiological responses and the thermal environment, which were then used in the meta-analysis to adjust regression models. The bibliometric analysis mapped the relationships among studies, highlighting their usefulness in interpreting research findings and biases. Addressing prior methodological critiques, the core of this study involves replacing the linear approach with a non-linear segmented regression model to accurately define the Thermal Neutral Zone (TNZ). The Segmented Regression Model was crucial, establishing the upper limit of the Thermal Neutral Zone (TNZ) at an air temperature (tair) of 34.64 °C, where trectal begins to increase abruptly. The model, while identifying a biologically significant breakpoint, exhibited a moderate Multiple R-squared of 0.3529, highlighting the high heterogeneity and methodological variability in the current Santa Inês literature. This non-linear approach offers a biologically superior tool for identifying the onset of thermal distress.

Animals↗

PubMed2026

Gonadal function and fertility outcomes after orchiopexy versus orchiectomy for testicular torsion: A systematic review and meta-analysis.

PURPOSE: To review the early and late changes in hormonal profiles, semen parameters, and clinical outcomes in patients treated with orchiopexy versus orchiectomy for testicular torsion. METHODS: A systematic search was conducted across MEDLINE, Scopus, Web of Science, Cochrane Library, and other databases, following PRISMA guidelines. PRIMARY OUTCOMES: FSH, LH, testosterone, inhibin-B, and semen parameters. Quality was assessed using the Newcastle-Ottawa Scale. Certainty of evidence was evaluated using the GRADE framework. Statistical analysis was performed using the random-effects model. RESULTS: Eleven studies involving 538 participants (197 orchiectomy, 341 orchiopexy) were included. Orchiectomy was associated with a significant increase in FSH (SMD: 1.63, P < 0.0001) and LH (SMD: 1.31, P < 0.0001) compared to orchiopexy. However, testosterone (MD: 0.31 ng/mL; P = 0.4) and inhibin-B (SMD: -0.14; P = 0.87) levels were comparable between groups. Regarding semen parameters, orchiectomy resulted in a significant reduction in sperm concentration (MD: -18 million/mL, P = 0.01). No significant differences were found in sperm count (MD: 13.9 million; P = 0.43), normal morphology (MD: 4.97%; P = 0.12), or total motility (MD: 4.05%; P = 0.49). The pooled rate for ipsilateral atrophy following orchiopexy was 38%, which likely depends on ischemia duration. CONCLUSION: Surgical choice in testicular torsion does not significantly affect the overall hormonal balance or most semen parameters due to compensatory mechanisms of the hypothalamic-pituitary-gonadal axis. Clinical decisions should consider individual case factors, as we lack reliable data on subsequent paternity rates.

Male↗

PubMed2025

Outcomes of Experiencing Interpersonal Violence in Autism: A Mixed Methods Systematic Review and Meta-Analysis.

In this review and meta-analysis, we aimed to examine outcomes of interpersonal violence among autistic people. Intersectionality and minority theories suggest that negative outcomes are heightened among people with multiple marginalized identities. Thus, we also aimed to investigate gender-related outcomes of interpersonal violence among autistic people. We conducted a systematic database search with inclusion criteria including mixed methods, peer-reviewed research examining any harmful interpersonal act (e.g., physical, sexual, and psychological) experienced by autistic people. We undertook a random-effects meta-analysis with pooled data from 9 studies, comprising 3,647 autistic participants aged 1 to 80 years. Violence was associated with worsened mental health, with the strongest association for internalizing symptoms (d = 0.66, p < .001; 95% CI [0.51, 0.80]) and suicidal thoughts and behavior (d = 0.63, p < .001; [0.44, 0.82]). Narrative synthesis of 57 studies comprising 37,418 participants (13,127 autistic, 24,291 non-autistic) found violence was associated with numerous adverse health, development, and functional outcomes, including worsened mental health and behavioral difficulties compared to non-autistic controls from childhood. Females and gender minorities reported greater intra- and interpersonal health and development difficulties related to violence, emerging in early childhood and enduring into adulthood. Findings provide strong evidence of lifelong negative outcomes associated with interpersonal violence experienced by autistic people, providing evidence for the relevance of minority stress and intersectionality theories in understanding risk. Indeed, our results raise concerns that autistic people, and particularly non-male (female, gender diverse) individuals, have higher susceptibility for abuse from a young age, while being conditioned to respond with social desirability, superficial adaptivity, and dissociation.

Humans↗

PubMed2026

The interplay between circadian misalignment or sleep disturbances and cognition and brain function in individuals with different degrees of insulin resistance - a systematic review.

Disruption of sleep increases the risk of type 2 diabetes and worsens cognitive outcomes, yet few studies have evaluated the interaction between insulin resistance and sleep parameters in relation to cognitive outcomes or the risk of dementia. This systematic review examines how circadian misalignment and sleep disturbances affect cognition and neuroimaging findings in individuals with varying degrees of insulin resistance. Across 27 studies, disrupted circadian rhythmicity and sleep disturbances were negatively associated with brain health, possibly through its effects on insulin sensitivity, whereas the impact of sleep duration and quality were inconclusive. Methodological heterogeneity, reliance on cross-sectional designs, and limited control for confounders restricted definitive conclusions and highlighted the need for longitudinal and interventional studies with objective measurements. Nonetheless, the findings support circadian rhythmicity as a potentially modifiable risk factor for preserving cognition in insulin-resistant populations. Future research should prioritise prospective and interventional studies and focus on biological markers rather than self-reported outcomes.

Humans↗

PubMed2026

Measurement of low-density lipoprotein cholesterol and other circulating lipids in Brazil: a systematic literature review.

Accurate laboratory assessment of circulating lipids underpins cardiovascular risk stratification, yet clinical interpretation depends not only on the assays but on the formula chosen to estimate low-density lipoprotein cholesterol (LDL-C). This review integrates the 2019-2025 evidence on laboratory methods for triglycerides (TG), total cholesterol (TC), and high-density lipoprotein cholesterol (HDLC), and on the formulas estimating LDL-C, VLDL-C, and non-HDL cholesterol, to determine how these should be measured, reported, and harmonized in Brazil, where lipid thresholds are adapted from international consensus. A PRISMA 2020 systematic search (PROSPERO CRD420251241064) of PubMed/MEDLINE, Scopus, SciELO, LILACS, Web of Science, and Embase retrieved 57,915 records; after removing 38,210 duplicates, 19,705 titles/abstracts were screened, 312 full texts assessed, and 25 sources included. Enzymatic colorimetric assays remain standard for TG, TC, and HDLC. For LDL-C, Martin/Hopkins classifies more accurately than Friedewald (89.6% vs 83.2% correct categorization in 5,051,467 patients), particularly at high TG and low LDL-C, while Sampson/NIH and modified Sampson/NIH extend reliable estimation into hypertriglyceridemia and very low LDL-C; direct measurement is reserved for TG beyond the validated range. Although the review centers on the Friedewald, Martin/Hopkins, and Sampson/NIH families that dominate guideline practice, other published equations exist and are addressed in context. In Brazil, atherogenic-lipid thresholds are risk-based decision limits rather than reference intervals; national surveys describe lipid distributions but were not designed to establish them. Analytical standardization through traceability programs, multicenter validation of formulas, and-where the distribution-based construct applies (HDLC, pediatrics)-nationally derived reference intervals are priorities for equitable cardiovascular risk assessment in Brazil.

Humans↗

PubMed2026

De-escalation of radiotherapy in HPV-negative non-nasopharyngeal head and neck squamous cell carcinoma: a systematic review.

BACKGROUND: Definitive and postoperative radiotherapy are central components of treatment for head and neck squamous cell carcinoma (HNSCC) but are associated with significant toxicities that can impair long-term function and quality of life. De-escalation strategies, aiming to reduce treatment-related morbidity while maintaining tumor control, have attracted increasing interest. However, most research has focused on HPV-positive oropharyngeal carcinoma. Systematic evidence for HPV-negative disease remains limited. METHODS: PubMed and EMBASE were searched for prospective studies investigating radio(chemo)therapy de-escalation in HPV-negative, HPV-unspecified, or mixed non-nasopharyngeal HNSCC populations. CLINICALTRIALS: gov was searched for ongoing prospective trials. Data extraction and verification were performed independently by three investigators. RESULTS: Screening of 3156 records identified 14 published prospective studies, 10 in the definitive and four in the postoperative setting. Strategies included reduction or omission of elective nodal volumes, dose reduction, and combined approaches. Additionally, 23 ongoing prospective trials were identified. Across studies, elective nodal failure rates were consistently low (0-4.6%), with most recurrences occurring within high-dose volumes rather than de-escalated elective regions. Randomized evidence for elective nodal dose reduction is mixed: two trials maintained regional control and reduced acute toxicity, whereas another was stopped for futility. CONCLUSION: Available evidence on de-escalation in HPV-negative HNSCC is limited, derived primarily from small, heterogeneous phase II studies with mixed HPV populations. Although data are promising in selected settings, notably for elective nodal control, the randomized evidence for elective nodal dose reduction is conflicting, and further adequately designed prospective randomized trials are required.

Humans↗

PubMed2026

Who Is the Ideal Candidate for High-Definition Liposuction? A Systematic Review and Meta-Analysis.

BACKGROUND: High-definition liposuction (HDL) enhanced muscular definition by selectively removing superficial subcutaneous fat. Despite its growing popularity and high satisfaction rates, no consensus exists regarding the ideal candidate. This systematic review evaluates demographic factors, patient selection criteria, and complication rates associated with HDL. METHODS: A systematic review and meta-analysis were conducted utilizing PRISMA-P guidelines. PubMed, Cochrane Library, Embase, and Web of Science were searched for studies published within the past 10 years. Seventeen studies met inclusion criteria, comprising 9570 patients. Study designs included randomized controlled trials, cohort studies, and observational analyses reporting demographics, procedural details, and complications. Standardized data extraction was performed. Pooled analyses were conducted for hematoma and seroma, and univariable meta-regression assessed associations between mean age, BMI, and proportion of female patients with complication rates. RESULTS: Mean age was 36.0 years and mean BMI was 25.8 kg/m 2 (range: 18 to 66); 55% of patients were female. Selection criteria varied; most studies applied BMI thresholds (≤30 to 34 kg/m 2 ) and excluded poorly controlled diabetes, heavy smoking, and thromboembolic history. The abdomen, flanks, and chest were most treated. Mean fat removal was 4268.8 mL, with an average operative time of 235 minutes. Complication rates were low; the pooled incidence of seroma was 7% and hematoma was 1%. Meta-regression showed no significant associations between complications and age, BMI, or sex. Patient satisfaction was high. CONCLUSION: HDL is safe and effective across diverse populations; however, variability in selection criteria and reporting limits evidence-based definitions of ideal candidates. Further prospective studies with standardized reporting are needed.

Humans↗