Search Results (10,512)

Scalp hair offers a non-invasive matrix for retrospective paediatric biomonitoring, although interpretation is complicated by endogenous incorporation, exogenous deposition and element-specific analytical detectability. We characterised B, Ca, Co, Fe, Li, Mg, Mo, Ni and Se in archived scalp hair collected in 2001 from 120 children aged 6–9 years and 97 adolescents aged 13–16 years residing in urban–industrial Alcalá de Henares, Spain. Samples were analysed in 2025 by ICP–MS using a common quality-controlled analytical workflow, with left-censored observations evaluated using censoring-aware methods. B and Li were highly censored (89.2–94.8% and 86.7–99.0%, respectively), whereas Fe, Mg, Mo and Se were consistently quantified. Adolescents showed higher median Ca (325 vs. 168 µg g⁻¹; q = 1.43 × 10⁻⁹), Mg (24.0 vs. 9.05 µg g⁻¹; q = 8.91 × 10⁻¹⁹) and Ni (0.169 vs. 0.0597 µg g⁻¹; q = 2.10 × 10⁻⁵), but lower Fe (5.16 vs. 7.54 µg g⁻¹; q = 2.28 × 10⁻¹¹), Co and Mo than children. Sex-associated differences were also observed for several elements, although their magnitude and detectability varied between age strata. Residential heterogeneity was strongest among adolescents: median Ca in the mixed residential–industrial Zone IV was 967 µg g⁻¹ compared with 232–385 µg g⁻¹ in Zones I–III (q = 2.75 × 10⁻¹²), while median Mg was 113 versus 18.8–24.3 µg g⁻¹ (q = 2.26 × 10⁻⁶). These specimens, collected in 2001, stored dry in paper envelopes for approximately 24 years, and analysed together in the 2025 ICP–MS campaign, provide a distinctive historical paediatric biomonitoring baseline from a well-defined Spanish urban–industrial population. The findings support scalp hair as a screening-level matrix for investigating population patterns across developmental stage, sex and residential setting, while not supporting its use as a direct measure of nutritional status, internal dose or health risk. Full article

Background: Gastroesophageal adenocarcinoma is predominantly a disease of older adults. However, older adults are underrepresented in randomised controlled trials (RCTs), and outcomes specific to this subgroup are underreported. Clinicians therefore extrapolate data from younger, fitter trial populations, which can lead to over- and undertreatment of older cancer patients. This study examines the inclusion and completeness of outcome reporting for older patients in practice-changing trials in gastroesophageal cancer. Methods: RCTs were identified from United States Food and Drug Administration (accelerated) approvals between 2010 and 2024. The primary study report, clinicaltrial.gov repository and all relevant secondary publications were assessed for the level of reporting of outcomes. Efficacy outcomes were reported as complete, partial, qualitative or quantitative based on availability of sample size, effect size and measures of precision. Baseline characteristics, toxicity outcomes and health-related quality of life (HRQOL) outcomes were assessed using minimum data thresholds. Results: In total, 13 trials, 53 publications and 13 repository webpages were assessed. A total of 9320 patients were included, of which 40.1% were classified as older adults. Among the patients, 42.2% had an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0, with all but one trial excluding patients with an ECOG PS of 2 (n = 63). Baseline characteristics and toxicity outcomes for older adults were fully reported in only two trials (15.4%). Reporting of HRQOL outcomes (25.0%), secondary (20.0%) and primary endpoints (66.7%) was more complete. Overall survival (76.9%) and progression-free survival (67.0%) were the most commonly reported primary or secondary endpoints. Conclusions: This study highlights deficits in the outcome reporting of older cancer patients in GOA trials. Simultaneously, this subgroup also remains heavily underrepresented in GOA trials compared to the real-world patient population. These findings highlight the need for improvements in both trial design and outcome reporting standards for older adults. Full article

Leishmaniasis is an emerging zoonotic disease recognized by WHO as a priority neglected tropical disease (NTD) targeted for elimination by 2030. The disease is transmitted through bites of infected female phlebotomine sand flies and presents in three main forms: cutaneous, mucocutaneous, and visceral leishmaniasis. Visceral leishmaniasis (VL) has two distinct epidemiological cycles: anthroponotic visceral leishmaniasis (AVL) cycle, caused by L. donovani and transmitted between humans, and zoonotic visceral leishmaniasis (ZVL) cycle, caused by L. infantum, with domestic dogs as the main reservoirs. ZVL represents the most severe clinical form and poses a public health risk due to a high fatality rate. In Kenya, the epidemiology and transmission dynamics of Leishmania infection among the canine population in endemic areas such as Baringo are poorly characterized. A cross-sectional epidemiological study was conducted in Baringo County, Kenya, one of the endemic foci for human visceral leishmaniasis. Blood samples were collected from 140 dogs in Rabai, Sabor, Mbechot, Kapkuikui, and Chemolingot and analyzed using Rapid Diagnostic Test (RDT) and Enzyme-linked immunosorbent assay (ELISA). Data on potential epidemiological factors and clinical status for dogs were collected using a questionnaire. Statistical analysis was performed using Pearson’s chi-square (χ²) test or Fisher’s exact test to assess associations between Leishmania seropositivity and potential risk factors. A stepwise logistic regression procedure with an entry significance level of p < 0.20 was employed to identify factors associated with leishmaniasis seroprevalence. Cohen’s kappa (κ) agreement was used to assess the diagnostic performance and accuracy of the two serological tests in the absence of a gold standard. The overall seropositivity in dogs was 7.79% and 12.14% at 95% CI for the RDT and ELISA, respectively. Multivariate analysis identified breed and clinical signs as significant factors associated with Leishmania seropositivity in dogs. Local-breed dogs were more likely to be Leishmania seropositive than mixed-breed dogs (OR = 11.92; 95% CI: 1.79–79.37; p = 0.010). Dogs without clinical signs exhibited significantly lower odds of ELISA seropositivity (OR = 0.06; 95% CI: 0.01–0.29; p < 0.001). Dogs with proper care and housing conditions had reduced risk of Leishmania seropositivity compared with poorly managed dogs. Significant association with seropositivity was observed for sex, age, origin, and reason for keeping dogs. Diagnostic evaluation showed that the RDT had an excellent specificity and Positive Predictive Value (100%), with good overall agreement with ELISA, although sensitivity was 64.7%. Hence, RDT can be a reliable alternative screening tool compared with ELISA as the reference standard. The study demonstrated the presence of Leishmania infection in the dog population in Baringo County, Kenya, a significant public health risk. Early detection and diagnosis of infections in dogs through an integrated One Health approach during routine surveillance are essential. This will facilitate treatment and/or culling of infected dogs and vector control, subsequently reducing the risk of human transmission. Hence, it will go a long way to achieving WHO’s roadmap of eliminating leishmaniasis by 2030. Full article

The success of HIV treatment is primarily measured through viral load suppression. However, little is known regarding the association between sexual union status and viral suppression among older adults. This study aimed to assess the association between sexual union status and HIV viral load suppression among adults aged 40 years and older living with HIV in rural Mpumalanga, South Africa. An observational analytical study design was followed, utilising data from the HIV After 40 study in Mpumalanga. The study focused on 4637 older men and women aged 40 years and above, living with HIV. Four nested unadjusted and adjusted binary logistic regression models assessed the association between sexual union status and HIV viral load suppression. All statistical analyses were done using SPSS Version 29.0; the significance level was set at p < 0.05. Viral suppression rates significantly differed by sexual union status (p = 0.003), with married/cohabiting participants showing lower suppression (40.6%) than single (45.1%) and divorced/widowed participants (45.9%). The fully adjusted logistic regression model showed a non-significant association between viral load suppression and sexual union status (p = 0.066); however, a significant association was found in the unadjusted (p = 0.020) and partially adjusted models. Having a primary education (p < 0.001), South African citizenship (p < 0.001), being aged ≥66 years (p < 0.001), and being female (p = 0.003) were independently associated with lower odds of being virally suppressed. Sexual union status was not significantly associated with viral suppression in the fully adjusted regression model. This underscores the need for gender-responsive, age-sensitive HIV treatment interventions in rural South Africa. Full article

Background: Handgrip strength has been proposed as an objective marker of post-COVID functional impairment, but its contribution relative to fatigue and sleep quality has not been formally evaluated in Latin American populations. Methods: We conducted an exploratory cross-sectional analysis of 130 adults with post-COVID condition in Palmira, Colombia. The outcome was any functional limitation on the Post-COVID Functional Status (PCFS) scale (grades 1–4 versus grade 0). Eight predictors were pre-specified on clinical grounds before examining outcome associations, and ridge-penalized logistic regression was pre-specified as the primary model. Sample size adequacy followed the criteria of Riley et al. Internal validation used bootstrap optimism correction (B = 1000), re-running the complete pipeline within each replicate. We assessed calibration, decision curves, prediction stability, SHapley Additive exPlanations (SHAP) with bootstrap rank intervals, and subgroup performance. Reporting followed TRIPOD + AI; risk of bias was self-assessed with PROBAST + AI. Results: Functional limitation affected 91/130 participants (70.0%). The minimum sample required for eight parameters was 566; the cohort met 23.0% of this requirement, so the analysis is exploratory. The optimism-corrected area under the curve was 0.748 (95% confidence interval (CI) 0.669–0.830), with calibration slope 1.15 (0.71–1.69). Fatigue ranked first in SHAP importance (54.0% of resamples), whereas grip strength ranked fifth (median rank 6). Net benefit exceeded both default strategies between thresholds 0.38 and 0.88. Thirty percent of participants changed classification in over 20% of resamples. Conclusions: Fatigue, sleep quality and acute-phase severity, rather than grip strength, emerged as the most influential correlates. These hypothesis-generating findings require confirmation in adequately powered cohorts. Full article

Background: Community-dwelling individuals at high cardiovascular risk are clinically heterogeneous, but whether distinct clinical-metabolic phenotypes differ in carotid plaque burden remains unclear. Methods: From 4191 participants in a community-based screening project conducted in two communities in Guangzhou, 1015 individuals in the high-cardiovascular-risk stage with nonmissing high-plaque-burden status were included. All 1015 participants underwent exploratory clustering using 17 clinical, metabolic, lifestyle-related, and disease-history variables. High plaque burden was defined as bilateral carotid plaques, multiple plaques, or maximum plaque thickness at or above the 75th percentile among plaque-positive participants. Logistic regression examined associations between phenotypes and high plaque burden. Results: Among the 1015 participants included in the clustering analysis, 329 (32.4%) met the definition of high plaque burden. Four phenotypes were identified: relatively low metabolic burden, older age–ASCVD burden, smoking–low HDL-C, and blood pressure-loaded phenotypes. The corresponding prevalences of high plaque burden were 15.9%, 44.4%, 49.7%, and 33.2%. After adjustment for age and sex, all three non-reference phenotypes showed higher odds of high plaque burden. In sensitivity analysis excluding age and prior ASCVD from clustering, the blood pressure-loaded phenotype remained associated with high plaque burden. Conclusions: Four exploratory clinical-metabolic phenotypes showed different levels of carotid plaque burden among community-dwelling individuals at high cardiovascular risk. The blood pressure-loaded and smoking–low HDL-C phenotypes were associated with greater plaque burden and may provide an exploratory framework for describing heterogeneity within high-risk populations. Full article

Glucagon-like peptide-1 (GLP-1) receptor agonists and dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonists have transformed obesity management by producing substantial, sustained weight loss and improving metabolic health. Alongside these benefits, their effects on appetite, food intake, and gastrointestinal function have raised increasing interest in the nutritional consequences of pharmacologically induced weight loss. Although reductions in energy intake contribute to therapeutic efficacy, they may also influence protein intake, dietary quality, micronutrient adequacy, and skeletal muscle health, particularly in individuals with pre-existing nutritional vulnerability. This narrative review summarizes current evidence regarding nutritional considerations during GLP-1-based therapy, including changes in dietary intake, protein and micronutrient adequacy, body composition, muscle health, and nutritional assessment. Particular attention is given to populations at increased nutritional risk, practical approaches to nutritional monitoring, and strategies to support adequate nutrition during treatment. Current evidence suggests that nutritional responses to GLP-1-based therapy are heterogeneous and cannot be adequately evaluated using body weight alone. Assessment of dietary intake, body composition, muscle function, physical performance, and individual clinical characteristics provides a more comprehensive understanding of nutritional status than anthropometric measures alone. While routine supplementation or intensive monitoring is not supported for all patients, a risk-based and individualized approach appears appropriate, particularly for older adults and individuals with sarcopenic obesity, previous bariatric surgery, chronic gastrointestinal disease, or persistent treatment-related gastrointestinal symptoms. Future research should establish clinically meaningful nutritional outcomes and determine which nutritional interventions improve patient-centered outcomes during long-term obesity management. Full article

Background: Periodontitis is a chronic inflammatory disease characterized by progressive destruction of the tooth-supporting tissues and may substantially impair oral health-related quality of life (OHRQoL). Although the clinical consequences of periodontitis are well documented, the extent to which disease severity is associated with patient-reported outcomes remains insufficiently understood. This study aimed to evaluate the association between periodontitis severity and OHRQoL and to examine sociodemographic, behavioral, and systemic factors associated with poorer OHRQoL. Methods: A cross-sectional analytical study was conducted among 136 adult patients diagnosed with stage II or stage IV periodontitis at the Periodontology Clinic of Universidad Tecnológica de México (UNITEC). OHRQoL was assessed using the Oral Health Impact Profile for Periodontal Disease (OHIP-14-PD). Sociodemographic characteristics, smoking status, and diabetes mellitus were recorded using a structured questionnaire. Periodontal status was determined through standardized clinical and radiographic examinations. The internal consistency of the OHIP-14-PD was evaluated using Cronbach’s alpha coefficient. Bivariate analyses were performed using non-parametric tests. An exploratory, partially adjusted multivariable linear regression model including sex, marital status, diabetes mellitus, and periodontitis stage was also performed. Results: Stage IV periodontitis was more prevalent than stage II periodontitis (55% vs. 45%). The mean OHIP-14-PD score was 24.9 ± 13.7, and the instrument demonstrated excellent internal consistency (Cronbach’s α = 0.89). Patients with stage IV periodontitis had significantly higher OHIP-14-PD scores than those with stage II disease (30.1 ± 12.4 vs. 18.6 ± 12.6; p < 0.001), indicating poorer OHRQoL. In the bivariate analyses, poorer OHRQoL was also observed among current smokers, participants with diabetes mellitus, those with lower educational attainment, and those with lower socioeconomic status (p < 0.05). In the exploratory partially adjusted model, male sex (β = 4.2; 95% CI: 0.1–8.2; p = 0.042), diabetes mellitus (β = 6.5; 95% CI: 2.1–10.9; p = 0.004), and stage IV periodontitis (β = 4.6; 95% CI: 0.4–8.7; p = 0.031) were associated with higher OHIP-14-PD scores. Conclusions: In this single-center cross-sectional sample, patients with stage IV periodontitis reported higher OHIP-14-PD scores than those with stage II periodontitis. These findings indicate an association within the studied clinical population and should not be interpreted as evidence of a causal effect or as directly generalizable to broader populations. Larger multicenter longitudinal studies including patients across all periodontitis stages are required to confirm the magnitude and external validity of this association. Full article

Background: Population aging has increased the prevalence of cognitive impairment and dementia, highlighting the need for personalized non-pharmacological interventions. Although socially assistive robots have shown therapeutic benefits, most rely on predefined interactions with limited adaptability. This study proposes an AI-enabled framework integrating continuous self-monitoring and explainable multicriteria decision-making to personalize robot-assisted interventions. Methods: A 12-week longitudinal quasi-experimental study was conducted involving 78 older adults with mild-to-moderate cognitive impairment allocated to three groups: an adaptive AI-based robot (n = 26), a sensor-based robot (n = 26), and a control group receiving conventional care (n = 26). The proposed framework combined continous self-monitoring, AI-based emotional-state estimation, and an Analytic Hierarchy Process (AHP) model to adapt robot behaviour according to participants’ clinical and behavioural profiles. Results: The AI-based robot achieved the greatest improvements in emotional status, social interaction, and functional performance. Depressive symptoms decreased by 42.9%, anxiety decreased by 39.1%, social interaction increased by 60.7%, and functional independence improved by 20.1%. Although the sensor-based robot showed slightly higher adherence (97.2% vs. 95.6%), the AI-based intervention achieved the highest overall effectiveness (AHP global score = 0.90). Conclusions: Integrating continuous self-monitoring, AI-based emotional-state estimation, and explainable multicriteria decision-making enables personalized robot-assisted interventions that improve emotional well-being, social engagement, and functional independence. These findings support the potential of adaptive socially assistive robots as AI-driven clinical decision-support systems for dementia care. Full article

Immune checkpoint inhibitors (ICIs) targeting PD-1/PD-L1 have improved outcomes across squamous cell carcinomas (SCCs) of the head and neck, lung, esophagus, and skin, yet durable responses remain confined to a subset of patients in every subtype. Objective response rates vary substantially across SCCs despite overlapping genomic alterations, comparable tumor mutational burden, and high PD-L1 expression, indicating that tumor-intrinsic biomarkers alone do not explain this variability. Growing evidence points to the tumor immune microenvironment, and in particular the myeloid compartment, as a critical determinant of immunotherapy responsiveness. In this review, we synthesize current evidence on myeloid-mediated immune regulation across SCC subtypes, focusing on tumor-associated macrophages, myeloid-derived suppressor cells/tumor-associated neutrophils, and dendritic cells, and the mechanisms by which these populations impair antigen presentation, restrict T cell infiltration, and sustain immunologically “cold” tumor states. We further examine therapeutic strategies aimed at reprogramming rather than simply depleting suppressive myeloid populations, including radiation therapy, STING agonism, and myeloid-targeted agents (CSF1R, PI3Kγ, and CXCR2 inhibition), each of which has shown encouraging preclinical and early clinical activity in combination with ICI. Collectively, this evidence supports a model in which the myeloid compartment functions as an actionable, convergent determinant of ICI resistance across SCC subtypes, rather than merely a passive biomarker. We propose that through the integration of spatial and single-cell profiling of myeloid states with clinical history it will be possible to predict response to immune checkpoint therapy and personalize myeloid-directed combination strategies, though the specific biomarkers needed to match individual patients to a given myeloid-targeted approach remain to be defined. We further discuss the toxicity considerations associated with both immune checkpoint blockade and radiation-based combination approaches, the early-phase status of most myeloid-targeted agents currently in clinical development, and the extent to which mechanistic insight, derived predominantly from HNSCC, generalizes to squamous cell carcinomas arising at other anatomic sites. Full article

Limited inclusion of ethnically diverse and socioeconomically disadvantaged populations in pain research undermines external validity, generalizability, and equity. This comprehensive review synthesized evidence on effective strategies to recruit and retain these populations in pain studies. We searched Medline, Web of Science, Embase, Scopus, and CENTRAL (12 April 2025) and included studies in which ethnically diverse and socioeconomically disadvantaged participants comprised ≥75% of the sample. Quantitative data were pooled using random-effects meta-analyses of proportions, with prespecified subgroup analyses, and qualitative findings were integrated through thematic synthesis. Certainty of evidence was evaluated using GRADE. Eighteen studies (n = 4611; 11 experimental, 5 observational, 2 qualitative), primarily from the United States and involving chronic pain, met inclusion criteria. Overall enrollment among ethnically diverse and socioeconomically disadvantaged groups was 37% (95% CI 18–58%), with significantly higher enrollment in observational studies (84%, 95% CI 78–90%) than in experimental trials (22%, 95% CI 10–36%; p < 0.001). Overall retention was 77% (95% CI 64–88%) and did not differ significantly by study design. Statewide disease-clinic networks, purposive community-leader engagement, and snowball sampling produced the highest enrollment, whereas medical-record screening yielded the lowest enrollment but the highest retention. Compensation and reminder strategies were similarly effective for retention. Thematic synthesis highlighted trust, culturally and linguistically tailored communication, hybrid and flexible visit schedules, transportation assistance, and clinician engagement as key facilitators. GRADE certainty was low for enrollment and moderate for retention. Community-engaged recruitment strategies, clinician referrals, culturally tailored materials, hybrid procedures, and modest incentives can substantially improve participation of ethnically diverse and socioeconomically disadvantaged populations in pain research. Standardized CONSORT-style reporting of recruitment/retention flowcharts according to strategy and ethnicity/socioeconomic status is essential to refine evidence-based strategies in the future. Full article

Objective: To investigate the impact of asymptomatic high-risk status for ischemic stroke on patients with abdominal aortic aneurysm undergoing endovascular aortic repair (EVAR). Methods: Eligible patients with abdominal aortic aneurysm who underwent EVAR between January 2011 and December 2021 were enrolled in this retrospective cohort study. Propensity score matching (PSM) was used to balance baseline characteristics between the cerebrovascular high-risk group and the standard control group. The impact of cerebrovascular high-risk status on short- and long-term outcomes was assessed using Cox proportional hazards regression and generalized linear models, with results presented as hazard ratios (HRs), odds ratios (ORs), and corresponding 95% confidence intervals (CIs). Results: A total of 1080 patients were included (299 high-risk, 781 standard). During the 13-year follow-up period, ischemic stroke occurred in 45 patients (15.1%) in the high-risk group (HR, 7.01; 95% CI, 4.11–11.94; p < 0.001). The high-risk group also had a higher incidence of major adverse cardiovascular and cerebrovascular events (MACCEs), which occurred in 129 patients (43.1%) (HR, 1.78; 95% CI, 1.43–2.24; p < 0.001). These findings remained consistent across inverse probability of treatment weighting (IPTW) and propensity score matching combined with multivariable generalized linear model (PSM+MVA-GLM) analyses. Conclusions: Although no significant increase in perioperative cerebrovascular adverse events was observed in asymptomatic patients with a preoperative cerebrovascular high-risk status, their worse long-term prognosis appears to be associated with this risk status. This association highlights the need for rigorous cardiovascular and cerebrovascular risk management in this vulnerable population after surgery. Full article

Background/Objectives: Male hypogonadism affects 35–50% of men with type 2 diabetes mellitus (T2DM) and obesity. The relationship between testosterone deficiency and response to incretin-based therapies (GLP-1 and GIP receptor agonists) remains incompletely understood. This systematic literature review, conducted following PRISMA 2020 guidelines, examines whether male hypogonadism represents a risk factor for poor response to incretin therapy or, conversely, whether these agents offer therapeutic benefits for this population. Methods: A comprehensive systematic literature search was conducted on 31 December 2024, across PubMed/MEDLINE, Scopus, and Web of Science using three search domains: (1) hypogonadism and incretin therapy response; (2) testosterone deficiency and GLP-1/GIP receptor agonists; (3) incretin response and testosterone. Eligibility criteria included human studies (randomized controlled trials [RCTs], observational studies, cohort studies, cross-sectional studies, systematic reviews, and meta-analyses) in adult men reporting testosterone levels and/or incretin response. Animal studies, pediatric populations, case reports with n < 5, editorials, and letters without data were excluded. Study selection followed PRISMA 2020 guidelines with independent dual screening. Risk of bias was assessed using the Cochrane Risk-of-Bias 2.0 tool (ROB2) for RCTs, the Newcastle–Ottawa Scale (NOS) for observational studies, and AMSTAR-2 for systematic reviews and meta-analyses. Due to substantial heterogeneity in study designs, populations, interventions, and outcome measures, a meta-analysis was not feasible; therefore, a narrative synthesis was performed. Results: From 326 records identified, 29 studies were included after deduplication and screening (primary studies: 14; systematic reviews/meta-analyses: five; narrative reviews/expert opinion: 10). Risk-of-bias assessment revealed moderate-to-high overall risk: RCTs had small sample sizes (n = 12–42) and short follow-up (12–24 weeks), raising concerns about statistical power; observational studies were of fair-to-good quality (NOS 4–7 stars) but subject to confounding; and systematic reviews were of low-to-moderate confidence (AMSTAR-2). Primary evidence from RCTs and observational studies demonstrates that GLP-1 receptor agonists (GLP-1RAs)—particularly semaglutide and liraglutide—and the dual GIP/GLP-1 receptor agonist tirzepatide significantly increase total testosterone levels in men with obesity-related functional hypogonadism (mean increase 2.5–5.2 nmol/L). This effect is largely mediated by weight loss and improvement of insulin resistance rather than direct androgenic action. Evidence regarding whether baseline hypogonadism impairs glycemic or weight-loss response to incretin therapy is limited and indirect; no adequately powered comparative trials stratified by baseline testosterone status were identified. Conclusions: Incretin-based therapies, particularly GLP-1 receptor agonists and the dual GIP/GLP-1 receptor agonist tirzepatide, appear to improve testosterone levels in men with obesity-related functional hypogonadism, an effect that is largely mediated by weight loss and improvement of insulin resistance rather than a direct androgenic action. However, direct comparative evidence between hypogonadal and eugonadal men regarding glycemic or weight-loss response to incretin therapy remains insufficient to draw firm conclusions. The hypothesis that male hypogonadism does not impair incretin therapy response is biologically plausible but is currently supported only by indirect evidence. Prospective, adequately powered trials stratified by baseline testosterone status are needed to resolve this question. Full article

Zinc is an essential micronutrient involved in many physiological processes in the human body, including immune system regulation, cellular survival, neurologic function, and erythropoiesis. Zinc deficiency can result in a wide range of clinical manifestations, including impaired immune function, dermatologic findings, and decreased growth. Anemia has been reported as a hematologic manifestation of zinc deficiency and may be underrecognized in clinical practice. This narrative review examines the pathophysiology of zinc deficiency-associated anemia, highlighting zinc’s role in erythropoiesis, heme biosynthesis, and red blood cell stability. It also outlines populations at increased risk for zinc deficiency, including patients with chronic kidney disease, sickle cell disease, malabsorptive disorders, chronic proton pump inhibitor use, and older adults. Emerging evidence suggests that zinc deficiency-associated anemia may represent a potentially modifiable contributor to anemia in selected at-risk populations, although the strength of evidence varies across clinical settings and study designs. Assessment of zinc status may be considered in patients with unexplained or refractory anemia and additional risk factors for deficiency. Further prospective studies are needed to clarify the role of zinc deficiency in anemia and define appropriate screening, supplementation, and monitoring strategies. Full article

Background/Objectives: Persistent spinal pain syndrome type 2 (PSPS-T2) is treated with two mechanistically distinct interventional families: epidural adhesiolysis (EA), directed at structural epidural pathology, and neuromodulation (NM), directed at modulation of nociceptive signaling. Epidural fibrosis is a biologically plausible candidate for treatment stratification, but whether it independently modifies treatment response remains unproven. This study reviewed the available evidence to determine both the comparative findings and the limitations imposed by the current evidence architecture. Methods: A PROSPERO-registered systematic review and frequentist random-effects network meta-analysis were performed. Studies were classified at the study level, rather than the individual-patient level, as fibrosis-positive (structurally confirmed) or unselected (without confirmed fibrosis). Treatment effects were synthesized separately within each stratum, and an exploratory study-level meta-regression evaluated fibrosis status as a potential moderator. Results: The final dataset comprised 87 studies including 33,504 patients: 40 fibrosis-positive studies (n = 4180) and 47 fibrosis-unselected studies (n = 29,324). Treatment family and fibrosis status were almost completely confounded. EA was evaluated almost exclusively in fibrosis-positive cohorts, whereas NM was evaluated almost exclusively in fibrosis-unselected studies. Although pooled improvements in pain (−0.97 vs. −0.63) and disability (−11.01 vs. −8.46) were greater in fibrosis-positive studies, these differences cannot be attributed independently to fibrosis. Residual heterogeneity remained substantial (I² 71–92%). Peripheral nerve field stimulation and EA protocols incorporating steroid, hyaluronidase, and hypertonic saline achieved the highest probability score for pain relief. All probability scores for the treatments should be interpreted as exploratory. Conclusions: Discordance between EA and NM in PSPS-T2 stems from structurally different populations, precluding pooled comparative classifications or claims that fibrosis modifies treatment effect. While fibrosis remains a promising candidate stratifier, proving it requires prospective trials that stratify randomization to EA versus NM following standardized fibrosis assessment. Full article