Search Results (3,406)

Cannabis use has increased substantially in the United States, driven by broader legalization, decriminalization, and expanding medical and recreational availability. For facial plastic surgeons, the clinical implications remain difficult to define because “cannabis use” encompasses heterogeneous products and routes, including smoked flower, vaping, concentrates, edibles, pharmaceutical cannabinoids, topical cannabidiol (CBD), and frequent co-use with tobacco or nicotine. Current evidence suggests that systemic cannabis use, particularly inhaled or heavy perioperative use, may be associated with increased surgical complications in selected populations; however, existing studies are limited by retrospective design, inconsistent exposure definitions, inadequate dose and route characterization, and confounding by tobacco use and comorbidities. Cannabinoids exert biologic effects through the endocannabinoid system, particularly CB1 and CB2 receptors, which are expressed in the central nervous system, immune cells, vasculature, and skin. These pathways influence inflammation, keratinocyte proliferation, fibroblast activity, angiogenesis, immune surveillance, pain signaling, and tissue remodeling. The net effect of cannabinoid exposure on wound healing is likely context dependent, varying based on receptor expression, wound-healing phase, route of administration, cannabinoid composition, local tissue environment, and patient-specific risk factors. Preclinical and early dermatologic literature suggests potential therapeutic roles for topical cannabinoids, especially CBD, in modulating inflammation and epithelial repair. In contrast, systemic perioperative cannabis use has been associated in several surgical cohorts with infection, delayed healing, hematoma, nonunion, and reoperation. Evidence specific to facial plastic surgery remains sparse. The most directly relevant study evaluated cannabis and tobacco use in patients undergoing operative mandibular fracture repair. Cannabis-only use was not associated with increased complications, although the cohort was small; concurrent cannabis and tobacco use was associated with higher rates of surgical site infection, facial nonunion, abscess, debridement, and malocclusion. To date, no published studies address cannabis-associated outcomes in rhinoplasty, rhytidectomy, blepharoplasty, browlift, or facial rejuvenation. This review summarizes the biologic rationale, available surgical evidence, and clinical considerations for incorporating cannabis use into individualized perioperative risk assessment in facial plastic surgery. Full article

Hepatocellular carcinoma (HCC) remains a major global health challenge and one of the leading causes of cancer-related mortality, with advanced disease continuing to be associated with limited therapeutic options and substantial heterogeneity in response to systemic treatment. Recent evidence has established the gut microbiota, through the gut–liver axis, as a critical determinant of immunotherapy efficacy, while also influencing antitumor immunity and liver carcinogenesis. Microbial dysbiosis may promote chronic inflammation, intestinal barrier disruption, bacterial translocation, and immune dysfunction, thereby contributing to hepatocarcinogenesis. Moreover, gut microbial composition and microbial-derived metabolites, including bile acids, short-chain fatty acids (SCFAs), and inosine, have been associated with modulation of antitumor immune responses and differential outcomes to immune checkpoint inhibitors (ICIs). Emerging clinical evidence in HCC has identified distinct gut microbial signatures associated with response to nivolumab, pembrolizumab, and atezolizumab-based regimens, including enrichment of Akkermansia muciniphila and SCFA-producing taxa such as Ruminococcaceae, Roseburia, and Prevotella in responders. However, these findings remain inconsistent across studies, with no reproducible microbial signature identified because of small cohort sizes, heterogeneous patient populations, geographic variation, cirrhosis-related confounding factors, and methodological differences in microbiome analysis. This review summarizes the current understanding of microbiome–immune interactions in HCC, examines mechanistic pathways linking the microbiota to immunotherapy response, critically evaluates available clinical evidence, and discusses current limitations and future therapeutic strategies, including fecal microbiota transplantation, probiotics, dietary modulation, and engineered bacterial platforms. Collectively, microbiome-based approaches may contribute to the development of personalized immunotherapeutic strategies in HCC, although larger standardized prospective studies are required before microbiome-derived biomarkers can be implemented in routine clinical practice. Full article

(1) Introduction: Early identification of patients at high risk of recurrent events after hospitalization for acute decompensated heart failure (ADHF) remains challenging. The Larissa Heart Failure Risk Score (LHFRS) is a simple prognostic tool based on hypertension, coronary artery disease, and red blood cell distribution width. Urinary sodium has recently emerged as an objective marker of natriuretic response and decongestion. We prospectively evaluated whether incorporation of urinary sodium improves the prognostic performance of the LHFRS. (2) Methods: This prospective single-center observational study enrolled 130 consecutive adults hospitalized with ADHF. Clinical, laboratory, electrocardiographic, and echocardiographic data were collected at admission. Spot urinary sodium and chloride were measured at admission and 2 h after intravenous loop diuretic administration according to a standardized decongestion protocol. The primary endpoint was heart failure rehospitalization within 3 months. Secondary endpoints included all-cause mortality and the composite of death or heart failure rehospitalization. Multivariable logistic regression with bootstrap internal validation (1000 resamples) was used to identify independent predictors of outcomes. (3) Results: The study population included patients across the spectrum of heart failure phenotypes (HFrEF 58%, HFmrEF 7%, HFpEF 35%). During follow-up, 48 patients (36.9%) experienced heart failure rehospitalization and 23 (17.7%) died. The LHFRS independently predicted 3-month rehospitalization (B = 0.490, p = 0.041). Admission urinary sodium and 2-h urinary sodium provided incremental prognostic information beyond the LHFRS and remained independently associated with rehospitalization after multivariable adjustment (p = 0.008 and p = 0.001, respectively). Urinary chloride demonstrated similar prognostic associations, whereas conventional renal biomarkers, including serum creatinine, urea, estimated glomerular filtration rate, serum sodium, and NT-proBNP, did not consistently retain independent prognostic significance. The LHFRS was also significantly associated with the composite endpoint of death or rehospitalization (B = 1.173, p = 0.002), while its association with mortality alone was not statistically significant (B = −5.551, p = 0.256). (4) Conclusions: Lower admission and 2-h urinary sodium concentrations were associated with 3-month HF rehospitalization after adjustment for the LHFRS. These findings are hypothesis-generating and require confirmation in larger, externally validated multicenter cohorts. Full article

Objectives: Women with a history of breast cancer are at increased risk of developing subsequent breast cancer, including ipsilateral recurrence and contralateral new primary breast cancer. This study evaluated the discriminatory performance of a mammogram-based artificial intelligence (AI) risk model for predicting subsequent breast cancer within one year after a negative screening mammogram. Methods: This enriched retrospective case–control study included women with a prior history of breast cancer who underwent screening digital breast tomosynthesis between January 2018 and December 2023 at three affiliated academic breast imaging centers. Digital breast tomosynthesis examinations classified as BI-RADS 1 or 2 were retrospectively analyzed using the ProFound AI^® Risk model version 1.0 to estimate 1-year breast cancer risk. Patients were classified according to whether they developed subsequent breast cancer within one year of the index screening examination. Model discrimination was evaluated using receiver operating characteristic analysis. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated at an exploratory cutoff selected by maximizing the Youden index. Results: The study included 96 women (mean age, 65.3 ± 8.7 years), of whom 32 developed subsequent breast cancer within one year, and 64 did not. The mean AI risk score was significantly higher in the subsequent breast cancer group than in the control group (1.18 ± 0.59 vs. 0.49 ± 0.41; p < 0.001). The AI model demonstrated an AUC of 0.824 (95% CI: 0.728–0.921). At an exploratory cutoff of 0.39, sensitivity was 81.3%, specificity was 76.6%, PPV was 63.4%, and NPV was 89.1%. In separate exploratory analyses, the AUC was 0.790 (95% CI: 0.641–0.939) for ipsilateral recurrence and 0.860 (95% CI: 0.752–0.974) for contralateral new primary breast cancer. AI risk scores were not significantly correlated with tumor size or age at subsequent breast cancer diagnosis. Conclusions: In this enriched retrospective case–control study, higher mammogram-based AI risk scores were associated with subsequent breast cancer within one year after a negative screening examination. The model demonstrated discriminatory performance for both ipsilateral recurrence and contralateral new primary breast cancer; however, these analyses were exploratory. Because the cohort was enriched for subsequent breast cancer events, the reported predictive values are specific to the study sample and should not be extrapolated to routine surveillance populations. Larger prospective cohorts are needed to validate discrimination, calibration, and clinical utility. Full article

Background/Objectives: Cleft palate is developmentally and clinically distinct from cleft lip with or without cleft palate. Prenatal ultrasound reliably identifies clefts involving the lip but performs poorly for the secondary palate, whereas early feeding difficulty is concentrated in palatal clefts. These two observations have not previously been quantified within a single cohort. We aimed to determine whether prenatal detectability and neonatal feeding support requirements follow opposite gradients across cleft phenotypes. Methods: We conducted an ambispective study of a nationally ascertained referral-centre cohort of 328 consecutive children with an orofacial cleft and no clinically recognised syndrome, managed at the national referral centre for cleft surgery in Croatia. The cohort comprises children reaching surgical care and is not a population-based birth registry. Documented prenatal ultrasound diagnosis and feeding method during the first weeks of life were abstracted from medical records; cleft phenotype was confirmed by clinical examination. Proportions were compared with chi-square tests and exact binomial confidence intervals, and factors independently associated with each outcome were identified by multivariable logistic regression. Results: Overall prenatal detection was 76/316 (24.1%; 95% CI 19.4–29.2). Detection differed markedly by phenotype: 38.2% for cleft lip only, 34.0% for cleft lip and palate and 2.0% for cleft palate only (p < 0.001). Nasogastric tube feeding was required by 46/325 children (14.2%; 95% CI 10.6–18.4) and followed the opposite gradient: 0.0%, 14.2% and 24.8%, respectively (p < 0.001). Isolated cleft palate showed the strongest independent negative association with prenatal detection (adjusted OR 0.037; 95% CI 0.009–0.154) and was independently associated with tube feeding (adjusted OR 3.07; 95% CI 1.37–6.89). Of children requiring tube feeding, 43/46 (93.5%; 95% CI 82.1–98.6) had not been detected prenatally. Observed detection rose with year of birth in unadjusted analysis (OR 1.095 per year; 95% CI 1.012–1.185; p = 0.023) but was attenuated and no longer significant after adjustment (OR 1.071; 95% CI 0.991–1.157; p = 0.082); the temporal trend is therefore reported descriptively. An initial refer result at newborn hearing screening was markedly more frequent in children with palatal involvement than in those with cleft lip only (2.8%, 31.6% and 25.5% for cleft lip only, cleft lip and palate and cleft palate only; p < 0.001), contrasting cleft lip only with clefts involving the palate rather than following a monotonic gradient. Conclusions: Prenatal detectability and neonatal nasogastric tube use follow opposite gradients across cleft phenotypes. Children with cleft palate only are simultaneously the least likely to be identified before birth and the most likely to require assisted feeding, and almost all tube-fed infants arrive without a prenatal diagnosis. These findings support, as a practice consideration, routine structured neonatal feeding assessment for every newborn with a palatal cleft irrespective of prenatal findings. Full article

Background: Anthropometric body-composition assessment in youth soccer commonly relies on equations developed in different source populations and based on distinct body-composition models, potentially altering nutritional and sport-related interpretation. This study compared body-fat estimates from equations intended to report the same outcome, body fat percentage, but based on different operational models, and quantified muscle-mass outputs from anthropometric approaches targeting total-body skeletal, whole-body, and tissue-level muscle compartments in a cohort of Chilean male U-15 and U-16 players. Methods: This secondary cross-sectional method-comparison study analyzed anonymized anthropometric records collected in 2018 from 50 male players. Slaughter, Faulkner, Carter, Deurenberg, and Sloan–Siri estimates of body fat were compared, together with Poortmans, Lee, Doupe, and Kerr muscle-mass approaches. Absolute agreement among adiposity equations was evaluated using a two-way random-effects, absolute-agreement, single-measure ICC [ICC(A,1)] and Bland–Altman analyses. Muscle-mass approaches were compared with repeated-measures analysis; pairwise difference-versus-mean summaries across different muscle constructs were interpreted descriptively rather than as formal agreement tests. Sensitivity analyses excluded Deurenberg and examined a maturation-related Slaughter scenario. Results: Deurenberg yielded the highest body-fat estimate (18.97 ± 3.07%), followed by Slaughter (13.32 ± 3.35%), Faulkner (10.84 ± 1.40%), Sloan-Siri (8.01 ± 2.80%), and Carter (7.91 ± 1.49%). Global differences were large (χ²(4) = 182.96; p < 0.001; Kendall’s W = 0.915), and individual absolute agreement was low [ICC(A,1) = 0.157; bootstrap 95% CI 0.102–0.212]. Excluding Deurenberg did not remove the between-method differences (χ²(3) = 124.44; p < 0.001; W = 0.830). For muscle mass, mean estimates ranged from 25.11 ± 3.07 kg with Poortmans to 31.26 ± 4.94 kg with Doupe, with a significant method effect after Greenhouse–Geisser correction (p < 0.001). Conclusions: The adiposity equations yielded substantially different numerical estimates of the same reported outcome, body fat percentage, and showed low individual-level absolute agreement. Muscle-mass approaches also produced large numerical differences, partly expected because they target different compartments. Outputs from different equations or constructs should not be treated as numerically interchangeable. Because no criterion reference method was included, this study quantifies method dependence rather than validity and cannot identify the most accurate equation. Full article

Background: Maintenance hemodialysis is characterized by repetitive changes in fluid distribution, blood pressure, and organ perfusion. Conventional clinical examination, empirical dry-weight adjustment, and biomarkers do not fully resolve the compartment-specific nature of congestion in this population. This narrative review reframes ultrasound-based volume assessment as a multimodal diagnostic problem involving pulmonary congestion, intravascular filling, systemic venous congestion, cardiac reserve, tissue response, and perfusion vulnerability. Methods: We synthesized clinically relevant evidence indexed in PubMed and Google Scholar for studies published between January 2016 and April 2026, prioritizing dialysis-specific randomized trials, prospective cohorts, systematic reviews, consensus statements, and methodological studies related to diagnostic ultrasound, Doppler-based congestion assessment, contrast-enhanced ultrasound, elastography, artificial intelligence, point-of-care ultrasound, and remote ultrasound monitoring. Results: Lung ultrasound currently has the strongest dialysis-specific evidence for detecting and tracking pulmonary congestion. Inferior vena cava ultrasound provides adjunctive information on intravascular filling and right-sided pressure but is not a surrogate for total body water. Echocardiographic parameters help characterize filling pressure and cardiac tolerance to fluid removal, whereas venous Doppler and the Venous Excess Ultrasound Score provide an emerging approach to systemic venous congestion. Elastography and contrast-enhanced ultrasound remain investigational tools for tissue characterization and perfusion vulnerability, while AI-assisted analysis, handheld point-of-care ultrasound, and tele-ultrasound may improve standardization, automated B-line quantification, and scalability. Conclusions: Different ultrasound modalities answer different diagnostic questions in maintenance hemodialysis. A compartment-specific framework integrating congestion, perfusion, and cardiac-reserve domains may better support individualized ultrafiltration planning, hemodynamic risk assessment, and future outcome-oriented research. 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

Background: To date, several studies have confirmed the fact that over 700 species of microbiota interacts with host, modulating immunity, controlling the homeostasis environment, and thus maintaining systemic condition. Dysbiosis in the subgingival biofilm can initiate chronic inflammation of the gingiva, potentially progressing to periodontitis. Advances in DNA sequencing analysis of the subgingival microbial community have shown that periodontal treatment causes a microbial shift in subgingival plaque, affecting the taxonomic composition (disease- and health-associated taxa). Yet, none of these have been investigated in Indonesia. Objective: The objective was to profile the composition of oral microbiome in Indonesian population with healthy, gingivitis, and periodontitis status. Further, we analyzed the subgingival bacterial alteration following the therapy in periodontitis group. Methods: Twelve subjects consisting of healthy, gingivitis, and periodontitis patients were included. Additionally, the periodontitis group was observed at baseline, 1-month, and 3-month. Subgingival dental plaque were sampled and 16S rRNA NGS analysis was performed. Alpha (Chao1, Shannon, and Simpson indices) and beta diversity (PCoA plots based on Bray–Curtis dissimilarity) were observed. Microbiota composition at the genus and species levels was analyzed. Results: No statistically significant differences (p > 0.05) were found for Chao1, Shannon, and Simpson indices amongst groups and in periodontitis patients across the observation. At the genus level, PCoA plots based on Bray–Curtis dissimilarity revealed that the clinical status accounted for 21.9% of the total variation (R² = 0.219, p = 0.197), while at the species level, it accounted for 19.8% (R²= 0.198, p = 0.281). Periodontitis samples across all timepoints showed no distinct clustering at either the genus 7.6% (R² = 0.076 p = 0.097) or species levels 9.7% (R² = 0.097 p = 0.995). Top five subgingival microbiota at the genus and species levels in all groups showed definite pattern of composition. Although no significant association was found (p > 0.05), it described that Veillonella parvula, Campylobacter gracilis, and Capnocytophaga granulosa were more abundant in healthy subjects than in gingivitis and periodontitis. Prevotella oris and Selenomonas noxia were less abundant in healthy subject than in gingivitis and periodontitis. In periodontitis subjects, Prevotella intermedia was increased by the therapy at 1 month and reduced again at 3 months. On the other hand, Capnocytophaga granulosa was increased by the therapy at 1 and 3 months. Hoylesella loescheii was reduced by the time. Porphyromonas gingivalis was reduced at 1 month and increased again at 3 months. Discussion: The result showed that the number of alpha diversity was notably higher in the gingivitis and periodontitis groups compared to health group, supporting a trend toward increased community richness and evenness in diseases states. The microbial richness and evenness remained relatively stable across the evaluated periods within periodontitis cohort. Oral microbial composition defines the periodontal status and disease. More abundance of Red Complex bacteria is associated with disease-associated condition. Pathogen re-colonization may occur 3 months after the therapy. Conclusions: These findings suggest that maintaining health-associated microbiome may be beneficial to the clinical status. Periodontal recall may be addressed from 1 to 3 months after the therapy to avoid bacterial re-colonization. Suppressing bacterial dysbiosis and regulating periodontal homeostasis are the main key in managing periodontal treatment. Full article

Background/Objectives: To characterize the clinical and imaging phenotypes of schwannomatosis (SWN) in children, adolescents, and young adults (AYAs). Methods: This single-center retrospective cohort study included patients (age ≤ 25 years) with suspected SWN with archived magnetic resonance imaging (MRI) at Johns Hopkins between 2020–2026. Clinical characteristics, genetic testing results, and tumor imaging (including anatomic distribution), and treatment approaches were reviewed. Descriptive statistics were performed. Results: In total, thirty-eight patients with suspected SWN were identified (median age 20 years, range 6–25; 32% female). NF2-related SWN was the most common diagnosis (31/38, 82%; de novo: 24/31 (77%) and familial: 7/31 (23%)), followed by LZTR1-SWN (n = 1) and SWN-NOS/NEC (n = 2). A total of four patients (asymptomatic LZTR1 carriers (n = 2) and possible SWN (n = 2)) did not fulfill diagnostic criteria based on craniospinal and whole-body MRI. Familial NF2-SWN demonstrated a trend toward earlier presentation (median 5 vs. 8 years; p = 0.12). Visual manifestations occurred at a younger age than hearing loss (median 8 vs. 16 years; p = 0.053). Imaging burden was high (median 23 MRI/patient (range: 1–60). Bilateral vestibular schwannomas were nearly universal (30/31, 97%). Familial disease demonstrated a trend toward increased cranial meningiomas (86% vs. 54%; p = 0.20), while peripheral schwannomas (43% vs. 67%; p = 0.38) and ependymomas (14% vs. 42%; p = 0.37) were less frequent compared with de novo disease. Operative and non-operative management was documented in 65% (20/31) each. Conclusions: NF2-related SWN is the predominant subtype in a pediatric and AYA patient population and was associated with substantial early tumor burden at a tertiary specialty NF center. Full article

Background/Objectives: Recurrent pregnancy loss (RPL) has traditionally been investigated predominantly through maternal factors, while the clinical role of paternal assessment remains inconsistently defined. Current guidelines differ substantially regarding semen analysis, sperm DNA fragmentation (SDF), genetic testing, and referral for andrological evaluation. This review aimed to compare contemporary guideline recommendations, critically appraise the directness, prognostic value, and clinical utility of the supporting evidence, and classify paternal assessment strategies as routine, selective, or investigational. Methods: A structured narrative review was conducted using PubMed and Scopus searches through June 2026. International RPL, obstetric, reproductive medicine, and andrology guidelines were compared. Evidence from systematic reviews, meta-analyses, clinical studies, and clinically relevant molecular investigations was evaluated according to its directness to RPL populations, diagnostic and prognostic value, and evidence that test-guided interventions improve miscarriage or live-birth outcomes. Results: Routine paternal assessment should include age, reproductive and medical history, body weight, lifestyle, medication exposure, and relevant environmental or occupational risks. Conventional semen analysis is appropriate primarily when RPL coexists with infertility or suspected male reproductive disease. SDF is the most extensively studied advanced paternal biomarker and is frequently elevated in RPL cohorts, but findings vary by assay and comparator population, while prospective prediction of subsequent live birth and benefit from SDF-directed treatment remain unproven. Parental karyotyping has established counselling value but should be risk-stratified. Sperm aneuploidy testing, oxidative stress assays, seminal microbiome profiling, epigenetic biomarkers, and biomarker-directed interventions remain investigational. Conclusions: Paternal assessment in RPL should be couple-based, clinically targeted, and evidence-informed. Current evidence supports routine clinical evaluation, selective use of semen analysis, SDF testing, genetic assessment, and reproductive urology referral, and restriction of unvalidated biomarkers and treatments to research settings. Full article

Background: Arrhythmia recurrence after cryoballoon ablation remains a clinically relevant problem in atrial fibrillation (AF). However, factors associated with documented recurrence in low-risk patients without major comorbidities are not well defined. This study aimed to evaluate factors associated with documented arrhythmia recurrence after cryoballoon ablation in a highly selected low-risk AF population. Methods: This retrospective, single-center study included 153 eligible patients selected from an institutional cryoablation database after application of predefined exclusion criteria. Only patients with a CHA₂DS₂-VA (congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, stroke/transient ischemic attack/thromboembolism, vascular disease, and age 65–74 years) score ≤ 1 and without major comorbidities, including diabetes mellitus, hypertension, coronary artery disease, chronic kidney disease, cerebrovascular disease, and heart failure, were included. Recurrence was defined as electrocardiographically documented AF or atrial tachyarrhythmia after the 3-month blanking period over 1 year of follow-up; Holter-detected episodes were required to last ≥30 s. The primary multivariable model included sex, age, AF type, and absolute left atrial diameter; a sensitivity model replaced absolute left atrial diameter with left atrial diameter indexed to body surface area (BSA). Results: The study population included 70 women (45.8%) and 83 men (54.2%). Paroxysmal AF was present in 125 patients (81.7%), whereas 28 patients (18.3%) had persistent AF. Documented arrhythmia recurrence occurred in 40 patients (26.1%). Female sex was more frequent in the recurrence group than in the no-recurrence group (62.5% vs. 39.8%, p = 0.013). The complete-case primary multivariable model included 126 patients with 36 recurrence events. Female sex was associated with documented arrhythmia recurrence (odds ratio [OR] 2.69, 95% confidence interval [CI] 1.14–6.37; p = 0.024). The estimate for left atrial diameter was directionally positive but statistically uncertain (OR 1.086 per mm, 95% CI 0.989–1.192; p = 0.085). In the BSA-indexed sensitivity model (n = 123), the female-sex estimate was attenuated and statistically uncertain (OR 2.16, 95% CI 0.90–5.18; p = 0.084), while left atrial diameter/BSA was also statistically uncertain (OR 1.145 per mm/m², 95% CI 0.977–1.343; p = 0.095). Conclusions: In this selected low-risk cohort undergoing second-generation cryoballoon ablation, female sex was associated with clinically detected, electrocardiographically documented arrhythmia recurrence in the primary model under an intermittent rhythm-surveillance strategy based on scheduled 12-lead electrocardiograms (ECGs) and symptom-driven evaluations. However, the estimate was attenuated and statistically uncertain after indexing left atrial diameter to BSA. Given the retrospective, single-center design, non-systematic rhythm monitoring, and sensitivity of the sex estimate to body-size adjustment, these findings should be interpreted as hypothesis-generating. Full article

Background: Hypertensive disorders of pregnancy (HDP), particularly gestational hypertension and preeclampsia, are major causes of maternal and perinatal morbidity. Metabolic disorders such as gestational diabetes mellitus (GDM), type 2 diabetes mellitus (T2DM), obesity, and polycystic ovary syndrome (PCOS) share mechanisms with HDP, including insulin resistance, inflammation, oxidative stress, endothelial dysfunction, and placental maladaptation. Metformin may influence these pathways, but its clinical effect on hypertensive outcomes remains uncertain. Methods: A focused narrative review was conducted using structured, targeted searches of PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar for literature published primarily from January 2015 through March 2026, supplemented by landmark studies, clinical guidelines, randomized trials, large observational cohorts, systematic reviews, meta-analyses, and mechanistic and placental studies. Evidence was selected for its relevance to the predefined phenotype-based framework and synthesized qualitatively across mechanistic, clinical, and translational domains. Results: Metformin improves insulin sensitivity and may reduce gestational weight gain, metabolic stress, inflammatory signaling, and oxidative stress. Some randomized trials and meta-analyses in GDM, obesity, and PCOS suggest lower rates of pregnancy-induced hypertension or preeclampsia, whereas recent randomized and population-based studies report neutral effects. Findings are limited by heterogeneous populations, late treatment initiation, variable comparators, supplemental insulin use, inconsistent HDP definitions, and insufficient statistical power. Conclusions: Metformin may act as a metabolic and vascular modifier in selected pregnancies, but current evidence does not support its routine use specifically for HDP prevention. Its public health value lies primarily in accessible metabolic treatment and integration into comprehensive antenatal and postpartum risk reduction pathways, rather than replacement of aspirin, blood pressure surveillance, or maternal–fetal monitoring. Full article

Background/Objectives: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is rapidly becoming one of the main Non-communicable Chronic Diseases (NCDs) in the global population. It is based on the presence of hepatic steatosis linked to other metabolic alterations. Currently, the gold standard techniques to evaluate hepatic steatosis are liver biopsy and hepatic ultrasound examinations (FIBROSCAN^®). However, liver biopsy is an invasive technique and ultrasonic examination is expensive. Therefore, the search for a possible low-cost and non-invasive examination has highlighted the C-reactive protein-triglycerides-glucose index (CTI index) as a possible alternative. This index has already been shown to be associated with cancer survival and with cardiovascular diseases and stroke in previous studies and was found to be predictive for the development of several cardiovascular diseases and stroke incidence. This analysis aimed to investigate the possible association between CTI and MASLD in a southeastern Italian cohort. Methods: This study included 1297 subjects from the NUTRI-HEP project: 629 (48.5%) were affected by MASLD and 668 (51.5%) were not. The CTI index was calculated using the formula proposed by Ruan et al. and was used as both a continuous and a categorical variable. Four logistic regression models were fitted using MASLD as the outcome and the CTI index as the exposure. They were adjusted for several covariates. Results: All logistic regression models indicated a positive association between the CTI index and MASLD development. Focusing on Model 4, using Q1 as a reference, the Odds Ratios were 1.48 (95% C.I. 1.00; 2.17, p = 0.049), 2.06 (95% C.I. 1.38; 3.08, p < 0.001) and 3.62 (95% C.I. 2.32; 5.64, p < 0.001). Conclusions: This study highlights a strong association between MASLD and the CTI index. This association strengthens the role of CTI in predicting the onset and development of MASLD. Full article

Background/Objectives: Forensic age estimation increasingly relies on non-ionizing magnetic resonance imaging (MRI) evaluation of the knee growth plates. The original five-stage classification proposed by Dedouit et al. was developed using spin-echo proton-density-weighted imaging, and its applicability to gradient-echo sequences with different contrast mechanisms has not been fully established. This study aimed to apply the original, unmodified Dedouit classification to a volumetric three-dimensional Multiple Echo Data Image Combination (3D MEDIC) sequence and to generate corresponding age thresholds in a Turkish sample. Methods: Knee MRI examinations of 309 individuals (153 males, 156 females; age range 9.18–25.97 years) were retrospectively evaluated at a 3-Tesla field strength. Two experienced observers independently staged the distal femoral and proximal tibial epiphyses; intra- and inter-observer agreement were assessed using Cohen’s kappa. Spearman’s correlation and the Mann–Whitney U test, with rank-biserial effect sizes and Bonferroni correction, were used to assess the relationship between age and stage and between-sex differences, respectively. To provide forensically applicable thresholds, we additionally modeled the age at which the probability of complete fusion (Stage V) reached 50%, with 95% bootstrap confidence intervals, and calculated the sensitivity, specificity, and area under the curve (AUC) of Stage V for identifying individuals ≥18 years. Results: Agreement was very good for both epiphyses (kappa = 0.808–0.833). Age correlated strongly with stage for both the femur (rho = 0.70–0.76) and tibia (rho = 0.68–0.74). The 50%-probability age for complete fusion ranged from 15.23 years (tibia, females) to 17.43 years (femur, males). Stage V showed high sensitivity (0.96–0.98) but markedly lower and sex-dependent specificity for the 18-year threshold (0.48–0.58 in females versus 0.77–0.85 in males), indicating that Stage V alone is a poor sole criterion for confirming adult status in females. The youngest age at which Stage V was observed was 14.67 years in females and 16.07–16.16 years in males, markedly younger than thresholds reported using spin-echo imaging in the original Dedouit cohort. However, as an extreme-value statistic based on a single individual, this minimum should not be used as a forensic threshold in isolation. Conclusions: The Dedouit classification remains reproducible when applied to a 3D gradient-echo sequence, but the resulting age thresholds may be influenced by acquisition technique, population-specific factors such as socioeconomic status, or both. Consequently, thresholds derived from different MRI sequences or populations should not be assumed to be interchangeable without local validation. Full article