Search Results (12,320)

The menstrual cycle represents a dynamic infradian rhythm characterized by coordinated fluctuations in ovarian steroids that extend beyond reproductive function and influence systemic metabolism. This narrative review synthesizes current evidence on how menstrual cycle phase modulates energy balance, macronutrient metabolism, micronutrient handling, and responses to dietary bioactive compounds. Across phases, small-to-moderate but consistent differences emerge in energy intake, resting energy expenditure, substrate utilization, and protein turnover, with a tendency toward increased energy intake and lipid oxidation during the mid-luteal phase compared with the early follicular and peri-ovulatory phases. Emerging metabolomics data further reveal coordinated cyclical variation in amino acids, B vitamins, and lipid species, suggesting temporally sensitive windows in which low energy availability or micronutrient insufficiency may more readily impair performance, recovery, or symptom burden. Importantly, menstrual cycle-related metabolic variability reflects not only estradiol and progesterone oscillations but also integrated adaptations across the hypothalamic–pituitary–adrenal axis, autonomic nervous system, immune signaling, and gut microbiota. These interconnected systems contribute to inter- and intra-individual heterogeneity in metabolic phenotype. From a clinical and applied perspective, the evidence supports “cycle-aware” but non-dogmatic nutritional strategies, particularly in contexts of metabolic dysfunction, high training loads, or reproductive disorders. Future research should systematically verify cycle phase, incorporate multi-system biomarkers, and adopt sex-specific analytical frameworks to improve translational relevance. Recognizing the menstrual cycle as a biologically meaningful metabolic variable may enhance precision nutrition, exercise prescription, and metabolic risk assessment in women. Full article

Background/Objectives: Sizeable between- and within-country inequalities in childhood immunization impair progress towards the goals set by the global Immunization Agenda 2030 (IA2030) of achieving universal coverage of all persons with essential life-saving vaccines. Monitoring global trends in immunization inequalities helps to identify population subgroups that are less likely to benefit from vaccines and provides evidence for tracking progress on regional and global goals and informing equity-oriented interventions. This paper assesses the state of within-country inequality in childhood immunization across low- and middle-income study countries. Methods: Using data from household health surveys, the analysis quantifies within-country inequality across up to 92 countries, areas and territories, for nine childhood immunization indicators (seven coverage indicators and two indicators of non-receipt of vaccines) by five dimensions of inequality (child sex, mother’s age, mother’s education, household economic status and place of residence). Absolute and relative summary measures of inequality (difference, ratio, slope index of inequality, relative index of inequality and population attributable risk) were calculated to assess the latest situation of inequality (i.e., using the most recent survey from 2014 to 2023) and change over time (i.e., comparisons with data from 2004 to 2013). Results: The latest situation of inequality revealed overall low or no inequality by child sex, mother’s age and place of residence, with more pronounced inequality related to mother’s education and household economic status. The median differences between the most and least educated subgroups ranged between 9 and 14 percentage points for immunization coverage indicators, and between 6 and 9 percentage points for non-receipt of vaccines indicators. The extent of inequality in childhood immunization tended to remain about the same as the previous decade, with modest reductions in absolute economic-related and place of residence inequality in DTP3 immunization, as well as place of residence inequality in full immunization (declining by 3.25, 2.42, and 2.16 percentage points over 10 years, respectively). Distinct patterns of economic-related inequality were evident across country income groups, with low-income countries reporting larger inequality than lower- and upper-middle-income countries; there was substantial variation at the country level. Conclusions: Economic- and education-related inequalities in childhood immunization within low- and middle-income countries have persisted over the past decade. Full article

Handgrip strength (HGS) is widely used as a biomarker of muscle function and overall health in older adults. However, conventional analyses based on peak force values may overlook relevant temporal features of the HGS curve. This cross-sectional study proposes a novel methodological approach that examines the shape and variability of HGS(t) curves recorded from community-dwelling older adults. Functional principal component analysis (FPCA) was applied to assess the consistency of individual trials and the representativeness of mean curves. Statistical non-parametric mapping (SnPM) was then used to identify time regions showing significant differences between groups. Complementary analyses of discrete and derivative parameters, together with non-parametric comparisons based on the Hodges–Lehmann estimator and corresponding 95% confidence intervals, were conducted to quantify effect sizes. FPCA revealed high within-participant consistency, supporting the use of mean curves for group-level comparisons. SPM analyses indicated significant differences in the early force development phase. Importantly, this approach shows that sex differences are attributable to magnitude effects, with men generating higher forces and faster early rates of force development, and not to differences in the neuromuscular strategy of force production. Traditional discrete parameters partly captured these patterns but failed to reflect the full temporal dynamics. This methodological approach to the HGS curve may provide further insights into neuromuscular control mechanisms that cannot be truly captured by the minimalistic HGS discrete parameters. Full article

Objective: The aim of this study was to determine the optimal region-of-interest (ROI) pixel size for fractal dimension analysis on panoramic radiographs that best reflects implant stability assessed by resonance frequency analysis (ISQ) and to investigate whether implant stability can be directly estimated from radiographic images. Materials and Methods: This retrospective cross-sectional study included 65 patients for whom panoramic radiographs and resonance frequency analysis measurements were available. All panoramic images were converted to TIFF format and standardized to a resolution of 2627 × 1646 pixels. All radiographic images were obtained using the same panoramic imaging device and standardized acquisition protocol. Exposure parameters were adjusted within the manufacturer’s recommended range to ensure optimal image quality while maintaining methodological consistency across patients. During ROI selection, care was taken to avoid cortical bone margins, overlapping anatomical structures, and radiographic artifacts in order to ensure that the analyzed regions represented trabecular bone adjacent to the implant surface. Fractal dimension analysis was performed in the cervical peri-implant bone region, starting from the first bone–implant contact and extending apically, using three different ROI configurations. The ROI size was defined as 30 pixels apically and 10 pixels horizontally for FMD1, 30 × 20 pixels for FMD2, and 30 × 30 pixels for FMD3. Implant stability was assessed using ISQ values. Data distribution was evaluated using the Shapiro–Wilk test. Associations between ISQ and fractal dimension measurements were analyzed using Pearson and Spearman correlation analyses. Multiple linear regression models adjusted for age and sex were constructed to assess independent associations. Results: The mean age of the participants was 50.0 ± 9.9 years, and the mean ISQ value was 78.6 ± 5.9. The mean fractal dimension values were 1.466 ± 0.055 for FMD1, 1.595 ± 0.031 for FMD2, and 1.655 ± 0.046 for FMD3. No significant association was found between ISQ and FMD1 or FMD3. A weak positive correlation was observed between ISQ and FMD2; however, this association did not remain statistically significant after correction for multiple comparisons. In multiple linear regression analysis, ISQ was identified as an independent predictor of FMD2, but not of FMD1 or FMD3. Age and sex had no significant effect on fractal dimension measurements. Conclusions: Fractal dimension measurements derived from panoramic radiographs showed a weak association with implant stability that was dependent on the selected ROI pixel size. Among the evaluated configurations, the 30 × 20-pixel ROI at the cervical peri-implant region demonstrated the strongest association with ISQ values, suggesting that this ROI configuration showed the most consistent association with ISQ values among the tested ROI sizes. Full article

Background: Carotid intima-media thickness (IMT) is a well-established surrogate marker of subclinical atherosclerosis and a predictor of cardiovascular risk. Carotenoids, particularly lycopene and β-carotene, have been proposed as protective antioxidants against vascular damage, but evidence from population-based studies is inconsistent. Objective: We aim to perform a systematic review and meta-analysis of the associations between circulating levels of lycopene and β-carotene and carotid IMT in the general adult population, including potential sex-specific effects. Methods: A systematic search was conducted in PubMed, Scopus, and Web of Science up to March 2025, following PRISMA guidelines (PROSPERO registration: CRD420251003810). Observational and experimental studies reporting cross-sectional associations between plasma carotenoids and IMT were included. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated via random effects models. Subgroup and meta-regression analyses explored potential modifiers, including sex and cardiovascular risk factors. Results: Thirteen studies (n = 9131; mean age 46.4–71.6 years) met the inclusion criteria, eight of which were eligible for meta-analysis. High circulating lycopene levels were significantly associated with low IMT (pooled OR = 0.70; 95% CI: 0.59–0.84; I² = 65.7%). The association was stronger in men (OR = 0.62; 95% CI: 0.45–0.84) than in women (OR = 0.74; 95% CI: 0.58–0.95). In contrast, β-carotene was only marginally associated with IMT (pooled OR = 0.96; 95% CI: 0.92–0.99; I² = 72.6%). Meta-regression suggested that systolic blood pressure modified the lycopene-IMT relationship, whereas body mass index and low-density lipoprotein cholesterol influenced the β-carotene-IMT association. No evidence of publication bias was found. Conclusions: Increased serum lycopene concentrations, and to a lesser extent β-carotene concentrations, are inversely associated with carotid IMT, suggesting a protective role of lycopene in vascular health. The effect appears more pronounced in men, highlighting potential sex-specific differences in carotenoid metabolism and cardiovascular risk modulation. Full article

Tuft cells (TCs) are rare chemosensory epithelial cells that regulate mucosal homeostasis in multiple organs, but their role in salivary gland (SG) biology remains poorly defined. This study aimed to define TC structure in mice submandibular glands (SMGs), determine how TC loss affects gland organization and function, and evaluate whether TC abundance in human minor SGs is associated with Sjögren’s disease (SjD) features. Specifically, TC ultrastructure and ductal localization were characterized in female and male C57BL/6J mouse SMGs by transmission electron microscopy and immunostaining. Wild-type and C57BL/6J-Pou2f3^-/- (TC-deficient mouse strain) SMGs were analyzed by histology and bulk RNA-seq, and salivary function was assessed by saliva flow and proteomics. Human minor SG biopsies from SjD and non-Sjögren sicca (nSjD) patients were analyzed by immunostaining and Poisson regression. In mice SMGs, TCs showed conserved ultrastructural features and localization in both sexes. TC loss was associated with marked sex-biased transcriptome remodeling, morphological disruption, and altered saliva quantity and quality. In humans, TC counts differed between nSjD and SjD groups and were associated with salivary flow, serologic status, and histopathologic features. These findings support a role for TCs in SG epithelial integrity and suggest TC abundance as a candidate biomarker of SG dysfunction. Full article

Background/Objectives: This study evaluated whether linear cephalometric measurements show systematic differences in their central values across birth cohort groups in adults from a clinical population and analyzed the implications of these differences for clinical interpretation when norms and clinical deviations are used as a reference framework. Methods: A cross-sectional observational analytical study was conducted based on 604 lateral cephalometric radiographs of adult patients. Eleven linear cephalometric measurements were obtained and compared across predefined birth cohort groups (<1980, 1980–1989, and 1990–1999) using robust estimators of central tendency through median regression models adjusted for sex, age group, and sagittal skeletal classification. Results: Several linear cephalometric measurements revealed different central values between the birth cohorts, even after adjusting for relevant covariates. Cranial length, anterior cranial base length, posterior facial height, and posterior cranial base length had lower adjusted median values in the 1990–1999 cohort than in the <1980 cohort. The effective maxillary length and maxillary length also differed between cohorts. Mandibular measurements, including mandibular length, corpus length, and ramus height, showed the largest adjusted median contrasts between cohorts. These cohort-associated differences were not uniform across all measurements. Conclusions: Routinely used linear cephalometric measurements present different central values across adult birth cohort groups under comparable clinical conditions. The relative position of a cephalometric value within its reference distribution may vary by birth cohort. This suggests that using fixed reference means and standard deviations could lead to systematic misestimation in adults from various birth cohorts. Cohort-aware interpretation is valuable in routine cephalometric assessments. Full article

Purpose: Opioids are widely used for pain management but are associated with adverse events that may differ between women and men. However, post-marketing safety data are rarely examined at the individual level to characterize these sex differences. This study aimed to identify sex disparities in opioid-associated adverse events using the FDA Adverse Event Reporting System (FAERS) to inform safer opioid selection for women. Methods: Opioid drugs were identified using the FDA’s Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS) list and official drug labeling. Relevant FAERS reports were extracted, and adverse events were classified into 27 System Organ Classes (SOCs) based on the Medical Dictionary for Regulatory Activities (MedDRA). Sex-specific signals of disproportionate reporting were evaluated using proportional reporting ratios and reporting odds ratios for drug–SOC pairs. Results: Across most opioid drugs and SOCs, adverse events were reported more frequently in women than in men. The largest sex disparities were observed for codeine, fentanyl, tapentadol, hydrocodone, and sufentanil, with significantly higher disproportionate reporting rates among women. These findings indicate pronounced sex-specific differences in the post-marketing safety profiles of several commonly used opioids. Conclusions: Women demonstrate higher disproportionate reporting of adverse events for certain opioid medications, particularly codeine and fentanyl. These results suggest the need for increased awareness of sex-specific safety differences and support sex-informed prescribing and monitoring strategies to improve opioid safety in women. Since pharmacists are medication experts and play a key role in promoting rational and safe use, our findings may further support pharmacists counseling patients and monitoring for opioid-related adverse events. Full article

Background/Objectives: Fentanyl test strips (FTS) are a harm reduction tool used to detect fentanyl in illicit substances. However, little is known regarding Americans’ beliefs regarding FTS. Therefore, the purpose of this study was to assess the U.S. general public’s FTS knowledge and perceptions. Methods: This study utilized a cross-sectional design. Adults ≥18 residing in the U.S. were recruited to participate in an anonymous online survey via Amazon Mechanical Turk (MTurk). Participants received $5 upon survey completion. The survey instrument was informed by the Health Belief Model, and primary outcome measures included: (1) FTS knowledge (13-items); (2) perceived susceptibility to fentanyl exposure (8-items); (3) perceived severity of fentanyl exposure (10-items); (4) perceived FTS benefits (9-items); (5) perceived barriers to FTS access (13-items); (6) comfort using and accessing FTS (15-items); (7) confidence using and accessing FTS (11-items); and (8) FTS utilization intentions (6-items). Outcomes were measured via 5-point Likert-type scales (1 = strongly disagree, 5 = strongly agree). Data were analyzed using descriptive statistics and Mann–Whitney U tests to compare differences in scale scores across participant sociodemographics. Predictors of FTS utilization intentions were assessed via multiple linear regression, controlling for participant age, race, sex, geographic setting (rural/urban), and recreational drug use history (yes/no) (α = 0.05). Results: Of n = 206 respondents, the majority were male (55.8%) and White (83.0%) with a mean age of 46.4. Approximately 81% resided in urban areas and 58.5% reported a history of recreational drug use. Participants who identified as Black, Asian, Indigenous, Pacific Islander, or Multiracial reported significantly higher mean (SD) perceived susceptibility compared to White participants (2.06 [0.54] vs. 1.91 [0.58]; p = 0.034). Participants residing in urban areas reported significantly higher comfort using and accessing FTS (3.61 [0.86]) than those in rural areas (3.29 [0.92]; p = 0.048), and younger individuals (≤44.5 years) were more confident in their ability to access FTS (3.75 [0.73]) compared to their older counterparts (3.60 [0.64]; p = 0.048). Perceived susceptibility (β = 0.442; p < 0.001), benefits (β = 0.250; p = 0.020), and comfort (β = 0.453; p < 0.001) were positive predictors of FTS utilization intention (R² = 0.417). Conclusions: Perceptions regarding FTS varied across race, geographic setting, and age. Perceived susceptibility, perceived benefits, and comfort positively predicted the U.S. general public’s FTS utilization intentions. Future interventions may leverage these influential factors to enhance FTS uptake. Full article

Background: Hyperuricemia frequently coexists with type 2 diabetes mellitus (T2DM), contributing to a heterogeneous patient population. While previous analyses compared the overall longitudinal effects of allopurinol and SGLT2 inhibitors in this cohort, it remains unclear whether baseline metabolic heterogeneity modifies treatment response. This study aimed to determine whether data-driven metabolic clustering identifies phenotypic subgroups with prognostic or predictive relevance in hyperuricemic T2DM. Methods: In a retrospective cohort of 224 patients with T2DM and hyperuricemia, model-based clustering was applied to age, diabetes duration, body mass index (BMI), serum uric acid (sUA), HbA1c, eGFR, and sex. A sensitivity analysis excluded outliers, yielding 207 patients. Longitudinal trajectories of eGFR and sUA were assessed using linear mixed-effects models and individual slopes. Effect modification by cluster was tested via three-way interactions and analysis of covariance. Results: Clustering identified two groups with weak separation: an adipose–metabolic cluster (n = 116; exclusively male, BMI 33.1 ± 5.7 kg/m², sUA 478 ± 62 µmol/L) and a lean–metabolic cluster (n = 91; exclusively female, BMI 31.3 ± 6.0 kg/m², sUA 426 ± 67 µmol/L). Treatment-agnostic analyses showed no differences in eGFR and sUA slopes or in all-cause mortality across clusters. In both clusters, SGLT2 inhibitors yielded significantly more favourable eGFR slopes than allopurinol, while sUA reductions were comparable across treatments. No significant three-way interactions were detected. Conclusions: In this cohort, although baseline metabolic characteristics differ among patients, using the selected baseline variables, no clinically actionable treatment-relevant phenotypes were identified. Full article

Background/Objectives: Liver fat represents an early metabolic lesion in the development of diabetes and its cardiometabolic complications. Diets high in free sugars, particularly from sugar-sweetened beverages (SSBs), are associated with abdominal obesity and increased cardiometabolic risk, prompting global guidelines to limit SSBs as a major public health strategy. Low-fat cow’s milk is promoted as the preferred caloric replacement strategy for SSBs due to its high nutritional value and cardiometabolic advantages. Fortified soymilk is a plant-based alternative with approved health claims for cholesterol and coronary heart disease risk reduction that offers an equivalent nutritional value to cow’s milk. However, given concerns about its classification as an ultra-processed food (UPF), it is unclear whether soymilk offers comparable metabolic health benefits to milk as part of clinical and public health strategies to reduce SSB intake. The Soy Treatment Evaluation for Metabolic (STEM) health trial seeks to evaluate the impact of replacing SSBs with either 2% soymilk or 2% cow’s milk on liver fat and other cardiometabolic risk factors in habitual adult consumers of SSBs with obesity. Methods: The STEM trial is a 24-week, pragmatic, 3-arm, parallel, randomized trial. We recruited adults with obesity (high BMI plus high waist circumference based on ethnic specific cut-offs) consuming ≥1 SSB/day. Participants were randomized to one of three groups based on their usual SSB intake at baseline (servings/day): continued SSB (355 mL can) intake; replacement with fortified, sweetened 2% soymilk (250 mL); or replacement with 2% cow’s milk (250 mL). The primary outcome is the change in intrahepatocellular lipid (IHCL) measured by ¹H-MRS at 24 weeks. Hierarchical testing will be done to reduce the familywise error rate. The superiority of cow’s milk to SSBs will be assessed first to establish assay sensitivity. If superiority is established, then the non-inferiority of soymilk to cow’s milk will be assessed using a pre-specified non-inferiority margin of 1.5% IHCL units (assessed by difference of means using a 90% confidence interval [CI]). Analyses will be conducted according to the intention-to-treat (ITT) principle using inverse probability weighting (IPW) for superiority testing and per-protocol analyses for non-inferiority testing, using ANCOVA adjusted for age, sex, metabolic dysfunction-associated steatotic liver disease (MASLD) status, medication use, intervention dose, and baseline levels. We hypothesize that soymilk will be non-inferior to cow’s milk (Clinicaltrials.gov NCT05191160). Results: Recruitment began in November 2021. A total of 3050 individuals were screened. We randomized 186 participants (62 per group) between 19 April 2022 and 16 April 2024. Participants are 57% male; with a mean [SD] age of 39.9 [11.8] years; BMI of 34.6 [6.1] kg/m², waist circumference of 112.6 [13.8] cm; IHCL of 10.0 [8.2] % with 64.1% meeting the criteria for MASLD; and SSBs intake of 2.3 [1.3] servings/day. Conclusions: Baseline characteristics were balanced across the study arms, with participants representing adults with a high-risk metabolic phenotype, and 64.1% meeting the criteria for MASLD. Findings will contribute to evidence on the cardiometabolic benefits of soymilk, informing clinical practice guidelines and public health policy. Full article

Background: Selective immunoglobulin A deficiency (sIgAD), the most common primary immunodeficiency, is associated with recurrent respiratory infections. Despite the established role of IgA in mucosal immunity, population-based data evaluating COVID-19 susceptibility and severity among individuals with sIgAD are scarce. Objectives: This study aimed to evaluate the association between selective IgA deficiency and the risk of SARS-CoV-2 infection, recurrent infection, COVID-19-related hospitalization, and vaccination uptake. Design and Setting: We conducted a retrospective population-based cohort study using the Clalit Health Services electronic health record database in Israel. Methods: Adults aged ≥18 years with documented serum IgA measurements between 2020 and 2022 were included. Selective IgA deficiency was defined as serum IgA < 7 mg/dL with normal IgG and IgM levels. Individuals with sIgAD were matched 1:4 with controls with normal IgA levels by age and sex. Outcomes included documented SARS-CoV-2 infection, recurrent infection (>2 episodes), COVID-19-related hospitalization, and vaccination status. Multivariable logistic regression models were adjusted for demographic characteristics, comorbidities, and vaccination status. Results: The matched cohort included 61,150 individuals (12,230 with sIgAD and 48,920 controls). The risk of primary SARS-CoV-2 infection did not differ significantly between groups (13.0% vs. 14.0%; adjusted OR 1.03, 95% CI 0.95–1.12). However, individuals with sIgAD had increased odds of recurrent infection (adjusted OR 1.15, 95% CI 1.09–1.22) and COVID-19-related hospitalization (adjusted OR 1.40, 95% CI 1.22–1.60). Booster vaccination uptake was slightly higher among individuals with sIgAD. Conclusions: Selective IgA deficiency was not associated with increased susceptibility to primary SARS-CoV-2 infection but was independently associated with recurrent infection and increased risk of hospitalization. These findings underscore the importance of mucosal immunity in post-infection viral control and suggest that individuals with sIgAD may benefit from closer monitoring after COVID-19 infection. Full article

Background: Clinical interpretation of the auditory brainstem response (ABR) relies on precise normative data. While our previous work provided evidence of sex-based differences in ABR latencies in a normative sample (N = 73), this larger-scale investigation (N = 244) validates these findings and extends them to other features of the ABR, such as wave amplitude and interaural latency asymmetry. Methods: This retrospective, cross-sectional study collected ABRs from 244 participants aged 3–79 years (134 men, 110 women) with normal hearing. All underwent basic audiological assessment and click-evoked ABR measurement with the NeuroAudio system. Wave latencies, interpeak intervals, and amplitudes were analyzed. Results: Absolute latencies for wave III and wave V, and all interpeak latency intervals, were significantly shorter in women versus men (p ≤ 0.001). No statistically significant sex-based differences were found for wave I and V amplitudes. Statistically significant right versus left ear differences were found for wave V absolute latency and for interpeak intervals I–III and I–V, with the left ear consistently showing prolonged responses compared to the right. No significant interaural differences were identified for waves I and III, or for the III–V interval. Conclusions: This study confirms the significant effect of sex on ABR temporal parameters, but not on wave amplitudes. There were also significant interaural asymmetries. These findings support the use of sex-specific, and potentially ear-specific, normative data to maximize diagnostic accuracy in audiology. Full article

Cyflumetofen (CYF) and its main metabolite, trifluoromethyl benzoic acid (B-1), both of which contain a trifluoromethyl group, are increasingly used in agriculture due to their high stability and efficacy. Structurally, these molecules share several physicochemical features with per- and polyfluoroalkyl substances (PFASs), including endocrine disruption and reproductive toxicity. This study aims to evaluate the reproductive toxicity effects of CYF and its metabolites using adult zebrafish as a model organism. The results indicate that exposure to CYF and B-1 at environmentally relevant concentrations for 21 days causes hormonal disruption and abnormal gonadal development in fish; moreover, as the concentrations increase, CYF and B-1 significantly impair the reproductive capacity of zebrafish and lead to developmental abnormalities in their offspring. Based on the ratio of E2/T and the alteration of key genes in the HPG axis, such as cyp17a2 and cyp11c1, it is hypothesized that CYF and B-1 disrupt hormonal homeostasis via the HPG axis. Notably, male fish were more susceptible when exposed to CYF or B-1, exhibiting sex-specific differences. RNA-seq analysis revealed that CYF/B-1 promotes Ca²⁺ release from the zebrafish brain and induces steroid hormone dysregulation based on the HPG axis via genes such as hsd17a and gnrh. In summary, this study provides key insights into the reproductive toxicity of CYF and its major metabolite, highlighting their risks to the environment and human health. Full article

Background/Objectives: Hidradenitis suppurativa (HS) is a chronic, immune-mediated inflammatory skin disease characterized by painful nodules, abscesses, sinus tracts, and progressive fibrosis. Vascular activation is becoming increasingly acknowledged as an important factor in HS pathogenesis; however, the effects of tumor necrosis factor alpha (TNF-α) blockade on vascular remodeling in HS remain poorly characterized. This study investigated the impact of TNF-α inhibition by adalimumab (ADA) on endothelial and fibroblast-associated markers in HS lesions. Methods: Formalin-fixed paraffin-embedded skin samples from 71 HS patients were analyzed, including treatment-naive (n = 38) and adalimumab-treated (n = 33) cases. Histopathology and immunofluorescence were performed using antibodies against CD31, von Willebrand factor (vWF), α-smooth muscle actin (αSMA), vimentin, Ki-67 (proliferation), and cleaved Caspase-3 (apoptosis). ImageJ software was used to determine the immunoexpression of selected markers and vascular density. Vascular density, assessed as vessel count per mm², was designated as the primary endpoint. Sex-related differences were analyzed as exploratory endpoints. Results: Adalimumab-treated tissue exhibited significantly reduced vascular density (p < 0.01) compared to the treatment-naive group. Conversely, vimentin immunoexpression was significantly higher (p < 0.01) in the adalimumab-treated group. No significant differences were found in endothelial Ki-67 or cleaved Caspase-3 expression between treatment groups, indicating that the observed reduction in vascular density is not associated with direct effects on endothelial cell proliferation or apoptosis, but rather may occur indirectly through attenuation of the pro-angiogenic inflammatory milieu. Exploratory sex-stratified analysis revealed that treatment-naive males had significantly higher endothelial proliferation (Ki-67; p = 0.031) and vimentin expression (p = 0.017) compared to treatment-naive females. In the ADA-treated group, males exhibited significantly lower vascular density (p = 0.036) and higher endothelial apoptosis (p = 0.039) compared to females, whereas females showed a significant increase in vimentin expression following treatment (p = 0.008), suggesting possible sex-dependent differences in vascular remodeling. Conclusions: TNF-α blockade is associated with reduced vascular density, consistent with indirect anti-angiogenic effects, suggesting that adalimumab exerts disease-modifying effects on the microenvironment beyond inflammatory cytokine suppression. Sex-dependent differences in vascular regression underscore the importance of considering sex as a biological variable in HS pathogenesis and treatment response. These results highlight the significance of vascular interactions in HS and support adalimumab as a disease-modifying treatment. These exploratory findings require confirmation in longitudinal studies with paired biopsies. Full article