Search Results (4,372)

Steatotic liver disease (SLD) is characterised by profound metabolic reprogramming, yet no single biomarker reliably distinguishes disease entities, stages or sex-specific risk profiles. By integrating serum metabolomic signatures as a liquid biopsy with tumour-associated CSC marker profiles in a sex-stratified analytical framework, we aimed to identify biologically meaningful differences and improve strategies for early, presymptomatic detection of SLD progression and HCC. The present study focuses on a targeted panel of 12 strongly dysregulated serum metabolites as candidate biomarkers of disease progression, quantified by NMR-based metabolomics and ELISA and complemented by CSC marker staining. We combined these NMR-based metabolomic ‘liquid biopsy’ data with circulating tumour-associated biomarkers, MELD-based risk assessment and tissue-level CSC marker expression across MetALD, MASLD, immune-mediated and cancerogenic liver disease, HCC and healthy controls. Female MetALD patients showed the second highest mortality after HCC, with lower survival than male cancer patients, despite MELD 3.0 assigning ~50% higher scores in women. MetALD mortality clustered with GP73, CD44, metabolomics and AA/3HB ratio, indicating a distinct, high-risk female phenotype. Integrating liquid-based metabolomic profiling, AA/3HB redox assessment, CSC markers and MELD 3.0 into sex-sensitive diagnostic pathways may improve early detection and risk stratification of alcohol-associated SLD, especially in women. Full article

Survivors of primary gastric lymphoma (PGL) face a significantly elevated and persistent risk of developing second primary malignancies (SPMs), with gastric adenocarcinoma representing the most frequent SPM and standardized incidence ratios reaching up to 16-fold above the general population. This excess risk persists for decades after initial treatment and is associated with increased cause-specific mortality compared to matched primary cancers. Among patients with PGL, approximately 5% develop gastric cancer (with two-thirds being metachronous), and nearly 15% harbor precancerous lesions including atrophic gastritis, intestinal metaplasia, and dysplasia. Beyond gastric malignancies, survivors also experience elevated rates of extra-gastric SPMs, particularly digestive system tumors (43%), respiratory cancers (21%), and urinary tract malignancies (13%). Key risk factors include treatment with immunochemotherapy or radiotherapy, advanced age, male sex, advanced stage at diagnosis, ulcerative-type lymphoma morphology, and persistent Helicobacter pylori (HP) infection. Patients receiving combined chemoradiotherapy demonstrate the highest SPM risk, particularly for gastric and pancreatic cancers. These findings underscore the critical importance of lifelong, risk-adapted surveillance strategies integrating both hematology and gastroenterology follow-up. Annual endoscopic surveillance is recommended for high-risk patients, with intervals adjusted according to lymphoma histology, HP status, and the presence of precancerous gastric lesions. Mandatory HP eradication with confirmation of response is essential for reducing gastric cancer risk. Future research priorities include prospective, standardized studies to better quantify SPM risk, validation of molecular and microbiological biomarkers for individualized risk stratification, and development of predictive models to enable personalized surveillance protocols and improve long-term outcomes in this vulnerable population. Full article

Background: As survival improves in transfusion-dependent β-thalassemia, long-term adult morbidity, including cognitive dysfunction, has become increasingly relevant. Adult data remain limited, particularly in Eastern Europe, and many studies rely on single screening tools with limited control for confounding. Methods: We conducted a single-center case–control study (2024–2025) at the Congenital Hemolytic Anemia Treatment Center, University Hospital “Sv. Georgi” Plovdiv, Bulgaria. Fifty adults with transfusion-dependent β-thalassemia (86% thalassemia major; 14% transfusion-dependent intermedia) and 30 frequency-matched healthy controls completed a multi-domain cognitive battery: Montreal Cognitive Assessment (MoCA), Mini-Mental State Examination (MMSE), Clock Drawing Test (CDT), Trail Making Test (TMT-A/B), and timed verbal fluency. Associations between thalassemia status and cognitive outcomes were estimated using three prespecified models: unadjusted, adjusted for age and sex, and a doubly robust model combining covariate balancing propensity score inverse probability weighting (balancing BMI, smoking, education, and comorbidity) with age/sex regression adjustment. Results: Patients performed worse than controls on global cognition and executive/visuospatial measures. MoCA scores were lower in patients (−2.26 unadjusted, p = 0.016; −2.83 doubly robust, p = 0.001), as were MMSE scores (−1.64, p = 0.015; −1.87, p = 0.002). CDT performance was consistently poorer (OR ≈ 0.28–0.30 across models). Patients were slower on TMT-B (time ratio 1.35 unadjusted, p = 0.003; 1.42 doubly robust, p < 0.001); TMT-A reached significance only after weighting (ratio 1.32, p = 0.001). Verbal fluency was modestly lower with borderline significance (p ≈ 0.05–0.06). Conclusions: Transfusion-dependent β-thalassemia in adults is associated with poorer cognitive performance, particularly in global cognition and executive/visuospatial domains, with results robust across adjustment strategies. Routine multi-domain cognitive screening may be warranted in adult thalassemia care. Full article

Sex control technology has become a key technique in aquatic animal breeding, as many aquatic species exhibit distinct sexual dimorphism in growth, reproduction, immunity, and other economically important traits. Therefore, methods such as regulating sex ratios and establishing unisexual populations can significantly enhance aquaculture productivity and breeding efficiency. Recent years have seen a rapid advancement in the field of research on the mechanisms of sex determination and differentiation in aquatic animals, as well as sex control technologies. This review summarizes the latest advances in research on the mechanisms of sex formation in aquatic animals, including genetic sex determination, environmental sex determination, and genotype-environment interactions. Furthermore, this review outlines the major sex-linked genes and molecular markers used for genetic sex identification, introduces key male and female regulatory factors involved in gonadal differentiation, and explores the application of major sex control methods in aquaculture breeding, including techniques such as interspecific hybridization, environmental regulation, hormone induction, parthenogenesis, and gene editing. Full article

Background: Stunting remains a major public health problem among ethnic minority children in mountainous areas of Vietnam. Picky eating has been suggested as a potential behavioral risk factor for poor child growth, but evidence from vulnerable rural populations remains limited. This study examined the association between picky eating and stunting among ethnic minority children aged 12–35 months in Vietnam. Methods: This cross-sectional study was conducted from October to November 2025 in two communes of Phu Tho province, formerly part of Lac Son District, Hoa Binh Province, Vietnam. A total of 341 children aged 12–35 months and their caregivers were included. Data were collected using structured interviewer-administered questionnaires on feeding practices and child characteristics. Picky eating was assessed based on caregiver-reported behaviors. Anthropometric measurements were performed according to standard procedures, and height-for-age Z-scores were calculated using the WHO Child Growth Standards. Zinc status was assessed in a subsample of children. Bivariate and multivariable logistic regression analyses were conducted to identify factors associated with stunting. Adjusted odds ratios (AORs) with 95% confidence intervals (95% CIs) were reported. Results: The prevalence of picky eating was 39.6%, while 24.9% of children were stunted. Zinc deficiency was identified in 41.9% of children with available blood samples. In multivariable analysis, picky eating was significantly associated with increased odds of stunting (AOR = 3.63; 95% CI: 1.71–7.70). Snacking before main meals was also independently associated with stunting (AOR = 1.81; 95% CI: 1.01–3.24). In contrast, zinc deficiency was associated with stunting in crude analysis but was not statistically significant after adjustment. Other factors, including child age, sex, caregiver identity, and timing of complementary feeding, were not independently associated with stunting. Conclusions: Picky eating was common and was independently associated with stunting among ethnic minority children in this mountainous setting. These findings suggest that behavioral feeding practices, particularly picky eating and pre-meal snacking, warrant attention in nutritional programs targeting this population; however, longitudinal studies are needed to confirm the direction of this relationship. Full article

Background/Objectives: Epidemiological studies over the first decades of the 21st century have reported a decrease in cardiovascular disease (CVD) morbidity and mortality. Changes in coronary care for acute myocardial infarction (AMI) over these years, including the COVID-19 pandemic period, have been less studied in Eastern and Central Europe. The study aimed to assess changes in coronary care—the time of medical assistance and treatment—for AMI patients over 2000–2023 in urban Kaunas residents aged 25–64. Methods: The data source was study cases from the Kaunas Ischemic Heart Disease Registry (Registry)—Kaunas city residents aged 25–64 years included in the Registry according to MONICA project protocol evaluation methodologies. Data were analyzed by sex and age group (25–54 and 55–64 years). Descriptive statistics (chi-square and z-score values) were used to evaluate the data; the significance level was p < 0.05. A logistic regression analysis was performed to assess the odds ratios of death within 28 days across six time periods. Results: The proportion of AMI patients hospitalized up to 2 h from the onset of pain accounted for about one-fifth of all hospitalized patients in 2000–2016, while in 2017–2023, it significantly decreased. In 2017–2023, compared with 2000–2004 and 2009–2016, significantly fewer men who developed AMI were hospitalized within the first 2 h of emergency presentation (p < 0.05). Over the whole study period, fewer women with AMI were hospitalized within the first 2 h of pain as compared to men (p < 0.05). There were no significant differences in time from pain onset to hospitalization between the age groups. At the same time, from 2009 to 2012, more young AMI patients were hospitalized within the first 2 h (p < 0.05). Percutaneous coronary angioplasty (PTCA) with stenting (PCI) increased 30 times from 2000–2004 to 2020–2023. PCI has been the most available treatment for men with AMI since 2009 and stayed stable from 2013 (66.0%) until 2023 (72.1%). Women with AMI tended to get less PCI, PTCA, and coronary artery bypass grafting (CABG) than men. The pre-pandemic and COVID-19 periods did not differ in the proportions of reperfusion treatment methods used in both men and women. Thrombolysis was very rare, and since 2017, it has not been used in Kaunas because PCI has become more accessible. PCI (2000–2016) and CABG (2009–2016) were more prevalent among the 25–54-year-old AMI patients (p < 0.05). From 2017 to 2023, there were no differences between age groups in the reperfusion procedures used, nor were there differences in treatment between these groups during the pre-pandemic (2017–2019) and peri-COVID-19 pandemic (2020–2023) periods. Conclusions: In Kaunas, the treatment of patients with AMI has improved significantly over the past 20 years. The use of PCI has increased greatly, and the rate of CABG surgery stayed stable, while only every fifth patient has been admitted to the hospital in a timely manner. Men were more likely to receive PCI, and older patients were more likely to undergo CABG. Compared to the period of 2000–2004, the chance of dying within 28 days after AMI was significantly lower in 2017. Full article

Background/Objectives: Alcoholic cardiomyopathy (ACM) is a major preventable cause of non-ischemic dilated cardiomyopathy (DCM), yet its specific cardiac magnetic resonance (CMR) remains incompletely defined. We aimed to characterize the CMR features of ACM, focusing on late gadolinium enhancement (LGE) subpatterns and biventricular function and to compare them with idiopathic DCM. Methods: In total, 148 consecutive patients (ACM n = 20, idiopathic DCM n = 128) referred for CMR at a single center were retrospectively analyzed. Sequential logistic regression adjusted for age, sex, left ventricular ejection fraction (LVEF), and right ventricular ejection fraction (RVEF) was used to identify independent association with LGE presence. Results: LVEF did not differ between groups (32.5% vs. 35.0%, p = 0.293). ACM patients showed significantly worse RVEF (40.5% vs. 52.0%, p = 0.010) and larger indexed right ventricle (RV) volumes. Any LGE was present in 70% vs. 40% (p = 0.015); when the non-specific RV insertion point pattern (non-RV-IP) was excluded, non-RV-IP LGE was 45% vs. 22.7% (p = 0.051), with a specific midwall linear pattern (25% vs. 8%, p = 0.033). ACM was independently associated with LGE across all models with an adjusted odds ratio (OR) of 3.06 [95% CI 1.05–8.95], p = 0.041, and RV dysfunction (RVEF < 45%) (OR 4.79 [95% CI 1.60–14.32], p = 0.005). No differences in major adverse cardiovascular events (MACEs) were observed at 24 months (log-rank p = 0.697). Conclusions: ACM has a distinct CMR phenotype characterized by midwall linear LGE fibrosis and more severe RV involvement, independent of left ventricle (LV) systolic function. These exploratory findings suggest that CMR may provide clinically relevant phenotypic information in ACM beyond LVEF, warranting confirmation in prospective studies. Full article

Datasets from 849 dogs ≤ 3 years of age were analysed retrospectively, considering breed, sex, anatomic sites, multiplicity, tumour diameter, grading, and immunohistochemistry by using IBM^® SPSS Statistics (version 29.0.2.0). Danish–Swedish farm dogs (OR: 8.11, 95% CI 3.33–19.77, p < 0.001) and English Setters (OR: 6.68, 95% CI 3.20–13.97, p < 0.001) showed the highest odds ratios (ORs) compared to crossbreeds. German Shepherd Dogs showed lower ORs (OR: 0.05, 95% CI 0.007–0.364, p < 0.01). The most common sites affected in the young dogs were the trunk (39.2%), hind limbs (24.9%), head (10.1%), fore limbs (7.4%), and pinnae (5%). Patnaik grading revealed 330 grade I (35.7%), 580 grade II (62.8%), and 14 grade III MCTs (1.5%). Kiupel “low grade” was found in 903 MCTs (97%), and 21 MCTs were “high grade” (3%). The prevalence of grade I MCTs was higher in Boxers (48.0%, p < 0.05) and Pugs (67.9%, p < 0.01). Pinnal MCTs were mostly grade I (58.3%, p < 0.01). In 6% (n = 51), multilocalised MCTs were found, and Golden Retrievers (12.5%, p = 0.02) and Pugs (21.4%, p = 0.005) were more affected than crossbreeds. Out of 87 dogs, 20 showed a Ki-67 count above the cut-off as well as KIT staining pattern II. The findings warrant heightened vigilance in evaluating cutaneous lesions in young dogs and highlight similarities and differences compared to the general dog population. Analysis of survival data is required to evaluate how the findings translate into a clinical setting. Full article

Background/Objectives: Nutrient profiling models are widely used to support healthier food choices, but their applicability may be limited in dietary cultures with multi-dish meals and high consumption of minimally processed foods. This study extended the Ajinomoto Group Nutrient Profiling System (ANPS), originally developed for dish- and meal-level assessment, to evaluate overall quality of daily intake (ANPS-Day) based on four components (protein, vegetables, saturated fatty acids [SFAs], and sodium), and examined its criterion-related validity using 24 h urinary biomarkers. Methods: A total of 324 healthy Japanese adults aged 20–69 years completed four-day semi-weighed dietary records and two non-consecutive 24 h urine collections. Urinary sodium, potassium and urea nitrogen were measured. Associations were examined using age- and sex-adjusted Spearman correlation coefficients and trend analyses. Results: The crude ANPS-Day score showed weak and inconsistent correlations with urinary biomarkers. In contrast, the energy-adjusted ANPS-Day score was positively correlated with estimated potassium intake (r = 0.25) and inversely correlated with the urinary sodium-to-potassium (Na/K) ratio (r = −0.24). In quartile analyses, higher energy-adjusted ANPS-Day scores were associated with higher protein and potassium intakes and with a lower Na/K ratio (all p for trend ≤ 0.001). In component analysis, vegetable points were positively associated with potassium intake, whereas sodium points were inversely associated with estimated sodium intake and the Na/K ratio. SFA points were not associated with urinary biomarkers. Conclusions: The energy-adjusted ANPS-Day score showed modest but biologically plausible associations with urinary biomarkers, providing partial evidence of criterion-related validity in assessing diet quality in multi-dish dietary settings. Full article

Background: Migraine is a neurological disorder affecting approximately 15% of the general population, and autonomic nervous system (ANS) dysfunction is a well-characterized feature of the condition. Sympathovagal imbalance during acute migraine attacks has been linked to cardiac electrical instability. This study aimed to evaluate atrial and ventricular myocardial repolarization markers in migraine patients at three serial electrocardiography (ECG) time points. Methods: A prospective observational cross-sectional study was conducted in a tertiary emergency department (ED), enrolling 70 migraine patients and 70 age- and sex-matched healthy controls. Three 12-lead ECGs were obtained per patient: during the migraine attack (within 60 min of ED admission), after analgesic treatment (verbal pain relief or Numeric Rating Scale [NRS] decrease greater than 4 points), and in the pain-free period (at least 24 h after the attack, within 7 days). Measured parameters included P-wave duration, P-wave dispersion, QT interval, QT dispersion, corrected QT (QTc) duration (Bazett formula), QTc dispersion, Tpeak–Tend (Tp-e) interval, Tp-e dispersion, and Tp-e/QTc ratio. ECGs were evaluated by two blinded emergency medicine specialists. Results: All repolarization markers were significantly higher in migraine patients than in controls (p < 0.05 for all). Comparing the first (ictal) with the second (post-treatment) measurements, all markers except P-wave dispersion decreased significantly (p < 0.05). All markers were significantly higher during the attack than in the pain-free period (p < 0.05 for all). Tp-e interval and Tp-e/QTc ratio showed a further significant reduction between the second and third measurements (p = 0.016 and p = 0.004, respectively). P-wave dispersion was significant only for the first-to-second comparison (p = 0.034) and did not differ significantly between the first and third (p = 0.137) or second and third (p = 0.725) measurements. Pulse rate was significantly higher in the migraine group than in controls (p = 0.012). Conclusions: Acute migraine attacks were associated with significant elevation of both atrial and ventricular repolarization markers, with near-normalization during pain-free periods. These findings are consistent with a proposed mechanism of ANS-mediated cardiac electrical instability during acute attacks, although direct confirmation in future studies is required. Clinicians managing acute migraine in the ED should consider ECG monitoring in patients with cardiovascular risk factors. For anesthesiologists and intensivists, the elevated Tp-e and Tp-e/QTc observed ictally indicate that preoperative ECG assessment in migraine patients may be warranted to guide anesthetic planning. Full article

Celiac disease (CD) is an autoimmune enteropathy of the small intestine affecting genetically susceptible individuals, characterized by an aberrant immune response to gliadin and sustained IgA-driven inflammation. IgA exists in two main subclasses, IgA1 and IgA2, which differ in distribution and function, but their profile in CD remains poorly characterized. Circulating free light chains (FLCs) are markers of B-cell activation and immune dysregulation, yet their role in CD has not been fully explored. The aim of this study was to characterize IgA subclasses and FLC profiles in newly diagnosed celiac patients. We analyzed sera from 108 CD patients and 29 healthy controls, assessing conventional serological markers (anti-tissue transglutaminase and anti-endomysial antibodies), together with total IgA, IgA1, IgA2, and FLC levels using a turbidimetric method. CD patients exhibited higher total IgA levels and an increased IgA1/IgA2 ratio, alongside a decreased k/λ ratio; these differences remained significant after adjustment for age and sex. When combined in a multivariable logistic model, these biomarkers yielded an AUC of 0.827, suggesting that the parameters identified in the univariate analyses provide complementary, non-redundant information that jointly highlights a reorganization of the humoral immune response. Due to the limited sample size, our results need confirmation in larger cohorts. However, our findings suggest a reorganization of the IgA compartment in CD, with selective expansion of IgA1 and preferential λ light chain usage, highlighting coordinated alterations in the humoral immune response. The integration of such markers, potentially in combination with -omics approaches, may contribute to a more refined and less invasive characterization of celiac disease. Full article

Background: Hypertension is being increasingly observed among young adults in urban India, alongside rapid dietary transitions and rising consumption of ultra-processed foods (UPFs). The current study aimed to assess the frequency and patterns of UPF consumption and examine their association with high blood pressure among urban college students. Methods: A cross-sectional study was conducted among 311 undergraduate students aged 18–24 years from three colleges in Hyderabad, India. Our study used a validated automated device to measure blood pressure. Dietary intake over the previous month was assessed using a 24-item food frequency questionnaire capturing commonly consumed UPFs. After adjusting for age, sex, and socioeconomic variables, multivariable logistic regression was performed to assess the relationships between UPF consumption categories and high blood pressure. Ninety-five percent confidence intervals (CIs) for adjusted odds ratios (AORs) were reported. Results: Overall, 12.5% of participants had high BP (≥140/90 mmHg). The prevalence was higher among males and those aged >20 years. In the adjusted analyses, males had significantly higher odds of having high BP (AOR: 4.96; 95% CI: 1.64–15.01), as did students from higher-income households (AOR: 3.22; 95% CI: 1.07–9.66). Consumption of high-fat and/or high-salt UPFs at or above the median was independently associated with high BP (AOR: 2.85; 95% CI: 1.16–6.99). Taste, availability, and low cost were common drivers of UPF intake. Conclusions: Higher consumption of high-fat and/or high-salt ultra-processed foods was associated with higher odds of elevated blood pressure among urban young adults. These findings warrant further longitudinal investigation and may help inform the development of targeted dietary awareness and food environment interventions in college settings. Full article

Background: Computed tomography-based body composition parameters are emerging prognostic markers in pancreatic cancer. While sarcopenia and myosteatosis have been widely studied, the prognostic significance of ectopic fat deposition within the psoas muscle remains unclear. We aimed to evaluate the prognostic impact of the fat ratio within the psoas muscle (FRPM) in patients with stage IV pancreatic cancer receiving first-line systemic chemotherapy. Methods: This retrospective cohort study included 99 patients with stage IV pancreatic cancer treated with first-line chemotherapy. Baseline CT images at the L3 level were analyzed, and FRPM was calculated as the proportion of intramuscular fat to total psoas muscle area. FRPM was analyzed primarily as a continuous variable. Exploratory low- and high-FRPM groups were defined using sex-specific medians for descriptive comparisons and Kaplan–Meier analyses. Overall survival (OS) and progression-free survival (PFS) were assessed using Kaplan–Meier and Cox regression analyses. Multivariable models were adjusted for age, sex, ECOG performance status, liver metastasis, and C-reactive protein (CRP). Results: Among 99 patients, 48 were categorized as having low FRPM and 51 as having high FRPM based on exploratory sex-specific median-based groups. Higher FRPM correlated with older age and higher BMI and inversely correlated with psoas muscle size and PMI. Median OS was 9.76 months in the low-FRPM group versus 5.78 months in the high-FRPM group, and median PFS was 5.29 versus 3.68 months. In the main multivariable Cox model, higher FRPM was associated with worse OS when analyzed as a continuous variable and reported per 1-standard deviation increase (adjusted HR: 1.43, 95% CI: 1.08–1.91, p = 0.014). After additional adjustment for first-line treatment-regimen category, the association remained directionally consistent but did not retain conventional statistical significance (adjusted HR: 1.32, 95% CI: 0.99–1.77, p = 0.060). Conclusions: Higher FRPM was associated with shorter OS and PFS in patients with stage IV pancreatic cancer receiving first-line systemic chemotherapy. These findings suggest that ectopic fat deposition within the psoas muscle may represent a potential CT-based muscle-quality marker associated with adverse prognosis. External validation and comparison with conventional adiposity parameters are required before clinical application. Full article

Background: Hepatitis C virus (HCV) remains a major cause of preventable liver-related mortality in the United States despite highly effective direct-acting antivirals (DAAs). Contemporary assessment of mortality trends and disparities is essential for elimination efforts. Methods: Using CDC WONDER multiple cause-of-death data (1999–2023), we identified HCV-related deaths using ICD-10 codes for acute and chronic HCV (B17.1, B18.2) and calculated age-adjusted mortality rates (AAMRs) per 100,000 (2000 US standard). Rates were stratified by sex, race/ethnicity, census region, and 2013 NCHS urban–rural classification. Joinpoint regression quantified temporal inflection points and annual percent changes (APCs). Results: Overall HCV-related AAMR increased from 1.8 (1999) to a peak of 5.0 (2014), then declined to 2.3 (2023), with a marked post-2014 decrease (APC −8.2%). Mortality was consistently higher in males than females (2023 rate ratio 2.57). In 2023, American Indian/Alaska Native individuals had the highest mortality (AAMR 8.7; rate ratio 3.48 vs. non-Hispanic White), followed by non-Hispanic Black individuals (AAMR 6.2; rate ratio 2.48). Mortality remained highest in the West and was higher in non-metropolitan than metropolitan counties (AAMR 2.8 vs. 2.3; rate ratio 1.22), with a slower post-2014 decline in non-metropolitan areas. Conclusions: Our findings indicate that while the DAA era has been associated with a substantial reduction in HCV-related mortality at the national level, this progress has not been uniform across all populations. Persistent excess mortality among Native American and non-Hispanic Black individuals may reflect inequities in the HCV care cascade, including screening, confirmatory testing, linkage to specialty care, insurance-related restrictions, and the high cost of antiviral therapy. These results highlight the need for policies and public health strategies that improve equitable and affordable access to curative HCV treatment. Full article

Aims: The aim of this study was to investigate the associations between symptomatic hearing loss (HL), neuropathy, and nephropathy in subjects with Type 2 diabetes mellitus (T2DM). Furthermore, the study evaluated whether HL was associated with chronic low-grade inflammation, assessed based on plasma levels of tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and high-sensitivity C-reactive protein (hsCRP), and explored potential sex-specific differences. Materials and Methods: We included 4245 subjects with T2DM from The Danish Centre for Strategic Research in Type 2 Diabetes cohort. Symptomatic HL was defined using ICD-10 codes. In 2016, a questionnaire was sent out to evaluate neuropathy using the Michigan Neuropathy Screening Instrument (MNSI ≥ 4). Nephropathy was defined as urinary albumin-to-creatinine ratio (UACR) >30 mg/g. Plasma levels of TNF-α, IL-6, and hsCRP were measured at enrolment from 2010 to 2016. Multivariable logistic regression was used, adjusting for covariates. Results: Neuropathy was significantly associated with HL (OR = 1.83, 95%CI [1.42, 2.35], p < 0.001), and the association was stronger in women (OR = 2.74 [1.81, 4.14], p < 0.001) compared to men (OR = 1.44 [1.04, 1.99], p < 0.05) (P-interaction = 0.020). No significant association was found between nephropathy and HL. Among inflammatory markers, only the highest tertile of TNF-α levels was significantly associated with HL compared to the lowest tertile (OR = 1.40 [1.07, 1.82], p < 0.05) without any sex interaction. Conclusions: In subjects with T2DM, neuropathy was associated with symptomatic HL, and the association seemed to be stronger in females. Among chronic low-grade inflammation markers, only TNF-α was significantly associated with symptomatic HL. Additionally, no significant association was found between nephropathy and HL. Full article