Minimally invasive techniques (MITs), including percutaneous ethanol injection (PEI) and radiofrequency ablation (RFA), are effective non-surgical options for benign thyroid nodules (BTN). However, predictors of response and technical determinants remain incompletely defined. We conducted a prospective single-center study including 120 BTNs (45 PEI, 75 RFA) treated between 2022 and 2025, with 12-month follow-up. The primary objective of this study was to identify clinical and procedural predictors of treatment response following MITs for BTNs. The primary outcome measure was the 12-month volume reduction ratio (VRR). Secondary endpoints included changes in cosmetic and symptomatic scores, thyroid function in autonomously functioning nodules (AFTN), and safety outcomes. Baseline mean nodule volume was 22.06 mL SD 14.52, cosmetic score 3.39 SD 0.93, and dysphagia score 3.33 SD 1.8. At 12 months, mean VRR was 84.24
Immune checkpoint inhibitors (ICIs) are widely used to treat various malignancies; however, the high incidence of immune-related adverse events, including thyroid dysfunction, is a major clinical concern. Thyroid dysfunction occurs frequently, affects patient health and quality of life, and can be life-threatening when severe, necessitating prompt identification and management. Herein, we aimed to identify pretreatment risk factors associated with ICI-induced thyroid dysfunction. Medical records of patients administered ICIs were retrospectively reviewed. Data on patient age, sex, and body weight; primary tumor type; ICI agent; programmed death-ligand 1 status; disease stage; line(s) of treatment; and laboratory parameters measured before treatment initiation were extracted. These characteristics were compared between patients who developed thyroid dysfunction and those who did not. An elevated pretreatment eosinophil count was significantly associated with thyroid dysfunction following ICI therapy. In the multivariable logistic regression analysis, eosinophil count remained significantly associated with thyroid dysfunction after adjustment for lactate dehydrogenase (LDH; adjusted odds ratio per 0.1 × 10³/µL increase, 2.18; 95
Sodium-glucose co-transporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) each provide cardiorenal protection in trials of selected populations, but their combined effect has not been tested in dedicated head-to-head randomized trials. We performed an exploratory network meta-analysis (NMA) that integrated subgroup data from existing randomized controlled trials (RCTs) to compare SGLT2i, GLP-1RA, and concomitant SGLT2i + GLP-1RA use against placebo on cardiorenal outcomes. We ran a frequentist random-effects NMA. Major databases were searched for RCTs or post-hoc analyses (> 1 year follow-up) that reported subgroup outcomes by background SGLT2i or GLP-1RA use. The primary outcome was major adverse cardiovascular events (MACE). Secondary outcomes were hospitalisation for heart failure (HHF), composite renal outcomes, and total estimated glomerular filtration rate (eGFR) slope. Surface Under the Cumulative Ranking Curve (SUCRA) values are reported as supportive ranking summaries. Sixteen RCTs were pooled. Compared with placebo (without background SGLT2i or GLP-1RA), all active strategies reduced MACE and HHF (all p < 0.05). For composite renal events, combined use (RR 0.63, 95
Diabetic foot ulcers (DFUs) arise from interacting clinical, microbial, and host processes, yet public datasets differ substantially in design, scale, and evidentiary strength. We curated eight public DFU cohorts and defined an evidence hierarchy. PRJNA287759 was reprocessed from raw 16 S reads; outcome tests used one baseline sample per patient (74 healed and 15 non-healed/adverse). GSE134431 compared 13 DFU with 8 diabetic foot skin samples using limma. Host discrimination underwent fold-confined leave-one-sample-out validation, 100 repeated nested five-fold analyses, 200 label permutations, and independent rank-score evaluation in GSE80178. Baseline diversity and community structure did not differ by outcome (Shannon P = 0.159; Observed ASVs P = 0.669; PERMANOVA R2 = 0.0157, P = 0.142). Rothia was the only nominal genus (P = 0.0307), and none survived FDR correction across prevalence thresholds. GSE134431 yielded 2,873 differentially expressed genes with coherent epidermal repair enrichment. Host leave-one-sample-out AUC was 0.990 (95
Although intensive weight management achieves considerable success in diabetes remission, individual response varies substantially. We aimed to evaluate the predictive ability of early β-hydroxybutyrate (BHB) for type 2 diabetes (T2D) remission following an intensive dietary intervention in Southeast Asian individuals, and explore the metabolomic signatures associated with remission. We analysed 45 adults with obesity and T2D (age:42 ± 10 years, 66.7
Aggressive thyroid cancer remains difficult to treat, partly because molecular programs linking malignant behavior to cancer-associated fibroblast (CAF)-related support are incompletely defined. This study investigated whether ATF4 and FGFR4 cooperate in thyroid cancer cells and whether this relationship persists in a CAF-associated context. Stable ATF4 and/or FGFR4 knockdown was established in 8305 C thyroid cancer cells. Proliferation, migration, invasion, apoptosis, cytokine secretion, transcriptomic changes, and xenograft growth were assessed under basal and CAF-conditioned culture conditions. Silencing ATF4 or FGFR4 reduced 8305 C cell proliferation, migration, and invasion, with the strongest inhibition after combined knockdown. These effects persisted in CAF-conditioned medium and were accompanied by increased apoptosis, reduced IL-6 and TNF-α secretion, and transcriptomic changes involving cell cycle, stress-response, apoptosis, and inflammatory pathways. In vivo, ATF4 and/or FGFR4 silencing suppressed xenograft growth, increased tumor apoptosis, and reduced CAF-associated marker expression. ATF4 and FGFR4 are functionally associated in thyroid cancer progression. Their cooperative program may contribute to cancer cell aggressiveness and to the maintenance of a CAF-associated tumor-promoting microenvironment.
The cardiovascular impact of hypothyroidism remains controversial, particularly regarding the distinction between cardiovascular disease occurrence and cardiovascular prognosis. We performed a systematic review and meta-analysis to separately evaluate the association between hypothyroidism and incident cardiovascular events and cardiovascular mortality. PubMed/MEDLINE, Scopus, and Web of Science were systematically searched for studies published between January 2014 and April 2026 evaluating cardiovascular outcomes in adult patients with overt or subclinical hypothyroidism compared with euthyroid controls. Separate random-effects meta-analyses were performed for cardiovascular events and cardiovascular mortality using pooled odds ratios (ORs) with 95
Metabolic dysfunction–associated steatotic liver disease (MASLD) is a systemic disorder associated with cardiovascular, renal, and metabolic comorbidities. We evaluated cardiovascular disease (CVD), four-domain cardiovascular–renal–hepatic–metabolic (CRHM) involvement, and their associations with non-invasive liver-related scores in patients with type 2 diabetes mellitus (T2DM) and MASLD. We retrospectively analyzed 216 patients with T2DM and MASLD. A study-specific four-domain CRHM phenotype was defined as the coexistence of T2DM, MASLD, chronic kidney disease (CKD), and atherosclerotic CVD. FIB-4, AST-to-ALT ratio (AAR), APRI, Hellenic Score II, Fibrotic NASH Index (FNI), and CORE model were evaluated. CVD was present in 75/216 participants (34.7
This paper was designed to reveal the effects of evidence-based rehabilitation nursing (EBRN) combined with early neck and shoulder exercises on cervical mobility in patients with thyroid cancer (TC) undergoing transoral endoscopic thyroidectomy via the vestibular approach (TOETVA). One hundred and twenty TOETVA patients were randomized into control (routine nursing) and study (EBRN plus early neck/shoulder exercises) groups (n = 60 each). Outcomes included related surgical indicators, adverse events, neck pain and mobility (NPDS), illness perception (BIPQ), quality of life (QLICP-HN), and nursing satisfaction (NSNS). No significant differences were observed between the two groups with respect to the 24-h postoperative drainage volume, drainage tube retention time, postoperative hospital stay, or the incidence of postoperative adverse events (all P > 0.05). At postoperative day 7, the study group had lower NPDS scores across all dimensions and greater cervical mobility in six directions than the control group (P < 0.05). At 1 month postoperatively, the study group had lower BIPQ scores and higher QLICP-HN and NSNS scores than the control group (all P < 0.05). EBRN plus early neck and shoulder exercises may effectively improve cervical mobility, alleviate postoperative pain and disability, and enhance disease perception, quality of life, and nursing satisfaction in TC patients undergoing TOETVA.
Tirzepatide and semaglutide are widely used for type 2 diabetes mellitus (T2DM) and obesity. However, the blood pressure–related adverse event profiles associated with tirzepatide and semaglutide remain unclear. This study systematically evaluated hypertension- and hypotension-related treatment-emergent adverse events (TEAEs) that occurred when using tirzepatide and semaglutide for the treatment of T2DM or obesity. A comprehensive search was performed in PubMed, Scopus, Web of Science, Embase, CENTRAL, and ClinicalTrials.gov from inception to September 26, 2025. Pooled risk ratios (RRs) with 95
Dyslipidemia, inflammation and angiogenesis pathways contribute to the genetic susceptibility to diabetic nephropathy (DN) in type 2 diabetes mellitus (T2DM). This study investigated the association of common genetic variants; Apolipoprotein C1 (APOC1) rs4420638, C-C chemokine receptor type 5 (CCR5) rs1799987, C-X-C motif chemokine ligand 8 (CXCL8) rs4073, Matrix metallopeptidase 9 (MMP9) rs17576, Erythropoietin (EPO) rs1617640 and Vascular Endothelial Growth Factor A (VEGFA) (rs833061 and rs3025039) with DN susceptibility in Tunisian T2DM patients. A total of 236 patients with T2DM were enrolled, including 47 with DN and 189 without diabetic nephropathy (WDN). Genotyping was performed using PCR-RFLP. Allelic combinations and statistical analyses were conducted using SNP Analyzer2.0 and SPSS20, respectively. All genotype frequencies were in Hardy-Weinberg equilibrium. After adjustment for potential confounding factors, the variant alleles of APOC1 rs4420638 (OR = 2.58, 95
The burden of type 2 diabetes (T2D) is increasing across BRICS countries, but cross-national comparative evidence on recent trends and drivers is limited. Using Global Burden of Disease (GBD) 2023 data, we analyzed T2D-related deaths, years of life lost (YLLs), years lived with disability (YLDs) and disability-adjusted life years (DALYs) from 1990 to 2023 in Brazil, Russia, India, China and South Africa. Age-standardized rates, estimated annual percentage changes, joinpoint trends, decomposition of changes in absolute burden, and Bayesian age-period-cohort projections were evaluated. Attributable burden was assessed using the GBD comparative risk assessment framework. As a secondary analysis, two-sample Mendelian randomization (MR) was performed for selected exposures using external GWAS datasets of predominantly European ancestry, without using the MR estimates to explain between-country differences or to validate the GBD attribution. In 2023, India had the largest absolute burden of type 2 diabetes, whereas South Africa had the highest age-standardized DALY and mortality rates. China ranked second in absolute burden but lowest in age-standardized rates. From 1990 to 2023, age-standardized DALY rates increased in all five countries, with the steepest increases in India and the Russian Federation. Epidemiological change drove burden increases in India and Russia, population ageing in China, and population growth in Brazil and South Africa. High fasting plasma glucose and high BMI accounted for the largest attributable DALY fractions. In complementary MR analyses, adiposity, several glycemic traits, smoking initiation, and television viewing time showed positive primary-analysis associations with T2D, although these provide etiological context rather than BRICS-specific causal estimates. T2D burden in BRICS countries is high, heterogeneous, and still increasing, highlighting the need for country-specific prevention and care strategies.
Type 1 diabetes mellitus (T1DM) is an insulin dependent diabetes treated with exogenous insulin therapy. A subset of individuals with T1DM develops reduced insulin sensitivity, a phenomenon often referred to as ‘double diabetes’, which is associated with an increased risk of complications. The pathophysiology of double diabetes in T1DM is not well understood. We hypothesize that changes in peripheral blood in T1DM may act as cellular correlates and provide insights into the development of double diabetes. A retrospective study (N = 343) was performed at a tertiary care centre in western India. An estimated insulin sensitivity (eIS) score was calculated using the Coronary Artery Calcification in T1DM (CACTI) equation. A partial correlation, univariate, and multiple regression were performed to study the association of eIS with the components of hemogram (lymphocytes, neutrophils, monocytes, eosinophils, platelets, erythrocytes, and hemoglobin). Additionally, stratified multiple regression analyses were performed to assess the association of eIS with age, sex, and Body Mass Index (BMI). Peripheral blood cell counts were associated with eIS in children and youth with T1DM. Across BMI, age, and sex strata, eosinophils consistently showed modest-to-moderate positive associations with eIS, whereas monocytes, neutrophils, lymphocytes, and platelets showed negative associations that varied by subgroup. In overall cohort, neutrophils and lymphocytes demonstrated statistically significant but minimal negative associations. The development of double diabetes may occur independent of obesity and the cellular patterns observed paralleled those reported in non-obese populations. Larger studies are warranted to confirm these findings and to identify population-specific cellular correlates of declining insulin sensitivity in T1DM. Children and youth with type 1 diabetes exhibit normal-to-low BMI yet low estimated insulin sensitivity. Peripheral blood cell counts associate with estimated insulin sensitivity in children and youth with type 1 diabetes. Eosinophils associate positively, whereas neutrophils, lymphocytes, and platelets associate negatively with insulin sensitivity, with extent of association varying by age, sex, and BMI.
Single nucleotide polymorphisms (SNPs) have been associated with BMD and bone fracture risk. The aim of this study was to assess the possible association between FRAX scores and specific SNPs in Italian osteopenic and osteoporotic postmenopausal women. We enrolled 54 postmenopausal women with osteoporosis or osteopenia. FRAX (a computer-based free algorithm that provides the 10-year probability of fractures on the basis of classic risk factors) and BMD were obtained in every patient. We included 13 SNPs in the ESR1, OPG, RANK-L, VDR, PTH, CASR, COL1A1, CALCR, ACTN3 and TPRV6 candidate genes. We tested the association of principal component analysis scores based on individual multi-locus genotypes with FRAX. A FRAX_M > = 20
Parathyroid carcinoma is a rare endocrine malignancy with limited therapeutic options. Immune checkpoint blockade targeting the PD-1/PD-L1 axis has transformed the management of several solid tumors; however, its role in parathyroid carcinoma remains largely unexplored. Given that the response to immunotherapy is influenced not only by PD-L1 expression but also by the tumor immune microenvironment (TIME), characterization of the immune landscape in parathyroid carcinoma may provide insights into its potential therapeutic vulnerability. To evaluate PD-L1 expression and comprehensively characterize the tumor immune microenvironment in parathyroid carcinoma, enabling identification of features predictive of immunotherapeutic responsiveness. Using immunohistochemistry and multiplex immunofluorescence, this ambispective study investigated parathyroid carcinoma, parathyroid adenoma, and normal parathyroid tissues for PD-L1 expression (clone SP263, Ventana), infiltrating immune cells, namely cytotoxic T lymphocytes (CTLs; CD3⁺CD8⁺), regulatory T cells (Tregs; CD4⁺CD25⁺FOXP3⁺), and monocytic myeloid-derived suppressor cells (MDSCs; CD11b⁺CD14⁺). Immune cell densities were quantified per mm², and the TIME was categorized into four types based on PD-L1 expression and the presence of CTLs: Type I (PD-L1⁺/CTL-rich, adaptive immune resistance), Type II (PD-L1⁻/CTL-poor, immune ignorance), Type III (PD-L1⁺/CTL-poor, intrinsic induction), and Type IV (PD-L1⁻/CTL-rich, immune tolerance). While 30
Ultrasound-guided thermal ablation (U-GTA) techniques, including radiofrequency ablation (RFA) and microwave ablation (MWA), have recently been proposed as minimally invasive alternatives to surgery or radioiodine (RAI) therapy for patients with Graves’ disease (GD) who are unresponsive to antithyroid drugs. However, evidence supporting its effectiveness and safety remains limited. A PubMed/MEDLINE, Web of Science, and Scopus research updated until January 31, 2026, was performed. The review question was: What is the euthyroidism rate (outcome) one year after U-GTA (intervention) in Graves’ disease (population)? Two reviewers independently conducted the study screening, data extraction, and risk of bias assessment. A random-effects model was adopted to pool the prevalence with corresponding 95
Ultrasound-guided thyroid needle procedures, including fine-needle aspiration (FNA), percutaneous ethanol injection (PEI), and thermal ablation, are widely regarded as safe and effective. Infectious complications are exceptionally rare and may be underrecognized because their presentation can overlap with expected post-procedural inflammatory reactions or aseptic nodule rupture. We performed a focused narrative review of reported infections following thyroid needle procedures, examining their clinical presentation, microbiological findings, risk factors, and management. Published cases indicate that infections may occur after FNA, PEI, and thermal ablation, with considerable heterogeneity in timing, clinical severity, microbiological findings, and therapeutic approach. Reported management strategies range from antibiotic therapy alone to image-guided drainage or surgery, and no standardized treatment pathway is currently available. Early recognition, careful clinical and ultrasound assessment, and management tailored to disease severity are essential to limit progression to abscess formation or local and systemic complications. Greater awareness of these uncommon events may facilitate timely diagnosis and reduce both adverse outcomes and unnecessary interventions.
Selective use of radioactive iodine is advocated in recent guidelines. We aimed to characterize clinical practice and factors associated with its prescription in low- or intermediate-risk differentiated thyroid cancer patients among Spanish physicians. A cross-sectional survey was conducted in 2022 among Spanish physicians. The survey assessed preferences for radioactive iodine administration in different differentiated thyroid cancer clinical scenarios with excellent response to surgery. Ninety-six responses were received. In low-risk differentiated thyroid cancer, radioactive iodine was most often used to facilitate follow-up (40
