Search Results (341)

Key mechanisms underlying immune thrombocytopenia (ITP) pathophysiology include impaired platelet production and macrophage-mediated platelet destruction, the latter of which is the disease driver in more than half of patients. Traditional sequential treatment approaches achieve suboptimal responses in many patients. This review summarizes ITP pathogenesis and the treatment landscape and proposes a personalized treatment approach for ITP after first-line treatment (corticosteroids, intravenous immunoglobulin, anti-D therapy) based on targeting underlying disease mechanisms with immunomodulatory and bone marrow-supportive therapies (fostamatinib, rituximab, and thrombopoietin receptor agonists [TPO-RAs]) prior to proceeding to later-line therapies. Clinical evidence of monotherapy and real-world studies of combination therapy are reviewed to support mechanism-based treatment selection, focusing on the complementary actions of fostamatinib (to target platelet destruction) and TPO-RAs (to stimulate platelet production). In prior studies, fostamatinib with or without TPO-RAs demonstrated durable platelet responses and manageable safety as second-line or later ITP treatment. The proposed treatment framework augments guidelines by recommending fostamatinib, rituximab, or TPO-RAs as second-line therapy options based on patient-specific disease characteristics and risks. Patients with inadequate response to fostamatinib or TPO-RA monotherapy may combine these therapies to address both platelet destruction and platelet production deficits. This novel framework tailors therapy to patient-specific pathophysiology by preferentially targeting both impaired platelet production and increased platelet destruction to support individualized care. Full article

Background/Objectives: Dendritic cells (DCs) are key regulators of immune responses in cardiovascular disease, yet their role in platelet homeostasis and thrombopoiesis remains incompletely understood. We previously demonstrated that chronic depletion of CD11c⁺ cells accelerates atherosclerotic plaque development. The objective of this study was to determine whether sustained loss of CD11c⁺ cells alters platelet production and systemic inflammatory signaling under atherogenic conditions. Methods: CD11c-DTR bone marrow chimeric mice on ApoE⁻/⁻ background were generated and fed a high-cholesterol diet. CD11c⁺ cells were depleted by repeated diphtheria toxin administration over six weeks. Circulating platelet counts were quantified by automated hematology analysis. Systemic inflammatory changes were assessed using serum cytokine and chemokine profiling, and serum thrombopoietin (TPO) levels were measured by ELISA. Results: Chronic CD11c⁺ cell depletion resulted in a significant increase in circulating platelet counts in ApoE⁻/⁻ mice. Serum cytokine profiling revealed broad inflammatory remodeling, including increased levels of cytokines associated with megakaryopoiesis and platelet activation, such as IL-4, MCP-1, CXCL9, IL-16, and IL-1α. In parallel, serum TPO levels were significantly elevated following CD11c⁺ cell depletion. Conclusions: In the specific context of hyperlipidemic CD11c-DTR bone marrow chimeric mice, these findings demonstrate that loss of CD11c⁺ cells is associated with a pro-thrombopoietic shift, elevated platelet counts, and systemic inflammatory changes. Our data identify a CD11c⁺ cell–TPO–platelet axis linking immune regulation to platelet homeostasis and thrombo-inflammatory signaling under these specific atherogenic conditions. Full article

Background: Endocrine disturbances are increasingly recognized as components of long COVID, yet long-term data remain limited. This study evaluated the prevalence of dysglycemia and thyroid autoimmunity four years after SARS-CoV-2 infection in adults without previously known endocrine disease. Methods: We conducted a retrospective longitudinal 4-year evaluation of adults hospitalized for COVID-19 between 2020 and 2021. Of 1009 eligible patients without prior diabetes or thyroid disease, 96 completed a standardized 4-year post-infection evaluation. Acute-phase data included COVID-19 severity, admission glucose, inflammatory markers, imaging findings, and treatments. The 4-year evaluation comprised fasting plasma glucose, thyroid function tests, anti-thyroid antibodies (anti-TPO, anti-Tg), and thyroid ultrasonography. Baseline HbA1c, thyroid autoantibodies, and thyroid imaging were not available. Results: At four years post-infection, 27.1% of patients exhibited dysglycemia compatible with type 2 diabetes mellitus, 41.6% showed thyroid autoimmunity, and 15.6% presented with both conditions. Overall, 47.9% developed at least one endocrine alteration. Admission hyperglycemia strongly predicted long-term dysglycemia (OR 6.67; 95% CI: 1.45–30.58), and diabetes prevalence increased with acute disease severity. Thyroid autoimmunity was frequent but not associated with initial COVID-19 severity. Conclusions: Four years after SARS-CoV-2 infection, a substantial proportion of patients exhibited persistent metabolic and autoimmune alterations, supporting a long COVID immunometabolic phenotype. In the absence of baseline endocrine data, the reported findings reflect long-term endocrine alterations identified at the 4-year evaluation, with a potential role of SARS-CoV-2 infection. These findings highlight the importance of baseline metabolic and thyroid assessment—including HbA1c and thyroid autoantibodies—in hospitalized COVID-19 patients and underscore the need for structured long-term endocrine monitoring. Full article

Background: Thyroid hormones regulate energy homeostasis, lipid/glucose metabolism, and protein turnover. Chronic Hepatitis C Virus (HCV) infection is highly associated with autoimmune hypothyroidism, which may have profound metabolic implications. This study evaluates thyroid dysfunction and anti-thyroid peroxidase (anti-TPO) autoimmunity in HCV patients and explores its potential metabolic implications in a high-prevalence region. Methods: In this comparative cross-sectional study adhering to STROBE guidelines, we enrolled 100 PCR-confirmed chronic HCV patients and 100 age/gender-matched controls from District Peshawar, Pakistan. Serum TSH, fT3, fT4, and anti-TPO antibodies were quantified. Multivariable logistic regression, adjusted for age, gender, and viral load, was used to compute adjusted odds ratios (aOR) with 95% confidence intervals (CI). Results: Thyroid dysfunction affected 41% of HCV patients vs. 12% of controls (aOR 5.2, 95% CI 2.8–9.6, p < 0.001), predominantly hypothyroidism (29% overall; 18% overt, 11% subclinical). Anti-TPO positivity was 38% in HCV vs. 8% in controls (aOR 6.7, 95% CI 3.1–14.5, p < 0.001). Anti-TPO titers correlated positively with TSH (r = +0.62, p < 0.001) and inversely with fT3/fT4. Subgroup analysis showed higher dysfunction in patients aged ≥40 years (52% vs. 28%, p = 0.012) and viral load ≥ 10⁶ IU/mL (48% vs. 32%, p = 0.041). We hypothesize that these findings may have significant metabolic implications, including impaired mitochondrial β-oxidation and insulin resistance. Conclusions: HCV infection is strongly associated with autoimmune hypothyroidism, which may amplify cardiometabolic risk. The paper has not explicitly identified metabolic parameters, including lipid profiles, indices of insulin resistance, and metabolomic signatures, and, therefore, any metabolic inferences are speculative and based on established thyroid and HCV pathophysiology. Routine thyroid screening pre- and post-DAA therapy is recommended, alongside metabolomic profiling to validate these proposed metabolic pathways. Full article

Background: Hashimoto’s thyroiditis (HT) is a prevalent autoimmune disorder, often diagnosed late due to its asymptomatic or nonspecific presentation. Emerging evidence suggests that gut-derived lipopolysaccharides (LPS) may contribute to autoimmune activation. Objective: The primary objective of this study was to assess circulating LPS concentrations and dietary patterns in patients with Hashimoto’s thyroiditis compared to healthy controls. Methods: A hospital-based case–control study was conducted involving 105 HT patients and 25 healthy controls. Serum LPS concentrations, thyroid hormone profiles, and autoantibody levels were assessed. Dietary patterns were evaluated using the validated KomPAN questionnaire. Results: HT patients exhibited significantly higher serum LPS levels, particularly those with elevated anti-TPO and TRAB antibodies. A positive correlation was found between LPS and the fT3/fT4 ratio (r = 0.247, p = 0.006), and a negative correlation with fT4 (r = −0.314, p < 0.001). Dietary analysis revealed lower Pro-Healthy Diet Index scores in HT patients (3.94 vs. 5.34, p = 0.001), with increased consumption of processed foods and reduced intake of whole grains and oats. Conclusions: Elevated levels of lipopolysaccharides (LPS) and unhealthy dietary patterns may play a role in the development of thyroid autoimmunity. Taken together, these observations are consistent with a multifactorial model that potentially involves gut barrier dysfunction, endotoxemia, and nutritional factors in HT pathogenesis. Full article

Background: Hashimoto’s thyroiditis (HT) is the result of a complex interplay between genetic, environmental, and epigenetic factors. The role of cellular and humoral immunity in the pathogenesis of the disease is well-established. Inflammatory infiltration of T and B lymphocytes is a key feature identified on ultrasound examination. The lack of data on the effect of L-thyroxine (LT-4) doses on the level of anti-TPO and anti-TG antibodies in Hashimoto’s thyroiditis and the relationship with anthropometric measurements resulted in the desire to fill this niche. Methods: A total of 70 Caucasian patients diagnosed with Hashimoto’s thyroiditis within the past two years were examined. The participants were divided into three groups based on their L-thyroxine dosage (≤50, 50–100, >100 μg). Results: The results revealed no correlation between the dosage of L-thyroxine and anthropometric measurements (age, height, body weight, and body fat content). No correlation was identified between the levels of anti-TPO and anti-TG and the dose of L-thyroxine in patients with Hashimoto’s thyroiditis. Conclusions: The mechanism regulating the levels of anti-TPO and anti-TG appears to be associated with a more advanced thyroid inflammation and disease process. Long-term observation of patients would be advisable. We present evidence of no effect of hormone dose on antibody levels in Hashimoto’s thyroiditis. Regardless of disease severity, immune regulation remains outside the scope of hormonal regulation. Full article

Down Syndrome (DS) is the most common chromosomal abnormality characterized by neurodevelopmental impairment. Apart from maternal age, its risk factors remain poorly understood. This prospective case-control study aimed to evaluate the role of maternal anti-zona pellucida (ZP) antibodies (Ab) and anti-thyroid-Ab in predicting DS. Correlations of anti-ZP-Ab and anti-thyroid-Ab with maternal age were also assessed. Anti-ZP-Ab were measured after childbirth using ELISA. Anti-thyroid peroxidase (aTPO) and anti-thyroglobulin (aTgII) antibodies were also analysed with the Allelica IM platform. Statistical analyses included receiver operating characteristic curve assessment, expressed as area under the curve (AUC) and linear regression modeling. Between September 2020 and October 2022, 58 women were enrolled. Anti-ZP-Ab levels were significantly higher in women with DS pregnancy with an odds ratio adjusted for maternal age of 71.52 (95% CI: 7.05–725.18) and an excellent predictive performance (AUC = 0.94; 95% CI: 0.88–1.00). For optical density levels > 1, the accuracy was 89.7% (95% CI: 78.2–100.0). No statistically significant differences were observed for aTPO and aTgII. Neither Anti-ZP-Ab nor anti-thyroid antibodies increased with age. These findings suggest that Anti-ZP-Ab are strongly associated with DS risk, suggesting a potential age-independent autoimmune contribution to trisomy 21. Their evaluation may support preconception counseling, especially for women aged > 35 years. Future studies could clarify causality and define the role of maternal autoimmunity in DS etiology. Full article

Background/Objectives: Thyroid eye disease (TED) can lead to structural and microvascular changes in the orbit and retina. This study aimed to investigate the associations between Clinical Activity Score (CAS), orbital magnetic resonance imaging (MRI) measurements, and retinal microvascular changes in TED patients. Methods: This cross-sectional study included 38 patients (76 eyes) with TED. Each patient underwent a comprehensive ophthalmological evaluation, CAS assessment, and a detailed medical history. Optical coherence tomography angiography (OCTA) was performed to quantify vessel density (VD) in the superficial and deep capillary plexus (SCP and DCP). Exophthalmos, extraocular muscle thickness and orbital fat thickness were measured on MRI scans to evaluate structural changes. Laboratory analyses included thyroid hormone levels, thyrotropin receptor antibodies (TRAb), anti-thyroid peroxidase antibodies (anti-TPO), and lipid profile. Results: Active TED patients (CAS ≥ 3) had significantly higher TRAb levels (p < 0.001), while anti-TPO did not differ between groups. Active eyes showed significantly higher DCP VD in the whole image (p = 0.013), parafovea (p = 0.012), and perifovea (p = 0.009) across all quadrants, with no difference in SCP or the foveal avascular zone (FAZ). In linear mixed model regression analyses, after adjusting for previous glucocorticosteroid therapy, higher triglycerides, greater medial rectus thickness, and whole-image DCP VD independently predicted higher CAS values (R² = 42, p < 0.001). After adjusting for age and sex, CAS remained significantly positive predictor of DCP VD in the parafovea (R² = 0.22, p < 0.001). Conclusions: Changes in DCP VD reflect TED activity and structural orbital involvement. Full article

Background and clinical significance: Idiopathic hypertrophic pachymeningitis (IHPM) is a rare inflammatory disorder characterized by diffuse or focal dural thickening and heterogeneous presentations. We report a corticosteroid-responsive IHPM with elevated anti-thyroglobulin (anti-Tg) antibodies despite oncologic control after thyroidectomy. This case suggests that systematic assessment for autoimmunity should be a standard component of the IHPM work-up. Case presentation: A 77-year-old woman presented with recurrent vertigo, imbalance, and headaches. Brain MRI showed diffuse pachymeningeal thickening with mild heterogeneous enhancement, radiologically stable over >2 years. Extensive evaluation excluded infectious, neoplastic (including paraneoplastic), cerebrospinal fluid hypotension and systemic autoimmune causes; findings did not support IgG4-related disease. Thyroid work-up revealed hypothyroidism with multinodular goiter; total thyroidectomy was performed, and there was no indication for adjuvant radioiodine therapy. Despite oncologic control, anti-Tg antibodies remained markedly elevated, while anti-thyroid peroxidase antibodies (anti-TPO) declined. Symptoms repeatedly improved with oral methylprednisolone and recurred on taper; adverse effects were mild and manageable. The patient remains under clinical and oncologic surveillance with symptom-guided steroid re-challenge. Conclusions: IHPM may exhibit a dissociation between clinical response and radiologic course. Persistently elevated anti-Tg after thyroidectomy can coexist with IHPM and may signal ongoing autoimmunity rather than active cancer. Full article

The sodium iodide symporter (NIS) is a key protein in thyroid function responsible for iodine uptake, and it may be involved in the pathogenesis of autoimmune thyroiditis. However, it is also expressed in the salivary glands, the primary target of autoreactive cells in Sjögren’s syndrome (SS). Given the common link between the two diseases, we computationally investigated whether the epitopes of NIS can trigger an immune response leading to SS in Hashimoto’s thyroiditis (HT) patients genetically predisposed to both diseases. The TepiTool 2016, ABCpred 2006, and DiscoTope 2.0 servers were used to predict T-cell and B-cell epitopes by inputting the FASTA sequences and 3D structures of NIS, thyroid peroxidase (TPO) and Ro60 Y RNA-binding protein (Ro60), which served as reference antigens for HT and SS, respectively. T-cell epitopes were selected based on their binding to a panel of human leukocyte antigen (HLA) alleles associated with both SS and HT. We identified a total of 376 linear T-cell epitopes, 64 linear B-cell epitopes and 68 conformational B-cell epitopes of NIS. Compared to TPO, NIS T-cell epitopes showed significantly lower affinity for HLA alleles (p < 0.0001), while no significant difference was found compared to Ro60. While linear B-cell epitopes of NIS, TPO, and Ro60 showed similar binding affinity, conformational epitopes of NIS were predicted to have higher immunogenicity than Ro60 (p = 0.04), while no significant difference was found compared to TPO. These pivotal findings, discovered by the methods of computer modeling, suggest that NIS can potentially activate T cells and B cells in patients with genetic predisposition to SS and HT and need to be confirmed by further laboratory studies. Full article

Background/Objectives: Iodine plays a key role in thyroid hormone synthesis and metabolic regulation in vertebrates. This study aimed to evaluate the in vivo bioavailability of iodine and assess selected biochemical parameters and thyroid-related gene expression in male Wistar rats fed lettuce (Lactuca sativa L.) biofortified with iodoquinolines (8-hydroxy-7-iodo-5-quinolinesulfonic acid or 5,7-diiodo-8-quinolinol) or potassium iodate. Methods: Two iodine intake levels were applied, a nutritionally adequate iodine level and a supranutritional level, to evaluate the nutritional safety of iodine obtained from biofortified vegetables. Results: A diet containing lettuce biofortified with iodoquinolines at the adequate level had no significant effect on thyroid hormone concentrations, the expression of Dio1, Dio2, Slc5a5, and Tpo genes, or thyroid morphology. While supranutritional iodine intake led to increased levels of T4, fT4, T3, and fT3, all hormone concentrations remained within the physiological range. No elevation in liver enzyme activity (ALT, AST, ALP) was observed, indicating the absence of hepatotoxic effects from high-iodine diets based on biofortified lettuce. Compared to potassium iodate, iodoquinolines demonstrated superior bioavailability, as evidenced by enhanced iodine accumulation in tissues and more efficient thyroid hormone synthesis. Conclusions: To the best of our knowledge, this is the first in vivo nutritional study assessing the physiological effects of supranutritional iodine intake from a biofortified plant source. These findings confirm the nutritional safety and efficacy of iodine biofortification using iodoquinolines and highlight the need for further research, including human nutritional clinical trials. Full article

Background/Objectives: Arteriovenous malformations (AVMs) in the dominant temporo-parieto-occipital (TPO) junction of the brain are extremely rare and very difficult to remove surgically because this area includes multiple sensory and language networks. Due to the fact that many patients present with bleeding, surgeons have to find a delicate balance between removing all of the AVM tissue and preserving the functional areas of the brain where important functions occur. This study is reporting a case demonstrating how precise clinical–radiologic correlation, detailed anatomical knowledge, and deliberate microsurgical techniques can allow safe removal of the AVM and improve the patient’s neurologic function without the need for additional intraoperative technology. Case Presentation: A 47-year-old right-handed male patient experienced persistent neurological deficits after experiencing a hemorrhage from an AVM in his dominant posterior hemisphere, which included mild language difficulties, right hemifacial–brachial spasticity, parietal sensory loss and a visual field defect of his right eye known as an inferior quadrantanopia localized to the TPO junction. Cerebral angiography identified a small, compact, high-flow AVM (40 × 30 mm) fed by distal branches of the middle cerebral artery (M4), posterior cerebral artery (P4), anterior cerebral artery (A4), as well as a small branch of the superior cerebellar artery (SCA). Blood drained into two veins of the Trolard and Labbé. The authors removed the AVM completely by circumferential dissection of the nidus along gliotic planes using a microscope. Feeders were then sequentially disconnected, and the venous outflow was preserved until the AVM could be removed en bloc. Post-operative angiograms demonstrated complete removal of the AVM with normalization of blood flow to the surrounding cortex. The patient’s neurologic function improved over time and at three months post-operatively, he was functioning independently (modified Rankin Scale = 1; Barthel Index = 100) and there was no evidence of residual nidus or edema on imaging. Conclusions: High-flow AVMs in the dominant TPO junction can be completely removed using a disciplined microsurgical approach and a feeder first/vein last disconnection method based on anatomy. The patient’s improvement in function represented reperfusion and reintegration of an injured but still functional network of the brain, reinforcing the idea that careful observation, a deep understanding of brain anatomy, and restrained surgical technique are critical to achieving long-term results in AVM surgery. Full article

Chronic low-grade inflammation is a central contributor to the development of cardiovascular disease, metabolic dysfunction, autoimmune disorders, and cognitive decline. Blood-based biomarkers, such as C-reactive protein (CRP), ferritin, homocysteine, white blood cell (WBC) count, and anti-thyroid peroxidase (anti-TPO) antibodies enable quantification and monitoring of systemic inflammation over time. We aimed to evaluate the impact of a 12-week personalized, biomarker-guided supplementation program including micronutrients, hormone support, and peptides on inflammatory and immune-related biomarkers across age- and sex-stratified adult cohorts. Participants (n = 48; 8 per group) were stratified by sex and age (40–49, 50–59, 60–69 years) and underwent blood testing at baseline and 12 weeks. Personalized protocols were developed based on individual biomarker profiles and included targeted interventions with vitamin D, omega-3 fatty acids, B vitamins, zinc, selenium, hormone optimization, and other supportive agents. Primary outcomes were percent changes in CRP, ferritin, homocysteine, WBC count, and anti-TPO antibody levels. CRP levels decreased by 33–46% across all groups, with similarly consistent declines in homocysteine (29–37%) and WBC count (22–28%). Ferritin reductions were most notable in men, particularly in older age groups (up to 48%), while anti-TPO antibody levels declined more prominently in women (up to 22%). These changes are consistent with reduced systemic inflammation, improved methylation status, and potential modulation of autoimmune activity. This biomarker-guided, personalized supplementation protocol was associated with clinically meaningful reductions in key markers of inflammation and immune dysregulation. These findings are suggestive of potential efficacy for precision-based health optimization programs and highlight the need for larger randomized controlled trials (RCTs) to confirm causal effects. Full article

Deep alterations in tumor cell gene profiles resulting in the loss of their specific functions are frequently the cause of resistance to traditional cancer treatments. Therefore, reprogramming the expression pattern of cancer cells toward a differentiated phenotype represents a promising therapeutic strategy. In this study, we investigated whether resveratrol (RSV) and its natural analogs—3,4′,5-trimethoxystilbene (3-MET-OX) and isorhapontigenin (ISOR-H-PG)—can modulate the SOX2/SOX17 balance and promote re-differentiation in anaplastic thyroid cancer (ATC) cells. Two human ATC cell lines (SW1736 and 8505c) and non-tumoral thyroid cells (Nthy-ori 3-1) were cultured in two-dimensional (2D) or three-dimensional (3D) systems and treated with polyphenols at sub-cytotoxic doses. In 2D cultures, cell viability and cell cycle analyses confirmed a cytostatic effect characterized by G1 arrest. In 3D cultures, polyphenol treatment caused morphological disruption of ATC spheroids and significantly modulated the gene expression profile. RSV and 3-MET-OX reduced stemness markers (SOX2, NANOG), increased the thyroid lineage transcription factor (SOX17), and enhanced differentiation genes (TTF-1, TPO, NIS). Overall, these results support our hypothesis that modulation of the SOX2/SOX17 ratio by polyphenols provides a mechanistic basis for re-differentiation, thereby improving therapeutic responsiveness in ATC. Full article

Background/Objectives: While it is known that Hashimoto’s thyroiditis (HT), goiter, thyroid nodules, and thyroid dysfunction may affect women’s reproductive health through hormonal and metabolic mechanisms, data are limited regarding the specific impacts on female sexual function. This study evaluated sexual function in women with thyroid disorders and examined its associations with thyroid function, age, menopausal status, and body mass index (BMI). Methods: A population-based survey was conducted in Kaunas, Lithuania, within the WHO MONICA framework. A random sample of 1569 women aged 25–69 years was included in the final analysis after applying the exclusion criteria. Anthropometric measurements were taken using standardized procedures, and the BMI was calculated. Sexual function was assessed using the 19-item Female Sexual Function Index (FSFI). Thyroid structure was evaluated by a team of trained physicians using ultrasound, while thyroid function was assessed via serum analysis (ELISA-based assays for TSH, fT4, and anti-TPO antibodies). Results: Of the 1569 women analyzed, 64.1% had sexual dysfunction (SD) (FSFI ≤ 26.55). Age and BMI showed significant negative correlations with all FSFI domains, with the strongest associations for arousal, lubrication, and total FSFI score (p < 0.01). SD was more prevalent among postmenopausal (43.6%) women than in premenopausal women (22.6%, p < 0.001) and increased with a higher BMI (p < 0.001). HT was found in 28.3% of participants. Compared with the reference group, women with HT were older, had higher BMI, higher TSH levels, and more hypothyroidism (p < 0.001). SD was more common in the HT group (71.7% vs. 64.2%, p < 0.001), with significantly lower lubrication and higher pain scores. In the multivariate analysis, only goiter remained an independent predictor of SD (p = 0.04). Conclusions: In conclusion, women with HT were older; had a higher BMI; and more frequently experienced SD, particularly reduced lubrication and increased pain, compared with the reference group. Although several thyroid conditions were associated with sexual dysfunction, only goiter remained an independent predictor after adjusting for age and BMI. Full article