Search Results (213)

Background/Objectives: SA001, a mofetil-ester prodrug of rebamipide, was developed to enhance gastrointestinal absorption and systemic exposure, which was confirmed in a prior Phase 1 study. Given the limited efficacy of current symptomatic therapies for primary Sjögren’s syndrome (pSS), this trial aimed to assess whether the improved bioavailability of SA001 could translate into clinical benefits. Methods: This multicenter, randomized, double-blind, placebo-controlled Phase 2a study enrolled adults who met the 2016 ACR–EULAR criteria for pSS. The participants were randomly assigned to one of four groups: SA001 at 360, 720, or 1080 mg/day (administered twice daily for 8 weeks) or placebo. Exploratory ocular assessments included tear break-up time, ocular surface staining, the Schirmer test, and the Standard Patient Evaluation of Eye Dryness. Oral endpoints included unstimulated whole salivary flow and the Xerostomia Inventory. Anti-SSA(Ro) antibodies were assessed both quantitatively and qualitatively. Safety evaluations comprised adverse events (AEs), ophthalmic examinations, laboratory tests, and vital signs. The efficacy outcomes were exploratory, and this study was not powered to formally test efficacy hypotheses. Results: Twenty-eight women (mean age 58.54 ± 9.29 years; range 41–75 years) were enrolled in this study and randomly assigned to one of the study groups. SA001 showed no statistically significant improvements versus placebo in ocular or oral endpoints, and no consistent dose–response relationship was observed. The anti-SSA(Ro) findings did not differ meaningfully across the groups. SA001 was generally well-tolerated, with infrequent, mostly mild-to-moderate AEs; however, one serious AE occurred in the placebo group. No clinically relevant ophthalmic or laboratory safety signals were detected. Conclusions: Despite the fact that markedly increased systemic exposure has been demonstrated previously, SA001 did not improve the dryness outcomes in pSS. These findings suggest that systemic exposure alone may be insufficient in established glandular disease and highlight the need for tissue-exposure-driven strategies and biomarker-informed patient selection in future studies. Predefined primary efficacy endpoints and objective, gland-proximal measures of target engagement (e.g., standardized salivary gland ultrasonography and salivary or tear fluid biomarker assessments) may help to better interpret local pharmacodynamic activity and the likelihood of a clinically meaningful benefit. Full article

Vitamin D is well established for its skeletal effects, being a cornerstone of several endocrine disorders. In recent years, it has come under investigation as a potential disease-modifying drug in several endocrine disorders through its immune modulatory and anti-tumorigenic action, particularly in thyroid disease, gynecologic disorders, and general fertility. Vitamin D supplementation is well established in the treatment of osteoporosis, osteomalacia, hypoparathyroidism, and primary hyperparathyroidism. In autoimmune thyroid disease, there is a negative correlation between 25(OH)D3 levels and prevalence. Currently available data are inconclusive on supplementation as a disease-modifying treatment. In Hashimoto’s thyroiditis, while some found improved thyroid function, a decline in progression, and antibody titers, these findings were not consistent, and some found no improvements. Painless postpartum thyroiditis severely lacks evidence. Interventional studies failed to demonstrate benefits in Graves’ disease. The literature consistently reports lower vitamin D levels in infertility, polycystic ovarian syndrome (PCOS), and endometriosis. In PCOS, data suggest that vitamin D supplementation is beneficial; however, results in exact benefits vary and there is no consensus on dosing. Current guidelines support supplementation as part of preconception nutritional care. In general, for female infertility and endometriosis, the results are conflicting, with a lack of high-quality evidence. The literature suggests there is a possible benefit regarding sperm motility, but not in testosterone levels for males. In conclusion, while in vitro studies and animal models are promising, the available evidence is often contradictory, with high heterogeneity in study designs and populations. Our paper highlights the need for further high-quality research to resolve current controversies. Full article

Background: Children with congenital heart disease (CHD) are at substantially increased risk for respiratory infections, which occur more frequently and with greater severity than in healthy peers. This heightened vulnerability stems from multifactorial immune impairment, including defects in innate and adaptive immunity, chronic inflammation related to abnormal hemodynamics and hypoxia, reduced thymic function, and genetic syndromes affecting both cardiac and immune development. Viral pathogens—particularly respiratory syncytial virus (RSV), influenza viruses, and SARS-CoV-2—account for most infections, although bacterial pathogens remain relevant, especially in postoperative settings. Methods: This narrative review summarizes current evidence on infection susceptibility in children with CHD, the epidemiology and clinical relevance of major respiratory pathogens, and the effectiveness of available preventive measures. Literature evaluating immunological mechanisms, infection burden, vaccine effectiveness, and passive immunization strategies was examined, along with existing national and international immunization guidelines. Results: Children with CHD consistently exhibit higher rates of hospitalization, intensive care unit admission, mechanical ventilation, and mortality following respiratory infections. RSV, influenza, and SARS-CoV-2 infections are particularly severe in this population, while bacterial infections, though less common, contribute substantially to postoperative morbidity. Preventive options—including routine childhood vaccines, pneumococcal and Haemophilus influenzae type b vaccines, influenza vaccines, COVID-19 mRNA vaccines, and RSV monoclonal antibodies—demonstrate strong protective effects. New long-acting RSV monoclonal antibodies and maternal vaccination markedly enhance prevention in early infancy. However, vaccine coverage remains insufficient due to parental hesitancy, provider uncertainty, delayed immunization, and limited CHD-specific evidence. Conclusions: Respiratory infections pose a significant and preventable health burden in children with CHD. Enhancing the use of both active and passive immunization is essential to reduce morbidity and mortality. Strengthening evidence-based guidelines, improving coordination between specialists and primary care providers, integrating immunization checks into routine CHD management, and providing clear, condition-specific counseling to families can substantially improve vaccine uptake and clinical outcomes in this vulnerable population. Full article

Background/Objectives: Primary steroid-resistant nephrotic syndrome (SRNS) in children is an ominous diagnosis due to limited therapeutic options and poor prognosis. The younger the child, the greater the probability of a genetic etiology which is typically resistant to immunosuppressive therapy. International guidelines recommend genetic testing and a search for rare infectious causes in the youngest age group. When no identifiable etiology is found, an immunologic cause of SRNS is suspected, with few therapeutic options available, which lately have included anti-CD20 therapy for children > 7 years of age. This is the first report on the successful use of obinutuzumab in a very young child with primary SRNS. Methods: Two consecutive doses of obinutuzumab, a humanized anti-CD20 antibody (300 mg/m² BSA), were administered two weeks apart to a 24-month-old boy with severe, complicated SRNS which had been refractory to cyclosporin A and rituximab and in whom previous genetic testing and a search for multiple infectious causes had been negative. Results: Complete remission of severe nephrotic syndrome was achieved 2 months after the last infusion with, to date, sustained resolution of proteinuria and normal serum albumin levels without further use of IMS drugs and no severe adverse effects noted. Conclusions: Obinutuzumab may be a rescue option for severe, multidrug-resistant ISN, even in young children, when no other therapeutic options are available. Full article

Polyneuropathy is a common condition that limits the quality of life among patients with primary Sjögren disease (pSjD). Somatic sensory fiber neuropathy involving small myelinated (A-δ) and unmyelinated C fibers may precede the development of sicca syndrome. The cutaneous silent period (CSP) is an inhibitory spinal reflex that can be used as a tool for evaluating the dysfunction of A-δ fibers. This study sought to examine CSP parameters, and their correlates, in patients with pSjD vs. healthy controls. We recruited 134 consecutive patients with a diagnosis of pSjD, of whom 109 subjects were included in the analysis. Electrodiagnostic tests comprised a nerve conduction study (NCS) and CSP analysis, alongside laboratory tests and questionnaires (the ESSPRI and SF-36). The examination of the healthy control (HC) group consisted of 113 NCSs and CSP studies. NCS tests of the median nerve in both groups were within the normal range. Statistical analysis revealed a significant difference in CSP duration (p < 0.001), S1 latency (p < 0.001) and S2 latency (p < 0.001) between the pSjD and HC groups. We observed prolonged CSP duration in approximately 38% of patients with pSjD and prolonged S2 latency in 18.35%. Small A-delta fiber neuropathy was diagnosed in 38% (41 subjects) patients. A regression analysis of CSP parameters indicated an association between the age of patients and PM Scl-75 antibodies (ab) levels in the pSjD cohort. As a new, noninvasive method of assessing A-δ nerve fibers, CSP was found to have a relation to the age and PM Scl-75 antibodies in patients with pSjD. The utility and sensitivity of CSP as a test for screening A-δ fiber function require further investigation in large cohorts of the pSjD population. Full article

Background: Complete fetal atrioventricular block (CAVB) is a rare but life-threatening condition, occurring in approximately 1–2% of pregnancies associated with maternal anti-Ro/SSA antibodies. The transplacental migration of anti-Ro/SSA and anti-La/SSB antibodies damages the fetal cardiac system, leading to sustained bradycardia, cardiomyopathy, fetal hydrops, and intrauterine fetal demise. Despite the use of fluorinated corticosteroids or β-agonists, therapeutic efficacy remains limited once a complete block is established. Case Presentation: We present the case of a 35-year-old primigravida with a pregnancy achieved through in vitro fertilization (IVF). At 20 weeks of gestation, she was referred to our emergency unit due to persistent fetal bradycardia. Fetal echocardiography confirmed CAVB with a ventricular rate of 64 bpm. Maternal serologic testing was positive for anti-Ro/SSA and anti-La/SSB antibodies, suggesting an autoimmune etiology. Treatment with oral dexamethasone and salbutamol was initiated, but follow-up echocardiography at 24 weeks showed worsening cardiac status, including reduced ventricular rate of 59 bpm, cardiomegaly, and pericardial effusion. Intrauterine fetal death occurred at 25 weeks of gestation. Management and Outcome: Four months postpartum, the patient underwent a minor salivary gland biopsy. Histopathological evaluation confirmed the diagnosis of primary Sjögren’s syndrome. Conclusions: This case illustrates the severe consequences of autoimmune-mediated CAVB and the limited effectiveness of available treatments once a complete block has developed. It underscores the importance of early fetal rhythm surveillance and targeted maternal autoimmune screening—particularly before assisted reproduction, where structured preconception evaluation offers an opportunity for earlier recognition and risk stratification. Earlier detection may improve counseling and management strategies in future pregnancies. Full article

Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease characterized by progressive destruction of intrahepatic bile ducts. PBC encompasses several clinical subtypes, including classical AMA-positive PBC (90–95% of cases), AMA-negative PBC (5–10%), and overlap syndromes such as AIH-PBC. These subtypes exhibit distinct serological profiles, with AMA-negative cases often presenting PBC-specific antinuclear antibodies (anti-gp210, anti-sp100) and overlap syndromes demonstrating combined autoantibody patterns characteristic of both conditions. Autoantibodies serve as central biomarkers for diagnosis, prognosis, and understanding disease pathogenesis. This review provides a comprehensive overview of classical and emerging autoantibodies associated with PBC, including AMA-M2, anti-gp210, anti-sp100, anti-KLHL12, and anti-RPL30. We discuss their diagnostic significance across PBC subtypes, pathogenic implications, and potential utility in patient stratification and therapeutic monitoring. Recent evidence suggests that bile acid-induced neoantigen formation, rather than classical loss of immune tolerance, may drive AMA production. Advances in autoantibody profiling, including subclass-specific analysis and multi-marker panels, may pave the way for personalized medicine and improved outcomes in PBC. Full article

Background: Numerous studies have proved the efficacy of vaccination in reducing Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) transmission and the coronavirus disease (COVID-19) burden. However, even though the COVID-19 vaccination coverage is high for primary doses, a booster dose is needed to sustain protection. Continuing our previous research, this study evaluates the immunogenicity and safety of full and half doses of two COVID-19 booster vaccines, ChAdOx1-S (AstraZeneca) and BNT162b2 (Pfizer-BioNTech), in individuals primed with ChAdOx1-S. Methods: This study was an observer-blind randomized controlled trial to evaluate the immunogenicity and safety of half and full doses of two COVID-19 booster vaccine types, BNT162b2 and ChAdOx1-S, among fully vaccinated, ChAdOx1-S-primed individuals in Jakarta, Indonesia. A total of 329 participants were randomized to receive either full or half doses of the booster vaccines, namely the ChAdOx1-S and BNT162b2 COVID-19 vaccines. Immunogenicity was assessed through SARS-CoV-2 antibody titers and neutralizing antibodies (NAbs) at 28 days post-booster, while safety was monitored via adverse event reporting. Results: The results showed that both vaccines demonstrated increased geometric mean titers (GMTs) post-booster. In the ChAdOx1-S booster group, at the baseline visit (day 0) and third visit (day 28), no statistically significant differences in GMT between the half- and full-dose groups were observed (p = 0.970 and 0.539, respectively). In the BNT162b2 group, no statistically significant difference was noted at the baseline visit, while the full dose was higher than the half dose at 28 days (Day 28, p = 0.011). Surrogate virus neutralization tests (sVNTs) and NAbs assays also revealed no significant differences between the half and full dose groups for both the Wuhan strain and the Delta variant. The BNT162b2 group compared to the ChAdOx1-S group revealed a statistically significant increase in IgG levels compared to ChAdOx1-S, with p-values of <0.001 and <0.001 for the half dose and full dose, respectively. This was also reflected in the NAbs test results, where BNT162b2 showed significantly higher levels against both the Wuhan strain and Delta variant. Adverse events were predominantly mild: 79.6% (n = 86/108) in the ChAdOx1-S full-dose group, 75.4% (n = 43/57) in the ChAdOx1-S half-dose group, 84.2% (n = 101/120) in the BNT162b2 full-dose group, and 92.6% (n = 88/95) in the BNT162b2 half-dose group, with pain at the injection site being the most common local reaction and myalgia and headache the most frequent systemic reactions. One serious adverse event was reported, assessed as unrelated to the vaccine. Conclusions: This study confirms that half doses of ChAdOx1-S and BNT162b2 are as immunogenic and safe as full doses, and a heterologous booster is more immunogenic than a homologous booster. Full article

The use of highly active combined antiretroviral therapy (cART) has increased life expectancy in people living with HIV (PLWH). As a result of ongoing monitoring and surveillance in established HIV out-patient clinics, thyroid dysfunction amongst this population has become increasingly reported. In this narrative review, primary studies, case reports, and meta-analyses published on PubMed, Embase, and Cochrane were analysed. The most reported thyroid dysfunction is subclinical hypothyroidism (SCH). The prevalence of subclinical hypothyroidism was as high as 40% in PLWH with CD4 T-cell count < 350 cells/mm³, which is a level indicating a state of immunosuppression. Some less commonly reported thyroid dysfunctional conditions include overt hyperthyroidism and thyroid malignancy. Reports have linked the development of thyroid dysfunction to the use of cART, leading to immune reconstitution inflammatory syndrome (IRIS), which has also been linked to the development of Grave’s disease (GD). It is also important to check for thyroid malignancy, as PLWH are prone to having a high risk of developing non-AIDS-related or -defining cancer (NADC). Most research suggests symptom-driven monitoring. However, evidence also suggests that monitoring with cART status change, monitoring for patients with significant comorbidities, or with immune reconstitution may be useful. The screening should include Free Thyroxine (FT4), triiodothyronine (FT3), and thyroid-stimulating hormone (TSH) testing. Furthermore, vigilance for Grave’s disease and performing thyroid antibody checks are advised, especially once the reconstitution of T-cells is achieved. Full article

Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive non-Hodgkin lymphoma (NHL) worldwide. Currently, approximately sixty percent of patients are cured with R-CHOP as frontline treatment, while the remaining patients experience primary refractory or relapsed (R/R) disease. Recently, the introduction of Pola-R-CHP as front-line therapy has represented a major advance in the management of DLBCL, resulting in improved outcomes. Prognosis of R/R DLBCL patients is poor, particularly for those eligible neither for chimeric antigen receptor (CAR) T-cell therapy nor autologous stem cell transplantation (ASCT), representing a significant unmet clinical need. The advent of bispecific monoclonal antibodies (BsAbs), such as bispecific T-cell engagers (BiTEs), dual affinity retargeting (DART) molecules and IgG-like bispecific antibodies, offers a novel promising therapeutic approach in the treatment of DLBCL, both as frontline treatment and in the R/R setting. BsAbs simultaneously engage two different antigens, a tumor-associated antigen and an immune cell antigen, redirecting T-cells against malignant cells and enhancing the immune response. Most BsAbs developed for the treatment of NHLs engage T-cells via CD3 and malignant B-cells via CD20, a surface antigen expressed on most lymphomatous cells. Engagement of malignant B-cells by BsAbs activates T-cells, leading to the release of multiple cytokines and potentially to two characteristic adverse events: cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). The most extensively studied BsAbs, in both the frontline and relapsed/refractory (R/R) settings, include epcoritamab, glofitamab, mosunetuzumab, and odronextamab. Epcoritamab and glofitamab have received FDA and EMA approval for R/R DLBCL after two or more systemic line of therapies. EMA has also approved glofitamab in combination with gemcitabine and oxaliplatin (GemOx) for patients with R/R DLBCL ineligible for ASCT, whereas this indication has not been approved by FDA. Odronextamab is approved by EMA for R/R DLBCL and FL in patients who have received at least two prior lines of therapy, but it has not been approved by FDA. Mosunetuzumab is approved by both agencies—but only for R/R follicular lymphoma (FL). BsAbs represent a breakthrough therapy in the treatment of DLBCL, especially in R/R diseases. The purpose of this article is to review the landscape of BsAbs in DLBCL. Full article

Low-density lipoprotein receptor-related protein 5 (LRP5) is a multifunctional transmembrane coreceptor that plays a pivotal role in development and disease. Wnt/β-catenin signaling is the primary downstream signaling pathway activated by LRP5. Furthermore, some LRP5 functions are mediated by noncanonical pathways, such as AKT/P21 and TGF-β/Smad signaling. Pathologically, both loss-of-function and gain-of-function mutations in LRP5 produce distinct phenotypes, ranging from osteoporosis-pseudoglioma syndrome to high bone mass disorders. Beyond the skeletal system, LRP5 has emerged as a key regulator of retinal angiogenesis, vascular integrity, renal tubular function, neurodevelopment, and lipid metabolism. Its physiological functions are highlighted by its ability to influence adipocyte differentiation, insulin sensitivity, and neuronal synaptic plasticity. Moreover, LRP5 displays a dual role in development and disease progression. Although it plays a protective role in acute injuries such as myocardial infarction and acute kidney injury, LRP5 also contributes to chronic pathologies such as tubulointerstitial fibrosis, polycystic kidney disease, and atherosclerosis through fibrotic and inflammatory pathways. Recent therapeutic interest has focused on modulating LRP5 activity using agents such as anti-Dickkopf-related protein 1 antibody, sclerostin inhibitors, polyclonal antibodies, CRISPR/Cas9 knockout, and some natural products. This review discusses the current understanding of LRP5's physiological and pathological roles across organ systems and highlights its therapeutic potential, emphasizing the need for targeted approaches considering its context-dependent effects. Full article

Alpha-gal syndrome (AGS) is an IgE-mediated allergy, triggered by a carbohydrate—galactose-α-1,3-galactose (α-Gal). AGS is marked by a delayed onset of symptoms, typically occurring 3–8 h after the ingestion of red meat or other mammalian-derived products. The primary risk factor is believed to be tick bites, which sensitize individuals through the introduction of α-Gal via tick saliva. Diagnosis of AGS is based on a combination of anamnesis and detection of α-Gal-specific IgE antibodies. We evaluated 28 patients with a history of unexplained anaphylaxis, angioedema, and/or urticaria, in whom the diagnostic work-up included the assessment of serum IgE specific to alpha-gal. Elevated alpha-gal-specific IgE levels were detected in five patients. Among them, four reported anaphylactic episodes following meat consumption. In three cases, symptoms developed during the evening or nighttime, typically 3 to 6 h after the last meal. One patient experienced anaphylaxis within one hour after a meal. Another patient presented angioedema up to 24 h after meat consumption and was also tested positive for specific IgE against beef and pork allergens. The AGS case series showed variability in clinical picture and time to reaction. In patients presenting idiopathic anaphylaxis and nonspecific symptoms after red meat consumption, AGS should be considered as a differential diagnosis. Full article

Background/Objectives: This study investigated susceptibility factors that may contribute to Post-Polio Syndrome (PPS) in elderly polio survivors. Methods: Serum immunoglobulin (Ig) levels, poliovirus neutralizing antibodies (PV NAb), and vitamin D status were evaluated in 80 PPS patients, 40 family members, and 89 healthy controls. Results: A significant number of PPS patients and their family members showed reduced levels of total IgG and/or IgA, and specific IgG subclasses, indicating a high prevalence of primary humoral immunodeficiencies within these groups. Despite these Ig deficits, PV NAb titers were similar across all groups, indicating high protection against poliovirus, likely due to vaccination campaigns with live virus in Italy and intense exposure to poliovirus, especially in long-term rehabilitation institutions. However, a small group of PPS subjects lacked neutralizing antibodies for specific poliovirus serotypes, suggesting more severe antibody deficiencies. Additionally, PPS subjects had a high prevalence of vitamin D deficiency, which likely increases their risk for osteoporosis/osteopenia and fractures. It is unclear if this deficiency was also present in their infancy, potentially enhancing their susceptibility to poliovirus. Conclusions: Overall, the findings indicate that genetic, immunological, or nutritional factors may increase individual susceptibility to the pathogenic effects of poliovirus. This study—limited to serum antibodies—highlights the complex relationship between immune status and long-term health in aging polio survivors. The results emphasize the need for potent poliovirus drugs and vaccines to help contain possible outbreaks but also—for poliomyelitis survivors—to avoid or mitigate the progression to PPS, the latest phase of this devastating disease. Full article

Nephrotic syndrome (NS) is a complex kidney disorder characterized by profound proteinuria, hypoalbuminemia, hyperlipidemia, and edema, significantly impacting patients’ quality of life. While corticosteroids and calcineurin inhibitors (CNIs) have traditionally been the primary treatments, B cell-targeted therapies, especially the anti-CD20 monoclonal antibody rituximab, have transformed the management of steroid-dependent and multidrug-resistant NS (MRNS). Rituximab has demonstrated efficacy in reducing relapse rates and steroid dependence by depleting CD20+ B cells, which play a pivotal role in autoantibody production and immune dysregulation. However, limitations such as incomplete B cell depletion, immunogenicity leading to anti-rituximab antibodies, and variable efficacy in refractory cases have led to the development of next-generation therapies. This review critically examines recent advances in B cell-targeted therapies for NS, with a particular focus on overcoming the limitations of conventional rituximab treatment. This review systematically analyzes next-generation anti-CD20 monoclonal antibodies, CD38-targeted therapies, and emerging CAR-T cell approaches, evaluating their distinct mechanisms of action and clinical trial outcomes. The analysis extends to innovative combination strategies and biomarker-guided treatment algorithms for refractory cases. By synthesizing preclinical data with clinical evidence, this work provides a framework for optimizing therapeutic decision-making in NS, while identifying key knowledge gaps that warrant future investigation. Collaborative research and translational studies are essential for advancing precision medicine in NS, ensuring that new therapies provide lasting clinical benefits for patients. The evolving field of anti-B cell therapies marks a new era in managing refractory NS, offering hope for better long-term prognoses. Full article

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by venous and arterial thrombosis and obstetric complications, driven by antiphospholipid antibodies (APLAs). This review synthesizes the latest advancements and current understanding, diagnosis, and treatment of APS. APLAs, including lupus anticoagulant (LAC), anticardiolipin (aCL), and anti-β2-glycoprotein I (aβ2-GPI), interfere with coagulation and endothelial function, as well as with placental health. APS can be primary or secondary; it is often associated with systemic autoimmune diseases like lupus. The pathogenesis of APS remains only partially understood. APLAs promote thrombosis through endothelial damage, platelet activation, and inflammatory signaling pathways. Laboratory diagnosis relies on persistent positivity for APLAs and LAC through tests like ELISA and clotting assays, following a three-step confirmation process. New integrated test systems have been introduced to improve standardization. Classification criteria have evolved, with the 2023 EULAR-ACR criteria providing a weighted, domain-based scoring system, enhancing diagnostic precision. Catastrophic APS (CAPS) is a severe, rare manifestation of APS, characterized by multi-organ failure due to rapid, widespread microthrombosis and systemic inflammation, which requires urgent anticoagulation. Seronegative APS is proposed for patients with clinical features of APS but negative standard antibody tests, possibly due to non-criteria antibodies or transient immunosuppression. Treatment primarily involves long-term anticoagulation with vitamin K antagonists; direct oral anticoagulants are generally not recommended. APS diagnosis and management remain complex due to clinical heterogeneity and laboratory challenges. Continued refinement of diagnostic tools and criteria is essential for improving outcomes in this life-threatening condition. Full article