Search Results (336)

Objective: Patients with systemic lupus erythematosus (SLE) exhibit elevated malignancy risk, with increased bladder cancer incidence. This study integrated Mendelian randomization (MR) with single-cell sequencing (scRNA-seq) to nominate exploratory prioritized candidate genes in SLE–bladder cancer comorbidity and their T cell regulatory roles. Methods: Single-cell datasets for SLE (GSE266852) and bladder cancer (GSE222315) were retrieved from GEO. Quality control, clustering, and annotation were performed using Seurat. T cell differentially expressed genes were intersected for bidirectional two-sample MR using IEU Open GWAS statistics. Heterogeneity, pleiotropy, and sensitivity analyses assessed robustness. GeneMANIA, miRNA databases, and CTD were used for network and functional analyses. Wilcoxon tests and Monocle 2 were used to characterize expression and T cell differentiation trajectories. Results: Cross-disease intersection nominated 1010 candidate genes. In an exploratory MR screen (uncorrected p < 0.05), four candidate genes were nominated (GBP3, LMAN1, SLC40A1, MIS18BP1); none survived FDR correction in both directions. At the uncorrected threshold, LMAN1 showed a shared risk direction (OR > 1) and MIS18BP1 a protective direction (OR < 1). Both showed significant T cell differential expression (p < 0.001) and elevated late differentiation expression. LMAN1 was involved in COPII vesicle transport; MIS18BP1 in CENP-A chromatin assembly. Twenty high-confidence miRNAs targeted each gene. CTD indicated liver injury associations and cisplatin/cyclosporine interactions. Conclusions: LMAN1 and MIS18BP1 are proposed as hypothesis-generating exploratory candidate genes in SLE–bladder cancer comorbidity, potentially involved in immune dysregulation through T cell terminal differentiation modulation. This study provides preliminary evidence suggestive of autoimmune–malignancy comorbidity mechanisms. Full article

Background/Objectives: Children with juvenile idiopathic arthritis (JIA) frequently develop additional autoimmune conditions during follow-up, yet the clinical and diagnostic profile of this comorbid subgroup is incompletely characterised in single-centre paediatric series. We aimed to describe the prevalence, clinical pattern, and diagnostic features of autoimmune comorbidities in a seven-year cohort of children with JIA monitored at a single tertiary paediatric centre, and to document the diagnostic protocols applied for each comorbidity. Methods: We conducted a retrospective descriptive observational study of 103 consecutive children with JIA classified according to the ILAR 2001 criteria and monitored at the Paediatric Rheumatology Unit of St. Mary Children’s Emergency Hospital, Iași, Romania, between 2017 and 2023, with the year 2020 excluded by design owing to the institutional reorganisation during the early COVID-19 pandemic. Autoimmune comorbidities were ascertained from medical records using ICD-10 coding and confirmed by subspecialty evaluation. The diagnostic approach for each comorbidity is reported in detail. Continuous variables are described using mean ± standard deviation, and categorical variables as frequencies (%). No inferential analysis was performed on predictor variables; the study is exploratory and hypothesis-generating. Results: Autoimmune comorbidity was identified in 21 of 103 children (20.4%; 95% confidence interval [CI] 13.1–29.5%), the JIA-AID subgroup. Patients were predominantly female (17 of 21, 81.0%) and aged over 12 years (10 of 21, 47.6%). Autoimmune thyroiditis was the most frequent comorbidity, present in 10 of 21 cases (47.6%) when the euthyroid, hypothyroid, and vitiligo-associated forms were combined, followed by inflammatory bowel disease (4 of 21, 19.0%), alopecia areata (4 of 21, 19.0%), localised scleroderma (2 of 21, 9.5%), and coeliac disease (1 of 21, 4.8%). Three patients (14.3%) had polyautoimmunity, defined as two or more autoimmune diagnoses in addition to JIA. The HLA-B27-positive enthesitis-related arthritis subtype, although small in absolute numbers, was over-represented within the JIA-AID subgroup: 5 of 7 HLA-B27-positive ERA patients (71.4%; 95% CI 29.0–96.3%) carried a coexisting autoimmune diagnosis, compared with 16 of 96 patients in the remainder of the cohort (16.7%; 95% CI 9.8–25.6%); the predominant comorbidity in this subtype was inflammatory bowel disease. Conclusions: Autoimmune comorbidity affected approximately one in five children with JIA in this single-centre cohort, with autoimmune thyroiditis and inflammatory bowel disease as the most frequent associations and a notable concentration of comorbidity within the HLA-B27-positive enthesitis-related arthritis subtype. These descriptive observations are hypothesis-generating and support the case for proactive multidisciplinary screening in selected subgroups. Prospective registry-based studies with explicit exposure classification and standardised functional outcomes will be needed to confirm the patterns reported here. Full article

Psoriasis is a chronic, autoimmune skin disease driven by persistent inflammation and immune dysfunction that severely impairs quality of life and is associated with serious comorbidities, including psoriatic arthritis, cardiovascular diseases (CVDs), and depression. Emerging epidemiological evidence suggests an association between psoriasis and an increased risk of certain malignancies, such as breast cancer (BC) and non-Hodgkin’s lymphoma (NHL), although the strength and consistency of these associations vary across study designs, and the underlying thrombo-inflammatory mechanisms remain incompletely understood. Several therapeutic approaches, including topical therapies, conventional systemic drugs (e.g., methotrexate and cyclosporine), and biological agents have been investigated for their potential associations with malignancy risk. However, the available evidence is heterogeneous and influenced by disease severity, treatment duration, cumulative exposure, and patient-related confounding factors. While some epidemiological studies have reported associations between conventional therapies and selected skin or hematological malignancies, combined or sequential treatment regimens further complicate the interpretation of treatment-related cancer risk. Similarly, Janus kinase (JAK) inhibitors have been associated with higher reported rates of lymphoma and non-melanoma skin cancer than tumor necrosis factor α inhibitors (TNFi-α) in some observational studies. Recent studies also highlight the clinical utility of inflammatory markers, specifically the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte (PLR) ratio, and systemic immune-inflammation index (SII), for monitoring systemic inflammation and treatment response, while certain therapies may additionally influence CVD risk. Despite these advances, substantial heterogeneity across observational studies, meta-analyses, and Mendelian randomization analyses preclude definitive conclusions regarding causality. Overall, this review synthesizes the current epidemiological and mechanistic evidence linking psoriasis, chronic inflammation, therapeutic interventions, cancer risk, and cardiovascular comorbidities, while highlighting the need for large prospective studies and standardized analytical approaches. Full article

Background/Objectives: 2-(2-Benzofuranyl)-2-imidazoline (2-BFI) is a selective imidazoline I₂-site ligand that has shown neuroprotective and neuromodulatory effects in preclinical central nervous system (CNS) studies. However, the primary preclinical literature remains fragmented across disease models, outcome types, mechanistic endpoints, and cellular targets, making it difficult to define where its therapeutic-development potential is strongest and how disease- or model-specific functional effects relate to molecular, cellular, tissue, and blood–brain barrier/neurovascular unit (BBB/NVU)-related findings. Methods: This systematic review integrated preclinical evidence from 36 original studies identified in the PubMed, Web of Science, Embase, and Scopus databases through searches last updated on May 19, 2026, to evaluate the strength of evidence for 2-BFI across CNS-related models and to connect functional, molecular, cellular, and neurovascular findings. The evidence categories included ischemic stroke/neurovascular outcomes (n = 13), traumatic CNS injury (n = 2), neuroinflammatory/neurodegeneration-related models (n = 9), behavioral pharmacology (n = 8), and cellular mechanisms (n = 4). Eligible studies were original CNS-related animal, cellular, or behavioral/pharmacological studies that directly evaluated 2-BFI and reported neuroprotective, neurological, cellular, molecular, vascular, inflammatory, neurotransmitter-related, or behavioral outcomes. Findings were synthesized qualitatively, and risk of bias in in vivo animal studies was assessed using SYRCLE’s risk-of-bias tool. Results: The most extensive preclinical evidence was found in ischemic stroke and neurovascular injury models, in which 2-BFI attenuated infarct size, neurological deficits, and edema, and suppressed apoptosis-related injury and blood–brain barrier/neurovascular unit (BBB/NVU) disruption. Across models, these effects are best interpreted as modulation of interconnected secondary injury processes involving N-methyl-D-aspartate receptor (NMDAR)/Ca²⁺-dependent excitotoxicity, oxidative and mitochondrial stress, inflammatory amplification, regulated cell death, and neurovascular destabilization. Evidence from traumatic CNS injury, autoimmune neuroinflammation, Alzheimer’s disease-related models, chronic epilepsy, and cellular stress models broadened the CNS relevance of 2-BFI but remained less replicated or more mechanistically indirect than the stroke/neurovascular evidence. Behavioral and pharmacological studies additionally indicated that 2-BFI modulates neurotransmitter-related systems associated with pain-, affective-, addiction-, opioid-, and compulsivity-related outcomes, although these findings should be distinguished from disease-modifying neuroprotective evidence. Conclusions: Meta-analysis was not conducted because of heterogeneity in models, dosing regimens, treatment timing, and outcomes. Overall, the current evidence does not yet support definitive dosing, treatment timing, or clinical development recommendations for 2-BFI. The strongest preclinical therapeutic rationale is currently found in ischemic stroke and neurovascular injury settings, whereas other CNS indications require further validation. Future studies should define dose–response relationships, therapeutic windows, pharmacokinetic and safety profiles, sex- and age-related effects, and efficacy in clinically relevant comorbid models before clinical translation is considered. The review was not prospectively registered. Funding was provided by a National Research Foundation of Korea grant funded by the Korean government. Full article

Background: Chronic corticosteroids are commonly prescribed for autoimmune and inflammatory disorders, yet their impact on perioperative outcomes following elective total hip arthroplasty (THA) remains incompletely defined. This study evaluated the association between chronic corticosteroid use and postoperative complications and hospital outcomes after elective primary THA. Methods: We performed a retrospective cohort study using the National Inpatient Sample (2016–2021). Adult patients undergoing elective primary THA were identified using ICD-10-PCS codes. Chronic corticosteroid use was defined by ICD-10-CM code Z79.52. The primary outcome was any postoperative complication, including venous thromboembolism (VTE), major bleeding, acute kidney injury, myocardial infarction, stroke, or sepsis. Secondary outcomes included prolonged length of stay, high hospital charges, discharge to rehabilitation, and in-hospital mortality. Multivariable weighted logistic regression and 1:1 propensity score matching (PSM) was applied. Results: The weighted cohort represented approximately 600,000 hospitalizations, of which 0.91% involved chronic steroid use. Steroid users had a higher burden of comorbidities. After adjustment, chronic corticosteroid use was independently associated with increased odds of any postoperative complication (OR 1.32), major bleeding (OR 1.46), prolonged hospitalization (OR 1.26), discharge to rehabilitation (OR 1.06), and in-hospital mortality (OR 2.53). In the matched cohort (1079 pairs), steroid use remained significantly associated with overall complications (OR 1.84) and acute kidney injury (OR 2.10). Conclusions: Although uncommon, chronic corticosteroid use is associated with a clinically meaningful increase in perioperative morbidity after elective THA. These findings highlight chronic corticosteroid use as a marker of increased perioperative risk that warrants greater clinical recognition, and they provide hypothesis-generating evidence to inform future studies of perioperative management in this population. Full article

Systemic lupus erythematosus (SLE) is a chronic, heterogeneous autoimmune disease characterized by multisystem involvement and substantial morbidity. Although survival has improved over recent decades, disease burden remains considerable due to cumulative organ damage, comorbidities, and treatment-related toxicity, particularly from long-term glucocorticoid use. Advances in the understanding of SLE immunopathogenesis have led to the development of targeted therapies. Currently approved agents include belimumab and anifrolumab, while obinutuzumab has been approved for lupus nephritis and has also demonstrated significant efficacy in phase III trials in SLE. Several additional agents are in late-stage clinical development, including litifilimab (targeting plasmacytoid dendritic cells), telitacicept and ianalumab (BAFF/APRIL and B-cell modulation), dapirolizumab pegol (CD40L blockade), deucravacitinib and upadacitinib (TYK2/JAK inhibition), and cenerimod (S1P1₁ modulation). This narrative review summarizes current phase III evidence and emerging therapeutic strategies, highlighting the ongoing transition toward precision medicine and individualized treatment approaches in SLE. Full article

Objective: Glutamic acid decarboxylase 65 (GAD65) antibody-associated epilepsy often presents as chronic focal epilepsy, usually with temporal lobe predominance, marked drug resistance, and inconsistent response to first-line immunotherapy. We assembled a large, harmonized, and literature-derived patient-level cohort to examine whether immunotherapy timing and regimen composition were associated with seizure outcome and to identify clinically meaningful prognostic signals. Methods: We performed a literature-derived patient-level analysis of 375 unique published cases linked to 132 contributory source publications from an audited full-text register of 166 reviewed studies. Descriptive analyses used the whole cohort. Treatment-response analyses assessed seizure outcome at the first evaluable post-immunotherapy assessment and at the last follow-up. Good seizure outcome was defined as seizure freedom and/or ≥50% seizure reduction. The primary timing comparison contrasted early treatment, defined as immunotherapy within 6 months of symptom onset, with late treatment, defined as immunotherapy after more than 12 months; four cases treated in the intermediate >6 to ≤12 month window were retained for descriptive timing summaries but excluded from the primary comparison. Statistical testing used the Fisher exact, Chi-square, Mann–Whitney U, and prespecified clustered logistic sensitivity analyses where appropriate. Results: The pooled phenotype was predominantly female, usually temporal-lobe-based, and frequently drug-resistant, with common autoimmune comorbidity and heterogeneous MRI abnormalities. Among timing-evaluable treated cases, earlier immunotherapy showed a class-specific, exploratory signal rather than a uniform regimen-independent effect. In rituximab/CD20-directed regimens, early treatment was associated with a higher rate of good seizure outcome than late treatment at both the first post-immunotherapy assessment and last follow-up (93.8% vs. 50.0%; risk difference [RD]: 43.8 percentage points; 95% CI: 7.7 to 72.7). A similar pattern was observed in the broader escalation group (94.4% vs. 55.6%; RD: 38.9 percentage points; 95% CI: 6.3 to 68.1). By contrast, steroid-containing regimens showed no clear early-versus-late advantage (84.6% vs. 88.2%; RD: −3.6 percentage points; 95% CI: −18.4 to 20.1). Shorter epilepsy duration before immunotherapy and absence of established drug resistance were the most clinically meaningful favorable baseline features. Significance: In GAD65 antibody-associated epilepsy, the therapeutic window may be most relevant for escalation strategies rather than for steroid-containing first-line regimens. However, these class-specific findings are exploratory and hypothesis-generating. They derive from non-randomized, literature-derived data and may reflect treatment intensity, center practice, publication era, and confounding by indication rather than isolated regimen superiority. Prospective collaborative registries with standardized longitudinal seizure outcome measures are needed to validate these observations. Full article

Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering disease, predominantly affecting elderly patients with multiple comorbidities. This multicentre retrospective cohort study aimed to characterize the clinical profile, treatment patterns, and drug-associated cases of BP in a real-world setting. The study included 156 patients newly diagnosed with BP between 2020 and 2024 in four dermatology departments in Poland. Diagnosis was based on clinical features, and immunological assessment, including direct immunofluorescence (DIF), ELISA, and BIOCHIP-based indirect immunofluorescence. The mean age at diagnosis was 75.5 ± 10.9 years, and 78.85% of patients had at least one comorbidity, most commonly arterial hypertension, type 2 diabetes mellitus, and dyslipidemia. Severe pruritus was reported in 74.14% of evaluated patients. Blisters and erosions were the predominant clinical manifestations. Topical glucocorticosteroids were the most frequently used treatment, followed by systemic glucocorticosteroids and methotrexate. New drug exposure within 6 months before disease onset was identified in 14.74% of patients and was associated with a shorter time to diagnosis. Drug-associated cases showed lower BP180 ELISA positivity, although this did not remain significant after correction for multiple testing. These findings highlight the clinical complexity of BP and the importance of medication review and direct immunofluorescence in diagnostic evaluation. Full article

Immune thrombocytopenia (ITP) is a heterogeneous autoimmune disorder characterized by immune-mediated platelet destruction and impaired platelet production. Increasing evidence suggests that systemic inflammation plays a significant role in disease pathogenesis and clinical outcomes. This study aimed to evaluate the prognostic significance of inflammatory indices and their association with complications, mortality, treatment response, and relapse in patients with ITP. In this single-center retrospective study, 166 adult patients diagnosed with primary ITP between January 2015 and December 2024 were analyzed. Demographic, clinical, and laboratory data at diagnosis were collected. Inflammatory indices derived from complete blood count parameters, including neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), were evaluated. Their associations with clinical outcomes were assessed using appropriate statistical methods. During the observation period based on retrospective medical records, complications occurred in 12% of patients, and mortality was observed in 6.6%. Patients with complications had significantly higher D-dimer levels and reduced bone marrow megakaryocyte production. In group comparisons, mortality was significantly associated with advanced age, male sex, and comorbidities. Laboratory findings revealed that lower hemoglobin, lymphocyte count, mean platelet volume, and albumin levels, along with higher PLR, erythrocyte sedimentation rate, bilirubin, and D-dimer levels, were significantly associated with mortality. Inflammatory indices such as NLR and PLR were not associated with complication development, but PLR was significantly associated with mortality. Response to intravenous immunoglobulin (IVIG) therapy was significantly associated with higher total protein, albumin, and fibrinogen levels, and lower erythrocyte sedimentation rate. Relapse was significantly associated in group comparisons with increased inflammatory activity, higher reticulocyte count, and positivity for antinuclear antibodies and Helicobacter pylori antigen. Systemic inflammation and impaired megakaryopoiesis play critical roles in the prognosis of ITP. While conventional inflammatory indices showed limited predictive value for complications, markers such as PLR, D-dimer, and albumin were associated with mortality and clinical outcomes. These findings suggest that readily available laboratory parameters may provide valuable insights for risk stratification and personalized management in patients with ITP. Full article

Background and Objectives: Neurological complications of SARS-CoV-2 infection frequently impair patients’ long-term quality of life. This study aimed to identify clinical and laboratory risk factors—including inflammatory markers and micronutrients—for the occurrence or worsening of neurocognitive disorders in long COVID patients. Materials and Methods: In this prospective observational study, patients presenting with long COVID neurological manifestations were stratified by baseline MoCA score into two groups (≥23 and <23). Clinical, laboratory (inflammatory markers, 25-hydroxy vitamin D, vitamin B12, folic acid), and neuroimaging assessments (global cortical atrophy scale, Fazekas score) were performed over 24 months. Propensity score matching (PSM) for age, gender, and neurological comorbidities yielded 54 patients per group. Results: In the MoCA ≥ 23 group, significant predictors of cognitive decline included severe COVID-19 (OR = 2.211, 95% CI = 1.819–5.973, p = 0.012), autoimmune comorbidities (OR = 1.676, 95% CI = 1.191–2.390, p = 0.043), and elevated neutrophil-to-lymphocyte ratio (NLR; OR = 1.586, 95% CI = 1.431–2.122, p = 0.011). In the MoCA < 23 group, independent predictors were diabetes mellitus (OR = 3.021, 95% CI = 2.65–14.004, p = 0.016), autoimmune comorbidities (OR = 4.987, 95% CI = 1.412–6.033, p = 0.021), and NLR (OR = 5.944, 95% CI = 2.353–19.321, p = 0.015). Serum vitamin D levels were significantly associated with MoCA scores in both groups. Conclusions: COVID-19 severity, autoimmune comorbidities, NLR, and serum vitamin D represent key risk factors for neurocognitive decline in long COVID, highlighting potential targets for early intervention. Full article

Background: Chung–Jansen syndrome (CHUJANS) is a rare autosomal dominant genetic condition caused by pathogenic variants in the PHIP gene, which encodes a protein involved in neurodevelopmental processes and IGF-1 signalling. The phenotype is characterised by variable degrees of intellectual disability, early-onset obesity or overweight, distinctive facial dysmorphisms, and behavioural disturbances. We here present a case of Chung–Jansen syndrome with a detailed endocrine work-up, highlighting the metabolic component of this syndrome. Case Presentation: We describe the case of a 21-year-old woman referred to our centre for evaluation of oligomenorrhea in the context of severe obesity (BMI 50.4 kg/m²), short stature (151 cm, <3rd percentile), and moderate-to-severe intellectual disability (full-scale IQ 38). Physical examination revealed dysmorphic features, including a round face, upslanting palpebral fissures, prominent zygomatic bones, anteverted nares, a prominent chin, and bilateral brachydactyly type E1. Laboratory investigations documented subclinical primary hypothyroidism of autoimmune origin, impaired glucose tolerance with associated hyperinsulinism, and polyendocrine metabolic ovarian syndrome (PMOS, previously known as PCOS). Exome analysis by next-generation sequencing (NGS) identified a heterozygous c.328C>T [p.(Arg110Cys)] variant in the PHIP gene, already reported in literature and classified as likely pathogenic (ACMG class 4). Segregation analysis in the mother (father was not available for the test) did not reveal the variant, suggesting a de novo origin in the patient. Concurrently, the same analysis revealed a variant of uncertain significance in the ANKRD17 gene, while array-CGH detected a maternally inherited microdeletion of uncertain significance on chromosome X (Xp11.23). Conclusions: This case confirms the association between the PHIP p.(Arg110Cys) variant and the phenotype of Chung–Jansen syndrome, providing a detailed characterisation of the endocrine and psychiatric comorbidities. Indeed, our report expands the knowledge on the endocrine phenotype providing further suggestion for personalised patient management. It underscores the importance of NGS in the diagnostic workup of syndromic obesity with intellectual disability, especially in the presence of negative family history and prior inconclusive genetic testing. This case suggests the inclusion of comprehensive endocrine evaluations in future studies on patients with Chung–Jansen syndrome, in order to support endocrine work-up and facilitate early identification and appropriate management of potentially treatable alterations. Full article

Objectives: Endocrine neoplasms, as a general rule, show systemic, neuro-inflammatory and metabolic consequences, known as paraneoplastic syndrome. The comorbidity of thyroid tumors with neurological and autoimmune diseases prompt looking for common neuro-immuno-endocrine mechanisms of these disorders. While most TCs are well described, there is a gap in the literature after the isolation of oncocytic/Hürthle cell carcinoma (HCC), as a unique type due to immunoendocrine and metabolic features (low TSH-receptor expression and radioiodine avidity). The aim of this study was to collect clearly defined reports of HCC (as a separate entity) and to attempt determining common clinical symptoms and the usefulness of various diagnostic techniques (comprehensive critical review). This may be an introduction to modern treatment (patient-centered care) since the main cause of mortality is not local progression or metastases. Results: Until now, due to misnomenclature and data misinterpretation, HCC has been treated according to general standards (with overuse of TSH-ST and RIA). High thyroglobulin level, decreased total thyroxin (with normal FT3 and spontaneous decrease in TSH), hypercalcemia, as well as the “reverse flip-flop” phenomenon, as common symptoms, indicate the neuroendocrine origin of HCC. Sparse, well-documented lymph node metastases are another feature, although from few studies. Most studies omit the N stage. Whole-body ¹³¹iodine and ¹⁸F-fluorodeoxyglucose scintigraphy may be useful before FNAB. Fine-needle aspiration biopsy (FNAB), as a “gold standard” in early diagnosis of thyroid nodules, delays HCC diagnosis because of the inability to determine a benign/malignant nature. Conclusions: Final HCC outcome may be affected by various overlapping immunoendocrine factors (paraneoplastic effects). Due to very few thyroid function tests performed in HCC, we have proposed a set of basic laboratory analyses, core biopsy in HCC differentiation, and diagnostic chain for standardization. According to the review, adaptation and treatment of HCC based on existing standards for other thyroid cancers seem to be insufficient, and the risks outweigh the benefits. The key recommendations resulting from the 5th edition of the WHO Classification of Endocrine Neoplasms are only the beginning of refuting many myths and biases. Full article

Background: Elderly patients have low utilization of adjuvant ICIs, although they achieve similar RFS benefits as younger patients. It remains unclear why elderly patients use adjuvant ICIs less frequently and whether toxicity impacts treatment utilization. Methods: Adult patients with stage III melanoma treated from 2017 to 2023 at a single academic cancer center were retrospectively identified. Multivariable logistic regressions evaluated the association of age with receipt of adjuvant ICIs and toxicity. RFS was assessed using Kaplan–Meier and multivariable Cox proportional hazards regression. Results: Among 240 patients, those aged ≥ 75 years were less likely to receive adjuvant ICI than those aged 18–74 years (aOR: 0.30; 95% CI: 0.11–0.80). Among 53 (22.1%) patients who did not receive adjuvant ICI, 58% declined treatment, 15% were not offered adjuvant ICI by provider, 9% had a comorbid autoimmunity, and 6% had another comorbidity. A total of 12% of patients aged 75–80 years old declined treatment versus 33% of those aged 80–90 years old. Older age was not associated with toxicity, treatment interruption, or discontinuation from adjuvant ICI. Adjuvant ICI was associated with low recurrence (aHR: 0.76; 95% CI: 0.63–0.92), whereas age ≥ 75 years was associated with higher recurrence risk (aHR: 1.79; 95% CI: 1.04–3.10) and low overall survival (aHR: 3.07; 95% CI: 1.43–6.57) compared to patients aged 18–74 years. Conclusions: Older patients with stage III melanoma were less likely to receive adjuvant ICIs, despite similar toxicity, treatment interruption, and discontinuation rates across age groups. Because adjuvant therapy is associated with lower recurrence risk, efforts to better understand and address age-related differences in treatment use are warranted. Full article

Systemic sclerosis (SSc) is a heterogeneous autoimmune disease characterized by immune dysregulation, microvascular injury, and progressive cutaneous and internal organ fibrosis. Despite advances in the understanding of SSc pathogenesis, effective disease-modifying therapies remain limited, and there is ongoing interest in targeted approaches that may modulate early inflammatory-vascular mechanisms linked to subsequent fibrotic remodeling. The IL-23/Th17 axis contributes to SSc biology, providing a rationale for IL-23p19 blockade as a potential therapeutic strategy. This focused narrative review summarizes currently available clinical signals of IL-23p19 inhibition in SSc, centered on guselkumab, and interprets reported outcomes using a domain-based framework. Published evidence remains confined to uncontrolled reports totaling 4 patients (one case report of early limited cutaneous SSc and a three-patient case series of early diffuse cutaneous SSc with comorbid psoriasis). Across these reports, investigators described improvements most consistently in the cutaneous domain (modified Rodnan skin score [mRSS], modified Rodnan total skin score [mRTSS], and the American College of Rheumatology Combined Response Index in Systemic Sclerosis [CRISS]) and in microvascular manifestations, including Raynaud’s phenomenon and nailfold microangiopathy, whereas pulmonary and gastrointestinal findings remain preliminary. We discuss key limitations of the current literature, including publication and reporting bias, the heterogeneity of phenotypes and endpoints, and confounding by comorbid psoriatic disease and natural disease fluctuation. Overall, IL-23p19 inhibition offers a pathway-specific approach in SSc, but establishing efficacy and defining responsive phenotypes requires adequately powered controlled evidence. Findings pertain specifically to guselkumab and cannot be generalized to IL-23 inhibition as a class. Full article

Background/Objectives: This report is an assessment of the characteristics associated with cardiovascular dysautonomia (CVD) in the context of long Coronavirus disease (COVID), which is currently inadequately characterized. Material and Methods: A retrospective cross-sectional study was performed involving 106 patients with long COVID, including 34 individuals diagnosed with CVD, among whom eight met the criteria for Postural Tachycardia Syndrome (PoTS). The variables assessed encompassed individual characteristics (e.g., age, sex, comorbidities), immunization parameters (e.g., vaccination/viral status, timing, frequency), cellular and humoral anti-Spike and anti-Nucleocapsid (Nuc) immune responses, inflammatory and allergic biomarkers, as well as an extensive panel of common autoantibodies comprising anti-nuclear antibodies, anti-central nervous system antibodies (cerebellum, brain), and anti-peripheral nervous system antibodies (gangliosides). Results: An age < 45 years, body mass index, hyperventilation syndrome as well as a higher cumulative number of antigenic contacts (vaccinations plus infections ≥ 3) and an elevated basophil count (≥0.06 G/L) were independently associated with CVD. There was no association between CVD and inflammatory markers or common autoantibodies. Patients with PoTS criteria had a strong anti-Spike cellular immune response and increased IgG anti-Nuc humoral immunity when compared with CVD and non-CVD long COVID counterparts. Conclusions: Compared to other long COVID patients, patients with long COVID-associated CVD have distinctive clinical and immunovirological features. Our results suggest the potential role of the immune response against Spike and of allergic pathways rather than humoral autoimmunity against common autoantibodies in long COVID CVD. Full article