Search Results (1,939)

Background/Objectives: Lipschutz ulcers were first described in 1912 by the Austrian dermatologist Benjamin Lipschutz. The onset presents with flu-like symptoms with consecutive development of painful vulvar ulcers. The term is currently used to describe painful genital lesions associated with an immunological reaction to an extragenital source of infection, usually viral or bacterial infections or certain vaccines. This disease affects predominantly adolescent non-sexually active females and is usually self-limiting. Methods : We searched PubMed, Research Gate and Google Scholar using the keywords “Lipschutz ulcer”, “Ulcus vulvae acutum Lipschutz”, “Acute genital ulcer”, and “Reactive non-sexually related acute genital ulcers”. A total of 24 articles in English between the years 2000 and 2025 were selected in order to mark the latest advancements towards diagnostic and treatment plans. Only 19 provided thorough information about the treatment and follow-up of the patients, encompassing a total of 69 girls and women. Results: This review synthesizes the most common etiological factors for Lipschutz ulcers and explores the mechanism behind their development. Different treatment approaches were also investigated. Based on our findings, we propose a diagnostic and treatment algorithm depending on the patient’s general condition and severity of the ulcers. We reported a 12-year-old girl’s case, diagnosed and treated at our department. Despite our efforts, conservative therapy proved inefficient. Surgery was performed. Conclusions: Lipschutz’s ulcer is a diagnosis often overlooked. Therefore, further research is needed to address the best treatment strategies. Surgery should be reserved only for patients who show no improvement with conservative treatment. Full article

Background: South Korea has documented HIV cases since 1985; however, comprehensive longitudinal analyses integrating incidence, mortality, transmission dynamics, and immunological staging across the full surveillance period remain limited. This study aimed to characterize epidemiological trends from 1985 to 2024 and project future trajectories through 2028. Methods: We analyzed nationally reported aggregate HIV/AIDS surveillance data from the Korea Disease Control and Prevention Agency (KDCA) via KOSIS (1985–2024). Annual HIV incidence, AIDS case notifications, HIV-related mortality, transmission route distributions, CD4+ T-cell counts at diagnosis, and cumulative prevalent cases stratified by sex were examined. Statistical methods included simple and multiple linear regression, Pearson and Spearman correlation, hierarchical regression analysis, and time series forecasting using Holt–Winters exponential smoothing and ARIMA (AutoRegressive Integrated Moving Average) modeling. Missing data in transmission route classification (29.6% non-response in 2024) were addressed through sensitivity analysis and explicit discussion of potential misclassification bias. Results: HIV annual incidence increased significantly from one case in 1985 to a peak of 1081 in 2014 (slope = +39.25 cases/year, R² = 0.912, p < 0.001), followed by a significant decline to 714 cases in 2024 (slope = −38.76 cases/year, R² = 0.879, p < 0.001). A strong positive correlation was observed between HIV and AIDS incidence (Pearson r = 0.627, p = 0.017; Spearman ρ = 0.785, p < 0.001). The AIDS/HIV notification ratio declined significantly from 0.307 in 2011 to 0.196 in 2024 (slope = −0.006/year, R² = 0.421, p = 0.012). The male-to-female notification ratio increased from 0.8:1 in 1987 to 22.0:1 in 2024 (R² = 0.600, p < 0.001). Among reported sexual transmissions, the proportion attributable to MSM increased from 0% in 1985 to 63.7% in 2024 (slope = +1.30%/year, R² = 0.804, p < 0.001). The proportional mortality rate declined significantly from 2.31% in 2011 to 0.93% in 2024 (slope = −0.105%/year, R² = 0.821, p < 0.001). Time series forecasting projected continued decline to approximately 666 new HIV cases and 105 AIDS notifications annually by 2028. Conclusions: The South Korean HIV epidemic has undergone a profound epidemiological transition—from heterosexual-predominant early growth through a 2014 peak toward a declining, MSM-concentrated trajectory—with mortality progressively decoupled from incidence through expanded antiretroviral therapy coverage. Targeted MSM-focused prevention, expansion of PrEP access, and sustained ART scale-up are essential to achieving national HIV elimination targets. Full article

Background: Nutritional abnormalities, alterations in body composition, and impaired muscle function are increasingly recognized as clinically relevant features in patients with Systemic Lupus Erythematosus (SLE). However, the relationship between multidimensional nutritional assessment and disease activity remains incompletely characterized. This study aimed to evaluate the associations between nutritional status, body composition, muscle strength, nutritional risk indices, and disease activity in patients with SLE. Materials and Methods: This exploratory retrospective study included hospitalized patients with SLE. Clinical data, anthropometric measurements, and nutritional status were assessed using the body mass index (BMI), prognostic nutritional index (PNI), controlling nutritional status (CONUT), and nutritional risk index (NRI). Muscle function was evaluated using the SARC-F scale. Disease activity was measured using the SLE Disease Activity Index 2000 (SLEDAI-2K). Multivariable linear regression models were constructed to assess the independent association between nutritional indices and disease activity, adjusting for age, sex, glucocorticoid exposure, and immunosuppressive therapy. Correlation analyses were performed between nutritional indices and disease activity-related variables, and supplementary exploratory Spearman correlations were performed between the SARC-F score and SLEDAI-2K, CRP, complement C3, complement C4, and ESR. False discovery rate correction using the Benjamini–Hochberg procedure was applied to exploratory correlation analyses. Results: A total of 67 patients were included. Nutritional indices (BMI, PNI, CONUT, and NRI) were not independently associated with SLEDAI-2K in multivariable regression analyses. In correlation analyses, after FDR adjustment, the PNI remained significantly associated with SLEDAI-2K, lymphocyte counts, and complement C3 levels, while CONUT remained significantly associated with lymphocyte count and C3 levels. The BMI and NRI were not significantly associated with disease activity or inflammatory markers after correction. SARC-F showed a weak positive correlation with SLEDAI-2K (r = 0.328; p = 0.008; qFDR = 0.040), which remained statistically significant after FDR correction. No significant correlations were observed between SARC-F and CRP, complement C3, complement C4, or ESR after FDR adjustment. Conclusions: Nutritional indices showed limited independent association with disease activity in SLE after adjustment for available confounders. Although the PNI and CONUT retained selected correlations with disease activity-related or immunological markers after FDR correction, these associations should be interpreted cautiously, as albumin- and lymphocyte-based indices may reflect inflammatory activity or disease burdens rather than nutritional status alone. SARC-F remains significantly associated with disease activity (SLEDAI-2K) after FDR adjustment. These findings should be validated in future prospective studies with a larger number of patients. Full article

Background: Acute lymphoblastic leukaemia (ALL) is the most common paediatric haematological malignancy. Treatment-related immunosuppression compromises mucosal integrity and contributes to oral and dento-maxillary complications, which remain a clinically relevant but insufficiently characterised source of morbidity. Salivary secretory immunoglobulin A (sIgA), the principal antibody of mucosal surfaces, may provide a non-invasive surrogate measure of local immune competence; however, its longitudinal behaviour and relationship with oral morbidity in paediatric ALL remain incompletely characterised. Methods: This prospective, single-centre pilot cohort study included 21 children with newly diagnosed ALL treated at the Fundeni Clinical Institute, Bucharest (March–November 2024). Salivary sIgA was measured at diagnosis (TP1) and after completion of intravenous chemotherapy (TP3). Oral mucositis (OM) was clinically assessed and graded according to WHO criteria at induction (TP2), as well as the predominant WHO grade across the post-induction chemotherapy course. Stomatological evaluation included DMFT/dmft and PUFA/pufa indices, and microbiological screening was performed at predefined time points. Statistical analyses were exploratory and included non-parametric tests and correlation analyses. Results: All patients developed OM at induction (TP2), with 38% experiencing severe forms (WHO grades 3–4). Baseline salivary sIgA (TP1) (n = 15) showed a non-significant weak inverse association with mucositis severity (Spearman ρ = −0.35, p = 0.20); differences across severity groups did not reach statistical significance (Kruskal–Wallis p = 0.43). When grouped, lower median salivary sIgA levels were observed in patients with severe mucositis compared with mild-to-moderate forms (median 91.0 mg/L (IQR 65.0–123.0) vs. 170.5 mg/L (IQR 125.0–231.8); non-significant p = 0.13). A non-significant decline in salivary sIgA was observed from TP1 to TP3 (median 174.5, IQR 127.2–213.8 versus median 111.5, IQR 33.2–142.7; Wilcoxon signed-rank p = 0.084; n = 10 paired measurements). Pre-existing dento-maxillary morbidity was substantial (median DMFT 4.0 (IQR 2.5–5.5), PUFA 3.0 (IQR 1.5–4); dmft 4.0 (IQR 3.0–5.0), pufa 3.0 (IQR 2.0–3.5)), but showed no statistically significant association with either mucositis grade or salivary sIgA levels. No clinically meaningful correlation was observed between salivary and intestinal sIgA levels (Spearman ρ = 0.33 overall; ρ = 0.16 after exclusion of an extreme outlier; p > 0.05 in both analyses), consistent with immunological compartmental independence. Conclusions: In this exploratory pilot cohort, no statistically significant associations were observed between salivary sIgA and oral mucositis severity or dento-maxillary indices. Although trends toward lower baseline salivary sIgA in severe mucositis and declining sIgA during induction therapy were observed, larger adequately powered studies are needed to determine whether these findings represent true biological associations. Full article

Background: Novel Sézary syndrome (SS) biomarker genes identified previously through transcription profiling were examined for changes in expression after mogamulizumab treatment. Incorporating new biomarkers for measuring response to disease would improve clinical care. Objective: To assess novel SS biomarker and cytokine genes in patients treated with mogamulizumab with clinical response, blood response, and immunologic parameters. Methods: We performed a real-world case–control and case–case study analyzing the expression of SS biomarker genes in peripheral blood mononuclear cells (PBMCs) from six SS patients treated with mogamulizumab using qRT-PCR. Results: We demonstrated a reduced expression of SS biomarker genes in PBMCs of SS patients following mogamulizumab therapy. In our cohort, five of the SS biomarker genes (PLS3, TWIST1, KCNK1, DNM3 and TOX) showed statistically consistent high expression compared to normal PBMCs at baseline. After treatment with mogamalizumab, these five SS biomarkers showed significant correlations with skin response (p < 0.05) and three (TOX, TCRL3 and DNM3) with blood response (p < 0.05). A decrease in GATA3 expression correlated to an improvement in skin severity, and STAT4 inversely correlated to Sézary cell decrease (p < 0.05). Two cytokine genes, IL4 and IFNG, reflective of an immune response that is abnormal in SS, showed a trend to normalized expression with IL-4 decreasing and IFNG increasing after treatment. Limitations: This was a real-world study of patients who failed prior treatments, with a small sample size and variable timing between patient sample collection. Conclusions: Unique SS biomarker, cytokine and T cell transcription factor genes are valuable in assessing molecular and immune responses following treatment. Full article

Background: Neonatal sepsis caused by multidrug-resistant (MDR) Gram-negative pathogens poses significant therapeutic challenges in neonatal intensive care units (NICUs), particularly in surgical neonates. Ceftazidime-avibactam (CAZ-AVI), a novel β-lactam/β-lactamase inhibitor combination, offers activity against extended-spectrum β-lactamases (ESBLs), AmpC, and serine carbapenemases, but neonatal experience remains limited. Methods and Results: We present a 35-week preterm neonate with long-gap esophageal atresia who developed late-onset sepsis caused by MDR Enterobacter hormaechei, including a KPC-producing carbapenem-resistant isolate, during postoperative recovery. After a multidisciplinary review, the patient received off-label CAZ-AVI at 25 mg/kg/dose (20/5 mg/kg) every 8 h, infused over 2 h, informed by available neonatal pharmacokinetic evidence and weight-adjusted dosing recommendations. Amikacin was administered contextually. Consecutive blood cultures obtained 48–72 h after dual antibiotic therapy initiation became negative and remained sterile, with concordant decline in inflammatory biomarkers, confirming rapid microbiological clearance. Unfortunately, the newborn died in the hours immediately following the final surgery performed to repair the esophageal atresia via end-to-end anastomosis; the cause was complications (hemothorax) unrelated to infectious diseases, although the onset of such severe sepsis may have compromised an already impaired immunological status. Discussion: This case shows mechanism-concordant antimicrobial selection and the feasibility of neonatal dosing when MDR Enterobacterales drive invasive infection. Our experience supports prospective evaluation of CAZ-AVI in carefully selected septic newborns while emphasizing the importance of rapid carbapenemase genotyping, susceptibility testing, and multidisciplinary oversight. Full article

Introduction: Long-term real-world data on bictegravir/emtricitabine/tenofovir alafenamide (BIC-STR), particularly in key subgroups, remain limited. The primary endpoints of the study were changes in CD4+ cell count and viral load after BIC-STR introduction. The secondary endpoints were the impact of the therapy on metabolic profile and body mass index. Methods: Retrospective observational cohort study including people living with HIV (PLWH) receiving BIC-STR with more than 6 months of follow-up at a tertiary Infectious Diseases clinic (Perugia, Italy). Immunovirological outcomes (HIV-RNA, CD4 count, CD4/CD8 ratio) and metabolic parameters were assessed up to 48 months, with subgroup analyses (treatment-naïve/experienced, >60 years, women, and foreign nationals). Results: 425 patients were included (median follow-up 37.7 months, IQR, 22.1–55.8 months). Most were treatment-experienced (367/425, 86.4%) and viral suppression improved after switching, reaching 90.7% with HIV-RNA < 50 cp/mL; HIV-RNA declined mainly within the first 6 months and then remained stable. CD4 count and CD4/CD8 ratio increased significantly over time, with similar immunovirological trends in older patients (>60 years; 138/425, 32.3%), women (94/425, 22.1%), and foreign nationals (143/425, 33.7%). In treatment-experienced patients not on statins, HDL and LDL did not change significantly, while triglycerides decreased (median from 110 mg/dL, IQR 78.0–164.0, to 103 mg/dL, IQR 70.3–147.8; p = 0.007). In ART-naïve patients (58/425, 13.6%), HDL (median from 41, IQR, 33.0–47.0 to 47, IQR 39.0–54.7, p = 0.0003) and BMI (median from 23.2, IQR 21.7–26.3 to 25.7, IQR 23.4–29.0, p < 0.0001) increased, whereas other lipid changes were not significant. BMI increased only in underweight and normal-weight naïve patients, not in overweight/obese individuals. Conclusions: BIC-STR showed sustained effectiveness, immunological benefit, and favourable metabolic outcomes in routine practice, including, PLWH > 60 years, women, and foreign nationals subgroups. Full article

Background/Objectives: Machine learning (ML) models have increasingly been applied to prognostic prediction in oral cavity squamous cell carcinoma (OCSCC), though their performance and methodological quality remain variably reported. This systematic review evaluated contemporary ML-based prognostic models for clinically relevant OCSCC outcomes, with emphasis on independently validated studies. Methods: A systematic review was conducted according to PRISMA guidelines using PubMed, Scopus, Cochrane Library, and CINAHL databases through 1 December 2025. Studies evaluating ML or artificial intelligence prognostic models in adult OCSCC patients were included. Outcomes included overall survival, recurrence, disease-free survival, recurrence-free survival, disease-specific survival, cancer-specific survival, progression, and nodal metastasis. Data extraction and risk-of-bias assessment using PROBAST + AI were performed independently by reviewers. Results: Forty studies comprising 105,619 patients met inclusion criteria. ML architectures included random forests, support vector machines, gradient boosting methods, neural networks, and deep learning frameworks. Most models incorporated clinical and pathologic variables, while many integrated radiologic, immunologic, or genomic features. For overall survival prediction, independently validated models generally demonstrated AUCs between 0.80 and 0.90. Recurrence prediction models similarly showed favorable discrimination, with most externally validated studies reporting acceptable predictive performance. Additional prognostic endpoints including disease-free survival, progression, and nodal metastasis demonstrated AUCs ranging from 0.70 to 0.90. Common methodological limitations included retrospective design, small sample size, inadequate external validation, and risk of overfitting. Conclusions: ML-based prognostic models in OCSCC demonstrate generally favorable predictive performance across survival and recurrence outcomes. However, substantial heterogeneity in methodology and limited external validation continue to restrict clinical implementation. Future work should prioritize prospective multicenter validation, standardized reporting, and reproducible modeling frameworks. Full article

Background: Adult parvovirus B19 (B19V) infection occurs with cyclic outbreaks and can be associated with inflammatory manifestations mimicking or heralding the onset of systemic autoimmune diseases. Little is known about clinical traits distinguishing patients with transient vs. persisting manifestations. Methods: Leveraging data from the 2024 B19V infection outbreak, we set up a retrospective, multicentre, observational study investigating the epidemiology and clinical phenotypes of patients with B19V infection presenting to tertiary care for immune-mediated manifestations, including patients with pre-existing autoimmunity. Results: A total of 39 B19V infections were identified, yielding an annual incidence of 1.78 cases/1000 patients. Autoimmune rheumatic diseases were pre-existing in 7/39 and newly diagnosed in 5/39. One patient was hospitalised. Arthritis was more frequent in new-onset (89%) than in pre-existing (14%; p = 0.010) or no autoimmunity (19%; p < 0.001). Anaemia was not found in patients with pre-existing autoimmunity in contrast to those with new autoimmune disease diagnoses (40%; p = 0.039) or transient manifestations (52%; p = 0.013). Skin manifestations were numerically less frequent in this latter group (56%) than in patients with pre-existing (100%) or newly onset autoimmunity (80%). Autoantibodies were detected in 44% of cases and were more frequent in patients with constitutional symptoms but were not confirmed in the long term in most cases. Glucocorticoids were more frequently employed in patients with new-onset rather than pre-existing autoimmune diseases (p = 0.006) or without chronic autoimmunity (p = 0.027). Conclusion: B19V-associated new-onset autoimmunity may occur in one in six cases observed in tertiary immunology care, show distinct clinical features, and require significant immunosuppression. Full article

Background/Objectives: Cancer metastasis is responsible for most cancer-related deaths, yet the precise anatomical and physiological routes by which cancer cells disseminate remain incompletely defined. This review aims to present an integrated model of lymphatic and hematogenous dissemination that provides a unified framework for understanding metastatic progression. Methods: The published literature on lymphatic biology, microvascular physiology, tumor immunology, and cancer metastasis was critically reviewed and integrated to develop a comprehensive anatomical and physiological model of cancer dissemination. Results: The proposed model identifies lymphatic dissemination as the predominant metastatic route in many solid tumors. Cancer cells enter structurally permissive initial lymphatic capillaries and are transported to the sentinel lymph node (SLN), where interactions with the tumor microenvironment may eliminate disseminated cells, maintain dormancy, or facilitate immune escape and further dissemination. Cancer cells that survive within or escape beyond the SLN subsequently travel through collecting lymphatics and the thoracic or right lymphatic duct to enter the systemic venous circulation. Following cardiopulmonary transit, surviving cells may be redistributed through the systemic arterial circulation to distant organs. A secondary pathway involves direct hematogenous intravasation through post-capillary venules, where reduced shear stress, increased endothelial permeability, and permissive endothelial biology facilitate entry into the venous circulation. Thus, lymphatic and direct venular pathways ultimately converge in the venous circulation before systemic arterial dissemination. Conclusions: This unified model integrates lymphatic and hematogenous dissemination into a coherent anatomical and physiological framework. By emphasizing the SLN as an early immunologic checkpoint and the arterial circulation as the final distribution network for disseminated cancer cells, this review provides a conceptual basis for understanding metastatic patterns and identifying biomarkers and therapeutic vulnerabilities. Full article

Background: Intestinal parasitic infections are common in tropical settings and may influence immune regulation, allergic responses, and respiratory health. In children with sickle cell disease (SCD), respiratory morbidity is multifactorial, and the contribution of intestinal parasites remains uncertain. This study assessed whether documented intestinal parasitic infections, particularly helminth infections, were associated with asthma-like respiratory phenotypes and clinical morbidity in children with SCD in French Guiana. Methods: We conducted a multicenter cross-sectional analysis of children and adolescents younger than 18 years with confirmed SCD who were being followed by the pediatric SCD centers of Saint-Laurent-du-Maroni, Cayenne, and Kourou between January 2022 and December 2025. Clinical, respiratory, and parasitological data were extracted from routine-care medical records. Intestinal parasitic infection was defined as at least one documented stool parasitology result identifying Strongyloides stercoralis, hookworm, or Entamoeba histolytica, according to the variables consistently available in the database. Respiratory outcomes included physician-diagnosed asthma, bronchial obstruction, bronchodilator reversibility, and an asthma-like respiratory phenotype. Results: Among 233 included children, 105 (45.1%) had at least one documented intestinal parasitic infection and 82 (35.2%) had a helminth infection. Hookworm was the most common parasite (75/233, 32.2%), followed by Entamoeba histolytica (33/233, 14.2%) and Strongyloides stercoralis (24/233, 10.3%). An asthma-like respiratory phenotype was observed in 32/105 infected children (30.5%) versus 44/128 non-infected children (34.4%). Bronchial obstruction and bronchodilator reversibility were also similar between groups. After adjustment for age, sex, genotype, hydroxyurea treatment, rural residence, site of follow-up, and environmental tobacco smoke exposure, intestinal parasitic infection was not associated with asthma-like respiratory phenotype (adjusted OR: 0.94, 95% CI: 0.51–1.72; p = 0.844), recurrent hospitalization, or history of acute chest syndrome. Conclusions: In this routine-care multicenter pediatric SCD cohort from French Guiana, intestinal parasitic infections were common but were not associated with respiratory phenotype or selected morbidity outcomes. Because testing and respiratory assessment were not systematic, these findings should be interpreted as showing that routine parasitological status alone could not identify children with respiratory morbidity. Prospective studies with standardized repeated parasitological, immunological, environmental, and respiratory assessments are needed. Full article

Background/Objectives: Discontinuation of long-term denosumab (Dmab) remains a major clinical challenge because of rebound activation of bone remodeling and increased vertebral fracture risk. Intravenous zoledronate (ZOL) is widely recommended as sequential therapy, although evidence after very prolonged Dmab exposure is limited. We report a patient who developed two rare adverse events—acute hepatocellular injury and delayed inflammatory polyarthritis—following a single ZOL infusion administered after 12 years of continuous Dmab treatment. The subsequent management of persistent rebound bone turnover with oral alendronate (ALN) highlights the therapeutic challenges encountered when repeat ZOL administration is not feasible. Methods: A 65-year-old woman with postmenopausal osteoporosis received a single 5 mg ZOL infusion 6 months after her final Dmab injection following 12 years of continuous therapy. Within 24 h, she developed a typical acute phase response. Three days later, marked hepatocellular injury was detected, characterized by substantial elevations in transaminases and gamma-glutamyl transferase, while viral and autoimmune hepatitis were excluded. Liver enzymes normalized within five days with supportive management. Thirty-two days after ZOL administration, she developed inflammatory polyarthritis in the absence of previous rheumatologic disease and with negative immunologic testing. Treatment with low-dose prednisone (5 mg/day) resulted in rapid clinical and biochemical remission. At 6 months, bone turnover markers remained markedly elevated (CTX 0.82 ng/mL, P1NP 95 ng/mL), indicating insufficient suppression of rebound bone turnover after Dmab discontinuation. Because of the adverse events, the patient declined repeat ZOL administration. Results: Weekly oral alendronate (ALN) (70 mg) was initiated and was associated with partial suppression of bone turnover markers. Despite a decline in bone mineral density (BMD) of approximately 5% at both the lumbar spine and total hip over 12 months, BMD remained within the osteopenic range, and no new fragility fractures occurred during follow-up. Conclusions: This case illustrates two rare sequential immune-mediated adverse events following ZOL infusion and underscores the therapeutic challenges of managing Dmab discontinuation after long-term treatment when repeat ZOL administration is contraindicated. Sequential intravenous ZOL and oral ALN therapy was associated with partial suppression of bone turnover markers and protection from incident fractures during follow-up, despite a modest decline in BMD of approximately 5%. Full article

Background/Objectives: Ustekinumab, targeting the shared p40 subunit of interleukin (IL)-12 and IL-23, is an effective therapy for Crohn’s disease (CD), yet reliable predictors of response remain lacking. Given the central role of the IL-12/IL-23 axis in intestinal inflammation, we aimed to characterize the baseline mucosal expression of IL-12/IL-23 pathway components in lamina propria immune cells, and to explore their association with clinical response and remission following ustekinumab therapy. Methods: In this prospective, single-center study, biopsy-derived lamina propria mononuclear cells (LPMCs) were obtained from patients with CD prior to ustekinumab initiation. Gene expression of IL-12/IL-23 cytokine subunits and receptors was assessed by quantitative real-time PCR. Flow cytometry was performed to evaluate the distribution of T helper and innate lymphoid cell subsets and the expression of IL-23R and IL-12Rβ2. Clinical outcomes were assessed at week 16. Results: Fifteen consecutive patients were enrolled and included in the study. At week 16, 14/15 (93.3%) and 9/15 (60.0%) of patients reached clinical response and remission, respectively. No statistically significant differences in baseline mucosal gene expression of IL-12/IL-23 pathway components were observed between remitters and non-remitters. A trend toward higher expression of receptor subunits (IL23R, IL12RB1, IL12RB2) was observed in remitters, albeit with high variability and overlapping distributions. Similarly, cytokine subunits (IL23p19, IL12/IL23p40, IL12p35) showed no consistent differential expression pattern between the groups. In contrast, flow cytometry revealed a significantly higher frequency of IL-23R-expressing Th1 cells in remitters compared with non-remitters (20.6% vs. 6.8%, p = 0.009). Conclusions: Baseline transcriptional profiling of IL-12/IL-23 pathway components was not associated with remission following ustekinumab therapy. However, increased expression of IL-23R on mucosal Th1 cells identified a distinct immunological signature associated with clinical remission, suggesting that IL-23R expression on mucosal Th1 cells may represent a promising candidate biomarker that requires validation in larger independent cohorts. Full article

Background: Cigarette smoking promotes persistent systemic alterations in COPD, yet the interplay among genetic susceptibility, oxidative stress, immune dysregulation, impaired control of persistent viral replication, and long-term outcomes remains incompletely understood. Methods: We conducted an observational study in 102 patients aged ≥70 years with severe-to-very-severe COPD undergoing pulmonary rehabilitation. Current smokers (n = 38) were compared with never/former smokers (n = 64). Analyses included Chr15q25 genotyping (rs16969968), oxidative stress biomarkers (tail intensity, 8-OHdG, MDA, and bilirubin), hematological and immunological parameters, α7nAChR expression, TTV load as a surrogate marker of immune competence, latent virus prevalence, and five-year survival assessed by multivariable Cox regression. Results: Current smokers exhibited significantly higher DNA damage (tail intensity, p = 0.001; 8-OHdG, p = 0.002), lower bilirubin levels (p = 0.031), increased neutrophil and CD4⁺ T-cell counts (p = 0.031 and p = 0.028, respectively), altered α7nAChR expression on CD4⁺ T cells (p = 0.030), and higher TTV load (p = 0.002) than never/former smokers. The rs16969968 AA genotype was more frequent among current smokers. In survival analyses, an elevated WBC count was independently associated with increased mortality risk (HR 1.12, 95% CI 1.01–1.23; p = 0.035), whereas higher bilirubin levels showed a protective association. TTV load, smoking status, and FEV1 were not independently associated with mortality. Conclusions: In severe-to-very-severe COPD, smoking is associated with a distinct biological profile characterized by enhanced oxidative DNA damage, systemic inflammation, immune remodeling, reduced antioxidant defenses, and impaired control of persistent viral replication. WBC and bilirubin emerged as the biomarkers most consistently associated with long-term outcomes. These findings support integrated biological profiling as a tool for risk stratification and precision-guided rehabilitation in advanced COPD. Full article

Background: Antinuclear antibodies (ANA) can be detected in patients with rheumatoid arthritis (RA) and pose many diagnostic challenges, especially when RA presents an atypical course and requires differentiation from other systemic connective tissue diseases (sCTDs). This study assessed ANA fluorescence patterns and immunoblot profiles, as well as the relationships between ANA titers, antibody expression intensity, and markers of disease activity in patients with RA. Methods: This single-center, cross-sectional, observational study included 81 RA patients (53 ANA-positive) meeting the 2010 ACR/EULAR classification criteria. ANA titers and fluorescence patterns were assessed using indirect immunofluorescence. Anti-extractable nuclear antigen (ENA) autoantibody profiles and expression intensity were assessed using immunoblot analysis. Demographic, clinical, and laboratory data were obtained. Spearman’s rank correlation coefficient was used to analyze the relationship between ANA titers and selected variables. Univariate and multivariate logistic regression analyses were performed to identify factors associated with ANA positivity. Results: The cohort consisted primarily of women (86.4%) with moderate disease activity. ANA fluorescence patterns were heterogeneous, with nucleolar and homogeneous patterns most frequently observed. Immunoblot analysis also revealed diverse autoantibody profiles without a clearly dominant specificity. Ro-52, SS-A, and Sm antibodies were detected more frequently, although their prevalence remained relatively low. No statistically significant correlations were found between ANA titers and inflammatory markers, serological parameters, or disease activity indices. Conclusions: RA patients with positive ANA demonstrated marked immunological heterogeneity, without concomitant symptoms of sCTD. A positive result in RA may reflect generalized immune dysregulation rather than a distinct clinical subtype. Further studies with larger cohorts are needed to clarify the clinical significance of ANAs in rheumatoid arthritis. Full article