Search Results (2,924)

Chronic hepatitis B (CHB) and Type 2 diabetes (T2DM) are major independent risk factors for Hepatocellular carcinoma (HCC). The bidirectional promotion between T2DM and CHB forms the biological basis for their synergistic carcinogenic effect. T2DM mainly accelerates the progression of CHB through mechanisms such as metabolic disorders, oxidative stress, chronic inflammation, and immunosuppression; CHB promotes the development of T2DM mainly through liver damage leading to dysfunction of the central glucose metabolism, HBx-driven gluconeogenesis, inhibition of the insulin signaling pathway, and potential β-cell damage. In comorbid conditions, these mechanisms intertwine to form a vicious cycle across four key aspects: metabolic and lipid disorders, activation of carcinogenic pathways, oxidative stress, and amplification of chronic inflammation, significantly accelerating the hepatocarcinogenesis. Regarding management strategies, we adopt the concept of three-level prevention, integrate various management plans and combine emerging drug therapies. We thus propose the establishment of a management strategy centered on “liver and glucose co-management” with multi-faceted joint control. This review aims to summarize the latest evidence on the mechanisms and management strategies by which the comorbidity of T2DM and CHB promotes the development of HCC, providing a theoretical basis for research on the mechanisms of this comorbidity and population-level HCC prevention strategies. Full article

Background: Cardiovascular disease (CVD) represents the second leading cause of death among kidney transplant recipients (KTRs). CVD risks post-transplantation increase with aging, obesity, dyslipidemia, diabetes, hypertension, inactivity, sleep disturbances, immunosuppressant medications use, and graft dysfunction. This study assessed CVD prevalence and risk factors among KTRs. Methods: A cross-sectional study was conducted at National Guard Hospital, Jeddah between 2012–2022. Information was collected from the patients’ medical records. Physical activity, sleep, and adherence to immunosuppressant therapy were evaluated via interviews with adult KTRs using the International Physical Activity Scale, Jenkins Sleep Scale, and Immunosuppressant Therapy Barrier Adherence Scale, respectively. Results: Sixty-four KTRs were included: 67% were males, and the median age was 44.7 years. Eighteen patients (28.1%) had CVD, and 61.1% of them developed ischemic heart disease. KTRs with CVD were older, had lower estimated glomerular filtration rate (eGFR), and higher Hemoglobin A1c (HbA1c), but these differences were not statistically significant (p > 0.05). Patients with CVD had significantly lower LDL (p = 0.02) and more aspirin and statin use (p < 0.05). Forty-five patients (70.3%) completed the interview; most of them had few sleep disturbances and good adherence to immunosuppressant therapy. Low physical activity was reported by KTRs with CVD. Conclusions: CVD was present in over one-quarter of KTRs. Patients with CVD were older, less active, had lower GFR, higher HbA1c, and significantly lower LDL. More use of aspirin and statin improved the glycemic control, physical activity, and medication adherence, and may help in reducing CVD burden among KTRs. Full article

Background: Neuromyelitis optica spectrum disease (NMOSD) is a severe and highly disabling autoimmune astrocytopathy in which humoral immunity, mediated by the presence of autoantibodies, and cellular immunity, through Th17 cells and related cytokines, are key contributors to the pathogenesis. This neuroglial disease affects the central nervous system and is predominantly described in the young productive population. For many years, NMOSD treatment lacked disease-specific therapies and relied on conventional immunosuppressive agents. Progress in elucidating underlying mechanisms of the disease has led to the development and approval of highly specific and effective pathology-modifying drugs. Objective: The objective of this paper is to analyze current and emerging monoclonal antibody-based therapies for NMOSD. Methods: A systematic review of the literature was conducted focusing on approved and investigational monoclonal antibodies targeting major immunopathogenic pathways in NMOSD. Both long-term maintenance therapies and treatments for acute relapses were considered. Results: Targeted monoclonal antibody therapies have significantly transformed the therapeutic management of NMOSD. Drugs directed at B-cell depletion, IL-6 receptor inhibition, and complement blockade have demonstrated substantial efficacy in reducing relapse rates and improving clinical outcomes. Emerging therapies and biomolecular engineering represent promising strategies aimed at further modulating disease activity. These treatments offer improved specificity compared with traditional immunosuppressive regimens and contribute to better long-term disease control. Conclusions: The growing understanding of NMOSD immunopathogenesis has led to the development of highly specific monoclonal antibody-based therapies that have substantially redefined long-term maintenance strategies. Emerging biological targets may expand future therapeutic options. Continued research is essential to optimize individualized treatment approaches and improve outcomes for patients with NMOSD. Full article

Background and Objectives: Cardiovascular disease is the leading cause of mortality in patients with ANCA-associated vasculitis (AAV) after the first year post-diagnosis. This study investigated relationships between traditional risk factors, echocardiographic findings, disease activity, and major adverse cardiovascular events (MACE) in AAV patients. Aim: This retrospective single-center study aimed to evaluate the impact of traditional cardiovascular risk factors and echocardiographic parameters on the occurrence of MACE in patients with AAV. Materials and Methods: This study included adult patients with AAV who were evaluated between 2020 and 2025. Data collected included demographics, cardiovascular risk factors, Birmingham Vasculitis Activity Score version 3 (BVASv3), laboratory parameters, immunosuppressive therapy, and transthoracic echocardiography (TTE) findings. MACE was defined as myocardial infarction, stroke, revascularization, cardiovascular hospitalization, or cardiovascular death. Results: The cohort comprised 32 females (61.5%) and 20 males (38.5%), with a mean age of 62.4 ± 12.4 years. MACE occurred in 38.5% of patients. Male gender (p = 0.002), overweight (p = 0.016), hyperlipidemia (p = 0.003), and prior cardiovascular disease (p = 0.002) were significantly associated with MACE in univariate analyses. Patients with MACE had larger left atrial anteroposterior dimensions on the parasternal long-axis view (median 3.9 vs. 3.3 cm, p = 0.002) and lower left ventricular ejection fraction assessed by the modified biplane Simpson’s method (median 53% vs. 60%, p = 0.002). Valvular dysfunction was not associated with MACE in a statistically significant manner. Disease activity markers (BVASv3 and CRP) showed no significant correlation with cardiovascular events or echocardiographic parameters. Conclusions: Our results demonstrate that traditional cardiovascular risk factors are stronger determinants of MACE in AAV patients than disease-specific parameters. Cardiac structural changes, including left atrial dilation and decreased left ventricular ejection fraction, were significantly associated with cardiovascular outcomes. These findings underscore the importance of integrating systematic cardiovascular risk assessment and aggressive risk factor modification into standard AAV management protocols. Full article

Background. Autoimmune sclerosing cholangitis (ASC) is a rare clinical entity characterized by overlapping features of autoimmune hepatitis and primary sclerosing cholangitis. It predominantly affects pediatric patients. Therapeutic management is often complex, requiring a multidisciplinary and individualized approach, especially in the context of associated autoimmune diseases. Case presentation. We present the case of a female patient diagnosed at the age of 10 with ASC, for which immunosuppressive therapy with prednisone, azathioprine (AZA), and ursodeoxycholic acid (UDCA) was initiated, with an initially favorable course. One year later, following a Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection, the patient experienced reactivation of liver disease and subsequently developed ulcerative pancolitis (UC), for which 5-aminosalicylic acid (5-ASA) therapy was initiated. Due to repeated hepatic flares and/or colitis relapses, therapy was escalated successively to mycophenolate mofetil, tacrolimus, and eventually infliximab (IFX). Despite treatment, the liver disease progressed, culminating in liver cirrhosis. Our patient developed portal hypertension and esophageal varices, with two episodes of upper gastrointestinal bleeding requiring endoscopic band ligation. At the age of 14, the patient developed recurrent episodes of non-infectious ulcerative stomatitis. Biopsy of the lesions revealed non-specific chronic inflammation, unrelated to colitis activity (confirmed microscopic remission of UC). By exclusion, an adverse drug reaction was suspected, with AZA being the most likely cause. Following its discontinuation, the lesions resolved. Beyond the physiological and therapeutic aspects, the patient displays marked emotional fragility due to prolonged and repeated hospitalizations (18 out of 60 months), which have impacted treatment adherence. Conclusions. This case highlights the complexity of managing pediatric patients with multiple autoimmune diseases. The necessary combination of immunosuppressive therapies may lead to significant adverse effects and further complicate disease progression. Moreover, psychological components play a crucial role in treatment compliance and therapeutic success, emphasizing the need for an integrated approach that includes specialized psychological support. Full article

CAR-T cell therapy has shown substantial efficacy in haematological malignancies, but its application to solid tumours remains limited by poor effector-cell infiltration, functional exhaustion, antigenic heterogeneity, and an immunosuppressive microenvironment. In this study, we develop a new spatiotemporal mathematical model of CAR-T therapy for solid tumours that integrates these resistance mechanisms within a single reaction–diffusion framework. The model is formulated as a system of partial differential equations describing functional and exhausted CAR-T cells, antigen-positive and antigen-low tumour subpopulations, and chemokine, immunosuppressive, and hypoxic fields. Steady-state analysis and finite-difference simulations showed that therapeutic outcome is governed by the interplay between CAR-T cell infiltration, exhaustion, and antigen escape. The model reproduces partial tumour regression followed by residual tumour persistence, therapy-driven enrichment of antigen-low cells, and reduced efficacy under stronger immunosuppressive and hypoxic conditions. In the combination therapy scenario considered here, repeated simulated CAR-T cell administration together with attenuation of the suppressive microenvironment improves tumour control. The proposed model provides a mechanistic basis for analysing resistance and for future optimisation studies of CAR-T therapy in solid tumours. Full article

Background: Liver transplant recipients are highly susceptible to infectious complications due to surgical invasiveness and immunosuppressive therapy, and post-transplant bloodstream infection is associated with substantial morbidity and mortality. Although several prediction models for bloodstream infection have been proposed, most focus on emergency department or general ward populations and rely on black-box approaches. This limits their applicability and clinical interpretability in liver transplant settings. Therefore, this study aimed to develop predictive models for post-transplant bloodstream infection using preoperative and perioperative clinical data and to derive an interpretable risk equation through symbolic regression. Methods: We conducted a retrospective observational study including 245 adult liver transplant recipients treated at a single tertiary center. Clinical and laboratory variables were extracted from electronic medical records and analyzed using standard statistical methods. For prediction tasks, multiple conventional machine learning models were developed and compared with a symbolic regression-based model. Predictive performance and model interpretability were evaluated using discrimination metrics and Shapley Additive Explanations. Results: Post-transplant bloodstream infection occurred in 82 patients (33.4%). In the test set, conventional machine learning models showed modest discriminative performance (area under the curve, 0.53–0.64). The symbolic regression model achieved comparable discrimination (area under the curve, 0.63) while providing transparent, threshold-based risk equations. While conventional models primarily relied on laboratory variables, symbolic regression additionally identified perioperative clinical factors and viral serologic markers as important predictors. Discussion: Although overall predictive performance was modest, symbolic regression highlighted viral serologic markers as potential indicators of immunologic vulnerability, extending beyond standard laboratory predictors. Conclusions: This interpretability-focused approach may inform future risk stratification models incorporating richer perioperative data. Full article

Background/Objectives: Dupilumab is a fully human IgG4 monoclonal antibody targeting the interleukin-4 receptor α subunit, inhibiting interleukin-4 and interleukin-13 signalling, and suppressing type 2 inflammation. It is approved for several eosinophilic and type 2 inflammatory diseases, including chronic rhinosinusitis with nasal polyps, asthma, atopic dermatitis, eosinophilic oesophagitis, and, more recently, eosinophilic chronic obstructive pulmonary disease. Although generally well tolerated, dupilumab has been associated with peripheral eosinophilia and, rarely, eosinophil-mediated complications. This study aims to describe cases of eosinophilic granulomatosis with polyangiitis (EGPA) occurring after dupilumab initiation and to review available evidence on this association. Methods: We describe two cases of new-onset EGPA developing after the introduction of dupilumab therapy, analysing clinical features, laboratory findings, management, and outcomes. A narrative review of published case reports and literature addressing dupilumab-associated eosinophilia and EGPA was also performed. Results: Both patients developed EGPA after starting dupilumab, presenting with marked peripheral eosinophilia and systemic manifestations consistent with the disease. Clinical improvement was observed following dupilumab discontinuation and initiation of appropriate immunosuppressive treatment. The literature review identified a small number of similar reports describing EGPA onset or unmasking in temporal association with dupilumab, mainly in patients with underlying type 2 inflammatory disorders. Conclusions: While a causal relationship between dupilumab and EGPA remains unproven, these findings highlight the importance of clinical awareness. Dupilumab remains an effective therapy for severe type 2 inflammatory diseases; careful monitoring may allow early recognition and management of rare eosinophilic complications. Full article

Lupus nephritis (LN) stands out as one of the most critical complications of systemic lupus erythematosus (SLE), affecting almost 60% of the patient population. Even though more therapies have been made available for LN in the past decade, clinical outcomes remain less than ideal: nearly 10% to 30% of LN cases still advance to end-stage kidney disease (ESKD), still making the management of LN a clinical challenge. Therefore, the primary aim of treatment of LN is simple: to halt the progression toward chronic kidney disease (CKD) and prevent renal failure. In this review, we briefly describe the immunopathological basis of LN, which provides the scientific rationale for new drug development. We will focus on the current in-use medications, especially on proliferative LN, building on the legacy of the 20th century, and we will outline new emerging targeted and innovative therapies. We will also present the standard-of-care as informed by international guidelines and review the management of special groups, including children and pregnant women. Full article

Tinea incognito is an atypical form of dermatophytosis caused by previous use of topical or systemic immunosuppressive therapy, most often corticosteroids. Modification of the clinical presentation frequently leads to diagnostic delay and misdiagnosis, especially in patients with concomitant chronic inflammatory skin diseases such as psoriasis. We present a narrative review of the literature on tinea incognito in patients with psoriasis during immunosuppressive therapy. We screened 386 abstracts and included 16 comparable case reports focusing on tinea incognito occurring in patients with psoriasis or during antipsoriatic treatment. The review summarizes clinical presentations, diagnostic challenges, and therapeutic approaches reported in the literature. Additionally, we present a clinical case of a 27-year-old man with a long history of plaque psoriasis treated with methotrexate and cyclosporine. The patient developed rapidly progressive skin lesions with pustular features and further deterioration despite systemic antipsoriatic therapy. Initial mycological examinations were negative. Histopathological examination revealed a chronic purulent perifollicular inflammatory process with extension into the subcutaneous tissue. The correct diagnosis was confirmed after a repeat skin biopsy with periodic acid–Schiff and Grocott staining and fungal culture of the skin tissue, which revealed Trichophyton rubrum. The review highlights that clinical features are often nonspecific and may overlap with inflammatory dermatoses. This underscores the need for a high index of clinical suspicion for fungal infection in atypical or refractory psoriatic lesions. It also emphasizes the importance of repeated mycological and histopathological examinations to achieve an accurate diagnosis, avoid inappropriate escalation of immunosuppression, and enable timely antifungal treatment. Full article

Cutaneous T-cell lymphoma (CTCL) comprises a heterogeneous group of extranodal non-Hodgkin lymphomas. With the publication of the fifth edition of the World Health Organization Classification of Hematolymphoid Tumors, the diagnostic framework for CTCL has shifted from primarily morphologic phenotypes toward an emphasis on molecular drivers. Current research suggests that malignant clones may arise from somatic mutations at the hematopoietic stem cell stage and may follow a continuous hematogenous dissemination model with bidirectional trafficking between the skin and systemic circulation. At the molecular level, genomic instability, often associated with somatic copy-number variations, may promote activation of the janus kinase-signal transducer and activator of transcription (JAK/STAT) signaling pathway through gene-dosage effects. In parallel, chromatin remodeling linked to EZH2 overexpression and reduced special SATB1 expression may support a Th2-polarized program. This phenotype may contribute to epidermal barrier impairment via cytokines such as Interleukins-4 (IL-4) and IL-13, potentially creating conditions permissive for Staphylococcus aureus colonization. Microbial superantigens and exotoxins may further contribute to tumor progression and therapeutic resistance by reinforcing JAK/STAT signaling, particularly STAT3, and reducing CD8+ T-cell–mediated immune surveillance. In the dermis, reprogramming of cancer-associated fibroblasts and polarization of macrophages toward an M2 phenotype may collectively contribute to an immunosuppressive niche. Emerging biomarkers, including CD74, and acquired resistance mechanisms after anti-C-C chemokine receptor 4 therapy further extend the translational relevance of recent pathologic findings. Overall, CTCL evolution appears to be a systemic process shaped by interactions between tumor-intrinsic genetic alterations and the skin microenvironment. Full article

Methotrexate (MTX) is widely used for its chemotherapeutic and immunosuppressive properties, but is limited by oxidative stress-mediated hepatotoxicity. Nanoantioxidant delivery systems can enhance the stability, solubility, and in vivo efficacy of natural antioxidants. This study investigated the hepatoprotective effects of myricetin (MYR), a flavonoid with potent antioxidant activity, and its liposomal nanoantioxidant formulation (MYR-loaded liposomal nanoparticles, MYR-LNPs) against MTX-induced liver injury in male albino Sprague Dawley rats. Sixty rats were randomly allocated to six groups: control, MTX, MYR, MYR-LNPs, and combinations of MTX with MYR-LNPs. MYR-LNPs were successfully formulated and physicochemically characterized, exhibiting a mean particle size of 95.6 nm, a zeta potential of −32 mV, and a narrow polydispersity index, collectively confirming their colloidal stability and suitability for hepatic delivery. MTX markedly disrupted liver function, increasing serum AST, ALT, ALP, and bilirubin and decreasing total protein, albumin, and globulin, whereas co-treatment with MYR-LNPs substantially restored these parameters and outperformed free MYR. MTX-induced oxidative stress, reflected by depleted hepatic GSH and antioxidant enzymes (GPx, SOD, CAT, GST), elevated reactive oxygen species (ROS), malondialdehyde (MDA), and protein carbonyls and downregulated NRF2/HO-1, was significantly counteracted by MYR-LNPs. In addition, MYR-LNPs mitigated MTX-evoked inflammation and nitrosative stress by reducing NF-κB, TNF-α, IL-1β, nitric oxide, and iNOS expression. They corrected apoptotic imbalance by lowering Bax and caspase 3 while increasing Bcl-2. Histopathological and ultrastructural assessments confirmed that MYR-LNPs preserved hepatic architecture and mitochondrial integrity. These findings indicate that MYR-loaded liposomal nanoantioxidants provide superior protection against MTX-induced hepatotoxicity by modulating oxidative stress, inflammation, and apoptosis, supporting their potential as an advanced nanodrug delivery strategy for antioxidant therapy. Full article

Alveolar echinococcosis (AE), caused by Echinococcus multilocularis larvae, is a severe zoonotic disease mimicking tumors, primarily affecting the liver with high mortality if untreated. Host immunity plays a pivotal role, shifting from Th1/Th17-mediated clearance to Th2/Treg-driven tolerance, enabling parasite survival. Liver macrophages, including Kupffer cells, polarize towards M2 phenotype under parasite antigens (e.g., phytic acid, exosomes), promoting immunosuppression, fibrosis, and T cell exhaustion via IL-10/TGF-β. This reshapes the tumor-like immune microenvironment with M2 macrophages recruiting Tregs, suppressing NK/DC functions, and fostering angiogenesis/fibrosis. Current treatment remains centered on surgery and benzimidazole therapy, both of which have notable limitations. Experimental immunomodulatory strategies, drug repurposing approaches, and targeted delivery systems may offer future therapeutic opportunities, but these concepts remain largely preclinical, unproven in AE, and require careful evaluation for safety and efficacy. Full article

Background: Thrombotic thrombocytopenic purpura (TTP) is a life-threatening condition resulting from a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13 (ADAMTS13) deficiency, leading to the accumulation of ultra-large von Willebrand factor (vWF) multimers and widespread microvascular thrombosis. While therapeutic plasma exchange and immunosuppression have significantly improved response, refractory and relapsed disease are significant challenges. N-acetylcysteine (NAC) has emerged as a biologically plausible adjunctive therapy due to its potential to reduce disulfide bonds in vWF multimers. However, its clinical role is unclear. This systematic review aimed to evaluate the clinical evidence regarding the efficacy and safety of N-acetylcysteine in patients with immune-mediated TTP. Methods: We performed a systematic review in accordance with the PRISMA guidelines. PubMed/MEDLINE, Google Scholar, and ClinicalTrials.gov were searched until January 2026. Studies involving patients with immune-mediated TTP treated with NAC were included. Case reports, case series, and observational studies involving patients with immune-mediated TTP treated with NAC were included. Risk of bias was evaluated using adapted quality assessment tools. Results: Sixteen studies encompassing 69 patients met the inclusion criteria. Most reports were case reports or small case series; two were larger observational cohorts. NAC was predominantly used as adjunctive therapy in relapsed or refractory TTP. Dose regimens varied. Platelet recovery following NAC was reported within 1–15 days in responding cases. Predominantly positive haematological responses were observed in small series. Significant heterogeneity in patient populations, timing of initiation, concomitant therapies, and outcome reporting limited causal inference. Conclusions: The current evidence suggests that NAC has a biologically rational and potentially adjunctive value in TTP, particularly in refractory disease or resource-constrained settings. However, current data are largely heterogeneous and derived from low-level evidence. Well-designed prospective studies and randomized controlled trials are needed to determine whether NAC provides significant clinical benefit beyond standard therapy. Full article