Introduction: Current medications for autoimmune disorders often induce broad-ranging side effects, prompting a growing interest in therapies with more specific immune system modulation. Pioglitazone, known for its anti-diabetic properties, is increasingly recognized for significant immunomodulatory potential. Beyond its traditional use in diabetes management, pioglitazone emerges as a promising therapeutic candidate for autoimmune disorders.
Areas covered: This comprehensive review explores pioglitazone's impact on four prominent autoimmune conditions: systemic lupus erythematosus, psoriasis, inflammatory bowel disease, and multiple sclerosis. We focus on pioglitazone's diverse effects on immune cells and cytokines in these diseases, highlighting its potential as a valuable therapeutic option for autoimmune diseases. Here we have reviewed the latest and most current research literature available on PubMed, based on research published in the last 15 years.
Expert opinion: Pioglitazone as an immunomodulatory agent can regulate T cell differentiation, inhibit inflammatory cytokines, and promote anti-inflammatory macrophages. While further clinical studies are needed to fully understand its mechanisms and optimize treatment strategies, pioglitazone represents a potential therapeutic approach to improve outcomes for patients with these challenging autoimmune conditions. The future of autoimmune disease research may involve personalized treatment approaches, and collaborative efforts to improve patient quality of life.
Introduction: Kawasaki disease [KD] is a systemic disorder characterized by acute febrile illness due to widespread medium-vessel vasculitis, mainly affecting children. Despite the ongoing advanced research into the disease pathophysiology and molecular mechanisms, the exact etiopathogenesis of KD is still an enigma. Recently, single-cell RNA sequencing [scRNA-seq], has been utilized to elucidate the pathophysiology of KD at a resolution higher than that of previous methods.
Area covered: In the present article, we re-emphasize the pivotal role of this high-resolution technique, scRNA-seq, in the characterization of immune cell transcriptomic profile and signaling/response pathways in KD and explore the diagnostic, prognostic, and therapeutic potential of this new technique in KD. Using combinations of the search phrases 'KD, scRNA-seq, CAA, childhood vasculitis' a literature search was carried out on Scopus, Google Scholar, and PubMed until the beginning of 2024.
Expert opinion: scRNA-seq presents a transformative tool for dissecting KD at the cellular level. By revealing rare cell populations, gene expression alterations, and disease-specific pathways, scRNA-seq aids in understanding the intricacies of KD pathogenesis. This review will provide new insights into pathogenesis of KD and the field of applications of scRNA-seq in personalized therapeutics for KD in the future.
Introduction: Pain in both peripheral and axial joints is a major symptom in patients with psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA). Emerging evidence demonstrates pain mechanisms, beyond those related to inflammation or joint damage, based on aberrant processing of nociceptive stimuli peripherally as well as centrally. The Janus kinase/signal transducers and activators of transcription (JAK-STAT) signaling pathway has been implicated in the processing of pain beyond its role in mediating inflammation and inhibitors of this pathway approved for the treatment of axSpA and PsA have been shown to alleviate a broad array of pain outcomes in both axial and peripheral joints.
Areas covered: We review recent definitions and standardization of the nomenclature for categorizing chronic pain according to causality, assessment tools to evaluate nociplastic pain, the pathophysiologic role of JAK-STAT signaling in nociplastic pain, evidence for the presence of nociplastic pain in axSpA and PsA, and the impact of JAK inhibitors (JAKi) on pain outcomes in clinical trials (PubMed: 01/01/2019-04/01-2024).
Expert opinion: Nociplastic pain assessment has been confined almost entirely to the use of a limited number of questionnaires in cross-sectional studies of these diseases. Though effective for alleviating pain, it is unclear if JAKi specifically impact nociplastic pain.
Objective: This study investigated the predictive value of albumin-related inflammatory markers for short-term outcomes in in-hospital cardiac arrest (IHCA) patients.
Methods: A linear mixed model investigated the dynamic changes of markers within 72 hours after return of spontaneous circulation (ROSC). Time-Dependent COX regression explored the predictive value. Mediation analysis quantified the association of markers with organ dysfunctions and adverse outcomes.
Results: Prognostic Nutritional Index (PNI) and RDW-Albumin Ratio (RAR) slightly changed (p > 0.05). Procalcitonin-Albumin Ratio (PAR1) initially increased and then slowly decreased. Neutrophil-Albumin Ratio (NAR) and Platelet-Albumin Ratio (PAR2) decreased slightly during 24-48 hours (all p<0.05). PNI (HR = 1.646, 95%CI (1.033,2.623)), PAR1 (HR = 1.69, 95%CI (1.057,2.701)), RAR (HR = 1.752,95%CI (1.103,2.783)) and NAR (HR = 1.724,95%CI (1.078,2.759)) were independently associated with in-hospital mortality. PNI (PM = 45.64%, 95%CI (17.05%,87.02%)), RAR (PM = 45.07%,95%CI (14.59%,93.70%)) and NAR (PM = 46.23%,95%CI (14.59%,93.70%)) indirectly influenced in-hospital mortality by increasing SOFA (central) scores. PNI (PM = 21.75%, 95%CI(0.67%,67.75%)) may also indirectly influenced outcome by increasing SOFA (renal) scores (all p < 0.05).
Conclusions: Within 72 hours after ROSC, albumin-related inflammatory markers (PNI, PAR1, RAR, and NAR) were identified as potential predictors of short-term prognosis in IHCA patients. They may mediate the adverse outcomes of patients by causing damages to the central nervous system and renal function.
Introduction: Rheumatoid arthritis (RA), the most prevalent autoimmune disease in reproductive years, exhibits a higher incidence in females, suggesting involvement of estrogens, genetics and environmental factors in disease onset. Literature shows smaller families in RA patients, driving increased interest in Assisted Reproductive Techniques.
Areas covered: This review elucidates how immunotolerance mechanisms contribute to favorable pregnancy outcomes in RA, emphasizing the need for a careful pregnancy planning to mitigate fetal complications and postnatal flares, which surpass those in the general population. A thorough medication evaluation, orchestrated by a multidisciplinary team, is imperative during pregnancy, weighing potential teratogenic effects against safer alternatives to balance medication safety with disease control. A systematic literature search on PubMed and MEDLINE, using specific terms, covered relevant academic journals up to the latest date.
Expert opinion: This narrative review comprehensively addresses pregnancy-related considerations in RA patients, prioritizing meticulous disease management with pregnancy and breastfeeding-compatible drugs in line with the latest recommendations and registry data. The focus remains on evaluating glucocorticoids, conventional, and biological disease-modifying drugs for compatibility during pregnancy and breastfeeding. Additionally, the evolving landscape of targeted synthetic drugs during pregnancy is explored, providing insights into the latest developments in rheumatological care.
Introduction: Systemic sclerosis (SSc) is a chronic autoimmune rheumatic disease characterized by microvascular alterations, immunopathology, and widespread fibrosis involving various organs. It is considered difficult to treat due to several reasons: complex pathogenesis, heterogeneity, late diagnosis, limited treatment options for certain organ manifestations, lack of personalized medicine.
Areas covered: This review presents the heterogeneity, survival and organ manifestations with their risk factors of systemic sclerosis and their current treatment options, while drawing attention to difficult-to-treat forms of the disease, based on literature indexed in PubMed.
Expert opinion: Despite recent advances in the management of SSc over the last decades, the disease presents significant morbidity and mortality. Although available treatment protocols brought significant advancements in terms of survival in SSc-associated interstitial lung disease and pulmonary arterial hypertension, less success has been achieved in the treatment of Raynaud's phenomenon and digital ulcers and the results are modest in case of heart, gastrointestinal, and renal manifestations. There are patients who do not respond to treatment and deteriorate even with adequate therapy. They can be considered difficult-to treat (D2T) cases. We have created a possible score system based on the individual organ manifestations and highlighted treatment options for the D2T SSc category.