Axial Spondyloarthritis: an overview of the disease.

Axial Spondyloarthritis (axSpA) is a chronic, inflammatory, immune-mediated rheumatic disease that comprises two subsets, non-radiographic and radiographic axSpA, and belongs to a heterogeneous group of spondyloarthritides (SpA). Over the years, the concept of SpA has evolved significantly, as reflected in the existing classification criteria. Considerable progress has been made in understanding the genetic and immunological basis of axSpA, in studying the processes of chronic inflammation and pathological new bone formation, which are pathognomonic for the disease. As a result, new medication therapies were developed, which bring more effective ways for disease control. This review presents a brief overview of the literature related to these aspects of disease after summarising the available information on the topic that we considered relevant. Specifically, it delves into recent research illuminating the primary pathological processes of enthesitis and associated osteitis in the context of inflammation in axSpA. The exploration extends to discussion of inflammatory pathways, with a particular focus on Th1/Th17-mediated immunity and molecular signaling pathways of syndesmophyte formation. Additionally, the review sheds light on the pivotal role of cytokine dysregulation, highlighting the significance of the IL-23/17 axis and TNF-α in this intricate network of immune responses which is decisive for therapeutic approaches in the disease.

EULAR recommendations for the non-pharmacological core management of hip and knee osteoarthritis: 2023 update.

INTRODUCTION: Hip and knee osteoarthritis (OA) are increasingly common with a significant impact on individuals and society. Non-pharmacological treatments are considered essential to reduce pain and improve function and quality of life. EULAR recommendations for the non-pharmacological core management of hip and knee OA were published in 2013. Given the large number of subsequent studies, an update is needed. METHODS: The Standardised Operating Procedures for EULAR recommendations were followed. A multidisciplinary Task Force with 25 members representing 14 European countries was established. The Task Force agreed on an updated search strategy of 11 research questions. The systematic literature review encompassed dates from 1 January 2012 to 27 May 2022. Retrieved evidence was discussed, updated recommendations were formulated, and research and educational agendas were developed. RESULTS: The revised recommendations include two overarching principles and eight evidence-based recommendations including (1) an individualised, multicomponent management plan; (2) information, education and self-management; (3) exercise with adequate tailoring of dosage and progression; (4) mode of exercise delivery; (5) maintenance of healthy weight and weight loss; (6) footwear, walking aids and assistive devices; (7) work-related advice and (8) behaviour change techniques to improve lifestyle. The mean level of agreement on the recommendations ranged between 9.2 and 9.8 (0-10 scale, 10=total agreement). The research agenda highlighted areas related to these interventions including adherence, uptake and impact on work. CONCLUSIONS: The 2023 updated recommendations were formulated based on research evidence and expert opinion to guide the optimal management of hip and knee OA.

Meteorin-like Protein and Zonulin in Polycystic Ovary Syndrome: Exploring Associations with Obesity, Metabolic Parameters, and Inflammation.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is a prevalent hormonal and metabolic disorder, wherein the adipose tissue and gut microbiome have been demonstrated to contribute to its pathogenesis. This study aims to assess the concentrations of the adipokine, meteorin-like protein (Metrnl) and the protein, zonulin, related to intestine permeability, in individuals with PCOS with a particular emphasis on their relationship with obesity, clinical manifestations, hormonal profiles, and metabolic parameters. METHODS: A cohort comprising 58 women with PCOS, classified according to the Rotterdam criteria, was enrolled. The study also considered age, body mass index (BMI), and ethnicity-matched controls (n = 30). Comprehensive anthropometric and clinical evaluations, hormonal assays, and biochemical analyses were conducted during the follicular phase. Subsequent subgroup analyses were executed within the PCOS cohort based on waist-to-height ratio (WHtR), insulin resistance (IR), and free androgen index (FAI). Serum concentrations of Metrnl and zonulin were quantified via the enzyme-linked immunosorbent assay (ELISA) technique. RESULTS: The Metrnl and zonulin levels exhibited no significant disparity between PCOS patients and controls. Nevertheless, within the entire participant cohort and the PCOS group exclusively, overweight/obese participants demonstrated higher Metrnl concentrations relative to their normal-weight counterparts (p < 0.001, p = 0.001, respectively). Furthermore, higher Metrnl concentrations were identified in subgroups characterized by high WHtR and IR in comparison to those with low WHtR (p = 0.001) and without IR (p = 0.001), respectively. A correlation emerged between Metrnl levels and various anthropometric and metabolic parameters, as well as sex-hormone-binding globulin (SHBG) and interleukin-18 (IL-18) within the PCOS group. Multiple linear regression analysis identified HOMA-IR as the sole independent predictor of Metrnl levels. CONCLUSION: While Metrnl and zonulin levels do not serve as diagnostic indicators of PCOS, elevated Metrnl concentrations exhibited robust associations with proinflammatory and metabolic irregularities within the PCOS population.

Adoption rates of recommended vaccines and influencing factors among patients with inflammatory arthritis: a patient survey.

To determine the scope of recommended vaccination uptake among patients with inflammatory arthritis (IA) receiving biologic and targeted synthetic disease-modifying antirheumatic agents (bDMARDs and tsDMARDs, respectively) and to determine factors, which influence their decision and are subject to modification. A single-center, cross-sectional study was conducted including patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), or ankylosing spondylitis (AS) on bDMARDs or tsDMARDs. Demographic, anthropometric, and clinical parameters were analyzed. Disease activity was determined using the validated indices DAS28-CRP and CDAI for RA and peripheral PsA, whereas BASDAI and ASDAS for AS and axial PsA. Patients completed a questionnaire with predefined response options assessing their vaccination status and attitudes about receiving a COVID-19 vaccination. A total of 201 patients with inflammatory joint diseases were included in the study, with a mean age of 54.6 (± 8.6) years and a disease duration of 11 (± 14.4) years. More than one-third of the study group had received full vaccination against SARS-CoV-2, with the majority (68.1%) receiving the BNT162b2 vaccine. The proportion of patients who had received recommended pneumococcal and influenza vaccinations and regular reimmunizations against diphtheria and tetanus was low, with only 13.9% (n = 28), 1.5% (n = 3), and 44.8% (n = 90), respectively. Patients who had a preceding discussions with a rheumatologist were more likely to get vaccinated. Considering the suboptimal vaccination rates and the prevalent uncertainty among individuals with IA in Bulgaria, there is an urgent need to devise novel strategies to promote vaccination uptake and enhance patient awareness. These strategies aim to educate patients about their autoimmune condition, as well as emphasize the safety and efficacy of vaccines.

The genesis of cardiovascular risk in inflammatory arthritis: insights into glycocalyx shedding, endothelial dysfunction, and atherosclerosis initiation.

This narrative review provides a comprehensive examination of the complex interplay between inflammatory arthritis (IA) and cardiovascular pathology. It particularly illuminates the roles of atherosclerosis initiation, endothelial dysfunction, and glycocalyx shedding. IA not only provokes tissue-specific inflammatory responses, but also engenders a considerable degree of non-specific systemic inflammation. This review underscores the accelerating influence of the chronic inflammatory milieu of IA on cardiovascular disease (CVD) progression. A focal point of our exploration is the critical function of the endothelial glycocalyx (EG) in this acceleration process, which possibly characterizes the earliest phases of atherosclerosis. We delve into the influence of inflammatory mediators on microtubule dynamics, EG modulation, immune cell migration and activation, and lipid dysregulation. We also illuminate the impact of microparticles and microRNA on endothelial function. Further, we elucidate the role of systemic inflammation and sheddases in EG degradation, the repercussions of complement activation, and the essential role of syndecans in preserving EG integrity. Our review provides insight into the complex and dynamic interface between systemic circulation and the endothelium.

COVID-19 related liver injuries in pregnancy.

While severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) quickly spread across the globe, our understanding of its pathogenic mechanisms evolved. Importantly, coronavirus disease 2019 (COVID-19) is now considered a syndromic multisystem inflammatory disease involving not only the respiratory system but also the cardiovascular, excretory, nervous, musculoskeletal, and gastrointestinal systems. Moreover, a membrane-bound form of angiotensin-converting enzyme 2, the entry receptor for SARS-CoV-2, is expressed on the surface of cholangiocytes and hepatocytes, suggesting the potential of COVID-19 to involve the liver. With the widespread distribution of SARS-CoV-2 throughout the population, infection during pregnancy is no longer a rare occurrence; however, little is known about the course of hepatic injuries and related outcomes in pregnant SARS-CoV-2-positive women. Thus, the understudied topic of COVID-related liver disease during pregnancy poses a great challenge for the consulting gynecologist and hepatologist. In this review, we aim to describe and summarize potential liver injuries in pregnant women with COVID-19.

Vascular effects of biologic and targeted synthetic antirheumatic drugs approved for rheumatoid arthritis: a systematic review.

BACKGROUND: Rheumatoid arthritis (RA) increases the risk of cardiovascular disease (CVD), with inflammation playing a key role. Biologic and targeted synthetic drugs used to treat RA can induce systemic immunomodulation and may have pleiotropic effects on vascular function, making it crucial to investigate their impact on CVD risk in RA patients. METHODS: A systematic review of the literature was conducted to investigate the impact of biologic and targeted synthetic treatments approved for RA on various cardiovascular markers, including endothelial function, arterial stiffness, and subclinical atherosclerosis. Our analysis included a search of the MedLine (via PubMed) and Web of Science databases using a pre-determined search strategy. We conducted a narrative synthesis of the included studies due to heterogeneity in study design and outcome measures. RESULTS: From an initial pool of 647 records, we excluded 327 studies based on their titles and abstracts, and we selected 182 studies for final examination. Ultimately, 58 articles met our inclusion criteria and were included in our systematic review. Our analysis of these studies revealed a positive effect of biologic and targeted synthetic therapies on vascular dysfunction associated with RA. However, the impact of these treatments on subclinical atherosclerosis was inconsistent. CONCLUSION: Overall, our systematic review provides important insights into the potential cardiovascular benefits of biologic and targeted synthetic treatments for RA by a still unknown mechanism. These findings can inform clinical practice and contribute to our understanding of their possible effects on early vascular pathology. Key Points • Great heterogeneity of methods are used to evaluate the endothelial function and arterial stiffness in patients with RA on biologic and targeted synthetic antirheumatic drugs. • Most studies have shown a considerable improvement in endothelial function and arterial stiffness with TNFi, despite some studies reporting only transient or no improvement. • Anakinra and tocilizumab may have a beneficial effect on vascular function and endothelial injury, as indicated by increased FMD, coronary flow reserve, and reduced levels of biomarkers of endothelial function, while the overall impact of JAKi and rituximab remains inconclusive based on the reviewed studies. • To fully comprehend the distinctions between biologic therapies, more long-term, well-designed clinical trials are necessary using a homogeneous methodology.

Intravenous Immunoglobulins as Immunomodulators in Autoimmune Diseases and Reproductive Medicine.

Intravenous administration of immunoglobulins has been routinely used for more than 60 years in clinical practice, developed initially as replacement therapy in immunodeficiency disorders. Today, the use of intravenous immunoglobulins (IVIGs) is embedded in the modern algorithms for the management of a few diseases, while in most cases, their application is off-label and thus different from their registered therapeutic indications according to the summary of product characteristics. In this review, we present the state-of-the-art use of IVIGs in various autoimmune conditions and immune-mediated disorders associated with reproductive failure, as approved therapy, based on indications or off-label. IVIGs are often an alternative to other treatments, and the administration of IVIGs continues to expand as data accumulate. Additionally, new insights into the pathophysiology of immune-mediated disorders have been gained. Therefore, the need for immunomodulation has increased, where IVIG therapy represents an option for stimulating, inhibiting and regulating various immune processes.

Takayasu arteritis associated with autoimmune/inflammatory syndrome induced by adjuvants: a case-based review.

Takayasu's arteritis (TA) is a chronic granulomatous vasculitis that predominantly affects the aorta and its major branches. Despite advancements in the understanding of the pathogenic pathways of vascular inflammation, the etiology and predisposing factors of TA remain to be fully understood. In susceptible individuals, exposure to adjuvants may trigger, unlock or unmask an autoimmune disorder, presenting as non-specific constitutional symptoms or a fully developed autoimmune syndrome such as vasculitis. Here, we hypothesize that TA could be triggered by siliconosis, a subtype of the autoimmune/inflammatory syndrome induced by adjuvants (ASIA). ASIA, also known as Shoenfeld syndrome, encompasses a wide range of autoimmune and immune-mediated diseases resulting from dysregulation of the immune response after exposure to agents with adjuvant activity. This case report describes the development of large artery vasculitis, TA, in an individual one year following the placement of silicone breast implants. The patient initially presented with non-specific symptoms, and multiple imaging methods were employed, including ultrasound diagnostics, CT angiography, and 18-fluorodeoxyglucose positron emission tomography/CT. These techniques revealed vasculitic alterations in the carotid arteries and thoracic aorta. Initial treatment with glucocorticosteroids proved ineffective, prompting the addition of steroid-sparing immunosuppressive agents. Due to the distinct clinical symptoms, disease progression, implant-associated fibrosis, and resistance to therapy, the potential involvement of implants in the development of large-vessel vasculitis was considered, and a potential association with ASIA was postulated. Although there is limited evidence to support a direct link between adjuvants and the pathogenesis of TA, similarities in cellular immunity between the two conditions exist. The diagnosis of this complex and potentially debilitating condition requires a comprehensive clinical examination, laboratory evaluation, and instrumental assessment. This will aid in identifying potential contributing factors and ensuring successful treatment.

Nonpharmaceutical interventions reduce the incidence and mortality of COVID-19: A study based on the survey from the International COVID-19 Research Network (ICRN).

The recently emerged novel coronavirus, "severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)," caused a highly contagious disease called coronavirus disease 2019 (COVID-19). It has severely damaged the world's most developed countries and has turned into a major threat for low- and middle-income countries. Since its emergence in late 2019, medical interventions have been substantial, and most countries relied on public health measures collectively known as nonpharmaceutical interventions (NPIs). We aimed to centralize the accumulative knowledge of NPIs against COVID-19 for each country under one worldwide consortium. International COVID-19 Research Network collaborators developed a cross-sectional online survey to assess the implications of NPIs and sanitary supply on the incidence and mortality of COVID-19. The survey was conducted between January 1 and February 1, 2021, and participants from 92 countries/territories completed it. The association between NPIs, sanitation supplies, and incidence and mortality were examined by multivariate regression, with the log-transformed value of population as an offset value. The majority of countries/territories applied several preventive strategies, including social distancing (100.0%), quarantine (100.0%), isolation (98.9%), and school closure (97.8%). Individual-level preventive measures such as personal hygiene (100.0%) and wearing facial masks (94.6% at hospitals; 93.5% at mass transportation; 91.3% in mass gathering facilities) were also frequently applied. Quarantine at a designated place was negatively associated with incidence and mortality compared to home quarantine. Isolation at a designated place was also associated with reduced mortality compared to home isolation. Recommendations to use sanitizer for personal hygiene reduced incidence compared to the recommendation to use soap. Deprivation of masks was associated with increased incidence. Higher incidence and mortality were found in countries/territories with higher economic levels. Mask deprivation was pervasive regardless of economic level. NPIs against COVID-19 such as using sanitizer, quarantine, and isolation can decrease the incidence and mortality of COVID-19.

Analysis of 2-Arachidonoylglycerol Levels in Polycystic Ovary Syndrome in the Context of Hormonal and Metabolic Alterations and Across the Classical Phenotypes.

Introduction: Ovarian folliculogenesis requires a fine balance between extra- and intra-ovarian factors. Endocannabinoids are found in the female reproductive system and are essential for a normal follicular growing process and ovulation. First, our study aimed to analyze levels of the endocannabinoid-2-arachidonoylglycerol (2-AG)-in patients with polycystic ovary syndrome (PCOS) and to compare with healthy controls. In addition, the study aimed to explore the association of 2-AG with hormonal and metabolic alterations, ovulatory dysfunction, and the presence of polycystic ovarian morphology (PCOM) across the classical PCOS phenotypes. Methods: Fifty-four women with PCOS were compared with 26 healthy controls. PCOS patients were diagnosed and phenotyped according to the Rotterdam criteria. Further analyses were performed with the classical PCOS phenotypes A and B comprising hyperandrogenism with oligo-anovulation with or without PCOM, respectively. Full medical history, clinical investigations, anthropometric measurements, laboratory tests, and ultrasound investigations were carried out in the follicular phase. Serum levels of 2-AG were measured by enzyme-linked immunosorbent assay. Results: PCOS patients (n=54) and healthy controls (n=26) showed similar metabolic parameters and anthropometric characteristics. PCOS patients were more hirsute than healthy women (p=0.001). Luteinizing hormone/follicle-stimulating hormone ratio and serum levels of androgens were significantly higher in the patient than in the control group (p=0.035, p<0.001, respectively). Free androgen index was also higher in the patient group (p=0.002). Serum levels of 2-AG did not significantly differ when comparing all PCOS patients versus healthy controls; however, further analysis of individual phenotype groups revealed that 2-AG levels in PCOS patients with phenotyope A (n=30) were significantly lower when compared with PCOS patients with phenotype B (n=20) and healthy controls (n=26). Conclusion: Serum levels of 2-AG were similar between PCOS patients and healthy controls. Nevertheless, phenotype A PCOS patients had significantly lower levels of the endocannabinoid compared with phenotype B patients and healthy controls. Collectively, these results suggest that overall serum levels of 2-AG are not a diagnostic marker for PCOS; however, their altered secretion or activity may influence normal follicular processes.

Anandamide is associated with waist-to-hip ratio but not with Body Mass Index in women with polycystic ovary syndrome.

BACKGROUND: The endocannabinoid system is involved in the regulation of energy balance and ovarian function and may be implicated in the pathogenesis of polycystic ovary syndrome (PCOS). The purpose of the present study is to determine anandamide (AEA) levels in PCOS patients and controls and to analyze its association with metabolic and hormonal disturbances in women with PCOS. METHODS: The study included 88 women - 58 patients with PCOS (25.9±5.2 years) and 30 healthy controls (27.6±5.2 years). Further, patients were divided into two subgroups according to their waist-to-hip ratio (WHR): android type PCOS (WHR≥0.85; N.=26) and gynoid type PCOS (WHR<0.85; N.=32). Detailed anthropometric measurements, hormonal and biochemical tests and pelvic ultrasound were obtained between the 3rd and 5th day of a menstrual cycle. AEA was examined by ELISA kits. RESULTS: Patients with PCOS and healthy controls did not differ in anthropometric, metabolic parameters, AEA, and sex hormone-binding globulin (SHBG) levels. The PCOS group had increased total testosterone, FAI, DHEAS, androstenedione, and 17-OH-progesterone levels (P<0.001) and elevated LH/FSH ratio (P=0.023). A negative correlation between AEA levels was found with glycaemia at 120 minutes (r=-0.304, P=0.020) and WHR (r=-0.266, P=0.044). In the subanalysis of patients, the gynoid type group had significantly higher levels of AEA than the android type PCOS (5.4 [2.3;8.8] vs. 2.5 [1.8;5.1]; P=0.020). CONCLUSIONS: AEA did not differ between healthy women and patients, but a significant difference in its levels was found in PCOS patients divided according to their body constitution type.

Elevated levels of interleukin-18 are associated with several indices of general and visceral adiposity and insulin resistance in women with polycystic ovary syndrome.

Objective: Our aim was to analyze levels of proinflammatory biomarker interleukin-18 (IL-18) in healthy controls and patients with polycystic ovary syndrome (PCOS) focusing on its association with obesity, clinical, hormonal, and metabolic characteristics. Methods: Fifty-eight patients with PCOS were enrolled in the study fulfilling the Rotterdam criteria and were matched for age, body mass index (BMI), and ethnicity with 30 healthy controls. Detailed anthropometric measurements, clinical investigations, hormonal and biochemical tests were obtained between the 3rd and 5th day of a menstrual cycle. A subanalysis of the PCOS group was performed separating patients into several groups according to a waist-to-height ratio (WHtR), insulin resistance (IR), and free androgen index (FAI). Serum IL-18 levels were measured using the ELISA method. Results: Levels of IL-18 were similar between PCOS patients and controls. IL-18 was higher in overweight/obese women compared to normal-weight women when analyzing all participants together and separately PCOS or controls group (p < 0.001, p < 0.001, p = 0.01, respectively). Additionally, IL-18 levels were higher in high-WHtR and IR subgroups compared to low-WHtR (p < 0.001) and non-IR PCOS women (p < 0.001). PCOS women with high FAI had greater serum IL-18 levels than normal-FAI patients (p = 0.002). Levels of IL-18 correlated positively with most of the anthropometric and metabolic parameters. In multiple linear regression, age, waist circumference, and fasting insulin were independently related factors with IL-18. Conclusion: Elevated levels of IL-18 were related to several indices of general and visceral adiposity and insulin resistance in PCOS.

Elevated levels of interleukin-18 are associated with several indices of general and visceral adiposity and insulin resistance in women with polycystic ovary syndrome

ABSTRACT Objective: Our aim was to analyze levels of proinflammatory biomarker interleukin-18 (IL-18) in healthy controls and patients with polycystic ovary syndrome (PCOS) focusing on its association with obesity, clinical, hormonal, and metabolic characteristics. Subjects and methods: Fifty-eight patients with PCOS were enrolled in the study fulfilling the Rotterdam criteria and were matched for age, body mass index (BMI), and ethnicity with 30 healthy controls. Detailed anthropometric measurements, clinical investigations, hormonal and biochemical tests were obtained between the 3rd and 5th day of a menstrual cycle. A subanalysis of the PCOS group was performed separating patients into several groups according to a waist-to-height ratio (WHtR), insulin resistance (IR), and free androgen index (FAI). Serum IL-18 levels were measured using the ELISA method. Results: Levels of IL-18 were similar between PCOS patients and controls. IL-18 was higher in overweight/obese women compared to normal-weight women when analyzing all participants together and separately PCOS or controls group (p < 0.001, p < 0.001, p = 0.01, respectively). Additionally, IL-18 levels were higher in high-WHtR and IR subgroups compared to low-WHtR (p < 0.001) and non-IR PCOS women (p < 0.001). PCOS women with high FAI had greater serum IL-18 levels than normal-FAI patients (p = 0.002). Levels of IL-18 correlated positively with most of the anthropometric and metabolic parameters. In multiple linear regression, age, waist circumference, and fasting insulin were independently related factors with IL-18. Conclusion: Elevated levels of IL-18 were related to several indices of general and visceral adiposity and insulin resistance in PCOS.

The role of IL-17 rs2275913, IL-17RC rs708567 and TGFB1 rs1800469 SNPs and IL-17A serum levels in patients with lupus nephritis.

Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease and polymorphisms in the cytokine genes and their receptors are thought to influence its development. The aim of this case-control study was to investigate the association of the IL-17A rs2275913, IL-17RC rs708567 and TGFB1 rs1800469 polymorphisms with SLE, its clinical manifestations and the polymorphisms influence on the IL-17A serum levels. Altogether 59 SLE patients with lupus nephritis and 95 healthy controls were genotyped by TaqMan assay. Serum levels were determined by Human IL-17A Platinum ELISA kit. From the studied polymorphisms, only TGFB1 T allele was found to be associated with SLE. Within the patient group, IL-17A GG genotype and TGFB1 -509T allele showed an association with the neurological disease and IL-17RC CC genotype appeared to be associated with lupus arthritis. The IL17A serum levels in the SLE and control groups (7.24 pg/ml and 5.76 pg/ml, respectively) did not show any statistical difference. A weak correlation between IL17A levels and SLEDAI-2K was observed. Our results indicate that IL-17A rs2275913, IL-17RCrs708567 and TGFB1 rs1800469 polymorphisms might play a role in the susceptibility and the clinical manifestations of SLE and IL-17A serum levels should be monitored in the course of the disease. The identification of subsets of SLE with an IL-17-driven disease could improve the therapeutic approach leading to more precise personalized treatment.

Targeting Inflammatory Cytokines to Improve Type 2 Diabetes Control.

Type 2 diabetes (T2D) is one of the most common chronic metabolic disorders in adulthood worldwide, whose pathophysiology includes an abnormal immune response accompanied by cytokine dysregulation and inflammation. As the T2D-related inflammation and its progression were associated with the balance between pro and anti-inflammatory cytokines, anticytokine treatments might represent an additional therapeutic option for T2D patients. This review focuses on existing evidence for antihyperglycemic properties of disease-modifying antirheumatic drugs (DMARDs) and anticytokine agents (anti-TNF-α, anti-interleukin-(IL-) 6, -IL-1, -IL-17, -IL-23, etc.). Emphasis is placed on their molecular mechanisms and on the biological rationale for clinical use. Finally, we briefly summarize the results from experimental model studies and promising clinical trials about the potential of anticytokine therapies in T2D, discussing the effects of these drugs on systemic and islet inflammation, beta-cell function, insulin secretion, and insulin sensitivity.

Polycystic ovary syndrome and (pre)osteoarthritis: assessing the link between hyperandrogenism in young women and cartilage oligomeric matrix protein as a marker of cartilage breakdown.

INTRODUCTION: OBJECTIVES: Our aim was to analyze the link between hyperandrogenism and early clinical manifestations of osteoarthritis (OA), knee cartilage thickness, and serum cartilage oligomeric matrix protein (sCOMP) levels in patients with polycystic ovary syndrome (PCOS) and to compare them with healthy volunteers. METHODS: Fifty-four PCOS patients who met the Rotterdam criteria with phenotypes A, B, and C were included. They were compared with 26 age- and body mass index (BMI)-matched controls. Detailed anthropometric measurements and clinical evaluation for hyperandrogenism were performed for all participants who also filled in the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire. Furthermore, laboratory tests including sCOMP and hormone quantification were performed in a fasting stage. Finally, an ultrasound assessment was carried out in randomly selected 56 study participants. RESULTS: PCOS women reported more prominent knee-related symptoms (p = 0.035) and more impaired activities of daily living (ADL) (p = 0.001) than controls. Cartilage thickness of the left and right medial condyle and left lateral condyle was significantly greater in PCOS group (n = 41) than in control group (n = 15) (p = 0.05, p = 0.006, and p = 0.036, respectively). COMP correlated significantly and negatively with testosterone levels (p = 0.029, r = - 0.297) in women with PCOS and the correlation remained significant after controlling for BMI. CONCLUSIONS: Women with PCOS may experience knee-related symptoms and impaired ADL. They had greater knee femoral cartilage thickness. Although sCOMP levels did not significantly differ between the groups, lower levels of sCOMP may be inherent to PCOS patients with higher testosterone levels. Key Points • Although PCOS patients may experience more prominent knee related symptoms, their femoral cartilage of the knee joint is found thicker than controls. • PCOS patients did not have significantly elevated levels of sCOMP. • Lower sCOMP levels were related to higher testosterone levels.

SARS-CoV-2 vaccines and autoimmune diseases amidst the COVID-19 crisis.

Coronavirus disease 2019 (COVID-19) pandemic has become challenging even for the most durable healthcare systems. It seems that vaccination, one of the most effective public-health interventions, presents a ray of hope to end the pandemic by achieving herd immunity. In this review, we aimed to cover aspects of the current knowledge of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines and vaccine candidates in the light of autoimmune inflammatory diseases (AIIDs) and to analyze their potential in terms of safety and effectiveness in patients with AIIDs. Therefore, a focused narrative review was carried out to predict the possible implications of different types of SARS-CoV-2 vaccines which confer distinct immune mechanisms to establish immune response and protection against COVID-19: whole virus (inactivated or weakened), viral vector (replicating and non-replicating), nucleic acid (RNA, DNA), and protein-based (protein subunit, virus-like particle). Still, there is uncertainty among patients with AIIDs and clinicians about the effectiveness and safety of the new vaccines. There are a variety of approaches towards building a protective immunity against SARS-CoV-2. Only high-quality clinical trials would clarify the underlying immunological mechanisms of the newly implemented vaccines/adjuvants in patients living with AIIDs.

Serum levels of matrix metalloproteinase-3 as a prognostic marker for progression of cartilage injury in patients with knee osteoarthritis.

OBJECTIVE: To evaluate serum matrix metalloproteinase (MMP)-3 levels as a prognostic marker for the progression of cartilage damage in patients with knee osteoarthritis (KOA). METHODS: Fifty-six patients, aged 40 to 80 years (62.59 ± 10.11 years) who met the ACR criteria for KOA, were included in a one-year observational prospective clinical study. Complete baseline and follow-up data were collected from 50 out of 56 patients. X-ray and magnetic-resonance images were carried out at baseline and after 12 months. They were evaluated according to the Kellgren-Lawrence and Whole-Organ magnetic Resonance iMaging Score (WORMS) semi-quantitative scales, respectively. Progression of cartilage damage in the medial tibiofemoral compartment was registered at the end of the follow-up using the change in WORMS. Serum levels of MMP-3 were measured during the baseline visit, using enzyme-linked immunosorbent assay. RESULTS: Significantly higher values of baseline MMP-3 levels were observed in patients with a registered progression of cartilage injury in the medial tibiofemoral compartment of the knee compared with patients with no progression (p = 0.005). Binary logistic regression analysis showed that levels of serum MMP-3 (ng/ml) were an independent predictor of subsequent progression of cartilage injury in the medial tibiofemoral compartment of the index knee (assessed by MRI) (OR = 1.042, CI 95%: 1.002-1.084). Receiver operating characteristic analysis was performed to delineate progressors from non-progressors. CONCLUSION: Serum MMP-3 levels may serve as a potential prognostic biomarker for cartilage injury in patients with KOA.

Complexities of diagnosis and management of COVID-19 in autoimmune diseases: Potential benefits and detriments of immunosuppression.

Recent advances in our understanding of coronavirus disease 2019 (COVID-19) and the associated acute respiratory distress syndrome might approximate the cytokine release syndrome of severe immune-mediated disease. Importantly, this presumption provides the rationale for utilization of therapy, until recently reserved mostly for autoimmune diseases (ADs), in the management of COVID-19 hyperinflammation condition and has led to an extensive discussion for the potential benefits and detriments of immunosuppression. Our paper intends to examine the available recommendations, complexities in diagnosis and management when dealing with patients with ADs amidst the COVID-19 crisis. Mimicking a flare of an underlying AD, overlapping pathological lung patterns, probability of higher rates of false-positive antibody test, and lack of concrete data are only a part of the detrimental and specific characteristics of COVID-19 outbreak among the population with ADs. The administration of pharmaceutical therapy should not undermine the physical and psychological status of the patient with the maximum utilization of telemedicine. Researchers and clinicians should be vigilant for upcoming research for insight and perspective to fine-tune the clinical guidelines and practice and to weigh the potential benefits and detrimental effects of the applied immunomodulating therapy.