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.

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.

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.

Bilateral rapidly destructive coxopathy in rheumatoid arthritis.

Rapidly destructive coxopathy (RDC) is a rare type of coxarthritis marked by swift deterioration of the hip joint. Although its cause remains unclear, several pathophysiological mechanisms are proposed. To comprehensively analyze this poorly understood condition, a literature search was conducted focusing on associations of bilateral RDC and rheumatoid arthritis (RA). The problem of long-standing RA, bilateral RDC with a febrile episode that preceded a rapid decline in mobility and severe hip pain, with radiological assessment confirmed bilateral hip destruction, was presented. Rapidly destructive coxopathy, especially when linked to RA, poses diagnostic and therapeutic challenges. Our review confirmed by the clinical picture emphasizes the need for vigilance in RA patients with hip involvement and calls for further research to understand RDC's mechanisms and enhance clinical care.

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.

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.

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.

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.

Multimodal approach to intraarticular drug delivery in knee osteoarthritis.

The expectations from any future disease-modifying treatment for knee osteoarthritis (KOA) are extremely high as it has to impact the joint as a whole leading to favorable alterations of diverse tissues and functions. In this light, targeting the knee only from the inside may not be biologically justified for the management of a whole joint disease such as KOA. Our hypothesis to test is whether any injectable therapeutic intervention alone can lead to disease modification of KOA which is viewed in the complexity of the modern concept of osteoarthritis (OA) as a whole joint disease. Therefore, we aimed at analyzing the intraarticular route to the KOA patient in an attempt to unveil its "biological" constraints. A comprehensive search through databases was carried out using specific keywords to add objectivity to the main messages. The literature analysis has shown that "cutting-edge" intraarticular therapies may offer a key to non-invasive symptomatic relief. Changing the course of KOA, however, may necessitate a multimodal approach towards the knee joint including a combination of intraarticular injections with interventions on multiple levels. Importantly, our understanding of OA has evolved redefining the concept of the disease, being in interaction with the human body as a whole. Any future conservative disease-modifying treatment of KOA should aim at a multimodal, holistic approach towards the knee joint including but not limited only to intraarticular injections. A combination with other interventions should be further researched.

Modifiable risk factors in knee osteoarthritis: treatment implications.

Optimal management of knee osteoarthritis (KOA) should include, where possible, modification of risk factors through targeted interventions. The objectives of the present narrative review were to identify, summarize, and cluster all the potentially modifiable risk factors that influence the course of KOA, and discuss their susceptibility to alteration via personal, clinical, and public strategy. For this purpose, Pubmed and Scopus databases were queried using the terms "knee osteoarthritis", "risk factors" and "improvement". Six main categories of modifiable risk factors were identified: (1) obesity and overweight, (2) comorbidity, (3) occupational factors, (4) physical activity, (5) biomechanical factors, (6) dietary exposures. In the era of age- and obesity-related diseases, the combined effects of local and systemic risk factors should be managed by combined measures. Femoral muscle-strengthening physical activities, complemented with proper diet, weight loss, vocational rehabilitation, management of comorbidities (especially diabetes and depression), and biomechanical support may add up to the holistic therapeutic approach towards the patient with KOA. An individual risk factor modification program should be developed in accordance with patient preferences and habits, workplace, medical history, and overall health condition. Due to its great impact on a wide range of functions and tissues, interventions on modifiable risk factors improve not only the symptoms of KOA but also affect the osteoarthritic joint as a whole.

Bulgarian rheumatology: science and practice in a cost-constrained environment.

Our aim was to appraise publications from Bulgaria, to assess their global impact, and to describe features and challenges unique to the rheumatology practice in Bulgaria characterized by stringent cost constraints. The Scopus database was queried on 25th July 2018 and data on the number of published documents, their Hirsch-indices and citations number were extracted. Published Bulgarian guidelines for the management of rheumatic diseases and the presented data on Bulgarian Rheumatology Society were identified based on prior knowledge of the authors. From all the identified 1082 document the most extensively researched areas were rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), osteoporosis, and osteoarthritis (OA). For the last five years (from Jan 2013 to 25th July 2018) the number of publications was 293. We found that Bulgaria's international scientific collaboration in the field of rheumatology is focused on a handful of countries mainly from Europe. Although Bulgarian rheumatologists have access to costly biologic agents for treating their patients with rheumatic diseases, their funding may not be granted according to the current recommendations of European League against Rheumatism (EULAR) and national guidelines for the management of rheumatic diseases. Although the western world clearly dominates the production of scientific publications in rheumatology, Bulgarian rheumatology may present another perspective for diagnosis and management of patients with rheumatic diseases in a cost-stringent environment. Nevertheless, both rheumatology science and practice in Bulgaria still have a long way to go to take its deserved place among the other European countries.

Clinical characteristics and disability in patients with knee osteoarthritis: real world experience from Bulgaria.

OBJECTIVES: Although knee osteoarthritis (KOA) is a leading cause of impaired functioning among older adults globally, little is still known about the complex mechanisms of disability accumulation in these patients. The aim of the study was to analyze the clinical parameters of patients with KOA in a Bulgarian population and to determine which of these clinical characteristics define disability to the greatest extent. MATERIAL AND METHODS: Patients aged 40-80 years with symptomatic KOA were included. The assessment tools for pain, clinical disease severity, and disability were the pain visual analogue scale (VAS) and disease-specific questionnaires: Algofunctional Index of Lequesne, Western Ontario and McMaster Universities OA Index (WOMAC), and the Health Assessment Questionnaire-Disability Index (HAQ-DI), respectively. Radiographs of the knees were obtained and graded according to the Kellgren-Lawrence (KL) system. RESULTS: One hundred and thirty-two patients (81% women) participated in the study. The median values of VAS (mm), WOMAC, Lequesne, and HAQ-DI scores were 52, 37.5, 11, 0.88, respectively. Men had milder disease, resulting in lower VAS, WOMAC, Lequesne, and HAQ-DI scores and less structural damage compared to women (p < 0.05). WOMAC index correlated positively with age of the patients but not with duration of the complaints. Patients with severe and very severe pain did not differ in their HAQ-DI, disease severity and KL grading. WOMAC physical function score and Lequesne index were independent predictors for the HAQ-DI in patients with KOA. CONCLUSIONS: Bulgarian patients with KOA had moderate disability which showed a strong relationship with physical function of WOMAC and disease severity. Multiple layers of causality coexist to determine the knee pain in Bulgarian patients with KOA.

Cartilage oligomeric protein, matrix metalloproteinase-3, and Coll2-1 as serum biomarkers in knee osteoarthritis: a cross-sectional study.

Biochemical markers reflecting joint remodeling in osteoarthritis (OA) are a promising diagnostic tool. The aim of this study was to investigate serum levels of candidate biomarkers in subjects with and without knee OA and assess their correlation with clinical parameters and knee structural damage. 56 patients with primary knee OA and 31 healthy controls participated in this study. Patients were separated into two groups: isolated knee OA and generalized OA. Clinical parameters were obtained by validated self-reported questionnaires and a visual analogue scale. Serum levels of cartilage oligomeric protein (COMP), matrix metalloproteinase-3 (MMP-3), and Coll2-1 were quantified by enzyme-linked immunosorbent assay. Knee structural damage was determined by plain X-ray and 1.5 T magnetic resonance imaging (MRI), using Kellgren-Lawrence (KL) grading scale and Whole-Organ Magnetic Resonance Imaging Score (WORMS), respectively. Compared to controls, patients had significantly higher median serum COMP (985 vs. 625 ng/ml; p < 0.001) and MMP-3 (36.85 vs. 22.10 ng/ml; p = 0.003) levels. Patients with radiographic evidence of KLII/III knee OA had greater median COMP levels than KLI patients (1095 vs. 720 ng/ml; p = 0.001). In the generalized OA group, mean MMP-3 levels were higher than in the isolated knee OA group (30.40 vs. 55.13 ng/ml; p < 0.001). COMP correlated positively with WORMS (r s = 0.454, p < 0.001) and MMP-3 (r s = 0.337, p = 0.003). Cut-off values for serum COMP and MMP-3 were determined. We observed higher serum COMP and MMP-3 levels in knee OA patients compared to controls. COMP may reflect knee structural damage, while MMP-3-OA "generalization".

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.

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.

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.

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.

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.