Molecular Mechanisms of Fetal and Neonatal Lupus: A Narrative Review of an Autoimmune Disease Transferal across the Placenta.

This study, conducted by searching keywords such as "maternal lupus", "neonatal lupus", and "congenital heart block" in databases including PubMed and Scopus, provides a detailed narrative review on fetal and neonatal lupus. Autoantibodies like anti-Ro/SSA and anti-La/SSB may cross the placenta and cause complications in neonates, such as congenital heart block (CHB). Management options involve hydroxychloroquine, which is able to counteract some of the adverse events, although the drug needs to be used carefully because of its impact on the QTc interval. Advanced pacing strategies for neonates with CHB, especially in severe forms like hydrops, are also assessed. This review emphasizes the need for interdisciplinary care by rheumatologists, obstetricians, and pediatricians in order to achieve the best maternal and neonatal health in lupus pregnancies. This multidisciplinary approach seeks to improve the outcomes and management of the disease, decreasing the burden on mothers and their infants.

Post-cardiac injury syndrome and pericardial effusion recurrence after pericardial effusion drainage in chronic idiopathic pericardial effusion.

INTRODUCTION: The management of even large pericardial effusions in asymptomatic patients is still a matter of debate. Aim of the present study is to explore, in a multicenter setting, the rate of post-cardiac injury syndromes (PCIS) and pericardial effusion recurrence after pericardial effusion drainage procedure. MATERIAL AND METHODS: This is a multicenter international retrospective study including a consecutive cohort of patients diagnosed with large, chronic and idiopathic pericardial effusions, prospectively evaluated from January 2003 to December 2021 who underwent a clinically indicated pericardial drainage procedure. Two separate end-points were recorded: 1) recurrence of pericardial effusion after drainage without any sign of pericardial inflammation 2) occurrence of PCIS, defined as the new onset of pericarditis 1 to 6 weeks after pericardial intervention. RESULTS: 124 patients were enrolled (50 % female, mean age 64 years old). A mean follow-up of 29.6 ± 25.6 months was obtained in 110 patients (88 %). 110 patients were treated with pericardiocentesis (89 %), 25 with pleuro-pericardial windows (20 %), and 1 with pericardiectomy (1 %). PCIS occurred in 21 out of 124 patients followed for at least 6 weeks (16.9%). Recurrence of pericardial effusion after drainage without any sign of pericardial inflammation occurred in 68 out of 110 patients at a longer follow-up (61.8 %). At multivariate analysis only inflammatory cells in pericardial fluid was associated with PCIS and pericardiocentesis with pericardial effusion recurrency. CONCLUSION: Our data support the need of caution with the use of pericardiocentesis in asymptomatic patients with large pericardial effusion as it is often associated with pericardial effusion recurrence. Of interest the presence of inflammatory cells in the pericardial fluid is associated with PCIS after pericardial drainage procedures.

Disinfectant caps in vitro effectiveness.

Background: Catheter-related bloodstream infections (CRBSIs) are a major cause of morbidity and mortality among hospitalized patients. Different studies suggest that the use of disinfectant caps (DCs) significantly reduces the rate of CRBSIs. The first purpose of this study is to analyze, through an in-vitro-model, the antiseptic effect of DCs produced by two manufacturers; the second aim is to assess potential differences in terms of effectiveness between the two manufacturers' products. Methods: A know concentration of thirteen different microorganisms was incubated with the sponge drenched in antimicrobial fluid inside DCs and cultured through several assays to investigate the disinfectant effectiveness of some commercially available caps. Disinfectant properties were evaluated under two different conditions: baseline (DCs placed on the needle-free connectors (NFCs) and stress test (DCs directly applied to the catheter hub). Results: Both manufacturers overcame the basal tests (fourteen different assays). Regarding stress tests: the only significant bacterial load was found for Serratia marcescens (104 CFU/mL in ICU Medical™), both at 90 and 180 minutes after incubation; due to the low load, MDR Acinetobacter baumannii was not considered significant (<103 CFU/mL in BD PureHub™). Conclusions: Our results confirm what was reported in BD PureHub™ datasheet and add data not previously shown by ICU Medical™. Moreover, no difference was observed between the two manufacturers products: the use of both DCs on NFCs was able to reclaim the catheter lumen. These findings support the routine use of DCs with NFCs, as part of a structured bundle of interventions, to reduce the incidence of CRBSIs.

Unfolding dermatologic spectrum of Behçet's disease in Italy: real-life data from the International AIDA Network Behçet's disease Registry.

Behçet's disease (BD) is a heterogeneous multifactorial autoinflammatory disease characterized by a plethora of clinical manifestations. Cutaneous lesions are considered hallmarks of the disease. However, their evolution over time and a thorough description are scarcely reported in non-endemic regions. The aim of this study was to detail BD skin manifestations and their evolution over time in Italy, as well as the dermatological prognostic impact of specific cutaneous features in long-standing disease. Data were collected in a double fashion, both retrospectively and prospectively, from the AutoInflammatory Disease Alliance (AIDA) international registry dedicated to BD, between January 2022 and December 2022. A total of 458 Italian patients were included. When assessing skin manifestations course, the constant or sporadic presence or absence of cutaneous involvement between onset and follow-up was considered. Oral ulcers (OU) (88.4%) and genital ulcers (GU) (52.6%), followed by skin involvement (53.7%) represented the most common presenting mucocutaneous manifestations at disease onset. Up to the time of enrolment into the AIDA registry, 411 (93.8%) patients had suffered from OU and 252 (57.9%) from GU; pseudofolliculitis (PF) accounted for the most common skin manifestation (170 patients, 37.1%), followed by erythema nodosum (EN) (102 patients, 22.3%), skin ulcers (9 patients, 2%) and pyoderma gangrenosum (4 patients, 0.9%). A prospective follow-up visit was reported in 261/458 patients; 24/148 (16.2%) subjects with skin involvement as early as BD onset maintained cutaneous lesions for the entire period of observation, while 120 (44.1%) patients suffered from sporadic skin involvement. Conversely, 94/113 (83.2%) with no skin involvement at disease onset did not develop skin lesions thereafter. At follow-up visits, cutaneous involvement was observed in 52 (20%) patients, with a statistically significant association between PF and constant skin involvement (p = 0.031). BD in Italy is characterized by a wide spectrum of clinical presentations and skin manifestations in line with what is described in endemic countries. Patients with skin disease at the onset are likely to present persistent cutaneous involvement thereafter; mucocutaneous lesions observed at the onset, especially PF, could represent a warning sign for future persistent skin involvement requiring closer dermatological care.

Acute pericarditis with pleuropulmonary involvement, fever and elevated C-reactive protein: A systemic autoinflammatory disease? A cohort study.

OBJECTIVES: This cohort study describes a systemic phenotype of pericarditis, comparing this phenotype with other forms of pericarditis. PATIENTS AND METHODS: Patients in our center were enrolled in a prospectively maintained registry from 2019 to 2022. 412 patients with idiopathic recurrent pericarditis were analyzed. "Systemic inflammatory" subset was defined as the presence of all the following criteria: fever ≥38C°, CRP ≥2 times normal values, pleural effusion detected with any imaging techniques. The absence of any of the 3 criteria was defined as "isolated" subset. RESULTS: We found that 211 (51.2%) of 412 patients (188 female) presented the systemic subset and the variables significantly associated with this subset in univariate analysis (p<0.001) were: higher mean age: 45.5 (±SD 17.2) vs 39.9 (±SD 16.4) years, higher mean CRP values: 128.8 vs 49.9 mg/L, higher proportion of pericardiocentesis: 19% vs 1.5%, higher mean leukocyte count: 13,143.3 vs 9910.3/mm3, higher mean neutrophils number: 10,402.5 vs 6779.8 /mm3 and lower mean lymphocyte count: 1693.9 vs 2079.3 /mm3. As results the neutrophil-to-lymphocyte ratio was higher in systemic inflammatory phenotype: 6.6 vs 3.4 (p< 0.001). Anti-IL1 therapy was started more frequently in the systemic subgroup (26%) than in the isolated subset (7.5%) (p < 0.001). On multivariate analysis neutrophil count and lymphopenia were statistically associated with the systemic subset (p < 0.001). CONCLUSION: This results demonstrate the relevance of the systemic inflammatory phenotype, characterized by pleural effusions, confirming its analogy with autoinflammatory diseases, thus possibly requiring an eventual escalation of therapy to IL-1 inhibitors.

Pericardial Diseases in Pregnancy.

Pericardial effusion is the most common manifestation of pericardial diseases during pregnancy. This effusion is benign, mild, or moderate, well tolerated, with spontaneous resolution after delivery; no specific treatment is required. Acute pericarditis is the second most common condition, usually requiring medical therapy during pregnancy. Cardiac tamponade and constrictive pericarditis are rare in pregnancy. Pre-pregnancy counselling is essential in women of childbearing age with recurrent pericarditis to plan pregnancy in a phase of disease quiescence and to review therapy. High-dose aspirin or nonselective nonsteroidal anti-inflammatory drugs, such as ibuprofen and indomethacin, can be used up to the 20th week of gestation. Low-dose prednisone (2.5-10 mg/d) can be administered throughout pregnancy. All of these medications, apart from high-dose aspirin, may be used during lactation. Colchicine is compatible with pregnancy and breastfeeding, and it can be continued throughout pregnancy to prevent recurrences. Appropriate follow-up with a multidisciplinary team with experience in the field is recommended throughout pregnancy to ensure good maternal and fetal outcomes.

Relapsing pericarditis: Peripheral blood neutrophilia, lymphopenia and high neutrophil-to-lymphocyte ratio herald acute attacks, high-grade inflammation, multiserosal involvement, and predict multiple recurrences.

AIMS: To identify peripheral blood cellular correlates of active pericarditis and to verify whether peripheral blood neutrophils, lymphocytes and the neutrophil to-lymphocyte ratio (NLR) are associated with disease phenotype or prognosis. METHODS: Observational prospective study on a cohort of 63 patients with idiopathic pericarditis followed for 12 months after each pericarditis recurrence. Two distinct analyses were performed: the "index attack" analysis focused on the first pericarditis episode in each patient, while the "all attacks" analysis included all episodes occurring during the study. RESULTS: Absolute and relative neutrophilia and lymphopenia, together with high NLR, were observed during active pericarditis, as compared with disease remission, at both analyses. Neutrophils showed a positive correlation with plasma C-reactive protein levels, while lymphocyte count showed a negative correlation. Relative neutrophil count was higher, and lymphocyte count lower in patients with pleural effusion; a higher NLR and lower absolute lymphocyte count were observed in those with peritoneal involvement. No correlations were found between peripheral blood neutrophil or lymphocyte counts and size of pericardial effusion, or with the presence of myocardial involvement. Peripheral neutrophilia, lymphopenia and NLR during acute attacks predicted the number of recurrences in the following 12 months. CONCLUSIONS: Peripheral blood neutrophilia and lymphopenia are typical of acute idiopathic pericarditis. Acute attacks of pericarditis are associated with neutrophilia and lymphopenia, as compared with disease remission. During acute attacks, neutrophilia and lymphopenia reflect the extent of serosal inflammation and could help to customize therapeutic management after remission has been achieved.

Immunomodulating Therapies in Acute Myocarditis and Recurrent/Acute Pericarditis.

The field of inflammatory disease of the heart or "cardio-immunology" is rapidly evolving due to the wider use of non-invasive diagnostic tools able to detect and monitor myocardial inflammation. In acute myocarditis, recent data on the use of immunomodulating therapies have been reported both in the setting of systemic autoimmune disorders and in the setting of isolated forms, especially in patients with specific histology (e.g., eosinophilic myocarditis) or with an arrhythmicburden. A role for immunosuppressive therapies has been also shown in severe cases of coronavirus disease 2019 (COVID-19), a condition that can be associated with cardiac injury and acute myocarditis. Furthermore, ongoing clinical trials are assessing the role of high dosage methylprednisolone in the context of acute myocarditis complicated by heart failure or fulminant presentation or the role of anakinra to treat patients with acute myocarditis excluding patients with hemodynamically unstable conditions. In addition, the explosion of immune-mediated therapies in oncology has introduced new pathophysiological entities, such as immune-checkpoint inhibitor-associated myocarditis and new basic research models to understand the interaction between the cardiac and immune systems. Here we provide a broad overview of evolving areas in cardio-immunology. We summarize the use of new imaging tools in combination with endomyocardial biopsy and laboratory parameters such as high sensitivity troponin to monitor the response to immunomodulating therapies based on recent evidence and clinical experience. Concerning pericarditis, the normal composition of pericardial fluid has been recently elucidated, allowing to assess the actual presence of inflammation; indeed, normal pericardial fluid is rich in nucleated cells, protein, albumin, LDH, at levels consistent with inflammatory exudates in other biological fluids. Importantly, recent findings showed how innate immunity plays a pivotal role in the pathogenesis of recurrent pericarditis with raised C-reactive protein, with inflammasome and IL-1 overproduction as drivers for systemic inflammatory response. In the era of tailored medicine, anti-IL-1 agents such as anakinra and rilonacept have been demonstrated highly effective in patients with recurrent pericarditis associated with an inflammatory phenotype.

Recent advances in pericarditis.

Pericardial diseases are an heterogeneous group of entities, ranging from acute pericarditis to asymptomatic pericardial effusions. New advances in understanding the processes underlying them have been made. In 2020 a prospective study defined the reference intervals of the component of normal pericardial fluid, that was found to be rich in nucleated cells, proteins, albumin and LDH, at levels compatible with the inflammatory exudates of other biological fluids such as pleural or peritoneal fluid; Light's criteria should not be used to evaluate it. Recently we also analyzed systematically large chronic idiopathic non-inflammatory pericardial effusions, observing that a non-invasive wait-and-see approach may be the best choice in clinical practice in oligosymptomatic cases. Concerning acute recurrent pericarditis (RP), an innovative interaction between cardiologists, internists and pediatric rheumatologists led to the intuition of a pivotal role of IL-1 in recurrent pericarditis characterized by an evident inflammatory recurrent phenotype, and recent data have shown the striking efficacy of anakinra and rilonacept in these patients. The proper selection of the patient is important; the ideal candidate for anti-IL-1 therapy is the patient with RP with high levels of serum C-reactive protein, high fever, neutrophil leukocitosis, pleuropulmonary involvement, frequent exacerbations and resistant to conventional therapy. On the contrary, anti-IL-1 drugs are not indicated in patients with pericardial effusion whose cause is not attributable to inflammatory phenomena. Finally, many patients with RP are women of childbearing age, and the possibility for these women to become pregnant must be addressed by multidisciplinary teams.

Autoimmune and Autoinflammatory Pericarditis: Definitions and New Treatments.

PURPOSE OF THE REVIEW: The purpose of the review is to analyze the pathogenetic mechanisms that underlie acute pericarditis, with attention to autoimmune and autoinflammatory pericarditis, and, in addition, to review the available therapeutic armamentarium. RECENT FINDINGS: Several studies have been published on the use of anti-IL-1 drugs in recurrent pericarditis, including anakinra and rilonacept. The latest, the RHAPSODY study, based on the use of rilonacept in recurrent pericarditis, has recently reached phase 3 with promising results in terms of efficacy and safety. Alterations in the function of the inflammasome and the consequent overproduction of IL-1 play a pivotal role in the genesis of autoinflammatory pericarditis. Recent studies added evidence to the importance of anti-IL-1 drugs in the treatment of recurrent pericarditis with raised C-reactive protein. In the era of tailored medicine, anti-IL-1 agents may be very useful in the subset of patients with recurrent pericarditis and a clear inflammatory phenotype.

Management of acute and recurrent pericarditis in pregnancy.

This review summarizes the currently available evidence on the management of acute and recurrent pericarditis during pregnancy, focusing on the safety of diagnostic procedures and treatment options for the mother and fetus. Family planning should be addressed in women with recurrent pericarditis of reproductive age and adjustment of therapy should be considered before a planned pregnancy. The treatment of pericarditis in pregnancy is similar to that for non-pregnant women but considers current knowledge on drug safety during pregnancy and lactation. The largest case series on this topic described 21 pregnancies with idiopathic recurrent pericarditis. Pregnancy should be planned in a phase of disease quiescence. Non-steroidal anti-inflammatory drugs can be used at high dosages until the 20th week of gestation (except low-dose aspirin 100 mg/die). Colchicine is allowed until gravindex positivity; after this period, administration of this drug during pregnancy and lactation should be discussed with the mother if its use is important to control recurrent pericarditis. Prednisone is safe if used at low-medium doses (2.5-10 mg/die). General outcomes of pregnancy in patients with pericarditis are good when the mothers are followed by a multidisciplinary team with experience in the field.

COVID-19 welbeing study: a protocol examining perceived coercion and psychological well-being during the COVID-19 pandemic by means of an online survey, asynchronous virtual focus groups and individual interviews.

INTRODUCTION: The COVID-19 pandemic has resulted in many countries applying restrictive measures, such as lockdown, to contain and prevent further spread. The psychological impact of lockdown and working as a healthcare worker on the frontline has been chronicled in studies pertaining to previous infectious disease pandemics that have reported the presence of depressive symptoms, anxiety, insomnia, and post-traumatic stress symptoms. Potentially linked to psychological well-being and not yet studied is the possibility that lockdown and working on the frontline of the pandemic are associated with perceptions of coercion. METHODS AND ANALYSIS: The present study aimed to examine perceived coercion in those who have experienced COVID-19-related lockdown and/or worked as a frontline healthcare worker across three European countries. It aimed to describe how such perceptions may impact on psychological well-being, coping and post-traumatic growth. It will employ an explanatory mixed-methods research methodology consisting of an online survey and online asynchronous virtual focus groups (AVFGs) and individual interviews. χ2 tests and analyses of variance will be used to examine whether participants from different countries differ according to demographic factors, whether there are differences between cohorts on perceived coercion, depression, anxiety and post-traumatic growth scores. The relationship between coercion and symptoms of distress will be assessed using multiple regression. Both the AVFGs and the narrative interviews will be analysed using thematic narrative analysis. ETHICS AND DISSEMINATION: The study has been approved by University College London's Research Ethics Committee under Project ID Number 7335/004. Results will be disseminated by means of peer-reviewed publications and at national and/or international conferences.

Use of viscosupplementation for the recovery of active football players complaining of knee pain.

OBJECTIVE: The aim of this study is to investigate the effect of intra-articular hyaluronic acid administration in active football players complaining of knee pain after sports activity. Efficacy and safety profiles of intra-articular hyaluronic acid and time needed for football players to recover and restart sports activity were examined. METHODS: Clinical data of active football players reporting knee pain after sports activity were included in this retrospective study. All patients who received an intra-articular injection at time 0 and after 2 weeks were included in the study. Patients underwent laboratory examination, knee X-ray, ultrasound, and clinical examination before receiving the intra-articular injection. Effusions or cysts were drained before injections. Lequesne index score, pain visual analog scale (VAS) score, and patient's global assessment score were recorded at time 0 (day of the first injection), 1 and 2 days after the first injection, at 2 weeks (day of the second injection), and at follow-up visits. Only data from patients completing the follow-up were analyzed. RESULTS: Data from 17 patients were analyzed: 16 males and one female, of which three were professional players (two males and one female) and 14 were nonprofessional players. The mean age of patients was 39.8±11.8 years. Two patients (one male and one female) showed joint effusion. Two patients reported relevant joint pain after injection that regressed without any medication. At the first week, all parameters examined indicated improvement that was maintained until the end of follow-up. One day after the first and second injection, patients reported a slight increase in pain VAS score, which was not statistically significant, and the pain resolved after 1 day. All patients successfully restarted playing after the first injection within 3.1±2.0 days and kept playing after the second injection following our indication (1 day of break). CONCLUSION: The use of a medium-molecular weight hyaluronic acid in football players affected by knee osteoarthritis seems efficacious and safe and resulted, in our experience, a stable improvement of symptoms; moreover, it allowed a rapid restart of sports activity. Larger studies on larger populations are needed to confirm these findings.

The challenge of the definition of early symptomatic knee osteoarthritis: a proposal of criteria and red flags from an international initiative promoted by the Italian Society for Rheumatology.

The aim of this study was to establish consensus for potential early symptomatic knee osteoarthritis (ESKOA) clinical definition and referral criteria from primary care to rheumatologists, based on available data from literature and a qualitative approach, in order to perform studies on patients fulfilling such criteria and to validate the obtained ESKOA definition. A complex methodological approach was followed including: (1) three focus groups (FG), including expert clinicians, researchers and patients; (2) a systematic literature review (SLR); (3) two discussion groups followed by a Delphi survey. FG and SLR were performed in parallel to inform discussion groups in order to identify relevant constructs to be included in the modified Delphi survey. ESKOA is defined in the presence of: (a) two mandatory symptoms (knee pain in the absence of any recent trauma or injury and very short joint stiffness, lasting for less than 10 min, when starting movement) even in the absence of risk factors, or (b) knee pain, and 1 or 2 risk factors or (c) three or more risk factors in the presence of at least one mandatory symptom, with symptoms lasting less than 6 months. These criteria are applicable in the absence of active inflammatory arthritis, generalized pain, Kellgren-Lawrence grade >0, any recent knee trauma or injury, and age lower than 40 years. Knee pain in the absence of any recent trauma lasting for less than 6 months was considered as the referral criterion to the rheumatologist for the suspicion of ESKOA. This consensus process has identified provisional clinical definition of ESKOA and defined potential referral criterion to rheumatologist, in order to test ESKOA obtained definition in prospective validation studies.

An update on the up and coming therapies to treat osteoarthritis, a multifaceted disease.

INTRODUCTION: The lack of a complete understanding of the complex processes involved in the etiopathogenesis and subsequent appropriate phenotyping makes it difficult to find therapies that may be efficacious in most patients with osteoarthritis (OA). Consensus recommendations involve mainly non-pharmacological approaches. Analgesics and NSAIDs are considered second choice options due to their poor efficacy/safety ratios. To some extent, OA may be considered an orphan disease. Therefore, there is an urgent need to identify effective and safe new pharmacologic modalities for treating OA. AREAS COVERED: This review is based on a Medline comprehensive literature search for published articles evaluating new formulations of current drugs and promising emerging therapies in OA. We discuss the current status of novel systemic agents in development including potent analgesic options, inhibitors of innate immunity, inducible nitric oxide synthase (iNOS), pro-inflammatory cytokines and cartilage proteases as well as bone agents. Furthermore, we also revise the potential benefit of intraarticular (IA) therapy with hyaluronic acid (HA), pro-inflammatory mediator blockers, cartilage anabolic agents, mesenchymal stem cell and gene transfer. EXPERT OPINION: Despite the renewed interest in the search of new compounds for treatment of OA, results have been limited. Novel systemic and IA administered agents are in active development. IA drug administration is particularly an attractive approach because can diminish some of the severe side effects associated with systemic drugs. Indeed, one of the most promising fields for pharmacology innovation in OA is joint injected therapy, as suggested by preliminary data from recent studies using IA sprifermin (rhFGF-18), mesenchymal stem cells or TGF-B1 transduced allogenic chondrocytes. Last, the effort to develop new drugs must be accompanied by the interest for establishing well-defined phenotypes, and only then, a more tailored therapy should be practiced in OA.