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.

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.

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.

A double blind randomized active-controlled clinical trial on the intra-articular use of Md-Knee versus sodium hyaluronate in patients with knee osteoarthritis ("Joint").

BACKGROUND: To evaluate the clinical outcomes of a group of patients affected by knee osteoarthritis (OA) treated with MD-Knee (Guna S.p.a., Milan, Italy) versus a group of patients treated with sodium hyaluronate. METHOD: This non-inferiority prospective randomized controlled trial involved 60 patients affected by knee OA, grade 2-3 of Kellgren-Lawrence scale. The MD-Knee Group, Group A (n = 29) was administered five intra-articular injections at 1 week interval; the sodium hyaluronate Group, Group B (n = 31), was administered five doses of intra-articular injection of sodium hyaluronate at 1 week interval. All patients were prospectively evaluated before and at 3 and 6 months after the treatment by the Lequesne Knee Index (LKI) as primary endpoint and the Visual Analogue Scale (VAS), Pain Killer consumption and SF-36 questionnaires as secondary endpoints. RESULTS: At the 3- and 6 month follow-up, LKI and VAS improved significantly in both groups compared to baseline and no statistically significant differences were observed between Group A and Group B. There was no statistically significant difference in the SF36 questionnaire score and pain killer consumption between two groups at any time point. CONCLUSIONS: This study shows that both preparations exert similar clinical effects as assessed through multiple outcome measures. MD-Knee is effective on knee OA symptoms over 6 months after a 5-weekly injection course, and it is equally effective as the reference sodium hyaluronate. TRIAL REGISTRATION NUMBER: ISRCTN93862496 . Registration date: January 18th, 2016.

Lanadelumab in a kidney transplant patient with hereditary angioedema due to C1-inhibitor deficiency and high cardiovascular risk - a case report.

Introduction: Cardiovascular pathologies represent the first cause of death in uremic patients and are among the leading causes of mortality in patients with hereditary angioedema due to C1-inhibitor deficiency (HAE-C1INH). Before 2020, the most common treatment for long-term prophylaxis in HAE-C1INH patients in Italy was attenuated androgen, which may increase cardiovascular risk by multiple mechanisms. Case description: We present a case report of a 56-year-old patient with HAE-C1INH type I affected by IgA nephropathy with severe kidney impairment. The patient experienced a first kidney transplant and, after late rejection, underwent a second kidney transplant. Further comorbidities included obesity, hypertensive cardiomyopathy, HCV liver disease, and dyslipidemia. His prophylactic therapy to prevent angioedema attacks had consisted of attenuated androgens for about 40 years. Since 2020, new modern targeted therapy for LTP, particularly lanadelumab, has shown promising results. The majority of patients with attenuated androgens have been successfully switched to lanadelumab, including our patient. Since introducing lanadelumab (300 mg subcutaneously every two weeks; after a six-month attack-free period, the dosing interval of lanadelumab was extended to four weeks), the patient has not experienced any acute HAE attack and did not report any adverse events. Moreover, we observed decreased total cholesterol, C-LDL, and body mass index, reducing the Matsushita et al. score for ten years of cardiovascular risk from 13.2% to 9.3%. Conclusion: lanadelumab is effective and safe in preventing hereditary angioedema attacks, as well as in reducing cardiovascular risk in an immunosuppressed patient with significant comorbidities. The successful outcomes of this case highlight the potential of lanadelumab as a promising prophylactic therapy.

Ultrasound assessment of short peripheral catheter failure.

INTRODUCTION: Short peripheral catheters (SPCs) are affected by a high complication rate that leads to catheter failure. Currently, the Visual Infusion Phlebitis score (VIP) is the most used tool to verify the presence of inflammatory complications (phlebitis and thrombophlebitis). However, ultrasound signs (US) may be an attractive alternative. OBJECTIVE: This study aims to evaluate the sensitivity and specificity of US and VIP score = 1 in identifying and recognizing early signs of SPC failure. The time to positivity for US and VIP scores was assessed as a secondary outcome. METHODS: An observational prospective study was conducted. In each patient, US (subcutaneous edema; fibroblastic sleeve; thrombophlebitis) and VIP of the exit site were performed every 24 h until 96 h after insertion. Compared to catheter failure, Sensitivity, Specificity, and Predictive values in both US and VIP were calculated. RESULTS: Two hundred patients were enrolled. The presence of ultrasonic pattern suggestive of edema at 72 h (p = 0.018), fibroblastic sleeve at 24, 48, 72, and 96 h (p < 0.001), thrombosis at 48 (p < 0.001) and 72 h (p = 0.005), and at least one of an abovementioned US at all checkpoints (p < 0.001) were highly significant predictors of complications. Both US and VIP effectively detect inflammatory events; however, the US showed better sensitivity in overall checkpoints and earlier predictive ability than VIP (1.9 vs 0.47 days). CONCLUSIONS: An ultrasound inflammatory pattern is correlated with SPC failure. An ultrasound protocol-requiring minimal training-is more effective than VIP in recognizing early signs of device failure.

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.

Decrease in Hemoglobin Levels during Acute Attacks in Patients with Idiopathic Recurrent Pericarditis: A Model of Anemia in Acute Disease.

Background/Objectives: Anemia during acute inflammation is not well described in the literature. We aimed to study whether patients develop a transient hemoglobin decrease during an acute attack of recurrent pericarditis. Methods: We retrospectively analyzed patients with recurrent pericarditis. The primary endpoint was the difference in hemoglobin levels during an acute attack and in the following remission. As secondary endpoints, we correlated this variation with laboratory and clinical features; we also evaluated the available baseline hemoglobin values. Results: Sixty-two patients, including thirty females (48.4%), with a median age of 39 years, were observed during an acute attack and remission. The attack indexed was the first in 21 patients and the second or the third in 41, with pre-attack hemoglobin levels available for the latter group. Median hemoglobin levels (IQR) were 13.8 (12.8-15.1) g/dL at baseline, 12.0 (11.2-13.4) during attacks and 13.6 (13.1-14.0) during remission (p < 0.001). The median hemoglobin reduction between an acute attack and remission was 1.4 g/dL. Their mean corpuscular volume remained in the normal range. Hb reduction significantly correlated with C-reactive protein (CRP) elevation, neutrophilia and the neutrophil-to-lymphocyte ratio, but not serosal involvement. Only CRP elevation remained associated with the variation of Hb in a multivariate analysis (p = 0.007). Conclusions: This study is a proof of concept: hemoglobin levels may decline rapidly during acute inflammation in correlation with CRP elevation, with transient normocytic anemia, followed by a rapid rebound. In this regard, idiopathic pericarditis may represent a pathogenetic model of this type of anemia.

D-Dimer and procalcitonin in patients with recurrent pericarditis: a prospective study.

Recurrent pericarditis, an inflammatory syndrome with a pathogenesis not fully elucidated, often presents diagnostic challenges. This study aims to assess the correlation of D-Dimer (D-D) and procalcitonin (PCT) levels with clinical, laboratory and imaging features in recurrent idiopathic pericarditis. We analyzed 412 patients with idiopathic recurrent pericarditis from 2019 to 2023 in our referral center. D-D and PCT values were obtained from emergency room in other Italian facilities. Among the cohort, PCT levels were assessed in 50 of 412 patients (12.1%), with only 4 showing marginal elevation. D-D levels were measured in 48 of 412 patients (11.6%), with 33 of them exhibiting elevated values. None of these patients had venous thromboembolism, and elevated D-D levels were significantly associated with pleural effusion, fever, higher CRP, increased white blood cell counts, higher neutrophil counts, reduced relative lymphocyte counts. Multivariate analysis revealed fever as the sole correlate of elevated D-D. PCT elevation was infrequent and unrelated to any variables. In idiopathic recurrent pericarditis unrelated to specific conditions, we observed a close association between elevated D-D levels and non-specific inflammation markers, including fever, increased CRP, and neutrophil leukocytosis. PCT levels were typically normal or mildly elevated.

Recurrent pericarditis in older adults: Clinical and laboratory features and outcome.

BACKGROUND: Current guidelines for the diagnosis and treatment of pericarditis refer to the general adult population. Few and fragmentary data regarding recurrent pericarditis in older adults exist. OBJECTIVE OF THE STUDY: Given the absence of specific data in scientific literature, we hypothesized that there might be clinical, laboratory and outcome differences between young adults and older adults affected by idiopathic recurrent pericarditis. MATERIALS AND METHODS: We performed an international multicentric retrospective cohort study analyzing data from patients affected by recurrent pericarditis (idiopathic or post-cardiac injury) and referring to tertiary referral centers. Clinical, laboratory, and outcome data were compared between patients younger than 65 years (controls) and patients aged 65 or older. RESULTS: One hundred and thirty-three older adults and 142 young adult controls were enrolled. Comorbidities, including chronic kidney diseases, atrial fibrillation, and diabetes, were more present in older adults. The presenting symptom was dyspnea in 54.1% of the older adults versus 10.6% in controls (p < 0.001); pain in 32.3% of the older adults versus 80.3% of the controls (p < 0.001). Fever higher than 38°C was present in 33.8% versus 53.5% (p = 0.001). Pleural effusion was more prevalent in the older adults (55.6% vs 34.5%, p < 0.001), as well as severe pericardial effusion (>20 mm) (24.1% vs 12.7%, p = 0.016) and pericardiocentesis (16.5% vs 8.5%, p = 0.042). Blood leukocyte counts were significantly lower in the older adults (mean + SE: 10,227 + 289/mm3 vs 11,208 + 285/mm3, p = 0.016). Concerning therapies, NSAIDS were used in 63.9% of the older adults versus 80.3% in the younger (p = 0.003), colchicine in 76.7% versus 87.3% (p = 0.023), corticosteroids in 49.6% versus 26.8% (p < 0.001), and anakinra in 14.3% versus 23.9% (p = 0.044). CONCLUSIONS: Older adults affected by recurrent pericarditis show a different clinical pattern, with more frequent dyspnea, pleural effusion, severe pericardial effusion, and lower fever and lower leukocyte count, making the diagnosis sometimes challenging. They received significantly less NSAIDs and colchicine, likely due to comorbidities; they were also treated less commonly with anti-IL1 agents, and more frequently with corticosteroids.

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.

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.

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.

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.

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.

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.

Viscosupplementation in the management of ankle osteoarthritis: a review.

INTRODUCTION: Osteoarthritis (OA) is a disease of synovial joints and is the most common cause of chronic pain. Viscosupplementation (VS) with hyaluronic acid (HA) is largely used for knee osteoarthritis therapy but the evidence for its usefulness in ankle osteoarthritis is limited. The objective of this review is to assess the efficacy of viscosupplementation treatment of ankle osteoarthritis in the current literature. METHODS: The following databases were searched: Medline (period 2006-2008), Database of Abstract on Reviews and Effectiveness and Cochrane Database of Systematic Reviews. Reference lists of relevant articles were controlled for additional references. The search terms Review, Viscosupplementation (VS), Osteoarthritis (OA), Hyaluronic acid (HA), Hyaluronan, Sodium hyaluronate, Ankle OA, Ankle joint were used to identify all studies relating to the use of VS therapy for the ankle OA. Methodological quality of included studies was assessed by assigning level of evidence as previously defined by the Centre for Evidence Based Medicine (CEBM). RESULT: Seven articles concerning the efficacy of a total of 275 patients undergoing VS treatment for ankle OA were included. One European study, one Taiwanese study, one Italian study, one Turkish study and three American studies with level of evidence ranging from I to IV evaluated the following products: Hyalgan, Synvisc, Supartz, Adant. CONCLUSION: Viscosupplementation is used widely in knee OA and is included in the professional guidelines for treatment of the disease in this joint. The potential for treating osteoarthritis of the ankle joint by viscosupplementation has been suggested in the literature, however, no dosing studies have been published to date, and dosing in the ankle joint remains an area for discussion. Viscosupplementation could potentially provide an useful alternative in treating such patients with painful ankle OA.

Intra-articular injection of hyaluronic acid (MW 1,500-2,000 kDa; HyalOne) in symptomatic osteoarthritis of the hip: a prospective cohort study.

INTRODUCTION: Clinical trials have demonstrated the safety and efficacy of hyaluronic acid-based products for the treatment of hip osteoarthritis, but data from observational studies of normal medical practice are scarce. This study investigated the long-term efficacy and tolerability of ultrasound-guided intra-articular sodium hyaluronate (MW 1,500-2,000 kDa; Hyalone) injections in daily clinical practice. METHODS: In this observational, cohort study of patients with hip osteoarthritis, Hyalone was administered under the ultrasound guidance, every 6 months, with the possibility of an additional injection at the intervening 3-month intervals on clinical request. Efficacy measurements included the Lequesne algofunctional index, self-reported pain via the visual analogue scale (VAS), the concomitant use of non-steroidal anti-inflammatory drugs (NSAIDs) and safety. The patients were followed up for 18 months after the first intra-articular injection. RESULTS: Data from 120 patients were collected. During the study, a statistically significant reduction in algofunctional indexes was demonstrated at 3 months after study product injection, while at 12 months 80% of the patients achieved a decrease of at least 30% in symptoms. These results were maintained over time through cyclical and personalized repetition of ultrasound guided injections, at least one injection every 6 months. CONCLUSIONS: The study treatment reduced pain and improved mobility in osteoarthritis of the hip. These results in daily clinical practice demonstrate a beneficial effect and the safety of the study product and suggest adding intra-articular injections of HyalOne to the armamentarium of conservative management of symptomatic hip osteoarthritis.