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Myocarditis represents the coexistence of myocardial inflammation and necrosis, with highly variable clinical severity and prog-nosis. Viruses are the most frequent aetiology followed by autoimmunity, either isolated or in the setting of systemic autoimmune diseases. This manuscript will focus on myocarditis occurring in patients with overt or smouldering systemic autoimmune dis-orders. The specificities in the clinical approach to these conditions and in diagnosis will be reviewed, together with the clinical heterogeneity associated to the different underlying autoimmune conditions and the most frequent clinical scenarios to be faced by the cardiologist in the outpatient clinic.

ObjectiveBiochemical and cytological pericardial fluid (PF) analysis is essentially based on the knowledge of pleural fluid composition. The aim of the present study is to identify reference intervals (RIs) for PF according to state-of-art methodological standards.MethodsWe prospectively collected and analysed the PF and venous blood of consecutive subjects undergoing elective open-heart surgery from July 2017 to October 2018. Exclusion criteria for study enrolment were evidence of pericardial diseases at preoperatory workup or at intraoperatory assessment, or any other condition that could affect PF analysis.ResultsThe final study sample included 120 patients (median age 69 years, 83 men, 69.1%). The main findings were (1) High levels of proteins, albumin and lactate dehydrogenase (LDH), but not of glucose and cholesterol (2) High cellularity, mainly represented by mesothelial cells. RIs for pericardial biochemistry were: protein content 1.7–4.6 g/dL PF/serum protein ratio 0.29–0.83, albumin 1.19–3.06 g/dL, pericardium-to-serum albumin gradient 0.18–2.37 g/dL, LDH 141–2613 U/L, PF/serum LDH ratio 0.40–2.99, glucose 80–134 mg/dL, total cholesterol 12–69 mg/dL, PF/serum cholesterol ratio 0.07–0.51. RIs for pericardial cells by optic microscopy were: 278–5608 × 106 nucleated cells/L, 40–3790 × 106 mesothelial cells/L, 35–2210 × 106 leucocytes/L, 19–1634 × 106 lymphocytes/L.ConclusionsPF is rich in nucleated cells, protein, albumin, LDH, at levels consistent with inflammatory exudates in other biological fluids. Physicians should stop to interpret PF as exudate or transudate according to tools not validated for this setting.

Background Pericarditis, along with myocarditis, is being increasingly reported after the coronavirus disease 2019 (COVID-19) vaccine, but the best treatment strategy in this specific setting is still unclear. Case summary We report a case of acute pericarditis after the second dose of mRNA COVID-19 vaccine with recurrence of large pericardial effusion after a previous pericardiocentesis and anti-inflammatory drugs tapering. The patient was successfully treated with the recombinant interleukin-1 receptor antagonist anakinra, with full reabsorption of the pericardial effusion and an abrupt drop of the inflammatory markers within 72 h. The patient was discharged a few days later, with a further decrease of the inflammatory markers and no residual symptoms. Discussion Anakinra is being increasingly used in the treatment of recurrent pericarditis due to its capability to interrupt the autoinflammatory response leading to deleterious cytokine storms. On account of its high efficacy and rapid onset, it has been reported to rapidly reverse large inflammatory pericardial effusions. Pericarditis and myocarditis have been reported after the COVID-19 vaccine, but this is the first case of COVID-19 vaccine-related pericarditis and pericardial effusion successfully treated with anakinra, avoiding a second pericardiocentesis.

Background While there is broad consensus that the use of digital tools would significantly improve patient empowerment, to date, an improvement in health outcomes has been elusive. Objective The objective of this study was to assess how to improve the ability of physicians to empower patients with digital tools. Methods We conducted a web-based survey using SurveyMonkey over nearly 6 months. A questionnaire was sent with an email, explaining the aims of the survey and providing a link to complete the web-based questionnaire, to the heads of each of the 37 medical national societies adhering to the EFIM (European Federation of Internal Medicine), inviting them to disseminate the questionnaire among their members. Results Two hundred and eighteen responses were received. They suggest that the main success factors in increasing and improving patient empowerment with digital tools and realizing health goals are clinical evidence, followed by patient/physician involvement in the design, tools designed around the real needs of the patient, and reimbursement. Most of the respondents who have already prescribed digital tools for patient empowerment are just enough satisfied with the results achieved by their patients. Interestingly, 18% of the respondents had spent more than 30 min on the visit of patient to doctor. However, the majority devoted only 5–9 min to illustrating the suggested digital tools. Conclusions According to the respondents, clinical evidence, motivation, physician and patient’s involvement in design, and reimbursement, as well as organizations’ appropriate business models and support, are the main determinants of the diffusion and effective adoption of digital tools for successful patient empowerment in internal medicine.

The COVID-19 pandemic is challenging our cardiovascular care of patients with heart diseases. In the setting of pericardial diseases, there are two possible different scenarios to consider: the patient being treated for pericarditis who subsequently becomes infected with SARS-CoV-2, and the patient with COVID-19 who develops pericarditis or pericardial effusion. In both conditions, clinicians may be doubtful regarding the safety of nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, colchicine, and biological agents, such as anti-IL1 agents (e.g. anakinra), that are the mainstay of therapy for pericarditis.For NSAIDs, there is no clear scientific evidence linking ibuprofen and other NSAIDs to worsening of COVID-19; however, it seems prudent to continue them, if necessary to control pericarditis, and on the other hand, to prefer paracetamol for fever and systemic symptoms related to COVID-19. Treatments with corticosteroids, colchicine, and anakinra appear well tolerated in the context of COVID-19 infection and are currently actively evaluated as potential therapeutic options for COVID infection at different stages of the disease. On this basis, currently most treatments for pericarditis do not appear contraindicated also in the presence of possible COVID-19 infection and should not be discontinued, and some (corticosteroids, colchicine, and anakinra) can be considered to treat both conditions.

Colchicine is an ancient drug, traditionally used for the treatment and prevention of gouty attacks; it has become standard of treatment for pericarditis with a potential role in the treatment of coronary artery disease. Atherosclerotic plaque formation, progression, destabilisation and rupture are influenced by active proinflammatory cytokines interleukin (IL)-1β and IL-18 that are generated in the active forms by inflammasomes, which are cytosolic multiprotein oligomers of the innate immune system responsible for the activation of inflammatory responses. Colchicine has a unique anti-inflammatory mechanism: it is not only able to concentrate in leucocytes, especially neutrophils, and block tubulin polymerisation, affecting the microtubules assembly, but also inhibits (NOD)-like receptor protein 3 (NLRP3) inflammasome. On this basis, colchicine interferes with several functions of leucocytes and the assembly and activation of the inflammasome as well, reducing the production of interleukin 1β and interleukin 18. Long-term use of colchicine has been associated with a reduced rate of cardiovascular events both in chronic and acute coronary syndromes, with an overall good safety profile. This review will focus on the influence of colchicine on the pathophysiology of coronary artery disease, reviewing essential pharmacology and discussing the most important and recent clinical studies. On the basis of current literature, colchicine is emerging as a possible new valuable, safe and cheap agent for the treatment of acute and chronic coronary syndromes.

© 2020 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved., The concept of Less is More medicine emerged in North America in 2010. It aims to serve as an invitation to recognize the potential risks of overuse of medical care that may result in harm rather than in better health, tackling the erroneous assumption that more care is always better. In response, several medical societies across the world launched quality-driven campaigns (“Choosing Wisely”) and published “top-five lists” of low-value medical interventions that should be used to help make wise decisions in each clinical domain, by engaging patients in conversations about unnecessary tests, treatments and procedures. However, barriers and challenges for the implementation of Less is More medicine have been identified in several European countries, where overuse is rooted in the culture and demanded by a society that requests certainty at almost any cost. Patients’ high expectations, physician's behavior, lack of monitoring and pernicious financial incentives have all indirect negative consequences for medical overuse. Multiple interventions and quality-measurement efforts are necessary to widely implement Less is More recommendations. These also consist of a top-five list of actions: (1) a novel cultural approach starting from medical graduation courses, up to (2) patient and society education, (3) physician behavior change with data feedback, (4) communication training and (5) policy maker interventions. In contrast with the prevailing maximization of care, the optimization of care promoted by Less is More medicine can be an intellectual challenge but also a real opportunity to promote sustainable medicine. This project will constitute part of the future agenda of the European Federation of Internal Medicine.

Purpose Paroxysmal Permeability Disorders (PPDs) comprise a variety of diseases characterized by recurrent and transitory increase of endothelial permeability. Idiopathic Systemic Capillary Leak Syndrome (ISCLS) is a rare PPD that leads to an abrupt massive shift of fluids and proteins from the intravascular to the interstitial compartment. In some cases, tissue edema may involve the myocardium, but its role in the development of shock has not been elucidated so far. Materials and methods Assessment of cardiac involvement during ten life-threatening ISCLS episodes admitted to ICU. Results Transthoracic echocardiographic examination was performed in eight episodes, whereas a poor acoustic window prevented cardiac ultrasound assessment in two episodes. Myocardial edema was detected by echocardiography in eight episodes and marked pericardial effusion in one-episode. Cardiac magnetic resonance showed diffuse myocardial edema in another episode. In one case, myocardial edema caused fulminant left ventricular dysfunction, which required extracorporeal life support. The mean septum thickness was higher during the shock phase compared to the recovery phase [15.5 mm (13.1–21 mm) vs. 9.9 mm (9–11.3 mm), p = .0003]. Myocardial edema resolved within 72 h. Conclusions During early phases of ISCLS, myocardial edema commonly occurs and can induce transient myocardial dysfunction, potentially contributing to the pathogenesis of shock.

Highlights •Pericarditis is the most common disease of the pericardium. Generally self-limiting, pericarditis can be fraught by a significant risk of acute complications and of recurrences. •Prompt diagnosis and appropriate treatment of acute pericarditis may reduce the risk of acute complications and recurrences. •New therapies, such as IL-1 blockers, show promising results in patients with recurrent/refractory pericarditis. •Future studies are needed to deepen the knowledge about pericarditis pathophysiology and provide targeted therapies.

Background:The presence of pectus excavatum(PEX) has been occasionally associated with pericardial effusion. Aim of the present study was to compare incidence and prognosis of pericardial effusion in a group of unselected patients with PEX vs a control group. Methods:From a prospective registry of consecutive patients who underwent chest CT for cardiovascular disease, subjects with a radiological diagnosis of PEX were retrospectively identified (cases); from the same registry patients (controls) without rib cage abnormalities were randomly selected, until a 1:2 ratio was reached. The presence of pericardial effusion at CT was quantified. Follow-up was obtained for a composite end-point: cardiac tamponade, need for pericardiocentesis, need for cardiac surgery for relapsing pericardial effusion. Results:A total of 43 patients with PEX (20 females) and a control group of 86 cases (31 females) without rib cage abnormalities were identified. Pericardial effusion evaluated at CT was significatively more prevalent in patients with PEX vs control group, 37.2% vs 13.9% (p < 0.001), respectively; four patients with PEX (9.3%) had at least moderate pericardial effusion vs no subjects among the controls (p = 0.004). PEX diagnosis was significantly associated to pericardial effusion at multi-variate analysis (OR95%CI 10.91[3.47-34.29], p < 0.001). At a mean follow-up of 6.5 ± 3.4 years no pericardial events were recorded. Conclusion:Our findings support the higher prevalence of pericardial effusion in patients with PEX when compared to a control group. The absence of adverse pericardial events at follow-up suggest the good prognosis of these effusions, that in the appropriate clinical setting might not be considered "idiopathic".

Autoimmune rheumatic diseases (ARD) can affect women and men during fertile age, therefore reproductive health is a priority issue in rheumatology. Many topics need to be considered during preconception counselling: fertility, the impact of disease-related factors on pregnancy outcomes, the influence of pregnancy on disease activity, the compatibility of medications with pregnancy and breastfeeding. Risk stratification and individualized treatment approach elaborated by a multidisciplinary team minimize the risk of adverse pregnancy outcomes (APO). Research has been focused on identifying biomarkers that can be predictive of APO. Specifically, preeclampsia and hypertensive disorders of pregnancy tend to develop more frequently in women with ARD. Placental insufficiency can lead to intrauterine growth restriction and small-for-gestational age newborns. Such APO have been shown to be associated with maternal disease activity in different ARD. Therefore, a key message to be addressed to the woman wishing for a pregnancy and to her family is that treatment with compatible drugs is the best way to ensure maternal and fetal wellbeing. An increasing number of medications have entered the management of ARD, but data about their use in pregnancy and lactation are scarce. More information is needed for most biologic drugs and their biosimilars, and for the so-called small molecules, while there is sufficient evidence to recommend the use of TNF inhibitors if needed for keeping maternal disease under control. Other issues related to the reproductive journey have emerged as “unmet needs”, such as sexual dysfunction, contraception, medically assisted reproduction techniques, long-term outcome of children, and they will be addressed in this review paper. Collaborative research has been instrumental to reach current knowledge and the future will bring novel insights thanks to pregnancy registries and prospective studies that have been established in several Countries and to their joint efforts in merging data.

Background: Currently, diabetes represents the seventh leading cause of death worldwide, with a significant economic burden. The number and severity of comorbidities increase with age, and are identified as important determinants that influence the prognosis. We aimed to investigate comorbidities and outcomes in a cohort of hospitalized elderly patients affected by diabetes. Methods: In this observational study, we retrospectively analyzed data collected from the REgistro dei pazienti per lo studio delle POlipatologie e politerapie in reparti della rete Simi (RePoSi) registry. Socio-demographic, clinical characteristics, and laboratory findings were considered. The association between variables and in-hospital and 1-year follow-up were analyzed. Results: Among 4708 in-patients, 1378 (29.3%) had a diagnosis of diabetes. Patients with diabetes had more previous hospitalization, a clinically significant disability, and more need for a urinary catheter in comparison with subjects without diabetes. Patients affected by diabetes took more drugs, both at admission, at in-hospital stay, at discharge, and at 1-year follow-up. Thirty-five comorbidities were more frequent in patients with diabetes, and the first five were hypertension (57.1%), ischemic heart disease (31.4%), chronic renal failure (28.8%), atrial fibrillation (25.6%), and chronic obstructive pulmonary disease (22.7%). Heart rate was an independent predictor of in-hospital mortality. At 1-year follow-up, cancer and male sex were strongly independently associated with mortality. Conclusions: Our findings showed the severity of the impact of diabetes and its comorbidities in the real life of internal medicine and geriatric wards, and provide data to be used for a better tailored management of elderly in-patients with diabetes.

Comorbidity indexes were designed in order to measure how the disease burden of a patient is related to different clinical outcomes such as mortality, especially in older and intensively treated people. Charlson's Comorbidity Index (CCI) is the most widely used rating system, based on diagnoses, but when this information is not available therapy-based comorbidity indices (TBCI) are an alternative: among them, Drug Derived Complexity Index (DDCI), Medicines Comorbidity Index (MCI), and Chronic Disease Score (CDS) are available.This study assessed the predictive power for 1-year mortality of these comorbidity indices and polypharmacy.Survival analysis and Receiver Operating Characteristic (ROC) analysis were conducted on three Italian cohorts: 2,389 nursing home residents (Korian), 4,765 and 633 older adults admitted acutely to geriatric or internal medicine wards (REPOSI and ELICADHE).Cox's regression indicated that the highest levels of the CCI are associated with an increment of 1-year mortality risk as compared to null score for all the three samples. DDCI and excessive polypharmacy gave similar results but MCI and CDS were not always statistically significant. The predictive power with the ROC curve of each comorbidity index was poor and similar in all settings.On the whole, comorbidity indices did not perform well in our three settings, although the highest level of each index was associated with higher mortality.

ObjectiveTo map existing organizational care pathways in clinical centers of expertise that care for pregnant women affected by rare and complex connective tissue diseases (rcCTDs).MethodsAn international working group composed of experts in the field of pregnancy in rcCTDs co-designed a survey focused on organizational aspects related to the patient's pathway before, during, and after pregnancy. The survey was distributed to subject experts through referral sampling.ResultsAnswers were collected from 69 centers in 21 countries. Patients with systemic lupus erythematosus and/or antiphospholipid syndrome were followed by more than 90% of centers, whereas those with disorders such as IgG4-related diseases were rarely covered. In the majority of centers, a multidisciplinary team was involved, including an obstetrician/gynecologist in 91.3% of cases and other healthcare professionals less frequently. Respondents indicated that 96% of the centers provided routine pre-pregnancy care, whereas the number of patient visits during pregnancy varied across centers. A formalized care pathway was described in 49.2% of centers, and 20.3% of centers had a predefined protocol for the monitoring of pregnant patients. Access to therapies during pregnancy also was heterogeneous among different centers.ConclusionIn international referral centers, a high level of care is provided to patients with rcCTDs before, during, and after pregnancy. No significant discrepancies were found between European and non-European countries. However, this work highlights a potential benefit to streamlining the care approaches across countries to optimize pregnancy and perinatal outcomes among patients with rcCTDs.

Cardiac magnetic resonance (CMR) was proposed as an accurate non-invasive tool to evaluate pericardial inflammation. Aim of the present study was to evaluate the role of CMR early in the course of the first episode of acute pericarditis.A clinical registry of consecutive patients who underwent clinical indicated CMR due to pericardial disease from January 2014 to January 2020 was screened. We analyzed patients with the clinical diagnosis of first episode of acute pericarditis needing hospitalization less than 7 days before CMR. Outcome measures were obtained using a single combined end-point, defined as pericardial event, including all the following: recurrent pericarditis, chronic constrictive pericarditis, surgery for pericardial disease.Twenty-six patients meet the study criteria and were enrolled. A mean follow-up of 34 ± 7 months was obtained and a second episode of pericardial event were recorded in 9 patients. At multivariate analysis adjusted for propensity score, based on clinical significative variable (younger age and higher CRP) the association between pericardial inflammation identified by CMR (positive late gadolinium enhancement on pericardium) and recurrence of pericardial events was confirmed [OR (95%CI) 8.94 (1.74-45.80), p = 0.008].Pericardial inflammation identified by CMR, with LGE images, has a prognostic value independently from clinical and bio-humoral variables.

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.

Aging with multimorbidity and polytherapy are the most significant factors that could led to inappropriate prescribing of contraindicated medications in patients with chronic kidney disease (CKD). The aim of this study was to evaluate the prescriptions of contraindicated drugs in older adults in CKD and to identify their associated factors in a hospital context. An observational retrospective study was carried out considering all patients ≥65 years with at least one serum creatinine value recorded into the REPOSI register into 2010–2016 period. The estimated glomerular filtration rate (eGFR) was applied to identify CKD. A descriptive analysis was performed to compare demographic and clinical characteristics; logistic regression models were used to estimate factors of inappropriate and percentage changes of drug use during hospitalization. A total of 4,713 hospitalized patients were recorded, of which 49.8% had an eGFR 2; the 21.9% were in treatment with at least one inappropriate drug at the time of hospital admission with a decrease of 3.0% at discharge (p = 0.010). The probability of using at least one contraindicated drug was significantly higher in patients treated with more several drugs (OR 1.21, 95% CI 1.16–1.25, p p < 0.001; G5: 19.38, 11.51–32.64, p < 0.001). Low-dose acetylsalicylic acid was the contraindicated drug mainly used at the time of admission, reducing 1.2% at discharge. An overall increase in therapeutic appropriateness in hospitalized older patients with CKD was observed, despite a small percentage of therapeutic inappropriateness at discharge that underlines the need for a closer collaboration with the pharmacologist to improve the drug management.

Background Incessant pericarditis is defined as pericarditis with persistent symptoms without a symptom-free interval of 4 to 6 weeks despite therapy. On the contrary, recurrent pericarditis is characterized by recurring symptoms after a symptom-free interval of at least 4 to 6 weeks, allowing the completion of therapy. Aims The aim of this study is to assess the risk of complicated pericarditis and related hospitalizations according to the clinical pattern of incessant or recurrent pericarditis. Methods From January 2017 to December 2018, all consecutive patients admitted to AOU Città della Salute (Turin, IT) for pericarditis were included in a prospective cohort study with a clinical and echocardiographic follow-up at 1, 3, and 6 months, and then every 6 months. Results We included 147 patients (median age, 50.9 years [IQR, 28.5]; 49.7% women, 89% had idiopathic aetiology, 11% had pericarditis related to systemic inflammatory disease/postcardiac injury syndrome, 80% had pericardial effusion, and 62% had elevated C-reactive protein >5 mg/L). Patients were treated according to ESC guidelines. After a median follow-up of 14 months (IQR, 9 months), adverse events were recorded in 54/147 patients (36.7%): nonidiopathic/viral aetiology in 16 of 147 cases (10.9%), recurrent pericarditis/persistent symptoms in 53 of 147 cases (36.1%), cardiac tamponade in 4/147 cases (2.7%), persistent CP in 4/147 cases (2.7%), and hospitalization related to pericarditis in 38/147 cases (25.9%). An incessant course was reported in 18 of 147 cases (12%). The risk of complications was higher in patients with incessant pericarditis (Figure) – especially CP – compared to nonincessant course (22.2% versus 0%, respectively; P5 mg/L (hazard ratio, 5.55 [95% CI, 1.87–16.44]), and incessant course (HR, 17.10 [95% CI, 7.63–38.33]). Conclusions This study highlights that an incessant course of pericarditis is a possible new risk factor for complications and especially for developing constriction. In clinical practice, the detection of an incessant course, as well as imaging findings of constriction and pericardial thickening, should prompt more diagnostic testing, a close follow-up, and more aggressive therapy to prevent complications and persistent constriction. Funding Acknowledgement Type of funding sources: None. Figure 1

Anti-interleukin (IL)-1 agents have been developed for the treatment of autoinflammatory diseases characterized by overproduction of IL-1. Idiopathic recurrent pericarditis with inflammatory phenotype (fever, leukocytosis, and elevation of C-reactive protein) has similar features and responds well to this treatment. At present, in Italy, prescription of anakinra is possible for idiopathic recurrent pericarditis with corticosteroid dependence and colchicine resistance. Anakinra is a recombinant antagonist of IL-1 receptor and blocks either IL-1α (released from pericardial cells) or IL-1β (derived for inflammatory cells, during pericarditis). Anakinra is prescribed at the dose of 2 mg/kg/day subcutaneously up to 100 mg/day subcutaneously for at least 3 to 6 months with subsequent tapering. Anakinra allows a quick control of symptoms after 1-2 doses and a fast and safe tapering and withdrawal of corticosteroids. Colchicine can be used together with anakinra. The most common side effect is represented by local skin injection site reactions after 1-2 weeks of therapy. These reactions are usually transient and can be treated by anti-histamines and topical corticosteroids. Less common side effects include elevation of transaminases (4-5%), cutaneous or respiratory infections (2-3%), and leukopenia (1-3%). Side effects are rarely responsible for permanent discontinuation of therapy. The aim of the present review is to provide a practical guide on the use of these drugs for cardiologists, who are often not familial with this new therapy for pericarditis.

Background To assess differences in the probability of COVID-19-related death between native Italians and immigrants hospitalised with COVID-19. Methods This was a retrospective study of prospectively collected data conducted at the ASST Fatebenefratelli-Sacco Hospital in Milan, Italy, between 21 February and 31 November 2020. Uni- and multivariable Cox proportional hazard models were used to assess the impact of the patients' origin on the probability of COVID-19-related death. Results The study population consisted of 1,179 COVID-19 patients: 921 Italians (78.1%) and 258 immigrants (21.9%) from Latin America (99, 38.4%), Asia (72, 27.9%), Africa (50, 19.4%) and central/eastern Europe (37, 14.3%). The Italians were older (p vs 12.8%; p vs 8.3%, 6% and 8.1%, respectively; p = 0.016). Multivariate analyses showed that a Latin American origin was independently associated with an increased risk of death (adjusted hazard ratio 1.95, 95% confidence interval 1.17–3.23). Conclusions Our findings support the need to strengthen COVID-19 information and prevention initiatives in the Latin American community living in Milan.

Colchicine is one of the more ancient drugs of vegetal origin still in use in clinical practice. It has been used for centuries as drug to treat gout, but its anti-inflammatory effects made it efficacious also in different cardiovascular indications (e.g. pericarditis, acute and chronic coronary syndromes, atrial fibrillation), that are well beyond its original indication. The treatment and prevention of pericarditis is the only registered cardiovascular indication in Italy (allowing prescription in class A by the National Healthcare System), while other indications are off-label. When used at low doses (0.5 mg/day), the drug is safe and efficacious with limited side effects, mainly gastrointestinal. Gastrointestinal absorption is fast since the drug is a small lipophilic molecule that is eliminated by cells through P-glycoprotein. Colchicine is metabolized by cytochrome P450 in the liver and mainly excreted into the biliary tract. It is also excreted, essentially unmodified, by the kidneys. It is concentrated in white blood cells, especially neutrophils, that are without P-glycoprotein. In these cells, blocking tubulin polymerization, colchicine reduces their function, also interfering with endothelial adhesion and platelet interactions. Moreover, it is responsible for a non-specific inhibition of the inflammasome, thus reducing the generation of pro-inflammatory cytokines, such as interleukin-1. The aim of this paper is to provide concise replies to the most common clinical questions on the use of colchicine for cardiovascular indications.

Orthostatic hypotension (OH) is a multifactorial disorder, often asymptomatic. The prevalence of OH increases with age, ranging from 5 to 11% among middle-aged patients to 55% in the frail elderly depending on age and associated comorbidities. OH is often unrecognized or misdiagnosed and little is known about its prevalence in hospitalized elderly patients. Our aims were: (1) to determine the prevalence of OH in a cohort of elderly patients hospitalized in two internal medicine wards in Italy; (2) and to describe their characteristics and symptoms. During the 5 months from March 1, 2017 to July 31, 2017, the first 85 consecutive patients (65 years or older) admitted in two internal medicine wards were enrolled. Patients were included in the study if they were able to get out of bed alone or with minor assistance, and able to stand up for at least 3 min. The study population comprised 85 patients with a mean age of 79.6 ( ± 7.2) years. OH was found in 64 (75.3%), occasional OH in 41 (48.2%), persistent OH in 23 (27.1%), and 21 (24.7%) patients had no OH. All patients had diastolic OH and 37 (57.8%) also systolic. Patients with persistent OH were oldest, with a higher percentage of renal failure. Twenty-six patients (40.6%) with OH reported symptoms. Dizziness was the most common symptom, especially after breakfast. No association was found between type of medications and risk of OH. Mortality risk was not statistically different between patients with or without OH 3 (p = 0.10) and 6 months after discharge (p = 0.18), but a trend was observed. We found that OH is very common in the patients admitted in the internal medicine wards, particularly diastolic OH. Close attention should be paid to OH and its symptoms, especially dizziness, in the oldest-old patients, and in patients with renal failure.

BACKGROUND The prognostic relevance and the prevalence of pericardial effusion in several diseases are not well established. The aim of this meta-analysis is to summarize the available evidence related to pericardial effusion prevalence and outcomes according to the cause. METHODS Articles investigating the prognosis of pericardial effusion were identified by literature search. Twenty-three studies were finally included (17 022 patients). All-cause mortality was the primary end-point. Secondary end-point was the prevalence of pericardial effusion in most common diseases related to this clinical condition. RESULTS The pooled prevalence of pericardial effusion was 19.5% [95% confidence interval (CI): 14.3-26]. After a mean follow-up of 36 ± 23 months, the risk of death was higher in pericardial effusion patients [hazard ratio (HR) 1.59, 95% CI 1.37-1.85, P

A surprising improvement in COVID-19 chest CT follow up gives hope regarding future clinical evolution of COVID-19 patients.

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. 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.

Current guidelines on the management of pericardial diseases suggest to identify high-risk features associated with an increased risk of non-idiopathic aetiology and complications. The aim of this study is to evaluate a "pericarditis score" to assess potential complicated pericarditis in order to facilitate initial clinical triage. Consecutive patients with pericarditis were included in a prospective cohort study from January 2017 to December 2018. Complicated pericarditis was defined as pericarditis with a non-idiopathic aetiology, and/or complications, and/or requiring hospitalization. A clinical and echocardiographic follow-up were performed at 1, 3, 6 months and then every 6 months. The study population was randomized in derivation and validation cohorts. In the derivation cohort, female gender (HR 2.57, p = 0.016), fever 38 °C (HR 2.86, p = 0.005), previous lack of colchicine use (HR 3.16, p = 0.006), previous use of corticosteroids (HR 3.01, p = 0.009), and echocardiographic signs of constriction (HR 2.26, p = 0.018) were selected by a stepwise procedure in a Cox regression model and constituted the score showing a C-statistics of 0.81. In the validation group, the score was significantly associated with the risk of complicated pericarditis (HR 1.438 per 10-points increase, 95% CI 1.208-1.711, p 0.001) and showed an increase in event rate with increasing score (low risk ≤ 20 points: complicated pericarditis in 4/19 patients, incidence 21%, p = 0.003, high risk 40 points: complicated pericarditis in 18/24 patients, incidence 75%, p = 0.006). In this study, we developed and tested a simple score to efficiently identify at presentation patients at high risk of developing complicated pericarditis.

Cardiac amyloidosis is a serious and progressive infiltrative disease that is caused by the deposition of amyloid fibrils at the cardiac level. It can be due to rare genetic variants in the hereditary forms or as a consequence of acquired conditions. Thanks to advances in imaging techniques and the possibility of achieving a non-invasive diagnosis, we now know that cardiac amyloidosis is a more frequent disease than traditionally considered. In this position paper the Working Group on Myocardial and Pericardial Disease proposes an invasive and non-invasive definition of cardiac amyloidosis, addresses clinical scenarios and situations to suspect the condition and proposes a diagnostic algorithm to aid diagnosis. Furthermore, we also review how to monitor and treat cardiac amyloidosis, in an attempt to bridge the gap between the latest advances in the field and clinical practice. [GRAPHICS]

The progressive cutting of hospital beds in some health systems, together with the increased needs related to the aging population, has led to the phenomenon of patients hospitalized outside the appropriate ward (outliers). This is particularly relevant in the context of Internal Medicine. Despite its relevance in daily clinical practice, available evidence for the potential impact of this phenomenon is limited. The aim of this study is to evaluate the effects of this situation on patients’ outcomes and possibly identify organizational and managerial aspects related to the presence of outliers. The multicenter, observational, prospective Study Protocol of Safety Issues and SurvIval For Medical Outliers (SISIFO) was promoted by the Italian Federation of Associations of Hospital Doctors on Internal Medicine (FADOI). The primary study endpoint is the evaluation of in-hospital mortality in outliers versus controls. A sample size of 2400 patients has been estimated by assuming a mortality rate of 12% and 8% in outliers and controls, respectively. By virtue of the multicentric dimension, the expected number of patients, and the controlled design, the FADOI-SISIFO study might provide interesting and useful findings to better manage the phenomenon of outliers.

Anti-interleukin (IL)-1 agents have been developed for the treatment of autoinflammatory diseases characterized by overproduction of IL-1. Idiopathic recurrent pericarditis with inflammatory phenotype (fever, leukocytosis, and elevation of C-reactive protein) has similar features and responds well to this treatment. At present, in Italy, prescription of anakinra is possible for idiopathic recurrent pericarditis with corticosteroid dependence and colchicine resistance. Anakinra is a recombinant antagonist of IL-1 receptor and blocks either IL-1α (released from pericardial cells) or IL-1β (derived for inflammatory cells, during pericarditis). Anakinra is prescribed at the dose of 2 mg/kg/day subcutaneously up to 100 mg/day subcutaneously for at least 3 to 6 months with subsequent tapering. Anakinra allows a quick control of symptoms after 1-2 doses and a fast and safe tapering and withdrawal of corticosteroids. Colchicine can be used together with anakinra. The most common side effect is represented by local skin injection site reactions after 1-2 weeks of therapy. These reactions are usually transient and can be treated by anti-histamines and topical corticosteroids. Less common side effects include elevation of transaminases (4-5%), cutaneous or respiratory infections (2-3%), and leukopenia (1-3%). Side effects are rarely responsible for permanent discontinuation of therapy. The aim of the present review is to provide a practical guide on the use of these drugs for cardiologists, who are often not familial with this new therapy for pericarditis.

Reduced estimated creatinine clearance (eCrCl) is prevalent in older patients and impacts on drug prescription. In this study, the burden of eCrCl reduction and its associated factors and impact on outcomes were analyzed. Moreover, the rate of inappropriate drug prescription according to eCrCl and its impact on outcomes were described.Data were obtained from "REgistro POliterapie SIMI" (REPOSI), a prospective observational register enrolling hospitalized patients aged ≥ 65 years. Patients enrolled from 2010-2016 with available data to calculate eCrCl according to the Cockcroft-Gault formula were included in this analysis.A total of 5046 patients were available for analysis. Among these, we found an eCrCl of 45-59 mL/min in 1163 patients (23.0%), an eCrCl of 30-44 mL/min in 1128 (22.4%), an eCrCl of 15-29 mL/min in 702 (13.9%), and an eCrCl 15 mL/min in 152 (3.0%), with several clinical factors associated with decreasing eCrCl. During follow-up, a progressively higher risk for all-cause death, cardiovascular (CV) death, any death/re-hospitalization, and CV death/re-hospitalization was found across the renal function classes. Among patients with hypertension, diabetes mellitus, atrial fibrillation, coronary artery disease, and heart failure, 476 (10.9%) were inappropriately prescribed medications according to eCrCl. During follow-up, inappropriate prescription was associated with increased risk of all-cause death (odds ratio [OR] 1.49, 95% confidence interval [CI] 1.13-1.97) and any death/re-hospitalization (OR 1.30, 95% CI 1.03-1.63).In older hospitalized patients, impaired eCrCl is prevalent and associated with several factors, polypharmacy in particular. Patients with reduced eCrCl have a higher risk of major clinical outcomes, and 10% of them are prescribed an inappropriate drug, with a higher risk for major clinical outcomes.

Cardiac amyloidosis is a serious and progressive infiltrative disease that is caused by the deposition of amyloid fibrils at the cardiac level. It can be due to rare genetic variants in the hereditary forms or as a consequence of acquired conditions. Thanks to advances in imaging techniques and the possibility of achieving a non-invasive diagnosis, we now know that cardiac amyloidosis is a more frequent disease than traditionally considered. In this position paper the Working Group on Myocardial and Pericardial Disease proposes an invasive and non-invasive definition of cardiac amyloidosis, addresses clinical scenarios and situations to suspect the condition and proposes a diagnostic algorithm to aid diagnosis. Furthermore, we also review how to monitor and treat cardiac amyloidosis, in an attempt to bridge the gap between the latest advances in the field and clinical practice.

A total of 48 internal medicine or geriatric wards among the 93 adhering to the register REPOSI answered an online questionnaire aimed to investigate the characteristics and activities of converted and non-converted wards in the crucial period of the first wave of the epidemic, 22 February-4 May 2020

Objectives Psycholeptic drugs have been used in the older population for years, especially to control delirium and neuropsychiatric symptoms (NPS) of dementia. However, data from the literature confirm that the prolonged use of psycholeptics may be responsible for adverse reactions in older patients. The aim of this study was (1) to identify how many patients receive the first prescription of a psycholeptic drug during the hospital stay; (2) to evaluate the main sociodemographic and clinical characteristics of these patients; and (3) to verify if the prescribed psycholeptic drugs are continued after 3 months from the hospital discharge. Design Our retrospective study was based on data from the REPOSI (REgistro POliterapie SIMI) registry, a cohort of older patients hospitalized in internal medicine and geriatric wards throughout Italy from 2010 to 2018. Setting and Participants Patients aged 65 years or older who were not on home therapy with psycholeptic drugs were considered in the analyses. Methods We did both univariate and multivariate analyses in order to find the variables associated independently to an increased risk for first psycholeptic prescription at hospital discharge. Results At hospital discharge, 193 patients (5.8%) out of a total sample of 3322 patients were prescribed at least 1 psycholeptic drug. Cognitive impairment was the main risk factor for the introduction of psycholeptic drugs at discharge. Among them, 89.1% were still on therapy with a psycholeptic drug after 3 months from the hospital discharge. Conclusions and Implications Cognitive impairment represents the main risk factor for psycholeptic initiation in hospitalized older patients. The vast majority of these treatments are chronically continued after the discharge. Therefore, special attention is needed in prescribing psycholeptics at discharge, because their prolonged use may lead to cognitive decline. Moreover, their continued use should be questioned by physicians providing post-acute care, and deprescribing should be considered.

Recurrent pericarditis is a true challenge for clinicians, especially when the patient becomes unresponsive or not tolerant to conventional treatments. An accurate diagnosis of recurrent pericarditis, possibly supported by advanced imaging tools, is critical to provide timely and appropriate treatment of symptoms and prevention of further episodes. The incessant research on the inflammatory pathways underlying cardiovascular diseases, led recently to the assessment of anti interleukin-1 agents in the setting of recurrent pericarditis. This review will focus on the diagnostic assessment of recurrent pericarditis, along with the most modern therapeutic advances in this field. Bibliographic databases were searched (MEDLINE/PubMed, BioMed Central, the Cochrane Collaboration Database of Randomized Trials, Scopus, ClinicalTrials.gov, EMBASE, Google Scholar) using the terms “recurrent pericarditis” AND “diagnosis” OR “treatment” OR “IL-1” OR “inflammation”.

Carlotta Franchi,1 Giulia Lancellotti,2 Marco Bertolotti,2 Simona Di Salvatore,2 Alessandro Nobili,1 Pier Mannuccio Mannucci,3 Chiara Mussi,2,&ast; Ilaria Ardoino1,&ast; On Behalf of the REPOSI (REgistro POliterapie SIMI and Società Italiana di Medicina Interna) Study Group1Department of Neuroscience, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milano, Italy; 2Division of Geriatrics, Department of Biomedical, metabolic and Neural Sciences and Center for Gerontological Evaluation and Research, Università di Modena e Reggio Emilia, Modena, Italy; 3Scientific Direction, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milano, Italy&ast;These authors contributed equally to this workCorrespondence: Carlotta FranchiUnit of Pharmacoepidemiological Research in Older People, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri 2, Milano, 20156, ItalyTel +39 02 39014580Fax +39 02 39001916Email carlotta.franchi@marionegri.itObjective: To assess how lipid-lowering drugs (LLDs) are administered in the hospitalized patients aged 65 and older and their association with clinical outcomes according to their health-related profiles.Design: This is a retrospective study based on data from REPOSI (REgistro POliterapie SIMI – Italian Society of Internal Medicine) register, an Italian network of internal medicine hospital wards.Setting and Participants: A total of 4642 patients with a mean age of 79 years enrolled between 2010 and 2018.Methods: Socio-demographic characteristics, functional abilities, cognitive skills, laboratory parameters and comorbidities were used to investigate the health state profiles by using multiple correspondence analysis and clustering. Logistic regression was used to assess whether LLD prescription was associated with patients’ health state profiles and with short-term mortality.Results: Four clusters of patients were identified according to their health state: two of them (Cluster III and IV) were the epitome of frailty conditions with poor short-term outcomes, whereas the others included healthier patients. The average prevalence of LLD use was 27.6%. The lowest prevalence was found among the healthier patients in Cluster I and among the oldest frail patients with severe functional and cognitive impairment in Cluster IV. The highest prevalence was among multimorbid patients in Cluster III (OR=4.50, 95% CI=3.76– 5.38) characterized by a high cardiovascular risk. Being prescribed with LLDs was associated with a lower 3-month mortality, even after adjusting for cluster assignment (OR=0.59; 95% CI = 0.44– 0.80).Conclusion: The prevalence of LLD prescription was low and in overall agreement with guideline recommendations and with respect to patients’ health state profiles.Keywords: statins, health state profile, multimorbidity, polypharmacy

We read with great interest the letter by Kawada in which the studies assessing colchicine as a treatment for COVID-19 were reviewed.1 Given its known inhibitory effect on NACHT-LRRPYD-containing protein 3 inflammasome2 and its possible antiviral properties,2 colchicine was hypothesised as a candidate therapy for COVID-19 since the very beginning of the pandemic.3 4 To the best of our knowledge, our observational retrospective study5 reported on the largest number of patients with COVID-19 treated with colchicine (122 consecutive patients), and they were compared with a control group treated with the Standard of Care (SoC, 140 consecutive patients).5 Kawada underlined the effectiveness of colchicine in reducing mortality and the need for non-invasive ventilation, as shown by different studies.5–7 After the hospital discharge, we observed additional deaths in patients treated with colchicine and in those treated with SoC (p=0.25). The long-term analysis of our cohort confirmed the original description of improved survival for patients treated with colchicine (mortality rate at 270 days: colchicine 20% vs SoC 44%; p=0.0001). We would like to point out the statement by Kawada reporting that ferritin and arterial oxygen tension (or pressure) (PaO2 …

Anti-interleukin (IL)-1 agents have been developed for the treatment of autoinflammatory and rheumatic conditions, where overproduction of IL-1 is an important pathophysiologic process. IL-1α and IL-1β are the most studied members of the IL-1 family of cytokines and have the strongest proinflammatory effects. A naturally occurring antagonist (IL-1Ra) mitigates their proinflammatory effects. Overproduction of both IL-1α (released by inflamed/damaged pericardial cells) and IL-1β (released by inflammatory cells) is now a well-recognized therapeutic target in patients with recurrent idiopathic pericarditis. Currently, there are three available anti-IL-1 agents: anakinra (recombinant human IL-1Ra), rilonacept (a soluble decoy receptor 'trap', binding both IL-1α and IL-1β), and canakinumab (human monoclonal anti-IL-1β antibody). For patients with corticosteroid-dependent and colchicine-resistant recurrent pericarditis with evidence of systemic inflammation, as evidenced by elevated C-reactive protein, the efficacy and safety of anakinra (2 mg/kg/day up to 100 mg/day subcutaneously usually for at least 6 months, then tapered) and rilonacept (320 mg subcutaneously for the first day followed by 160 mg subcutaneously weekly) have been clearly demonstrated in observational studies and randomized controlled clinical trials. Severe side effects are rare and discontinuation rates are very low ({\textless}4\%). The most common reported side effect is injection site reactions ({\textgreater}50\% of patients). In this article, we describe the historical and pathophysiological background and provide a comprehensive review of these agents, which appear to be the most significant advance in medical therapy of recurrent pericarditis in the last 5 years.

Background: To know burden disease of a patient is a key point for clinical practice and research, especially in the elderly. Charlson’s Comorbidity Index (CCI) is the most widely used rating system, but when diagnoses are not available therapy-based comorbidity indices (TBCI) are an alternative. However, their performance is debated. This study compares the relations between Drug Derived Complexity Index (DDCI), Medicines Comorbidity Index (MCI), Chronic Disease Score (CDS), and severe multimorbidity, according to the CCI classification, in the elderly. Methods: Logistic regression and Receiver Operating Characteristic (ROC) analysis were conducted on two samples from Italy: 2579 nursing home residents (Korian sample) and 7505 older adults admitted acutely to geriatric or internal medicine wards (REPOSI sample). Results: The proportion of subjects with severe comorbidity rose with TBCI score increment, but the Area Under the Curve (AUC) for the CDS (Korian: 0.70, REPOSI: 0.79) and MCI (Korian: 0.69, REPOSI: 0.81) were definitely better than the DDCI (Korian: 0.66, REPOSI: 0.74). All TBCIs showed low Positive Predictive Values (maximum: 0.066 in REPOSI and 0.317 in Korian) for the detection of severe multimorbidity. Conclusion: CDS and MCI were better predictors of severe multimorbidity in older adults than DDCI, according to the CCI classification. A high CCI score was related to a high TBCI. However, the opposite is not necessarily true probably because of non-evidence-based prescriptions or physicians’ prescribing attitudes. TBCIs did not appear selective for detecting of severe multimorbidity, though they could be used as a measure of disease burden, in the absence of other solutions.

INTRODUCTION Pericarditis is an inflammatory disease of the pericardium. Progress has been done in recent years in the understanding of its pathophysiology. In particular, preclinical and clinical studies have contributed to increasing our knowledge on the role of interleukin (IL)-1 and NLRP3 (NACHT, leucine-rich repeat, and pyrin domain-containing protein 3) inflammasome. EVIDENCE ACQUISITION Information for this study has been retrieved in original articles, reviews, systematic reviews, and meta-analyses identified through PubMed using the following search terms (or combination of terms): "pericarditis," "acute pericarditis," "recurrent pericarditis," "idiopathic recurrent acute pericarditis," "autoimmunity," "autoinflammation," "outcomes." Only articles published in English were included. Additional papers identified from the reference list of the retrieved articles were also considered. EVIDENCE SYNTHESIS Based on current evidence, pericarditis should be considered as an inflammatory reaction to various stimuli, including chemical/physical, infectious, or ischemic ones, with a viral infection being a common etiology. Interaction of pathogens or irritants with toll-like receptor (TLRs) and stimulation of IL-1 receptor by IL-1α and IL-1β leads to an increased transcription of proinflammatory genes, including those needed for NLRP3 inflammasome assembly. This pathway is confirmed indirectly by the beneficial effect of colchicine (an indirect NLRP3 inflammasome inhibitor) and IL-1 blockers in patients with recurrent pericarditis. More recently, a direct evidence of the NLRP3 inflammasome within the inflamed pericardium has been provided as well. It may, however, occur that self-antigens on the surface of mesothelial cells or microbial peptides may stimulate autoreactive T cells along with B cells producing antiheart antibodies, although less evidence is available on this. CONCLUSIONS Some uncertainties still remain about the role of neutrophils, neutrophil extracellular traps (NETs), and pericardial interstitial cells in recurrent and constrictive pericarditis. Unraveling these aspects might have a direct impact on the development of novel targeted therapies, especially considering the increasing number of drugs targeting NETs.

Background Recurrent pericarditis is very difficult to treat, especially when symptoms become refractory to conventional treatments (nonsteroidal anti-inflammatory drugs,colchicine,corticosteroids). Interleukin-1 (IL-1) blockade with anakinra has been proved to be useful in this setting. Indeed, persistent inflammation of the pericardium may lead to pericardial constriction, worsening prognosis. Purpose This study was aimed to assess the incidence and clinical course of pericardial constriction in patients with corticosteroid-dependent, colchicine-resistant recurrent pericarditis (CCRP) undergoing anti IL-1 treatment. Methods We selected patients included in the IRAP (International Registry of Anakinra for Pericarditis). A subgroup of 39 CCRP patients enrolled at the coordinating center underwent echocardiographic and clinical assessment for pericardial constriction. Results Thirty-nine patients were assessed, aged 42±12 years old, 67% females, 74% idiopathic etiology, with a median disease duration of 12 months (IQR 9–20) and a recurrence rate of 2.79 flares-patient/year before starting anakinra. Echocardiographic signs of pericardial constriction were demonstrated in 8 patients (21%). After starting anakinra, in 5/8 patients (63%) a complete resolution of pericardial constriction was observed within a median of 1.2 months,IQR 1–4. In other 3/8 patients (37%) pericardial constriction persisted and became chronic, requiring pericardiectomy within a median of 2.8 months, IQR 2–5. Compared with others, the 8 patients with pericardial constriction hadn't had a greater burden of pericardial flares before anakinra (3.87 flares-patient/year vs. 2.62/patient-year, p=0.07) and after anakinra (0.71 flares-patient/year vs. 0.72/patient-year, p=0.99). However, among 11 patients (28%) with incessant symptoms, an higher incidence of pericardial constriction was observed, compared with patients with recurrent symptoms (respectively 64% vs. 3.6%, RR=47, 95% CI 4.5–492, p Conclusions In CCRP patients, pericardial constriction may be reversed by anti IL-1 agents. The risk of pericardial constriction is associated with incessant symptoms rather than simple recurrent course. Funding Acknowledgement Type of funding source: None

We read with interest the paper from Navarro-Millan about the use of anakinra in severe COVID-19 patients (1). On the other hand, there is the issue of patients treated with anakinra for their underlying condition and who develop COVID-19 (2).

Introduction: Acute pericarditis is an inflammatory condition causing the occurrence of pericardial effusion. In a third of patients, the disease is recurrent. First line treatment of idiopathic pericarditis consists in non-steroidal anti-inflammatory drugs (NSAIDs) and colchicine; glucocorticoids represent the second line treatment in resistant or intolerant cases. A recent clinical trial has enlightened the effectiveness of anakinra in adults and paediatric patients with colchicine-resistant recurrent pericarditis. Objectives: To describe the clinical characteristics and response to treatment in a cohort of paediatric patients with recurrent pericarditis treated with IL inhibitors. Methods: paediatric patients with recurrent pericarditis followed at 19 Italian centers of paediatric rheumatology or cardiology and treated with IL1 inhibitors were included in the study. Demographic, clinical and response to treatment data were retrospectively collected. Results: 55 patients were included in the study. The mean age at onset of the first episode of pericarditis was 12.53 years. The mean number of relapses of pericarditis before the beginning of treatment with IL1 inhibitors was of 3.4 (range 1 -10). 53 out of 55 patients had previously received treatment with NSAIDS and 44 with colchicine. 44 patients received steroidal treatment: 2 of them displayed a steroidal-resistance and 39 steroidal-dependence with reoccurrence of the symptoms following any attempt to reduce or withdraw this treatment. Anakinra (mean dosage of 1.67 mg/kg/day) was used as first Il-1 inhibitor in 54 of the 55 patients, Canakinumab (150 mg every 4 weeks) in one. 53 out of 54 patients treated with anakinra displayed a complete clinical response to treatment within a mean of 2 days (range 1-7): NSAIDs, glucocorticoids and colchicine were withdraw in 25 out of 26, 31 out of 35 and 15 out of 32 patients respectively. 50 of 54 patients displayed a complete response; among these, three were switched to Canakinumab, 17 patients continued treatment at the same dosage while in 30 patients a reduction of treatment was attempted. 12 patients presented, during anakinra tapering, a disease flare, promptly resolved after an increasing of the dosage. The remaining 18 patients did not present any flare despite the reduction of the drug. Anakinra was withdrawn in 16 patients, with recurrence of the symptoms in 11. 5 patients were treated with Canakinumab: 1 as first anti-IL1 drug, 4 were switched from anakinra (two for poor compliance, one for side effects and one for incomplete control of the disease). 2 out of five patients had a complete control of the diseases, 2 patients discontinued the treatment because of inefficacy and 1 patient required low dose of glucocorticoids to control the disease. At last follow-up 34 patients were on anakinra, 7 on anakinra and colchicine, 2 on canakinumab, 1 on canakinumab plus colchicine and NSAIDs. In 9 patients all treatments were withdrawn for complete control of the disease. Conclusion: This study confirm the effectiveness of IL-1 blockade in paediatric patients with recurrent pericarditis. However most of the patients require prolonged treatment to maintain clinical remission. Moreover, in our cohort of patients the rate of response was higher for anakinra then for canakinumab, suggesting a possible role of IL1α in the pathogenesis of this condition.

The published experience with biologics in childbearing age with autoimmune and inflammatory diseases mainly deals with the use of TNFα inhibitors (TNFα-i). Limited data are available for biologics targeting other cytokines or immunocompetent cells, especially for the inflammasome targeted therapy including IL-1 inhibitors and colchicine. We conducted a nested case-control study by using the US Food and Drug Administration Adverse Event Reporting System database aimed at quantifying the association between the use of IL-1 inhibitors/colchicine in pregnant women and the occurrence of maternal/fetal adverse effects. The reporting odds ratio was used as a measure of disproportional reporting. From the total cohort (40,033 pregnant women), we retrieved 7,620 reports related to neonatal AEs, 2,889 to fetal disorders, 8,364 to abortion, 8,787 to congenital disorders, and 7,937 to labor/delivery complications. Inflammasome-targeted drugs did not present any disproportionate reporting for all these clusters of AEs. TNFα-i confirmed their safety during pregnancy with aROR < 1 for all clusters of AEs except for labor complications. Finally, we performed a systematic review of the current literature. Data from the eligible studies (12 observational studies and 6 case reports; yielding a total of 2,075 patients) were reassuring. We found no major safety issues on malformations risk of inflammasome targeted therapies in pregnancy. However, due to limited data, the routine use of these agents should be considered in pregnancy only if risk benefit assessment justifies the potential risk to the fetus.