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BACKGROUND Despite having many benefits, frequently-used medications may still have potential risks and can cause harm. Hemopericardium is a lethal pathology with a high risk of mortality and a lower differential diagnosis consideration. When adding both mentioned elements, their consideration as a differential diagnosis would require a higher threshold. This report presents a 66-year-old man with atrial fibrillation, heart failure, and aortic stenosis status post transcatheter aortic valve replacement (TAVR) 1 year ago with hemopericardium while treated with apixaban. CASE REPORT We present the case of a 66-year-old man with multiple medical conditions, including atrial fibrillation, heart failure, and aortic stenosis post-transcatheter aortic valve replacement 1 year before admission, who presented with 2 weeks of dyspnea and lower-limb swelling. Initial assessments revealed atrial fibrillation, elevated brain natriuretic peptide, and a chest X-ray indicating possible left pleural effusion and cardiomegaly. On day 4, an echocardiogram identified a large hemopericardium and tamponade, prompting urgent surgery. A pericardial window was performed, draining 1700 cc of bloody fluid. The postoperative improvement included normalized hemodynamics and echocardiographic findings. Pathology confirmed hemopericardium. The follow-up echocardiogram showed improved cardiac function, and the patient was transferred to the general medical floor. CONCLUSIONS This case sheds light on the uncommon but critical complications associated with direct oral anticoagulant therapy. With only a handful of reported cases, the rarity of this condition underscores the need for heightened awareness among clinicians. The patient's intricate medical history accentuates the challenges in managing anticoagulation in individuals with multiple comorbidities.

Background: Programmed cell death 1 (PD-1) inhibitors can induce various adverse reactions associated with immunity, of which cardiotoxicity is a serious complication. Limited research exists on the link between PD-1 inhibitor use and pericardial effusion (PE) occurrence and outcomes., Methods: We conducted a retrospective study at the First Affiliated Hospital of Xi'an Jiaotong University from 2017 to 2019, comparing cancer patients who developed PE within 2 years after PD-1 inhibitor therapy to those who did not. Our primary outcome was the all-cause mortality rate at one year. We applied the Kaplan-Meier method for survival analysis. Multivariate logistic regression was utilized to identify PE risk factors, adjusting for potential confounders., Results: A total of 91 patients were finally included, of whom 39 patients had PE. Compared to non-PE group, one-year all-cause mortality was nearly 5 times higher in PE group (64.10% vs. 13.46%, P < 0.001). Patients who developed PE within 2 years of taking PD-1 inhibitors were significantly associated with increased all-cause mortality compared with those who did not (HR: 6.26, 95%CI: 2.70-14.53, P < 0.001). Multivariable logistic regression showed that use of sintilimab (OR: 14.568, 95%CI: 3.431-61.857, P < 0.001), history of lung cancer (OR: 15.360, 95%CI: 3.276-72.017, P = 0.001), and history of hypocalcemia (OR: 7.076, 95%CI: 1.879-26.649, P = 0.004) were independent risk factors of PE development in patients received PD-1 inhibitors therapy., Conclusions: In cancer patients receiving PD-1 inhibitors, PE was associated with higher one-year mortality. Use of sintilimab, and history of lung cancer or hypocalcemia were linked to PE occurrence., Competing Interests: Declaration of competing interest None declared., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The literature has paid very little attention to pericarditis, pericardial effusion and pancreatitis during clozapine treatment in children and adolescents., Methods: Cases of clozapine-associated pericarditis and pancreatitis in children were studied using searches in: 1) PubMed (June 16, 2023), and 2) the World Health Organization's pharmacovigilance database (June 1, 2022), VigiBase. VigiBase uses a logarithmic measure of disproportionality called the information component (IC)., Results: The PubMed search yielded 3 clozapine-associated pericarditis cases, 1 pancreatitis case and 1 with both. VigiBase provided a significant clozapine-associated pericarditis IC = 3.6 with an IC 025  = 2.9 (only 3 cases were expected while 22 were observed). VigiBase provided a significant clozapine-associated pancreatitis IC = 2.2 with an IC 025  = 1.4 (only 3 cases were expected while 16 were observed). In VigiBase clozapine-associated pericarditis and pericardial effusion in youth looked similar and on a continuum with myocarditis, as myocarditis, pericarditis and pancreatitis appeared to occur mainly during clozapine titration. Combining PubMed and VigiBase we identified: 1) 29 cases of at least possible clozapine-associated pericarditis/pericardial effusion (6 probable and 23 possible) including 7 cases with and 22 without myocarditis, and 2) 17 cases of clozapine-associated pancreatitis (1 definite and 16 possible). Two of the pancreatitis cases occurred during overdoses. No fatal outcomes were found in any clozapine-associated pericarditis and pancreatitis cases., Conclusions: Despite the lack of attention in the literature to clozapine-associated pericarditis and pancreatitis, results demonstrate that they can happen in youth, particularly during titration. Pericarditis and pancreatitis appear to be forms of clozapine-associated inflammation during dose titration., Competing Interests: Declaration of competing interest No commercial organizations had any role in the writing of this paper for publication. In the last 3 years, RdF has received speaker fee from Janssen Pharmaceutica and travel support from Janssen Pharmaceutica and ROVI; CUC has been a consultant and/or advisor to or has received honoraria from: AbbVie, Acadia, Alkermes, Allergan, Angelini, Aristo, Biogen, Boehringer-Ingelheim, Cardio Diagnostics, Cerevel, CNX Therapeutics, Compass Pathways, Darnitsa, Denovo, Gedeon Richter, Hikma, Holmusk, IntraCellular Therapies, Jamjoom Pharma, Janssen/J&J, Karuna, LB Pharma, Lundbeck, MedAvante-ProPhase, MedInCell, Merck, Mindpax, Mitsubishi Tanabe Pharma, Mylan, Neurocrine, Neurelis, Newron, Noven, Novo Nordisk, Otsuka, Pharmabrain, PPD Biotech, Recordati, Relmada, Reviva, Rovi, Sage, Seqirus, SK Life Science, Sumitomo Pharma America, Sunovion, Sun Pharma, Supernus, Takeda, Teva, Tolmar, Vertex, and Viatris. He provided expert testimony for Janssen and Otsuka. He served on a Data Safety Monitoring Board for Compass Pathways, Denovo, Lundbeck, Relmada, Reviva, Rovi, Supernus, and Teva. He has received grant support from Janssen and Takeda. He received royalties from UpToDate and is also a stock option holder of Cardio Diagnostics, Kuleon Biosciences, LB Pharma, Mindpax, and Quantic; GS has received speaker/consultation fees from Dexcel Pharma, HLS Therapeutics and Thermo Fisher. In the last 3 years, the remaining authors report no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Abstract: A patient with a large pericardial effusion and impending tamponade exhibited clinical improvement with urgent pericardiocentesis. Further workup ruled minoxidil to be the likely cause of the effusion. After discontinuation of minoxidil, the effusion did not recur., (Copyright © 2023 American Academy of Physician Associates.)

We report an interesting case of pericardial effusion associated with idiopathic systemic capillary leak syndrome (ISCLS) following administration of SARS-CoV-2 vaccine. This patient initially presented with dyspnoea and chest pain, with non-pitting oedema and clear lung fields. The diagnosis of ISCLS was made based on the clinical syndrome and laboratory evidence of polycythaemia and hypoalbuminaemia. An enlarging pericardial effusion was diagnosed on transthoracic echocardiogram. Daily point-of-care ultrasound (POCUS)-guided volume management and serial transthoracic echocardiograms contributed to avoidance of refractory shock, cardiac tamponade and critical care admission., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: This study aimed to conduct a thorough analysis of fluid retention-associated adverse events (AEs) associated with BCR::ABL inhibitors., Design: A retrospective pharmacovigilance study., Setting: Food and Drug Administration Adverse Event Reporting System (FAERS) database for BCR::ABL inhibitors was searched from 1 January 2004 to 30 September 2021., Main Outcome Measures: Reporting OR (ROR) and 95% CI were used to detect the signals. ROR was calculated by dividing the odds of fluid retention event reporting for the target drug by the odds of fluid retention event reporting for all other drugs. The signal was considered positive if the lower limit of 95% CI of ROR was >1. The analysis was run only considering coupled fluid retention events/BCR::ABL inhibitors with at least three cases., Results: A total of 97 823 reports were identified in FAERS. Imatinib had the most fluid retention signals, followed by dasatinib and nilotinib, while bosutinib and ponatinib had fewer signals. Periorbital oedema (ROR=24.931, 95% CI 22.404 to 27.743), chylothorax (ROR=161.427, 95% CI 125.835 to 207.085), nipple swelling (ROR=48.796, 95% CI 26.270 to 90.636), chylothorax (ROR=35.798, 95% CI 14.791 to 86.642) and gallbladder oedema (ROR=77.996, 95% CI 38.286 to 158.893) were the strongest signals detected for imatinib, dasatinib, nilotinib, bosutinib and ponatinib, respectively. Pleural effusion, pericardial effusion and pulmonary oedema were detected for all BCR::ABL inhibitors, with dasatinib having the highest RORs for pleural effusion (ROR=37.424, 95% CI 35.715 to 39.216), pericardial effusion (ROR=14.146, 95% CI 12.649 to 15.819) and pulmonary oedema (ROR=11.217, 95% CI 10.303 to 12.213). Patients aged ≥65 years using dasatinib, imatinib, nilotinib or bosutinib had higher RORs for pleural effusion, pericardial effusion and pulmonary oedema. Patients aged ≥65 years and females using imatinib had higher RORs for periorbital oedema, generalised oedema and face oedema., Conclusions: This pharmacovigilance study serves as a clinical reminder to physicians to be more vigilant for fluid retention-associated AEs with BCR::ABL inhibitors., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction : Insulin induced edema (IIE) is a rare condition, usually found in newly diagnosed diabetes patients, either after insulin treatment initiation or after dose increment. It is a self-limited process, rarely associated with serosal effusions. Teenage girls with type 1 diabetes (T1DM) are most commonly affected. Patient and Methods : A 12-year-old girl was diagnosed with ketoacidosis (DKA). Seven days after initiation of the insulin treatment, at a stable total daily dose of insulin (TDDI) of 0.55 IU/kg, she came with two kilograms weight gain in only two days and edema of the feet and calves. Ultrasound of the heart found a 7 mm pericardial effusion. The diagnostic workout included clinical examination, biochemical, hormonal, allergen analyses and imaging which excluded other known causes of swelling. Conclusions : We describe an adolescent girl with newly diagnosed T1DM and a rare association of peripheral insulin-induced edema and pericardial effusion. Short-term diuretic treatment and salt restriction resolved this rare complication of insulin treatment., (© 2023 Aleksandra Janchevska et al., published by Sciendo.)

Chylous pericardial effusions are extremely rare outside of thoracic and cardiac surgery patients. We report the case of an 8-year-old girl with history of recurrent benign giant cell granulomas who developed a large chylous pericardial effusion with cardiac tamponade soon after beginning therapy with imatinib. In this article, we discuss the presentation, diagnosis, and management and review the published literature of this rarely reported side effect of this medication.

Background: Nivolumab has been used for the treatment of various types of cancers and has achieved improvements in overall survival. However, nivolumab can cause a variety of adverse events (AEs). Among these, cardiac-specific AEs have received little attention in clinical trials, despite their life-threatening potential., Objective: The present study aimed to determine the risk of nivolumab-induced cardiac AEs, time to onset, incidence rates, and post hoc outcomes using the Japanese Adverse Drug Event Report database., Methods: We analyzed data for the period between April 2004 and March 2021. Data on cardiac AEs were extracted and relative risk of AEs was estimated using the reporting odds ratio (ROR)., Results: We analyzed 1,772,494 reports and identified 18,721 reports of AEs caused by nivolumab. Of these, 409 reports involved cardiac AEs. Signals were detected for four cardiac AEs: myocarditis; pericardial effusion; pericarditis; and immune-mediated myocarditis. Among these, myocarditis was the most frequently reported (35.0%) and included fatal cases. A histogram of times to onset showed nivolumab-associated AEs occurring 41-127 days after starting administration, with outlier cases of myocarditis or pericardial effusion occurring after more than one year, both with catastrophic consequences., Conclusion: This study focused on cardiac AEs caused by nivolumab as post-marketing AEs. Myocarditis and pericardial effusion have been associated with some fatal cases after administration of nivolumab. Patients should be monitored for signs of onset for these AEs, not only at the start of administration, but also over an extended period after nivolumab administration., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Introduction: The treatment of non-small cell lung cancer (NSCLC) has profoundly changed on account of the arrival of new therapies, like immunotherapy. Within this group of drugs, those aimed at the programmed cell death-1 or programmed cell death ligand-1(PD1/PDL-1) are very relevant, for example, Pembrolizumab. Although its adverse reactions are generally mild and well tolerated, it has been associated with certain immune-related adverse events (IrAEs) than can be serious and affect any organ., Case Report: A 62-year-old woman diagnosed with stage IV NSCLC with a single bone metastasis and PD-L1 expression of 60% started treatment with cisplatin-pemetrexed-pembrolizumab, and maintenance with pembrolizumab., Management and Outcome: The patient attended the ER with pericardial effusion that was assumed to be a Pembrolizumab IrAE and was managed with corticosteroids. The patient fully recovered but immunotherapy was not reintroduced due to the severity of the AE., Discussion: The cardiovascular system is among the least affected organs by immunotoxicity, with an incidence between 0.09-0.6%. However, some authors suspect the incidence is underestimated. Median time to onset is highly variable, ranging from 6 weeks since the first dose to 2 years after discontinuation of the treatment. There are not guidelines on the most effective management of the IrAEs, but according to the pharmaceutical reference, corticosteroids should be initiated followed by a progressive reduction. If no response is obtained, another immunosuppressive agent should be added. The determination to restart immunotherapy depends on the severity of the adverse reaction, the availability of other alternative treatments, and the cancer response.

Introduction: The most common kind of leukemia in adults is chronic lymphocytic leukemia (CLL). CLL is treated with ibrutinib. During the course of ibrutinib therapy, bleeding and cardiac arrhythmias may occur. Non-hemorrhagic adverse events are extremely infrequent in individuals using ibrutinib., Case Report: A 64 year-old man was diagnosed with CLL in June 2016. He was treated with 6 courses of FCR, he stayed in remission for 3 years and then relapsed. He achieved partial remission after two months of therapy with ibrutinib. The patient was admitted to the hospital with fever and shortness of breath. Pericardial tamponade and effusion was diagnosed during his evaluation., Management & Outcome: Non-hemorrhagic exudative effusion was drained by pericardiocentesis and a pericardial catheter was inserted to drain pericardial effusion. In all pleural and pericardial effusion samples, pathological and flow cytometric examination revealed no atypical malignant cells for malignancy, including CLL. Infections, both bacterial and viral, were also undetectable in the samples, as were rheumatological markers of collagen vascular disease. Ibrutinib therapy was discontinued. The pericardial effusion and tamponade were linked to ibrutinib treatment after evaluating the adverse drug reaction probability scale with a total score of 6. Colchicine was administered to reduce the pericardial effusion. The catheter was removed; pericardial effusion did not reoccur during follow up visits., Discussion: Serious adverse events of ibrutinib are seen when treating CLL patients. This group of individuals should be closely monitored for potentially serious complications such as pericardial effusion and cardiac tamponade.

Background: Spontaneous hemopericardium, associated with direct oral anticoagulant (DOAC) use, is one of the uncommon complications with high morbidity that has not been extensively studied We aimed to determine demographic characteristics, clinical features, lab evaluation, management, and outcomes of the studies focusing on hemopericardium as a DOAC use., Methods: PubMed, Web of Science, Google Scholar, and CINAHL databases were searched for relevant articles using MeSH key-words and imported into referencing/review software. The data regarding demographics, clinical characteristics, cardiac investigations, and management were analyzed in IBM Statistics SPSS 21. t-Test and Chi-square test were used. A P score of <0.05 was considered statistically significant., Results: After literature search, a total of 41 articles were selected for analysis. The mean age of the patients was 70.09 ± 11.06 years (p < 0.05); the majority of them were males (58.5%). Most of the patients presented with shortness of breath (75.2%) and had more than 3 co-morbid conditions (43.9%). The most frequently used anticoagulant was rivaroxaban (15/41; 36.6%); the common indication being arrhythmia (78.0%). CYP4503A4/P-Gp inhibitors (22.2%) were commonly used by the patients. Majority of the cases had a favorable outcome (95.1%). Pericardial tamponade was noted in 31/41 cases. Pericardiocentesis was performed in 37/41 cases., Conclusions: Hemopericardium from DOAC use has a favorable outcome but requires urgent pericardiocentesis. However, long term mortality, monitoring of DOAC activity, and drug-drug interactions have not been widely studied., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: Pericardial effusions are rare yet potentially fatal conditions in children. Azacitidine is a DNA-hypomethylating agent used in the treatment of myelodysplastic syndrome. Although seldomly described in adults, no cases of azacitidine-induced pericardial effusion have been reported in children., Case Report: A 7-year-old boy with myelodysplastic syndrome presented with a large pericardial effusion with risk for cardiac tamponade after his first azacitidine cycle., Management & Outcome: The patient was admitted to a pediatric ICU, antibiotic and steroid therapy were initiated. Pericardiocentesis was done due to hemodynamic instability. Serum and pericardial fluid complementary evaluation excluded infectious and malignant causes. The pericardial effusion did not reappear and additional pleural and ascitic slight effusions responded well to diuretics. Follow-up azacitidine cycles were administered by tapering daily dosages and using adjunctive steroid therapy, with no additional adverse events., Discussion: We report the first pediatric case of large pericardial effusion secondary to azacitidine therapy in a child with MDS. This adverse reaction has not been described in pediatric patients, in which this therapeutic option has been increasingly used. We seek to raise awareness on the potential life-threatening cardiotoxicity of azacitidine in pediatric patients.

Background: Immunotherapy has become a critical class of anticancer therapy in recent years, functioning by releasing brakes on the immune system that ultimately results in immune cell activation which eliminates cancer cells. Immune related adverse events (IRAEs) are a specific type of adverse event described in patients taking checkpoint inhibitor immunotherapy which results from unrestrained immune activation. Immune related pericardial effusion has been described however has not been comprehensively characterized. Here, we present the most extensive report to date detailing this adverse event., Methods: We queried our medical record system to retrospectively identify patients on checkpoint inhibitor therapy for lung cancer who subsequently developed pericardial effusion. We analyzed the clinical and radiographic characteristics, prior therapies, treatment for the effusion, and outcomes in patients with immune related pericardial effusion and compared them to similar patients with pericardial effusion not attributable to checkpoint inhibitor therapy., Results: Our data demonstrate that most of these pericardial effusions were small and not clinically significant. The majority were successfully treated with steroids or resolved spontaneously. Anti-PD-1 inhibitors were the most common checkpoint inhibitor preceding pericardial effusion, and a significant number of patients who went on to develop IRAE pericardial effusion previously had treatment with carboplatin for their cancer., Conclusions: These data suggest that IRAE pericardial effusion is not a clinically significant adverse event however it sometimes leads to permanent discontinuation of checkpoint inhibitor therapy which is not necessary., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Intrapericardial triamcinolone can be used to treat chronic pericardial effusion (PE) in adults; however, pediatric data are lacking. In this case series we aim to evaluate the efficacy, safety, and side effects of intrapericardial triamcinolone in children with PE. The incidence and treatment of post-surgical PE from 2009 to 2019 were determined using the institutional surgical database and electronic patient records. Furthermore, a retrospective analysis of efficacy, safety, and side effects of intrapericardial triamcinolone treatment for chronic post-surgical PE was performed. The incidence of postoperative PE requiring treatment was highest after atrial septal defect (ASD) closure when compared to other types of cardiac surgery (9.7% vs 4.3%). Intrapericardial treatment with triamcinolone resolved pericardial effusion in 3 out of 4 patients. All patients developed significant systemic side effects. Surgical ASD closure is associated with an increased risk of development of PE requiring treatment. Intrapericardial triamcinolone is an effective treatment for chronic postoperative PE in children, but is always associated with significant systemic side effects. Close monitoring and treatment of adrenal insufficiency are mandatory in these cases., (© 2021. The Author(s).)

Introduction: Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate which combine trastuzumab (T), a monoclonal antibody targeting the human epidermal growth factor receptor-2 (HER2), and a cytotoxic molecule derived from maytansine (DM1)., Case Report: We report the first case of T-DM1-associated pleural and pericardial effusions three weeks after the second course of T-DM1 in a patient with breast cancer. Drug-induced pleural and pericardial effusions was implicated in the absence of other etiologies. The Naranjo Scale indicated a probable drug-induced adverse reaction. Management & outcome: The patient fully recovered after thoracentesis and discontinuation of T-DM1. The patient has reported no side effect after the sixth course of trastuzumab., Discussion: To our knowledge, this is the first case in the literature of bilateral pleural and pericardial effusions in a patient treated with T-DM1. The successful initiation of treatment with trastuzumab following withdrawal of T-DM1 suggests that emtansine played a role in the development of bilateral pleural and pericardial effusions. We hypothesize that the patient's condition was a result of a local inflammatory reaction to emtansine by direct toxicity.

A 67-year-old man with primary lung adenocarcinoma was hospitalized due to massive bilateral pleural effusion and pericardial effusion after 94 cycles of nivolumab therapy. We were unable to identify the cause of these effusions using blood tests, cytology tests, or bacterial culture of pleural effusion and thoracoscopy. Finally, we administrated corticosteroids, which immediately improved the fluid accumulation. This case may support the introduction of corticosteroids for late-onset pleural and pericardial effusion during immune checkpoint inhibitor (ICI) treatment. However, the safety of rechallenge of ICIs after the improvement of fluid accumulation is controversial.

Background: Pericardial effusion and tamponade have been recognized as potentially serious complications in patients who have undergone renal transplantation. Our study aims to analyze the association between sirolimus and the development of pericardial effusion in renal transplant recipients., Methods: This is a single-center retrospective study of 585 consecutive patients who underwent renal transplantation between 2005 and 2016. The study included 82 patients (14%) who developed new pericardial effusion after transplantation. Baseline demographics, medical comorbidities, medication use, echocardiographic parameters, and time to occurrence of effusion were assessed. Patients were divided into 2 groups based on timing of effusion development: early onset, ≤4 years after transplantation (51%); and late onset, >4 years after transplantation (49%). We examined the likelihood of immunosuppressant use and timing of effusion development using univariate and multivariate logistic regression analysis., Results: The mean age of the cohort was 55.1 ± 11.5 years, 58.5% were men, 81.7% were white, and mean time from transplantation to the development of effusion was 4 ± 3.1 years. There were no significant differences between the early and late effusion groups in the demographic characteristics and medical comorbidities. However, sirolimus therapy was more common in the late effusion group. Furthermore, after adjusting for comorbidities, sirolimus use was associated with greater risk for developing late-onset effusion, adjusted odds ratio of 3.58 (95% confidence interval 1.25-10.20, P = .017)., Conclusion: Pericardial effusion is prevalent in renal transplant recipients. In our cohort, treatment with sirolimus was associated with late-onset pericardial effusion. Awareness of pericardial disease in this population is important, and further studies are needed to identify predisposing factors., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: Cardiovascular toxicity of immunotherapy represents an underreported but potentially fatal side effect. A relatively high incidence of pericardial disease has been noticed in patients with non-small cell lung cancer (NSCLC)., Methods: We retrospectively analyzed a population of patients with advanced NSCLC receiving immune checkpoint inhibitors (ICIs) looking for the presence of pericardial effusion at baseline or during treatment. The study population was compared with a control group treated with chemotherapy. All patients were checked for the presence of concomitant pleural effusion., Results: We identify 60 patients (36 male/24 female, median age 70 years [range 43-81]). Prevalent histology was adenocarcinoma (65%) followed by squamous cell carcinoma (28%) and large cell or not otherwise specified (NOS) carcinoma (7%). Treatment consisted of nivolumab 3 mg/kg every 14 days (52 cases; 45 as second-line and 7 as third-line treatment) or pembrolizumab 200 mg (8 cases; all first-line treatment) for a total of 302 cycles delivered. Four out of 60 patients (6.7%) developed pericardial effusion during treatment, in two cases (3.3%) without concomitant pleural effusion, compared to 2 out of 60 (3.3%) in the control group in one case without concomitant pleural effusion (1.6%). Median time of onset was 40 days. Myocarditis was not observed., Conclusion: Our findings confirm pericardial effusion as a relatively frequent side effect of immunotherapy in NSCLC. Clinicians should be aware of this specific toxicity in patients with metastatic NSCLC receiving immunotherapy and refer to a cardiologist for a multidisciplinary approach.

Introduction: Dasatinib is a potent tyrosine-kinase inhibitor which is used for chronic myeloid leukemia treatment. Pleural effusion is a frequent side effect in patients during dasatinib treatment. Pulmonary arterial hypertension is a rare and life-threatening adverse event of dasatinib. The relationship between dasatinib and autoimmune disorders is unclear, but there are reports of possible mechanisms that have triggered autoimmunity by dasatinib., Case Report: A 53-year-old male was diagnosed with chronic myeloid leukemia and initiated imatinib mesylate as a treatment. Imatinib was changed to dasatinib as the patient was unresponsive in the first year of treatment. In the fourth year of dasatinib when chronic myeloid leukemia was in both hematological and cytogenetical remission, the patient presented with bilateral massive exudative pleural effusion. Echocardiography was consistent with pericardial effusion with right ventricle enlargement and normal left-side cardiac function. Pulmonary arterial hypertension was diagnosed with high systolic pulmonary arterial pressure. When he had fever and arthralgia, further investigation showed positivity of anti-nuclear antibodies (1/160 titer) and anti-RNP/Sm, which have high specificity for the diagnosis of Systemic Lupus Erythematosus (SLE)., Management and Outcome: Dasatinib was discontinued and nilotinib was initiated. As the pleural effusion persisted despite diuretics and methylprednisolone, mycophenolate mofetil was initiated as a steroid-sparing immune-suppressive agent. The lupus-like symptoms disappeared, and antibodies became undetectable after dasatinib discontinuation. Pericardial effusion improved and pleural effusion did not relapse., Discussion: Screening for auto-antibodies may be recommended for patients with a history or symptoms of autoimmune disease before starting dasatinib. All patients who develop pleural effusion while on dasatinib treatment should be investigated for antibodies for lupus.

Introduction - Valproic acid is an effective antiepileptic and mood stabilizer used in the treatment of many neurological and psychiatric disorders. Although there are frequently seen side effects, effusions between layers of pleural and pericardial membranes are rare to be seen. Case - Pleuropericardial effusion was detected in a 23 years old woman who was under valproic acid treatment because of epileptic seizure. After 1 year of valproic acid treatment, patient complained of dyspnea. As all the researches intended on etiology were usual, valproic acid has been thought to be responsible for the matter. Control examination after 1.5 months regarding the end of treatment revealed complete recovery of pleuropericardial effusion. Discussion - Pleural and pericardial effusions are rarely seen complications related to the use of valproic acid. It must also be kept in mind that valproic acid causes a potential for such side effects which can be blamed etiologically when the other possibilities for patients are excluded.

Immunotherapy drugs are associated with a multitude of immune-related adverse events. We describe a case of cardiac tamponade in a patient with stage IV lung adenocarcinoma, with almost 100% expression of PDL-1, treated with pembrolizumab. The patient is a 62-year-old male who developed worsening shortness of breath after five cycles of pembrolizumab. He was diagnosed with large pericardial effusion on computed tomography chest. Echocardiogram confirmed tamponade physiology. He was treated with discontinuation of pembrolizumab and urgent pericardial window followed by high dose prednisone with tapering. The patient responded very well to the treatment. We have comprehensively reviewed cases of pericardial effusion secondary to either immune mediated mechanisms or pseudoprogression.

Background: Nivolumab, a programmed death-1 (PD-1) inhibitor, is an immune checkpoint inhibitor particularly used in the treatment of malignant melanoma, non-small cell lung cancer and renal cell carcinoma. Immune-related adverse events are frequent under immunotherapies. Cardiotoxic side effects, initially thought to be rare, are more often encountered paralleling the expanding use of immune checkpoint blockade. Among them, pericardial effusion and tamponade deserve attention as they may present with unusual symptomatology., Case Presentation: We report three cases of pericardial effusion under nivolumab for lung adenocarcinoma. Two cases of early and late-onset pericardial effusion were symptomatic with tamponade and one case occurred without any symptoms. Pericardiocentesis with pericardial biopsy was performed in symptomatic pericardial effusion followed by the administration of a corticotherapy. Pericardial biopsies showed infiltration of T-lymphocytes, mostly CD4 + . Nivolumab was stopped in two cases and resumed for one patient. Pericardial effusion evolved positively in all cases with or without treatment., Conclusions: We review the literature on pericardial effusion under nivolumab to further discuss the hallmarks of pericardial effusion under nivolumab and the management of nivolumab therapy in this situation. In conclusion, pericardial effusion as an immune-related adverse event under nivolumab appears less rare than initially thought and may require particular attention.

The advent of immune checkpoint inhibitors has revolutionized cancer treatment. These novel agents have provided promising treatment options in patients with different types of cancers. One of these agents is pembrolizumab, which works by blocking the binding of T-lymphocytes to programmed cell death ligand 1 receptors on tumor cells, thus enabling immune activation of T-lymphocytes against tumor cells. Pembrolizumab is commonly used in metastatic nonsmall cell lung cancer and melanoma. However, despite the remarkable efficacy this agent has achieved, multiple immune-related adverse events have been reported including hepatitis, colitis, thyroid dysfunction, and pneumonitis. Only 2 other cases of pericardial effusion as a side effect of pembrolizumab have been cited in the literature; however, its incidence may be on the rise. Despite the rarity of this side effect, its complications are potentially life threatening and no clear platform currently exists to help guide healthcare professionals in the management of these adverse events. Herein we present the case of a 66-year-old female who developed pericardial effusion as a side effect of pembrolizumab and review the data currently available to assist in the management of this life-threatening condition., (Copyright © 2019 Elsevier Inc. All rights reserved.)

A 12-year-old boy presented with central chest pain, shortness of breath and type 1 respiratory failure. He had a background of graft versus host disease (GvHD), which was currently managed with imatinib therapy. A focused bedside ultrasound scan was performed revealing a large pericardial effusion. The child was referred to a tertiary paediatric cardiology centre where he underwent emergency pericardiocentesis, draining a total of 800 mL of pericardial fluid. Fluid analysis excluded infection, and with no other concerns for a GvHD flare the diagnosis of an imatinib-induced pericardial effusion was made. On terminating the therapy, the pericardial collection did not reaccumulate. Tyrosine kinase inhibitor-induced pericardial and/or pleural effusion should be considered as a differential diagnosis in paediatric patients on this therapy presenting in a similar manner., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

An 82-year-old female was admitted with chest pain and non-specific T wave changes on her ECG. After 72 hours of conservative management she deteriorated with non-specific symptoms including nausea and a single episode of vomiting. Abdominal and Chest X-rays were unremarkable, blood tests showed worsening Acute Kidney Injury (AKI) on Chronic Kidney Disease (CKD); and raised C-Reactive Protein (CRP) with no obvious symptoms or focus of infection. She rapidly deteriorated going into asystole cardiac arrest and attempts at resuscitation failed. Post-mortem examination suggested the most likely cause of death was acute spontaneous Haemopericardium due to Rivaroxaban therapy which she was on for non-valvular Atrial Fibrillation (AF). We believe that this might be the first reported mortality with Rivaroxaban-associated spontaneous haemopericardium in the UK., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

A 72-year-old female with left renal cell carcinoma and lymphadenopathy had undergone hand-assisted laparoscopic left nephrectomy and dissection of the lymph node (papillary renal cell carcinoma, type 2, pT3a pN2 M1). She had been treated with adjuvant chemotherapy with sunitinib, temsirolimus and pazopanib. However, the patient was started on nivolumab due to disease progression. After receiving 5 cycles of nivolumab, she was admitted to our emergency room for chest discomfort and appetite loss. Since computed tomographic (CT) scan showed pericardial effusion, we performed pericardiocentesis. Cytological examination of the pericardial effusion demonstrated leukocytes and no malignant cells. CT scan two weeks after cardiocentesis showed no recurrent pericardial effusion. She became stable with nivolumab, but the administration of nivolumab was discontinued and she started receiving axitinib.

Sirolimus is an important immunosuppressive drug in renal transplantation but contains numerous side effects. In this study, we describe a case of renal transplant recipient treated with sirolimus who developed pericardial effusion associated with interstitial pneumonia. An extensive search for alternative causes were all negative, and all symptoms disappeared after sirolimus interruption. Therefore, this case demonstrates that sirolimus can cause pericardial effusion possibly through a proinflammatory mechanism., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Azacitidine, a deoxyribonucleic acid hypomethylating agent, is used in the treatment of myelodysplastic syndrome. Common adverse effects of azacitidine include bone marrow suppression, injection site reactions, nausea, vomiting, diarrhea, and fatigue. This report focuses on pleuropericardial effusions, an infrequently reported and potentially reversible adverse effect of azacitidine. In this case report, pleuropericardial effusion manifested as the sole radiographic finding in the evaluation of cough occurring during the eighth cycle of treatment with azacitidine. Symptoms and radiographic abnormalities resolved with corticosteroids and diuretics, and the patient could continue with therapy.

Pericardial effusion and cardiac tamponade following renal transplantation have been recognized as a potentially serious complications associated with the use of sirolimus for immunosuppression. Our study aims to analyze the development of sirolimus-associated pericardial effusion. Patients who underwent renal transplantation at our institution between 2001 and 2014 were reviewed and the correlation between sirolimus exposure and pericardial effusion was determined. Nineteen out of 792 patients who received a renal transplant over this 14-year period (incidence 2.4%) developed symptomatic pericardial effusion (determined by the need for pericardiocentesis or a pericardial window). All patients had a pre-transplantation cardiac workup, including echocardiogram, which did not reveal the presence of pericardial effusion. Our cohort of patients is mostly male (57.9%) and Caucasian (73.7%), which is consistent with the makeup of transplant recipients at our center. The mean age was 52.42 years at the time of transplantation. The development of symptomatic pericardial effusions occurred at a mean of 5.06 (.5-9.8) years after renal transplant while on sirolimus therapy. Sirolimus levels at diagnosis were 5.19-7.47 ng/mL. No significant pericardial effusion (resulting in tamponade physiology) recurred after therapeutic intervention, including cessation of sirolimus with or without pericardial drainage. This study is the largest single-center report of the possible association between pericardial effusion in renal transplant recipients who received sirolimus. Due to the widespread use of sirolimus in organ transplantation, clinicians must remain vigilant for this potential cardiac complication., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The aim of this paper was to report an outbreak of avocado poisoning in rabbits in Salta, Argentina. Fourteen rabbits died of congestive heart failure within 30 h of ingesting fresh avocado leaves from pruned trees. They showed clinical signs of respiratory and cardiac distress. Full necropsies of four rabbits were performed and samples were collected for histopathology. The gross pathological observation included pleural and pericardial effusion, pulmonary oedema, slight ascites; the hearts appeared flabby and markedly pale. In addition, the stomach content consisted mostly of green feed with large amounts of avocado leaves. Epidermal fragments of Persea americana were identified by microhistological analysis of gastric content to get most efficiently to a correct diagnosis. Histopathological examination revealed degeneration and necrosis of myocytes and a mononuclear cellular infiltration mainly involving the myocardium and, to a lesser extent, the liver, lung and kidneys. Our observations indicate that avocado leaves should be avoided in the green diet of rabbits., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Aim To report the first case of cardiac tamponade related to Infliximab induction therapy in an Ulcerative Colitis patient. Methods Review of published case reports. Results This complication was likely due to a type 3 hypersensitivity immune-complex reaction resulting in a reactive pericardial effusion Discussion Though rare, this case demonstrates how autoimmune reaction to anti-TNF𝛼 therapy can initially mimic infection, as our patient presented with tachycardia, hypotension, raised inflammatory and infective markers and fever., Competing Interests: The authors have no conflicts to declare.

Four novel oral anticoagulant agents are currently available for the prevention and treatment of thromboembolic events in patients with nonvalvular atrial fibrillation. We present an unusual case of spontaneous hemopericardium and tamponade in an 87-year-old man with atrial fibrillation who was taking one such agent, dabigatran, as thromboprophylaxis. Our case highlights both a rare bleeding complication of dabigatran use and the effectiveness of idarucizumab, its newly approved reversal agent. Especially in elderly patients, we recommend that clinicians evaluate risk factors, closely monitor patient status, and consider alternatives to the newer anticoagulants when the risk of bleeding is high.