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The systemic inflammatory response after cardiopulmonary bypass has been widely studied. However, there is a paucity of studies that focus on the local inflammatory changes that occur in the pericardial cavity. The purpose of this study is to assess the inflammatory mediators in the pericardial fluid of patients undergoing cardiac surgery. We conducted a prospective cohort study on patients undergoing aortic valve replacement. Pericardial fluid and peripheral venous blood samples were collected after the opening of the pericardium. Additional samples were obtained from peripheral blood and the pericardial fluid shed through mediastinal drains 24 and 48 h after surgery. Levels of interleukin 1α (IL-1α), interleukin 1β (IL-1β), interleukin 2 (IL-2), interleukin 4 (IL-4), interleukin 6 (IL-6), interleukin 8 (IL-8), interleukin 10 (IL-10), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), vascular endothelial growth factor (VEGF), monocyte chemotactic protein-1 (MCP-1), epidermal growth factor (EGF), soluble E-selectin, L-selectin, P-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) were determined in all pericardial fluid and serum samples. A total of 45 patients with a mean age of 74 years were included, of which 66% were males. Serum levels of IL-6, IL-8, and MCP-1 were significantly increased at 24 and 48 h after surgery. No significant changes were observed in the serum levels of the remaining mediators. A significant increase of postoperative pericardial fluid levels of IL-1α, IL-1β, IL-6, IL-8, IL-10, IFN-γ, VEGF, MCP-1, VCAM-1, and P-selectin was observed at 24 and 48 h after surgery. There is a robust systemic and pericardial inflammatory response after cardiac surgery on cardiopulmonary bypass. However, postoperative pericardial inflammatory activity shows a distinct pattern and is more marked than at the systemic level. These findings suggest that there is a compartmentalization of the inflammatory response within the pericardial cavity after cardiac surgery. [ABSTRACT FROM AUTHOR]

Pericardial fluid (PF) has been suggested as a reservoir of molecular targets that can be modulated for efficient repair after myocardial infarction (MI). Here, we set out to address the content of this biofluid after MI, namely in terms of microRNAs (miRs) that are important modulators of the cardiac pathological response. PF was collected during coronary artery bypass grafting (CABG) from two MI cohorts, patients with non-ST-segment elevation MI (NSTEMI) and patients with ST-segment elevation MI (STEMI), and a control group composed of patients with stable angina and without previous history of MI. The PF miR content was analyzed by small RNA sequencing, and its biological effect was assessed on human cardiac fibroblasts. PF accumulates fibrotic and inflammatory molecules in STEMI patients, namely causing the soluble suppression of tumorigenicity 2 (ST-2), which inversely correlates with the left ventricle ejection fraction. Although the PF of the three patient groups induce similar levels of fibroblast-to-myofibroblast activation in vitro, RNA sequencing revealed that PF from STEMI patients is particularly enriched not only in pro-fibrotic miRs but also anti-fibrotic miRs. Among those, miR-22-3p was herein found to inhibit TGF-β-induced human cardiac fibroblast activation in vitro. PF constitutes an attractive source for screening diagnostic/prognostic miRs and for unveiling novel therapeutic targets in cardiac fibrosis. [ABSTRACT FROM AUTHOR]

Soluble growth stimulation expressed gene 2 protein (sST2) is a myocardial protein induced by biomechanical stress. sST2 is widely present in the serum of patients with heart failure and is recommended as an important indicator to predict adverse outcomes in these patients. However, no postmortem biochemical analysis of sST2 in forensic practice has been reported. The present pilot study aimed to investigate the expression of sST2 in the pericardial fluid of patients with sudden cardiac death (SCD) caused by ischemic heart disease (IHD). In addition, to explore the relationship of sST2 with CK-MB, cTnT, and NT-proBNP, which have been proven to be auxiliary biomarkers for the diagnosis of SCD, we analyzed CK-MB, cTnT, NT-proBNP, and sST2 levels in twenty-one pericardial fluid samples from the Center of Forensic Investigation, China Medical University, with a Roche cobas e 411 electrochemiluminescence automatic immunoassay system and ST2/IL-33R Valukine™ enzyme-linked immunosorbent assay kit. The levels of sST2 in the pericardial fluid of patients with SCD caused by IHD were significantly increased (P < 0.01) and positively correlated with CK-MB and NT-proBNP (P < 0.0001). Receiver operating characteristic curve analysis indicated that the combined measurement of sST2 and NT-proBNP has a higher diagnostic value for SCD caused by IHD than the measurement of either indicator alone. This study preliminarily demonstrated that sST2 in the pericardial fluid was significantly increased in patients with SCD caused by IHD and might be used as a novel auxiliary biomarker for postmortem diagnosis of SCD in forensic practice. [ABSTRACT FROM AUTHOR]

Bisphenols may negatively impact human health. In this study, we propose the use of HPLC–FLD for the simultaneous determination of bisphenols in pericardial fluid samples collected from patients with coronary artery disease undergoing coronary artery bypass surgery. For sample preparation, a fast, simple, and ”green” DLLME method was used, achieving mean recovery values in the range of 62%–98% with relative standard deviations between 2% and 6% for all analytes. Quantitative analysis of bisphenols in the samples was then performed by LC–MS/MS on a triple quadrupole (QqQ) mass spectrometer and electrospray ionization (ESI-/ESI+) was applied in the negative and positive ion modes, respectively. The LODs and LOQs ranged from 0.04 ng/mL to 0.37 ng/mL and 0.12 ng/mL to 1.11 ng/mL, respectively. Pericardial fluid was collected from patients with coronary artery disease during coronary artery bypass surgery. Bisphenol residues were identified and quantified in samples from 19 patients. The procedure was successfully applied to the biomonitoring of free forms of 14 bisphenols in pericardial fluid. After statistical examination of the relationships between the selected variables, a strongly positive correlation was found between creatinine kinase and troponin I, as well as the number of venous anastomoses, circulation time, and clamp cap time.

Background: The cytological analysis of body fluids is the preliminary investigation performed for the diagnostic evaluation of body fluids, helping the physician make the diagnosis and plan proper treatment. The International System for Reporting Serous Fluid Cytology (ISFRSFC) was created using best international practises, current literature and expert consensus to make a uniform reporting system for serous fluids. Aims: The present study was conducted with the aim of recategorising the effusion fluids as per the guidelines prescribed by ISRFRC, knowing the distribution of cases into various categories and assessing their feasibility in day-to-day reporting. Patients and Methods: This study was performed on serous fluids (ascitic, pleural, peritoneal and pericardial) received over a period of 5 years, from January 2017 to April 2022, in the cytology unit of the Department of Pathology, ABVIMS, Dr. Ram Manohar Lohia Hospital, New Delhi. Wherever possible, clinicoradiological and histopathological data were obtained and correlated with cytological findings. Serous fluids were categorised into reporting formats as prescribed by ISRFRC and its feasibility was assessed in day-to-day reporting. Results: A total of 1115 cases of serous effusion fluid were examined. The male-to-female ratio was 1:1.12. Pleural fluid constituted the majority of the sample (436, 39.10%). Overall, 56 (5.02%) cases were non-diagnostic (ND), 1013 (90.85%) cases were negative for malignancy, 8 (0.72%) were atypia of undetermined significance, 11 (0.99%) were suspicious of malignancy and 27 (2.42%) were malignant (MAL). Conclusion: The current study emphasises the significance of cytological analysis of serous fluid as a comprehensive diagnostic investigation that also aids in determining the cause and monitoring the disease process. With the introduction of ISFRSFC, serous fluid reporting is now uniform and more comprehensive, both for cytopathologists and clinicians.

There is paucity of studies that focus on the composition of pericardial fluid under resting conditions. The purpose of this study is to determine the levels of inflammatory mediators in pericardial fluid and their correlation with plasma levels in patients undergoing elective cardiac surgery. We conducted a prospective cohort study on candidates for elective aortic valve replacement surgery. Pericardial fluid and peripheral venous blood samples were collected after opening the pericardium. Levels of interleukin 1α (IL-1α); interleukin 1β (IL-1β); interleukin 2 (IL-2) interleukin 4 (IL-4); interleukin 6 (IL-6); interleukin 8 (IL8); interleukin 10 (IL10); tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), vascular endothelial growth factor (VEGF), monocyte chemotactic protein-1 (MCP-1) epidermal growth factor (EGF), soluble E-selectin, L-selectin, P-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) were determined in both pericardial fluid and serum samples. A total of 45 patients with a mean age of 74 years were included of which 66% were males. Serum levels of all study mediators were within normal limits. Serum and pericardial levels of IL-1 α, IL-1 β, IL-2, IL-4, and IL-10 were similar. Levels of VEGF, EGF, VCAM-2, ICAM 1, E-selectin, P-selectin, and L-selectin were significantly lower in pericardial fluid than in serum. However, levels of IL-6, IL-8, TNF-α, IFN-γ, MCP-1, and MCP-1 were significantly higher in the pericardial fluid than in serum. Under normal conditions, the pattern of distribution of different inflammatory mediators in the pericardial fluid does not reflect serum levels. This may either reflect the condition of the underlying myocardium and epicardial fat or the activity of the mesothelial and mononuclear cells present in pericardial fluid. [ABSTRACT FROM AUTHOR]

Background: The cytological analysis of body fluids is the preliminary investigation performed for the diagnostic evaluation of body fluids, helping the physician make the diagnosis and plan proper treatment. The International System for Reporting Serous Fluid Cytology (ISFRSFC) was created using best international practises, current literature and expert consensus to make a uniform reporting system for serous fluids. Aims: The present study was conducted with the aim of recategorising the effusion fluids as per the guidelines prescribed by ISRFRC, knowing the distribution of cases into various categories and assessing their feasibility in day-to-day reporting. Patients and Methods: This study was performed on serous fluids (ascitic, pleural, peritoneal and pericardial) received over a period of 5 years, from January 2017 to April 2022, in the cytology unit of the Department of Pathology, ABVIMS, Dr. Ram Manohar Lohia Hospital, New Delhi. Wherever possible, clinicoradiological and histopathological data were obtained and correlated with cytological findings. Serous fluids were categorised into reporting formats as prescribed by ISRFRC and its feasibility was assessed in day-to-day reporting. Results: A total of 1115 cases of serous effusion fluid were examined. The male‑to‑female ratio was 1:1.12. Pleural fluid constituted the majority of the sample (436, 39.10%). Overall, 56 (5.02%) cases were non‑diagnostic (ND), 1013 (90.85%) cases were negative for malignancy, 8 (0.72%) were atypia of undetermined significance, 11 (0.99%) were suspicious of malignancy and 27 (2.42%) were malignant (MAL). Conclusion: The current study emphasises the significance of cytological analysis of serous fluid as a comprehensive diagnostic investigation that also aids in determining the cause and monitoring the disease process. With the introduction of ISFRSFC, serous fluid reporting is now uniform and more comprehensive, both for cytopathologists and clinicians. [ABSTRACT FROM AUTHOR]

Introduction: Epicardial ablation is an important approach in the management of patients with complex ventricular arrhythmias. Irrigated ablation catheters present a challenge in this potential space due to fluid accumulation that can cause hemodynamic compromise, requiring frequent manual fluid aspiration. In this series, we report our initial experience with the use of a dry suction water seal system for pericardial fluid management during epicardial ablation. Methods: Consecutive patients undergoing epicardial ventricular tachycardia (VT) ablation at a single center were included. All patients underwent epicardial access via a subxiphoid approach with a single operator. A deflectable sheath was advanced into the pericardial space, and the side port was attached to a dry suction water seal system attached to wall suction at −20 mmHg. Procedural information including patient characteristics, outcomes, and adverse events. After a period of initial experience, pericardial fluid infusion and aspiration volumes were recorded. Results: Eleven patients were included in this series. All patients underwent epicardial ablation with complete success achieved in 8 of the 11 patients and partial success in the remaining patients. Pericardial fluid intake ranging from 485 to 3050 mL with aspiration of 350–3050 mL using the dry suction water seal system. No adverse events occurred. Conclusion: Dry suction water seal drainage systems can provide a safe strategy for efficient pericardial fluid management during epicardial VT ablation, potentially shortening procedure duration. [ABSTRACT FROM AUTHOR]

Medical considerations for early diagnosis of tuberculous pericarditis (TBP) include Xpert MTB/RIF Ultra and TB lipoarabinomannan (LAM) antigen (Ag) tests, with immunological status influencing the performance of the latter. An evaluation of the efficiency of Xpert MTB/RIF Ultra and TB LAM Ag in detecting TBP was conducted using pericardial fluid samples from 46 patients with suspected TBP. Fifteen patients (34.1%) were diagnosed with TBP according to culture results. TB LAM Ag's sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR), and negative likelihood ratio (NLR) were 33.3%, 100%, 100%, 74.4%, 0, and 0.67, respectively. The sensitivity, specificity, PLR, NLR, PPV, and NPV of Xpert MTB/RIF Ultra were 80%, 93.1%, 11.6, 0.21, 85.7%, and 90%, respectively. There was an association observed between a positive TB LAM Ag test and HIV status. When compared to the Xpert MTB/RIF Ultra test, TB LAM Ag has lower accuracy for the detection of microbiologically proven tuberculous pericarditis, yet its usage in HIV-positive populations may be worth exploring. The TB LAM Ag assay is not the best first-line test for the diagnosis of tuberculous pericarditis, and it should be used in conjunction with other diagnostic tests. [ABSTRACT FROM AUTHOR]

Extramedullary hematopoiesis (EMH) is a rare complication of solid tumor malignancies. We describe the first case of a patient who developed EMH in the pericardium secondary to metastatic gastrointestinal or pancreaticobiliary cancer. A 58-year-old man presented with recurrent episodes of fatigue and shortness of breath and was treated with thoracocentesis and pericardiocentesis for pleural and pericardial effusions, respectively. Owing to a markedly elevated alkaline phosphatase, a bone scan was performed and demonstrated diffuse sclerotic lesions. Evaluation of pleural effusion diagnosed metastatic adenocarcinoma, and cytospin morphology of the pericardial fluid demonstrated EMH. While EMH secondary to solid tumors is commonly suggested to be due to cytokine signaling, we propose the mechanism of EMH in this patient was due to extensive disruption of bone marrow hematopoiesis, similar to what is seen in myeloproliferative neoplasms.

Background: This study investigates the utility of the International System for Reporting Serous Fluid Cytopathology (ISRSFC) in the categorization of pericardial fluid and assesses the diagnostic performance and risk of malignancy (ROM) for each of the diagnostic categories. Methods: All pericardial fluid cases at the Yale School of Medicine between January 1, 2017, and December 31, 2020, were reviewed. The diagnoses were reclassified into five categories according to the ISRSFC: nondiagnostic (ND), negative for malignancy (NFM), atypia of uncertain significance (AUS), suspicious for malignancy (SFM), and malignant (MAL). ROM and performance parameters of each category were calculated. Results: After reclassification, the distribution of 465 pericardial fluid cases in each category was as follows: ND, 19 (4.1%); NFM, 332 (71.4%); AUS, 21 (4.5%); SFM, 11 (2.4%); and MAL, 82 (17.6%). Confirmatory follow‐ups were available for 16 ND (66.7%), 299 NFM (90%), 15 AUS (71%), 5 SFM (45.5%), and 30 MAL cases (36.6%). The ROM was 0% for ND, 1.3% for NFM (4 of 332), 20% for AUS (3 of 15), and 100% for both SFM (5 of 5) and MAL (27 of 27). The diagnostic performance was as follows: sensitivity, 87% (27 of 31); specificity, 100% (292 of 292); positive predictive value (PPV), 100% (27 of 27); negative predictive value (NPV), 98.6% (292 of 296); and diagnostic accuracy, 98.8% (319 of 323). Conclusions: The ISRSFC is a highly useful system for the reporting of pericardial fluid and risk assessment, given that it offers high sensitivity, specificity, PPV, NPV, and diagnostic accuracy. The application of this system may help to better categorize pericardial fluid and facilitate the standardization of cytopathology reporting. This study investigates the utility of the International System for Reporting Serous Fluid Cytopathology (ISRSFC) in the categorization of pericardial fluid and assesses the diagnostic performance and risk of malignancy for each diagnostic category. The ISRSFC is a highly useful system for the reporting of pericardial fluid and risk assessment, given that it offers high sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy. The application of this system may help to better categorize pericardial fluid and facilitate the standardization of cytopathology reporting. [ABSTRACT FROM AUTHOR]

• Cardiac fibrosis continues to affect a growing number of patients globally. • Micro-RNAs and exosomes have been the centre of much attention over the past 2 decades for their functional properties. • Recent work has shown that miRNAs and exosomes can have pro- and antifibrotic properties. • There is now an increased appreciation for the potential role local miRNAs and exosomes may have in driving or blunting cardiac fibrosis. The potential of the pericardial space as a therapeutic delivery tool for cardiac fibrosis and heart failure (HF) treatment has yet to be elucidated. Recently, miRNAs and exosomes have been discovered to be present in human pericardial fluid (PF). Novel studies have shown characteristic human PF miRNA compositions associated with cardiac diseases and higher miRNA expressions in PF compared to peripheral blood. Five key studies found differentially expressed miRNAs in HF, angina pectoris, aortic stenosis, ventricular tachycardia, and congenital heart diseases with either atrial fibrillation or sinus rhythm. As miRNA-based therapeutics for cardiac fibrosis and HF showed promising results in several in vivo studies for multiple miRNAs, we hypothesize a potential role of miRNA-based therapeutics delivered through the pericardial cavity. This is underlined by the favorable results of the first phase 1b clinical trial in this emerging field. Presenting the first human miRNA antisense drug trial, inhibition of miR-132 by intravenous administration of a novel antisense oligonucleotide, CDR132L, established efficacy in reducing miR-132 in plasma samples in a dose-dependent manner. We screened the literature, provided an overview of the miRNAs and exosomes present in PF, and drew a connection to those miRNAs previously elucidated in cardiac fibrosis and HF. Further, we speculate about clinical implications and potential delivery methods. [ABSTRACT FROM AUTHOR]

Extramedullary hematopoiesis (EMH) is a rare complication of solid tumor malignancies. We describe the first case of a patient who developed EMH in the pericardium secondary to metastatic gastrointestinal or pancreaticobiliary cancer. A 58-year-old man presented with recurrent episodes of fatigue and shortness of breath and was treated with thoracocentesis and pericardiocentesis for pleural and pericardial effusions, respectively. Owing to a markedly elevated alkaline phosphatase, a bone scan was performed and demonstrated diffuse sclerotic lesions. Evaluation of pleural effusion diagnosed metastatic adenocarcinoma, and cytospin morphology of the pericardial fluid demonstrated EMH. While EMH secondary to solid tumors is commonly suggested to be due to cytokine signaling, we propose the mechanism of EMH in this patient was due to extensive disruption of bone marrow hematopoiesis, similar to what is seen in myeloproliferative neoplasms. [ABSTRACT FROM AUTHOR]

Introduction: Cardiac tamponade (CT) is one of the most common and dangerous complications of transvenous lead extraction (TLE). So far, however, there has been little discussion about the problem. Methods: We analyzed the occurrence of CT in a group of 1226 patients undergoing TLE at a single reference center between June, 2015 and February, 2021. Using standard mechanical devices as first‐line tools, a total of 2092 leads had been extracted. Results: CT occurred in 18 patients (1.47%): due to injury to the wall of the right atrium in 14 patients (1.14%) and other cardiac walls in four patients (0.33%). Younger patient age at first implantation, female gender, high left ventricular ejection fraction (LVEF), lower New York Heart Association class, low Charlson comorbidity index, longer implant duration, and the number of previous procedures related to cardiac implantable electronic devices (CIED) are important patient‐related risk factors for CT. Significant procedure‐related risk factors include the number of extracted leads, extraction of atrial leads and longer dwell time of extracted leads. Intraoperative transoesophageal echocardiography (TEE) provides a lot of information about pulling on various cardiac structures and is able to detect a very early phase of bleeding to the pericardial sac. As a result of implementing best practices guidance in performing extraction procedures and close collaboration with cardiac surgeons that allowed immediate rescue intervention in our series of 18 CT cases, there were no procedure‐related deaths (mortality 0%). Conclusions: The need for rescue surgery due to CT has no influence on clinical and procedural success. Early diagnosed (TEE monitoring) and properly managed CT does not generate any additional risk in short‐ and long‐term follow‐up after TLE. [ABSTRACT FROM AUTHOR]

Studies of the immune response at the site of disease in extra-pulmonary tuberculosis (EPTB) disease are scarce. In this study, we compared the cellular profile of Mycobacterium tuberculosis (Mtb)-specific T cells in pericardial fluid and peripheral blood in patients with pericardial TB (PCTB). Whole blood and pericardial fluid (PCF) samples were collected at the time of diagnostic sampling, with repeat blood sampling after completion of anti-tubercular treatment (ATT) in 16 PCTB patients, most of them being HIV-1 infected (n=14). These samples were stimulated ex vivo and the phenotypic and functional cellular profile of PCF and blood was assessed by flow cytometry. We found that lymphocytes were the predominant cell type in PCF in PCTB, with a preferential influx of CD4 T cells. The frequencies of TNF-a producing Mtb-specific granulocytes and Mtb-specific CD4 T cells were significantly higher in PCF compared to blood. Mtb-specific CD4 T cells in PCF exhibited a distinct phenotype compared to those in blood, with greater GrB expression and lower CD27 and KLRG1 expression. We observed no difference in the production IFNg, TNF or IL-2 by Mtb-specific CD4 T cells between the two compartments, but MIP-1b production was lower in the PCF T cells. Bacterial loads were not associated with alterations in the phenotype or function of Mtbspecific CD4 T cells. Upon ATT completion, HLA-DR, Ki-67 and GrB expression was significantly decreased, and relative IL-2 production was increased in peripheral Mtb-specific CD4 T cells. Overall, using an ex vivo assay to compare the immune response towards Mtb in PCF and in blood, we identified significant difference in the phenotypic profile of Mtb-specific CD4 T response between these two compartments. Moreover, we show that the activation profile of peripheral Mtb-specific CD4 T cells could be used to monitor treatment response in PCTB. [ABSTRACT FROM AUTHOR]

Extracellular vehicles such as exosomes which lie in the size range of 30-150 nm have gained significant attention due to their ability to contain molecular cargoes. These vesicles are released by various cells and are found to stably carry their molecular cargoes to recipient cells via different biological fluids. Therefore, exosomes isolated from various fluids such as plasma, urine, and pericardial fluid have been extensively studied in recent years. However, due to the miniscule nature of exosomes, isolation of exosomes from biological fluids has been a challenge, mainly due to low yields, contamination from large vesicles and proteins, and variable starting sample volumes. The following protocol describes the isolation of exosomes from human pericardial fluid samples collected from patients undergoing coronary artery bypass graft surgery. The exosomes isolated from these samples have been previously shown to have increased expression of cardiovascular molecular markers. Due to the precious nature of the patient samples, the exosomes isolated from this protocol have been validated to confirm their purity and viability for downstream applications., (© 2025. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Malignant pericardial effusions are associated with a poor prognosis. Pericardial fluid cytology and pericardial biopsy are the primary methods for diagnosis. This study aimed to conduct a multi-institutional analysis to compare the diagnostic sensitivity of cytology and biopsy, and to investigate potential explanations for false-negative results in cytology., Methods: A retrospective review of pericardial fluid cytology cases with concurrent biopsy was conducted across four different institutions. Results were compared using standard statistical methods with attention to sensitivity and histologic distribution. False-negative cytology cases were investigated for further exploration., Results: A total of 309 cases were collected, of which 99 (32.0%) were confirmed malignant through repeat sampling or clinical history. Pericardial fluid cytology and biopsy identified 84 and 64 malignant cases, respectively. Our findings confirmed significantly higher sensitivity of cytology compared to biopsy (84.8% vs 65.7%). The most common sites of origin were lung, breast, and gastrointestinal, with adenocarcinoma being the most prevalent histologic subtype. Histologic review of 12 false-negative cytology cases revealed three key explanations; lymphoma was the most common missed diagnosis (33.3%); fibrinous pericarditis obscures neoplastic cells on the pericardial surface; and pericardial involvement can be seen without extension into the pericardial space., Conclusion: This study demonstrated diagnostic superiority of pericardial fluid cytology over biopsy in the evaluation of malignant pericardial effusions. We identified several limitations in fluid cytology causing false negatives. In the context of an underlying malignancy with pericardial effusion, pathologists should consider immunohistochemistry studies to aid on the diagnosis., (© 2024 John Wiley & Sons Ltd.)

Background: Biochemical analyses of N-terminal pro-brain natriuretic peptide (NT-proBNP), cardiac troponin T (cTnT), and creatine kinase MB (CK-MB) have been reported to be valuable for the auxiliary diagnosis of sudden cardiac death (SCD) in previous forensic studies. Aims and Objectives: The present study aimed to evaluate the diagnostic efficiency of combined analyses of NT-proBNP, cTnT and CK-MB in the pericardial fluid for forensic diagnosis of SCD caused by ischemic heart disease. Materials and Methods: Levels of NT-proBNP, cTnT, and CK-MB in the pericardial fluid of 132 medicolegal autopsy cases were obtained through electrochemiluminescence method. Results: NT-proBNP, cTnT, and CK-MB levels were significantly elevated in SCD cases (P < 0.05). Receiver-operating characteristics (ROC) analysis showed that NT-proBNP, cTnT, and CK-MB have diagnostic value for the diagnosis of SCD: NT-proBNP, cutoff value of 2236 pg/ml; cTnT, cutoff value of 199.51 ng/ml; CK-MB: cutoff value of 2742.5 ng/ml, and the combined analyses of these three biomarkers have better diagnostic efficiency than each single biomarker alone. Moreover, the causes of SCD were sub-divided into acute ischemic heart disease, acute myocardial infarction (AMI), and recurrent myocardial infarction subgroups for further analysis, which revealed that the ratio of cTnT/CK-MB could be used to distinguish AMI with the cutoff value of 0.1085 estimated by ROC analysis. Conclusion: These observations suggested that the postmortem biochemical analyses of NT-proBNP, cTnT, and CK-MB in the pericardial fluid may assist to diagnose SCD in forensic practice, and the combined analyses of multiple biomarkers have better diagnostic efficiency than each single biomarker alone. On the basis of the postmortem biochemical analyses of NT-proBNP, cTnT and CK-MB, combining the ratio of cTnT/CK-MB could be used to distinguish AMI.

Studies of the immune response at the site of disease in extra-pulmonary tuberculosis (EPTB) disease are scarce. In this study, we compared the cellular profile of Mycobacterium tuberculosis (Mtb)-specific T cells in pericardial fluid and peripheral blood in patients with pericardial TB (PCTB). Whole blood and pericardial fluid (PCF) samples were collected at the time of diagnostic sampling, with repeat blood sampling after completion of anti-tubercular treatment (ATT) in 16 PCTB patients, most of them being HIV-1 infected (n=14). These samples were stimulated ex vivo and the phenotypic and functional cellular profile of PCF and blood was assessed by flow cytometry. We found that lymphocytes were the predominant cell type in PCF in PCTB, with a preferential influx of CD4 T cells. The frequencies of TNF-α producing Mtb-specific granulocytes and Mtb-specific CD4 T cells were significantly higher in PCF compared to blood. Mtb-specific CD4 T cells in PCF exhibited a distinct phenotype compared to those in blood, with greater GrB expression and lower CD27 and KLRG1 expression. We observed no difference in the production IFNγ, TNF or IL-2 by Mtb-specific CD4 T cells between the two compartments, but MIP-1β production was lower in the PCF T cells. Bacterial loads were not associated with alterations in the phenotype or function of Mtb-specific CD4 T cells. Upon ATT completion, HLA-DR, Ki-67 and GrB expression was significantly decreased, and relative IL-2 production was increased in peripheral Mtb-specific CD4 T cells. Overall, using an ex vivo assay to compare the immune response towards Mtb in PCF and in blood, we identified significant difference in the phenotypic profile of Mtb-specific CD4 T response between these two compartments. Moreover, we show that the activation profile of peripheral Mtb-specific CD4 T cells could be used to monitor treatment response in PCTB.

Medical considerations for early diagnosis of tuberculous pericarditis (TBP) include Xpert MTB/RIF Ultra and TB lipoarabinomannan (LAM) antigen (Ag) tests, with immunological status influencing the performance of the latter. An evaluation of the efficiency of Xpert MTB/RIF Ultra and TB LAM Ag in detecting TBP was conducted using pericardial fluid samples from 46 patients with suspected TBP. Fifteen patients (34.1%) were diagnosed with TBP according to culture results. TB LAM Ag’s sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR), and negative likelihood ratio (NLR) were 33.3%, 100%, 100%, 74.4%, 0, and 0.67, respectively. The sensitivity, specificity, PLR, NLR, PPV, and NPV of Xpert MTB/RIF Ultra were 80%, 93.1%, 11.6, 0.21, 85.7%, and 90%, respectively. There was an association observed between a positive TB LAM Ag test and HIV status. When compared to the Xpert MTB/RIF Ultra test, TB LAM Ag has lower accuracy for the detection of microbiologically proven tuberculous pericarditis, yet its usage in HIV-positive populations may be worth exploring. The TB LAM Ag assay is not the best first-line test for the diagnosis of tuberculous pericarditis, and it should be used in conjunction with other diagnostic tests.

Background: Osteoprotegerin (OPG) is a molecule which belongs to the tumor necrosis factor receptor superfamily. OPG concentration is elevated in patients with left ventricle hypertrophy, heart failure and acute myocardial infarction. OPG concentrations rise in chronic kidney disease (CKD). The aim of this study was to investigate the association between OPG concentrations and cardiovascular complications, such as left ventricle hypertrophy, systolic and diastolic dysfunction of left ventricle and dysfunction of right ventricle in chronic kidney disease patients not treated with dialysis. The relation between OPG and the amount of pericardial fluid was also examined. Methods: One hundred and one men with CKD stage 3–5 not treated with dialysis were included in the study. Overhydration, body fat mass and lean body mass were measured using bioimpedance spectroscopy (BIS). Echocardiography was performed to evaluate the amount of pericardial fluid and to measure the thickness of the interventricular septum (IVS), systolic and diastolic function of left ventricle, as well as systolic function of right ventricle. Results: We observed a significant positive association between OPG and the thickness of the interventricular septum, the size of the left atrium (LA) and the presence of pericardial fluid. A negative relationship was observed between OPG and ejection fraction (EF). Conclusions: Our results suggest that OPG can be an independent marker of left ventricular hypertrophy, systolic and diastolic dysfunction of left ventricle and the presence of pericardial fluid in chronic kidney disease patients. [ABSTRACT FROM AUTHOR]

Abstract Introduction: The growth Stimulation expressed gene 2 (ST2) (or interleukin 1 receptor-like 1, also known as IL1RL1) is considered a biomarker of poor prognosis in cardiovascular diseases. The aims of this study are to investigate ST2 in the pericardial fluid (PF) of coronary artery disease patients and to contribute to the understanding of the pathophysiology of coronary artery disease. Methods: 40 patients (blood plasma and PF) who underwent coronary artery bypass surgery and 40 controls (blood plasma only) were included in this study. Soluble ST2 (sST2) level was determined by enzyme-linked ımmunosorbent assay method in plasma and PF, and sST2 gene expression was determined by quantitative real-time polymerase chain reaction (QRT-PCR) method. Results: The sST2 level was found to be 44.89 ng/ml and 390.357 ng/ml in the control and patient groups’ plasma, and 223.992 ng/ml in the PF of the patient group. An increase in sST2 level was detected in the patient group compared to the control group (P

Background: Homocysteine (Hcy) is involved in various methylation processes, and its plasma level is increased in cardiac ischemia. Thus, we hypothesized that levels of homocysteine correlate with the morphological and functional remodeling of ischemic hearts. Thus, we aimed to measure the Hcy levels in the plasma and pericardial fluid (PF) and correlate them with morphological and functional changes in the ischemic hearts of humans. Methods: Concentration of total homocysteine (tHcy) and cardiac troponin-I (cTn-I) of plasma and PF were measured in patients undergoing coronary artery bypass graft (CABG) surgery (n = 14). Left-ventricular (LV) end-diastolic diameter (LVED), LV end-systolic diameter (LVES), right atrial, left atrial (LA) area, thickness of interventricular septum (IVS) and posterior wall, LV ejection fraction (LVEF), and right ventricular outflow tract end-diastolic area (RVOT EDA) of CABG and non-cardiac patients (NCP; n = 10) were determined by echocardiography, and LV mass was calculated (cLVM). Results: Positive correlations were found between Hcy levels of plasma and PF, tHcy levels and LVED, LVES and LA, and an inverse correlation was found between tHcy levels and LVEF. cLVM, IVS, and RVOT EDA were higher in CABG with elevated tHcy (>12 µM/L) compared to NCP. In addition, we found a higher cTn-I level in the PF compared to the plasma of CABG patients (0.08 ± 0.02 vs. 0.01 ± 0.003 ng/mL, p < 0.001), which was ~10 fold higher than the normal level. Conclusions: We propose that homocysteine is an important cardiac biomarker and may have an important role in the development of cardiac remodeling and dysfunction in chronic myocardial ischemia in humans.

Human pericardial fluid (PF) is a rich reservoir of biologically active markers. The acellular compartment of PF can drive cardiac fibroblast activity in vitro. This process is mediated through the transforming growth factor-β pathway. Of clinical importance, the PF of patients with coronary artery disease has an increased profibrotic capacity compared with the PF of patients without coronary artery disease., Competing Interests: Dr Fatehi Hassanabad was supported by a Canadian Institutes of Health Research–Vanier Canada Graduate Scholarship, a Killam Foundation Doctoral Award, an Alberta Innovates: Health Solutions Doctoral Scholarship, and a Kertland Family Doctoral Award. A Canadian Institutes of Health Research Grant supports Drs Dundas and Fedak. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

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

Introduction: The growth Stimulation expressed gene 2 (ST2) (or interleukin 1 receptor-like 1, also known as IL1RL1) is considered a biomarker of poor prognosis in cardiovascular diseases. The aims of this study are to investigate ST2 in the pericardial fluid (PF) of coronary artery disease patients and to contribute to the understanding of the pathophysiology of coronary artery disease. Methods: 40 patients (blood plasma and PF) who underwent coronary artery bypass surgery and 40 controls (blood plasma only) were included in this study. Soluble ST2 (sST2) level was determined by enzyme-linked ımmunosorbent assay method in plasma and PF, and sST2 gene expression was determined by quantitative real-time polymerase chain reaction (QRT-PCR) method. Results: The sST2 level was found to be 44.89 ng/ml and 390.357 ng/ml in the control and patient groups' plasma, and 223.992 ng/ml in the PF of the patient group. An increase in sST2 level was detected in the patient group compared to the control group (P<0.001). The sST2 expression in plasma was higher in the patient group than in the control group. Additionally, sST2 was more expressed in the plasma of the patient group than PF (P<0.001). Conclusion: The fact that sST2 was detected for the first time in a high level in PF showed that this biomarker was closely related with the heart and strengthened its potential to be used as a biomarker. Therefore, sST2 can contribute to the understanding of the pathophysiology of coronary artery disease. [ABSTRACT FROM AUTHOR]

• The pericardial space is a rich reservoir of biologically active factors. • Pericardial troponin levels increase after heart surgery, which is distinct from circulating troponin levels. • Further work is indicated to determine whether pericardial troponin levels can be used for diagnostic and/or prognostic purposes. Pericardial Fluid (PF) is a rich reservoir of biologically active factors. Due to its proximity to the heart, the biochemical structure of PF may reflect the pathological changes in the cardiac interstitial environment. This manuscript aimed to determine whether the PF level of cardiac troponins changes in patients undergoing cardiac surgery. This scoping review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Medline, EMBASE, Cochrane, ClinicalTrials.gov , and Google Scholar databases were electronically searched for primary studies using the keywords "pericardial fluid," "troponin," and "cardiac surgery." The primary outcome of interest was changes in troponin levels within the PF preoperatively and postoperatively. Secondary outcomes of interest included comparisons between troponin level changes in the PF compared to plasma. A total of 2901 manuscripts were screened through a title and abstract stage by two independent blinded reviewers. Of those, 2894 studies were excluded, and the remaining seven studies underwent a full-text review. Studies were excluded if they did not provide data or failed to meet inclusion criteria. Ultimately, six articles were included that discussed cardiac troponin levels within the PF in patients who had undergone cardiac surgery. Pericardial troponin concentration increased over time after surgery, and levels were significantly higher in PF compared to serum. All studies found that the type of operation did not affect these overall observations. Our review of the literature suggest that the PF level of cardiac troponins increases in patients undergoing cardiac surgery, irrespective of the procedure type. However, these changes' exact pattern and clinical significance remain undefined. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is associated with "flu-like" upper respiratory tract symptoms and pneumonia. Body cavity effusions develop in a subset of patients with advanced disease. Although SARS-CoV-2 is known to be present in certain body fluids (eg, blood) of COVID patients, it remains unclear if body cavity fluids are sites of infection. Our aim was to characterize the cytologic and clinical findings in COVID-19 patients with effusions. A record search for all cases of body cavity effusion cytology in SARS-CoV-2 positive patients from March 1, 2020, to September 1, 2020, was performed. Clinical history, fluid chemical analysis, cytologic findings, and patient outcomes were recorded. All cytology slides were reviewed. In situ hybridization (ISH) targeting SARS-CoV-2 spike protein transcript (V-nCoV2019-S) was performed on cell block material in all cases. A total of 17 effusion cytology cases were identified among 15 COVID patients, including 13 pleural, 2 pericardial, and 2 peritoneal. Most (13 of 15) patients were hospitalized for COVID complications. Eight patients died during hospitalization, 7 from COVID complications. All fluids were transudative by protein criteria. Lymphocytic or histiocytic inflammation predominated in 12 of 17 cases. Five exhibited hemophagocytosis. No viral cytopathic changes or extra-medullary megakaryocytes were seen. Viral RNA was not detected in any case by ISH. Body cavity effusion is an ominous finding in patients with advanced COVID-19 disease. Such effusions tend to be transudative with lymphohistiocytic inflammation, and commonly exhibit hemophagocytosis, an otherwise rare finding in effusion cytologies. No direct infection of cellular elements by SARS-CoV-2 was identified by ISH. Erythrocytosis and leukocytosis noted on cell block material from a pleural effusion specimen in an 81-year-old female patient with COVID-19 pneumonia. [Display omitted] [ABSTRACT FROM AUTHOR]

Introduction: Pericardial fluid is enriched with biologically active molecules of cardiovascular origin including microRNAs. Investigation of the disease-specific extracellular microRNAs could shed light on the molecular processes underlying disease development. Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart disease characterized by life-threatening arrhythmias and progressive heart failure development. The current data about the association between microRNAs and ARVC development are limited.Methods and Results: We performed small RNA sequence analysis of microRNAs of pericardial fluid samples obtained during transcutaneous epicardial access for ventricular tachycardia (VT) ablation of six patients with definite ARVC and three post-infarction VT patients. Disease-associated microRNAs of pericardial fluid were identified. Five microRNAs (hsa-miR-1-3p, hsa-miR-21-5p, hsa-miR-122-5p, hsa-miR-206, and hsa-miR-3679-5p) were found to be differentially expressed between patients with ARVC and patients with post-infarction VT. Enrichment analysis of differentially expressed microRNAs revealed their close linkage to cardiac diseases.Conclusion: Our data extend the knowledge of pericardial fluid microRNA composition and highlight five pericardial fluid microRNAs potentially linked to ARVC pathogenesis. Further studies are required to confirm the use of pericardial fluid RNA sequencing in differential diagnosis of ARVC.

ObjectiveThe aim of the present study is to isolate and analyze the characterization of pericardial fluid cells (PFCs) from rat and provides a morphological basis for the basic research and clinical application of PFCs.MethodsAfter aseptic thoracotomy was performed, normal saline was injected into the pericardial cavity of 50 adult Sprague–Dawley rats. The mixture of diluted pericardial fluid was extracted, centrifuged, and cultured. The cell morphology of different generations in the pericardial fluid was observed on an inverted microscope. The expression levels of CD44, CD29, CD90, and pan-hematopoietic marker CD45 were analyzed via flow cytometry. The third-generation cells were used for osteogenic, adipogenic, and cardiac differentiation.ResultsPFCs were successfully isolated and subcultured. PFCs were predominantly circular in shape after 24 h of culture. Following subculture for 3 days, the cells demonstrated a spindle shape. The rat pericardial fluid contains cell populations with uniform morphology, good growth state, and strong proliferation ability. Flow cytometry results showed that CD29 (100%) and CD90 (99.3%) were positively expressed, whereas CD45 (0.30%) and CD44 (0.48%) were negatively expressed. The PFCs could differentiate into osteoblasts and adipocytes after being induced. Cardiac differentiation was also confirmed by cardiac troponin T (cTnT) and α-sarcomeric actin (α-SA) staining.ConclusionThis study revealed that a subpopulation of cells was isolated from pericardial fluid, which exhibited progenitor cell features and multiple differentiation potency. PFCs could serve as an alternative cell source for myocardial tissue repair, engineering, and reconstruction.

Coronary artery disease (CAD) is a major health issue. This study focused on pericardial macrophages and small extracellular vesicles (sEVs) in CAD. The macrophages in CAD patients showed reduced expression of protective markers and unchanged levels of proinflammatory receptors. Similar changes were observed in buffy-coat-derived macrophages when stimulated with CAD pericardial fluid-derived sEVs. The sEV contained miRNA-6516-5p, which inhibited CD36 and affected macrophage lipid uptake. These findings indicate that sEV-mediated miRNA actions contribute to the decrease in protective pericardial macrophages in CAD., Competing Interests: This study was supported by the British Heart Foundation (BHF) Programme Grant-RG/15/5/31446 and Personal Chair Awards-CH/15/1/31199 (to Dr Emanueli); BHF Transitional Fellowship (Imperial College London BHF Centre of Research Excellence-RE/18/4/34215) and BHF Project Grant (BHF- PG/23/11336) (both to Dr Ben-Aicha); UKRI Postdoctoral Fellowship-EP/X023729/1 (to Dr Martino); a grant from The Leducq Foundation (to Dr Sattler); PLEC2021–007664-Unión Europea NextGeneration EU/PRTR, grant PID2021-128891OB-I00, and grant M-ERA-NET-3 / PCI2023-143431 - European Funds (all to Dr Vilahur). This study was also funded by MCIN/AEI/10.13039/501100011033 and Fondo Europeo de Desarrollo Regional, A way of making Europe. This manuscript was also supported by the UK National Institute of Heart Research (NIHR) for funding this research. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Post-operative atrial fibrillation (POAF) is a common complication of cardiac surgery which is associated with longer hospital stay, diminished quality of life, and increased mortality. Yet, the pathophysiology of POAF is poorly understood and it is unclear which patients are at highest risk. Pericardial fluid (PCF) analysis is emerging as an important tool for the early detection of biochemical and molecular changes in the cardiac tissue. With the epicardium acting as a semi-permeable membrane, the composition of PCF reflects the activity of the cardiac interstitium. Emerging research on PCF composition has identified promising biomarkers which may help stratify the risk for developing POAF. These include inflammatory molecules, such as interleukin-6, mitochondrial deoxyribonucleic acid, and myeloperoxidase, as well as natriuretic peptides. Additionally, PCF appears to be superior to serum analysis in detecting changes in these molecules during the early postoperative period after cardiac surgery. The aim of the present narrative review is to summarize the current literature on the temporal changes in the levels of potential biomarkers in PCF after cardiac surgery and their association with the development of new-onset postoperative atrial fibrillation., Competing Interests: Declaration of Competing Interest None declared by all authors., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Pericardial effusions can be caused by diverse etiologies, including heart-related conditions, kidney failure, trauma, infections, autoimmune diseases, and cancer. This systematic review aimed to assess the role of cytology in identifying the most prevalent cancers related to malignant pericardial effusions (MPEs), the ability of cytology, compared to histology, to detect cancer while evaluating pericardial effusions, and the prognostic impact of MPEs. Four electronic databases were investigated using a predefined algorithm, and specific inclusion and exclusion criteria. We found that the most prevalent primaries associated with MPEs were lung (especially NSCLCs), breast, hematolymphoid, and gastrointestinal cancers. MPEs tended to be hemorrhagic rather than serous or serosanguinous and to occupy larger volumes compared to non-neoplastic effusions. In addition, cytology was shown to exhibit an enhanced ability to detect cancer compared to biopsy in most of the included studies. Lastly, the presence of an MPE was associated with poor prognosis, while survival depended on the specific cancer type detected. Particularly, prognosis was found to be worse when MPEs were caused by lung or gastric cancer, rather than breast or hematolymphoid malignancies. In conclusion, evidence suggests that cytologic evaluation has a significant diagnostic and prognostic impact in patients with MPEs.

Abstract Background Injury may induce a sequential activation of intrinsic reparative activity that supports the maintenance of tissue homeostasis. Method In the present experiments, we investigated whether myocardial infarction (MI) was able to reinstate the expression of Wilms’ tumor factor 1 (WT1) as a key hallmark of fetal reprograming in the pericardial adipose-derived stem cells (pADSC). We characterized the immunophenotypical markers, cardiac potential, and reparative activity of WT1-expressing pADSC (WT1pos) isolated MI Wistar rats with an intact pericardial sac in which cardiac transudate was accumulated, sampled, and analyzed. Results The WT1pos cells formed colony-like aggregates in culture that subsequently generated phase-bright cells that homogenously constituted WT1 expression (> 98%). The WT1pos cells shared identical surface markers with canonical pADSC, but enhanced transcripts for cardiogenesis (isl-1, gata-4, Sox2 and Tbx18) as well as cardiac commitment (endothelial: 28%; cardiomyogenic: 12.3%) in defined conditions. Remarkably, cardiac transplantation of WT1pos cells promoted regional angiogenesis and myogenesis which led to significant functional amelioration of the infarcted hearts. Furthermore, we demonstrated that WT1pos cells uniquely secreted hepatocyte growth factor (HGF) as a key antiapoptotic factor that promotes cardiac repair. Conclusion Injury-associated fetal reprogramming in pADSC facilitates cardiac differentiation and promotes the reparative activity by enhancing HGF production. As such, injury-“conditioned” pADSC may represent a useful autologous cell donor from infarcted patients for cell-based therapy.