Pericardial Fluid Research Articles

Human macrophages are immunnoprofiled by pericardial fluid small extracellular vesicles modulating lipid metabolism mechanisms

Abstract Background Coronary artery disease (CAD) is the main cause of myocardial infarction and consequent ischemic heart disease (IHD). Macrophages are central to CAD. Small extracellular vesicles (sEVs) can shuttle microRNAs and other molecular cargos from cell to cell, mediating response in target cells. Recent evidence supports the sEVs role in modulating macrophage phenotype. The pericardial fluid (PF) contains sEVs and immune cells including cavity-like macrophages. Purpose This study investigates whether PF-sEVs regulate macrophages, contributing to a specific immunophenotype in CAD patients. Methods PF was collected from CAD patients undergoing coronary bypass surgery (CABG) and non-atherosclerotic patients operated for mitral valve repair (control group). sEVs were isolated and characterised for size (Nanosight tracking analysi), tetrasapanin content (Nanoview chips) and microRNA content (RNA seq analysis). Monocytes from healthy donors were isolated from buffy coats and differentiated into macrophages following established protocols. Macrophages were incubated with either CAD-sEVs or non-CAD sEVs for 24h at 37oC. The cells were collected and processed for mRNA analyses (qRT-PCR) and flow cytometry. Further bioinformatics were employed to understand functional pathways targeted by PF-sEVs-miRNA. Results In line with the human-PF macrophages profile, exposure to CAD-sEVs reduces the anti-inflammatory profile of human macrophages. CAD-sEVs treated macrophages showed a CCR2-, CD36+low, CD206+low profile. While non-CAD-sEVs did not statistically differ from PBS nor untouched groups, CAD-sEVs increased the mRNA level of IL1a, IL1b, TNFa and decreased MRC1. Bioinformatic analysis showed that 861 miRNAs were decreased in the PF-sEVs from CAD patients compared to non-CAD. miRNA targets prediction and pathway analyses reported that clusters of PF-miRNAs could regulate CD36, decreased in PF-macrophages. Conclusions We demonstrate, that sEVs isolated from PF-CAD reduce the anti-inflammatory profile of human macrophages, and target crucial lipid metabolism pathways. These clinically relevant results could drive to decipher improved therapeutics to modulate the epicardial/myocardial immune response in CAD patients.

Re-Categorization and Risk of Malignancy of Atypical Effusions According to the International System for Reporting Serous Fluid Cytopathology (TIS): An Institutional Experience.

Serous effusion fluids serve as crucial cytological materials in diagnosing the underlying causes of fluid accumulation in various body cavities. The International System for Reporting Serous Fluid Cytopathology (TIS) outlined atypia of undetermined significance (AUS) and suspicious for malignancy (SFM) as two intermediate categories for atypical fluids. In our study, cases diagnosed as "atypical" by an experienced cytopathologist in the Hacettepe University Department of Pathology, between 2014 and 2023, were re-categorized according to TIS. The risk of malignancy (ROM) for AUS and SFM categories was calculated. Additionally, cases were re-evaluated according to the 5-tier categorical system by two observers with different level of experience. A total of 3501 effusion fluids were included in the study, evaluated between 2014 and 2023. 50.7% of the cases were male, and 49.3% were female. 55.2% of the cases were pleural fluid, 41.5% were peritoneal fluid, and 3.3% were pericardial fluid. Two hundred sixty five cases (7.6%) were non-diagnostic, 2160 (61.7%) were negative for malignancy, 111 (3.2%) were AUS, 83 (2.4%) were SFM, and 883 (25.2%) were malignant (M). ROM calculated 27% for AUS, 49% for SFM 49%. The interobserver agreement for AUS was 46% with kappa value of 0.162, and 42% for SFM with kappa value of 0.188. The differentiation of atypical cases into AUS and SFM is effective in determining the ROM. The interobserver agreement tends to be lower in intermediate categories compared to others, emphasizing the potential significance of clinical expertise in diagnosis.

Cardiac Angiosarcoma with Unusual Cytologic Features Causing Cardiac Tamponade in a Young Adult Patient

Abstract Introduction/Objective Cardiac angiosarcoma is a rare endothelial malignancy with poor prognosis, frequent metastasis, and short median survival of only a few months. The disease has a wide age spectrum and can occur in young adult patients. The cytological diagnosis of cardiac angiosarcomas is challenging as cases are rare and its cytology is not extensively described or reported in literature. Here, we describe a rare case of cardiac angiosarcoma with unusual cytologic features. Methods/Case Report Our patient is a 30 year old male presenting with three days of worsening dyspnea and palpitations and was discovered on ultrasound to have large pericardial effusion compressing the right ventricle and causing cardiac tamponade. CT/MRI imaging revealed a 4.5 x 4.3 x 2.6 cm mass inside the right ventricle with extra- cardiac invasion through the pericardium and into the anterior mediastinum. Pericardiocentesis yielded 1.5 liters of hemorrhagic, brown, pericardial fluid with elevated LDH and protein levels. Cytology of the pericardial fluid revealed numerous tumor cells occurring singly or in monolayered, acinar clusters or cohesive spheres containing amorphous, eosinophilic cores made of collagen as evidenced on trichrome stain. The tumor cells possessed hyperchromatic, irregular, variably sized nuclei, prominent nucleoli, and cytoplasmic vacuoles. The tumor cells were positive for vimentin, CD31, and CD34, and showed high Ki67 proliferation index > 50%. A catheter-mediated biopsy of the right ventricular mass revealed spindled and epithelioid tumor cells strongly positive for CD31, CD34, and vimentin, focally positive for Factor VIII and AE1/AE3, and showing high Ki67 proliferation index of roughly 50%. The cytological, histological, and immunohistochemical findings were most consistent with cardiac angiosarcoma as the diagnosis. The patient eventually developed worsening chronic left chest pain and expired from cardiac arrest six months after his diagnosis. Results (if a Case Study enter NA) NA Conclusion We report a rare case of cardiac angiosarcoma with unusual cytologic features, manifesting as acinar clusters and cohesive spheres with collagenous cores that are not typical of malignant endothelial neoplasms. Currently there are no effective, standardized therapies that can significantly prolong survival for this malignancy, and treatment is often palliative. The cytological diagnosis of cardiac angiosarcoma is challenging given the rarity of this disease and the paucity of literature describing its cytology.

Confluence of Challenges: Massive Tubercular Pericardial Effusion Entangled with Heart Failure and Diabetes Mellitus - A Multidisciplinary Odyssey

This case report describes a rare and compelling presentation of Massive Tubercular Pericardial Effusion (MTPE) concomitant with Heart Failure (HF) and Diabetes Mellitus (DM). Tuberculosis, once thought to be a disease of the past, continues to manifest in diverse clinical scenarios, emphasizing the importance of maintaining a high index of suspicion, particularly in endemic regions. The patient, a 60-year-old male with a known history of DM and HF, presented with symptoms of worsening dyspnea, fatigue, and peripheral edema. A diagnostic workup revealed a massive pericardial effusion with characteristics suggestive of tubercular etiology, subsequently confirmed by pericardial fluid analysis. The challenges in managing this triad of conditions: MTPE, HF, and DM were addressed through a multidisciplinary approach involving cardiology, infectious disease, and endocrinology specialists. This case underscores the significance of a comprehensive diagnostic evaluation and collaborative management in optimizing outcomes for patients with complex cardiovascular and infectious comorbidities. KYAMC Journal Volume: 15, No: 01, April 2024: 56-58.

Injury-induced myosin-specific tissue-resident memory T cells drive immune checkpoint inhibitor myocarditis

Cardiac myosin-specific (MyHC) T cells drive the disease pathogenesis of immune checkpoint inhibitor-associated myocarditis (ICI-myocarditis). To determine whether MyHC T cells are tissue-resident memory T (TRM) cells, we characterized cardiac TRM cells in naive mice and established that they have a distinct phenotypic and transcriptional profile that can be defined by their upregulation of CD69, PD-1, and CXCR6. We then investigated the effects of cardiac injury through a modified experimental autoimmune myocarditis mouse model and an ischemia-reperfusion injury mouse model and determined that cardiac inflammation induces the recruitment of autoreactive MyHC TRM cells, which coexpress PD-1 and CD69. To investigate whether the recruited MyHC TRM cells could increase susceptibility to ICI-myocarditis, we developed a two-hit ICI-myocarditis mouse model where cardiac injury was induced, mice were allowed to recover, and then were treated with anti-PD-1 antibodies. We determined that mice who recover from cardiac injury are more susceptible to ICI-myocarditis development. We found that murine and human TRM cells share a similar location in the heart and aggregate along the perimyocardium. We phenotyped cells obtained from pericardial fluid from patients diagnosed with dilated cardiomyopathy and ischemic cardiomyopathy and established that pericardial T cells are predominantly CD69+ TRM cells that up-regulate PD-1. Finally, we determined that human pericardial macrophages produce IL-15, which supports and maintains pericardial TRM cells.

8705 Autoimmune Polyglandular Syndrome Type 2 Presenting As Recurrent Cardiac Tamponade

Abstract Disclosure: E.M. Niedzialkowska: None. D. Shelden: None. Introduction: Autoimmune polyglandular syndrome type 2 (APS2) is a rare endocrinopathy with co-occurrence of autoimmune adrenal insufficiency, autoimmune thyroiditis and/or type 1 diabetes. In rare cases, APS2 can predispose patients to recurrent pericardial effusion and tamponade. Case presentation: 32 y.o male with medical history of hypothyroidism on replacement therapy diagnosed 2 weeks prior to admission presented with progressive dyspnea and hypotension. The patient was found to have pericardial effusion with tamponade requiring pressor support. Initial lab tests showed TSH 148.7 uIU/ml (N 0.4-4.5), free t4 0.7 ng/dl(N 0.7-1.5 ), free t3 2 pg/ml (N 1.7-3.5), Hb a1c 4.7% (N <5.6%), thyroglobulin antibody 851 IU/ml (N <20), TPO antibody >1 000 IU/ml (N<=35), TSI 0.1 IU/l (<0.1), sodium 127 mmol/l (N 135-145), and a negative adrenal antibody panel. The patient was started on IV levothyroxine (400 mcg daily) and stress dose steroids in the setting of shock requiring 4 pressors. Shock resolved after pericardiocentesis and the patient was weaned off pressor support. Pericardial fluid showed neutrophil predominance and was negative for an infectious process, lab tests showed negative ANA, ANCA and GBM. The day following admission lab tests showed TSH of 23.86 uIU/ml, ft4 1.3 ng/dl, the patient was transitioned to oral levothyroxine 125 mcg and the steroid regimen was tapered and discontinued. Follow up tests showed normal TSH and resolution of pericardial effusion. Four weeks after initial admission the patient was readmitted due to hypotension. Laboratory tests showed random cortisol <1.0 ug/dl (N 2.9-19.4), ACTH 17 pg/ml (N 6-48), adrenal antibody titers 1:20 (N < 1:10), cosyntropin stimulation test was positive for adrenal insufficiency and the patient was started on steroid regimen with symptomatic improvement. He was diagnosed with APS type 2 based on his constellation of endocrinopathies. Repeat echocardiogram was negative for pericardial effusion. Two months later, the patient presented with chest pain. Imaging was positive for recurrent pericardial effusion requiring pressor support and pericardiocentesis. The patient was subsequently started on colchicine. Infectious and rheumatologic workup continued to be negative. The patient did not exhibit symptoms of connective tissue disease. Seven months after the initial presentation the patient was readmitted with COVID-19 infection complicated by hypotension and a small pericardial effusion. Symptoms improved after initiation of stress dose steroids. Conclusion: Cardiac tamponade is a rare presentation of APS2 with 9 cases reported in the literature up to date. Increased incidence of pericardial effusion is presumed to be a result of autoimmune inflammation leading to fluid accumulation. The patients are prone to tamponade due to intravascular volume depletion, decreased vascular tone and impaired stress response. Presentation: 6/3/2024

6517 Cardiac Tamponade Secondary to Occult Primary Hypothyroidism

Abstract Disclosure: L. Javed: None. H. Al jumaili: None. A. Mahaldar: None. I. Goyal: None. N. Shakir: None. E. Punni: None. Introduction: The incidence of pericardial effusion in hypothyroidism seems to correlate with severity and duration of the condition and ranges from 3% to 37%. Cardiac tamponade resulting from hypothyroidism is exceptionally rare. We present a case of a patient presenting with this complication.Case Summary:A 38-year-old woman presented during a routine clinic visit with symptoms of fatigue and was found to have elevated liver functions enzymes with ALT 107 (N<48 U/L ) and AST 70 (N<47 U/L)Further evaluation through abdominal imaging revealed incidental finding of a partially imaged moderate pericardial effusion. A subsequent echocardiogram showed circumferential pericardial effusion with early tamponade physiology, necessitating immediate referral to the emergency room (ER) for further assessment and management.Upon admission to the ER, the patient reported progressive fatigue, increased sleep and menorrhagia over 8 months. There were no accompanying symptoms of weight gain or constipation. Family history was positive for thyroid disease in her grandmother. Initial vital signs on admission were Blood pressure: 119/86, Pulse: 55, Respiratory Rate: 13, Temp: 36.7 °C. Electrocardiogram showed sinus bradycardia. Laboratory findings were significant for: Hgb 8.7 (N>11.5), MCV 77.5 (N>80 fL), mildly elevated ALT 56, markedly elevated TSH 255 (N<5 IU/mL), low free T4 <0.1 (N ≥ 0.7 ng/dL), low free T3 <0.6 (N ≥2.0 pg/m), and elevated TPO 472 (N 35 IU/mL). Infectious and rheumatologic work-up were negative. Thyroid ultrasound showed heterogenous echogenicity consistent with thyroiditis.Patient underwent urgent pericardiocentesis draining 750 ml of clear yellowish pericardial fluid. Simultaneously, the patient was initiated on daily levothyroxine at a dose of 112 mcg.Stability in hemodynamics and repeat echocardiogram showcasing no pericardial effusion facilitated the patient’s discharge. Notable improvement with reduction in TSH from 260 to 20 was seen at the one-month follow-up in endocrinology clinic. Conclusion: Hypothyroidism should be considered in patients diagnosed with cardiac tamponade presenting with bradycardia, as in this case. It's been observed that hypothyroidism can affect LFTs which typically resolve with thyroid replacement. Treatment of cardiac tamponade depends on the patient's hemodynamic status. For early mildly affected cases of tamponade, a conservative approach involving close monitoring and limiting fluid intake may suffice, but drainage is often necessary. Since the pericardial effusion and tamponade stem from hypothyroidism, there's a high chance of effusion recurring after drainage. Hence, administering levothyroxine is essential, often leading to effusion resolution within 2-12 months without recurrence. Presentation: 6/3/2024

Postmortem study of adrenomedullin and cortisol in femoral serum and pericardial fluid related to acute pulmonary edema.

Currently, various tools aid in determining the cause of death and the circumstances surrounding it. Thanatochemistry is one such method that provides insights into the physiopathological mechanisms of death and the behavior of specific biomarkers in different body fluids postmortem. Certain biomarkers, characterized by their stability and specificity to vital tissues like the lungs, are associated with mechanisms contributing to death, such as acute pulmonary edema (APE). This study aims to analyze the behavior of midregional pro-adrenomedullin (MR-proADM) and cortisol levels, measured in pericardial fluid and femoral serum, in relation to the severity of APE, categorized according to specific criteria. Samples were collected from a total of 92 corpses (77 males, 15 females) with a mean age of 56.7 ± 15.2 years. The severity of APE associated with the deaths was classified into three groups: slight or absent (n = 7; 8.6%), medium or moderate (n = 16; 19.8%), and intense (n = 58;71.6%).The determination of MR-proADM and cortisol levels was conducted using ELISA kits and an Immunoassay Analyzer, respectively. Our results reveal a significant increase in MR-proADM concentration with the severity of APE. Furthermore, a correlation was established between cortisol and MR-proADM concentrations in both pericardial fluid and femoral serum samples. This indicates that the severity of APE influences the production of ADM, regardless of the specific underlying pathophysiological mechanisms. Cortisol values were also found to be higher in the intense APE group compared to the moderate group.This study contributes to our understanding of the relationship between MR-proADM and cortisol, and the severity of APE, shedding light on potential applications in postmortem investigations.

Clinical and radiological characteristics of mediastinal melioidosis: A four-year retrospective cohort from Sabah, Malaysia

BackgroundMelioidosis is a potentially fatal tropical infection. Little is known about mediastinal involvement in melioidosis. This study aimed to (a) describe the prevalence and demographics of various morphologies of mediastinal melioidosis, (b) propose a classification for radiological morphologies of mediastinal melioidosis. MethodsA retrospective cohort study was performed. Case records of consecutive patients with culture-positive melioidosis who underwent computed tomography (CT) thorax from January 1, 2018–February 28, 2022, were reviewed. Results486 culture-positive melioidosis patients were identified, of which 70 underwent CT thorax. 41 patients demonstrating mediastinal involvement were included in the final analysis, of which four were mediastinal collections, while the rest were classified into those with necrotic or matted appearances, and subcentimeter and larger than 1 cm. Culture-positivity was proven from blood in 83 % of patients (n = 34), with the remaining from chest wall pus, neck abscess pus, sputum, liver abscess, seminal vesicle, pleural, pericardial and peritoneal fluid. The most commonly associated pulmonary manifestations were consolidation and pleural effusion. Half had diabetes; a quarter had chronic kidney disease, while one had syphilis. Exposure to soil was present in six patients: quarry (n = 1), construction (n = 2), farmer (n = 1), living environment (n = 2). Seven patients succumbed before the end of 6-week intensive phase antibiotic treatment. ConclusionMediastinal melioidosis is a spectrum with multiple overlapping features consisting of necrosis, matted lymph nodes, multiseptated and non-septated collections. Further studies will elucidate the prognostic implications of mediastinal melioidosis.

Higher sensitivity of pericardial fluid cytology than biopsy in malignant effusions with potential explanation of false‐negative cytology: A multi‐institutional analysis

Higher sensitivity of pericardial fluid cytology than biopsy in malignant effusions with potential explanation of false‐negative cytology: A multi‐institutional analysis

Pericardiocentesis: History, Current Practice, and Future Directions.

To discuss the evolution in the approach to pericardial effusions and drainage from a historical perspective, the present state, and pathways for future innovative therapies. Incorporation of advanced imaging tools has dramatically improved the safety profile of pericardial interventions. Outcome data allow for refined approaches to management of pericardial disease in special populations, such as pulmonary arterial hypertension. Consideration of intrapericardial interventions and pharmacotherapy represent novel and promising approaches to management of pericardial effusions moving forward. Although the impact of excess or rapidly accumulating pericardial fluid on hemodynamics has been recognized for centuries, the therapeutic approaches have only recently become more refined with the routine incorporation of such tools as echocardiography and fluoroscopy. The most utilized approaches for pericardiocentesis include the apical, subxiphoid, and parasternal, and the most favorable approach is that in which the pericardial fluid is closest to the body surface, where intervening vital structures are least likely to be damaged. With the notable exception of patients with pre-existing pulmonary hypertension, complete decompression of pericardial fluid with careful drain management reduces likelihood of pericardial effusion recurrence. In addition, percutaneous balloon pericardiotomies have been demonstrated to reduce recurrence in nonmalignant effusions.

Purulent pericarditis and cardiac tamponade in HIV: a case report on a dreaded complication of streptococcus pneumoniae

Introduction and importance: Purulent pericarditis is an uncommon complication of Streptococcus pneumoniae, which commonly occurs in an immunocompromised state such as HIV and can lead to life-threatening complications such as cardiac tamponade and potentially death if untreated. Early identification, pericardiocentesis, and general measures such as antibiotics and anti-inflammatory medications can be life-saving. Case presentation: We present a case of a 64-year-old male with HIV who presented with clinical symptoms suggestive of pericarditis. Chest imaging revealed multifocal airspace diseases and moderate pericardial effusion. He had worsening lactic acidosis, and bedside point-of-care ultrasound showed pericardial effusion with features suggestive of cardiac tamponade. His lactic acidosis improved with emergency pericardiocentesis. Blood and pericardial fluid cultures revealed Streptococcus pneumoniae. He was further treated with intravenous antibiotics, colchicine, and ibuprofen. Clinical discussion: Although Streptococcus pneumoniae is a common etiology of community-acquired pneumonia (CAP), it has not been cited as the leading cause of pericarditis or pericardial effusion. In immunocompromised patients, it is necessary to consider a broad differential diagnosis as an etiology of acute chest pain, as it may be challenging to differentiate pleuritic and pericarditic chest pain from clinical presentation only. Moreover, infectious etiology of acute pericarditis and pericardial effusion should be considered in this patient population, especially those with HIV. At the same time, it is crucial to promptly identify and treat cardiac tamponade to prevent further deterioration. Conclusion: Our case provides insight into the diagnosis and management of CAP and its potential complication of purulent pericarditis and cardiac tamponade in immunocompromised patients.

Postmortem-Derived Exosomal MicroRNA 486-5p as Potential Biomarkers for Ischemic Heart Disease Diagnosis.

Exosomes are nanovesicles 30-150 nm in diameter released extracellularly. Those isolated from human body fluids reflect the characteristics of their cells or tissues of origin. Exosomes carry extensive biological information from their parent cells and have significant potential as biomarkers for disease diagnosis and prognosis. However, there are limited studies utilizing exosomes in postmortem diagnostics. In this study, we extended our initial research which identified the presence and established detection methodologies for exosomes in postmortem fluids. We analyzed exosomal miRNA extracted from plasma and pericardial fluid samples of a control group (n = 13) and subjects with acute myocardial infarction (AMI; n = 24). We employed next-generation sequencing (NGS) to investigate whether this miRNA could serve as biomarkers for coronary atherosclerosis leading to acute myocardial infarction. Our analysis revealed 29 miRNAs that were differentially expressed in the AMI group compared to the control group. Among these, five miRNAs exhibited more than a twofold increase in expression across all samples from the AMI group. Specifically, miR-486-5p levels were significantly elevated in patients with high-grade (type VI or above) atherosclerotic plaques, as per the American Heart Association criteria, highlighting its potential as a predictive biomarker for coronary atherosclerosis progression. Our results indicate that postmortem-derived exosomal microRNAs can serve as potential biomarkers for various human diseases, including cardiovascular disorders. This finding has profound implications for forensic diagnostics, a field critically lacking diagnostic markers.

Medical Students' Competency in EFAST (Extended Focused Assessment Sonography for Trauma) Components: A Prospective Observational Study.

Ultrasound training in undergraduate medical education is developing, and its incorporation into the curriculum requires careful planning. Extended Focused Assessment Sonography for Trauma (EFAST) is commonly taught to medical students as one of the primary applications of ultrasound. Because false-negative EFAST scans can affect patients' clinical outcomes, it is essential to evaluate the individual components of this skill. We aim to determine which EFAST components students perform sub-optimally after initial training. In this prospective observational study, 90 medical students from two final-year cohorts were assessed in EFAST components after uniform training during the emergency medicine clerkship. All validated components of the standard EFAST exam were assessed, and a descriptive analysis of individual components of EFAST was performed. The hepatorenal space, splenorenal space, and pelvic space fluid investigations had the lowest completion rates. Pericardial fluid, pelvic free fluid, and right thoracic pleural fluid investigations were often incorrectly applied. Fanning was most commonly missed in hepatorenal, splenorenal, and pelvic free fluid investigations, and between 12% and 50% of EFAST components had omitted reporting. There were significant incomplete assessments for free intraperitoneal fluid, primarily due to a lack of fanning in the hepatorenal, splenorenal, and pelvic areas. Trainers can effectively enhance student performance and outcomes by targeting these challenging areas. Further research might reveal whether residents and physicians show similar trends in EFAST completion.

Pericardial Fluid Accumulates microRNAs That Regulate Heart Fibrosis after Myocardial Infarction.

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.

Methicillin-Sensible Staphylococcus aureus (MSSA) Pericardial Effusion Causing Cardiac Tamponade: A case report

Background: Methicillin-Sensible Staphylococcus aureus (MSSA) as the pathogen of the pericardial space is an uncommon case that can be fatal if untreated. The underlying disease accompany with infection that lead to cardiac tamponade can increase mortality rate of the patient. Case description: We present a 29 years old male patient with severe dispnea who was found to have cardiac tamponade secondary to a purulent pericardial effusion. He was also had end stage renal disease with regular hemodialysis. The diagnosis was suggested by clinical context, imaging, pericardial fluid analysis and was confirmed by culture. MSSA were isolated from 2 times pericardial fluid, peripheral blood and double lumen catheter exit site swab that were growth in blood agar only. Identification and susceptibility to antibiotics was assessed by Vitek2 Compact automated system (BioMerieux), represent sensitive to penicillin, cephalosporin, quinolone, aminoglycoside except macrolides. Administration of cefazolin intravenous for 5 days and also pericardial drainage result in a full recovery for the patient. Discussion: Purulent pericardial effusion is a rare condition that carries a high mortality rate as it can rapidly progress into cardiac tamponade. In developing countries, Mycobacterium tuberculosis is the most frequent cause of acute pericarditis followed by Haemophilus, Staphylococcus and Streptococcus. Prior to the advent of antibiotics, Staphylococcus aureus takes role as the predominant pathogen, this event was common as the result of hematogenous seeding such as catheter related hemodialysis in this patient. Conclusion: Prompt diagnosis of purulent pericardial effusion also initiation of appropriate antibiotic and pericardial drainage treatment are the mainstays of successful management of this rare but potentially lethal case.

A Carrier-Based Quantitative Proteomics Method Applied to Biomarker Discovery in Pericardial Fluid

Data-dependent liquid chromatography tandem mass spectrometry is challenged by the large concentration range of proteins in plasma and related fluids. We adapted the SCoPE method from single-cell proteomics to pericardial fluid, where a myocardial tissue carrier was used to aid protein quantification. The carrier proteome and patient samples were labeled with distinct isobaric labels, which allowed separate quantification. Undepleted pericardial fluid from patients with type 2 diabetes mellitus and/or heart failure undergoing heart surgery was analyzed with either a traditional liquid chromatography tandem mass spectrometry method or with the carrier proteome. In total, 1398 proteins were quantified with a carrier, compared to 265 without, and a higher proportion of these proteins were of myocardial origin. The number of differentially expressed proteins also increased nearly four-fold. For patients with both heart failure and type 2 diabetes mellitus, pathway analysis of upregulated proteins demonstrated the enrichment of immune activation, blood coagulation, and stress pathways. Overall, our work demonstrates the applicability of a carrier for enhanced protein quantification in challenging biological matrices such as pericardial fluid, with potential applications for biomarker discovery. Mass spectrometry data are available via ProteomeXchange with identifier PXD053450.

Pyopericardium progresses to cardiac tamponade in patient of hypothyroidism due to Staphylococcus aureus

Pyopericardium is a rare condition with a high mortality rate, in which, infection propagates into pericardial space, leading to pus-filled pericardial effusion and cardiac tamponade which can lead to cardiogenic shock and death, if there is any delay in diagnosis and treatment with antibiotics and pericardial drainage. We report the case of a 28-year-old female, a known case of hypothyroidism from the last 6 years who presented with 2 months of fever and recent onset shortness of breath diagnosed as pyopericardium due to Staphylococcus aureus, and having clinical features of cardiac tamponade. She was a known case of hypothyroidism non-compliant with treatment. Pyopericardium conformed with transthoracic 2D echocardiography-guided aspiration of pericardial fluid. After pericardial pus drainage, the patient symptomatically improved initially but remained in shock due to ongoing sepsis and died due to septic shock and multi-organ failure.

Evaluation of Inoculating Sterile Pericardial Fluid into Blood Culture Bottles

Background: There is limited data regarding the benefits of direct inoculation of sterile pericardial fluid into blood culture bottles. We discovered widespread adoption of this practice at our institution during pericardiocenteses and became concerned about over-capturing of skin flora contaminants. We aimed to understand how organisms detected in pericardial fluid inoculated into blood culture bottles were interpreted clinically. Methods: We investigated a cluster of four patients with coagulase-negative Staphylococcus (CoNS) isolated in pericardial fluid inoculated blood culture bottles (PF-BCxBs) over a 2-week period; three of these patients had recent cardiac surgery and were initially flagged as potential SSIs. We further expanded to a retrospective review and identified 28 patients with ≥1 organism isolated from PF-BCxBs from 7/2021 to 6/2023. Clinical, microbiological, and pharmacy data were abstracted. The primary outcome was the proportion of patients with a clinically diagnosed infection. Results: Investigation into the initial cluster revealed a pseudo-outbreak - three of four patients had no clinical evidence of infection (CoNS was deemed a contaminant); one was treated for a potential infection. All patients had concomitant negative routine fluid cultures. Discussions with the cardiology teams revealed areas for improvement in the process for inoculating fluid into blood culture bottles. From the two-year review, 18% (5/28) of patients were clinically diagnosed with an infection (two Staphylococcus aureus; two CoNS; one Candida rugosa). Of the patients without Staphylococcus aureus, all three had a concomitant negative routine fluid culture, were receiving antibiotics prior to pericardiocentesis, and had white blood cell counts (WBC) >12 K/uL. The remaining 82% (23/28) of patients were deemed not to have an infection. Of these 23 patient without infection, organisms isolated were 16 CoNS (70%) and seven Cutibacterium species (30%). None of these patients had a fever, one (4%) was receiving pre-pericardiocentesis antibiotics, and three (9%) had WBC >12 K/uL. 70% (16/23) of these patients were started on antibiotics after gram-stain results; all were eventually discontinued (mean antibiotic days = 2, range 1-5 days). 83% (19/23) of these patients had a concomitant negative routine fluid culture. Conclusion: The majority of patients with an organism isolated from PF-BCxBs had either CoNS or Cutibacterium species and were deemed not to have a clinical infection. Within the small cohort limitations, clinical utility of blood culture bottle inoculation seems highest for patients with pre-procedural concern for infection. IPC teams should be aware of the non-pathogenic skin flora frequency and potential implication on SSI surveillance.

Diagnostic utility of echocardiography and ultrasonography in buffaloes suffering from pericarditis

Pericarditis remains a serious problem faced by bovine producers in the developing countries. This study was designed to evaluate the echocardiographic and ultrasonographic changes in dairy buffaloes affected with pericarditis presented to Large Animal Clinic, Teaching Veterinary Hospital of Guru Angad Dev Veterinary and Animal Sciences University (GADVASU), Ludhiana, India. 49 buffaloes were included and selected on the basis one or more of the clinical signs viz., brisket edema, dyspnoea, muffled heart sounds and distended jugular veins. Animals were subjected to clinical examination, thoracic and abdominal ultrasonography and M- mode echocardiography. The CVS examination revealed normal intensity of heart sounds in 17 and muffled in 32 cases with splashing/pericardial rub in 9 cases. Ultrasonography revealed spleenic congestion, liver was congested in majority of the cases with visible dilatation of the caudal vena cava. Heart was normal in 7 and visibly compressed in 42 cases due to the pericardial fluid. Massive pleural fluid was seen in 28 cases. Buffaloes in our study had pericardial effusions (n=49), pleural and pericardial effusions (n=45) and pleural, pericardial and peritoneal effusions (n=19). The predominant echocardiographic findings were significantly decreased dimensions of the heart chambers in both systole and diastole. The left ventricular contractility indices (FS% and EF%) were significantly high. The clinical findings alone do not allow a definitive diagnosis of pericarditis as characteristic signs were not present in all the cases. The combined use of ultrasonography and echocardiography provides a comprehensive idea about such cases and aids in early diagnosis of pericarditis.