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Circulation Research Oct 2022Mesenchymal stem cell (MSC)-derived exosomes are well recognized immunomodulating agents for cardiac repair, while the detailed mechanisms remain elusive. The...
BACKGROUND
Mesenchymal stem cell (MSC)-derived exosomes are well recognized immunomodulating agents for cardiac repair, while the detailed mechanisms remain elusive. The Pericardial drainage pathway provides the heart with immunosurveillance and establishes a simplified model for studying the mechanisms underlying the immunomodulating effects of therapeutic exosomes.
METHODS
Myocardial infarction (MI) models with and without pericardiectomy (corresponding to Tomy MI and NonTomy MI) were established to study the functions of pericardial drainage pathway in immune activation of cardiac-draining mediastinal lymph node (MLN). Using the NonTomy MI model, MSC exosomes or vehicle PBS was intrapericardially injected for MI treatment. Via cell sorting and RNA-seq (RNA-sequencing) analysis, the differentially expressed genes were acquired for integrated pathway analysis to identify responsible mechanisms. Further, through functional knockdown/inhibition studies, application of cytokines and neutralizing antibodies, western blot, flow cytometry, and cytokine array, the molecular mechanisms were studied. In addition, the therapeutic efficacy of intrapericardially injected exosomes for MI treatment was evaluated through functional and histological analyses.
RESULTS
We show that the pericardial draining pathway promoted immune activation in the MLN following MI. Intrapericardially injected exosomes accumulated in the MLN and induced regulatory T cell differentiation to promote cardiac repair. Mechanistically, uptake of exosomes by major histocompatibility complex (MHC)-II antigen-presenting cells (APCs) induced Foxo3 activation via the protein phosphatase (PP)-2A/p-Akt/forkhead box O3 (Foxo3) pathway. Foxo3 dominated APC cytokines (IL-10, IL-33, and IL-34) expression and built up a regulatory T cell (Treg)-inducing niche in the MLN. The differentiation of Tregs as well as their cardiac deployment were elevated, which contributed to cardiac inflammation resolution and cardiac repair.
CONCLUSIONS
This study reveals a novel mechanism underlying the immunomodulation effects of MSC exosomes and provides a promising candidate (PP2A/p-Akt/Foxo3 signaling pathway) with a favorable delivery route (intrapericardial injection) for cardiac repair.
Topics: Humans; Exosomes; Forkhead Box Protein O3; Mesenchymal Stem Cells; Myocardial Infarction; Proto-Oncogene Proteins c-akt; Signal Transduction; Heart Injuries
PubMed: 36252111
DOI: 10.1161/CIRCRESAHA.122.321384 -
The Pan African Medical Journal 2022Purulent pericarditis is an infection of the pericardial space that produces pus that is found on gross examination of the pericardial sac or on the tissue microscopy....
Purulent pericarditis is an infection of the pericardial space that produces pus that is found on gross examination of the pericardial sac or on the tissue microscopy. In this case report, we will discuss a 31-year-old male who presented with a chief complaint of low-grade fevers, dry cough and difficulty breathing for about two weeks which preceded after removing of dental also two weeks prior. He was admitted and treated as COVID-19 in the isolation ward, he later developed cardiac tamponade and during pericardiocentesis thick pus was discharged. Pus culture and Gene Xpert tests were all negative. After his condition improved, the patient was transferred to the general ward with the pericardial window still discharging pus. Pericardiectomy was chosen as definitive management. The key takeaway in this report is that Empirical treatment with RHZE (rifampin, isoniazid, pyrazinamide, and ethambutol) in resource-limited settings is recommended due to difficulty in identifying the exact cause at a required moment.
Topics: Adult; COVID-19; Ethambutol; Humans; Isoniazid; Male; Mediastinitis; Pericarditis; Pericardium; Pyrazinamide; Rifampin; Sclerosis; Suppuration
PubMed: 36160276
DOI: 10.11604/pamj.2022.42.145.34018 -
Clinical Cardiology Oct 2017A rising prevalence of end-stage renal disease (ESRD) has led to a rise in ESRD-related pericardial syndromes, calling for a better understanding of its pathophysiology,... (Review)
Review
A rising prevalence of end-stage renal disease (ESRD) has led to a rise in ESRD-related pericardial syndromes, calling for a better understanding of its pathophysiology, diagnoses, and management. Uremic pericarditis, the most common manifestation of uremic pericardial disease, is a contemporary problem that calls for intensive hemodialysis, anti-inflammatories, and often, drainage of large inflammatory pericardial effusions. Likewise, asymptomatic pericardial effusions can become large and impact the hemodynamics of patients on chronic hemodialysis. Constrictive pericarditis is also well documented in this population, ultimately resulting in pericardiectomy for definitive treatment. The management of pericardial diseases in ESRD patients involves internists, cardiologists, and nephrologists. Current guidelines lack clarity with respect to the management of pericardial processes in the ESRD population. Our review aims to describe the etiology, classification, clinical manifestations, diagnostic imaging tools, and treatment options of pericardial diseases in this population.
Topics: Heart; Hemodynamics; Humans; Incidence; Kidney; Kidney Failure, Chronic; Pericardial Effusion; Pericarditis, Constrictive; Prevalence; Risk Factors; Treatment Outcome; Uremia
PubMed: 28873222
DOI: 10.1002/clc.22770 -
The Journal of International Medical... Nov 2020Chronic massive pericardial effusion without cardiac tamponade is relatively rare. Nearly half of all patients with chronic large pericardial effusion are asymptomatic.... (Review)
Review
Chronic massive pericardial effusion without cardiac tamponade is relatively rare. Nearly half of all patients with chronic large pericardial effusion are asymptomatic. We report a case of a 77-year-old man who presented with an asymptomatic chronic massive pericardial effusion, with no evidence of cardiac tamponade or pericardial constriction during a 10-year follow-up. The patient had a complex history of lymph node tuberculosis, hypertension, hypothyroidism, and polycythemia vera, as well as high-dose P radiation exposure 45 years ago. There was no evidence of tuberculosis infection, hypothyroidism, malignant tumor, severe heart failure, uremia, trauma, severe bacterial or fungal infection, chronic myeloid leukemia, or bone marrow fibrosis after admission. The patient underwent pericardiocentesis twice. The pericardial effusion comprised exudate fluid with a high proportion of monocytes. The patient refused indwelling catheter drainage or pericardiectomy. The likely final diagnosis was recurrent chronic large idiopathic pericardial effusion.
Topics: Aged; Cardiac Tamponade; Humans; Male; Pericardial Effusion; Pericardiectomy; Pericardiocentesis; Pericarditis
PubMed: 33233991
DOI: 10.1177/0300060520973091 -
Brazilian Journal of Cardiovascular... May 2023The mainstay of the treatment of constrictive pericarditis is pericardiectomy. However, surgery is associated with high early morbidity and mortality and low long-term...
INTRODUCTION
The mainstay of the treatment of constrictive pericarditis is pericardiectomy. However, surgery is associated with high early morbidity and mortality and low long-term survival. The aim of this study is to describe our series of pericardiectomies performed over 30 years.
METHODS
A descriptive, observational, and retrospective analysis of all pericardiectomies performed at the Institute of Cardiology and Cardiovascular Surgery of the Favaloro Foundation was performed.
RESULTS
A total of 45 patients underwent pericardiectomy between June 1992 and June 2022, mean age was 52 years (standard deviation ± 13.9 years), and 73.3% were men. Idiopathic constrictive pericarditis was the most prevalent (46.6%). The variables significantly associated with prolonged hospitalization were preoperative advanced functional class (incidence of 38.4%, P<0.04), persistent pleural effusion (incidence of 81.8%, P<0.01), and although there was no statistical significance with the use of cardiopulmonary bypass, a trend in this association is evident (P<0.07). We found that 100% of the patients with an onset of symptoms greater than six months had a prolonged hospital stay. In-hospital mortality was 6.6%, and 30-day mortality was 8.8%. The preserved functional class is 17 times more likely to improve their symptomatology after pericardiectomy (odds ratio 17, 95% confidence interval 2.66-71; P<0.05).
CONCLUSION
Advanced functional class at the time of pericardiectomy is the variable most strongly associated with mortality and prolonged hospitalization. Onset of the symptoms greater than six months is also a poor prognostic factor mainly associated with prolonged hospitalization; based on these data, we strongly support the recommendation of early intervention.
Topics: Male; Humans; Middle Aged; Female; Pericarditis, Constrictive; Retrospective Studies; Pericardiectomy; Morbidity; Time Factors; Treatment Outcome
PubMed: 36692052
DOI: 10.21470/1678-9741-2022-0302 -
Heart Asia 2018A 32-year-old woman with no other medical history presented with 1-month history of fever, weight loss and dyspnoea. On examination she had elevated jugular venous...
CASE PRESENTATION
A 32-year-old woman with no other medical history presented with 1-month history of fever, weight loss and dyspnoea. On examination she had elevated jugular venous pressure and tachycardia. Her chest X-ray posterioranterior view (figure 1A) showed a rounded mass in the right cardiophrenic angle obscuring the right atrial margin, producing a 'silhouette' sign. Echocardiography showed a large cystic mass with thickened pericardium, lateral to the right atrium, causing right atrial compression (figure 1B). CT image of the chest showed a cystic lesion compressing the right atrium with thickened pericardium (figure 2A). There were no other lesions found in the lungs or other organs. Laboratory tests showed elevated erythrocyte sedimentation rate (ESR: 96 mm/hour) and C reactive protein (CRP: 32 mg/L). Excision of the mass with partial pericardiectomy was done. Intraoperatively, there was a cyst with thickened pericardial wall and thick yellowish brown fluid. Histopathology of the tissue is shown in figure 2B.Figure 1(A) Chest X-ray posterioranterior view showing a rounded mass in the right cardiophrenic angle. (B) Transthoracic echocardiography apical four-chamber view showing the cystic mass.Figure 2(A) CT of the chest sagittal view showing cystic lesion compressing the right atrium with thickened pericardium. (B) Histopathology specimen of the pericardial tissue.
QUESTION
What is the diagnosis and what should be the management strategy?Congenital pericardial cyst and no further evaluation required.Features are suggestive of tuberculous pericardial cyst and needs treatment with antituberculosis regimen.Features suggestive of pericardial hydatid cyst and requires treatment with albendazole.Features are suggestive of viral pericarditis with encysted effusion.
PubMed: 30116306
DOI: 10.1136/heartasia-2018-011071 -
Texas Heart Institute Journal Apr 2017Constrictive pericarditis is the final stage of a chronic inflammatory process characterized by fibrous thickening and calcification of the pericardium that impairs... (Review)
Review
Constrictive pericarditis is the final stage of a chronic inflammatory process characterized by fibrous thickening and calcification of the pericardium that impairs diastolic filling, reduces cardiac output, and ultimately leads to heart failure. Transthoracic echocardiography, computed tomography, and cardiac magnetic resonance imaging each can reveal severe diastolic dysfunction and increased pericardial thickness. Cardiac catheterization can help to confirm a diagnosis of diastolic dysfunction secondary to pericardial constriction, and to exclude restrictive cardiomyopathy. Early pericardiectomy with complete decortication (if technically feasible) provides good symptomatic relief and is the treatment of choice for constrictive pericarditis, before severe constriction and myocardial atrophy occur. We describe our surgical approach to constrictive pericarditis, summarize our results in 93 patients, and provide a brief overview of the literature.
Topics: Cardiac Catheterization; Humans; Pericardiectomy; Pericarditis, Constrictive; Predictive Value of Tests; Recovery of Function; Treatment Outcome; Ventricular Function
PubMed: 28461794
DOI: 10.14503/THIJ-16-5772 -
JTCVS Open Jun 2022
PubMed: 36004268
DOI: 10.1016/j.xjon.2022.04.039 -
Colombia Medica (Cali, Colombia) Apr 2021Definitive management of hemodynamically stable patients with penetrating cardiac injuries remains controversial between those who propose aggressive invasive care... (Review)
Review
Definitive management of hemodynamically stable patients with penetrating cardiac injuries remains controversial between those who propose aggressive invasive care versus those who opt for a less invasive or non-operative approach. This controversy even extends to cases of hemodynamically unstable patients in which damage control surgery is thought to be useful and effective. The aim of this article is to delineate our experience in the surgical management of penetrating cardiac injuries via the creation of a clear and practical algorithm that includes basic principles of damage control surgery. We recommend that all patients with precordial penetrating injuries undergo trans-thoracic ultrasound screening as an integral component of their initial evaluation. In those patients who arrive hemodynamically stable but have a positive ultrasound, a pericardial window with lavage and drainage should follow. We want to emphasize the importance of the pericardial lavage and drainage in the surgical management algorithm of these patients. Before this concept, all positive pericardial windows ended up in an open chest exploration. With the coming of the pericardial lavage and drainage procedure, the reported literature and our experience have shown that 25% of positive pericardial windows do not benefit and/or require further invasive procedures. However, in hemodynamically unstable patients, damage control surgery may still be required to control ongoing bleeding. For this purpose, we propose a surgical management algorithm that includes all of these essential clinical aspects in the care of these patients.
Topics: Algorithms; Colombia; Drainage; Heart Injuries; Hemorrhage; Hemostatic Techniques; Humans; Medical Illustration; Pericardial Window Techniques; Postoperative Complications; Therapeutic Irrigation; Ultrasonography; Wounds, Penetrating
PubMed: 34188321
DOI: 10.25100/cm.v52i2.4519