Nr4a1-dependent Ly6C(low) monocytes monitor endothelial cells and orchestrate their disposal.

The functions of Nr4a1-dependent Ly6C(low) monocytes remain enigmatic. We show that they are enriched within capillaries and scavenge microparticles from their lumenal side in a steady state. In the kidney cortex, perturbation of homeostasis by a TLR7-dependent nucleic acid "danger" signal, which may signify viral infection or local cell death, triggers Gαi-dependent intravascular retention of Ly6C(low) monocytes by the endothelium. Then, monocytes recruit neutrophils in a TLR7-dependent manner to mediate focal necrosis of endothelial cells, whereas the monocytes remove cellular debris. Prevention of Ly6C(low) monocyte development, crawling, or retention in Nr4a1(-/-), Itgal(-/-), and Tlr7(host-/-BM+/+) and Cx3cr1(-/-) mice, respectively, abolished neutrophil recruitment and endothelial killing. Prevention of neutrophil recruitment in Tlr7(host+/+BM-/-) mice or by neutrophil depletion also abolished endothelial cell necrosis. Therefore, Ly6C(low) monocytes are intravascular housekeepers that orchestrate the necrosis by neutrophils of endothelial cells that signal a local threat sensed via TLR7 followed by the in situ phagocytosis of cellular debris.

Transcription factor Nr4a1 couples sympathetic and inflammatory cues in CNS-recruited macrophages to limit neuroinflammation.

The molecular mechanisms that link the sympathetic stress response and inflammation remain obscure. Here we found that the transcription factor Nr4a1 regulated the production of norepinephrine (NE) in macrophages and thereby limited experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis. Lack of Nr4a1 in myeloid cells led to enhanced NE production, accelerated infiltration of leukocytes into the central nervous system (CNS) and disease exacerbation in vivo. In contrast, myeloid-specific deletion of tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis, protected mice against EAE. Furthermore, we found that Nr4a1 repressed autocrine NE production in macrophages by recruiting the corepressor CoREST to the Th promoter. Our data reveal a new role for macrophages in neuroinflammation and identify Nr4a1 as a key regulator of catecholamine production by macrophages.

Deleting an Nr4a1 Super-Enhancer Subdomain Ablates Ly6Clow Monocytes while Preserving Macrophage Gene Function.

Mononuclear phagocytes are a heterogeneous family that occupy all tissues and assume numerous roles to support tissue function and systemic homeostasis. Our ability to dissect the roles of individual subsets is limited by a lack of technologies that ablate gene function within specific mononuclear phagocyte sub-populations. Using Nr4a1-dependent Ly6Clow monocytes, we present a proof-of-principle approach that addresses these limitations. Combining ChIP-seq and molecular approaches we identified a single, conserved, sub-domain within the Nr4a1 enhancer that was essential for Ly6Clow monocyte development. Mice lacking this enhancer lacked Ly6Clow monocytes but retained Nr4a1 gene expression in macrophages during steady state and in response to LPS. Because Nr4a1 regulates inflammatory gene expression and differentiation of Ly6Clow monocytes, decoupling these processes allows Ly6Clow monocytes to be studied independently.

The transcription factor NR4A1 (Nur77) controls bone marrow differentiation and the survival of Ly6C- monocytes.

The transcription factors that regulate differentiation into the monocyte subset in bone marrow have not yet been identified. Here we found that the orphan nuclear receptor NR4A1 controlled the differentiation of Ly6C- monocytes. Ly6C- monocytes, which function in a surveillance role in circulation, were absent from Nr4a1-/- mice. Normal numbers of myeloid progenitor cells were present in Nr4a1-/- mice, which indicated that the defect occurred during later stages of monocyte development. The defect was cell intrinsic, as wild-type mice that received bone marrow from Nr4a1-/- mice developed fewer patrolling monocytes than did recipients of wild-type bone marrow. The Ly6C- monocytes remaining in the bone marrow of Nr4a1-/- mice were arrested in S phase of the cell cycle and underwent apoptosis. Thus, NR4A1 functions as a master regulator of the differentiation and survival of 'patrolling' Ly6C- monocytes.

A machine-learning model that incorporates CD45 surface expression predicts hematopoietic progenitor cell recovery after freeze-thaw.

BACKGROUND AIMS: Sufficient doses of viable CD34+ (vCD34) hematopoietic progenitor cells (HPCs) are crucial for engraftment. Additional-day apheresis collections can compensate for potential loss during cryopreservation but incur high cost and additional risk. To aid predicting such losses for clinical decision support, we developed a machine-learning model using variables obtainable on the day of collection. METHODS: In total, 370 consecutive autologous HPCs, apheresis-collected since 2014 at the Children's Hospital of Philadelphia, were retrospectively reviewed. Flow cytometry was used to assess vCD34% on fresh products and thawed quality control vials. The ratio of vCD34% thawed to fresh, which we call "post-thaw index," was used as an outcome measure, with a "poor" post-thaw index defined as <70%. HPC CD45 normalized mean fluorescence intensity (MFI) was calculated by dividing CD45 MFI of HPCs to the CD45 MFI of lymphocytes in the same sample. We trained XGBoost, k-nearest neighbor and random forest models for the prediction and calibrated the best model to minimize falsely-reassuring predictions. RESULTS: In total, 63 of 370 (17%) products had a poor post-thaw index. The best model was XGBoost, with an area under the receiver operator curve of 0.83 evaluated on an independent test data set. The most important predictor for a poor post-thaw index was the HPC CD45 normalized MFI. Transplants after 2015, based on the lower of the two vCD34% values, showed faster engraftment than older transplants, which were based on fresh vCD34% only (average 10.6 vs 11.7 days, P = 0.0006). CONCLUSIONS: Transplants taking into account post-thaw vCD34% improved engraftment time in our patients; however, it came at the cost of unnecessary multi-day collections. The results from applying our predictive algorithm retrospectively to our data suggest that more than one-third of additional-day collections could have been avoided. Our investigation also identified CD45 nMFI as a novel marker for assessing HPC health post-thaw.

Paediatric In-hospital cardiopulmonary resuscitation quality and outcomes in children with CHD during nights and weekends.

BACKGROUND: Survival after paediatric in-hospital cardiac arrest is worse on nights and weekends without demonstration of disparity in cardiopulmonary resuscitation quality. It is unknown whether these findings differ in children with CHD. This study aimed to determine whether cardiopulmonary resuscitation quality might explain the hypothesised worse outcomes of children with CHD during nights and weekends. METHODS: In-hospital cardiac arrest data collected by the Pediatric Resuscitation Quality Collaborative for children with CHD. Chest compression quality metrics and survival outcomes were compared between events that occurred during day versus night, and during weekday versus weekend using multivariable logistic regression. RESULTS: We evaluated 3614 sixty-second epochs of chest compression data from 132 subjects between 2015 and 2020. There was no difference in chest compression quality metrics during day versus night or weekday versus weekend. Weekday versus weekend was associated with improved survival to hospital discharge (adjusted odds ratio 4.56 [1.29,16.11]; p = 0.02] and survival to hospital discharge with favourable neurological outcomes (adjusted odds ratio 6.35 [1.36,29.6]; p = 0.02), but no difference with rate of return of spontaneous circulation or return of circulation. There was no difference in outcomes for day versus night. CONCLUSION: For children with CHD and in-hospital cardiac arrest, there was no difference in chest compression quality metrics by time of day or day of week. Although there was no difference in outcomes for events during days versus nights, there was improved survival to hospital discharge and survival to hospital discharge with favourable neurological outcome for events occurring on weekdays compared to weekends.

Serial Neurologic Assessment in Pediatrics (SNAP): A New Tool for Bedside Neurologic Assessment of Critically Ill Children.

OBJECTIVES: We developed a tool, Serial Neurologic Assessment in Pediatrics, to screen for neurologic changes in patients, including those who are intubated, are sedated, and/or have developmental disabilities. Our aims were to: 1) determine protocol adherence when performing Serial Neurologic Assessment in Pediatrics, 2) determine the interrater reliability between nurses, and 3) assess the feasibility and acceptability of using Serial Neurologic Assessment in Pediatrics compared with the Glasgow Coma Scale. DESIGN: Mixed-methods, observational cohort. SETTING: Pediatric and neonatal ICUs. SUBJECTS: Critical care nurses and patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Serial Neurologic Assessment in Pediatrics assesses Mental Status, Cranial Nerves, Communication, and Motor Function, with scales for children less than 6 months, greater than or equal to 6 months to less than 2 years, and greater than or equal to 2 years old. We assessed protocol adherence with standardized observations. We assessed the interrater reliability of independent Serial Neurologic Assessment in Pediatrics assessments between pairs of trained nurses by percent- and bias- adjusted kappa and percent agreement. Semistructured interviews with nurses evaluated acceptability and feasibility after nurses used Serial Neurologic Assessment in Pediatrics concurrently with Glasgow Coma Scale during routine care. Ninety-eight percent of nurses (43/44) had 100% protocol adherence on the standardized checklist. Forty-three nurses performed 387 paired Serial Neurologic Assessment in Pediatrics assessments (149 < 6 mo; 91 ≥ 6 mo to < 2 yr, and 147 ≥ 2 yr) on 299 patients. Interrater reliability was substantial to near-perfect across all components for each age-based Serial Neurologic Assessment in Pediatrics scale. Percent agreement was independent of developmental disabilities for all Serial Neurologic Assessment in Pediatrics components except Mental Status and lower extremity Motor Function for patients deemed "Able to Participate" with the assessment. Nurses reported that they felt Serial Neurologic Assessment in Pediatrics, compared with Glasgow Coma Scale, was easier to use and clearer in describing the neurologic status of patients who were intubated, were sedated, and/or had developmental disabilities. About 92% of nurses preferred to use Serial Neurologic Assessment in Pediatrics over Glasgow Coma Scale. CONCLUSIONS: When used by critical care nurses, Serial Neurologic Assessment in Pediatrics has excellent protocol adherence, substantial to near-perfect interrater reliability, and is feasible to implement. Further work will determine the sensitivity and specificity for detecting clinically meaningful neurologic decline.

Antibody Fragment F(ab')2 Targeting Caveolae-Associated Protein PV1 for Selective Kidney Targeting and Retention.

Targeted strategies to deliver and retain drugs to kidneys are needed to improve drug accumulation and efficacy in a myriad of kidney diseases. These drug delivery systems show potential for improving the therapeutic windows of drugs acting in the kidney. Biodistribution of antibody-based therapeutics in vivo is governed by several factors including binding affinity, size, and valency. Investigations of how the biophysical and biochemical properties of biologics enable them to overcome biological barriers and reach kidneys are therefore of interest. Although renal accumulation of antibody fragments in cancer diagnostics and treatment has been observed, reports on effective delivery of antibody fragments to the kidneys remain scarce. Previously, we demonstrated that targeting plasmalemma vesicle-associated protein (PV1), a caveolae-associated protein, can promote accumulation of antibodies in both the lungs and the kidneys. Here, by fine-tuning the binding affinity of an antibody toward PV1, we observe that the anti-PV1 antibody with reduced binding affinity lost the capability for kidney targeting while retaining the lung targeting activity, suggesting that binding affinity is a critical factor for kidney targeting of the anti-PV1 antibody. We next use the antibody fragment F(ab')2 targeting PV1 to assess the dual effects of rapid kidney filtration and PV1 targeting on kidney-selective targeting. Ex vivo fluorescence imaging results demonstrated that after rapidly accumulating in kidneys at 4 h, PV1-targeted F(ab')2 was continually retained in the kidney at 24 h, whereas the isotype control F(ab')2 underwent urinary elimination with significantly reduced signaling in the kidney. Confocal imaging studies confirmed the localization of PV1-targeted F(ab')2 in the kidney. In addition, the monovalent antibody fragment (Fab-C4) lost the capability for kidney homing, indicating that the binding avidity of anti-PV1 F(ab')2 is important for kidney targeting. Our findings suggest that PV1-targeted F(ab')2 might be useful as a drug carrier for renal targeting and highlight the importance of affinity optimization for tissue targeting antibodies.

Low-density granulocytes activate T cells and demonstrate a non-suppressive role in systemic lupus erythematosus.

OBJECTIVES: The presence of proinflammatory low-density granulocytes (LDG) has been demonstrated in autoimmune and infectious diseases. Recently, regulatory neutrophilic polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC) were identified in systemic lupus erythematosus (SLE). Because LDG and PMN-MDSC share a similar phenotype with contrasting functional effects, we explored these cells in a cohort of patients with SLE. METHODS: LDG and normal-density granulocytes (NDG) were isolated from fresh blood of healthy donors (HD) and patients with SLE. Associations between LDG and clinical manifestations were analysed. Multicolor flow cytometry and confocal imaging were performed to immunophenotype the cells. The ability of LDG and NDG to suppress T cell function and induce cytokine production was quantified. RESULTS: LDG prevalence was elevated in SLE versus HD, associated with the interferon (IFN) 21-gene signature and disease activity. Also, the LDG-to-lymphocyte ratio associated better with SLE disease activity index than neutrophil-to-lymphocyte ratio. SLE LDG exhibited significantly heightened surface expression of various activation markers and also of lectin-like oxidised low-density lipoprotein receptor-1, previously described to be associated with PMN-MDSC. Supernatants from SLE LDG did not restrict HD CD4+ T cell proliferation in an arginase-dependent manner, suggesting LDG are not immunosuppressive. SLE LDG supernatants induced proinflammatory cytokine production (IFN gamma, tumour necrosis factor alpha and lymphotoxin alpha) from CD4+ T cells. CONCLUSIONS: Based on our results, SLE LDG display an activated phenotype, exert proinflammatory effects on T cells and do not exhibit MDSC function. These results support the concept that LDG represent a distinct proinflammatory subset in SLE with pathogenic potential, at least in part, through their ability to activate type 1 helper responses.

Nonclassical patrolling monocyte function in the vasculature.

Nonclassical patrolling monocytes are characterized by their unique ability to actively patrol the vascular endothelium under homeostatic and inflammatory conditions. Patrolling monocyte subsets (CX3CR1(high)Ly6C(-) in mouse and CX3CR1(high)CD14(dim)CD16(+) in humans) are distinct from the classical monocyte subsets (CCR2(high)Ly6C(+) in mouse and CCR2(high)CD14(+)CD16(-) in humans) and exhibit unique functions in the vasculature and inflammatory disease. Patrolling monocytes function in several disease settings to remove damaged cells and debris from the vasculature and have been associated with wound healing and the resolution of inflammation in damaged tissues. This review highlights the unique functions of these patrolling monocytes in the vasculature and during inflammation.

Molecular imaging of the paracrine proangiogenic effects of progenitor cell therapy in limb ischemia.

BACKGROUND: Stem cells are thought to enhance vascular remodeling in ischemic tissue in part through paracrine effects. Using molecular imaging, we tested the hypothesis that treatment of limb ischemia with multipotential adult progenitor cells (MAPCs) promotes recovery of blood flow through the recruitment of proangiogenic monocytes. METHODS AND RESULTS: Hind-limb ischemia was produced in mice by iliac artery ligation, and MAPCs were administered intramuscularly on day 1. Optical imaging of luciferase-transfected MAPCs indicated that cells survived for 1 week. Contrast-enhanced ultrasound on days 3, 7, and 21 showed a more complete recovery of blood flow and greater expansion of microvascular blood volume in MAPC-treated mice than in controls. Fluorescent microangiography demonstrated more complete distribution of flow to microvascular units in MAPC-treated mice. On ultrasound molecular imaging, expression of endothelial P-selectin and intravascular recruitment of CX(3)CR-1-positive monocytes were significantly higher in MAPC-treated mice than in the control groups at days 3 and 7 after arterial ligation. Muscle immunohistology showed a >10-fold-greater infiltration of monocytes in MAPC-treated than control-treated ischemic limbs at all time points. Intravital microscopy of ischemic or tumor necrosis factor-α-treated cremaster muscle demonstrated that MAPCs migrate to perimicrovascular locations and potentiate selectin-dependent leukocyte rolling. In vitro migration of human CD14(+) monocytes was 10-fold greater in response to MAPC-conditioned than basal media. CONCLUSIONS: In limb ischemia, MAPCs stimulate the recruitment of proangiogenic monocytes through endothelial activation and enhanced chemotaxis. These responses are sustained beyond the MAPC lifespan, suggesting that paracrine effects promote flow recovery by rebalancing the immune response toward a more regenerative phenotype.

NR4A1 (Nur77) deletion polarizes macrophages toward an inflammatory phenotype and increases atherosclerosis.

RATIONALE: NR4A1 (Nur77) is a nuclear receptor that is expressed in macrophages and within atherosclerotic lesions, yet its function in atherosclerosis is unknown. OBJECTIVE: Nur77 regulates the development of monocytes, particularly patrolling Ly6C(-) monocytes that may be involved in resolution of inflammation. We sought to determine how absence of nuclear receptor subfamily 4, group A, member 1 (NR4A1) in hematopoietic cells affected atherosclerosis development. METHODS AND RESULTS: Nur77(-/-) chimeric mice on a Ldlr(-/-) background showed a 3-fold increase in atherosclerosis development when fed a Western diet for 20 weeks, despite having a drastic reduction in Ly6C(-) patrolling monocytes. In a second model, mice deficient in both Nur77 and ApoE (ApoE(-/-)Nur77(-/-)) also showed increased atherosclerosis after 11 weeks of Western diet. Atherosclerosis was associated with a significant change in macrophage polarization toward a proinflammatory phenotype, with high expression of tumor necrosis factor-α and nitric oxide and low expression of Arginase-I. Moreover, we found increased expression of toll-like receptor 4 mRNA and protein in Nur77(-/-) macrophages as well as increased phosphorylation of the p65 subunit of NFκB. Inhibition of NFκB activity blocked excess activation of Nur77(-/-) macrophages. CONCLUSIONS: We conclude that the absence of Nur77 in monocytes and macrophages results in enhanced toll-like receptor signaling and polarization of macrophages toward a proinflammatory M1 phenotype. Despite having fewer monocytes, Nur77(-/-) mice developed significant atherosclerosis when fed a Western diet. These studies indicate that Nur77 is a novel target for modulating the inflammatory phenotype of monocytes and macrophages and may be important for regulation of atherogenesis.

NR4A nuclear receptors in immunity and atherosclerosis.

PURPOSE OF REVIEW: To understand chronic inflammatory diseases such as atherosclerosis, we require in-depth knowledge on immune-cell differentiation, function of specific immune-cell subsets and endothelial cell-mediated extravasation. In this review, we summarize a number of very recent observations on the pivotal function of NR4A nuclear receptors in immunity and atherosclerosis. RECENT FINDINGS: NR4A nuclear receptors are involved in negative selection of thymocytes, Treg differentiation and the development of Ly6C monocytes. Nur77 and Nurr1 attenuate atherosclerosis in mice whereas NOR-1 aggravates vascular lesion formation. SUMMARY: These exciting, novel insights on the function of NR4A nuclear receptors in immunity, vascular cells and atherosclerosis will initiate a plethora of studies to understand the underlying molecular mechanisms, which will culminate in the identification of novel NR4A targets to modulate chronic inflammatory disease.

Ideal Cardiovascular Health and Risk of Cardiovascular Events or Mortality: A Systematic Review and Meta-Analysis of Prospective Studies.

Cardiovascular diseases (CVD) remain the leading cause of morbidity and mortality worldwide, hence significant efforts have been made to establish behavior and risk factors associated with CVD. The American Heart Association proposed a 7-metric tool to promote ideal cardiovascular health (CVH). Recent data demonstrated that a higher number of ideal CVH metrics was associated with a lower risk of CVD, stroke, and mortality. Our study aimed to perform a systematic review and meta-analysis of prospective studies investigating the association of ideal CVH metrics and CVD, stroke, and cardiovascular mortality (CVM) in the general population. Medline and Scopus databases were searched from January 2010 to June 2022 for prospective studies reporting CVH metrics and outcomes on composite-CVD, coronary heart disease, myocardial infarction, stroke, and CVM. Each CVH metrics group was compared to another. Twenty-two studies totaling 3,240,660 adults (57.8% men) were analyzed. The follow-up duration was 12.0 ± 7.2 years. Our analysis confirmed that a higher number of ideal CVH metrics led to lower risk for CVD and CVM (statistically significant for composite-CVD, stroke, and CVM; p < 0.05). Conclusion: Even modest improvements in CVH are associated with CV-morbidity and mortality benefits, providing a strong public health message about the importance of a healthier lifestyle.

Amiodarone Pharmacovigilance Through an Intelligent Electronic Health Record Application.

BACKGROUND: Amiodarone is the most effective and commonly used antiarrhythmic medication. Given its risk of toxicity, routine monitoring is recommended but is challenging to ensure in clinical practice. METHODS: We created an intelligent application, built within our electronic health record, that identified every living patient with an active outpatient prescription by a clinician in our health system. The application was designed to identify patients with lapses in recommended monitoring and facilitate scheduling of overdue testing. RESULTS: The percentage of patients with overdue monitoring tests decreased with use of the application, with greatest improvement in pulmonary function testing. DISCUSSION: Implementing a program to monitor and mitigate adverse reactions to amiodarone by using programable features of an electronic health record is feasible.

Automation of Hematopoietic Cell Transplantation Outcomes Reporting Leads to Dramatic Reduction in Errors Reported to Real-World Data Registry.

Institutions that perform hematopoietic cell transplantation (HCT) are required by law to report standardized, structured data on transplantation outcomes. A key post-transplantation outcome is engraftment, the time between HCT infusion and reemergence of circulating neutrophils and platelets. At our center, we found that manual chart abstraction for engraftment data was highly error-prone. We developed a custom R/Shiny application that automatically calculates engraftment dates and displays them in an intuitive format to augment the manual chart review. Our hypothesis was that use of the application to assist with calculating and reporting engraftment dates would be associated with a decreased error rate. The study was conducted at a single tertiary care institution. The application was developed in a collaborative, multidisciplinary fashion by members of an embedded cellular therapy informatics team. Retrospective validation of the application's accuracy was conducted on all malignant HCTs from February 2016 to December 2020 (n = 198). Real-world use of the application was evaluated prospectively from April 2021 through April 2022 (n = 53). The Welch 2-sample t test was used to compare error rates preimplementation and postimplementation. Data were visualized using p charts, and standard special cause variation rules were applied. The accuracy of reported data postdeployment increased dramatically; the engraftment error rate decreased from 15% to 3.8% for neutrophils (P = .003) and from 28% to 1.9% for platelets (P < .001). This study demonstrates the effective deployment of a custom R/Shiny application that was associated with significantly reduced error rates in HCT engraftment reporting for operational, research, and regulatory purposes. Users reported subjective satisfaction with the application and that it addressed difficulties with the legacy manual process. Identifying and correcting erroneous data in engraftment reporting could lead to a more efficient and accurate nationwide assessment of transplantation success. Furthermore, we show that it is possible and practical for academic medical centers to create and support embedded informatics teams that can quickly build applications for clinical operations in a manner compliant with regulatory requirements.

Bioprosthetic Aortic Valve Thrombosis and Literature Review.

An 83-year-old gentleman with a history of 23-mm Hancock-II-bioprosthetic aortic valve (BAV) replacement ten-years prior presented with symptoms of dyspnea and lower extremity edema. During the preceding seven-years, he had been noted to have asymptomatic increased mean transvalvular gradients (MG; 36-50 mmHg) felt to be due to either early bioprosthetic degeneration, pannus formation, or patient-prosthesis mismatch. An echocardiogram at the time of symptom development demonstrated significant flow acceleration through the aortic valve, mild regurgitation, and severely increased MG (48 mmHg) with prolonged acceleration time (AT, 140 msec). A trial of warfarin anticoagulation resulted in dramatic improvement after only 6 weeks with laminar flow through the AV, near-total resolution of regurgitation, and a decrease in MG to 14 mmHg and AT to 114 msec. These findings strongly suggest that BAV thrombosis was the predominant mechanism responsible for the longstanding high MG. Our case highlights that BAV thrombosis should be considered in the differential of elevated gradients regardless of the age of prosthesis, and that a trial of warfarin anticoagulation may be beneficial even if elevated gradients have been present for a prolonged period. Valvular gradients are often abnormal long before a formal diagnosis; however, these may reverse quickly with anticoagulation therapy.

Fulminant Influenza A Myocarditis Complicated by Transient Ventricular Wall Thickening and Cardiac Tamponade.

Myocarditis is an infrequent complication of influenza infection that is most often diagnosed clinically in the setting of confirmed influenza infection and elevated cardiac enzymes. Pericarditis can also occur in cases of influenza myocarditis and may require pericardiocentesis for tamponade. Patients with fulminant myocarditis have cardiogenic shock; however, echocardiographic findings may be subtle, showing a preserved ejection fraction and diffuse left ventricular wall thickening (compared to baseline) due to inflammatory edema. Recognizing these echocardiographic findings in the appropriate clinical setting facilitates the early recognition of fulminant myocarditis. Therefore, we report a case of fulminant influenza A myocarditis in healthy 37-year-old women complicated by transient left ventricular wall thickening and tamponade, highlighting the importance of early diagnosis and supportive management for a successful outcome.

Influenza Myopericarditis and Pericarditis: A Literature Review.

Myopericarditis is a rare complication of influenza infection. The presentation may range from mild and frequently unrecognized, to fulminant and potentially complicated by cardiogenic and/or obstructive shock (tamponade), which is associated with high mortality. We performed a review of literature on all influenza pericarditis and myopericarditis cases according to PRISMA guidelines using the PubMed search engine of the Medline database. Seventy-five cases of influenza myopericarditis and isolated pericarditis were identified from 1951 to 2021. Influenza A was reported twice as often as influenza B; however, influenza type did not correlate with outcome. Men and elderly patients were more likely to have isolated pericarditis, while women and younger patients were more likely to have myopericarditis. All included patients had pericardial effusion, while 36% had tamponade. Tamponade was more common in those with isolated pericarditis (41.2%) than myopericarditis (13.8%). Cardiogenic shock was more common in patients with myopericarditis (64%), with an overall mortality rate of 14.7%. Nearly 88% of the recovered patients remained without long-term complications reported. Conclusion: Influenza A appears a more common cause of pericarditis and myopericarditis. Isolated pericarditis was more commonly associated with tamponade but without reported deaths, whereas myopericarditis was more commonly associated with cardiogenic shock and death (19%).

Community-associated Methicillin-resistant Staphylococcus aureus pericarditis in an immunocompetent patient.

Background: Pericarditis caused by Methicillin-resistant Staphylococcus aureus (MRSA) is a rare infection, often seen in patients with chronic kidney disease, immunosuppression, or previous pericardial disease. The presentation can be dramatic with acute illness leading to septic and/or obstructive shock due to pericardial tamponade. Occasionally disease can have a more protracted, indolent, subacute clinical course. Case report: We report a case of a 57-year-old male patient with a previous history of smoking and moderate alcohol use who presented with progressive dyspnea and cough. He was found to have a disseminated MRSA infection with pericarditis complicated by pericardial tamponade. Urgent pericardiocentesis yielded 1.1 liters of purulent fluid that grew MRSA. MRSA was also isolated from the blood and pleural fluid. The patient underwent left thoracotomy, decortication, and pericardial window and completed 3 weeks of intravenous vancomycin therapy, concluding in an excellent outcome. Conclusion: Bacterial pericarditis is an exceptionally rare form of pericarditis which been traditionally associated with chronic medical conditions requiring a prolonged healthcare stay. However, it has lately been observed in healthy individuals with social habits such as smoking and alcohol consumption. Bacterial pericarditis must be recognized in a timely fashion and managed aggressively to prevent a devastating outcome. A multidisciplinary approach is advised, which includes a combination of pericardial drainage and aggressive antibiotic therapy. Such treatment often yields a positive outcome and good long-term prognosis.