Single-Cell Analysis Reveals a Subset of High IL-12p40-Secreting Dendritic Cells within Mouse Bone Marrow-Derived Macrophages Differentiated with M-CSF.

Macrophages and dendritic cells (DCs), although ontogenetically distinct, have overlapping functions and exhibit substantial cell-to-cell heterogeneity that can complicate their identification and obscure innate immune function. In this study, we report that M-CSF-differentiated murine bone marrow-derived macrophages (BMDMs) exhibit extreme heterogeneity in the production of IL-12, a key proinflammatory cytokine linking innate and adaptive immunity. A microwell secretion assay revealed that a small fraction of BMDMs stimulated with LPS secrete most IL-12p40, and we confirmed that this is due to extremely high expression of Il12b, the gene encoding IL-12p40, in a subset of cells. Using an Il12b-YFP reporter mouse, we isolated cells with high LPS-induced Il12b expression and found that this subset was enriched for genes associated with the DC lineage. Single-cell RNA sequencing data confirmed a DC-like subset that differentiates within BMDM cultures that is transcriptionally distinct but could not be isolated by surface marker expression. Although not readily apparent in the resting state, upon LPS stimulation, this subset exhibited a typical DC-associated activation program that is distinct from LPS-induced stochastic BMDM cell-to-cell heterogeneity. Overall, our findings underscore the difficulty in distinguishing macrophages and DCs even in widely used in vitro murine BMDM cultures and could affect the interpretation of some studies that use BMDMs to explore acute inflammatory responses.

Outcomes of lower extremity peripheral arterial interventions in patients with and without chronic kidney disease or end-stage renal disease.

INTRODUCTION: Peripheral arterial disease (PAD) is a progressive vascular condition characterized by the narrowing or blockage of arteries, primarily attributed to atherosclerosis. PAD's prevalence in the general population is estimated at approximately 5.9%. Notably however, among patients with chronic kidney disease (CKD), PAD's prevalence is substantially higher, ranging from 17% to 48%. This review paper emphasizes the pervasiveness of PAD and its intricate relationship with CKD and end-stage renal disease (ESRD). It demonstrates the importance of early detection, proactive screening, and understanding the formidable challenges associated with treating heavily calcified lesions. EVIDENCE ACQUISITION: Comprehensive literature searches encompassed the PubMed/MEDLINE, Cochrane Library, and Embase databases, in order to identify studies involving lower extremity peripheral arterial interventions in patients both with and without CKD or ESRD. The search spanned the timeframe from January 2001 to July 2023. The search strategy included vocabulary terms concerning peripheral artery disease, lower extremities, revascularization, chronic kidney disease, and end-stage renal disease. EVIDENCE SYNTHESIS: Initial searches were used to identify articles based on title. Exclusion criteria was then applied, and any redundant articles were removed. The articles abstracts were then reviewed, and relevant articles were selected. Once selected the articles were thoroughly reviewed including the references to find other relevant articles that were missed during the initial search process. In total 28 articles were selected and included for review of clinical data in regard to PAD outcomes in patients with advanced kidney disease. CONCLUSIONS: The findings highlight the need for personalized approaches in diagnosing and treating PAD in CKD and ESRD patients. Interdisciplinary collaboration, such as those between nephrologists, vascular surgeons, and interventional radiologists, is vital to optimize outcomes. Further research should focus on innovative, tailored interventions to enhance limb preservation, reduce mortality, prolong patency, and cut healthcare costs.

3D Model of the Early Melanoma Microenvironment Captures Macrophage Transition into a Tumor-Promoting Phenotype.

Tumor immune response is shaped by the tumor microenvironment (TME), which often evolves to be immunosuppressive, promoting disease progression and metastasis. An important example is melanoma tumors, which display high numbers of tumor-associated macrophages (TAMs) that are immunosuppressive but also have the potential to restore anti-tumor activity. However, to therapeutically target TAMs, there is a need to understand the early events that shape their tumor-promoting profile. To address this, we built and optimized 3D in vitro co-culture systems, composed of a collagen-I matrix scaffolding murine bone-marrow-derived macrophages (BMDMs), YUMM1.7 melanoma cells, and fibroblasts to recreate the early melanoma TME and study how interactions with fibroblasts and tumor cells modulate macrophage immune activity. We monitored BMDM behavior and interactions through time-lapse imaging and characterized their activation and secretion. We found that stromal cells induced a rapid functional activation, with increased motility and response from BMDMs. Over the course of seven days, BMDMs acquired a phenotype and secretion profile that resembled melanoma TAMs in established tumors. Overall, the direct cell-cell interactions with the stromal components in a 3D environment shape BMDM transition to a TAM-like immunosuppressive state. Our systems will enable future studies of changes in macrophage-stromal cross-talk in the melanoma TME.

The Impact of Cardiology Consultation on Medical Intensive Care Unit Patients with Elevated Troponin Levels.

BACKGROUND: Cardiac troponin (cTn) is mainly used to diagnose acute coronary syndrome (ACS). However, cTn can also be elevated in critically ill patients secondary to demand ischemia or myocardial injury. The impact of cardiology consultation on the clinical outcomes of patients admitted to medical intensive care unit (ICU) with elevated cTn is unclear. METHODS: A retrospective analysis of medical ICU patients with elevated cTn without evidence of ACS between January 2013 through December 2018. Patients were stratified based on documentation of cardiology consultation. The primary outcome was 1-year mortality. Secondary outcomes were in-hospital and 30-day mortality, the length of stay (LOS), further cardiac testing, 30-day readmission rate, new prescription of cardiac medications, and the predictors of a cardiology consultation. RESULTS: Of 846 patients screened, 766 patients were included, of whom 63.2% had cardiology consultation. Cardiology consultation group had longer median LOS (7 vs. 5 days, P = 0.007), additional cardiac testing (90.3% vs. 67.7%, P < 0.001), and more new cardiac medications (52.1% vs. 16.3%, P < 0.001). No difference was noted in-hospital mortality (adjusted odds ratio [aOR], 0.6, 95% CI, 0.4-1.1, P = .117), 30-day mortality (aOR = 0.8, 95% CI, 0.5-1.4, P = .425), 1- year mortality (aOR, 1.4, 95% CI, 0.9-2.2, P = .193), or cardiac-specific 30-day readmission rate (aOR, 7.0, 95% CI, 0.7-14.9, P = .137). History of coronary artery disease (CAD) was the most independent predictor for a cardiology consult (aOR, 2.2, 95% CI, 1.3-3.8, P < .001). CONCLUSION: Cardiology consultation for elevated cTn in medical ICU patients was associated with increased cardiac testing and LOS, without significant impact on mortality.

Cell shape, and not 2D migration, predicts extracellular matrix-driven 3D cell invasion in breast cancer.

Metastasis, the leading cause of death in cancer patients, requires the invasion of tumor cells through the stroma in response to migratory cues, in part provided by the extracellular matrix (ECM). Recent advances in proteomics have led to the identification of hundreds of ECM proteins, which are more abundant in tumors relative to healthy tissue. Our goal was to develop a pipeline to easily predict which ECM proteins are more likely to have an effect on cancer invasion and metastasis. We evaluated the effect of four ECM proteins upregulated in breast tumor tissue in multiple human breast cancer cell lines in three assays. There was no linear relationship between cell adhesion to ECM proteins and ECM-driven 2D cell migration speed, persistence, or 3D invasion. We then used classifiers and partial-least squares regression analysis to identify which metrics best predicted ECM-driven 2D migration and 3D invasion responses. We find that ECM-driven 2D cell migration speed or persistence did not predict 3D invasion in response to the same cue. However, cell adhesion, and in particular cell elongation and shape irregularity, accurately predicted the magnitude of ECM-driven 2D migration and 3D invasion. Our models successfully predicted the effect of novel ECM proteins in a cell-line specific manner. Overall, our studies identify the cell morphological features that determine 3D invasion responses to individual ECM proteins. This platform will help provide insight into the functional role of ECM proteins abundant in tumor tissue and help prioritize strategies for targeting tumor-ECM interactions to treat metastasis.

A Transesophageal Echocardiogram Finding: From Infection to Malignancy.

Nonbacterial thrombotic endocarditis (NBTE) is illustrated by thrombi deposition on normal heart valves without the presence of bacteremia. It typically occurs in the setting of chronic debilitating diseases such as cancer or autoimmune disease. The pathogenesis involves an endothelial injury in the presence of a hypercoagulable state secondary to the effects of circulatory cytokines, which triggers platelet deposition. It usually forms on the upstream atrial surface of the mitral and tricuspid valves and the ventricular surface of the pulmonic and aortic valves and occurs most commonly in the fourth to eighth decades of life with no specific gender predisposition. These vegetations have a distinct morphology that varies from infective endocarditis (IE). Cerebrovascular lesions due to NBTE have a distinctive pattern of multiple, widely distributed small and large strokes on brain magnetic resonance imaging (MRI). We present a case of a 78-year-old man who was initially diagnosed as pneumonia and IE; he underwent a trans-esophageal echocardiogram (TEE), which revealed Libman-Sacks findings that have changed his diagnosis to lung cancer. We aim to highlight the characteristic TEE findings of NBTE to help clinicians search for underlying etiologies, including malignancies if NBTE is suspected.

Low-Risk Transcatheter Versus Surgical Aortic Valve Replacement - An Updated Meta-Analysis of Randomized Controlled Trials.

OBJECTIVES: To perform a meta-analysis including all available randomized controlled trials (RCTs) to date comparing transcatheter aortic valve replacement (TAVR) to surgical aortic valve replacement (SAVR) in patients with severe aortic stenosis (AS) and low surgical risk. BACKGROUND: Current guidelines recommend SAVR for patients with severe symptomatic AS and low surgical risk. A few RCTs have evaluated TAVR in low surgical risk patients but equipoise exists related to TAVR valve durability, paravalvular leak (PVL) and role of TAVR in younger, low surgical risk patients. METHODS: Five databases were analyzed from January-2000 to March-2019 for RCTs comparing SAVR to TAVR in low-risk severe AS patients. RESULTS: Four RCTs on low-risk TAVR patients with 2887 patients were included. Mean follow-up was ~24.1 ±â€¯24 months. Early mortality was lower with TAVR compared to SAVR (RR: 0.44, 95% CI: 0.20-0.95, P = 0.038) whereas long-term mortality was similar (RR: 0.67, 95% CI: 0.39-1.14, P = 0.141). Both early and long-term stroke rates were similar. TAVR was associated with lower risk of atrial fibrillation, major bleeding, acute kidney injury (AKI) and rehospitalization, but higher rates of permanent pacemaker implantation (PPM) and moderate or severe PVL. There was no difference in major vascular complications, myocardial infarction, endocarditis, aortic valve gradients and valve area at follow-up. CONCLUSIONS: In low-risk patients with severe AS, TAVR has a lower early mortality compared to SAVR with no difference in long-term mortality. Although complication rates varied between TAVR and SAVR, our study findings suggest that transfemoral-TAVR is an appropriate treatment option for severe symptomatic AS in patients with low surgical risk.

Marijuana-induced Coronary Vasospasm with Persistent Inter-coronary Connection: A Case Report and Review of Literature.

Coronary vasospasm is a well-known entity causing acute chest syndrome and can lead to myocardial infarction, ventricular arrhythmias, and even sudden cardiac death. While there are extensive case series showing the association of coronary vasospasm with cocaine, studies reporting marijuana-induced coronary vasospasm are limited in number. We herein present a case of coronary vasospasm in a middle-aged African-American male who presented to the emergency department after an episode of syncope. His urine drug screen was positive only for marijuana. He had a transient elevation of ST segments on his EKG with concomitant wall motion abnormalities on echocardiogram and was later found to have vasospasm of coronary arteries on coronary angiogram without any evidence of focal atherosclerotic disease. Another interesting finding was the persistent inter-coronary communication or coronary arcade connecting the left circumflex artery to the right coronary artery. There was bi-directional flow through the inter-coronary communication and hence, we believe this communication prevented our patient from experiencing acute chest symptoms or myocardial infarction. It is important for the clinicians to recognize the association of marijuana with coronary vasospasm. At the same time, these patients should be treated as acute coronary syndromes until proven otherwise by ischemia evaluation.

Human Herpesvirus-8 Negative Multicentric Castleman Disease in a Patient with Human Immunodeficiency Virus Treated with Highly Active Antiretroviral Therapy and Chemotherapy.

Multicentric Castleman disease (MCD) is a rare lymphoproliferative disorder with a high mortality rate in undiagnosed patients. Traditionally, human immunodeficiency virus (HIV) positive MCD occurs due to infection with human herpes virus-8 (HHV), which is thought to play a role in the pathogenesis of MCD. We present the case of a 49-year-old woman who was referred to our oncology clinic for generalized lymphadenopathy in a waxing and waning pattern for the last four years. She was found to be HIV positive. Here we report a rare case of HIV-positive, HHV-negative MCD that responded to prompt treatment with highly active antiretroviral therapy (HAART) followed by chemotherapy as evidenced by improved CD4+ T cell numbers and reduction in lymphadenopathy. The findings in this HHV seronegative patient may indicate an alteration in the virulence and tropism between HHV and HIV, and further demonstrate the need for continued investigation into the pathogenesis of Castleman disease.

Bivalirudin versus heparin in percutaneous coronary intervention-a systematic review and meta-analysis of randomized trials stratified by adjunctive glycoprotein IIb/IIIa strategy.

BACKGROUND: Bivalirudin has been shown to be associated with less major bleeding than heparin in patients undergoing percutaneous coronary intervention (PCI); but the confounding effect of concomitant glycoprotein IIb/IIIa inhibitors (GPI) limits meaningful comparison. We performed a systematic review and meta-analysis to compare bivalirudin to heparin, with and without adjunctive GPI in PCI. METHODS: We searched PubMed, Cochrane, EMBASE, CINAHL and WOS from January 2000 to December 2017 for clinical trials comparing bivalirudin to heparin, with and without adjunctive GPI during PCI. Cochrane's Q statistics were used to determine heterogeneity. Random effects model was used. RESULTS: Twenty-six comparison groups (22 original studies and 4 subgroup analyses) with 53,364 patients were included. Mean follow-up was 192±303 days. There was no difference between the two groups in all-cause mortality [risk ratio (RR: 0.93; 95% CI: 0.82-1.05, P=0.260), target vessel revascularization (TVR) (RR: 1.17; 95% CI: 0.93-1.46, P=0.174) or stroke (RR: 0.91; 95% CI: 0.71-1.18, P=0.490). Major bleeding was lower in the bivalirudin group with concomitant GPI in one or both arms (RR: 0.64; 95% CI: 0.53-0.77, P<0.001) and without (RR: 0.71; 95% CI: 0.51-0.99, P=0.041) provisional or routine GPIs. Bivalirudin appeared to have a higher risk of stent thrombosis (RR: 1.32; 95% CI: 1.04-1.68, P=0.022) and a trend towards more myocardial infarction (RR: 1.12; 95% CI: 0.98-1.28, P=0.098) though without statistical significance. However, exclusion of studies with GPI showed no difference in stent thrombosis or myocardial infarction with bivalirudin. CONCLUSIONS: Bivalirudin is associated with less major bleeding compared to heparin, regardless of GPI use. The lower anticoagulant effect of bivalirudin is linked with higher stent thrombosis and a trend towards more MI, however a confounding effect of GPI use in the heparin arm cannot be excluded.

Late-onset pulmonary arterial hypertension in repaired D-transposition of great arteries: an uncommon complication.

Late-onset pulmonary arterial hypertension (PAH) is a rare but fatal complication in patients with childhood surgical repair of dextro-transposition of great arteries (D-TGA), especially with the Mustard and Senning procedures. The pathogenic mechanisms of PAH in patients with repaired D-TGA are not well understood and treatment is not standardized. In this manuscript, we present a case of late-onset PAH in an adult D-TGA patient after Mustard repair and discuss the pathogenic mechanisms, diagnosis, and treatment of pulmonary hypertension in repaired D-TGA.

Ivabradine in the treatment of systolic heart failure - A systematic review and meta-analysis.

AIM: To perform a systematic-review and meta-analysis to compare outcomes of ivabradine combined with beta-blocker to beta-blocker alone in heart failure with reduced ejection fraction (HFrEF). METHODS: We searched PubMed, Cochrane, EMBASE, CINAHL and Web of Science for trials comparing ivabradine + beta-blocker to beta-blocker alone in HFrEF. We performed a systematic-review and meta-analysis of published literature. Primary end-point was combined end point of cardiac death and hospitalization for heart failure. RESULTS: Six studies with 17671 patients were included. Mean follow-up was 8.7 ± 7.9 mo. Combined end-point of heart failure readmission and cardiovascular death was better in ivabradine + beta-blocker group compared to beta-blocker alone (RR: 0.93, 95%CI: 0.79-1.09, P = 0.354). Mean difference (MD) in heart rate was higher in the ivabradine + beta-blocker group (MD: 6.14, 95%CI: 3.80-8.48, P < 0.001). There was no difference in all cause mortality (RR: 0.98, 95%CI: 0.89-1.07, P = 0.609), cardiovascular mortality (RR: 0.99, 95%CI: 0.86-1.15, P = 0.908) or heart failure hospitalization (RR: 0.87, 95%CI: 0.68-1.11, P = 0.271). CONCLUSION: From the available clinical trials, ivabradine + beta-blocker resulted in a significantly greater reduction in HR coupled with improvement in combined end-point of heart failure readmission and cardiovascular death but with no improvement in all cause or cardiovascular mortality. Given the limited evidence, further randomized controlled trials are essential before widespread clinical application of ivabradine + beta-blocker is advocated for HFrEF.

Surgical Repair of Moderate Ischemic Mitral Regurgitation-A Systematic Review and Meta-analysis.

Introduction Moderate mitral regurgitation (MR) of ischemic etiology has been associated with worse outcomes after coronary artery bypass grafting (CABG). Studies comparing concomitant mitral valve replacement/repair (MVR/Re) with CABG and standalone CABG have reported conflicting results. We performed a systematic review and meta-analysis of the published literature. Patients and Methods We searched using PubMed, Cochrane, EMBASE, CINAHL, and Google scholar databases from January 1960 to June 2016 for clinical trials comparing CABG to CABG + MVR/Re for moderate MR. Pooled risk ratio or mean difference (MD) with 95% confidence intervals (CI) for individual outcomes were calculated using random effects model and heterogeneity was assessed using Cochrane's Q-statistic. Results A total of 11 studies were included. Mean follow-up was 35.3 months. All-cause mortality (Mantel-Haenszel [MH] risk ratio [RR]: 0.96, 95% CI: 0.75-1.24, p = 0.775), early mortality (MH RR: 0.65, 95% CI: 0.39-1.07, p = 0.092), and stroke rates (MH RR 0.65, 95% CI: 0.21-2.03, p = 0.464) were similar between CABG and CABG + MVR/Re groups. Adverse event at follow-up was lower with CABG (MH RR: 0.90, 95% CI: 0.61-1.32, p = 0.584). MD of change from baseline in left ventricular (LV) end-systolic dimension (MD: - 2.50, 95% CI: - 5.21 to - 0.21, p = 0.071) and LV ejection fraction (MD: 0.48, 95% CI: - 2.48 to 3.44, p = 0.750) were not significantly different between the groups. Incidence of moderate MR (MH RR: 3.24, 95% CI: 1.79-5.89, p < 0.001) was higher in the CABG only group. Conclusion Addition of MVR/Re to CABG in patients with moderate ischemic MR did not result in improvement in early or overall mortality, stroke risk, or intermediate markers of LV function when compared with CABG alone.

Efficacy of Implantable Cardioverter-Defibrillator Therapy in Patients With Nonischemic Cardiomyopathy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVES: This study sought to evaluate the efficacy of implantable cardioverter-defibrillator (ICD) therapy with or without cardiac resynchronization therapy (CRT) in patients with nonischemic cardiomyopathy (NICM). BACKGROUND: The effect of ICD on mortality of patients with NICM and left ventricular ejection fraction ≤35% has recently been questioned. Prior randomized controlled trials (RCTs) evaluating ICD efficacy in patients with NICM have yielded conflicting results. Furthermore, whether ICD therapy benefits NICM patients with concomitant CRT is unknown. METHODS: Relevant RCTs published between 2000 and 2016 were identified. Patients with ischemic cardiomyopathy were excluded. Study sample was stratified into CRT and non-CRT groups. The efficacy of having a defibrillator in each group was compared using random effects meta-analysis techniques. RESULTS: Six RCTs (N = 3,544) were included. Among the 2,347 patients who did not have CRT, ICD use was associated with a 24% reduction in mortality (relative risk [RR]: 0.76; 95% confidence interval [CI]: 0.63 to 0.91; p = 0.003). However, among the 1,197 patients with CRT, having a CRT defibrillator was not associated with a statistically significant reduction in mortality (RR: 0.74; 95% CI: 0.46 to 1.16; p = 0.19) compared to CRT-pacemaker. Subgroup analysis in non-CRT patients showed that ICD use reduced sudden cardiac death by 73% (RR: 0.27; 95% CI: 0.15 to 0.50; p < 0.001) compared to medical therapy. CONCLUSIONS: Compared to medical therapy, ICD use significantly improved survival among patients with NICM and ejection fraction ≤35%. Although CRT-defibrillator was not associated with a statistically significant mortality benefit compared to CRT-pacemaker, the apparent lack of power in this analysis warrants further investigation.

What is the optimal approach to a non- culprit stenosis after ST-elevation myocardial infarction - Conservative therapy or upfront revascularization? An updated meta-analysis of randomized trials.

BACKGROUND: Non-culprit percutaneous coronary intervention (PCI) during a ST-segment elevation myocardial infarction (STEMI) remains controversial. We performed a meta-analysis of the published literature comparing a strategy of complete revascularization (CR) with culprit or target vessel revascularization (TVR)-only after STEMI in patients with multi-vessel disease. METHODS: We searched PubMed/Medline, Cochrane, EMBASE, Web of Science, CINAHL, Scopus and Google-scholar databases from inception to March-2016 for clinical trials comparing CR with TVR during PCI for STEMI. Mantel-Haenszel risk ratio (MH-RR) with 95% confidence intervals (CI) for individual outcomes was calculated using random-effects model. RESULTS: A total of 7 randomized trials with 2004 patients were included in the final analysis. Mean follow-up was 25.4months. Major adverse cardiac events (MACE) (MH-RR: 0.58, 95% CI: 0.43-0.78, P<0.001), cardiac deaths (MH-RR: 0.42, 95% CI: 0.24-0.74, P=0.003) and repeat revascularization (MH-RR: 0.36, 95% CI: 0.27-0.48, P<0.001) were much lower in the CR group when compared to TVR. However, there was no significant difference in the risk of all-cause mortality (0.84, 95% CI: 0.57-1.25, P=0.394) or recurrent MI (MH-RR: 0.66, 95% CI: 0.34-1.26, P=0.205) between the two groups. CR appeared to be safe with no significant increase in adverse events including stroke rates (MH-RR: 2.19, 95% CI: 0.59-8.12, P=0.241), contrast induced nephropathy (MH-RR: 0.73, 95% CI: 0.34-1.57, P=0.423) or major bleeding episodes (MH-RR: 0.72, 95% CI: 0.34-1.54, P=0.399). CONCLUSIONS: CR strategy in STEMI patients with multivessel coronary artery disease is associated with reduction in MACE, cardiac mortality and need for repeat revascularization but with no decrease in the risk of subsequent MI or all-cause mortality. CR was safe however, with no increase in adverse events including stroke, stent thrombosis or contrast nephropathy when compared to TVR.

Early versus late surgical intervention or medical management for infective endocarditis: a systematic review and meta-analysis.

OBJECTIVE: Infective endocarditis is associated with high morbidity and mortality and optimal timing for surgical intervention is unclear. We performed a systematic review and meta-analysis to compare early surgical intervention with conservative therapy in patients with infective endocarditis. METHODS: PubMed, Cochrane, EMBASE, CINAHL and Google-scholar databases were searched from January 1960 to April 2015. Randomised controlled trials, retrospective cohorts and prospective observational studies comparing outcomes between early surgery at 20 days or less and conservative management for infective endocarditis were analysed. RESULTS: A total of 21 studies were included. OR of all-cause mortality for early surgery was 0.61 (95% CI 0.50 to 0.74, p<0.001) in unmatched groups and 0.41 (95% CI 0.31 to 0.54, p<0.001) in the propensity-matched groups (matched for baseline variables). For patients who had surgical intervention at 7 days or less, OR of all-cause mortality was 0.61 (95% CI 0.39 to 0.96, p=0.034) and in those who had surgical intervention within 8-20 days, the OR of mortality was 0.64 (95% CI 0.48 to 0.86, p=0.003) compared with conservative management. In propensity-matched groups, the OR of mortality in patients with surgical intervention at 7 days or less was 0.30 (95% CI 0.16 to 0.54, p<0.001) and in the subgroup of patients who underwent surgery between 8 and 20 days was 0.51 (95% CI 0.35 to 0.72, p<0.001). There was no significant difference in in-hospital mortality, embolisation, heart failure and recurrence of endocarditis between the overall unmatched cohorts. CONCLUSION: The results of our meta-analysis suggest that early surgical intervention is associated with significantly lower risk of mortality in patients with infective endocarditis.

Malignant Course of Anomalous Left Coronary Artery Causing Sudden Cardiac Arrest: A Case Report and Review of the Literature.

Sudden cardiac arrest has been reported to occur in patients with congenital anomalous coronary artery disease. About 80% of the anomalies are benign and incidental findings at the time of catheterization. We present a case of sudden cardiac arrest caused by anomalous left anterior descending artery. 61-year-old African American female was brought to the emergency department after sudden cardiac arrest. Initial EKG showed sinus rhythm with RBBB and LAFB with nonspecific ST-T wave changes. Coronary angiogram revealed no atherosclerotic disease. The left coronary artery was found to originate from the right coronary cusp. Cardiac CAT scan revealed similar findings with interarterial and intramural course. Patient received one-vessel arterial bypass graft to her anomalous coronary vessel along with a defibrillator for secondary prevention. Sudden cardiac arrest secondary to congenital anomalous coronary artery disease is characterized by insufficient coronary flow by the anomalous left coronary artery to meet elevated left ventricular (LV) myocardial demand. High risk defects include those involved with the proximal coronary artery or coursing of the anomalous artery between the aorta and pulmonary trunk. Per guidelines, our patient received one vessel bypass graft to her anomalous vessel. It is important for clinicians to recognize such presentations of anomalous coronary artery.