SARS-CoV-2: Current Tools to Fight COVID-19 ST-Elevation Myocardial Infarction.

The capacity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to wreak havoc on the inflammatory and coagulation pathways via the cytokine storm has led to over 6.3 million fatalities globally. Based on recent data, the mechanism predominately involves the formation of microvascular thrombosis when pertaining to cardiovascular disease. However, a subset of coronavirus disease-2019 (COVID-19)-positive patients present emergently with acute ST-elevation myocardial infarction (STEMI) are found to have severe epicardial thrombosis which is refractory to traditional coronary revascularization. We have noted mortality in these patients presenting to our facility to be as high as 90% and all angiographically confirmed to have thrombus which was refractory to traditional therapy. We present a case series of COVID-19-positive patients presenting with STEMI found to have epicardial thrombus who were treated with different traditional STEMI therapies but with fatal outcomes. Other possible techniques including mechanical thrombectomy, optimizing traditional and nontraditional anticoagulation therapy with the use of early hemodynamic support may prove more efficacious to destroy thrombus and potentially improve mortality.

Extensive Coronary Thrombosis as a Sequelae of COVID-19 Presenting as a STEMI.

Thrombotic complications, in particular ST-elevation myocardial infarction (STEMI), have been described in active Coronavirus disease 2019 (COVID-19) cases. This is a result of systemic inflammation that often leads to endothelial activation, microvascular thrombosis and a hypercoagulable state. However, it is unknown how long patients who have cleared the COVID-19 infection remain at risk for coronary thrombosis as a sequela of disease burden. We present a case of a patient who presented three to four weeks following the initial infection.

The Effect of Starting a New Residency Program on the Quality of Care Measures at a Community Hospital: A 2-Year Follow-Up.

Background: Introducing graduate medical education to a non-teaching hospital has been a challenging issue due to its perceived possible negative impact on quality and cost of care. Objective: To assess the impact of starting a new Internal Medicine (IM) residency program on the quality of care measures in a Graduate Medical Education (GME) naïve community hospital. Methods: In a retrospective longitudinal study, we compared quality of care parameters (mortality rate, 30-day readmission rate, length of stay, case mix index and severity level) for a hospitalist group ten months before (September 2015-June 2016) and two consecutive years (July 2016-June 2018) after the implementation of an IM residency program at a community hospital. Results: We compared the aggregated data from 1,295 patients before starting the residency program to 2,532 and 3,061 patients, in two consecutive academic years after initiating an IM residency. For the hospitalist group that became the teaching group, the mortality rate decreased significantly from 10 months pre- and the two post-residency periods (2%, 1% and 0.2%, p-value < 0.01), while the mortality rate among non-teaching hospitalist group patients at the same hospital remained unchanged over the same time period (p = 0.70). Length of stay decreased significantly from 10-months pre-residency to 1-year post-residency (6.23 and 5.31, p-value = 0.01). Furthermore, there were no other significant differences between the groups in terms of 30-day readmission rate, complications in care and average cost per case. Conclusions: Starting a new residency program in a non-teaching hospital improves mortality rate without significantly affecting other quality measures.

A Fistula Where? Left Anterior Descending to Pulmonary Artery Fistula.

Fistulas are abnormal passageways between two organs or vessels that usually do not connect. Coronary artery fistulas occur when one of the coronary arteries is connected to either a heart chamber or another blood vessel. This case presents a coronary artery fistula which may or may not be impacting the patient's heart function. A 69-year-old male with multiple comorbidities presents with a chief complaint of shortness of breath. Catheterization reveals an anomalous left anterior descending to pulmonary artery fistula without a step up in oxygen saturation at the level of the pulmonary artery. Surgical management was deferred as this fistula was not deemed to contribute to the patient's declining cardiac function. Operative management versus embolization would be a feasible alternative for patients who are symptomatic secondary to the coronary artery fistula and remains to be controversial in patients who are asymptomatic. Given the possibility of these fistulae eventually causing symptoms it would be practical to close them early on before symptoms arise or before size of the fistulae becomes an issue. Further research should be conducted to understand the management strategies for patients who present with coronary artery fistulas.

Cor Triatriatum Dexter: A Case Report in a 70-Year-Old Male.

Cor triatriatum dexter (CTD) is a rare congenital heart disease resulting from persistence of the right valve of the sinus venosus. The persistent valve forms a membrane that divides the right atrium into a proximal and a distal chamber. This disorder exhibits varying clinical manifestations depending on the degree of partitioning or septation of the right atrium. In asymptomatic patients, the disease may be discovered during surgical procedures, diagnostic testing such as echocardiography, or hemodynamic monitoring. Severe septation abnormalities may cause right-sided heart failure and elevated central venous pressures due to obstruction of the tricuspid valve, right ventricular outflow tract, or inferior vena cava. Here we report a case of CTD in a patient presenting with symptoms of dyspnea and fatigue, followed by a short discussion of the embryology and clinical implications of this congenital disease, as well as current advances in management.

Chronic Kidney Disease Increases Cerebral Microbleeds in Mouse and Man.

Brain microbleeds are increased in chronic kidney disease (CKD) and their presence increases risk of cognitive decline and stroke. We examined the interaction between CKD and brain microhemorrhages (the neuropathological substrate of microbleeds) in mouse and cell culture models and studied progression of microbleed burden on serial brain imaging from humans. Mouse studies: Two CKD models were investigated: adenine-induced tubulointerstitial nephritis and surgical 5/6 nephrectomy. Cell culture studies: bEnd.3 mouse brain endothelial cells were grown to confluence, and monolayer integrity was measured after exposure to 5-15% human uremic serum or increasing concentrations of urea. Human studies: Progression of brain microbleeds was evaluated on serial MRI from control, pre-dialysis CKD, and dialysis patients. Microhemorrhages were increased 2-2.5-fold in mice with CKD independent of higher blood pressure in the 5/6 nephrectomy model. IgG staining was increased in CKD animals, consistent with increased blood-brain barrier permeability. Incubation of bEnd.3 cells with uremic serum or elevated urea produced a dose-dependent drop in trans-endothelial electrical resistance. Elevated urea induced actin cytoskeleton derangements and decreased claudin-5 expression. In human subjects, prevalence of microbleeds was 50% in both CKD cohorts compared with 10% in age-matched controls. More patients in the dialysis cohort had increased microbleeds on follow-up MRI after 1.5 years. CKD disrupts the blood-brain barrier and increases brain microhemorrhages in mice and microbleeds in humans. Elevated urea alters the actin cytoskeleton and tight junction proteins in cultured endothelial cells, suggesting that these mechanisms explain (at least in part) the microhemorrhages and microbleeds observed in the animal and human studies.

Pulmonic valve infective endocarditis from staph lugdunensis.

Pulmonic valve endocarditis is an extremely rare entity. Only 1.1% of all cases of all infective endocarditis affect the pulmonic valve. Furthermore, it is even more uncommon for such a disease process to occur in a young and healthy individual without risk factors. It takes a unique case of circumstances to have pulmonic valve infective endocarditis to occur. Staph lugdunensis is one uncommonly isolated organism that has the ability to cause infective endocarditis in various atypical manifestations. Here we describe a case of a 20-year-old male who did not possess any of the common risk factors of infective endocarditis, who developed isolated pulmonic valve endocarditis caused by Staphylococcus lugdunensis (S. lugdunensis). Based upon our literature review, only 1 other case of S. lugdunensis endocarditis affective the pulmonic valve has been reported.

Transcatheter Double Valve-in-Valve Replacement of Aortic and Mitral Bioprosthetic Valves.

Transcatheter aortic valve replacement (TAVR) is an evolving method which has become the treatment of choice in high-risk patients with severe aortic stenosis. Unlike TAVR, the experience with transcatheter mitral valve replacement (TMVR) remains at an early stage because of challenges of valve development and possible complications such as valve displacement and subsequent left ventricular outlet tract (LVOT) obstruction. Here we report a case of transcatheter double valve-in-valve replacement (TDVIVR) in a patient with severe mitral and aortic bioprosthetic valve stenosis, followed by an extensive literature review of the latest techniques and challenges in this field.

Noninvasive Treatment Approach of Radial Pseudoaneurysm.

Transradial approach for cardiac catheterization is a viable alternative to transfemoral approach given its ease of access, lessened complication risk, and post procedural comfort for patients. Radial pseudoaneurysm presents as a rare complication in less than 1% of these procedures. The use of external compression banding is an approach that shows promise as a noninvasive attempt towards resolving this complication. However, it has been documented in very few reports. We describe a case of an 82-year-old woman who underwent transradial approach to cardiac catheterization, and developed a radial pseudoaneurysm following the procedure as confirmed by Doppler ultrasonography. We used compressive banding as a technique to attempt to resolve this radial pseudoaneurysm. Following a strict protocol of pneumatic banding, repeat ultrasonography revealed complete resolution of radial pseudoaneurysm. This case highlights a potentially noninvasive technique that could serve as a first-line approach towards resolving this rare phenomenon.

Utility of Cardiac Biomarkers in the Setting of Kidney Disease.

Cardiovascular disease is prevalent in patients with chronic kidney disease (CKD) and responsible for approximately half of all CKD-related deaths. Unfortunately, the presence of CKD can lead to a challenging interpretation of cardiac biomarkers essential in accurate diagnosis and prompt management of heart failure and acute coronary syndrome. There is growing interest in novel cardiac biomarkers that may improve diagnostic accuracy reflecting myocardial injury, inflammation, and remodeling. Interpretation of these biomarkers in CKD can be complicated, since elevated levels may not reflect myocardial injury or wall tension but rather decreased urinary clearance with retention of solutes and/or overall CKD-associated chronic inflammation. In this review, we discuss the latest data on major and emerging cardiac biomarkers including B-type natriuretic peptide, troponin, suppression of tumorigenicity 2, growth and differentiation factor-15, galectin-3, and matrix gla protein, and their diagnostic and prognostic utility in the CKD population.

Impact of Gut Dysbiosis on Neurohormonal Pathways in Chronic Kidney Disease.

Chronic kidney disease (CKD) is a worldwide major health problem. Traditional risk factors for CKD are hypertension, obesity, and diabetes mellitus. Recent studies have identified gut dysbiosis as a novel risk factor for the progression CKD and its complications. Dysbiosis can worsen systemic inflammation, which plays an important role in the progression of CKD and its complications such as cardiovascular diseases. In this review, we discuss the beneficial effects of the normal gut microbiota, and then elaborate on how alterations in the biochemical environment of the gastrointestinal tract in CKD can affect gut microbiota. External factors such as dietary restrictions, medications, and dialysis further promote dysbiosis. We discuss the impact of an altered gut microbiota on neuroendocrine pathways such as the hypothalamus⁻pituitary⁻adrenal axis, the production of neurotransmitters and neuroactive compounds, tryptophan metabolism, and the cholinergic anti-inflammatory pathway. Finally, therapeutic strategies including diet modification, intestinal alpha-glucosidase inhibitors, prebiotics, probiotics and synbiotics are reviewed.

Altered microbiome in chronic kidney disease: systemic effects of gut-derived uremic toxins.

In chronic kidney disease (CKD), influx of urea and other retained toxins exerts a change in the gut microbiome. There is decreased number of beneficial bacteria that produce short-chain fatty acids, an essential nutrient for the colonic epithelium, concurrent with an increase in bacteria that produce uremic toxins such as indoxyl sulphate, p-cresyl sulphate, and trimethylamine-N-oxide (TMAO). Due to intestinal wall inflammation and degradation of intercellular tight junctions, gut-derived uremic toxins translocate into the bloodstream and exert systemic effects. In this review, we discuss the evidence supporting a role for gut-derived uremic toxins in promoting multiorgan dysfunction via inflammatory, oxidative stress, and apoptosis pathways. End-organ effects include vascular calcification, kidney fibrosis, anemia, impaired immune system, adipocyte dysfunction with insulin resistance, and low turnover bone disease. Higher blood levels of gut-derived uremic toxins are associated with increased cardiovascular events and mortality in the CKD population. Clinical trials that have examined interventions to trap toxic products or reverse gut microbial dysbiosis via oral activated charcoal AST-120, prebiotics and probiotics have not shown impact on cardiovascular or survival outcomes but were limited by sample size and short trials. In summary, the gut microbiome is a major contributor to adverse cardiovascular outcomes and progression of CKD.

Dietary tetrahydrocurcumin reduces renal fibrosis and cardiac hypertrophy in 5/6 nephrectomized rats.

Tetrahydrocurcumin (THC) is the principal metabolite of curcumin and has antioxidant properties. In the present investigation, the effect of THC on renal and cardiovascular outcomes was studied in rats with chronic kidney disease (CKD). CKD rats were randomized following 5/6 nephrectomy to a special diet for 9 weeks which contained 1% THC (CKD+THC group). Low-dose polyenylphosphatidylcholine was used as a lipid carrier to increase bioavailability. Endpoints included tail blood pressure, normalized heart weight, plasma and urine biochemical data, and kidney tissue analyses. CKD animals demonstrated increased proteinuria, decreased creatinine clearance, hypertension, and cardiac hypertrophy. The antioxidant proteins CuZn SOD and glutathione peroxidase were decreased in the remnant kidney, while apoptosis (caspase-3) and fibrosis (alpha-SM actin) were increased. Renal fibrosis was confirmed histologically on trichrome staining. These pathologic changes were ameliorated in the CKD+THC group with significant decrease in proteinuria, hypertension, and kidney fibrosis. THC therapy restored levels of CuZn SOD and glutathione peroxidase. Consistent with prior reports, dietary THC did not improve nuclear Nrf2 levels. In summary, dietary THC therapy improved expression of antioxidant proteins in the remnant kidney, decreased renal fibrosis and proteinuria, and ameliorated hypertension in 5/6 nephrectomized rats.

Warfarin Use and Increased Mortality in End-Stage Renal Disease.

BACKGROUND: Controversy exists regarding the benefits and risks of warfarin therapy in chronic kidney disease (CKD) and end-stage renal disease (ESRD) patients. In this study, we assessed mortality and cardiovascular outcomes associated with warfarin treatment in patients with stages 3-5 CKD and ESRD admitted to the University of California-Irvine Medical Center. METHODS: In a retrospective matched cohort study, we identified 59 adult patients with stages 3-6 CKD initiated on warfarin during the period 2011-2013, and 144 patients with stages 3-6 CKD who had indications for anticoagulation therapy but were not initiated on warfarin. All-cause mortality risk associated with warfarin treatment was estimated using Cox proportional hazard regression analysis, and the risk of significant bleeding and major adverse cardiovascular events were analyzed with Poisson regression analysis. Adjustment models were used to account for age, gender, diabetes mellitus, use of antiplatelet agents, and preexisting cardiovascular disease, and stratified by pre-dialysis CKD stages 3-5 vs. ESRD. FINDINGS: During 5.8 years of follow-up, unadjusted mortality risk was higher in CKD patients on warfarin therapy (hazard ratio [HR] 2.34 with 95% CI 1.25-4.39; p < 0.01). After multivariate adjustment and stratification by CKD stage, the mortality risk remained significant in ESRD patients receiving warfarin (HR 6.62 with 95% CI 2.56-17.16; p < 0.001). Furthermore, adjusted rates of significant bleeding (incident rate ratio, IRR 3.57 with 95% CI 1.51-8.45; p < 0.01) and myocardial infarction (IRR 4.20 with 95% CI 1.78-9.91; p < 0.01) were higher among warfarin users. No differences in rates of ischemic or hemorrhagic strokes were found between the 2 groups. CONCLUSIONS: Warfarin use was associated with several-fold higher risk of death, bleeding, and myocardial infarction in dialysis patients. If additional studies suggest similar associations, the use of warfarin in dialysis patients warrants immediate reconsideration.

Remote ischemic preconditioning for prevention of contrast-induced acute kidney injury in diabetic patients.

INTRODUCTION: There are some clinical trials showing that short-term ischemia in one organ can protect different organs against higher intensity and longer ischemic insult. We designed a study to assess whether remote ischemic preconditioning (RIPC) on one organ can decrease the rate of contrast-induced acute kidney injury (AKI) in diabetic patients who undergo coronary artery angiography (CAA). MATERIALS AND METHODS: This randomized control trial included 96 diabetic patients who were candidates for CAA. Exclusion criteria were congestive heart failure and complications during CAA. All of the patients received 1000 mL of normal saline before CAA. The RIPC group underwent 3 cycles of 5-minute ischemia in their right arm. Serum creatinine was measured before and 24 hours after CAA. RESULTS: Contrast-induced AKI was reported in 5 cases in the control group and 1 case in the RIPC group (P = .13, odds ratio, 5.4). The differences in serum creatinine level before and after the procedure was significantly lower in RIPC group than that in the control group (P = .04, odds ratio, 0.08). Serum creatinine rise significantly correlated with contrast dose (P = .02) and a history of hypertension (P = .02) in both groups. CONCLUSIONS: Ischemic preconditioning had a protective effect on contrast-induced AKI in our study. Since this method is harmless and cost effective, further studies on patients with chronic kidney disease is required to evaluate addition of ischemic preconditioning to our clinical practice for prevention of contrast-induced AKI.

Interferon-gamma release assay agreement with tuberculin skin test in pretransplant screening for latent tuberculosis in a high-prevalence country.

INTRODUCTION: Tuberculosis reactivation is one of significant complications after transplantation. Tuberculin skin test (TST) has been the major available screening test in end-stage renal disease patients, but it is associated with a low accuracy. Recently, an interferon-gamma release assay (IGRA) has been approved as a substitution test in diagnosis of Mycobacterium tuberculosis infection. This study aimed to compare the ability of the TST and IGRA in the diagnosis of latent tuberculosis in hemodialysis patients and investigate risk factors of having positive test results. MATERIALS AND METHODS: Forty-seven hemodialysis patients underwent the IGRA and TST tests. Demographic data and blood samples were collected and chest radiography was done for all participants. RESULT: Abnormal chest radiography was reported in 24% of the study group. The IGRA and TST were positive in 11 (23.4%) and 20 patients (43.5%), respectively. The agreement coefficient (kappa) between the IGRA and TST was 0.31. Positive TSTs were significantly associated with male sex and abnormal chest radiography. Diabetes mellitus was a risk factor for a positive IGRA result (P = .01). CONCLUSIONS: The IGRA test is not a sensitive test for detection of latent tuberculosisin hemodialysis patients residing in high-prevalence areas. We suggest that assessment of cellular immunity response in end-stage renal disease patient be a priority before reliance on the IGRA test result.

Massive proteinuria and autosomal dominant polycystic kidney disease: a rare coincidence.

Autosomal dominant polycystic kidney disease (ADPKD) with nephrotic syndrome is a rare coincidence. Among 19 reported cases since 1972, focal glomerulosclerosis is the dominant reported pathology. Here, we report the 6th case of focal segmental glomerulosclerosis with ADPKD. A 29-year-old man with a history of APCDK presented with massive proteinuria. He had a history of concurrent leptospirosis and brucellosis, and trace proteinuria and mild hypertension had been diagnosed 4 years earlier. Urine study showed proteinuria (21 g/d) and hematuria. Kidney biopsy report was compatible with focal and segmental sclerosis. The patient received prednisolone and cyclosporine. After 4 months, proteinuria decreased to 600 mg/d. Patients with ADPKD who show massive proteinuria should undergo kidney biopsy. It is possible that different mutations in these patients could clarify the nature of this coincidence.