Improved Utilization of Serial Testing Without Increased Admissions after Implementation of High-Sensitivity Troponin I: a Controlled Retrospective Cohort Study.

BACKGROUND: Guidelines recommend high-sensitivity cardiac troponin (hs-cTn) for diagnosis of myocardial infarction. Use of hs-cTn is increasing across the U.S., but questions remain regarding clinical and operational impact. Prior studies have had methodologic limitations and yielded conflicting results. OBJECTIVE: To evaluate the impact of transitioning from conventional cardiac troponin (cTn) to hs-cTn on test and resource utilization, operational efficiency, and patient safety. DESIGN: Retrospective cohort study in two New York City hospitals during the months before and after transition from conventional cTn to hs-cTn at Hospital 1. Hospital 2 served as a control. PARTICIPANTS: Consecutive emergency department (ED) patients with at least one cTn test resulted. INTERVENTION: Multifaceted hs-cTn intervention bundle, including a 0/2-h diagnostic algorithm for non-ST-elevation myocardial infarction, an educational bundle, enhancements to the electronic medical record, and nursing interventions to facilitate timed sample collection. MAIN MEASURES: Primary outcomes included serial cTn test utilization, probability of hospital admission, ED length of stay (LOS), and among discharged patients, probability of ED revisit within 72 h resulting in hospital admission. Multivariable regression models adjusted for age, sex, temporal trends, and interhospital differences. KEY RESULTS: The intervention was associated with increased use of serial cTn testing (adjusted risk difference: 48 percentage points, 95% CI: 45-50, P < 0.001) and ED LOS (adjusted geometric mean difference: 50 min, 95% CI: 50-51, P < 0.001). There was no significant association between the intervention and probability of admission (adjusted relative risk [aRR]: 0.99, 95% CI: 0.89-1.1, P = 0.81) or probability of ED revisit within 72 h resulting in admission (aRR: 1.1, 95% CI: 0.44-2.9, P = 0.81). CONCLUSIONS: Implementation of a hs-cTn intervention bundle was associated with an improvement in serial cTn testing, a neutral effect on probability of hospital admission, and a modest increase in ED LOS.

High-Sensitivity Cardiac Troponin Algorithms and the Value of Likelihood Ratios.

High-sensitivity cardiac troponin (hs-cTn) is now the recommended biomarker for diagnosis of non-ST-elevation myocardial infarction, but proper interpretation varies based on the assay being used. Nearly uniformly, suggested interpretations of assay-specific hs-cTn results are based on predictive values, which are not applicable to most patients. Through application of a published hs-cTn algorithm to several patient scenarios, we will demonstrate that likelihood ratios are superior to predictive values for patient-centered test interpretation and decision-making. Furthermore, we will provide a blueprint for how to use existing published data presented with predictive values to calculate likelihood ratios. Changing the output of diagnostic accuracy studies and diagnostic algorithms from predictive values to likelihood ratios can improve patient care.

Research Methods: How to Perform an Effective Peer Review.

Scientific peer review has existed for centuries and is a cornerstone of the scientific publication process. Because the number of scientific publications has rapidly increased over the past decades, so has the number of peer reviews and peer reviewers. In this paper, drawing on the relevant medical literature and our collective experience as peer reviewers, we provide a user guide to the peer review process, including discussion of the purpose and limitations of peer review, the qualities of a good peer reviewer, and a step-by-step process of how to conduct an effective peer review.

Cardiac Point-of-Care Ultrasound for the Diagnosis of Infective Endocarditis in a Patient with Non-Specific Rheumatologic Symptoms and Glomerulonephritis.

BACKGROUND Point-of-care ultrasound (POCUS) is performed at the bedside by a healthcare professional who is directly caring for the patient. Subacute infective endocarditis can be challenging to diagnose, as patients often present with non-specific symptoms. The modified Duke criteria include echocardiographic findings as a major criterion, but the role of POCUS has not been established. This report is of a case of infective endocarditis diagnosed using POCUS. CASE REPORT A 57-year-old man was admitted to hospital with a presumptive diagnosis of rapidly progressive glomerulonephritis secondary to vasculitis associated with a non-specific rheumatologic condition that had developed during the previous three months. Several specialist physicians had previously examined him. On hospital admission, POCUS was performed by the internal medicine physician, which showed mitral valve endocarditis resulting in a change in clinical management from steroid therapy to antibiotic therapy. Blood cultures were performed, which grew Streptococcus mutans. CONCLUSIONS To our knowledge, this is the first reported case of infective endocarditis diagnosed by an internist using POCUS in a patient admitted to hospital with an alternative diagnosis and management plan in place. This case highlights the potential role of POCUS in the acute hospital setting and supports the need for studies to compare the diagnostic performance of POCUS with transthoracic echocardiography for the detection of valvular vegetations. POCUS may be considered for patients with a possible diagnosis of infective endocarditis that cannot be excluded using the modified Duke criteria, potentially resulting in earlier diagnosis and management, with an improved clinical outcome.

CXCR1-mediated neutrophil degranulation and fungal killing promote Candida clearance and host survival.

Systemic Candida albicans infection causes high morbidity and mortality and is now the leading cause of nosocomial bloodstream infection in the United States. Neutropenia is a major risk factor for poor outcome in infected patients; however, the molecular factors that mediate neutrophil trafficking and effector function during infection are poorly defined. Using a mouse model of systemic candidiasis, we found that the neutrophil-selective CXC chemokine receptor Cxcr1 and its ligand, Cxcl5, are highly induced in the Candida-infected kidney, the target organ in the model. To investigate the role of Cxcr1 in antifungal host defense in vivo, we generated Cxcr1(-/-) mice and analyzed their immune response to Candida. Mice lacking Cxcr1 exhibited decreased survival with enhanced Candida growth in the kidney and renal failure. Increased susceptibility of Cxcr1(-/-) mice to systemic candidiasis was not due to impaired neutrophil trafficking from the blood into the infected kidney but was the result of defective killing of the fungus by neutrophils that exhibited a cell-intrinsic decrease in degranulation. In humans, the mutant CXCR1 allele CXCR1-T276 results in impaired neutrophil degranulation and fungal killing and was associated with increased risk of disseminated candidiasis in infected patients. Together, our data demonstrate a biological function for mouse Cxcr1 in vivo and indicate that CXCR1-dependent neutrophil effector function is a critical innate protective mechanism of fungal clearance and host survival in systemic candidiasis.

CX3CR1-dependent renal macrophage survival promotes Candida control and host survival.

Systemic Candida albicans infection causes high morbidity and mortality and is associated with neutropenia; however, the roles of other innate immune cells in pathogenesis are poorly defined. Here, using a mouse model of systemic candidiasis, we found that resident macrophages accumulated in the kidney, the main target organ of infection, and formed direct contacts with the fungus in vivo mainly within the first few hours after infection. Macrophage accumulation and contact with Candida were both markedly reduced in mice lacking chemokine receptor CX3CR1, which was found almost exclusively on resident macrophages in uninfected kidneys. Infected Cx3cr1-/- mice uniformly succumbed to Candida-induced renal failure, but exhibited clearance of the fungus in all other organs tested. Renal macrophage deficiency in infected Cx3cr1-/- mice was due to reduced macrophage survival, not impaired proliferation, trafficking, or differentiation. In humans, the dysfunctional CX3CR1 allele CX3CR1-M280 was associated with increased risk of systemic candidiasis. Together, these data indicate that CX3CR1-mediated renal resident macrophage survival is a critical innate mechanism of early fungal control that influences host survival in systemic candidiasis.

Chemokine receptor Ccr1 drives neutrophil-mediated kidney immunopathology and mortality in invasive candidiasis.

Invasive candidiasis is the 4(th) leading cause of nosocomial bloodstream infection in the US with mortality that exceeds 40% despite administration of antifungal therapy; neutropenia is a major risk factor for poor outcome after invasive candidiasis. In a fatal mouse model of invasive candidiasis that mimics human bloodstream-derived invasive candidiasis, the most highly infected organ is the kidney and neutrophils are the major cellular mediators of host defense; however, factors regulating neutrophil recruitment have not been previously defined. Here we show that mice lacking chemokine receptor Ccr1, which is widely expressed on leukocytes, had selectively impaired accumulation of neutrophils in the kidney limited to the late phase of the time course of the model; surprisingly, this was associated with improved renal function and survival without affecting tissue fungal burden. Consistent with this, neutrophils from wild-type mice in blood and kidney switched from Ccr1(lo) to Ccr1(high) at late time-points post-infection, when Ccr1 ligands were produced at high levels in the kidney and were chemotactic for kidney neutrophils ex vivo. Further, when a 1∶1 mixture of Ccr1(+/+) and Ccr1(-/-) donor neutrophils was adoptively transferred intravenously into Candida-infected Ccr1(+/+) recipient mice, neutrophil trafficking into the kidney was significantly skewed toward Ccr1(+/+) cells. Thus, neutrophil Ccr1 amplifies late renal immunopathology and increases mortality in invasive candidiasis by mediating excessive recruitment of neutrophils from the blood to the target organ.