Purulent Streptococcus intermedius Pericarditis in the Setting of Histoplasma Mediastinal Lymphadenitis: A Case Report and Literature Review.

Purulent pericarditis is a rare and potentially life-threatening condition characterized by infection of the pericardial space. We describe a case of purulent bacterial pericarditis in a 41-year-old male with no significant medical or surgical history who had concomitant pulmonary Histoplasma infection. Streptococcus intermedius was the bacteria directly responsible for the pericardial infection, though co-infection with histoplasmosis likely predisposed him to develop purulent pericarditis. We hypothesize histoplasmosis caused mediastinal lymphadenopathy, facilitating contact between a necrotic lymph node and the pericardium and contiguous suppuration of bacteria to the pericardial space. We treated S. intermedius and Histoplasma capsulatum with ceftriaxone and amphotericin B, respectively. Additionally, the patient presented in cardiac tamponade requiring emergent pericardiocentesis and drain placement. His course was also complicated by pericardial constriction. Cardiac magnetic resonance confirmed this, showing inflamed pericardium and abnormal septal motion with inspiration, and he had symptoms refractory to antimicrobials and anti-inflammatories. As such, he required pericardiectomy. This case demonstrates maintaining suspicion for secondary infectious foci as a contributor to the pathogenesis of purulent pericarditis is important, as pulmonary histoplasmosis played a pivotal role in allowing S. intermedius to spread to the pericardium but was not the primary infection. It also highlights the multifaceted evaluation and management of purulent pericarditis, highlighting the role of echocardiography and emergent pericardial drainage if cardiac tamponade is present, the importance of targeted antimicrobial therapy, the superior ability of cardiac magnetic resonance to identify pericardial constriction as a sequela of purulent pericarditis, and indications for pericardiectomy.

Optimizing Use of High-Sensitivity Troponin for Risk-Stratification of Acute Pulmonary Embolism.

BACKGROUND: High-sensitivity troponin T (HS-TnT) may improve risk-stratification in hemodynamically stable acute pulmonary embolism (PE), but an optimal strategy for combining this biomarker with clinical risk-stratification tools has not been determined. STUDY HYPOTHESIS: We hypothesized that different HS-TnT cutoff values may be optimal for identifying (1) low-risk patients who may be eligible for outpatient management and (2) patients at increased risk of clinical deterioration who might benefit from advanced PE therapies. METHODS: Retrospective analysis of hemodynamically stable patients in the University of Michigan acute ED-PE registry with available HS-TnT values. Primary and secondary outcomes were 30-day mortality and need for intensive care unit-level care. Receiver operating characteristic curves were used to determine optimal HS-TnT cutoffs in the entire cohort, and for those at higher risk based on the simplified Pulmonary Embolism Severity Index (PESI) or imaging findings. RESULTS: The optimal HS-TnT cutoff in the full cohort, 12 pg/mL, was significantly associated with 30-day mortality (odds ratio [OR]: 3.94, 95% confidence interval [CI]: 1.48-10.50) and remained a significant predictor after adjusting for the simplified PESI (sPESI) score and serum creatinine (adjusted OR: 3.05, 95% CI: 1.11-8.38). A HS-TnT cutoff of 87 pg/mL was associated with 30-day mortality (OR: 5.01, 95% CI: 2.08-12.06) in patients with sPESI ≥1 or right ventricular dysfunction. CONCLUSION: In this retrospective, single-center study of acute PE patients, we identified distinct optimal HS-TnT values for different clinical uses-a lower cutoff, which identified low-risk patients even in the absence of other risk-stratification methods, and a higher cutoff, which was strongly associated with adverse outcomes in patients at increased risk.

Fatty acids and inflammatory stimuli induce expression of long-chain acyl-CoA synthetase 1 to promote lipid remodeling in diabetic kidney disease.

Fatty acid handling and complex lipid synthesis are altered in the kidney cortex of diabetic patients. We recently showed that inhibition of the renin-angiotensin system without changes in glycemia can reverse diabetic kidney disease (DKD) and restore the lipid metabolic network in the kidney cortex of diabetic (db/db) mice, raising the possibility that lipid remodeling may play a central role in DKD. However, the roles of specific enzymes involved in lipid remodeling in DKD have not been elucidated. In the present study, we used this diabetic mouse model and a proximal tubule epithelial cell line (HK2) to investigate the potential relationship between long-chain acyl-CoA synthetase 1 (ACSL1) and lipid metabolism in response to fatty acid exposure and inflammatory signals. We found ACSL1 expression was significantly increased in the kidney cortex of db/db mice, and exposure to palmitate or tumor necrosis factor-α significantly increased Acsl1 mRNA expression in HK-2 cells. In addition, palmitate treatment significantly increased the levels of long-chain acylcarnitines and fatty acyl CoAs in HK2 cells, and these increases were abolished in HK2 cell lines with specific deletion of Acsl1(Acsl1KO cells), suggesting a key role for ACSL1 in fatty acid ß-oxidation. In contrast, tumor necrosis factor-α treatment significantly increased the levels of short-chain acylcarnitines and long-chain fatty acyl CoAs in HK2 cells but not in Acsl1KO cells, consistent with fatty acid channeling to complex lipids. Taken together, our data demonstrate a key role for ACSL1 in regulating lipid metabolism, fatty acid partitioning, and inflammation.

Prediction of in-hospital deterioration in normotensive pulmonary embolism remains elusive: external validation of the calgary acute pulmonary embolism score.

Acute pulmonary embolism (PE) is a frequently diagnosed condition. Prediction of in-hospital deterioration is challenging with current risk models. The Calgary Acute Pulmonary Embolism (CAPE) score was recently derived to predict in-hospital adverse PE outcomes but has not yet been externally validated. Retrospective cohort study of normotensive acute pulmonary embolism cases diagnosed in our emergency department between 2017 and 2019. An external validation of the CAPE score was performed in this population for prediction of in-hospital adverse outcomes and a secondary outcome of 30-day all-cause mortality. Performance of the simplified Pulmonary Embolism Severity Index (sPESI) and Bova score was also evaluated. 712 patients met inclusion and exclusion criteria, with 536 patients having a sPESI score of 1 or more. Among this population, the CAPE score had a weak discriminative power to predict in-hospital adverse outcomes, with a calculated c-statistic of 0.57. In this study population, an external validation study found weak discriminative power of the CAPE score to predict in-hospital adverse outcomes among normotensive PE patients. Further efforts are needed to define risk assessment models that can identify normotensive PE patients at risk for in hospital deterioration. Identification of such patients will better guide intensive care utilization and invasive procedural management of PE.