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.

A simplified methodology for the activation of organic charcoal.

One in three people globally are challenged to live on hazardous, unsanitary water, and this relates to higher risks of death and development of diseases. According to scientific research, activated charcoal can be used to clean water contaminants to help make water safer.•Carbonization: this study demonstrates an inexpensive method of producing activated charcoal that can be performed in any setting using locally available biomass materials.•Activation: thermal air oxidation between moderate temperatures of 450-550 °C. Our data indicate that this technique produces charcoal with an adsorptive capacity near to that of commercial-grade charcoal as demonstrated by spectrophotometric analysis. This simple approach to charcoal activation may benefit rural communities where sources of sanitary water are low or nonexistent.

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.

Adverse Clinical Outcomes Among Patients With Acute Low-risk Pulmonary Embolism and Concerning Computed Tomography Imaging Findings.

Importance: Most patients presenting to US emergency departments (EDs) with acute pulmonary embolism (PE) are hospitalized, despite evidence from multiple society-based guidelines recommending consideration of outpatient treatment for those with low risk stratification scores. One barrier to outpatient treatment may be clinician concern regarding findings on PE-protocol computed tomography (CTPE), which are perceived as high risk but not incorporated into commonly used risk stratification tools. Objective: To evaluate the association of concerning CTPE findings with outcomes and treatment of patients in the ED with acute, low-risk PE. Design, Setting, and Participants: This cohort study used a registry of all acute PEs diagnosed in the adult ED of an academic medical center from October 10, 2016, to December 31, 2019. Acute PE cases were divided into high- and low-risk groups based on PE Severity Index (PESI) class alone or using a combination of PESI class and biomarker results. The low-risk group was further divided based on the presence of concerning CTPE findings: (1) bilateral central embolus, (2) right ventricle-to-left ventricle ratio greater than 1.0, (3) right ventricle enlargement, (4) septal abnormality, or (5) pulmonary infarction. Data analysis was conducted from June to October 2022. Main Outcomes and measures: The primary outcome was all-cause mortality at 7 and 30 days. Secondary outcomes included hospitalization, length of stay, need for intensive care, use of echocardiography and/or bedside ultrasonography, and activation of the PE response team (PERT) . Results: Of 817 patients (median [IQR] age, 58 [47-71] years; 417 (51.0%) female patients; 129 [15.8%] Black and 645 [78.9%] White patients) with acute PEs, 331 (40.5%) were low risk and 486 (59.5%) were high risk by PESI score. Clinical outcomes were similar for all low-risk patients, with no 30-day deaths in the low-risk group with concerning CTPE findings (0 of 151 patients) vs 4 of 180 (2.2%) in the low-risk group without concerning CTPE findings and 88 (18.1%) in the high-risk group (P < .001). Low-risk patients with concerning CTPE findings were less frequently discharged from the ED than those without concerning CTPE findings (3 [2.0%] vs 14 [7.8%]; P = .01) and had more frequent echocardiography (87 [57.6%] vs 49 [27.2%]; P < .001) and PERT activation for consideration of advanced therapies (34 [22.5%] vs 11 [6.1%]; P < .001). Conclusions and Relevance: In this single-center study, CTPE findings widely believed to confer high risk were associated with increased hospitalization and resource utilization in patients with low-risk PE but not short-term adverse clinical outcomes.

Effect of pulmonary embolism response team on advanced therapies administered: The University of Michigan experience.

BACKGROUND: Pulmonary Embolism Response Teams (PERT) were employed at multiple institutions to bridge the gap between varied treatment options for acute PE and unclear evidence for optimal management. There is limited data regarding the impact of PERT on the use of advanced therapies and clinical outcomes. METHODS: We performed a retrospective single-center cohort study comparing patients that presented to the ED with an acute PE before and after the creation of PERT in June 2017 at our institution. We assessed utilization of advanced therapies, LOS, and mortality. RESULTS: A total of 817 patients (168 pre-PERT, 649 post-PERT) were evaluated in the ED with an acute PE between October 2016 and December 2019. Both groups were similar in demographics, comorbidities, and PESI score. There was a decrease in advanced therapy use (16 % vs. 7.5 %, p = 0.006) after PERT creation. Most notable decreases were in catheter-based therapies (8.5 % vs. 2.2 %, p = 0.008) and IVC filter placement (5.3 % vs. 3.2 %, p < 0.001). Median ICU LOS (2.5 days vs. 2.3 days, p = 0.55) and hospital LOS (3.1 vs. 3.0, p = 0.92) did not vary pre-PERT vs. post-PERT. In-hospital mortality (8.5 % vs. 5.0 %, p = 0.29) and 30-day all-cause mortality (1.2 % vs. 0.5 %, p = 0.28) were not different between the two groups as well. CONCLUSION: At our institution, PERT was associated with a decrease in advanced therapies administered to acute PE patients without affecting mortality or LOS. Additional studies to assess impact of this multi-disciplinary care team model on interventional therapies and clinical outcomes for PE at a broader level are necessary.

A Matched Case-Control Analysis of Clinical Outcomes for Patients With Inflammatory Bowel Disease and Rectal Cancer Treated With Pelvic Radiation Therapy.

PURPOSE: Inflammatory bowel disease (IBD) is a known risk factor for rectal cancer, and RT is often an important part of therapy for these patients. Previously published studies have raised concerns for increased rates of RT toxicity in patients with IBD. We performed a matched case-control analysis to assess RT-related toxicity in a large sample of U.S. veterans afflicted with IBD and rectal cancer. METHODS AND MATERIALS: We identified 186 veterans with rectal cancer (71 Patients with IBD treated with RT, 71 matched controls without IBD treated with RT, and 44 nonmatched controls with IBD treated without RT) diagnosed between 2000 and 2015. We analyzed short- and long-term toxicity and mortality in multivariable logistic regression, Fine-Gray, and frailty models, adjusting for potential confounders. RESULTS: When comparing patients with and without IBD treated with RT there were no differences in RT breaks (adjusted odds ratio [aOR], 1.70; 95% confidence interval [CI], 0.38-4.76; P = .49) or the need for antidiarrheal medication during RT (aOR, 1.53; 95% CI, 0.70-3.35; P = .29). There was a trend toward higher risk of hospital admission during RT for RT + patients with IBD (aOR, 2.69; 95% CI, 0.88-8.22; P = .08). There were higher rates of small bowel obstruction (OR, 15; 95% CI, 1.9-115; P = .009) and a trend toward higher rates of abdominopelvic adhesions (OR, 3.6; 95% CI, 0.98-13; P = .05) in the RT + IBD cohort. However, compared with a nonmatched cohort of patients with IBD treated without RT there were no differences in long-term complications. No differences were found in other acute or long-term toxicities. Rectal cancer-specific mortality appeared similar across all cohorts. CONCLUSIONS: RT does not appear to increase the rates of acute or long-term toxicity in patients with IBD and should be considered a standard part of therapy when otherwise indicated.

Chronic Myocardial Ischemia Leads to Loss of Maximal Oxygen Consumption and Complex I Dysfunction.

BACKGROUND: Cardiomyocytes rely heavily on mitochondrial energy production through oxidative phosphorylation. Chronic myocardial ischemia may cause mitochondrial dysfunction and affect ATP formation. Metabolic changes due to ischemia alters cardiac bioenergetics and hence myocardial function and overall bioenergetic state. Here, we evaluate differences in functional status of respiratory complexes in mitochondrial isolates extracted from left atrial appendage tissue (LAA) from patients undergoing cardiac surgery, with and without chronic ischemia. METHODS: Mitochondrial isolates were extracted from LAA in ischemic coronary artery bypass grafting patients (n = 8) and non-ischemic control patients (n = 6) undergoing other cardiac surgery (valve repair/replacement). Coupling and electron transport chain assays were performed using Seahorse XFe 96 (Agilent Technologies, Santa Clara, CA) analyzer. Oxygen consumption rates were measured to calculate respiration states. RESULTS: Respiratory control rate (RCR) in ischemic patients was significantly lower than control patients (6.17 ± 0.27 vs 7.11 ± 0.31, respectively; p < 0.05). This is the result of minimal, non-significant state 3ADP and state 4O changes in chronic ischemia. Complex I respiration is diminished in ischemic tissue (99.1 ± 14.9 vs 257.8 ± 65.2 in control; p < 0.01). Maximal complex I/II respiration ratio was significantly lower in ischemic patients (58.9% ± 5.5% vs 90.9% ± 8.8%; p < 0.05), a difference that was also seen in complex I/IV ratios (p < 0.05). There was no significant difference in complex II/IV ratios between groups. CONCLUSIONS: Ischemic patients have aberrant mitochondrial function, highlighted by a lowered RCR. All ratios involving complex I were affected, suggesting that the insufficient ATP formation is predominantly due to complex I dysfunction. Complex II and IV respiration may be impaired as well, but to a lesser extent.