Kidney-specific biomarkers for predicting acute kidney injury following cardiac arrest.

AIM: To evaluate the performance of kidney-specific biomarkers (neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and cystatin-C) in early detection of acute kidney injury (AKI) following cardiac arrest (CA) when compared to serum creatinine. METHODS: Adult CA patients who had kidney-specific biomarkers of AKI collected within 12 h of return of spontaneous circulation (ROSC) were included. The association between renal biomarker levels post-ROSC and the development of KDIGO stage III AKI within 7 days of enrollment were assessed as well as their predictive value of future AKI development, neurological outcomes, and survival to discharge. RESULTS: Of 153 patients, 54 (35%) developed stage III AKI within 7 days, and 98 (64%) died prior to hospital discharge. Patients who developed stage III AKI, compared to those who did not, had higher median levels of creatinine, NGAL, and cystatin-C (p < 0.001 for all). There was no statistically significant difference in KIM-1 between groups. No biomarker outperformed creatinine in the ability to predict stage III AKI, neurological outcomes, or survival outcomes (p > 0.05 for all). However, NGAL, cystatin-C, and creatinine all performed better than KIM-1 in their ability to predict AKI development (p < 0.01 for all). CONCLUSION: In post-CA patients, creatinine, NGAL, and cystatin-C (but not KIM-1) measured shortly after ROSC were higher in patients who subsequently developed AKI. No biomarker was statistically superior to creatinine on its own for predicting the development of post-arrest AKI.

Lactate and hypotension as predictors of mortality after in-hospital cardiac arrest.

AIM: Guidance on post-cardiac arrest prognostication is largely based on data from out-of-hospital cardiac arrest (OHCA), despite clear differences between the OHCA and in-hospital cardiac arrest (IHCA) populations. Early prediction of mortality after IHCA would be useful to help make decisions about post-arrest care. We evaluated the ability of lactate and need for vasopressors after IHCA to predict hospital mortality. METHODS: Single center retrospective observational study of adult IHCA patients who achieved sustained return of spontaneous circulation (ROSC), required mechanical ventilation peri-arrest and had a lactate checked within 2 h after ROSC. We evaluated the association of post-ROSC lactate and need for vasopressors with mortality using multivariate logistic regression. RESULTS: A total of 364 patients were included. Patients who received vasopressors within 3 h after ROSC had significantly higher mortality compared to patients who did not receive vasopressors (58% vs. 43%, p = 0.03). Elevated lactate level was associated with mortality (44% if lactate <5 mmol/L, 58% if lactate 5-10 mmol/L, and 73% if lactate >10 mmol/L, p < 0.01). A multivariable model with lactate group and post-ROSC vasopressor use as predictors demonstrated moderate discrimination (AUC 0.64 [95%CI:0.59-0.70]). Including other variables, the most parsimonious model included lactate, age, body mass index, race, and history of arrhythmia, cancer and/or liver disease (AUC 0.70 [95% CI: 0.64-0.75]). CONCLUSION: Post-ROSC lactate and need for vasopressors may be helpful in stratifying mortality risk in patients requiring mechanical ventilation after IHCA.

Ubiquinol (Reduced Coenzyme Q10) and Cellular Oxygen Consumption in Patients Undergoing Coronary Artery Bypass Grafting.

Ubiquinol is a fundamental component of cellular metabolism. Low ubiquinol levels have been associated with mortality. This was a substudy of a randomized trial in patients undergoing coronary artery bypass grafting. We drew blood before and after surgery. Ubiquinol or placebo was added to peripheral blood mononuclear cells for oxygen consumption (OCR) measurements. In vivo ubiquinol levels were lower postsurgery compared to presurgery (0.16 µmol/L [quartiles: 0.02-0.39], P = .01), although the difference disappeared when adjusting for hemoglobin levels (P = .30). There was no difference in presurgical basal (1.0 mL/min/mg [95% confidence interval [CI]: -0.9 to 2.2], P = .08) and maximal (0.5 mL/min/mg [95% CI: -4.3 to 7.3], P = .56) OCR in cells receiving ubiquinol or placebo. There was a difference in postsurgical basal (1.1 mL/min/mg [95% CI: 0.9-1.6], P < .001) and maximal (4.2 mL/min/mg [95% CI: 0.3-7.0], P = .01) OCR between the groups. We found no association between ubiquinol and OCR levels (all P > .05).

Performance of the CURB-65 Score in Predicting Critical Care Interventions in Patients Admitted With Community-Acquired Pneumonia.

STUDY OBJECTIVE: Confusion, uremia, elevated respiratory rate, hypotension, and aged 65 years or older (CURB-65) is a clinical prediction rule intended to stratify patients with pneumonia by expected mortality. We assess the predictive performance of CURB-65 for the proximal endpoint of receipt of critical care intervention in emergency department (ED) patients admitted with community-acquired pneumonia. METHODS: We performed a retrospective analysis of electronic health records from a single tertiary center for ED patients admitted as inpatients with a primary diagnosis of pneumonia from 2010 to 2014. Patients with a history of malignancy, tuberculosis, bronchiectasis, HIV, or readmission within 14 days were excluded. We assessed the predictive accuracy of CURB-65 for receipt of critical care interventions (ie, vasopressors, large-volume intravenous fluids, invasive catheters, assisted ventilation, insulin infusions, or renal replacement therapy) and inhospital mortality. Logistic regression was performed to assess the increase in odds of critical care intervention or inhospital mortality by increasing CURB-65 score. RESULTS: There were 2,322 patients admitted with community-acquired pneumonia in the study cohort; 630 (27.1%) were admitted to the ICU within 48 hours of ED triage and 343 (14.8%) received a critical care intervention. Of patients with a CURB-65 score of 0 to 1, 181 (15.6%) were admitted to the ICU, 74 (6.4%) received a critical care intervention, and 7 (0.6%) died. Of patients with a CURB-65 score of 2, 223 (27.0%) were admitted to the ICU, 127 (15.4%) received a critical care intervention, and 47 (5.7%) died. Among patients with CURB-65 score greater than or equal to 3, 226 (67.0%) were admitted to the ICU, 142 (42.1%) received a critical care intervention, and 43 (12.8%) died. The areas under the receiver operating characteristic for CURB-65 as a predictor of critical care intervention and mortality were 0.73 and 0.77, whereas sensitivity of CURB-65 score greater than or equal to 2 in predicting critical care intervention was 78.4%; for mortality, 92.8%. CONCLUSION: Patients with CURB-65 score less than or equal to 2 were often admitted to the ICU and received critical care interventions. Given this finding and the relatively low sensitivity of CURB-65 for critical care intervention, clinicians should exercise caution when using CURB-65 to guide disposition. Future ED-based clinical prediction rules may benefit from calibration to proximal endpoints.

The Effects of Thiamine on Breast Cancer Cells.

(1) Background: Thiamine is an important cofactor for multiple metabolic processes. Its role in cancer has been debated for years. Our aim is to determine if thiamine can convert the cellular metabolic state of breast cancer cells from anaerobic to aerobic, thus reducing their growth. (2) Methods: Breast cancer (MCF7) and non-tumorigenic (MCF10A) cell lines were treated with various doses of thiamine and assessed for changes in cell growth. The mechanism of this relationship was identified through the measurement of enzymatic activity and metabolic changes. (3) Results: A high dose of thiamine reduced cell proliferation in MCF7 (63% decrease, p < 0.0001), but didn't affect apoptosis and the cell-cycle profile. Thiamine had a number of effects in MCF7; it (1) reduced extracellular lactate levels in growth media, (2) increased cellular pyruvate dehydrogenase (PDH) activities and the baseline and maximum cellular oxygen consumption rates, and (3) decreased non-glycolytic acidification, glycolysis, and glycolytic capacity. MCF10A cells preferred mitochondrial respiration instead of glycolysis. In contrast, MCF7 cells were more resistant to mitochondrial respiration, which may explain the inhibitory effect of thiamine on their proliferation. (4) Conclusions: The treatment of MCF7 breast cancer cells with 1 µg/mL and 2 µg/mL of thiamine for 24 h significantly reduced their proliferation. This reduction is associated with a reduction in glycolysis and activation of the PDH complex in breast cancer cells.

The association between hemoglobin concentration and neurologic outcome after cardiac arrest.

PURPOSE: The purpose of the study is to determine the association between hemoglobin concentration (Hgb) and neurologic outcome in postarrest patients. METHODS: We conducted a retrospective cohort study using the Penn Alliance for Therapeutic Hypothermia (PATH) cardiac arrest registry. Inclusion criteria were resuscitated cardiac arrest (inhospital or out of hospital) and an Hgb value recorded within 24 hours of return of spontaneous circulation. The primary outcome was favorable neurologic status at hospital discharge. Survival to hospital discharge was a secondary outcome. RESULTS: There were 598 eligible patients from 21 hospitals. Patients with favorable neurologic outcome had significantly higher median Hgb in the first 2 hours (12.7 vs 10.5 g/dL; P<.001) and 6 hours (12.6 vs 10.6 g/dL; P<.001) postarrest. Controlling for age, pulseless rhythm, etiology, location of arrest, receipt of targeted temperature management, hematologic or metastatic malignancy, or preexisting renal insufficiency, there was a significant relationship between Hgb and neurologic outcome within the first 6 hours after arrest (odds ratio, 1.23; 95% confidence interval, 1.09-1.38) and survival to hospital discharge (odds ratio, 1.20; 95% confidence interval, 1.08-1.34). CONCLUSION: Higher Hgb after cardiac arrest is associated with favorable neurologic outcome, particularly within the first 6 hours. It is unclear if this effect is due to impaired oxygen delivery or if Hgb is a marker for more severe illness.

Inflammatory markers following resuscitation from out-of-hospital cardiac arrest-A prospective multicenter observational study.

AIM: The post-cardiac arrest syndrome is a complex set of pathophysiological processes including a systemic inflammatory response. The goal of the current investigation was to test the hypothesis that early inflammatory markers are independently associated with in-hospital mortality and poor neurological outcome in patients initially resuscitated from out-of-hospital cardiac arrest. METHODS: This was a preplanned analysis of data collected from a prospective observational multicenter study in adult out-of-hospital cardiac arrest patients. Blood was drawn at baseline, 12 and 24h after return of spontaneous circulation and plasma levels of interleukin (IL)-1ß, IL-1 receptor antagonist (IL-1Ra), IL-6, IL-8, IL-10 and tumor necrosis factor (TNF)-α were measured. The primary outcome measure was survival to hospital discharge. We utilized a mixed linear model to compare the levels of cytokines in survivors and non-survivors over time. We used multivariable logistic regression to assess the association between IL-6 levels and mortality. RESULTS: A total of 102 patients were analyzed. Non-survivors and patients with poor functional outcome had statistical significant higher IL-1Ra, IL-6, IL-8, and IL-10 levels (all p<0.001) at all time points (0, 12 and 24h) compared to survivors. Baseline IL-6 levels were a good predictor of mortality (AUC=0.83 [95%CI: 0.75-0.92]). Baseline IL-6 levels were strongly associated with mortality in multivariable analysis (OR: 2.58 [95%CI: 1.93-3.45], p<0.001) but were not associated with neurological outcome in multivariable analysis (OR: 1.33 [95%CI: 0.62-2.86], p=0.47). CONCLUSION: Early inflammatory markers, especially IL-6, are higher in patients with a poor outcome after OHCA. IL-6 remained associated with mortality, but not functional outcome, in multivariable analysis adjusting for patient and event characteristics.

Initial clinical predictors of significant coronary lesions after resuscitation from cardiac arrest.

Urgent coronary angiography following cardiac arrest is an important consideration as part of a therapeutic hypothermia/postresuscitation care bundle. Few data exist to guide the selection of patients who should receive postarrest angiography. This investigation sought to evaluate patient-level variables on initial postarrest presentation and their association with significant coronary lesions on subsequent angiography. Clinical and angiographic data were collected on consecutive postarrest patients from July 2007 to April 2012 who underwent coronary angiography during hospitalization. Univariate and multivariable analyses were performed to determine the relationship between patient characteristics, clinical data, and the outcome measure, defined as the presence of at least one coronary lesion with >75% stenosis. Of 527 cardiac arrest patients, 267 achieved return of spontaneous circulation; 106 of these initial survivors received coronary angiography. This cohort had a mean age of 58.1±13.5 years and a survival to discharge of 73/106 (69%), with therapeutic hypothermia utilized in 79/106 (75%) patients. Significant coronary lesions were found on angiography in 68/106 (64%) patients. Multivariable adjusted analysis demonstrated that significant lesions were associated with a prior known history of coronary disease and/or prior myocardial infarction (odds ratio [OR] 6.2, 95% confidence interval [CI] 1.6-24.4, p=0.009), and with initial rhythm of ventricular fibrillation/ventricular tachycardia (OR 2.9, 95% CI 1.1-7.7, p=0.033), but not with hypertension, tobacco use, age, or initial troponin measurements. Prior known history of coronary disease and a shockable arrest rhythm were associated with significant coronary lesions on subsequent angiography. Normal initial troponin values and younger age did not exclude clinically relevant lesions postarrest.