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Introduction: High-dose catecholamines can impair hypoxic pulmonary vasoconstriction and increase shunt fraction. We aimed to determine if Angiotensin II (Ang-2) is associated with improved PaO2/FiO2 and SpO2/FiO2 in patients in shock. Methods: Adult patients at four tertiary care centers and one community hospital in the United States who received Ang-2 from July 2018-September 2020 were included in this retrospective, observational cohort study. PaO2, SpO2, and FiO2 were measured at 13 timepoints during the 48-h before and after Ang-2 initiation. Piecewise linear mixed models of PaO2/FiO2 and SpO2/FiO2 were created to evaluate hourly changes in oxygenation after Ang-2 initiation. The difference in the proportion of patients with PaO2/FiO2 ≤ 300 mm Hg at the time of Ang-2 initiation and 48 h after was also examined. Results: The study included 254 patients. In the 48 h prior to Ang-2 initiation, oxygenation was significantly declining (hourly PaO2/FiO2 change −4.7 mm Hg/hr, 95% CI − 6.0 to −3.5, p <.001; hourly SpO2/FiO2 change −3.1/hr, 95% CI−3.7 to −2.4, p <.001). Ang-2 treatment was associated with significant improvements in PaO2/FiO2 and SpO2/FiO2 in the 48-h after initiation (hourly PaO2/FiO2 change +1.5 mm Hg/hr, 95% CI 0.5-2.5, p =.003; hourly SpO2/FiO2 change +0.9/hr, 95% CI 0.5-1.2, p <.001). The difference in the hourly change in oxygenation before and after Ang-2 initiation was also significant (p interaction < 0.001 for both PaO2/FiO2 and SpO2/FiO2). This improvement was associated with significantly fewer patients having a PaO2/FiO2 ≤ 300 mm Hg at 48 h compared to baseline (mean difference −14.9%, 95% CI −25.3% to −4.6%, p =.011). Subgroup analysis found that patients with either a baseline PaO2/FiO2 ≤ 300 mm Hg or a norepinephrine-equivalent dose requirement >0.2 µg/kg/min had the greatest associations with oxygenation improvement. Conclusions: Ang-2 is associated with improved PaO2/FiO2 and SpO2/FiO2. The mechanisms for this improvement are not entirely clear but may be due to catecholamine-sparing effect or may also be related to improved ventilation-perfusion matching, intrapulmonary shunt, or oxygen delivery. [ABSTRACT FROM AUTHOR]

Introduction: Angiotensin II (Ang-2) is a non-catecholamine vasopressor that targets the renin-angiotensin-aldosterone system by agonism of the angiotensin type 1 receptor. Its utility as a vasopressor and a catecholamine-sparing agent was demonstrated in the pivotal ATHOS-3 trial, and numerous post-hoc analyses have shown reduced mortality in certain subsets of the population. Methods: Consecutive adult patients at 5 centers who received Ang-2 from 2017-2020 were included in this multicenter, retrospective observational cohort study. Patient demographics, hemodynamics, and adverse events were collected. The primary outcomes of the study were the mean difference in MAP and norepinephrine (NEpi)-equivalent dose at hours 0 and 3 following initiation of Ang-2 therapy. Results: One hundred and sixty-two patients were included in this study. The primary outcomes of an increase in MAP (mean difference 9.3 mmHg, 95% CI 6.4-12.1, p < 0.001) and a reduction in NEpi equivalent dose (mean difference 0.16 µg/kg/min, 95% CI 0.10-0.22, p < 0.001) between hours 0 and 3 were statistically significant. The median time to reach a MAP ≥65 was 16 minutes (IQR 5-60 min). After stratifying patients by the NED dose and number of vasopressors administered prior to the initiation of Ang-2, those with a NED dose < 0.2 µg/kg/min, NED dose < 0.3 µg/kg/min, or those on ≤ 3 vasopressors had a significantly greater reduction in NED by hour 3 than those patients above these thresholds. Conclusion: Ang-2 is an effective vasopressor and reduces catecholamine dose significantly. Its effect is rapid, with target MAP obtained within 30 minutes in most patients. Given the critical importance of adequate blood pressure to organ perfusion, Ang-2 should be considered when target MAP cannot be achieved with conventional vasopressors. Ang-2 should be utilized early in the course of shock, before the NED dose exceeds 0.2-0.3 µg/kg/min and before the initiation of the fourth-line vasopressor. [ABSTRACT FROM AUTHOR]

Sepsis is one of the biggest risks to patient safety, with a natural mortality rate between 25% and 50%. It is difficult to diagnose, and no validated standard for diagnosis currently exists. A commonly used scoring criteria is the quick sequential organ failure assessment (qSOFA). It demonstrates very low specificity in ICU populations, however. We develop a method to personalize thresholds in qSOFA that incorporates easily to measure patient baseline characteristics. We compare the personalized threshold method to qSOFA, five previously published methods that obtain an optimal constant threshold for a single biomarker, and to the machine learning algorithms based on logistic regression and AdaBoosting using patient data in the MIMIC-III database. The personalized threshold method achieves higher accuracy than qSOFA and the five published methods and has comparable performance to machine learning methods. Personalized thresholds, however, are much easier to adopt in real-life monitoring than machine learning methods as they are computed once for a patient and used in the same way as qSOFA, whereas the machine learning methods are hard to implement and interpret. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine whether fungicidal versus fungistatic pharmacotherapy of invasive candidiasis/candidemia yields superior outcomes. Data sources included MEDLINE (1966-June 2017), EMBASE (1980-June 2017), PubMed (1966-June 2017), Global Health-Ovid (inception to June 2017), LILACS Virtual Health Library (inception to June 2017) and the Cochrane Central Register of Controlled Trials (to 2nd quarter 2017). The ClinicalTrial.gov database, the SCOPUS database, SIGLE (System for Information on Grey Literature) and Google Scholar were also utilised to search for relevant studies. Randomised studies of any pharmacotherapy of invasive candidiasis including candidemia using a fungicidal (amphotericin B or echinocandin compound) versus a fungistatic (triazole) compound in adolescent or adult non-neutropenic patients. Eight studies met the inclusion criteria. Pooled odds ratios demonstrated an advantage of fungicidal therapy with respect to early therapeutic success (OR 1.61, 95% CI 1.27-2.03, p < 0.0001, I2 = 0%) and persistence or recurrence of infection (OR 0.51, 95% CI 0.35-0.74, p = 0.0005, I2 = 0%) but no advantage for late survival (OR 0.97, 95% CI 0.77-1.21, p = 0.77, I2 = 0%). Fungicidal therapy of invasive candidiasis and candidemia is associated with a higher probability of early therapeutic success and decreased probability of persistent or recurrent infection. However, there is no improvement in survival. [ABSTRACT FROM AUTHOR]

Objectives: To determine the clinical characteristics and outcomes of culture-negative septic shock in comparison with culture-positive septic shock. Design: Retrospective nested cohort study. Setting: ICUs of 28 academic and community hospitals in three countries between 1997 and 2010. Subjects: Patients with culture-negative septic shock and culturepositive septic shock derived from a trinational (n = 8,670) database of patients with septic shock. Interventions: None. Measurements and Main Results: Patients with culture-negative septic shock (n = 2,651; 30.6%) and culture-positive septic shock (n = 6,019; 69.4%) were identified. Culture-negative septic shock compared with culture-positive septic shock patients experienced similar ICU survival (58.3% vs 59.5%; p = 0.276) and overall hospital survival (47.3% vs 47.1%; p = 0.976). Severity of illness was similar between culture-negative septic shock and culture-positive septic shock groups ([mean and SD Acute Physiology and Chronic Health Evaluation II, 25.7 ± 8.3 vs 25.7 ± 8.1]; p = 0.723) as were serum lactate levels (3.0 [interquartile range, 1.7–6.1] vs 3.2 mmol/L [interquartile range, 1.8–5.9 mmol/L]; p = 0.366). As delays in the administration of appropriate antimicrobial therapy after the onset of hypotension increased, patients in both groups experienced congruent increases in overall hospital mortality: culture-negative septic shock (odds ratio, 1.56; 95% CI [1.47–1.66]; p < 0.0001) and culture-positive septic shock (odds ratio, 1.65; 95% CI [1.59–1.71]; p < 0.0001). Conclusions: Patients with culture-negative septic shock behave similarly to those with culture-positive septic shock in nearly all respects; early appropriate antimicrobial therapy appears to improve mortality. Early recognition and eradication of infection is the most obvious effective strategy to improve hospital survival. [ABSTRACT FROM AUTHOR]

There is a large body of experimental evidence in research animals and in vitro models that opioids suppress the immune system. If this effect occurs in acute human disease, then patients cared for in Intensive Care Units (ICUs) would be a particularly vulnerable population. ICU patients have the most severe forms of acute infection, have the greatest risk of acquiring new infections in the hospital, and are exposed to high doses of opioids for long periods of time. We review the epidemiology of ICU infections and the pharmacoepidemiology of opioid use in critically ill patients. We critique the limited human research examining the relationship between opioids and infection and make recommendations on designing future clinical studies that could close the knowledge gap about the true hazards of opioid use in hospitalized patients. [ABSTRACT FROM AUTHOR]

Pulmonary epitheloid hemangioendothelioma (PEHE) is a rare, often incidentally diagnosed, endothelial tumor of the lung. We present a case of a young adult who presented with acute hypoxemic respiratory failure and severe pulmonary hypertension with subsequent imaging and tissue biopsy confirming a diagnosis of PEHE. We briefly highlight the unique clinical, radiographic and histopathologic aspects of this rare disease. We propose that PEHE should be considered in the differential diagnosis for acute hypoxemic respiratory failure associated with bilateral pulmonary cavitary nodules and bronchoscopy should be considered as an initial diagnostic test. [ABSTRACT FROM AUTHOR]

Background: Developing a decision support system based on advances in machine learning is one area for strategic innovation in healthcare. Predicting a patient's progression to septic shock is an active field of translational research. The goal of this study was to develop a working model of a clinical decision support system for predicting septic shock in an acute care setting for up to 6 h from the time of admission in an integrated healthcare setting. Method: Clinical data from Electronic Health Record (EHR), at encounter level, were used to build a predictive model for progression from sepsis to septic shock up to 6 h from the time of admission; that is, T = 1, 3, and 6 h from admission. Eight different machine learning algorithms (Random Forest, XGBoost, C5.0, Decision Trees, Boosted Logistic Regression, Support Vector Machine, Logistic Regression, Regularized Logistic, and Bayes Generalized Linear Model) were used for model development. Two adaptive sampling strategies were used to address the class imbalance. Data from two sources (clinical and billing codes) were used to define the case definition (septic shock) using the Centers for Medicare & Medicaid Services (CMS) Sepsis criteria. The model assessment was performed using Area under Receiving Operator Characteristics (AUROC), sensitivity, and specificity. Model predictions for each feature window (1, 3 and 6 h from admission) were consolidated. Results: Retrospective data from April 2005 to September 2018 were extracted from the EHR, Insurance Claims, Billing, and Laboratory Systems to create a dataset for septic shock detection. The clinical criteria and billing information were used to label patients into two classes-septic shock patients and sepsis patients at three different time points from admission, creating two different case-control cohorts. Data from 45,425 unique in-patient visits were used to build 96 prediction models comparing clinical-based definition versus billing-based information as the gold standard. Of the 24 consolidated models (based on eight machine learning algorithms and three feature windows), four models reached an AUROC greater than 0.9. Overall, all the consolidated models reached an AUROC of at least 0.8820 or higher. Based on the AUROC of 0.9483, the best model was based on Random Forest, with a sensitivity of 83.9% and specificity of 88.1%. The sepsis detection window at 6 h outperformed the 1 and 3-h windows. The sepsis definition based on clinical variables had improved performance when compared to the sepsis definition based on only billing information. Conclusion: This study corroborated that machine learning models can be developed to predict septic shock using clinical and administrative data. However, the use of clinical information to define septic shock outperformed models developed based on only administrative data. Intelligent decision support tools can be developed and integrated into the EHR and improve clinical outcomes and facilitate the optimization of resources in real-time. [ABSTRACT FROM AUTHOR]