bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of an Updated Risk Stratification Index to Hierarchical Condition Categories
Authors: Chamoun George F. , Li Linyan , Chamoun Nassib G. , Saini Vikas , Sessler Daniel I. 
Published: October 2017

Abstract

Background
The Risk Stratification Index and the Hierarchical Condition Categories model baseline risk using comorbidities and procedures. The Hierarchical Condition categories are rederived yearly, whereas the Risk Stratification Index has not been rederived since 2010. The two models have yet to be directly compared. The authors thus rederived the Risk Stratification Index using recent data and compared their results to contemporaneous Hierarchical Condition Categories.

Methods
The authors reimplemented procedures used to derive the original Risk Stratification Index derivation using the 2007 to 2011 Medicare Analysis and Provider review file. The Hierarchical Condition Categories were constructed on the entire data set using software provided by the Center for Medicare and Medicaid Services. C-Statistics were used to compare discrimination between the models. After calibration, accuracy for each model was evaluated by plotting observed against predicted event rates.

Results
Discrimination of the Risk Stratification Index improved after rederivation. The Risk Stratification Index discriminated considerably better than the Hierarchical Condition Categories for in-hospital, 30-day, and 1-yr mortality and for hospital length-of-stay. Calibration plots for both models demonstrated linear predictive accuracy, but the Risk Stratification Index predictions had less variance.

Conclusions
Risk Stratification discrimination and minimum-variance predictions make it superior to Hierarchical Condition Categories. The Risk Stratification Index provides a solid basis for care-quality metrics and for provider comparisons.
Mortality After High-Energy Pelvic Fractures in Patients of Age 65 Years or Older
Authors: Keil Dayley S. , Gross Steven , Seymour Rachel B. , Sims Stephen , Karunakar Madhav A. 
Published: October 2017

Objectives:
To document in-hospital and 1-year mortality rates after high-energy pelvic fracture in patients 65 years of age or older as compared to a younger cohort.

Design:
Retrospective review.

Setting:
Urban Level 1 academic trauma center.

Patients:
Seventy consecutive patients 65 years of age and older treated for pelvic fracture resulting from high-energy mechanism from 2008 to 2011. A total of 140 patients 18–64 years of age were matched to the study population based on mechanism of injury and OTA Code 61 subtype for comparison.

Intervention:
Review of demographics, injury characteristics, hospital management, and mortality.

Main Outcome Measurements:
Mortality.

Results:
The overall inpatient mortality rate was 10%. The older cohort exhibited an inpatient mortality rate 3 times higher than the younger cohort (18.6% vs. 5.7%, P = 0.003). There was no difference in mortality 1 year post discharge (5.3% vs. 3.8%, P = 0.699). No significant differences in initial Glasgow Coma Scale or Injury Severity Score were identified (GCS 12.9 vs. 12.4, P = 0.363; ISS 24.7 vs. 23.4, P = 0.479). Multivariate analysis identified the Charlson Comorbidity Index (CCI) (P = 0.012) and Abbreviated Injury Scale (AIS)-chest (P = 0.005) as independent predictors of in-hospital mortality, and CCI (0.005) and AIS-abdomen (0.012) for 1-year mortality.

Conclusions:
After controlling for mechanism of injury and pelvic fracture classification, we found that adults ≥65 and those with multiple comorbidities were more likely to die in the hospital than younger adults. However, mortality within 1-year postdischarge was low and did not differ between groups. This is in sharp contrast to the high rates of postdischarge mortality observed in elderly patients with a hip fracture.

Level of Evidence:
Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
The β-Blocker Esmolol Restores the Vascular Waterfall Phenomenon After Acute Endotoxemia*
Authors: Du Wei , Liu Dawei , Long Yun , Wang Xiaoting 
Published: October 2017

Background:
A vascular waterfall occurs when the critical closing pressure is greater than the mean systemic filling pressure. Because the waterfall phenomenon likely exists in the microcirculation, β1-receptor blockers such as esmolol could have some effect on microcirculation and vascular waterfall.

Objectives:
To determine whether a vascular waterfall exists during septic shock and to assess the effects of vasopressors and β-blockers on vascular waterfall.

Design:
Sixteen mongrel dogs were mounted with ultrasonic flow probes to measure renal blood flow. The hemodynamic variables of 16 animals were measured at baseline, after induction of acute endotoxemia; then, they underwent volume expansion, and norepinephrine was used to achieve baseline. After achieving septic myocardial depression, the animals were randomly divided into two groups (esmolol vs control groups) after reaching septic myocardial depression.

Measurements and Main Results:
There was a pressure gap of 41.9 ± 13.9 mm Hg between the arterial critical closing pressure and the mean systemic filling pressure, indicating that a vascular waterfall was present under baseline conditions. Endotoxemia caused a decrease in cardiac output, mean arterial pressure, and critical closing pressure. Endotoxemia also caused the vascular waterfall to disappear. Neither volume expansion nor norepinephrine had any effect on the vascular waterfall. Esmolol infusion restored the vascular waterfall effect following endotoxemia and resuscitation. The 24-hour survival was 75% in the esmolol group versus 12.5% in controls (p = 0.041).

Conclusions:
Vascular pressure gradients in renal vasculature suggest the presence of a vascular waterfall at baseline. Although this phenomenon disappeared in endotoxemic dogs, it could be restored with β-blocker therapy (esmolol).
Evaluation of Vasopressin for Septic Shock in Patients on Chronic Renin-Angiotensin-Aldosterone System Inhibitors
Authors: Erwin Beth L. , Denaburg Michael A. , Barker Andrew B. , McArdle Philip J. , Windham Samuel T. , Morgan Charity J. 
Published: October 2017

Objectives:
To compare the hemodynamic response in septic shock patients receiving vasopressin who were on chronic renin-angiotensin-aldosterone system inhibitor therapy with those who were not.

Design:
Single-center, retrospective cohort study.

Setting:
Medical and surgical ICUs at a 1,100-bed academic medical center.

Patients:
Medical and surgical ICU patients with septic shock who received vasopressin infusion added to at least one concomitant vasopressor agent between January 2014 and December 2015, then divided into two cohorts: 1) patients who were on chronic renin-angiotensin-aldosterone system inhibitor therapy as outpatients and 2) patients who were not on chronic renin-angiotensin-aldosterone system inhibitor therapy as outpatients.

Interventions:
None.

Measurements and Main Results:
Mean arterial pressure at 6 hours was 72.2 mm Hg in the renin-angiotensin-aldosterone system inhibitor group versus 69.7 mm Hg in the non–renin-angiotensin-aldosterone system inhibitor group (p = 0.298). There was no difference in mean arterial pressure at 1, 24, or 48 hours between groups. Total concomitant vasopressor requirements, based on norepinephrine equivalents excluding vasopressin, were significantly lower at 24 hours in the renin-angiotensin-aldosterone system inhibitor group versus the non–renin-angiotensin-aldosterone system inhibitor group (10.7 vs 18.1 µg/min, respectively; p = 0.007), but no significant differences were seen at the other time points assessed. There were no significant differences in ICU or hospital length of stay or mortality.

Conclusions:
There was no significant difference in the primary outcome of 6-hour mean arterial pressure in septic shock patients receiving vasopressin who were on chronic renin-angiotensin-aldosterone system inhibitor therapy versus those receiving vasopressin who were not on chronic renin-angiotensin-aldosterone system inhibitor therapy. Renin-angiotensin-aldosterone system inhibitor patients had lower total concomitant vasopressor requirements at 24 hours compared with non–renin-angiotensin-aldosterone system inhibitor patients.
Relationship of at Admission Lactate, Unmeasured Anions, and Chloride to the Outcome of Critically Ill Patients
Authors: Masevicius Fabio Daniel , Rubatto Birri Paolo Nahuel , Risso Vazquez Alejandro , Zechner Facundo Emanuel , Motta María Fernanda , Valenzuela Espinoza Emilio Daniel , Welsh Sebastián , Guerra Arias Ernesto Fidel , Furche Mariano Andrés , Berdaguer Fernando Daniel , Dubin Arnaldo 
Published: October 2017

Objectives:
To investigate the association between the concentration of the causative anions responsible for the main types of metabolic acidosis and the outcome.

Design:
Prospective observational study.

Setting:
Teaching ICU.

Patients:
All patients admitted from January 2006 to December 2014.

Interventions:
None.

Measurements and Main Results:
Four thousand nine hundred one patients were admitted throughout the study period; 1,609 met criteria for metabolic acidosis and 145 had normal acid-base values. The association between at admission lactate, unmeasured anions, and chloride concentration with outcome was assessed by multivariate analysis in the whole cohort and in patients with metabolic acidosis. We also compared the mortality of patients with lactic, unmeasured anions, and hyperchloremic metabolic acidosis with that of patients without acid-base disorders. In the whole population, increased lactate and unmeasured anions were independently associated with increased mortality, even after adjusting for potential confounders (odds ratio [95% CI], 1.14 (1.08–1.20); p < 0.0001 and 1.04 (1.02–1.06); p < 0.0001, respectively). In patients with metabolic acidosis, the results were similar. Patients with lactic and unmeasured anions acidosis, but not those with hyperchloremic acidosis, had an increased mortality compared to patients without alterations (17.7%, 12.7%, 4.9%, and 5.8%, respectively; p < 0.05).

Conclusions:
In this large cohort of critically ill patients, increased concentrations of lactate and unmeasured anions, but not chloride, were associated with increased mortality. In addition, increased unmeasured anions were the leading cause of metabolic acidosis.
Sepsis Reduces Bone Strength Before Morphologic Changes Are Identifiable
Authors: Puthucheary Zudin A. , Sun Yao , Zeng Kaiyang , Vu Lien Hong , Zhang Zhi Wei , Lim Ryan Z. L. , Chew Nicholas S. Y. , Cove Matthew E. 
Published: October 2017

Objectives:
Survivors of critical illness have an increased prevalence of bone fractures. However, early changes in bone strength, and their relationship to structural changes, have not been described. We aimed to characterize early changes in bone functional properties in critical illness and their relationship to changes in bone structure, using a sepsis rodent model.

Design:
Experimental study.

Setting:
Animal research laboratory.

Subjects:
Adult Sprague-Dawley rats.

Interventions:
Forty Sprague-Dawley rats were randomized to cecal ligation and puncture or sham surgery. Twenty rodents (10 cecal ligation and puncture, 10 sham) were killed at 24 hours, and 20 more at 96 hours.

Measurements and Main Results:
Femoral bones were harvested for strength testing, microCT imaging, histologic analysis, and multifrequency scanning probe microscopy. Fracture loads at the femoral neck were significantly reduced for cecal ligation and puncture–exposed rodents at 24 hours (83.39 ± 10.1 vs 103.1 ± 17.6 N; p = 0.014) and 96 hours (81.60 ± 14.2 vs 95.66 ± 14.3 N; p = 0.047). Using multifrequency scanning probe microscopy, collagen elastic modulus was lower in cecal ligation and puncture–exposed rats at 24 hours (1.37 ± 0.2 vs 6.13 ± 0.3 GPa; p = 0.001) and 96 hours (5.57 ± 0.5 vs 6.13 ± 0.3 GPa; p = 0.006). Bone mineral elastic modulus was similar at 24 hours but reduced in cecal ligation and puncture–exposed rodents at 96 hours (75.34 ± 13.2 vs 134.4 ± 8.2 GPa; p < 0.001). There were no bone architectural or bone mineral density differences by microCT. Similarly, histologic analysis demonstrated no difference in collagen and elastin staining, and C-X-C chemokine receptor type 4, nuclear factor kappa beta, and tartrate-resistant acid phosphatase immunostaining.

Conclusions:
In a rodent sepsis model, trabecular bone strength is functionally reduced within 24 hours and is associated with a reduction in collagen and mineral elastic modulus. This is likely to be the result of altered biomechanical properties, rather than increased bone mineral turnover. These data offer both mechanistic insights and may potentially guide development of therapeutic interventions.
Pediatric Sepsis Endotypes Among Adults With Sepsis
Authors: Wong Hector R. , Sweeney Timothy E. , Hart Kimberly W. , Khatri Purvesh , Lindsell Christopher J. 
Published: October 2017

Objectives:
Recent transcriptomic studies describe two subgroups of adults with sepsis differentiated by a sepsis response signature. The implied biology and related clinical associations are comparable with recently reported pediatric sepsis endotypes, labeled “A” and “B.” We classified adults with sepsis using the pediatric endotyping strategy and the sepsis response signature and determined how endotype assignment, sepsis response signature membership, and age interact with respect to mortality.

Design:
Retrospective analysis of publically available transcriptomic data representing critically ill adults with sepsis from which the sepsis response signature groups were derived and validated.

Setting:
Multiple ICUs.

Patients:
Adults with sepsis.

Interventions:
None.

Measurements and Main Results:
Transcriptomic data were conormalized into a single dataset yielding 549 unique cases with sepsis response signature assignments. Each subject was assigned to endotype A or B using the expression data for the 100 endotyping genes. There were 163 subjects (30%) assigned to endotype A and 386 to endotype B. There was a weak, positive correlation between endotype assignment and sepsis response signature membership. Mortality rates were similar between patients assigned endotype A and those assigned endotype B. A multivariable logistic regression model fit to endotype assignment, sepsis response signature membership, age, and the respective two-way interactions revealed that endotype A, sepsis response signature 1 membership, older age, and the interactions between them were associated with mortality. Subjects coassigned to endotype A, and sepsis response signature 1 had the highest mortality.

Conclusions:
Combining the pediatric endotyping strategy with sepsis response signature membership might provide complementary, age-dependent, biological, and prognostic information.
Mortality Benefit of Recombinant Human Interleukin-1 Receptor Antagonist for Sepsis Varies by Initial Interleukin-1 Receptor Antagonist Plasma Concentration*
Authors: Meyer Nuala J. , Reilly John P. , Anderson Brian J. , Palakshappa Jessica A. , Jones Tiffanie K. , Dunn Thomas G. , Shashaty Michael G. S. , Feng Rui , Christie Jason D. , Opal Steven M. 
Published: October 2017

Objective:
Plasma interleukin-1 beta may influence sepsis mortality, yet recombinant human interleukin-1 receptor antagonist did not reduce mortality in randomized trials. We tested for heterogeneity in the treatment effect of recombinant human interleukin-1 receptor antagonist by baseline plasma interleukin-1 beta or interleukin-1 receptor antagonist concentration.

Design:
Retrospective subgroup analysis of randomized controlled trial.

Setting:
Multicenter North American and European clinical trial.

Patients:
Five hundred twenty-nine subjects with sepsis and hypotension or hypoperfusion, representing 59% of the original trial population.

Interventions:
Random assignment of placebo or recombinant human interleukin-1 receptor antagonist × 72 hours.

Measurements and Main Results:
We measured prerandomization plasma interleukin-1 beta and interleukin-1 receptor antagonist and tested for statistical interaction between recombinant human interleukin-1 receptor antagonist treatment and baseline plasma interleukin-1 receptor antagonist or interleukin-1 beta concentration on 28-day mortality. There was significant heterogeneity in the effect of recombinant human interleukin-1 receptor antagonist treatment by plasma interleukin-1 receptor antagonist concentration whether plasma interleukin-1 receptor antagonist was divided into deciles (interaction p = 0.046) or dichotomized (interaction p = 0.028). Interaction remained present across different predicted mortality levels. Among subjects with baseline plasma interleukin-1 receptor antagonist above 2,071 pg/mL (n = 283), recombinant human interleukin-1 receptor antagonist therapy reduced adjusted mortality from 45.4% to 34.3% (adjusted risk difference, –0.12; 95% CI, –0.23 to –0.01), p = 0.044. Mortality in subjects with plasma interleukin-1 receptor antagonist below 2,071 pg/mL was not reduced by recombinant human interleukin-1 receptor antagonist (adjusted risk difference, +0.07; 95% CI, –0.04 to +0.17), p = 0.230. Interaction between plasma interleukin-1 beta concentration and recombinant human interleukin-1 receptor antagonist treatment was not statistically significant.

Conclusions:
We report a heterogeneous effect of recombinant human interleukin-1 receptor antagonist on 28-day sepsis mortality that is potentially predictable by plasma interleukin-1 receptor antagonist in one trial. A precision clinical trial of recombinant human interleukin-1 receptor antagonist targeted to septic patients with high plasma interleukin-1 receptor antagonist may be worthy of consideration.
Respiratory Viruses in Invasively Ventilated Critically Ill Patients—A Prospective Multicenter Observational Study
Authors: van Someren Gréve Frank , Juffermans Nicole P. , Bos Lieuwe D. J. , Binnekade Jan M. , Braber Annemarije , Cremer Olaf L. , de Jonge Evert , Molenkamp Richard , Ong David S. Y. , Rebers Sjoerd P. H. , Spoelstra–de Man Angelique M. E. , van der Sluijs Koenraad F. , Spronk Peter E. , Verheul Kirsten D. , de Waard Monique C. , de Wilde Rob B. P. , Winters Tineke , de Jong Menno D. , Schultz Marcus J. 
Published: October 2017

Objectives:
The presence of respiratory viruses and the association with outcomes were assessed in invasively ventilated ICU patients, stratified by admission diagnosis.

Design:
Prospective observational study.

Setting:
Five ICUs in the Netherlands.

Patients:
Between September 1, 2013, and April 30, 2014, 1,407 acutely admitted and invasively ventilated patients were included.

Interventions:
None.

Measurements and Main Results:
Nasopharyngeal swabs and tracheobronchial aspirates were collected upon intubation and tested for 14 respiratory viruses. Out of 1,407 patients, 156 were admitted because of a severe acute respiratory infection and 1,251 for other reasons (non–severe acute respiratory infection). Respiratory viruses were detected in 28.8% of severe acute respiratory infection patients and 17.0% in non–severe acute respiratory infection (p < 0.001). In one third, viruses were exclusively detected in tracheobronchial aspirates. Rhinovirus and human metapneumovirus were more prevalent in severe acute respiratory infection patients (9.6% and 2.6% vs 4.5 and 0.2%; p = 0.006 and p < 0.001). In both groups, there were no associations between the presence of viruses and the number of ICU-free days at day 28, crude mortality, and mortality in multivariate regression analyses.

Conclusions:
Respiratory viruses are frequently detected in acutely admitted and invasively ventilated patients. Rhinovirus and human metapneumovirus are more frequently found in severe acute respiratory infection patients. Detection of respiratory viruses is not associated with worse clinically relevant outcomes in the studied cohort of patients.
Development and Validation of an Empiric Tool to Predict Favorable Neurologic Outcomes Among PICU Patients*
Authors: Gupta Punkaj , Rettiganti Mallikarjuna , Gossett Jeffrey M. , Daufeldt Jennifer , Rice Tom B. , Wetzel Randall C. 
Published: October 2017

Objectives:
To create a novel tool to predict favorable neurologic outcomes during ICU stay among children with critical illness.

Design:
Logistic regression models using adaptive lasso methodology were used to identify independent factors associated with favorable neurologic outcomes. A mixed effects logistic regression model was used to create the final prediction model including all predictors selected from the lasso model. Model validation was performed using a 10-fold internal cross-validation approach.

Setting:
Virtual Pediatric Systems (VPS, LLC, Los Angeles, CA) database.

Patients:
Patients less than 18 years old admitted to one of the participating ICUs in the Virtual Pediatric Systems database were included (2009–2015).

Interventions:
None.

Measurements and Main Results:
A total of 160,570 patients from 90 hospitals qualified for inclusion. Of these, 1,675 patients (1.04%) were associated with a decline in Pediatric Cerebral Performance Category scale by at least 2 between ICU admission and ICU discharge (unfavorable neurologic outcome). The independent factors associated with unfavorable neurologic outcome included higher weight at ICU admission, higher Pediatric Index of Morality-2 score at ICU admission, cardiac arrest, stroke, seizures, head/nonhead trauma, use of conventional mechanical ventilation and high-frequency oscillatory ventilation, prolonged hospital length of ICU stay, and prolonged use of mechanical ventilation. The presence of chromosomal anomaly, cardiac surgery, and utilization of nitric oxide were associated with favorable neurologic outcome. The final online prediction tool can be accessed at https://soipredictiontool.shinyapps.io/GNOScore/. Our model predicted 139,688 patients with favorable neurologic outcomes in an internal validation sample when the observed number of patients with favorable neurologic outcomes was among 139,591 patients. The area under the receiver operating curve for the validation model was 0.90.

Conclusions:
This proposed prediction tool encompasses 20 risk factors into one probability to predict favorable neurologic outcome during ICU stay among children with critical illness. Future studies should seek external validation and improved discrimination of this prediction tool.