bluuebunny/crossref_metadata_2025 huggingface dataset:
Police Misconduct: Mapping its Location, Seriousness and Theoretical Underpinning
Authors: Moss Brian
Published: October 2017

Police misconduct and the location of street crimes and deviance have received much research attention. The location of police misconduct, by contrast, has not. Taking the case of Ireland, where policing underwent significant reform in 2007, police oversight data are mapped to determine the location and nature of complaints and any clustering of police misconduct, particularly in areas of greatest deprivation usually associated with people coming into most frequent contact with police. The implications of the findings for police, police oversight, and existing theories by which geography of deviance is framed are discussed.
Leader Prototypicality and Displayed Power in the Police: An Empirical Analysis of the Impact on Leader Endorsement and Trust
Authors: Barth-Farkas Faye , Vera Antonio
Published: October 2017

The aim of this article is to advance scholarly knowledge on the impact of leader prototypicality and displayed power on leader endorsement and trust in the police. Drawing on theoretical arguments from psychology and organizational behaviour, we develop eight hypotheses and submit them to an empirical test. In a pre-study, we explore what characteristics are prototypical of police leaders. Based on these findings, we develop vignettes describing different types of police leaders and administer these in an experimental study using a between-subjects design. Our sample consists of 34 German top-level police leaders for the pre-study and 142 German mid-level police leaders for the main study. Regression analyses provide evidence for a positive effect of leader prototypicality on leader endorsement and trust, a positive moderating effect of organizational identification on these relationships, and a negative effect of displayed power on leader endorsement and trust.
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

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.
Adaptation of a Biomarker-Based Sepsis Mortality Risk Stratification Tool for Pediatric Acute Respiratory Distress Syndrome*
Authors: Yehya Nadir , Wong Hector R.
Published: October 2017

Objectives:

The original Pediatric Sepsis Biomarker Risk Model and revised (Pediatric Sepsis Biomarker Risk Model-II) biomarker-based risk prediction models have demonstrated utility for estimating baseline 28-day mortality risk in pediatric sepsis. Given the paucity of prediction tools in pediatric acute respiratory distress syndrome, and given the overlapping pathophysiology between sepsis and acute respiratory distress syndrome, we tested the utility of Pediatric Sepsis Biomarker Risk Model and Pediatric Sepsis Biomarker Risk Model-II for mortality prediction in a cohort of pediatric acute respiratory distress syndrome, with an a priori plan to revise the model if these existing models performed poorly.

Design:

Prospective observational cohort study.

Setting:

University affiliated PICU.

Patients:

Mechanically ventilated children with acute respiratory distress syndrome.

Interventions:

Blood collection within 24 hours of acute respiratory distress syndrome onset and biomarker measurements.

Measurements and Main Results:

In 152 children with acute respiratory distress syndrome, Pediatric Sepsis Biomarker Risk Model performed poorly and Pediatric Sepsis Biomarker Risk Model-II performed modestly (areas under receiver operating characteristic curve of 0.61 and 0.76, respectively). Therefore, we randomly selected 80% of the cohort (n = 122) to rederive a risk prediction model for pediatric acute respiratory distress syndrome. We used classification and regression tree methodology, considering the Pediatric Sepsis Biomarker Risk Model biomarkers in addition to variables relevant to acute respiratory distress syndrome. The final model was comprised of three biomarkers and age, and more accurately estimated baseline mortality risk (area under receiver operating characteristic curve 0.85, p < 0.001 and p = 0.053 compared with Pediatric Sepsis Biomarker Risk Model and Pediatric Sepsis Biomarker Risk Model-II, respectively). The model was tested in the remaining 20% of subjects (n = 30) and demonstrated similar test characteristics.

Conclusions:

A validated, biomarker-based risk stratification tool designed for pediatric sepsis was adapted for use in pediatric acute respiratory distress syndrome. The newly derived Pediatric Acute Respiratory Distress Syndrome Biomarker Risk Model demonstrates good test characteristics internally and requires external validation in a larger cohort. Tools such as Pediatric Acute Respiratory Distress Syndrome Biomarker Risk Model have the potential to provide improved risk stratification and prognostic enrichment for future trials in pediatric acute respiratory distress syndrome.
Sepsis Survivors Admitted to Skilled Nursing Facilities: Cognitive Impairment, Activities of Daily Living Dependence, and Survival*
Authors: Ehlenbach William J. , Gilmore-Bykovskyi Andrea , Repplinger Michael D. , Westergaard Ryan P. , Jacobs Elizabeth A. , Kind Amy J. H. , Smith Maureen
Published: October 2017

Objective:

Severe sepsis survivors frequently experience cognitive and physical functional impairment. The degree of impairment and its association with mortality is understudied, particularly among those discharged to a skilled nursing facility. Our objective was to quantify the cognitive and physical impairment among severe sepsis survivors discharged to a skilled nursing facility and to investigate the relationship between impairment and long-term mortality.

Design:

Retrospective cohort study.

Setting:

United States.

Subjects:

Random 5% sample of Medicare patients discharged following severe sepsis hospitalization, 2005–2009 (n = 135,370).

Measurement and Main Results:

Medicare data were linked with the Minimum Data Set; Minimum Data Set-Cognition Scale was used to assess cognitive function, and the Minimum Data Set activities of daily living hierarchical scale was used to assess functional dependence. Associations were evaluated using multivariable logistic regression, Kaplan-Meier curves, and Cox proportional hazards regression. Of 66,540 beneficiaries admitted to a skilled nursing facility following severe sepsis, 34% had severe or very severe cognitive impairment, and 72.5% had maximal, dependence, or total dependence in activities of daily living. Median survival was 19.4 months for those discharged to a skilled nursing facility without having been in a skilled nursing facility in the preceding 1 year and 10.4 months for those discharged to a skilled nursing facility who had spent time in a skilled nursing facility in the prior year. The adjusted hazard ratio for death was 3.1 for those with very severe cognitive impairment relative to those who were cognitively intact (95% CI, 2.9–3.2; p < 0.001) and 4.3 for those with “total dependence” in activities of daily livings relative to those who were independent (95% CI, 3.8–5.0; p < 0.001).

Conclusions:

Discharge to a skilled nursing facility following severe sepsis hospitalization among Medicare beneficiaries was associated with shorter survival, and cognitive impairment and activities of daily living dependence were each strongly associated with shortened survival. These findings can inform decision-making by patients and physicians and underscores high palliative care needs among sepsis survivors discharged to skilled nursing facility.
Improvements in Radiation Monitoring Trending
Authors: Passmore Christopher Neil , Kirr Mirela
Published: October 2017

One of the main goals for Radiation Safety Professionals is to help maintain radiation worker doses below administrative control levels. In the radiation safety field there is an increasing recognition of the value of dosimetry-related data that can be used to enhance safety programs and regulatory compliance. Mining radiation dosimetry data and rendering results in the form of dashboards provides insights for the Radiation Safety Professionals that could help improve the radiological protection programs effectiveness, enhances quality, and reduces cost. Quite often the professionals spend more time assembling data than analyzing for trends and acting to improve the radiation safety program. Data analysis tools were developed allowing the radiation safety professionals to perform surveillance on key parameters in the dosimetry program that can help identifying risks and insure early intervention. More than 2,200 institutions chosen from different industries were surveyed for more than 2 years after the implementation of this tool. Four indicators: dose per participant, collective dose, dosimeter return compliance, and number of workers exceeding ALARA levels were chosen as meaningful parameters in characterizing the health of the program. These parameters were tracked, analyzed, and compared to benchmarks developed based on more than 1 million monitored workers.
Donor Tissue Preparation for Descemet Membrane Endothelial Keratoplasty: An Updated Review
Authors: Birbal Rénuka S. , Sikder Shameema , Lie Jessica T. , Groeneveld-van Beek Esther A. , Oellerich Silke , Melles Gerrit R. J.
Published: October 2017

Purpose:

To provide an overview of the current literature on donor tissue preparation for Descemet membrane endothelial keratoplasty (DMEK).

Methods:

A comprehensive database search without date restrictions was performed in PubMed and in The Cochrane Library in May, 2017. Keywords included Descemet membrane endothelial keratoplasty, corneal transplantation, graft, harvest, dissection, preparation, endothelial cell, and endothelial cell density. Articles aiming to describe or evaluate a technique for DMEK graft preparation were considered eligible and were included in this review.

Results:

A graft dissection technique that provides consistent tissue qualities and a low risk of preparation failure is essential for surgeons and eye banks preparing DMEK tissue. Various techniques have been described aiming to facilitate DMEK graft dissection, including manual dissection, pneumatic dissection, and hydrodissection. All show a trend toward a no-touch technique, for example, without direct physical tissue manipulation during tissue harvesting, as a potential ideal approach to minimize graft damage.

Conclusions:

An overview of the current harvesting techniques available for DMEK may benefit corneal surgeons and eye banks in choosing the best approach for each specific user.
Subbasal Nerve Plexus Changes in Chronic Migraine
Authors: Shetty Rohit , Deshmukh Rashmi , Shroff Rushad , Dedhiya Charmy , Jayadev Chaitra
Published: October 2017

Purpose:

Migraine is a multifactorial disorder that presents with unilateral headache and several sensory symptoms. Photophobia is one of the ophthalmic manifestations that cause significant morbidity. The trigeminal pathway that innervates the cornea in the form of afferents has been implicated in photophobia associated with chronic migraine. This study investigates changes in the corneal subbasal nerve plexus (SBNP) in chronic migraine patients with and without photophobia.

Methods:

Thirty-six patients with migraine and photophobia (group 1), 24 patients with migraine without photophobia (group 2), and 24 age- and sex-matched controls (group 3) were studied. A detailed history analysis and ophthalmic evaluation were performed on all subjects. In vivo confocal microscopy (IVCM) with automated CCMetrics software was used to quantify changes in the SBNP in all 3 groups. Measured parameters were compared using analysis of variance.

Results:

Analysis of corneal SBNP features revealed a significant decrease in the corneal nerve fiber length (14.76 ± 3.98 mm/mm2), total branch density (43.37 ± 21.63 branch points/mm2), nerve branch density (30.19 ± 15.76 number of branches/mm2), and fiber area (0.005 ± 0.001 total nerve fiber area/mm2) in patients of group 1 compared with group 2 (P < 0.05).

Conclusions:

Structural changes in nociceptive corneal axons in the SBNP of patients with migraine with photophobia lend further support to the hypothesis that the trigeminal system plays a critical role in the pathogenesis of ocular symptoms in migraine. Our observations demonstrate that SBNP changes on IVCM may serve as a potential imaging marker for ocular symptoms of chronic migraine, and this warrants further investigation.
Long-Term Visual Outcomes, Complications, and Retention of the Boston Type I Keratoprosthesis
Authors: Aravena Carolina , Yu Fei , Aldave Anthony J.
Published: October 2017

Purpose:

To report the long-term outcomes of the Boston type I keratoprosthesis (KPro).

Methods:

Data were collected regarding preoperative characteristics, surgical procedure(s) performed, and postoperative outcomes of patients who underwent KPro implantation from May 1, 2004, to May 1, 2011, and were followed for 5 years after surgery.

Results:

Seventy-four KPro procedures were performed in 58 eyes (55 patients), with more than 1 KPro implanted in 10 eyes. The mean follow-up duration was 82.8 ± 20.5 months (range 57–145 months), and the most common indication for keratoprosthesis implantation was corneal transplant failure (50%). Preoperative corrected distance visual acuity (CDVA) was ≥20/200 in 5%; between 1 and 8 years after surgery, the percentage of eyes with CDVA ≥20/200 varied between 57% (4 years) and 82% (8 years). Nineteen (25.7%) KPros implanted were removed (retention failure rate 0.047/eye-year), although a KPro was retained at final follow-up in 55 eyes (94.8%). The most common postoperative complication was retroprosthetic membrane formation in 51.7% of eyes. The incidence of each postoperative complication decreased significantly over the first 10 years after surgery.

Conclusions:

The KPro provides significant visual improvement in most eyes, with more than 50% regaining and maintaining 20/200 CDVA each year through 8 years after surgery. The incidence of each postoperative complication decreases significantly over the first 10 years after surgery. Although almost one-quarter of implanted keratoprostheses were removed, over 90% of eyes reaching 5 years of follow-up retain a keratoprosthesis at final follow-up.
Intermediate-Term and Long-Term Outcomes With the Boston Type 1 Keratoprosthesis in Aniridia
Authors: Shah Kevin J. , Cheung Albert Y. , Holland Edward J.
Published: October 2017

Purpose:

To report the intermediate- and long-term visual outcomes and complications with the Boston type 1 keratoprosthesis (KPro) for the management of aniridic keratopathy.

Methods:

A retrospective chart review of 46 eyes of 34 patients (20 females and 14 males) with aniridic keratopathy who underwent Boston type 1 KPro surgery by a single surgeon from 2004 to 2012 with minimum 2-year follow-up was conducted. Preoperative, intraoperative, and postoperative parameters were collected and analyzed. The primary outcome was the change in best-corrected visual acuity. Secondary outcomes included the rate of retroprosthetic membrane formation, glaucoma progression, glaucoma tube revisions, and KPro retention.

Results:

Mean age of the patients was 43.5 ± 19.8 years with a mean follow-up period of 4.5 ± 1.6 years (range 2–7.4 years). Thirty-four eyes (74%) had previously failed keratoplasty. Thirty-five eyes (76%) previously underwent ocular surface stem cell transplantation, specifically a keratolimbal allograft. Within the first 6 months postoperatively, 74% (34/46) of patients experienced a gain of ≥2 lines of vision. Overall, there was a gain of ≥2 lines of vision in 43.5% (20/46) of patients at last follow-up. The rate of retroprosthetic membrane formation was 61%, the rate of glaucoma onset/progression was 26%, the rate of tube revision was 31%, and the KPro retention rate was 87%.

Conclusions:

This study confirms that initial visual improvement in aniridic keratopathy cases occurs at a high rate with the Boston type 1 KPro but also found progressive loss of these initial visual improvements.
Trends in Drug Resistance Prevalence, HIV-1 Variants and Clinical Status in HIV-1-infected Pediatric Population in Madrid: 1993 to 2015 Analysis
Authors: Rojas Sánchez Patricia , Domínguez Sara , Jiménez De Ory Santiago , Prieto Luis , Rojo Pablo , Mellado Pepa , Navarro Marisa , Delgado Rafael , Ramos José Tomas , Holguín África
Published: October 2017

Background:

The expanded use of long-term antiretroviral treatments in infected children may exacerbate the problem of drug resistance mutations selection, which can compromise treatment efficiency.

Objective:

We describe the temporal trends of HIV drug resistance mutations and the HIV-1 variants during 23 years (1993 to March 2016) in the Madrid cohort of HIV-infected children and adolescents.

Methods:

We selected patients with at least one available HIV-1 pol sequence/genotypic resistance profile, establishing different groups according to the sampling year of first resistance data. We determined the prevalence of transmitted drug resistance mutations or acquired drug resistance mutations (DRM), the drug susceptibility among resistant viruses and HIV-1 variants characterized by phylogeny across time.

Results:

A total of 245 pediatric patients were selected, being mainly female, Spanish native, perinatally infected and carrying HIV-1 subtype B. At first sampling, most pediatric patients were on antiretroviral therapy and heavily pretreated. During 1993 to 2016, transmitted drug resistance mutations was found in 13 (26%) of 50 naive children [non-nucleoside reverse transcriptase inhibitors (NNRTI), 14.6%; nucleoside reverse transcriptase inhibitors (NRTI), 10.4%; protease inhibitors, 8.7%]. DRM appeared in 139 (73.2%) of 190 pretreated patients (NRTI, 64.5%; NNRTI, 36%; protease inhibitors, 35.1%). DRM to NNRTI was higher in last 5 years. Non-B variants infected 14.5% of children and adolescents of the Madrid Cohort, being mainly intersubtype recombinants (76.5%), including complex unique recombinant strains. They caused 3.4% infections before 2000, rising to 85.7% during 2011 to 2016.

Conclusions:

Periodic surveillance resistance and molecular epidemiology studies in long-term pretreated HIV-infected pediatric populations are required to optimize treatment regimens. Results will permit a better understanding of long-time dynamics of viral resistance and HIV-1 variants in Spain.
Orbital Inflammation as a Presenting Sign for CREST Syndrome
Authors: Hamed-Azzam Shirin W. , D’Cruz David P. , Verity David H.
Published: October 2017

A 61-year-old male was referred with a week’s history of a painful and swollen left eye. Examination revealed normal visual acuities, left proptosis and global restriction of ocular ductions, and subretinal fluid at the macula. CT imaging confirmed thickening of the posterior scleral coat, with an associated choroidal effusion. Serology revealed positive antinuclear antibodies with a centromere staining pattern; subsequent rheumatology review revealed extensive telangiectasia with digital ulceration in both hands, and a diagnosis of limited cutaneous systemic sclerosis was made. Orbital inflammatory disease is often the initial presentation of systemic diseases such as sarcoidosis, granulomatosis with polyangiitis, and IgG4 disease. Limited cutaneous systemic sclerosis is rarely encountered in the context of orbital inflammation, but is a further systemic association, reminding the clinician of the diagnostic importance of peripheral symptoms and serological markers in patients presenting with orbital inflammation and scleritis.
Bicanalicular Canaliculops and its Dacryoendoscopic Findings
Authors: Ramyil Alice Venyir , Gupta Shweta , Ali Mohammad Javed , Naik Milind N.
Published: October 2017

Canaliculops is a noninflammatory ectasia of the canaliculus and so far only 7 histopathologically confirmed cases have been reported worldwide. The authors present a middle aged female with right-sided bicanalicular cystic swellings associated with punctal agenesis. Ultrasound biomicroscopy showed a cystic dilatation of the canaliculus and dacryoendoscopy showed a cavity lined by whitish canalicular mucosa, thrown into numerous irregular folds with a blind medial end. Histopathological examination confirmed the diagnosis of canaliculops. To the best of authors’ knowledge, this is the first description of a bicanalicular canaliculops and its dacryoendoscopic findings.
Inferior Transplant Outcomes of Adolescents and Young Adults Bridged with a Ventricular Assist Device
Authors: Rizwan Raheel , Bryant Roosevelt , Zafar Farhan , Villa Chet R. , Lorts Angela , Morales David L.
Published: October 2017

Adolescents, who are thought to have compliance issues, are well known to have poor heart transplant (HTx) outcomes. This “effect” has recently been demonstrated to extend to age 29. The study sought to investigate whether the poor outcomes for HTx related to adolescent age are also observed in recipients who are bridged to transplant (BTT) with a ventricular assist device (VAD) and whether this effect extends beyond the standard definition of adolescent age 12–18 years. All HTx BTT with a VAD in recipients 8–39 years were identified in the United States Organ Sharing (UNOS) database (1 January 2005 to 30 June 2016). Based on the Kaplan-Meier survival comparison for age year, patients were divided into three groups: Group 1 (8–14 years), group 2 (15–29 years), and group 3 (30–39 years). A total of 1,848 HTx were bridged with a VAD. A decline in post-HTx 5 years survival was noted after 14 years of age, which improved at around 30 years of age. Group 1 had 237 (13%) HTx, group 2 had 787 (43%) HTx, and group 3 had 823 (44%) HTx. Group 2 (15–29 years) had worse post-HTx survival compared with group 1 (p < 0.001) and group 3 (p = 0.005). On subdividing group 2 (15–29 years) into “older adolescents” (15–17 years) and “young adults” (18–29 years), post-HTx survival was similar between the two subgroups (p = 0.353). In conclusion, older adolescents and young adults, both, have similarly poor post-HTx survival when BTT with a VAD compared with other age groups. These groups are generally categorized into different broad pediatric and adult age groups; however, these similarities should be carefully considered when formulating treatment protocols for older adolescents and young adults.
Fatty Acid–Mediated Stromal Reprogramming of Pancreatic Stellate Cells Induces Inflammation and Fibrosis That Fuels Pancreatic Cancer
Authors: Hata Tomoki , Kawamoto Koichi , Eguchi Hidetoshi , Kamada Yoshihiro , Takamatsu Shinji , Maekawa Tomohiro , Nagaoka Satoshi , Yamada Daisaku , Iwagami Yoshifumi , Asaoka Tadafumi , Noda Takehiro , Wada Hiroshi , Gotoh Kunihito , Masamune Atsushi , Miyoshi Eiji , Mori Masaki , Doki Yuichiro
Published: October 2017

Objectives

Pancreatic ductal adenocarcinoma is one of the deadliest diseases worldwide. Fatty acids (FAs) have properties that affect both cancer cells and tumor environment. We assessed the effects of FAs on malignant characteristics in a pancreatic cancer and pancreatic stellate cell (PSC) coculture model. This study aimed to clarify the FA signature of PSC-derived inflammation and fibrosis in vitro and in a clinicopathological analysis.

Methods

The in vitro model involved coculture of the human pancreatic cancer cell lines PANC-1 and MIA PaCa-2 with human PSCs. Clinical histological samples were analyzed to characterize the surgical margins of samples from patients who received distal pancreatectomies.

Results

The pancreatic cancer cells took up lipids from the culture media. Saturated and unsaturated FAs were required to induce inflammatory responses in human PSCs, and the cocultures showed fibrotic changes. Clinical samples from pancreatic ductal adenocarcinoma patients had more fatty and fibrotic changes in the normal tissue in the surgical margins than samples from noncancer patients.

Conclusions

Inflammation and fibrosis levels were increased in pancreatic cancer specimens, supporting the in vitro observations and suggesting that PSCs contribute to pancreatic carcinogenesis. Pancreatic stellate cells thus represent a potential therapeutic target for suppressing stromal changes in pancreatic cancer.
Cell Cycle Protein Expression in Neuroendocrine Tumors
Authors: Shi Yan , Qian Zhi Rong , Zhang Sui , Li Wanwan , Masugi Yohei , Li Tingting , Chan Jennifer A. , Yang Juhong , Da Silva Annacarolina , Gu Mancang , Liu Li , Hamada Tsuyoshi , Kosumi Keisuke , Dutton Trevor , Brais Lauren K. , Nishihara Reiko , Fuchs Charles S. , Ogino Shuji , Kulke Matthew H.
Published: October 2017

Objectives

Dysregulation of the cell cycle has been observed and implicated as an etiologic factor in a range of human malignancies, but remains relatively unstudied in neuroendocrine tumors (NETs). We evaluated expression of key proteins involved in cell cycle regulation in a large cohort of NETs.

Methods

We evaluated immunohistochemical expression of CDKN1B, CDKN1A, CDKN2A, CDK2, CDK4, CDK6, cyclin D1, cyclin E1, and phosphorylated retinoblastoma protein (phospho-RB1) in a cohort of 267 patients with NETs. We then explored associations between cell cycle protein expression, mutational status, histologic features, and overall survival.

Results

We found that high expression of CDK4, CDK6, CCND1, and phospho-RB1 was associated with higher proliferative index, as defined by MKI67. We additionally observed a trend toward shorter overall survival associated with low expression of CDKN1B. This association seemed strongest in SINETs (multivariate hazards ratio, 2.04; 95% confidence interval, 1.06–3.93; P = 0.03). We found no clear association between CDKN1B mutation and protein expression.

Conclusions

Our results suggest that dysregulation and activation of the CDK4/CDK6-CCND1-phospho-RB1 axis is associated with higher proliferative index in NETs. Investigation of the therapeutic potential of CDK4/CDK6 inhibitors in higher grade NETs is warranted.