bluuebunny/crossref_metadata_2025_split huggingface dataset:
Benchmarking Sepsis Gene Expression Diagnostics Using Public Data*
Authors: Sweeney Timothy E. , Khatri Purvesh 
Published: September 2016

Objective:
In response to a need for better sepsis diagnostics, several new gene expression classifiers have been recently published, including the 11-gene “Sepsis MetaScore,” the “FAIM3-to-PLAC8” ratio, and the Septicyte Lab. We performed a systematic search for publicly available gene expression data in sepsis and tested each gene expression classifier in all included datasets. We also created a public repository of sepsis gene expression data to encourage their future reuse.

Data Sources:
We searched National Institutes of Health Gene Expression Omnibus and EBI ArrayExpress for human gene expression microarray datasets. We also included the Glue Grant trauma gene expression cohorts.

Study Selection:
We selected clinical, time-matched, whole blood studies of sepsis and acute infections as compared to healthy and/or noninfectious inflammation patients. We identified 39 datasets composed of 3,241 samples from 2,604 patients.

Data Extraction:
All data were renormalized from raw data, when available, using consistent methods.

Data Synthesis:
Mean validation areas under the receiver operating characteristic curve for discriminating septic patients from patients with noninfectious inflammation for the Sepsis MetaScore, the FAIM3-to-PLAC8 ratio, and the Septicyte Lab were 0.82 (range, 0.73–0.89), 0.78 (range, 0.49–0.96), and 0.73 (range, 0.44–0.90), respectively. Paired-sample t tests of validation datasets showed no significant differences in area under the receiver operating characteristic curves. Mean validation area under the receiver operating characteristic curves for discriminating infected patients from healthy controls for the Sepsis MetaScore, FAIM3-to-PLAC8 ratio, and Septicyte Lab were 0.97 (range, 0.85–1.0), 0.94 (range, 0.65–1.0), and 0.71 (range, 0.24–1.0), respectively. There were few significant differences in any diagnostics due to pathogen type.

Conclusions:
The three diagnostics do not show significant differences in overall ability to distinguish noninfectious systemic inflammatory response syndrome from sepsis, though the performance in some datasets was low (area under the receiver operating characteristic curve, < 0.7) for the FAIM3-to-PLAC8 ratio and Septicyte Lab. The Septicyte Lab also demonstrated significantly worse performance in discriminating infections as compared to healthy controls. Overall, public gene expression data are a useful tool for benchmarking gene expression diagnostics.
Influence of Genotype on Warfarin Maintenance Dose Predictions Produced Using a Bayesian Dose Individualization Tool
Authors: Saffian Shamin M. , Duffull Stephen B. , Roberts Rebecca L. , Tait Robert C. , Black Leanne , Lund Kirstin A. , Thomson Alison H. , Wright Daniel F. B. 
Published: September 2016

Background:
A previously established Bayesian dosing tool for warfarin was found to produce biased maintenance dose predictions. In this study, we aimed (1) to determine whether the biased warfarin dose predictions previously observed could be replicated in a new cohort of patients from 2 different clinical settings, (2) to explore the influence of CYP2C9 and VKORC1 genotype on predictive performance of the Bayesian dosing tool, and (3) to determine whether the previous population used to develop the kinetic–pharmacodynamic model underpinning the Bayesian dosing tool was sufficiently different from the test (posterior) population to account for the biased dose predictions.

Methods:
The warfarin maintenance doses for 140 patients were predicted using the dosing tool and compared with the observed maintenance dose. The impact of genotype was assessed by predicting maintenance doses with prior parameter values known to be altered by genetic variability (eg, EC50 for VKORC1 genotype). The prior population was evaluated by fitting the published kinetic–pharmacodynamic model, which underpins the Bayesian tool, to the observed data using NONMEM and comparing the model parameter estimates with published values.

Results:
The Bayesian tool produced positively biased dose predictions in the new cohort of patients (mean prediction error [95% confidence interval]; 0.32 mg/d [0.14–0.5]). The bias was only observed in patients requiring ≥7 mg/d. The direction and magnitude of the observed bias was not influenced by genotype. The prior model provided a good fit to our data, which suggests that the bias was not caused by different prior and posterior populations.

Conclusions:
Maintenance doses for patients requiring ≥7 mg/d were overpredicted. The bias was not due to the influence of genotype nor was it related to differences between the prior and posterior populations. There is a need for a more mechanistic model that captures warfarin dose–response relationship at higher warfarin doses.
Comparative Study of a Novel Tool for Follicular Unit Extraction for Individuals with Afro-textured Hair
Authors: Umar Sanusi 
Published: September 2016

Background:
Hair transplantation involving patients with tightly curled Afro-textured hair using follicular unit extraction (FUE) employing conventional rotary punches frequently leads to unacceptably high transection rates. These patients are unsuitable candidates for FUE hair transplantation. Transection rates were observed during FUE in a case series of 18 patients with tightly curled Afro-textured hair using different punches.

Methods:
Three different punches were sequentially used in patients to extract follicular units with several needle gauges until satisfactory transection rates occurred: conventional sharp and dull rotary punches, followed by a 2-pronged curved nonrotary punch.

Results:
In all instances, the curved nonrotary punch had the best transection rate of <5%. Sharp and dull rotary punches completely failed or had excessive transection rates in 8 patients. The dull rotary punch performed better than the sharp rotary punch in 9 patients in whom it was used with few restrictions compared to 5 patients in whom there were more restrictions.

Conclusions:
A curved nonrotary punch configured to accommodate the curliness of tightly curled Afro-textured hair can overcome high transection rates experienced using conventional sharp or dull rotary punches. Limitations of this study include it being a small, retrospective case series, and that the new technique that could require additional training by current FUE hair transplant practitioners.
Direction of the Relationship Between Acceptance of Illness and Health-Related Quality of Life in Chronic Heart Failure Patients
Authors: Obiegło Monika , Siennicka Agnieszka , Jankowska Ewa A. , Danel Dariusz P. 
Published: September 2016

Background:
This study provides an in-depth insight into the relationships between illness acceptance and health-related quality of life (HRQoL) of chronic heart failure (CHF) patients. Although HRQoL is a well-established endpoint in CHF, little is known on illness acceptance in this group.

Aims:
The aim of this study is to critically reconsider the direction of a relationship between HRQoL and illness acceptance in CHF patients.

Methods:
The study included 204 patients (160 men and 44 women; mean age, 63 ± 11 years) with at least 6-month clinical evidence of CHF corresponding to New York heart Association (NYHA) classes I to IV. All the patients were examined with the Minnesota Living With Heart Failure Questionnaire (MLHFQ) and Acceptance of Illness Scale (AIS).

Results:
Univariate analysis showed that the level of illness acceptance correlated inversely with patient age, and the level of HRQoL decreased with the severity of CHF (NYHA class). A relationship between illness acceptance and HRQoL was analyzed by structural equation modeling. Model 1 was based on the assumption that HRQoL is modulated by illness acceptance, and model 2 tested the opposite relationship. Both models included patient age and NYHA class as extrinsic determinants of AIS and MLHFQ scores, respectively. Model 2 proved to be well fitted (χ
2 [df = 2] = 3.22, P = .20, root-mean-square error of approximation = 0.055). Scores on the AIS correlated inversely with age (b
age->AIS = −0.15, SE = 0.05, P = .002) and HRQoL (b
QoL->AIS = −0.15, SE = 0.02, P < .001), and an increase in NYHA class was reflected by an increase in HRQoL scores (b
NYHA->QoL = 5.75, SE = 1.97, P = .004).

Conclusion:
Patients with CHF may not accept their disease due to deteriorated HRQoL. As a result, they may be uninvolved in the therapeutic process, which leads to exacerbation of CHF, further deterioration of HRQoL, and inability to accept the illness.
Causes and Outcomes of Esophageal Perforation in Eosinophilic Esophagitis
Authors: Runge Thomas M. , Eluri Swathi , Cotton Cary C. , Burk Caitlin M. , Woosley John T. , Shaheen Nicholas J. , Dellon Evan S. 
Published: September 2016

Goals:
To characterize patients who suffer perforation in the context of eosinophilic esophagitis (EoE) and to identify predictors of perforation.

Background:
Esophageal perforation is a serious complication of EoE.

Materials and Methods:
We conducted a retrospective cohort study of the University of North Carolina EoE clinicopathologic database from 2001 to 2014. Subjects were included if they had an incident diagnosis of EoE and met consensus guidelines, including nonresponse to a PPI trial. Patients with EoE who had suffered perforation at any point during their course were identified, and compared with EoE cases without perforation. Multiple logistic regression was performed to determine predictors of perforation.

Results:
Out of 511 subjects with EoE, 10 (2.0%) had experienced an esophageal perforation. Although those who perforated tended to have a longer duration of symptoms before diagnosis (11.4 vs. 7.0 y, P=0.13), a history of food impaction (odds ratio, 14.9; 95% confidence interval, 1.7-129.2) and the presence of a focal stricture (odds ratio, 4.6; 95% confidence interval, 1.1-19.7) were the only factors independently associated with perforation. Most perforations (80%) occurred after a prolonged food bolus impaction, and only half of individuals (5/10) carried a diagnosis of EoE at the time of perforation; none occurred after dilation. Six patients (60%) were treated with nonoperative management, and 4 (40%) required surgical repair.

Conclusions:
Esophageal perforation is a rare but serious complication of eosinophilic esophagitis, occurring in ∼2% of cases. Most episodes are due to food bolus impaction or strictures, suggesting that patients with fibrostenotic disease due to longer duration of symptoms are at increased risk.
Effect of Chicory-derived Inulin on Abdominal Sensations and Bowel Motor Function
Authors: Azpiroz Fernando , Molne Laura , Mendez Sara , Nieto Adoración , Manichanh Chaysavanh , Mego Marianela , Accarino Anna , Santos Javier , Sailer Manuela , Theis Stephan , Guarner Francisco 
Published: September 2016

Goal:
To determine the effect of a prebiotic chicory-derived inulin-type fructan on the tolerance of intestinal gas.

Background:
Subjects with gas-related complaints exhibit impaired handling of intestinal gas loads and we hypothesized that inulin would have a beneficial effect.

Study:
Placebo-controlled, parallel, randomized, double-blind trial. Subjects with abdominal symptoms and reduced tolerance of intestinal gas (selected by a pretest) received either inulin (8 g/d, n=18) or maltodextrin as a placebo (8 g/d, n=18) for 4 weeks. A gas challenge test (4 h jejunal gas infusion at 12 mL/min while measuring abdominal symptoms and gas retention for 3 h) was performed before and at the end of the intervention phase. Gastrointestinal symptoms and bowel habits (using daily questionnaires for 1 wk) and fecal bifidobacteria counts were measured before and at the end of the intervention.

Results:
Inulin decreased gas retention during the gas challenge test (by 22%; P=0.035 vs. baseline), while the placebo did not, but the intergroup difference was not statistically significant (P=0.343). Inulin and placebo reduced the perception of abdominal sensations in the gas challenge test to a similar extent (by 52% and 43%, respectively). Participants reported moderate gastrointestinal symptoms and normal bowel habits during baseline examination, and these findings remained unchanged in both groups during the intervention. Inulin led to a higher relative abundance of bifidobacteria counts (P=0.01 vs. placebo).

Conclusions:
A daily dose of inulin that promotes bifidobacteria growth and may improve gut function, is well tolerated by subjects with gastrointestinal complaints.
Strategic Planning for Research in Pediatric Critical Care
Authors: Tamburro Robert F. , Jenkins Tammara L. , Kochanek Patrick M. 
Published: September 2016

Objective:
To summarize the scientific priorities and potential future research directions for pediatric critical care research discussed by a panel of experts at the inaugural Strategic Planning Conference of the Pediatric Trauma and Critical Illness Branch of the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

Data Sources:
Expert opinion expressed during the Strategic Planning Conference.

Study Selection:
Not applicable.

Data Extraction:
Chaired by an experienced expert from the field, issues relevant to the conduct of pediatric critical care research were discussed and debated by the invited participants.

Data Synthesis:
Common themes and suggested priorities were identified and coalesced.

Conclusions:
Of the many pathophysiologic conditions discussed, the multiple organ dysfunction syndrome emerged as a topic in need of more study that is most relevant to the field. Additionally, the experts offered that the interrelationship and impact of critical illness on child development and family functioning are important research priorities. Consequently, long-term outcomes research was encouraged. The expert group also suggested that multidisciplinary conferences are needed to help identify key knowledge gaps to advance and direct research in the field. The Pediatric Critical Care and Trauma Scientist Development National K12 Program and the Collaborative Pediatric Critical Care Research Network were recognized as successful and important programs supported by the branch. The development of core data resources including biorepositories with robust phenotypic data using common data elements was also suggested to foster data sharing among investigators and to enhance disease diagnosis and discovery. Multicenter clinical trials and innovative study designs to address understudied and poorly understood conditions were considered important for field advancement. Finally, the growth of the pediatric critical care research workforce was offered as a priority that could be spawned in many ways including by expanded transdisciplinary and multiprofessional collaboration and diversity representation.
Pediatric Out-of-Hospital Cardiac Arrest Characteristics and Their Association With Survival and Neurobehavioral Outcome*
Authors: Meert Kathleen L. , Telford Russell , Holubkov Richard , Slomine Beth S. , Christensen James R. , Dean J. Michael , Moler Frank W. 
Published: September 2016

Objective:
To investigate relationships between cardiac arrest characteristics and survival and neurobehavioral outcome among children recruited to the Therapeutic Hypothermia after Pediatric Cardiac Arrest Out-of-Hospital trial.

Design:
Secondary analysis of Therapeutic Hypothermia after Pediatric Cardiac Arrest Out-of-Hospital trial data.

Setting:
Thirty-six PICUs in the United States and Canada.

Patients:
All children (n = 295) had chest compressions for greater than or equal to 2 minutes, were comatose, and required mechanical ventilation after return of circulation.

Interventions:
Neurobehavioral function was assessed using the Vineland Adaptive Behavior Scales, Second Edition at baseline (reflecting prearrest status) and 12 months postarrest. U.S. norms for Vineland Adaptive Behavior Scales, Second Edition scores are 100 (mean) ± 15 (sd). Higher scores indicate better functioning. Outcomes included 12-month survival and 12-month survival with Vineland Adaptive Behavior Scales, Second Edition greater than or equal to 70.

Measurement and Main Results:
Cardiac etiology of arrest, initial arrest rhythm of ventricular fibrillation/tachycardia, shorter duration of chest compressions, compressions not required at hospital arrival, fewer epinephrine doses, and witnessed arrest were associated with greater 12-month survival and 12-month survival with Vineland Adaptive Behavior Scales, Second Edition greater than or equal to 70. Weekend arrest was associated with lower 12-month survival. Body habitus was associated with 12-month survival with Vineland Adaptive Behavior Scales, Second Edition greater than or equal to 70; underweight children had better outcomes, and obese children had worse outcomes. On multivariate analysis, acute life threatening event/sudden unexpected infant death, chest compressions more than 30 minutes, and weekend arrest were associated with lower 12-month survival; witnessed arrest was associated with greater 12-month survival. Acute life threatening event/sudden unexpected infant death, other respiratory causes of arrest except drowning, other/unknown causes of arrest, and compressions more than 30 minutes were associated with lower 12-month survival with Vineland Adaptive Behavior Scales, Second Edition greater than or equal to 70.

Conclusions:
Many factors are associated with survival and neurobehavioral outcome among children who are comatose and require mechanical ventilation after out-of-hospital cardiac arrest. These factors may be useful for identifying children at risk for poor outcomes, and for improving prevention and resuscitation strategies.
A New Approach for Reconstruction of Diabetic Foot Wounds Using the Angiosome and Supermicrosurgery Concept
Authors: Suh Hyun Suk , Oh Tae Suk , Lee Ho Seung , Lee Seung Hwan , Cho Yong Pil , Park Joong Ryul , Hong Joon Pio 
Published: September 2016

Background:
Major vessels in the diabetic foot are often calcified and inadequate for use as recipient vessels. Thus, a supermicrosurgery technique using small branches or perforators from other collateral vessels with an adequate pulse may be an alternative method. This study evaluated outcome using the supermicrosurgery concept and the risk factors involved.

Methods:
Ninety-five cases of diabetic foot reconstruction were reviewed; the average patient age was 57 years; average follow-up was 43.5 months. Débridement was performed according to the angiosome concept, and reconstruction was performed with perforator flaps using the supermicrosurgery approach. Correlation between total flap loss and 16 preoperative risk factors (age, sex, diabetes mellitus type, smoking, immunosuppression, flap size, hemoglobin A1c, ankle-brachial index, preoperative transcutaneous partial pressure of oxygen, C-reactive protein, computed tomographic angiography, amputation history, peripheral artery disease, American Society of Anesthesiologists physical status, osteomyelitis, and chronic renal failure) were analyzed.

Results:
Of 95 cases, nine cases of total loss and 12 of minor complication were noted. Among the risk factors, the odds for failure after peripheral artery disease was 10.99 (p = 0.035), and that associated with a history of amputation was 9.44 (0.0006). Other factors had no correlation with flap loss, including cases with no or one major vessel. Flap survival rate was 90.5 percent, and the overall limb salvage rate was 93.7 percent.

Conclusions:
Despite the high risk of failure related to peripheral artery disease and history of amputation, the supermicrosurgery approach using a recipient vessel with good pulsation regardless of the source can achieve limb salvage. This approach extends the possibility for reconstruction in patients with severe ischemic diabetic foot.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, IV.
Postmastectomy Radiation Therapy and Two-Stage Implant-Based Breast Reconstruction: Is There a Better Time to Irradiate?
Authors: Santosa Katherine B. , Chen Xiaoxue , Qi Ji , Ballard Tiffany N. S. , Kim Hyungjin M. , Hamill Jennifer B. , Bensenhaver Jessica M. , Pusic Andrea L. , Wilkins Edwin G. 
Published: September 2016

Background:
The ideal timing of postmastectomy radiation therapy (PMRT) in the setting of two-stage implant-based breast reconstruction remains unclear. In this cohort study, the authors sought to determine whether complication rates differed between patients who received PMRT following tissue expander placement (TE-XRT) and those who received PMRT after exchange for permanent implants (Implant-XRT) utilizing using prospective, multicenter data.

Methods:
Eligible patients in the Mastectomy Reconstruction Outcomes Consortium study from 11 institutions across North America were included in the analysis. All patients had at least 6-month follow-up after their last intervention (i.e., implant exchange for TE-XRT patients, and radiation for Implant-XRT patients). Complications including seroma, hematoma, infection, wound dehiscence, capsular contracture, and implant loss were recorded.

Results:
The authors identified a total of 150 patients who underwent immediate, two-stage implant-based breast reconstruction and received PMRT. Of these, there were TE-XRT 104 patients (69.3 percent) and 46 (30.7 percent) Implant-XRT patients. There were no differences in the incidence of any complications or complications leading to reconstructive failure between the two cohorts. After adjusting for patient characteristics and site effect, the timing of PMRT (i.e., TE-XRT versus Implant-XRT) was not a significant predictor in the development of any complication, a major complication, or reconstructive failure.

Conclusion:
In the setting of PMRT and two-stage implant-based reconstruction, patients who received PMRT after expander placement (TE-XRT) did not have a higher incidence or increased odds of developing complications than those who received PMRT after exchange for a permanent implant (Implant-XRT).

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, III.