bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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.
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.
Serum Osteocalcin Levels in Children With Nonalcoholic Fatty Liver Disease
Authors: Amin Saleh , El Amrousy Doaa , Elrifaey Shaymaa , Gamal Rasha , Hodeib Hossam 
Published: October 2017

ABSTRACTObjectives:The aim of the study was to investigate the relationship between osteocalcin and nonalcoholic fatty liver disease (NAFLD) in children with obesity.Method:60 obese children with NAFLD were taken as a patient group and 60 obese children and normal liver with matching age, sex, and body mass index were taken as a control group. Anthropometric measurements, abdominal ultrasonography for diagnosis and grading of NAFLD, and laboratory investigations in the form of liver function tests, lipid profile, fasting serum glucose and insulin, and serum osteocalcin levels were done for all children. Patients with NAFLD were further divided into patients with metabolic syndrome (MS) and patients without MS.Results:Age of NAFLD children was (10.55 ± 2.71), 20 boys and 40 girls, whereas age of children in control group was (10.05 ± 3.51), 24 boys and 36 girls (P > 0.05). Patients with NAFLD showed significant increase in waist and hip circumference, alanine aminotransferase, alkaline phosphatase, total cholesterol, triglycerides, insulin resistance (IR), fasting serum glucose, and insulin, but lower serum osteocalcin level than control group. Serum osteocalcin level is inversely correlated with waist circumference, triglyceride, liver enzymes, fasting serum insulin, fasting serum glucose, IR, and grades of fatty liver. Increase in alanine aminotransferase, total cholesterol, triglycerides, fasting insulin, and IR went with increase in degree of hepatic steatosis. Serum osteocalcin level <44.5 ng/mL is a good predictor for severity of hepatic steatosis with sensitivity and specificity of 80%.Conclusions:Osteocalcin plays an important role in glucose and lipid metabolism for protection against NAFLD occurrence and progression. Moreover, it could be a useful marker for progression of NAFLD in children with obesity.
The Relation Between Malnutrition and the Exocrine Pancreas
Authors: Bartels Rosalie H. , van den Brink Deborah A. , Bandsma Robert H. , Boele van Hensbroek Michael , Tabbers Merit M. , Voskuijl Wieger P. 
Published: October 2017

ABSTRACTObjective:The relation between malnutrition and exocrine pancreatic insufficiency (EPI) has been described previously, but it is unclear if malnutrition leads to EPI or vice versa. We systematically synthesized current evidence evaluating the association between malnutrition and EPI in children.Methods:Pubmed, Embase, and Cochrane databases were searched from inception until February 2017. We included cohort or case‐controlled studies in children reporting on prevalence or incidence of EPI and malnutrition. Data generation was performed independently by 2 authors. Quality was assessed by using quality assessment tools from the National Heart, Lung, and Blood Institute.Results:Nineteen studies were divided into 2 groups: 10 studies showing EPI leading to malnutrition, and 9 studies showing malnutrition leading to EPI. Because of heterogeneity in design, definitions, and outcome measures, pooling of results was impossible. Quality was good in 4 of 19 studies. Pancreatic insufficiency was linked to decreased nutritional status in 8 of 10 articles, although this link was not specified properly in most articles. In malnourished children, improvement was seen in pancreatic function in 7 of 9 articles after nutritional rehabilitation. The link between the 2 was not further specified. Heterogeneity exists with respect to definitions, outcome measures, and study design.Conclusions:There is sufficient evidence for an association between EPI and malnutrition. We could not confirm whether there is a correlation or causality between EPI or malnutrition. It was therefore not possible to draw firm conclusions from this systematic review on underlying pathophysiological mechanisms between EPI and malnutrition. More observational clinical trials are crucially needed.