bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regional brain signal variability: a novel indicator of pain sensitivity and coping
Authors: Rogachov Anton , Cheng Joshua C. , Erpelding Nathalie , Hemington Kasey S. , Crawley Adrian P. , Davis Karen D. 
Published: July 2016

Abstract
Variability in blood oxygen level–dependent (BOLD) functional magnetic resonance imaging (fMRI) signals reflects the moment-by-moment fluctuations in resting-state fMRI (rs-fMRI) activity within specific areas of the brain. Regional BOLD signal variability was recently proposed to serve an important functional role in the efficacy of neural systems because of its relationship to behavioural performance in aging and cognition studies. We previously showed that individuals who better cope with pain have greater fluctuations in interregional functional connectivity, but it is not known whether regional brain signal variability is a mechanism underlying pain coping. We tested the hypothesis that individual pain sensitivity and coping is reflected by regional fMRI BOLD signal variability within dynamic pain connectome–brain systems implicated in the pain experience. We acquired resting-state fMRI and assessed pain threshold, suprathreshold temporal summation of pain, and the impact of pain on cognition in 80 healthy right-handed individuals. We found that regional BOLD signal variability: (1) inversely correlated with an individual's temporal summation of pain within the ascending nociceptive pathway (primary and secondary somatosensory cortex), default mode network, and salience network; (2) was correlated with an individual's ability to cope with pain during a cognitive interference task within the periaqueductal gray, a key opiate-rich brainstem structure for descending pain modulation; and (3) provided information not captured from interregional functional connectivity. Therefore, regional BOLD variability represents a pain metric with potential implications for prediction of chronic pain resilience vs vulnerability.
Increased cutaneous miR-let-7d expression correlates with small nerve fiber pathology in patients with fibromyalgia syndrome
Authors: Leinders Mathias , Doppler Kathrin , Klein Thomas , Deckart Maximiliane , Rittner Heike , Sommer Claudia , Üçeyler Nurcan 
Published: July 2016

Abstract
Fibromyalgia syndrome (FMS) is a chronic widespread pain condition probably comprising subgroups with different underlying pathomechanisms. There is increasing evidence for small nerve fiber impairment in subgroups of patients with FMS. MicroRNAs (miRNAs) regulate molecular factors determining nerve de- and re-generation. We investigated whether systemic and cutaneous miRNA expression in patients with FMS is related to small nerve fiber pathology. We confirmed previous findings of disturbed small fiber function and reduced intraepidermal nerve fiber density in subgroups of patients with FMS. We found 51 aberrantly expressed miRNAs in white blood cells of patients with FMS, of which miR-let-7d correlated with reduced small nerve fiber density in patients with FMS. Furthermore, we demonstrated miR-let-7d and its downstream target insulin-like growth factor-1 receptor as being aberrantly expressed in skin of patients with FMS with small nerve fiber impairment. Our study gives further evidence of small nerve fiber pathology in FMS subgroups and provides a missing link in the pathomechanism that may lead to small fiber loss in subgroups of patients with FMS.
A Quality Improvement Project to Increase Breast Milk Expression
Authors: Connolly Mary Ellen , Buckley Kathleen M. 
Published: July 2016

Breast milk is recognized as the ideal nutrition for all infants especially for infants in the neonatal intensive care unit (NICU). Breast milk diet for critically ill infants is associated with decreased septic events and length of stay and reduced risk of surgical necrotizing enterocolitis. Purpose This quality improvement project focused on the development of a breast pumping program for mothers with infants in the NICU. Methods NICU nurse breast milk champions received education on benefits of breast milk and key factors in maintaining adequate milk supply. Champions engaged mothers in conversations to provide support and used a “Coming to Volume Assessment” tool as a guide to assess pumping effectiveness. Champions were interviewed about the benefits, ease of use of assessment tool, and future directions for the pumping program. Results Daily contact with the bedside nurse had a positive effect on breast milk expression rates. Six of 14 mothers, who met with a champion greater than three times in a 2-week period, reached goal volumes. Average maximum milk produced was 836.6 ml ( SD = 228.5 ml, 95% confidence interval [596, 1076]) on infants’ eighth day of life. Champions described the program as a positive experience for the mothers and themselves and the tool as easy to use. They also endorsed continued implementation of the pumping program. Conclusions A pumping program in the NICU that incorporates staff education and use of the “Coming to Volume Assessment” tool with frequent dialogue with mothers to evaluate effectiveness of breast milk expression can aide in the promotion of breast milk expression.
Evaluating the Efficacy and Safety of Epidural Analgesia for Postoperative Pain Management in Neonates/Infants Undergoing Abdominal or Thoracic Surgery
Authors: Duran Melissa S. , Meeker Tamara M. , Rintoul Natalie E. , Maxwell Lynne G. 
Published: July 2016

Introduction The purpose of this study was to evaluate the efficacy and safety of epidural analgesia in neonates/infants after open abdominal or thoracic surgery. Efficacy was measured by recorded pain score and need for additional continuous opioid. Safety was measured by length of time infusion was administered, complications, and adverse events. Methods This study was a nonexperimental, descriptive, retrospective design conducted in the newborn/infant intensive care unit at an urban quaternary care pediatric hospital. Subjects were neonates/infants 0–12 months admitted after abdominal or thoracic surgery with an epidural for postoperative pain management. Results Ninety-four neonates/infants were identified. Patients received a continuous intravenous opioid, in addition to the epidural, 45% of the time. There was no statistically significant correlation of the addition of a continuous opioid infusion with gender ( p = .83), gestational age ( p = .59), or race ( p = .98). The surgical site was statistically significant, with infants who had a thoracotomy requiring a continuous opioid infusion 24% of the time versus 67% of the time in those who had a laparotomy ( p = .0003). There were minor complications related to epidurals 21% of the time and no adverse events. Regardless of the need for a continuous opioid infusion, pain scores were greater for all patients between 8 and 16 hours postoperatively. Discussion Epidural analgesia was shown to be safe and effective in surgical neonates/infants. Epidurals were most effective as monotherapy in neonates/infants after thoracotomies. The addition of a continuous opioid should be considered in all neonates/infants after laparotomies. The results of this study will help guide practice in the future, increase patient safety, and improve postoperative outcomes.
Combination Therapy of All-Trans Retinoic Acid With Ursodeoxycholic Acid in Patients With Primary Sclerosing Cholangitis
Authors: Assis David N. , Abdelghany Osama , Cai Shi-Ying , Gossard Andrea A. , Eaton John E. , Keach Jill C. , Deng Yanhong , Setchell Kenneth D.R. , Ciarleglio Maria , Lindor Keith D. , Boyer James L. 
Published: July 2016

Goals:
To perform an exploratory pilot study of all-trans retinoic acid (ATRA) combined with ursodeoxycholic acid (UDCA) in patients with primary sclerosing cholangitis (PSC).

Background:
PSC is a progressive disorder for which there is no accepted therapy. Studies in human hepatocyte cultures and in animal models of cholestasis indicate that ATRA might have beneficial effects in cholestatic disorders.

Study:
ATRA (45 mg/m2/d, divided and given twice daily) was combined with moderate-dose UDCA in patients with PSC who had incomplete response to UDCA monotherapy. The combination was administered for 12 weeks, followed by a 12-week washout in which patients returned to UDCA monotherapy. We measured alkaline phosphatase (ALP), alanine aminotransferase (ALT), bilirubin, cholesterol, bile acids, and the bile acid intermediate 7α-hydroxy-4-cholesten-3-one (C4) at baseline, week 12, and after washout.

Results:
Fifteen patients completed 12 weeks of therapy. The addition of ATRA to UDCA reduced the median serum ALP levels (277±211 to 243±225 U/L, P=0.09) although this, the primary endpoint, did not reach significance. In contrast, median serum ALT (76±55 to 46±32 U/L, P=0.001) and C4 (9.8±19 to 7.9±11 ng/mL, P=0.03) levels significantly decreased. After washout, ALP and C4 levels nonsignificantly increased, whereas ALT levels significantly increased (46±32 to 74±74, P=0.0006), returning to baseline.

Conclusions:
In this human pilot study, the combination of ATRA and UDCA did not achieve the primary endpoint (ALP); however, it significantly reduced ALT and the bile acid intermediate C4. ATRA appears to inhibit bile acid synthesis and reduce markers of inflammation, making it a potential candidate for further study in PSC (NCT 01456468).
Upper Versus Lower Endoscopy in the Diagnosis of Graft-Versus-Host Disease
Authors: Cloutier Justin , Wall Donna A. , Paulsen Kristjen , Bernstein Charles N. 
Published: July 2016

Background and Aim:
The optimal endoscopic approach to patients with suspected gut graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation (HSCT) is uncertain. We aimed to assess the diagnostic yield of upper and lower endoscopies performed in patients post-HSCT.

Methods:
We identified a cohort post-HSCT with acute and chronic GVHD who underwent gastrointestinal endoscopies for GVHD diagnosis. Hospital charts were reviewed and results were stratified according to patients’ symptoms.

Results:
From 1990 to 2013 433 HSCTs were performed. Fifty-six patients underwent 141 endoscopies, of which 117 were done to evaluate for GVHD or an alternative diagnosis. A total of 28/43 (65%) of the lower endoscopies and 41/74 (55%) of the upper endoscopies diagnosed GVHD or an alternative disease process on pathology. A total of 15/43 (35%) of lower endoscopies were flexible sigmoidoscopies, and 11/15 (73%) of these diagnosed GVHD or an alternative diagnosis. Upper endoscopy performed in patients with diarrhea as their only symptom diagnosed GVHD in 44% and an alternative diagnosis in 11%. In comparison, lower endoscopy in patients with only diarrhea diagnosed GVHD in 50%, and 18% offered an alternative diagnosis. Upper endoscopy provided a diagnosis of opportunistic viral and fungal infections of the upper gastrointestinal tract in 7 patients, while lower endoscopy diagnosed pseudomembranous colitis in 2.

Conclusions:
Upper and lower endoscopy had a similar diagnostic yield in patients with known or suspected GVHD involving the gut, even for patients presenting only with diarrhea. Because of its ease and safety upper endoscopy is the preferred initial endoscopic approach in patients with suspected gut GVHD, however flexible sigmoidoscopy is a reasonable other option.
On-treatment and off-treatment efficacy of entecavir in a real-life cohort of chronic hepatitis B patients
Authors: Park Chung-Hwa , Kim Hee Yeon , Lee Sung Won , Song Do Seon , Song Myeong Jun , Kwon Jung Hyun , You Chan Ran , Jang Jeong Won , Kim Chang Wook , Choi Sang Wook , Bae Si Hyun , Choi Jong Young , Yoon Seung Kew 
Published: July 2016

Background and aims
Entecavir (ETV) is a potent nucleoside analogue with high genetic barrier to resistance. In this study, real-life clinical experiences in the long-term use of ETV and the durability of its off-treatment effectiveness were analyzed.

Materials and methods
This study was based on a large real-life cohort of 2240 chronic hepatitis B patients treated with ETV between January 2006 and December 2012 using a centralized electronic data repository.

Results
Among 2240 patients, 804 patients were treatment naive and underwent ETV monotherapy. Their mean treatment duration was 712±493 days, with a cumulative proportion of patients achieving HBV DNA less than 300 copies/ml in 85.8, 95.7, and 97.6% at years 1, 2, and 3, respectively. Predictors for earlier virologic response were female sex, lower HBV DNA, higher alanine transaminase, lower platelet count, and HBeAg negativity at baseline. In patients who achieved virologic response and HBeAg loss, the cumulative relapse rate was 91.3% in 2 years after the cessation of treatment. During the treatment, 34 patients developed hepatocellular carcinoma, among whom 30 patients had cirrhosis before treatment initiation. ETV treatment showed efficient virologic response as the treatment duration was extended, but off-treatment efficacy was not durable, and the antiviral treatment showed some limitation in preventing hepatocellular carcinoma among liver cirrhosis patients, implying that treatment cessation should be taken into consideration more carefully.

Conclusion
This study from a real-life cohort may provide data on treating chronic hepatitis B patients more close to everyday clinical practice.
Advances in pediatric cardiac MRI
Authors: Banka Puja , Geva Tal 
Published: July 2016

Purpose of review
Spurred by numerous recent technological advances, cardiac MRI (CMR) is now the gold standard for anatomic evaluation, quantitative assessment of chamber size and function, flow quantification, and tissue characterization. This review focuses on recent advances in pediatric and congenital CMR, highlighting recent safety data, and discussing future directions.

Recent findings
CMR has become an important component of risk stratification and procedural planning in numerous congenital and pediatric heart diseases. Innovative approaches to image acquisition and reconstruction are leading the way toward fast, high-resolution, three- and four-dimensional datasets for delineation of cardiac anatomy, function, and flow. In addition, techniques for assessing the composition of the myocardium may help elucidate the pathophysiology of late complications, identify patients at risk for heart failure, and assist in the evaluation of therapeutic strategies.

Summary
CMR provides invaluable morphologic, hemodynamic, and functional data that help guide diagnosis, assessment, and management of pediatric and adult congenital heart disease. As imaging techniques advance and data accumulate on the relative and additive value of CMR in patient care, its role in a multimodality approach to the care of this population of patients is becoming clear and is likely to continue to evolve.
Making a heart: advances in understanding the mechanisms of cardiac development
Authors: Dees Ellen , Baldwin H. Scott 
Published: July 2016

Purpose of review
The study of cardiac development is critical to inform management strategies for congenital and acquired heart disease. This review serves to highlight some of the advances in this field over the past year.

Recent findings
Three main areas of study are included that have been particularly innovative and progressive. These include more precise gene targeting in animal models of disease and in moving from animal models to human disease, more precise in-vitro models including three-dimensional structuring and inclusion of hemodynamic components, and expanding the concepts of genetic regulation of heart development and disease.

Summary
Targeted genetics in animal models are able to make use of tissue and time-specific promotors that drive gene expression or knockout with high specificity. In-vitro models can recreate flow patterns in blood vessels and across cardiac valves. Noncoding RNAs, once thought to be of no consequence to gene transcription and translation, prove to be key regulators of genetic function in health and disease.
Early Posthepatoportoenterostomy Predictors of Native Liver Survival in Biliary Atresia
Authors: Nightingale Scott , Stormon Michael O. , O'Loughlin Edward V. , Shun Albert , Thomas Gordon , Benchimol Eric I. , Day Andrew S. , Adams Susan , Shi Edward , Ooi Chee Y. , Kamath Binita M. , Fecteau Annie , Langer Jacob C. , Roberts Eve A. , Ling Simon C. , Ng Vicky L. 
Published: July 2016

ABSTRACTObjectives:Most infants with biliary atresia (BA) require liver transplantation (LT) after hepatoportoenterostomy (HPE), including those who initially clear jaundice. The aim of the present study was to identify clinical and routine laboratory factors in infants with BA post‐HPE that predict native liver survival at 2 years.Methods:A retrospective cohort study was conducted in 217 patients with BA undergoing HPE in Sydney, Australia and Toronto, Canada between January 1986 and July 2009. Univariate and multivariate logistic regression using backwards‐stepwise elimination identified variables at 3 months after HPE most associated with 2‐year native liver survival.Results:Significant variables (P < 0.05) on univariate analysis included serum total bilirubin (TB) and albumin at 3 months post‐HPE, bridging fibrosis or cirrhosis on initial liver biopsy, ascites of <3 months post‐HPE, type 3 BA anatomy, age at HPE of >45 days, change in length z scores within 3 months of HPE, and center. On multivariate analysis, TB (P < 0.0001) and albumin (P = 0.02) at 3 months post‐HPE, and center (P = 0.0003) were independently associated with native liver survival. Receiver operating characteristic analysis revealed an optimal cut‐off value of TB <74 μmol/L (4.3 mg/dL; area under the receiver operating characteristic curve 0.8990) and serum albumin level >35 g/L (3.5 mg/dL; area under the receiver operating characteristic curve 0.7633) to predict 2‐year native liver survival. TB and albumin levels 3 months post‐HPE defined 3 groups (1: TB ⩽74 μmol/L, albumin >35 g/L; 2: TB ⩽74 μmol/L, albumin ⩽35 g/L; 3: TB >74 μmol/L) with distinct short‐ and long‐term native liver survival rates (log‐rank P < 0.001). Length z scores 3 months post‐HPE were poorer for group 2 than group 1 (−0.91 vs −0.30, P = 0.0217) with similar rates of coagulopathy.Conclusions:Serum TB and albumin levels 3 months post‐HPE independently predicted native liver survival in BA when controlling for center. Serum albumin level <35 g/L in infants with BA who were no longer jaundiced at 3 months post‐HPE was a poor prognostic indicator. Poorer linear growth and absence of significant coagulopathy suggest a role for early aggressive nutritional therapy in this group.
Oral Tocofersolan Corrects or Prevents Vitamin E Deficiency in Children With Chronic Cholestasis
Authors: Thébaut Alice , Nemeth Antal , Le Mouhaër Jeannie , Scheenstra René , Baumann Ulrich , Koot Bart , Gottrand Fredéric , Houwen Roderick , Monard Laure , de Micheaux Sylvie Lafaye , Habes Dalila , Jacquemin Emmanuel 
Published: July 2016

ABSTRACTObjectives:D‐Alpha‐tocopheryl polyethylene glycol 1000 succinate (Tocofersolan, Vedrop), has been developed in Europe to provide an orally bioavailable source of vitamin E in children with cholestasis. The aim was to analyze the safety/efficacy of Vedrop in a large group of children with chronic cholestasis.Methods:Two hundred seventy‐four children receiving Vedrop for vitamin E deficiency or for its prophylaxis were included from 7 European centers. Median age at treatment onset was 2 months and median follow‐up was 11 months. Vedrop was prescribed at a daily dose of 0.34 mL/kg (25 IU/kg) of body weight. Three methods were used to determine a sufficient serum vitamin E status: vitamin E, vitamin E/(total cholesterol), vitamin E/(total cholesterol + triglycerides).Results:Before Vedrop therapy, 51% of children had proven vitamin E deficiency, 30% had normal vitamin E status and 19% had an unknown vitamin E status. During the first months of treatment, vitamin E status was restored in the majority of children with insufficient levels at baseline (89% had a normal status at 6 months). All children with a normal baseline vitamin E status had a normal vitamin E status at 6 months. Among children with an unknown vitamin E status at baseline, 93% had a normal vitamin E status at 6 months. A sufficient vitamin E status was observed in 80% of children with significant cholestasis (serum total bilirubin >34.2 μmol/L). No serious adverse reaction was reported.Conclusions:Vedrop seems a safe and effective oral formulation of vitamin E that restores and/or maintains sufficient serum vitamin E level in the majority of children with cholestasis, avoiding the need for intramuscular vitamin E injections.
Guideline for the Evaluation of Cholestatic Jaundice in Infants
Authors: Fawaz Rima , Baumann Ulrich , Ekong Udeme , Fischler Björn , Hadzic Nedim , Mack Cara L. , McLin Valérie A. , Molleston Jean P. , Neimark Ezequiel , Ng Vicky L. , Karpen Saul J. 
Published: July 2016

ABSTRACTCholestatic jaundice in infancy affects approximately 1 in every 2500 term infants and is infrequently recognized by primary providers in the setting of physiologic jaundice. Cholestatic jaundice is always pathologic and indicates hepatobiliary dysfunction. Early detection by the primary care physician and timely referrals to the pediatric gastroenterologist/hepatologist are important contributors to optimal treatment and prognosis. The most common causes of cholestatic jaundice in the first months of life are biliary atresia (25%–40%) followed by an expanding list of monogenic disorders (25%), along with many unknown or multifactorial (eg, parenteral nutrition‐related) causes, each of which may have time‐sensitive and distinct treatment plans. Thus, these guidelines can have an essential role for the evaluation of neonatal cholestasis to optimize care. The recommendations from this clinical practice guideline are based upon review and analysis of published literature and the combined experience of the authors. The committee recommends that any infant noted to be jaundiced after 2 weeks of age be evaluated for cholestasis with measurement of total and direct serum bilirubin, and that an elevated serum direct bilirubin level (direct bilirubin levels >1.0 mg/dL or >17 μmol/L) warrants timely consideration for evaluation and referral to a pediatric gastroenterologist or hepatologist. Of note, current differential diagnostic plans now incorporate consideration of modern broad‐based next‐generation DNA sequencing technologies in the proper clinical context. These recommendations are a general guideline and are not intended as a substitute for clinical judgment or as a protocol for the care of all infants with cholestasis. Broad implementation of these recommendations is expected to reduce the time to the diagnosis of pediatric liver diseases, including biliary atresia, leading to improved outcomes.