bluuebunny/crossref_metadata_2025 huggingface dataset:
Phenotypes of wheezing and asthma in preschool children
Authors: Kwong Christina G. , Bacharier Leonard B.
Published: January 2019

Purpose of review

The purpose of this review is to provide an overview of the identified phenotypes of preschool wheezing.

Recent findings

Early life wheezing patterns have been described in multiple populations, with several commonalities found between cohorts. Early life environmental exposures have been found to be differentially associated with preschool wheezing phenotypes and their future trajectories. These include allergen and microbe exposure, environmental tobacco smoke exposure, and maternal stress and depression. Elevated IgE in early life may also influence future asthma risk.

Preschool wheezing phenotypes are heterogeneous and complex, with trajectories that are related to factors including environmental exposures. More research is needed to characterize these relationships, hopefully leading to targeted prevention strategies.
Precision medicine in childhood asthma
Authors: Slob Elise M. , Maitland-Van der Zee Anke-Hilse , Koppelman Gerard H. , Pijnenburg Mariëlle W.
Published: January 2019

Purpose of review

Childhood asthma is a heterogeneous disease and many children have uncontrolled disease. Therefore an individualized approach is needed to improve asthma outcomes in children. Precision medicine using clinical characteristics, biomarkers, and the rapidly involving field of genomics and pharmacogenomics aims to achieve asthma control and reduce future risks with less side-effects in individual children with asthma.

Recent findings

It is not yet possible to select treatment options on clinical characteristics. Novel monoclonal antibodies are efficacious in patients with severe, eosinophilic asthma. Reduced lung function growth and early decline is a prevalent finding in children with persistent asthma. Pharmacogenetic studies have identified children at risk for cortisol suppression when using inhaled corticosteroids.

Clinical characteristics and simple biomarkers like eosinophils, IgE, and the fraction of exhaled nitric oxide may be used in clinical practice for a basic precision medicine approach, deciding which children will have the best chance to respond to inhaled corticosteroids and to the biologicals omalizumab and mepolizumab.

Further application of pharmacogenomics and breathomics needs additional studies before they can be applied as tools for precision medicine in individual children with asthma.
Practical Implications of Compassionate Off-Ramps for Medical Students
Authors: Aagaard Eva M. , Moscoso Lisa
Published: January 2019

Attrition from medical school remains uncommon even when a medical student performs poorly, has a change in interests, or experiences an unexpected life event that alters his/her ability to succeed as a physician. In this issue, Bellini and colleagues describe the scope of this problem and make recommendations to support the implementation of compassionate off-ramps for students. These recommendations include enabling ongoing assessment of commitment to career path via a professional identity formation curriculum; implementing competency-based education and training to identify struggling learners; using career advisors and coaches who understand alternative career pathways; providing credit or credentials for competencies already achieved; requiring financial counseling and supporting debt forgiveness; and requiring schools to report on their remediation programs and handling of debt. In this Invited Commentary, the authors describe a representative student—a composite of several students they have counseled whose medical school paths have been impacted by poor performance, unanticipated life events and stressors, changing career interests, and/or physical and mental health issues—who may have benefited from these recommendations. The authors elaborate on Bellini and colleagues’ recommendations and describe what they think would be necessary to ensure that the recommendations effectively meet the goal of providing compassionate off-ramps for students in need. The authors describe the potential impact of the recommendations on the representative and similar students. Although this impacts a small proportion of students, the recommendations would help schools achieve the moral imperatives of humanistic care for students while honoring the social contract of the medical profession.
Growth-Friendly Spine Surgery in Escobar Syndrome
Authors: Margalit Adam , Sponseller Paul D. , McCarthy Richard E. , Pawelek Jeff B. , McCullough Lynn , Karlin Lawrence I. , Shirley Eric D. , Schwend Richard M. , Samdani Amer F. , Akbarnia Behrooz A.
Published: January 2019

Background:

The aims of this study were to characterize the spinal deformity of patients with Escobar syndrome, describe results of growth-friendly treatments, and compare these results with those of an idiopathic early-onset scoliosis (EOS) cohort to determine whether the axial stiffness in Escobar syndrome limited correction.

Methods:

We used 2 multicenter databases to review the records of 8 patients with EOS associated with Escobar syndrome who had at least 2-year follow-up after initiation of growth-friendly treatment from 1990 to 2016. An idiopathic EOS cohort of 16 patients matched for age at surgery (±1 y), postoperative follow-up (±1 y), and initial curve magnitude (±10 degrees) was identified. A randomized 1:2 matching algorithm was applied (α=0.05).

Results:

In the Escobar group, spinal deformity involved 7 to 13 vertebrae and ranged from no vertebral anomalies in 3 patients to multiple segmentation defects in 6 patients. Mean age at first surgery was 5 years (range, 1.4 to 7.8 y) with a mean follow-up of 7.5 years (range, 4.0 to 10 y). Mean major curve improved from 76 degrees at initial presentation, to 43 degrees at first instrumentation, to 37 degrees at final follow-up (both P<0.001). Mean pelvic obliquity improved from 16 degrees (range, 5 to 31 degrees) preoperatively to 4 degrees (range, 0 to 8 degrees) at final follow-up (P=0.005). There were no differences in the mean percentage of major curve correction between the idiopathic EOS and Escobar groups at the immediate postoperative visit (P=0.743) or final follow-up (P=0.511). There were no differences between the cohorts in T1-S1 height at initial presentation (P=0.129) or in growth per month (P=0.211).

Conclusions:

Multiple congenital fusions and spinal curve deformity are common in Escobar syndrome. Despite large areas of congenital fusion, growth-friendly constructs facilitate spinal growth and improve curve correction. These results are comparable to those in idiopathic EOS.

Level of Evidence:

Level III—case-control study.
Nonarticular Base and Shaft Fractures of Children’s Fingers: Are Follow-up X-rays Needed? Retrospective Study of Conservatively Treated Proximal and Middle Phalangeal Fractures
Authors: Vonlanthen Janine , Weber Daniel M. , Seiler Michelle
Published: January 2019

Background:

Phalangeal fractures of the hand are common in children, and most extra-articular fractures can be treated with nonoperative management. Minimally or nondisplaced fractures may simply be immobilized, whereas displaced fractures need closed reduction before immobilization. Although few of these fractures displace secondarily, most schemes currently recommend follow-up x-rays after initial diagnosis. Our primary objective was to identify subgroups of finger fractures that are stable, thus requiring no radiographic monitoring.

Methods:

This study was designed as a retrospective, single-center analysis of conservatively treated pediatric finger fractures of the proximal and middle phalanges. We included patients up to 16 years with base or shaft fractures of the index to little fingers who underwent nonoperative treatment and standardized follow-up controls in our pediatric hand surgery outpatients’ clinic between 2010 and 2016. Fracture angular deformity in x-rays taken at diagnosis and after 1 and 3 weeks were reassessed blinded, and a statistical analysis was conducted to identify fracture types that are prone to secondary angular deformity.

Results:

A total of 478 patients were eligible; 113 were lost due to missing final radiographic controls. Overall, 365 patients were analyzed; they had a mean age of 9.7 years (range, 1 to 16), and 33.4% required a primary closed reduction. A secondary angular deformity occurred in 2.2% (8/365) of all finger fractures. No secondary angulation occurred in primary minimally and nondisplaced fractures, but 6.6% (8/122) of the reduced fractures showed a subsequent loss of reduction.

Conclusions:

Minimally angulated (<10 degrees) and nondisplaced metaphyseal and diaphyseal fractures of proximal and middle phalanges of the index to little fingers are stable and therefore do not need radiographic follow-ups. However, initially angulated fractures requiring closed reduction bear a risk of subsequent loss of reduction.

Level of Evidence:

Level III—retrospective study.
Maternal Feeding Practices, Health Cognitions, and Children's Eating Styles and Weight Status
Authors: Camfferman Roxanna , Van der Veek Shelley Maria Cornelia , Rippe Ralph Christian Alexander , Mesman Judi
Published: January 2019

Objective:

To examine the relationship between maternal cognitions related to promoting a healthy lifestyle in their child, maternal feeding practices, children's eating styles, and child weight status in children aged 4 to 6 years.

Methods:

Cross-sectional questionnaire data were collected in 251 Dutch mothers of preschoolers. Structural equation modeling was used to test the fit of a model that assumed maternal health cognitions would predict maternal feeding practices, which in turn would predict children's eating styles and child weight status. Explorative analyses were conducted to examine child characteristics as predictors of maternal health cognitions and feeding practices.

Results:

Mothers with higher self-efficacy used fewer pressure-to-eat feeding techniques, which in turn was related to less avoidant eating styles in children. In addition, mothers who perceived more benefits of a healthy lifestyle used more restriction techniques, which in turn predicted a more approach-oriented eating style in children, which was also related to higher child standard deviation scores body mass index. Finally, children with an avoidant eating style had mothers who perceived more barriers and reported less self-efficacy.

Conclusion:

Self-efficacy and perceived benefits relate to maternal feeding practices and eating styles of the child. However, more perceived benefits of a healthy lifestyle were associated with inadequate feeding practices. Therefore, interventions targeted at mothers to reduce child overweight should focus not only on reinforcing perceived benefits of a healthy lifestyle but also on how the mother can translate her attitudes into adaptive parenting to achieve the desired health outcomes.
Endoscopic Phenotype of Monoallelic Carriers of MUTYH Gene Mutations in the Family of Polyposis Patients: A Prospective Study
Authors: El Hachem Noha , Abadie Caroline , Longy Michel , Colas Chrystelle , Fert-Ferrer Sandra , Leroux Dominique , Grandval Philippe , Prieur Fabienne , Collonge-Rame MarieAgnes , Faivre Laurence , Fricker Jean-Pierre , Zerbib Frank , Coupier Isabelle , Cauchin Estelle , Pinson Stephane , Saurin Jean Christophe
Published: January 2019

BACKGROUND:

Almost no prospective data on endoscopy in MUTYH monoallelic carriers are available.

OBJECTIVE:

This study aimed to define the prevalence of colorectal and duodenal adenomas in a population of people presenting with a single mutation of the MUTYH gene and being first-degree relatives of biallelic MUTYH mutation carriers.

DESIGN:

This study is a prospective cohort evaluation.

PATIENTS:

Patients were first-degree relatives of a patient who had polyposis with biallelic MUTYH mutation and carrying a single gene mutation of the gene from 12 French centers.

SETTINGS:

This is a multicenter study.

INTERVENTION:

Detailed data on life habits (tobacco, alcohol, and nonsteroidal anti-inflammatory drugs), extraintestinal manifestations, and germline analysis were recorded. Complete endoscopic evaluation (colonoscopy and upper endoscopy) with chromoendoscopy was performed.

RESULTS:

Sixty-two patients were prospectively included (34 women (55%), mean age of 54, range 30–70 years). Thirty-two patients (52%) presented with colorectal polyps at colonoscopy. Of these patients with polyps, 15 (25%) had only adenomas, 8 (13%) had only hyperplastic polyps, 1 (1%) had sessile serrated adenomas, and 8 (13%) had adenomas and/or sessile serrated adenomas. We detected, in total, 29 adenomas with low-grade dysplasia, 5 adenomas with high-grade dysplasia, and 6 sessile serrated adenomas. Fourteen patients (23%) presented with a single adenoma, and 10 (16%) had 1 to 5 adenomas. No patient had more than 5 adenomas. At upper endoscopy, 3 had a limited number of fundic gland polyps; none had duodenal adenomas. The 2 main missense mutations c.1145G>A, p.Gly382Asp and c.494A>G, p.Tyr165Cys were associated with the development of colorectal adenomas/serrated polyps in these monoallelic carriers.

LIMITATIONS:

This study was limited by the small number of patients.

CONCLUSIONS:

This prospective study provides unique prospective data suggesting that monoallelic mutation carriers related to patients with polyposis show no colorectal polyposis and have very limited upper GI manifestations justifying an endoscopic follow-up. See Video Abstract at http://links.lww.com/DCR/A862.
The 5-Step Filler Hand Rejuvenation: Filling with Hyaluronic Acid
Authors: Khosravani Nima , Weber Lee , Patel Rina , Patel Anup
Published: January 2019

Many patients are pursuing simultaneous facial and hand rejuvenation with the latter receiving increased interest in recent years. Various materials have been purported to rejuvenate the hands including fat, calcium hydroxyapatite, and hyaluronic fillers. Despite the seemingly ubiquitous use of fillers, the Food and Drug Administration has approved only a select number for hand rejuvenation. This year, Restylane Lyft (Galderma, Texas) became the first hyaluronic acid filler to garner Food and Drug Administration approval for hand rejuvenation. The purpose of this video plus article was to demonstrate the technical nuances in administering hyaluronic filler in a safe and effective manner as it relates to hand rejuvenation.
Implications of Aging in Plastic Surgery
Authors: Roh Danny S. , Panayi Adriana C. , Bhasin Shalender , Orgill Dennis P. , Sinha Indranil
Published: January 2019

Given the rapidly aging population, investigating the effect of age on plastic surgery outcomes is imperative. Despite this, the topic has received relatively little attention. Furthermore, there appears to be little integration between the basic scientists investigating the mechanisms of aging and the plastic surgeons providing the majority of “antiaging” therapies. This review first provides a description of the effects and mechanisms of aging in 5 types of tissue: skin, adipose tissue, muscles, bones and tendons, and nervous tissue followed by an overview of the basic mechanisms underlying aging, presenting the currently proposed cellular and molecular theories. Finally, the impact of aging, as well as frailty, on plastic surgery outcomes is explored by focusing on 5 different topics: general wound healing and repair of cutaneous tissue, reconstruction of soft tissue, healing of bones and tendons, healing of peripheral nerves, and microsurgical reconstruction. We find mixed reports on the effect of aging or frailty on outcomes in plastic surgery, which we hypothesize to be due to exclusion of aged and frail patients from surgery as well as due to outcomes that reported no postsurgical issues with aged patients. As plastic surgeons continue to interact more with the growing elderly population, a better appreciation of the underlying mechanisms and outcomes related to aging and a clear distinction between chronological age and frailty can promote better selection of patients, offering appropriate patients surgery to improve an aged appearance, and declining interventions in inappropriate patients.
Associations between Orofacial Clefting and Neonatal Abstinence Syndrome
Authors: Mullens Cody L. , McCulloch Ian L. , Hardy Kristen M. , Mathews Russell E. , Mason A. Corde
Published: January 2019

Background:

Orofacial clefting (OFC) is the most common developmental craniofacial malformation, and causal etiologies largely remain unknown. The opioid crisis has led to a large proportion of infants recovering from neonatal abstinence syndrome (NAS) due to in-utero narcotics exposure. We sought to characterize the prevalence of OFC in infants with NAS.

Methods:

This cohort study analyzed live births at our institution from 2013 to 2017 to identify any association between OFC and NAS.

Results:

Prevalence of OFC was 6.79 and 1.63 (per 1,000 live births) in the NAS and general population, respectively. Odds ratios for NAS patients having developed OFC, isolated cleft palate, isolated cleft lip, and combined cleft lip and palate compared with the general population were found to be 4.18 (P = 0.001), 5.92 (P = 0.001), 3.79 (P = 0.05), and 2.94 (P = 0.35), respectively. Analyses performed comparing the NAS and general populations to control for potential confounding variables influencing the NAS population yielded no significant differences with exception of in-utero exposure to physician prescribed opioids.

Conclusions:

Prevalence of OFC in infants with NAS was higher than the general live birth population. Isolated cleft palate and isolated cleft lip, specifically, were significantly more prevalent in NAS patients compared with the general population and were associated with in-utero opioid exposure.
Epi-Bowman Blunt Keratectomy Versus Diluted EtOH Epithelial Removal in Myopic Photorefractive Keratectomy: A Prospective Contralateral Eye Study
Authors: Vingopoulos Filippos , Kanellopoulos Anastasios John
Published: January 2019

Purpose:

To compare the outcomes and complications of Epi-Bowman blunt keratectomy (EBK) using a blunt epikeratome (Epi-Clear, Orca Surgical, Israel), with alcohol delamination of the corneal epithelium during photorefractive keratectomy (PRK) in contralateral eyes.

Methods:

This prospective, randomized contralateral eye study included 44 eyes of 22 patients undergoing PRK for bilateral myopia or myopic astigmatism. In each patient, epithelial delimitation was performed using an Epi-Clear epikeratome EBK (EBK group) on 1 eye and diluted ethanol (EtOH) on the fellow eye (EtOH group). Postoperative pain, epithelial healing, epithelial profile, and visual outcome were compared between the 2 groups.

Results:

The mean postoperative pain scores were 0.37 ± 0.25 for the EBK group and 0.82 ± 0.22 for the EtOH group (P = 0.043). The mean epithelial defect size at day 3 postoperatively was 1.61 ± 1.46 and 2.25 ± 1.69 mm2, respectively (P = 0.034). The postoperative 3-month remaining mean spherical equivalent was 0.04 ± 0.49 diopters for the EBK group and 0.21 ± 0.26 D for the EtOH group (P = 0.520). There was no significant difference in UCVA and BCVA between the groups.

Conclusions:

Our data suggest that this novel EBK device and technique may minimize postoperative pain, accelerate re-epithelialization, and offer earlier visual recovery, compared with EtOH when used for myopic PRK.
Clinical Characteristics of Autosomal Dominant GJA1 Missense Mutation Linked to Oculodentodigital Dysplasia in a Korean Family
Authors: Park Do Young , Cho Sung Yoon , Jin Dong-Kyu , Kee Changwon
Published: January 2019

Purpose:

We aimed to present a comprehensive assessment of the ophthalmic characteristics of genetically confirmed oculodentodigital dysplasia (ODDD) in 4 members of a single Korean family across 3 generations.

Patients and Methods:

The characteristics of 4 affected ODDD patients were evaluated. Comprehensive ophthalmic and medical examinations were performed in 3 patients including the proband, together with genetic analysis, and retrospective chart review was conducted for an affected ancestor. For genetic analysis, targeted gene panel sequencing was conducted using genomic DNA extracted from peripheral blood.

Results:

All affected individuals in this family showed shared ophthalmic abnormalities of microcornea, microphthalmia, elevated intraocular pressure, and shallow anterior chamber, all of which have been reported as typical ocular features of ODDD. Myopic refractive error despite short axial length and thick cornea were highlighted as new findings of ODDD. Facial abnormalities were common in all affected members, but their fingers were normal. Severity of glaucoma was different among the affected individuals and seemed to depend on elevation of intraocular pressure, which occurred in narrow, but open-angle. Genetic analysis revealed the presence of c.119C>T (p.Ala40Val) in GJA1, which is responsible for ODDD, but not found in the control population.

Conclusions:

This report describes detailed ocular characteristics in a genetically confirmed ODDD family, including unreported findings of thick cornea and myopic refractive error despite short axial length. The ocular features derived from the A40V mutation in GJA1 showed complete penetrance, suggesting a possible role of Cx43 in regulation of IOP and pathogenesis of glaucoma.
Improving Colorectal Cancer Screening Rates in Patients Referred to a Gastroenterology Clinic
Authors: Bick Benjamin L. , El-Halabi Mustapha , Jones Keaton R. , Kahi Charles J. , Fayad Nabil F.
Published: January 2019

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related death in the United States. Colonoscopy and fecal immunochemistry testing (FIT) are the primary recommended CRC screening modalities. The purpose of this study is to improve rates of CRC screening in Veterans and County hospital patients referred to gastroenterology fellow's clinics. A total of 717 patients between ages of 49 and 75 years were seen. Previous CRC screening was not performed in 109 patients (15.2%) because of not being offered (73.4%) or declining (26.6%) screening. Patients who received previous CRC screening compared with no previous screening were older (mean age 62.3 years vs. 60.3 years, p < .003), white (88.6% vs. 78.3%, p < .027), and more likely to be Veterans patients (90.8% vs. 77.5%, p < .001). After systematically discussing options for screening with 78 of the 109 unscreened patients, 56 of them (71.8%) underwent screening with either colonoscopy (32) or FIT (24). Patients seen by fellows in their last year of training agreed to undergo screening more often than those seen by other fellows (100% vs. 66.2%, p < .033). Systematic discussions about both colonoscopy and FIT can improve the overall rates of CRC screening.
Chylomicron retention disease: genetics, biochemistry, and clinical spectrum
Authors: Levy Emile , Poinsot Pierre , Spahis Schohraya
Published: January 2019

Purpose of review

Chylomicron retention disease (CRD) is an autosomic recessive disorder, in which intestinal fat malabsorption is the main cause of diverse severe manifestations. The specific molecular defect was identified in 2003 and consists of mutations in the SAR1B or SARA2 gene encoding for intracellular SAR1B GTPase protein. The aim of this review is first to provide an update of the recent biochemical, genetic and clinical findings, and second to discuss novel mechanisms related to hallmark symptoms.

Recent findings

CRD patients present with SAR1B mutations, which disable the formation of coat protein complex II and thus blocks the transport of chylomicron cargo from the endoplasmic reticulum to the Golgi. Consequently, there is a total absence of chylomicron and apolipoprotein B-48 in the blood circulation following a fat meal, accompanied by a deficiency in liposoluble vitamins and essential fatty acids. The recent discovery of Transport and Golgi organization and Transport and Golgi organization-like proteins may explain the intriguing export of large chylomicron, exceeding coat protein complex II size. Hypocholesterolemia could be accounted for by a decrease in HDL cholesterol, likely a reflection of limited production of intestinal HDL in view of reduced ATP-binding cassette family A protein 1 and apolipoprotein A-I protein. In experimental studies, the paralog SAR1A compensates for the lack of the SAR1B GTPase protein.

Molecular testing for CRD is recommended to distinguish the disease from other congenital fat malabsorptions, and to early define molecular aberrations, accelerate treatment, and prevent complications.
Clinical Practice Approach to Nonalcoholic Fatty Liver Disease by Pediatric Gastroenterologists in the United States
Authors: Shapiro Warren L. , Yu Elizabeth L. , Arin Jennifer C. , Murray Karen F. , Ali Sabina , Desai Nirav K. , Xanthakos Stavra A. , Lin Henry C. , Alkhouri Naim , Abdou Reham , Abrams Stephanie H. , Butler Megan W. , Faasse Sarah A. , Gillis Lynette A. , Hadley Timothy A. , Jain Ajay K. , Kavan Marianne , Kordy Kattayoun , Lee Peter , Panganiban Jennifer , Pohl John F. , Potter Carol , Rudolph Bryan , Sundaram Shikha S. , Joshi Shivali , Proudfoot James A. , Goyal Nidhi P. , Harlow Kathryn E. , Newton Kimberly P. , Schwimmer Jeffrey B.
Published: January 2019

Objectives:

Nonalcoholic fatty liver disease (NAFLD) is common; however, no information is available on how pediatric gastroenterologists in the United States manage NAFLD. Therefore, study objectives were to understand how pediatric gastroenterologists in the US approach the management of NAFLD, and to identify barriers to care for children with NAFLD.

Methods:

We performed structured one‐on‐one interviews to ascertain each individual pediatric gastroenterologist's approach to the management of NAFLD in children. Responses were recorded from open‐ended questions regarding screening for comorbidities, recommendations regarding nutrition, physical activity, medications, and perceived barriers to care.

Results:

Response rate was 72.0% (486/675). Mean number of patients examined per week was 3 (standard deviation [SD] 3.5). Dietary intervention was recommended by 98.4% of pediatric gastroenterologists. Notably, 18 different dietary recommendations were reported. A majority of physicians provided targets for exercise frequency (72.6%, mean 5.6 days/wk, SD 1.6) and duration (69.9%, mean 40.2 minutes/session, SD 16.4). Medications were prescribed by 50.6%. Almost one‐half of physicians (47.5%) screened for type 2 diabetes, dyslipidemia, and hypertension. Providers who spent more than 25 minutes at the initial visit were more likely to screen for comorbidities (P = 0.003). Barriers to care were reported by 92.8% with 29.0% reporting ≥3 barriers.

Conclusions:

The majority of US pediatric gastroenterologists regularly encounter children with NAFLD. Varied recommendations regarding diet and exercise highlight the need for prospective clinical trials. NAFLD requires a multidimensional approach with adequate resources in the home, community, and clinical setting.
Biliary Atresia–associated Cholangitis
Authors: Ginström Daniel A. , Hukkinen Maria , Kivisaari Reetta , Pakarinen Mikko P.
Published: January 2019

Objectives:

Cholangitis and bile lakes are incompletely understood complications after portoenterostomy (PE). We investigated relationships between recurrent cholangitis, bile lakes, and clinical outcomes as well as surgical management of bile lakes.

Methods:

In this retrospective observational single institution study medical records and imaging studies of all patients who had undergone PE for biliary atresia during 1987 to 2016 (N = 61) were reviewed. We related occurrence of cholangitis episodes with the presence of intrahepatic bile lakes, patient characteristics, and PE outcomes. Risk factors for recurrent cholangitis and bile lakes, and management of bile lakes were analyzed.

Results:

Despite routine antibiotic prophylaxis median of 3.0 cholangitis episodes (0.75 episodes/year) occurred in 48 (79%) patients. Intrahepatic bile lakes were discovered in 8 (13%) patients by 16 months after PE. Overall, 54% had survived with their native liver at median age of 7.3 years and 28 (46%) patients had ≥1 cholangitis episodes/year. Number and frequency of cholangitis episodes were >5 times higher among patients with bile lakes (P < 0.001). Six patients underwent Roux‐en‐Y bile lake‐jejunostomy, resulting in regression/disappearance of bile lakes and normalization of serum bilirubin in 5 with reduction of median yearly cholangitis rate from 8.8 to 1.1 (P = 0.028) and native liver survival of 6.3 (range, 1.3–17) years after the operation.

Conclusions:

Bile lakes are a significant risk factor for recurrent cholangitis after PE and efficiently treated by operative intestinal drainage providing prolonged jaundice‐free native liver survival. Bile lakes should be actively screened among patients presenting with recurrent cholangitis after PE.
Pediatric Osteosarcoma of Extremities: A 15-year Experience From a Tertiary Care Cancer Center in Upper Egypt
Authors: Morsy Ahmed M. , Abdelgawad Marwa I. , Ahmed Badawy M. , Rezk Khalid M. , Aboelgheit Amir M. , Ramadan Islam K.-A. , Kamel Hosam E.M. , Fouad Doaa M. , Herdan Rania A. , Shabaan Shimaa H. , Eltyb Hanan A.
Published: January 2019

Aim:

To assess the outcome and determine predictors of survival in pediatric patients with osteosarcoma of the extremities treated with a unified chemotherapy protocol at a single institution over a 15-year period.

Materials and Methods:

We performed a retrospective analysis of medical records of 48 pediatric patients with histologically verified osteosarcoma of the extremities diagnosed at South Egypt Cancer Institute and received treatment between January 2001 and December 2015.

Results:

With a median follow-up of 61 months for the entire cohort, estimates of overall survival (OS) for 3- and 5-year were 50.9% and 42.1%, respectively. While the estimates of OS for 3- and 5-year in the nonmetastatic group were 79% and 65.2%, respectively. In the multivariable analysis, both metastatic disease at diagnosis and poor response to chemotherapy retained their statistical significance as independent predictors for event-free survival. Whereas for OS, a metastatic disease at diagnosis remained as the lone predictor of a dismal outcome, while a poor response to chemotherapy became marginally associated with an inferior outcome.

Conclusions:

In Upper Egypt, whereas slightly less than two thirds of children with localized osteosarcoma of extremities survives their disease, metastasis at presentation remains the key predictor of dismal survival outcomes.
Delay in Seeking Health Care Services After Onset of Urethritis Symptoms in Men
Authors: Aaron Kristal J. , Van Der Pol Barbara , Jordan Stephen J. , Schwebke Jane R. , Hook Edward W.
Published: January 2019

Background

Symptom awareness, behavioral factors, and other barriers associated with timely sexually transmitted infection (STI) health care provision in men is not well studied.

Methods

Men attending an STI clinic answered a questionnaire regarding their symptoms, sexual behavior, and sociodemographic and behavioral characteristics. Characteristics of symptomatic men were compared between those who did and did not delay seeking health care services. Delayed care seeking was defined as clinic attendance longer than 7 days after symptoms, whereas early care seeking was defined as clinic attendance of 7 days or less.

Results

Over a quarter (n = 43 [27.7%]) of men with urethritis symptoms (urethral discharge or dysuria) delayed seeking care for more than 7 days. Compared with men who sought treatment within 7 days, those that delayed care worried for longer periods that their symptoms were STI-related, were more likely to attempt self-treatment of STI symptoms, were more likely to continue engaging in sexual activity, and were less likely to use a condom during their last sexual encounter. Conversely, men that delayed care seeking were less likely to have urethral discharge on physical examination, to have 5 or more polymorphonuclear leukocytes, and to test positive for Neisseria gonorrhoeae. When compared with men that sought care earlier, men that delayed care seeking had fewer overall and new partners in the past 30 days.

Conclusions

Our data suggest that over a quarter of men aware of STI symptoms delay seeking health services. Interventions that promote better patient understanding of the importance of symptom recognition and that facilitate timely access to care may provide new opportunities to reduce STI transmission.
Network Meta-Analysis of Various Nonpharmacological Interventions on Pain Relief in Older Adults With Osteoarthritis
Authors: Zhang Qi , Young Lufei , Li Feng
Published: January 2019

To compare the effectiveness of different nonpharmacological interventions on pain relief in older adults with osteoarthritis, literature databases, bibliographies, and other relevant sources were searched. No language limitations were applied. Thirty-two trials published from 1997 to 2017 were included in the systematic review and network meta-analyses. We included only randomized controlled trials and studies that evaluated the effects of nonpharmacological interventions on alleviating pain in elderly adults (age ≥60 yrs or mean age > 65 yrs) who experience osteoarthritis, irrespective of sex. In the network meta-analysis, resistance training was ranked as the most effective among all nonpharmacological interventions (surface under the cumulative ranking = 82.9%, standardized mean difference = 1.96, confidence interval = −1.39 to 5.31). In subgroup analyses, resistance training still ranked the most effective pain reduction intervention, followed by strengthening exercise and yoga. Among female subjects with intervention adherence rate more than 90%, the most effective intervention was yoga. Strengthening exercise was superior to all other forms of interventions when comparing long-term effect of selected interventions. Among older adults with osteoarthritis, resistance training can be considered a treatment option for pain relief. Yoga is an effective intervention strategy for female elderly, and strengthening exercise has a better long-term beneficial effect.
A Multiplex HIV Incidence Assay for Inferring Recent HIV-1 Transmission and Time of Infection
Authors: Curtis Kelly A. , Campbell Ellsworth M. , Hanson Debra L. , Rudolph Donna L. , Duwve Joan , J. Blosser Sara , Gentry Jessica , Lovchik Judith , Peters Philip J. , Owen Sherry Michele , Switzer William M.
Published: January 2019

Background:

Laboratory assays for determining recent HIV-1 infection are an important public health tool for aiding in the estimation of HIV incidence. Some incidence assay analytes are remarkably predictive of time since seroconversion and may be useful for additional applications, such as predicting recent transmission events during HIV outbreaks and informing prevention strategies.

Methods:

Plasma samples (n = 154) from a recent HIV-1 outbreak in a rural community in Indiana were tested with the customized HIV-1 Multiplex assay, based on the Bio-Rad Bio-Plex platform, which measures antibody response to HIV envelope antigens, gp120, gp160, and gp41. Assay cutoffs for each analyte were established to determine whether an individual seroconverted within 30, 60, or 90 days of the sample collection date. In addition, a novel bioinformatics method was implemented to infer infection dates of persons newly diagnosed with HIV during the outbreak.

Results:

Sensitivity/specificity of the HIV-1 Multiplex assay for predicting seroconversion within 30, 60, and 90 days, based on a training data set, was 90.5%/95.4%, 94.1%/90%, and 89.4%/82.9%, respectively. Of 154 new diagnoses in Indiana between December 2014 and August 2016, the majority (71%) of recent infections (≤3 months since seroconversion) were identified between February and May 2016. The epidemiologic curve derived from the bioinformatics analysis indicated HIV transmission began as early as 2010, grew exponentially in 2014, and leveled off in April 2015.

Conclusions:

The HIV-1 Multiplex assay has the potential to identify and monitor trends in recent infection during an epidemic to assess the efficacy of programmatic or treatment interventions.
Considerations for Mandibular Reconstruction in the Pediatric Patient Following Resection of Malignant Tumors
Authors: Nam Jung Woo , Nam Woong , Cha In Ho , Kim Hyung Jun
Published: January 2019

We recently achieved favorable results in 3 pediatric patients with mandibular osteosarcomas that were treated at our hospital, including with immediate reconstructive surgery performed after tumor resection. Based on a literature review and practical investigation, we discuss the considerations for mandibular reconstruction after malignant lesions are removed from the mandible in children. Mandibular reconstruction for pediatric patients requires an understanding of the changes in bone and soft-tissue architecture due to growth and development at both the donor and recipient sites. Immediate mandibular reconstruction with a free flap can be considered a reasonable option even for young children who require extensive mandibular surgery. However, the variables affecting decisions about treatment planning vary between the different conditions in individual patients, and moreover, these cases are not common in the pediatric population. Therefore, long-term follow-up treatment and further investigations are required for the optimized diagnosis, treatment, and prognosis of pediatric mandibular malignancies.
Various Applications of Nonincisional Blepharoptosis Repair Technique in Secondary Surgeries
Authors: Bae Sangmo , Han Jungkyu
Published: January 2019

Surgical correction of blepharoptosis is one of the most challenging procedures to oculoplastic surgeons. Based on our previous results in primary cases, we tried our nonincisional blepharoptosis correction technique in secondary operations. We mainly used our technique in reoperations with undercorrected ptosis, asymmetric eyelids, loosening of the supratarsal crease, and just for contour adjustments of eyelids. From March 2015 to August 2017, we performed the nonincisional blepharoptosis correction technique on total 93 patients in our clinic. We analyzed the results of the patients with after at least 6-month follow-up. Total 64 of 93 (69%) patients showed satisfactory results with non-ncisional technique. For the other 29 patients, we converted surgical method to the incisional approach during the operation. There was no major complication that required surgical intervention. Nonincisional blepharoptosis correction technique is a safe and reliable method, which can also be applied in secondary surgeries with proper indications.
Comparison Between Continuous and Intermittent Administration of Hydrocortisone During Septic Shock: A Randomized Controlled Clinical Trial
Authors: Tilouche Nejla , Jaoued Oussama , Ali Habiba Ben Sik , Gharbi Rim , Fekih Hassen Mohamed , Elatrous Souheil
Published: January 2019

Objectives:

The best modality of administration of hydrocortisone during septic shock has been poorly evaluated and the guidelines remain unclear in this respect. This study aimed to compare bolus of hydrocortisone to a continuous infusion during septic shock.

Design:

Randomized controlled, open-label trial.

Setting:

Medical ICU of a university hospital.

Patients:

Adult patients with septic shock requiring more than 2 mg/h (approximately 33.3 μg/mn) of norepinephrine after adequate fluid administration were eligible.

Patients already receiving corticosteroids or who have a contraindication to corticosteroids, patients who died within 24 h and those with a decision of not to resuscitate were excluded.

Interventions:

Patients were randomized either to receive hydrocortisone 200 mg/d by continuous infusion or by boluses of 50 mg every 6 h throughout the prescription of vasopressors with a maximum of 7 days.

Results:

Twenty-nine patients were included in each group. Shock reversal was significantly higher in the HC bolus group (66% vs. 35%, P = 0.008). The median time to shock reversal was 5 days (95% CI, 4.31–5.69) in the HC bolus group compared to 6 days (95% CI, 4.80–7.19) in the HC continuous infusion group (log Rank = 0.048). The number of hours spent with blood glucose ≥ 180 mg/dL was higher in the HC continuous infusion group with a median of 64 h [IQR (2–100)] versus 48 h [IQR (14–107)] in the HC bolus group, (P = 0.60), and daily insulin requirements were similar between the two groups (P = 0.63). The occurrence of other side effects, mortality, and ICU LOS were similar between the study groups.

Conclusion:

Hydrocortisone administered by intermittent bolus was associated with higher shock reversal at day 7 compared with a continuous infusion.
Multi-institution Evaluation of Adherence to Comprehensive Postoperative VTE Chemoprophylaxis
Authors: Yang Anthony D. , Hewitt Daniel Brock , Blay Eddie , Kreutzer Lindsey J. , Quinn Christopher M. , Cradock Kimberly A. , Prachand Vivek , Bilimoria Karl Y.
Published: January 2019

Objectives:

The aims of this study were to: (1) measure the rate of failure to provide defect-free postoperative venous thromboembolism (VTE) chemoprophylaxis, (2) identify reasons for failure to provide defect-free VTE chemoprophylaxis, and (3) examine patient- and hospital-level factors associated with failure.

Summary Background Data:

Current VTE quality measures are inadequate. VTE outcome measures are invalidated for interhospital comparison by surveillance bias. VTE process measures (e.g., SCIP-VTE-2) do not comprehensively capture failures throughout patients’ entire hospitalization.

Methods:

We examined adherence to a novel VTE chemoprophylaxis process measure in patients who underwent colectomies over 18 months at 36 hospitals in a statewide surgical collaborative. This measure assessed comprehensive VTE chemoprophylaxis during each patient's entire hospitalization, including reasons why chemoprophylaxis was not given. Associations of patient and hospital characteristics with measure failure were examined.

Results:

The SCIP-VTE-2 hospital-level quality measure identified failures of VTE chemoprophylaxis in 0% to 3% of patients. Conversely, the novel measure unmasked failure to provide defect-free chemoprophylaxis in 18% (736/4086) of colectomies. Reasons for failure included medication not ordered (30.4%), patient refusal (30.3%), incorrect dosage/frequency (8.2%), and patient off-unit (3.4%). Patients were less likely to fail the chemoprophylaxis process measure if treated at nonsafety net hospitals (OR 0.62, 95% CI 0.39–0.99, P = 0.045) or Magnet designated hospitals (OR 0.45, 95% CI 0.29–0.71, P = 0.001).

Conclusions:

In contrast to SCIP-VTE-2, our novel quality measure unmasked VTE chemoprophylaxis failures in 18% of colectomies. Most failures were due to patient refusals or ordering errors. Hospitals should focus improvement efforts on ensuring patients receive VTE prophylaxis throughout their entire hospitalization.
Armet, an aphid effector protein, induces pathogen resistance in plants by promoting the accumulation of salicylic acid
Authors: Cui Na , Lu Hong , Wang Tianzuo , Zhang Wenhao , Kang Le , Cui Feng
Published: January 2019

Effector proteins present in aphid saliva are thought to modulate aphid–plant interactions. Armet, an effector protein, is found in the phloem sap of pea-aphid-infested plants and is indispensable for the survival of aphids on plants. However, its function in plants has not been investigated. Here, we explored the functions of Armet after delivery into plants. Examination of the transcriptomes of
Nicotiana benthamiana
and
Medicago truncatula
following transgenic expression of Armet or infiltration of the protein showed that Armet activated pathways associated with plant–pathogen interactions, mitogen-activated protein kinase and salicylic acid (SA). Armet induced a fourfold increase in SA accumulation by regulating the expression of
SAMT
and
SABP2
, two genes associated with SA metabolism, in Armet-infiltrated tobacco. The increase in SA enhanced the plants' resistance to bacterial pathogen
Pseudomonas syringae
but had no detectable adverse effects on aphid survival or reproduction. Similar molecular responses and a chlorosis phenotype were induced in tobacco by Armet from two aphid species but not by locust Armet, suggesting that the effector function of Armet may be specific for aphids. The results suggest that Armet causes plants to make a pathogen-resistance decision and reflect a novel tripartite insect–plant–pathogen interaction.

This article is part of the theme issue ‘Biotic signalling sheds light on smart pest management’.
Recent progress on the interaction between insects and
Bacillus thuringiensis
crops
Authors: Xiao Yutao , Wu Kongming
Published: January 2019

Extensive use of chemical pesticides poses a great threat to the environment and food safety. The discovery of
Bacillus thuringiensis
(Bt) toxins with effective insecticidal activity against pests and the development of transgenic technology of plants opened a new era of pest control. Transgenic Bt crops, including maize, cotton and soya bean, have now been produced and commercialized to protect against about 30 major coleopteran and lepidopteran pests, greatly benefiting the environment and the economy. However, with the long-term cultivation of Bt crops, some target pests have gradually developed resistance. Numerous studies have indicated that mutations in genes for toxins activation, toxin-binding and insect immunization are important sources in Bt resistance. An in-depth exploration of the corresponding Bt-resistance mechanisms will aid in the design of new strategies to prevent and control pests. Future research will focus on Bt crops expressing new genes and multiple genes to control a broader range of pests as part of an integrated pest management programme.

This article is part of the theme issue ‘Biotic signalling sheds light on smart pest management’.
Interaction of viral pathogen with porin channels on the outer membrane of insect bacterial symbionts mediates their joint transovarial transmission
Authors: Wu Wei , Huang Lingzhi , Mao Qianzhuo , Wei Jing , Li Jiajia , Zhao Yu , Zhang Qian , Jia Dongsheng , Wei Taiyun
Published: January 2019

Many hemipteran insects that can transmit plant viruses in a persistent and transovarial manner are generally associated with a common obligate bacterial symbiont
Sulcia
and its β-proteobacterial partner. Rice dwarf virus (RDV), a plant reovirus, can bind to the envelope of
Sulcia
through direct interaction of the viral minor outer capsid protein P2 with the bacterial outer membrane protein, allowing the virus to exploit the ancient oocyte entry path of
Sulcia
in rice leafhopper vectors. Here, we show that RDV can hitchhike with both
Sulcia
and its β-proteobacterial partner
Nasuia
to ensure their simultaneous transovarial transmission. Interestingly, RDV can move through the outer envelope of
Nasuia
and reside in the periplasmic space, which is mediated by the specific interaction of the viral major outer capsid protein P8 and the porin channel on the bacterial outer envelope.
Nasuia
porin-specific antibody efficiently interferes with the binding between RDV and the
Nasuia
envelope, thus strongly preventing viral transmission to insect offspring. Thus, RDV has evolved different strategies to exploit the ancient oocyte entry paths used by two obligate bacterial symbionts in rice leafhoppers. Our results thus reveal that RDV has formed complex, cooperative interactions with both
Sulcia
and
Nasuia
during their joint transovarial transmission.

This article is part of the theme issue ‘Biotic signalling sheds light on smart pest management’.