The Predictors of Patient Safety Culture in Hospital Setting: A Systematic Review.

INTRODUCTION: Patient safety (PS) is a global public health concern. It is estimated that 10% of patients experience preventable harm while hospitalized. Patient safety culture (PSC) has been recognized as essential to improving PS, drawing inspiration from other high-risk industries. In PS research, however, PSC poses conceptual challenges, with inconsistent terminology, a lack of definitions, and limited use of substantiating theory. Despite these challenges, PSC remains widely used in PS research and practice, as it is seen as a potential gateway to understanding sociotechnical complex aspects of the healthcare system and improving safe patient treatment and care. OBJECTIVES: This review explores the concept of PSC in a hospital setting. How PSC is used as an outcome, thus exploring the theoretical position underpinning PSC, which predictors impact PSC, and how these predictors are related to PSC. METHOD: Using a search of 3 electronic databases, 23 studies that met the inclusion criteria were selected for review. RESULTS: The review identified 81 predictors of PSC. Study population, unit of analysis and method varied widely. PSC as an outcome was assessed based on one of 4 surveys. Thus, the underpinning position of the PSC construct is dominated by an organizational/managerial approach. CONCLUSIONS: The large number of predictors explored and the range in outcome measures, units of analysis, and methods make it hard to establish any causal relationship. We argue that studies closer to actual practices in the messy conditions of clinical practice are needed.

Factors associated with thrombotic and hemorrhagic complications in pediatric liver transplant: A multi-center analysis from the Starzl Network for Excellence in Pediatric Transplantation.

BACKGROUND: Survival after pediatric liver transplantation (PLT) is negatively impacted by thrombotic and hemorrhagic complications. Limited data exists regarding factors associated with these complications and utilization of anticoagulation. METHODS: Retrospective review of donor, recipient variables and outcomes from four centers participating in the Starzl Network for Excellence in Pediatric Transplantation. RESULTS: 76 PLT included 39 (51%) technical variant transplants, with mean follow-up 628 ± 193.6 days. Median age/weight at transplant were 59.3 ± 53.8 months and 19.6 ± 17.2 kg. Seven (9.2%) transplants experienced intraoperative hepatic artery thrombosis (iHAT), all successfully corrected. Four HAT recurred postoperatively on POD 1,7,8 and 616. All three portal vein thromboses (PVT) occurred on POD1. Anticoagulation protocols were initiated intraoperatively in 50 and postoperatively in 66 and were active for all thrombotic and hemorrhagic events. Two patients were re-transplanted for HAT. Two patients died without having thrombotic or hemorrhagic complications. iHAT and post-operative HAT were associated with lower hepatic arterial flows. iHAT was associated with donor variant anatomy, reduced allografts and intraoperative blood loss. Intraoperative ultrasound could not predict post-operative HAT nor PVT. Surgeon pre-operative concern regarding the native portal vein correlated with postoperative PVT. Lower hepatic arterial and portal flows, higher estimated blood losses, higher prothrombin time and use of arterial interposition grafts were associated with postoperative hemorrhagic complications. CONCLUSIONS: Thrombotic and hemorrhagic complications after pediatric liver transplant remain rare but significant events. Their occurrence can be predicted with pre-operative assessment of donor and recipient vascular anatomy and direct flow measurement but may not be predicted with ultrasound evaluation nor prevented with anticoagulation.

Fractionated plasma N-glycan profiling of novel cohort of ATP6AP1-CDG subjects identifies phenotypic association.

ATP6AP1-CDG is an X-linked disorder typically characterized by hepatopathy, immunodeficiency, and an abnormal type II transferrin glycosylation pattern. Here, we present 11 new patients and clinical updates with biochemical characterization on one previously reported patient. We also document intrafamilial phenotypic variability and atypical presentations, expanding the symptomatology of ATP6AP1-CDG to include dystonia, hepatocellular carcinoma, and lysosomal abnormalities on hepatic histology. Three of our subjects received successful liver transplantation. We performed N-glycan profiling of total and fractionated plasma proteins for six patients and show associations with varying phenotypes, demonstrating potential diagnostic and prognostic value of fractionated N-glycan profiles. The aberrant N-linked glycosylation in purified transferrin and remaining plasma glycoprotein fractions normalized in one patient post hepatic transplant, while the increases of Man4GlcNAc2 and Man5GlcNAc2 in purified immunoglobulins persisted. Interestingly, in the single patient with isolated immune deficiency phenotype, elevated high-mannose glycans were detected on purified immunoglobulins without glycosylation abnormalities on transferrin or the remaining plasma glycoprotein fractions. Given the diverse and often tissue specific clinical presentations and the need of clinical management post hepatic transplant in ATP6AP1-CDG patients, these results demonstrate that fractionated plasma N-glycan profiling could be a valuable tool in diagnosis and disease monitoring.

State of pediatric liver transplantation in the United States and achieving zero wait list mortality with ideal outcomes: A statement from the Starzl Network for Excellence in Pediatric Transplant Surgeon's Working Group.

BACKGROUND: Liver transplant is a life-saving therapy that can restore quality life for several pediatric liver diseases. However, it is not available to all children who need one. Expertise in medical and surgical management is heterogeneous, and allocation policies are not optimally serving children. Technical variant grafts from both living and deceased donors are underutilized. METHODS: Several national efforts in pediatric liver transplant to improve access to and outcomes from liver transplant for children have been instituted and include adjustments to allocation policies, UNOS-sponsored collaborative improvement projects, and the emergence of national learning networks to study ongoing challenges in the field the Surgical Working group of the Starzl Network for Excellence in Pediatric Transplantation (SNEPT) discusses key issues and proposes potential solutions to eliminate the persistent wait list mortality that pediatric patients face. RESULTS: A discussion of the factors impacting pediatric patients' access to liver transplant is undertaken, along with a proposal of several measures to ensure equitable access to life-saving liver transplant. CONCLUSIONS: Pediatric liver transplant wait list mortality can and should be eliminated. Several measures, including collaborative efforts among centers, could be leveraged to acheive this goal.

Health Care Transition for Adolescents and Young Adults With Pediatric-Onset Liver Disease and Transplantation: A Position Paper by the North American Society of Pediatric Gastroenterology, Hepatology, and Nutrition.

Advances in medical therapies and liver transplantation have resulted in a greater number of pediatric patients reaching young adulthood. However, there is an increased risk for medical complications and morbidity surrounding transfer from pediatric to adult hepatology and transplant services. Health care transition (HCT) is the process of moving from a child/family-centered model of care to an adult or patient-centered model of health care. Successful HCT requires a partnership between pediatric and adult providers across all disciplines resulting in a transition process that does not end at the time of transfer but continues throughout early adulthood. Joint consensus guidelines in collaboration with the American Society of Transplantation are presented to facilitate the adoption of a structured, multidisciplinary approach to transition planning utilizing The Six Core Elements of Health Care Transition TM for use by both pediatric and adult specialists. This paper provides guidance and seeks support for the implementation of an HCT program which spans across both pediatric and adult hepatology and transplant centers.

APOL1 variant-expressing endothelial cells exhibit autophagic dysfunction and mitochondrial stress.

Polymorphisms in the Apolipoprotein L1 (APOL1) gene are common in ancestrally African populations, and associate with kidney injury and cardiovascular disease. These risk variants (RV) provide an advantage in resisting Trypanosoma brucei, the causal agent of African trypanosomiasis, and are largely absent from non-African genomes. Clinical associations between the APOL1 high risk genotype (HRG) and disease are stronger in those with comorbid infectious or immune disease. To understand the interaction between cytokine exposure and APOL1 cytotoxicity, we established human umbilical vein endothelial cell (HUVEC) cultures representing each APOL1 genotype. Untreated HUVECs were compared to IFNÉ£-exposed; and APOL1 expression, mitochondrial function, lysosome integrity, and autophagic flux were measured. IFNÉ£ increased median APOL1 expression across all genotypes 22.1 (8.3 to 29.8) fold (p=0.02). Compared to zero risk variant-carrying HUVECs (0RV), HUVECs carrying 2 risk variant copies (2RV) showed both depressed baseline and maximum mitochondrial oxygen consumption (p<0.01), and impaired mitochondrial networking on MitoTracker assays. These cells also demonstrated a contracted lysosomal compartment, and an accumulation of autophagosomes suggesting a defect in autophagic flux. Upon blocking autophagy with non-selective lysosome inhibitor, hydroxychloroquine, autophagosome accumulation between 0RV HUVECs and untreated 2RV HUVECs was similar, implicating lysosomal dysfunction in the HRG-associated autophagy defect. Compared to 0RV and 2RV HUVECs, HUVECs carrying 1 risk variant copy (1RV) demonstrated intermediate mitochondrial respiration and autophagic flux phenotypes, which were exacerbated with IFNÉ£ exposure. Taken together, our data reveal that IFNÉ£ induces APOL1 expression, and that each additional RV associates with mitochondrial dysfunction and autophagy inhibition. IFNÉ£ amplifies this phenotype even in 1RV HUVECs, representing the first description of APOL1 pathobiology in variant heterozygous cell cultures.

An overview of pediatric peritoneal dialysis and renal replacement therapy in infants: A review for the general pediatric surgeon.

Currently, there are about 10,000 pediatric patients in the United States who rely on dialysis for renal replacement therapy. Dialysis allows children with chronic kidney disease a means of support until renal transplant is feasible. All forms of renal replacement therapy require a surgical intervention, whether the modality is hemodialysis or peritoneal dialysis. Despite peritoneal dialysis being the most common modality of dialysis in children, there is not prospectively collected much evidence in the literature which can guide the pediatric surgeon about best practices on access placement, management of complications, and timing of removal. Most available studies are small, single-center retrospective reviews. This limits the power of the data collected to help guide decision-making in the management of peritoneal dialysis catheters. The purpose of this review is to provide a consolidated source of best available evidence and identify important areas for future study. Furthermore, this is an area of pediatric surgical care that lacks up to date outcomes research with robust surgeon participation. Lack of coordinated, evidence-based best practices likely results in heterogenous surgical practices and uneven strategies for managing complications. Furthermore, with improvements in neonatal critical care and fetal interventions available for obstructive uropathies and other congenital kidney disorders, there is increased likelihood of the need for dialysis access in more infants, who represent a particularly vulnerable patient population. Importantly, peritoneal dialysis access should be instituted into the national PEDScore curriculum for pediatric surgical fellows, as this procedure is common enough that any pediatric surgeon could be consulted for catheter placement and management. Surgeon awareness of, and participation in the formulation, of guidelines and prospective studies is of paramount importance to ensure optimal care of this vulnerable population of children.

Achieving Optimal Correction for Young Myopic Children: A Concept Study.

The purpose of this article is to explore alternative ways of achieving optimal correction for myopic children who cannot cooperate to subjective manifest refraction (SR). The study included myopic children aged 9-12 years who underwent non-cycloplegic SR and autorefraction with and without cycloplegia using the Shin-Nippon Nvision-K 5001 autorefractor (AR) as well as non-cycloplegic autorefraction using the Topcon KR-800S AR. There were 21 children (mean age, 10.62 years) included. The spherical equivalent refractive error of SR was not significantly different from that of non-cycloplegic AR measurements, but it was significantly different from that of cycloplegic Shin-Nippon Nvision-K 5001 measurements (p < 0.001). Compared with SR, cycloplegic Shin-Nippon Nvision-K 5001 measured a less myopic refractive error (median: -2.44 D vs. -2.88 D, p < 0.001). For both ARs, the axis measurements and astigmatic dioptre values between SR and autorefraction were not significantly different. Compared with non-cycloplegic SR, cycloplegic measurements showed a lesser degree of myopic refractive error. There was no significant difference between SR and non-cycloplegic autorefraction. Therefore, the Topcon KR-800S and the Shin-Nippon Nvision-K 5001 ARs may be useful for prescribing glasses in myopic children who cannot cooperate during SR. However, caution should be taken with cylinders <0.75 D because the agreement in axis between SR and AR measurement is poor. Therefore, in such cases, we suggest to add half the cylinder to the spherical component.

Clinical regression of inguinal hernias in premature infants without surgical repair.

BACKGROUND: The incidence of inguinal hernias in premature infants is approximately 30%. Due to concerns about a high risk of incarceration, early repair is commonly performed. We present a series of patients whose families opted to delay repair until after 55 weeks corrected gestational age (GA) and experienced safe clinical regression of their hernias. METHODS: Between June 2015 and July 2020, premature infants (< 37 weeks GA) diagnosed with inguinal hernias on physical examination were identified. Families of eligible infants were offered either immediate or delayed repair after 55 weeks corrected GA. Infants whose families elected to delay were followed until their hernia(s) clinically regressed, or until older than 55 weeks. RESULTS: Families of 68 infants consented to delay repair. 23 infants (33.8%) had hernias that clinically regressed at median follow up from diagnosis of 14.1 weeks. Univariate analysis demonstrated female sex as a significant predictor of hernia clinical regression (OR: 3.08; p = 0.046). Of the 45 infants who underwent repair, 84.4% safely progressed to 55 weeks corrected GA prior to. CONCLUSION: Delaying inguinal hernia repair in this series of premature infants until after 55 weeks corrected GA revealed that one third of hernias, especially in females, safely regressed upon follow-up examination.

A Learning Health System for Pediatric Liver Transplant: The Starzl Network for Excellence in Pediatric Transplantation.

OBJECTIVE: Learning health systems (LHS) integrate research, improvement, management, and patient care, such that every child receives "the right care at the right time...every time," that is, evidence-based, personalized medicine. Here, we report our efforts to establish a sustainable, productive, multicenter LHS focused on pediatric liver transplantation. METHODS: The Starzl Network for Excellence in Pediatric Transplantation (SNEPT) is the first multicenter effort by pediatric liver transplant families and providers to develop shared priorities and a shared agenda for innovation in clinical care. This report outlines SNEPT's structure, accomplishments, and challenges as an LHS. RESULTS: We prioritized 4 initial projects: immunosuppression, perioperative anticoagulation, quality of life, and transition of care. We shared center protocols/management to identify areas of practice variability between centers. We prioritized actionable items that address barriers to providing "the right care at the right time" to every pediatric liver transplant recipient: facilitating transparency of practice variation and the connection of practices to patient outcomes, harnessing existing datasets to reduce the burden of tracking outcomes, incorporating patient-reported outcomes into outcome metrics, and accelerating the implementation of knowledge into clinical practice. This has allowed us to strengthen collaborative relationships, design quality improvement projects, and collect pilot data for each of our priority projects. CONCLUSIONS: The field of pediatric liver transplantation can be advanced through application of LHS principles. Going forward, SNEPT will continue to unite patient advocacy, big data, technology, and transplant thought leaders to deliver the best care, while developing new, scalable solutions to pediatric transplantation's most challenging problems.

Upregulation of human endogenous retrovirus-K (HML-2) mRNAs in hepatoblastoma: Identification of potential new immunotherapeutic targets and biomarkers.

PURPOSE: Hepatoblastoma is the most common liver malignancy in children. In order to advance therapy against hepatoblastoma, novel immunologic targets and biomarkers are needed. Our purpose in this investigation is to examine hepatoblastoma transcriptomes for the expression of a class of genomic elements known as Human Endogenous Retrovirus (HERVs). HERVs are abundant in the human genome and are biologically active elements that have been associated with multiple malignancies and proposed as immunologic targets in a subset of tumors. A sub-family of HERVs, HERV-K(HML-2) (HERV-K), have been shown to be tightly regulated in fetal development, making investigation of these elements in pediatric tumors paramount. METHODS: We first created a HERVK-FASTA file utilizing 91 previously described HML-2 proviruses. We then concatenated the file onto the GRCh38.95 cDNA library from Ensembl. We used this reference database to evaluate existing RNA-seq data from 10 hepatoblastoma tumors and 3 normal liver controls (GEO accession ID: GSE8977575). Quantification and differential proviral expression analysis between hepatoblastoma and normal liver controls was performed using the pseudo-alignment program Salmon and DESeq2, respectively. RESULTS: HERV-K mRNA was expressed in hepatoblastoma from multiple proviral loci. All expressed HERV-K proviral loci were upregulated in hepatoblastoma compared to normal liver controls. Five HERV-K proviruses (1q21.3, 3q27.2, 7q22.2, 12q24.33 and 17p13.1) were significantly differentially expressed (p-adjusted value <0.05, |log2 fold change| > 1.5) across conditions. The provirus at 17p13.1 had an approximately 300-fold increased expression in hepatoblastoma as compared to normal liver. This was in part due to the near absence of HERV-K mRNA at the 17p13.1 locus in fully differentiated liver samples. CONCLUSIONS: Our investigation demonstrates that HERV-K is expressed from multiple loci in hepatoblastoma and that the expression is increased for several proviruses compared to normal liver controls. Our results suggest that HERV-K mRNA expression may be useful as a biomarker in hepatoblastoma, given the large differential expression profiles in hepatoblastoma, with very low mRNA levels in liver control samples.

A Quality Improvement Intervention to Reduce Postoperative Opiate Use in Neonates.

BACKGROUND AND OBJECTIVES: Opiate use in neonates can affect clinical outcomes after surgery and may alter future neurodevelopment. We implemented a multimodal opioid reduction strategy in our NICU for infants undergoing nonemergent gastrointestinal surgery. METHODS: After multiple stakeholder's meetings, our opioid reduction intervention included giving neonates postoperative standing intravenous acetaminophen every 6 hours for 48 hours, a standardized postsurgical sign-out with the NICU team in which pain control was directly addressed, and a series of postsurgical pain education seminars with NICU providers. To assess the impact of our quality improvement project, we used process control charts to investigate trends in postoperative opioid use in our preintervention (January 2012 to April 2016) and postintervention (May 2016 to September 2019) cohorts. RESULTS: A total of 77 infants were included in the study (40 in the preintervention cohort and 37 in the postintervention cohort). Patient characteristics were equivalent. The intervention significantly reduced the trend in postoperative morphine equivalents (median: 7.96 mg/kg in preintervention cohort versus 0.095 mg/kg in postintervention cohort; P < .0001). The Neonatal Pain, Agitation, and Sedation Scale pain scores and safety profiles were equivalent in both groups. The intervention was also associated with a 24-hour reduction in postoperative ventilation time (P < .048) and a 7-day reduction in the use of total parenteral nutrition (P < .017). CONCLUSIONS: Standing intravenous acetaminophen coupled with provider education can successfully reduce opioid use in postsurgical neonates. Given the concern for opioid exposure in neonatal neurodevelopment as well as clinical benefits of reduced opioids, similar strategies for opioid reduction may prove useful at other institutions.

Strictures, stones and cysts: an unusual cause of pancreatitis in a 20-month-old female child.

Choledochal cysts are dilations of the biliary tree that cause a variety of clinical symptoms and can lead to several types of complications. Choledochal cysts are most commonly diagnosed in childhood and frequently present with abdominal pain, jaundice and, in infants, an abdominal mass. Although the most concerning complication is malignant transformation of the cyst epithelium, other complications such as stone formation, acute pancreatitis and stricture can also occur and lead to patient morbidity. Treatment is aimed at not only relieving patient symptoms, but also decreasing a long-term cancer risk. We present a case of a child presenting with abdominal pain and vomiting secondary to a type IVa choledochal cyst complicated by acute pancreatitis, a common bile duct stricture and cystolithiasis.

Human endogenous retrovirus-K mRNA expression and genomic alignment data in hepatoblastoma.

Human Endogenous Retroviruses are a class of genomic elements that are the result of ancient retroviral infection of the human germline. Many are biologically active elements that have been implicated in multiple diseases including cancer. The most recent class to invade the human genome is the HERV-K(HML-2) (HERV-K) family. Approximately 90 HERV-K proviruses and many smaller elements have been identified to date in the human genome. Additional proviruses are continually being discovered with the rapid advancement of deep-sequencing and long-read sequencing technologies. HERV-K proviruses are poorly annotated in human transcriptome databases making their analysis in RNA-seq data difficult. To enable analysis, we compiled the sequences of 91 HERV-K proviruses identified in NCBI GenBank (ID JN675007-JN675097) and created a proviral alignment tool for visualizing RNA-seq reads aligned across individual proviruses. This allowed us to analyse publicly available RNA-seq data from 10 hepatoblastoma samples and 3 normal liver controls (GEO Accession ID: GSE89775). This data report includes the raw FASTA sequence files of the HERV-K proviruses from NCBI, a differential gene expression list between hepatoblastoma samples, and genomic alignment figures from 5 HERV-K proviruses identified as differentially expressed in the companion research article "Upregulation of Human Endogenous Retrovirus-K (HML-2) mRNAs in hepatoblastoma: Identification of potential new immunotherapeutic targets and biomarkers [1]. The data provided here are available for other research groups interested in evaluating individual HERV-K proviral expression using RNA-seq data. Furthermore, the data analysis is highly flexible and will accommodate the addition of other HERV-K proviruses.

A learning health network for pediatric liver transplantation: Inaugural meeting report from the Starzl Network for Excellence in Pediatric Transplantation.

Learning Health Networks (LHN) improve the well-being of populations by aligning clinical care specialists, technology experts, patients and patient advocates, and other thought leaders for continuous improvement and seamless care delivery. A novel LHN focused on pediatric transplantation, the Starzl Network for Excellence in Pediatric Transplantation (SNEPT), convened its inaugural meeting in September 2018. Clinical care team representatives, patients, and patient families/advocates partnered to take part in educational sessions, pain point exercises, and project identification workshops. Participants discussed the global impact of transplant from both a population and individual perspective, identifying challenges and opportunities where the Starzl Network could work to improve outcomes at scale across a variety of transplant-related conditions.

Close to the Bedside: A Systematic Review of Endogenous Retroviruses and Their Impact in Oncology.

BACKGROUND: Human endogenous retroviruses (HERVs) are genetic elements in the human genome, which resulted from ancient retroviral germline infections. HERVs have strong transcriptional promoters and enhancers that affect a cell's transcriptome. They also encode proteins that can exert effects in human cells. This review examines how our increased understanding of HERVs have led to their potential use as biomarkers and immunologic targets. MATERIAL AND METHODS: PubMed/Medline, Embase, Web of Science, and Cochrane databases were used in a systematic search to identify all articles studying the potential impact of HERVs on surgical diseases. The search included studies that involved clinical patient samples in diseases including cancer, inflammatory conditions, and autoimmune disease. Articles focused on conditions not routinely managed by surgeons were excluded. RESULTS: Eighty six articles met inclusion and quality criteria for this review and were included. Breast cancer and melanoma have robust evidence regarding the use of HERVs as potential tumor markers and immunologic targets. Reported evidence of the activity of HERVs in colorectal cancer, pancreatic cancer, hepatocellular cancer, prostate and ovarian cancer, germ cell tumors as well as idiopathic pulmonary hypertension, and the inflammatory response in burns was also reviewed. CONCLUSIONS: Increasingly convincing evidence indicates that HERVs may play a role in solid organ malignancy and present important biomarkers or immunologic targets in multiple cancers. Innovative investigation of HERVs is a valuable focus of translational research and can deepen our understanding of cellular physiology and the effects of endogenous retroviruses on human biology. As strategies for treatment continue to focus on genome-based interventions, understanding the impact of endogenous retroviruses on human disease will be critical.

A novel retroviral vector system to analyze expression from mRNA with retained introns using fluorescent proteins and flow cytometry.

The ability to overcome cellular restrictions that exist for the export and translation of mRNAs with retained introns is a requirement for the replication of retroviruses and also for the expression of many mRNA isoforms transcribed from cellular genes. In some cases, RNA structures have been identified in the mRNA that directly interact with cellular factors to promote the export and expression of isoforms with retained introns. In other cases, a viral protein is also required to act as an adapter. In this report we describe a novel vector system that allows measurement of the ability of cis- and trans-acting factors to promote the export and translation of mRNAs with retained introns. One reporter vector used in this system is derived from an HIV proviral clone engineered to express two different fluorescent proteins from spliced and unspliced transcripts. The ratio of fluorescent signals is a measurement of the efficiency of export and translation. A second vector utilizes a third fluorescent protein to measure the expression of viral export proteins that interact with some of the export elements. Both vectors can be packaged into viral particles and be used to transduce cells, allowing expression at physiological levels from the integrated vector.

Associations between adult height and type 2 diabetes mellitus: a systematic review and meta-analysis of observational studies.

BACKGROUND: Although short adult height is generally associated with increased risks of type 2 diabetes mellitus (T2DM), there are large inconsistencies across studies. The aims of this study were to describe and quantify currently available evidence on the association between adult height and T2DM, to examine whether the reported associations differ by sex, and to examine the shapes of the height and T2DM associations. METHODS: Relevant literature was identified using PubMed (1966-May 2018), EMBASE (1947-May 2018) and Google Scholar (May 2018). We identified cross-sectional and cohort studies with original publications on human subjects, which were included in a random-effects meta-analysis. RESULTS: From 15 971 identified sources, 25 studies met the inclusion criteria for the systematic review (N=401 562 individuals). From these 25 studies, 16 (9 cross-sectional studies and 7 cohort studies) were included in the meta-analysis (n=261 496 individuals). The overall random-effects meta-analysis indicated an inverse association between adult height and T2DM (effect estimate=0.88, 95% CI 0.81 to 0.95). No sex differences in the associations between adult height and T2DM were found (effect estimate for men: 0.86, 95% CI 0.75 to 0.99; effect estimate for women: 0.90; 95% CI 0.80 to 1.01; p value for sex interaction=0.80). Due to lack of data, results on the shape of the association between height and T2DM were inconclusive. CONCLUSIONS: Shorter height is associated with an increased risk of T2DM and the association does not significantly differ by sex. The currently available data are insufficient to support conclusions regarding the shape of the association between height and T2DM. TRIAL REGISTRATION NUMBER: CRD42017062446.

Sutureless closure: a versatile treatment for the diverse presentations of gastroschisis.

OBJECTIVE: Case series have demonstrated sutureless closures to be safe for the correction of gastroschisis. We hypothesize that sutureless closure is efficacious in patients requiring silo reduction without need for intubation. STUDY DESIGN: We conducted a retrospective case control study of infants who underwent gastroschisis repair at our institution (January 2011-August 2018). Patient characteristics and clinical outcomes were compared between sutureless closure and primary fascial repair groups. RESULTS: Seventeen patients in the sutureless group and 28 patients in the primary fascial repair group were included. Success of sutureless closure was 94%. Mechanical ventilation was reduced by 2.8 days in the sutureless group (P < 0.0001) and fewer patients required general anesthesia (29.4% vs. 100%, P < 0.0001). CONCLUSIONS: Sutureless closure is effective for the diverse presentations of gastroschisis. Given the concerns of effects of general anesthesia on the developing brain, sutureless closure should be strongly considered.

Human low-affinity IgG receptor FcγRIIA polymorphism H131R associates with subclinical atherosclerosis and increased platelet activity in systemic lupus erythematosus.

Essentials Systemic lupus erythematosus (SLE) patients are at increased risk for premature CVD. Platelet activity, vascular dysfunction and carotid artery plaque are associated with FcγRIIA genotype in SLE. FcγRIIA genotype was not associated with platelet activity or carotid plaque in healthy controls. FcγRIIA represents a link that connects platelet activity, vascular health and CVD in SLE. SUMMARY: Background Systemic lupus erythematosus (SLE) is a complex autoimmune disease associated with an elevated risk of premature cardiovascular disease. Platelets express receptors contributing to inflammation and immunity, including FcγRIIA, the low affinity receptor of the Fc portion of IgG antibodies. The variation at a single amino acid substitution, H131R, in the extracellular binding domain alters the affinity for IgG, which may account for individual variation in platelet activity and platelet-mediated disease. Objectives This study was performed to investigate the association between FcγRIIA genotype, preclinical atherosclerosis, platelet reactivity and vascular health. Methods FcγRIIA was genotyped in 80 SLE patients and 30 healthy controls. Carotid ultrasound plaque, soluble E-selectin and platelet aggregability were evaluated in SLE and matched controls. Results Carotid plaque was significantly more prevalent in SLE patients carrying a variant allele compared to those with a homozygous ancestral allele (58% vs. 25%, P = 0.04). In contrast, prevalent carotid plaque was not associated with genotype in controls. Consistently, SLE variant FcγRIIA carriers vs. ancestral allele carriers had a significant increase in the levels of soluble E-selectin, which was not observed in controls. Monocyte and leukocyte-platelet aggregation and platelet aggregation in response to submaximal agonist stimulation were significantly elevated in SLE patients with the variant vs. ancestral genotype. Conclusions Carotid ultrasound plaque, soluble E-selectin levels and platelet activity were more frequently prevalent in SLE patients carrying variant FcγRIIA. The interplay between FcγRIIA-mediated platelet activation and endothelial cells might represent a mechanism underlying the pathogenesis of cardiovascular disease in SLE patients.