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.

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.

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.

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.

Siglec-1 Macrophages and the Contribution of IFN to the Development of Autoimmune Congenital Heart Block.

Given that diseases associated with anti-SSA/Ro autoantibodies, such as systemic lupus erythematosus and Sjögren syndrome, are linked with an upregulation of IFN and type I IFN-stimulated genes, including sialic acid-binding Ig-like lectin 1 (Siglec-1), a receptor on monocytes/macrophages, recent attention has focused on a potential role for IFN and IFN-stimulated genes in the pathogenesis of congenital heart block (CHB). Accordingly, three approaches were leveraged to address the association of IFN, IFN-stimulated genes, and the phenotype of macrophages in affected fetal cardiac tissue: 1) cultured healthy human macrophages transfected with hY3, an anti-SSA/Ro-associated ssRNA, 2) RNA isolated from freshly sorted human leukocytes/macrophages after Langendorff perfusion of three fetal hearts dying with CHB and three healthy gestational age-matched hearts, and 3) autopsy tissue from three additional human CHB hearts and one healthy heart. TLR ligation of macrophages with hY3 led to the upregulation of a panel of IFN transcripts, including SIGLEC1, a result corroborated using quantitative PCR. Using independent and agnostic bioinformatics approaches, CD45+CD11c+ and CD45+CD11c- human leukocytes flow sorted from the CHB hearts highly expressed type I IFN response genes inclusive of SIGLEC1. Furthermore, Siglec-1 expression was identified in the septal region of several affected fetal hearts. These data now provide a link between IFN, IFN-stimulated genes, and the inflammatory and possibly fibrosing components of CHB, positioning Siglec-1-positive macrophages as integral to the process.

Cesarean Section Induces Microbiota-Regulated Immune Disturbances in C57BL/6 Mice.

Epidemiological studies have shown that children born by cesarean section (CS) are at higher risk of developing chronic inflammatory diseases, and it has been suggested that a skewed gut microbial colonization process early in life and altered priming of the immune system are causative. The aim of this study was to clarify whether impaired regulatory immunity in CS-delivered C57BL/6 mice is dependent on gut microbiota (GM) disturbances. The GM of conventionally bred mice born by CS differed clearly from mice born by vaginal delivery. The proportion of regulatory T cells was reduced in mice born by CS, whereas the invariant NKT (iNKT) cell subset was increased compared with vaginal delivery mice. In addition, regulatory markers (Foxp3, Il10, Ctla4) and macrophage markers (Cd11c, Egr2, Nos2) were downregulated, whereas iNKT markers (Il4, Il15) were upregulated in ileum of CS-delivered mice. The GM of CS-delivered mice was sufficient to transfer the shifts in immunity associated with delivery mode when inoculated into germ-free mice. Feeding a prebiotic diet reestablished gene expression of intestinal immune markers and iNKT cells in CS mice but was not sufficient to restore the level of regulatory T cells. The results support that CS delivery is associated with microbiota-mediated shifts in regulatory immunity and, therefore, provide a basis for future microbiota-directed therapeutics to infants born by CS.

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.

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.

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 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.

Hypoalgesia after bicycling at lactate threshold is reliable between sessions.

PURPOSE: Exercise decreases pain sensitivity known as exercise-induced hypoalgesia (EIH). However, the consistency of EIH after an acute exercise protocol based on subjective ratings of perceived exertion has been questioned. Objectives were to compare the effect on pressure pain thresholds (PPTs) after bicycling with work-rate at the lactate threshold compared with quiet rest, and investigate between-session reliability of EIH. METHODS: Thirty-four healthy subjects completed three sessions with 7 days in-between. In session 1, the lactate threshold was determined via blood samples (finger-tip pinprick, > 2 mmol/l increase from warm-up) during a graded bicycling task. In session 2 and 3, all subjects performed (1) 15 min quiet-rest, and (2) 15 min bicycling (work-rate corresponding to the lactate threshold) in the two identical sessions. PPTs at the quadriceps and trapezius muscles were assessed before and after both conditions. Reliability was assessed by intraclass correlations (ICCs). RESULTS: Bicycling increased quadriceps PPT compared with quiet-rest in both sessions [mean difference: 45 kPa (95% CI 19-72 kPa), P = 0.002]; however, the increase in trapezius PPT was not significant after exercise. The EIH responses demonstrated fair between-session test-retest reliability (quadriceps: ICC = 0.45; trapezius: ICC = 0.57, P < 0.05), and agreement in EIH responders and non-responders between sessions was significant (quadriceps: κ = 0.46 and trapezius: κ = 0.43, P < 0.05). CONCLUSIONS: In conclusion, bicycling at the lactate threshold increased PPT at the exercising muscle with fair reliability of the local EIH response. The results have implications for future EIH studies in subjects with and without pain and for clinicians who design exercise programs for pain relief.

Antibiotic exposure in early life and childhood overweight and obesity: A systematic review and meta-analysis.

We conducted a systematic review and meta-analysis of observational studies investigating the association between antibiotic exposure in infancy and risk of childhood overweight and obesity. Thirteen studies, including a total of 527 504 children, were included in the systematic review and 8 were included in meta-analyses. Exposure to antibiotics in infancy was associated with an increased odds ratio (OR) of childhood overweight and obesity (OR 1.11, 95% confidence interval [CI] 1.02-1.20). Whereas exposure to 1 treatment only and exposure between 6 and 24 months were not associated with increased risk of childhood overweight and obesity, exposure to >1 treatment was associated with an OR of 1.24 (95% CI 1.09-1.43) and exposure within the first 6 months of life was associated with an OR of 1.20 (95% CI 1.04-1.37). In conclusion, antibiotic exposure in infancy was associated with a slightly increased risk of childhood overweight and obesity, mainly if children were exposed to repeated treatments or treatment within the first 6 months of life. It is unclear whether this association is mediated via direct effects of antibiotics on the gut microbiota.

Activated Platelets Induce Endothelial Cell Activation via an Interleukin-1ß Pathway in Systemic Lupus Erythematosus.

OBJECTIVE: Systemic lupus erythematosus (SLE) is associated with the premature development of cardiovascular disease. The platelet-endothelium interaction is important in the pathogenesis of cardiovascular disease. In this study, we investigated the platelet phenotype from patients with SLE and matched controls, and their effect on endothelial cells. APPROACH AND RESULTS: Platelet aggregability was measured in 54 SLE subjects off antiplatelet therapy (mean age 40.1±12.8 years; 82% female; 37% white) with age- and sex-matched controls. Platelets were coincubated with human umbilical vein endothelial cells (HUVECs) and changes to gene expression assessed by an RNA array and quantitative reverse transcription polymerase chain reaction. SLE disease activity index ranged from 0 to 22 (mean 5.1±3.9). Compared with controls, patients with SLE had significantly increased monocyte and leukocyte-platelet aggregation and platelet aggregation in response to submaximal agonist stimulation. An agnostic microarray of HUVECs cocultured with SLE platelets found a platelet-mediated effect on endothelial gene pathways involved in cell activation. Sera from SLE versus control subjects significantly increased (1) activation of control platelets; (2) platelet adhesion to HUVECs; (3) platelet-induced HUVEC gene expression of interleukin-8, and intercellular adhesion molecule 1; and (4) proinflammatory gene expression in HUVECs, mediated by interleukin-1ß-dependent pathway. Incubation of SLE-activated platelets with an interleukin-1ß-neutralizing antibody or HUVECs pretreated with interleukin-1 receptor antibodies attenuated the platelet-mediated activation of endothelial cells. CONCLUSIONS: Platelet activity measurements and subsequent interleukin-1ß-dependent activation of the endothelium are increased in subjects with SLE. Platelet-endothelial interactions may play a role in the pathogenesis of cardiovascular disease in patients with SLE.

Cardiac fibroblast transcriptome analyses support a role for interferogenic, profibrotic, and inflammatory genes in anti-SSA/Ro-associated congenital heart block.

The signature lesion of SSA/Ro autoantibody-associated congenital heart block (CHB) is fibrosis and a macrophage infiltrate, supporting an experimental focus on cues influencing the fibroblast component. The transcriptomes of human fetal cardiac fibroblasts were analyzed using two complementary approaches. Cardiac injury conditions were simulated in vitro by incubating human fetal cardiac fibroblasts with supernatants from macrophages transfected with the SSA/Ro-associated noncoding Y ssRNA. The top 10 upregulated transcripts in the stimulated fibroblasts reflected a type I interferon (IFN) response [e.g., IFN-induced protein 44-like (IFI44L), of MX dynamin-like GTPase (MX)1, MX2, and radical S-adenosyl methionine domain containing 2 (Rsad2)]. Within the fibrotic pathway, transcript levels of endothelin-1 (EDN1), phosphodiesterase (PDE)4D, chemokine (C-X-C motif) ligand (CXCL)2, and CXCL3 were upregulated, while others, including adenomedullin, RAP guanine nucleotide exchange factor 3 (RAPGEF3), tissue inhibitor of metalloproteinase (TIMP)1, TIMP3, and dual specificity phosphatase 1, were downregulated. Agnostic Database for Annotation, Visualization and Integrated Discovery analysis revealed a significant increase in inflammatory genes, including complement C3A receptor 1 (C3AR1), F2R-like thrombin/trypsin receptor 3, and neutrophil cytosolic factor 2. In addition, stimulated fibroblasts expressed high levels of phospho-MADS box transcription enhancer factor 2 [a substrate of MAPK5 (ERK5)], which was inhibited by BIX-02189, a specific inhibitor of ERK5. Translation to human disease leveraged an unprecedented opportunity to interrogate the transcriptome of fibroblasts freshly isolated and cell sorted without stimulation from a fetal heart with CHB and a matched healthy heart. Consistent with the in vitro data, five IFN response genes were among the top 10 most highly expressed transcripts in CHB fibroblasts. In addition, the expression of matrix-related genes reflected fibrosis. These data support the novel finding that cardiac injury in CHB may occur secondary to abnormal remodeling due in part to upregulation of type 1 IFN response genes.NEW & NOTEWORTHY Congenital heart block is a rare disease of the fetal heart associated with maternal anti-Ro autoantibodies which can result in death and for survivors, lifelong pacing. This study provides in vivo and in vitro transcriptome-support that injury may be mediated by an effect of Type I Interferon on fetal fibroblasts.

Unconventional Natural Gas Development and Birth Outcomes in Pennsylvania, USA.

BACKGROUND: Unconventional natural gas development has expanded rapidly. In Pennsylvania, the number of producing wells increased from 0 in 2005 to 3,689 in 2013. Few publications have focused on unconventional natural gas development and birth outcomes. METHODS: We performed a retrospective cohort study using electronic health record data on 9,384 mothers linked to 10,946 neonates in the Geisinger Health System from January 2009 to January 2013. We estimated cumulative exposure to unconventional natural gas development activity with an inverse-distance squared model that incorporated distance to the mother's home; dates and durations of well pad development, drilling, and hydraulic fracturing; and production volume during the pregnancy. We used multilevel linear and logistic regression models to examine associations between activity index quartile and term birth weight, preterm birth, low 5-minute Apgar score and small size for gestational age birth, while controlling for potential confounding variables. RESULTS: In adjusted models, there was an association between unconventional natural gas development activity and preterm birth that increased across quartiles, with a fourth quartile odds ratio of 1.4 (95% confidence interval = 1.0, 1.9). There were no associations of activity with Apgar score, small for gestational age birth, or term birth weight (after adjustment for year). In a posthoc analysis, there was an association with physician-recorded high-risk pregnancy identified from the problem list (fourth vs. first quartile, 1.3 [95% confidence interval = 1.1, 1.7]). CONCLUSION: Prenatal residential exposure to unconventional natural gas development activity was associated with two pregnancy outcomes, adding to evidence that unconventional natural gas development may impact health.See Video Abstract at http://links.lww.com/EDE/B14.

Assistant instructors facilitate simulation for medical students.

BACKGROUND: A procedural training protocol for medical students must be cognizant of faculty opportunity costs, which may preclude individually supervised practice. Meanwhile, sporadic exposure in large group settings yields suboptimal proficiency. The purpose of this study is to assess the effectiveness of undergraduate assistant instructors in providing one-on-one simulation-based instruction for basic invasive techniques. MATERIALS AND METHODS: Investigators designed proficiency-based checklists by faculty consensus for three simulation tasks as follows: orotracheal intubation, central venous catheterization, and suturing. Four undergraduate students were trained as instructors. Interrater agreement between instructors using the task checklists ranged from 0.754-0.866. Instructors conducted up to seven flexibly scheduled, one-on-one practice sessions with clinically inexperienced medical student participants. Sessions comprised repetitive task attempts with an evaluation after every attempt. On completion of the training protocol, participants underwent evaluation by an experienced surgeon blinded to practice session performance. Study participants were surveyed to assess satisfaction. RESULTS: Twenty-nine participants completed the study. Median total practice time was 8.75 h (interquartile range 7.12-8.75). Posttest pass rates were 93% (26/28), 71% (20/28), and 68% (19/28) for suturing, intubation, and central venous catheterization, respectively. Ninety-seven percent (27/28) of participants were satisfied with their experience, and 62% (18/29) advocated for protocol adoption into the standard preclinical curriculum. Estimated cost saved using student instructors, based on departmental collections for surgical faculty, was $43,760. CONCLUSIONS: Clinically inexperienced assistants may be trained as instructors for basic simulation tasks with excellent interrater reliability. Deploying these assistant instructors makes effective, one-on-one technical training for preclinical medical students financially feasible.

Vessel ligation training via an adaptive simulation curriculum.

BACKGROUND: A cost-effective model for open vessel ligation is currently lacking. We hypothesized that a novel, inexpensive vessel ligation simulator can efficiently impart transferrable surgical skills to novice trainees. MATERIALS AND METHODS: VesselBox was designed to simulate vessel ligation using surgical gloves as surrogate vessels. Fourth-year medical students performed ligations using VesselBox and were evaluated by surgical faculty using the Objective Structured Assessments of Technical Skills global rating scale and a task-specific checklist. Subsequently, each student was trained using VesselBox in an adaptive practice session guided by cumulative sum. Posttesting was performed on fresh human cadavers by evaluators blinded to pretest results. RESULTS: Sixteen students completed the study. VesselBox practice sessions averaged 21.8 min per participant (interquartile range 19.5-27.7). Blinded posttests demonstrated increased proficiency, as measured by both Objective Structured Assessments of Technical Skills (3.23 versus 2.29, P < 0.001) and checklist metrics (7.33 versus 4.83, P < 0.001). Median speed improved from 128.2 s to 97.5 s per vessel ligated (P = 0.001). After this adaptive training protocol, practice volume was not associated with posttest performance. CONCLUSIONS: VesselBox is a cost-effective, low-fidelity vessel ligation model suitable for graduating medical students and junior residents. Cumulative sum can facilitate an adaptive, individualized curriculum for simulation training.

Verification of accurate technical insight: a prerequisite for self-directed surgical training.

Simulation-based surgical skills training during preclinical education is a persistent challenge due to time constraints of trainees and instructors alike. Self-directed practice is resource-efficient and flexible; however, insight into technical proficiency among trainees is often lacking. The purpose of this study is to prospectively assess the accuracy of self-assessments among medical students learning basic surgical suturing. Over seven weekly practice sessions, preclinical medical students performed serial repetitions of a simulation-based suturing task under one-on-one observation by one of four trainers. Following each task repetition, self- and trainer-assessments (SA-TA) were performed using a 36-point weighted checklist of technical standards developed a priori by expert consensus. Upon study completion, agreement between SA and TA was measured using weighted Cohen's kappa coefficients. Twenty-nine medical students each performed a median of 25 suture task repetitions (IQR 21.5-28). Self-assessments tended to overestimate proficiency during the first tertile of practice attempts. Agreement between SA and TA improved with experience, such that the weighted kappa statistics for the two-handed and instrument ties were >0.81 after 18-21 task attempts. Inexperienced trainees frequently overestimate technical proficiency through self-assessments. However, this bias diminishes with repetitive practice. Only after trainees have attained the capacity to accurately self-assess can effective self-directed learning take place.

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.