Clinical and Host Biological Factors Predict Colectomy Risk in Children Newly Diagnosed With Ulcerative Colitis.

Background: Develop a clinical and biological predictive model for colectomy risk in children newly diagnosed with ulcerative colitis (UC).

Methods: This was a multicenter inception cohort study of children (ages 4-17 years) newly diagnosed with UC treated with standardized initial regimens of mesalamine or corticosteroids (CS) depending upon initial disease severity. Therapy escalation to immunomodulators or infliximab was based on predetermined criteria.

SARS-CoV-2 does not have a strong effect on the nasopharyngeal microbial composition.

The coronavirus disease 2019 (COVID-19) has rapidly spread around the world, impacting the lives of many individuals. Growing evidence suggests that the nasopharyngeal and respiratory tract microbiome are influenced by various health and disease conditions, including the presence and the severity of different viral disease. To evaluate the potential interactions between Severe Acute Respiratory Syndrome Corona 2 (SARS-CoV-2) and the nasopharyngeal microbiome.

NHLBI-CMREF Workshop Report on Pulmonary Vascular Disease Classification: JACC State-of-the-Art Review.

The National Heart, Lung, and Blood Institute and the Cardiovascular Medical Research and Education Fund held a workshop on the application of pulmonary vascular disease omics data to the understanding, prevention, and treatment of pulmonary vascular disease. Experts in pulmonary vascular disease, omics, and data analytics met to identify knowledge gaps and formulate ideas for future research priorities in pulmonary vascular disease in line with National Heart, Lung, and Blood Institute Strategic Vision goals. The group identified opportunities to develop analytic approaches to multiomic datasets, to identify molecular pathways in pulmonary vascular disease pathobiology, and to link novel phenotypes to meaningful clinical outcomes.

Clinical, neuroimaging, and molecular spectrum of TECPR2-associated hereditary sensory and autonomic neuropathy with intellectual disability.

Bi-allelic TECPR2 variants have been associated with a complex syndrome with features of both a neurodevelopmental and neurodegenerative disorder. Here, we provide a comprehensive clinical description and variant interpretation framework for this genetic locus. Through international collaboration, we identified 17 individuals from 15 families with bi-allelic TECPR2-variants.

Mucosal Genomics Implicate Lymphocyte Activation and Lipid Metabolism in Refractory Environmental Enteric Dysfunction.

Background & Aims: Environmental enteric dysfunction (EED) limits the Sustainable Development Goals of improved childhood growth and survival. We applied mucosal genomics to advance our understanding of EED.

Methods: The Study of Environmental Enteropathy and Malnutrition (SEEM) followed 416 children from birth to 24 months in a rural district in Pakistan.

Opportunities for Stewardship in the Transition From Intravenous to Enteral Antibiotics in Hospitalized Pediatric Patients.

Background/objective: Pediatric patients hospitalized with bacterial infections often receive intravenous (IV) antibiotics. Early transition to enteral antibiotics can reduce hospital duration, cost, and complications. We aimed to identify opportunities to transition from IV to enteral antibiotics, describe variation of transition among hospitals, and evaluate feasibility of novel stewardship metrics.

Association of Baseline Luminal Narrowing With Ileal Microbial Shifts and Gene Expression Programs and Subsequent Transmural Healing in Pediatric Crohn Disease.

Background: Transmural healing (TH) is associated with better long-term outcomes in Crohn disease (CD), whereas pretreatment ileal gene signatures encoding myeloid inflammatory responses and extracellular matrix production are associated with stricturing. We aimed to develop a predictive model for ileal TH and to identify ileal genes and microbes associated with baseline luminal narrowing (LN), a precursor to strictures.

Materials And Methods: Baseline small bowel imaging obtained in the RISK pediatric CD cohort study was graded for LN.

Host fibrinogen drives antimicrobial function in peritonitis through bacterial-mediated prothrombin activation.

The blood-clotting protein fibrinogen has been implicated in host defense following infection, but precise mechanisms of host protection and pathogen clearance remain undefined. Peritonitis caused by staphylococci species is a complication for patients with cirrhosis, indwelling catheters, or undergoing peritoneal dialysis. Here, we sought to characterize possible mechanisms of fibrin(ogen)-mediated antimicrobial responses.

Systematic Review: Assessment of Sluggish Cognitive Tempo Over the Past Decade.

Objective: To conduct a systematic review of the measures designed to assess sluggish cognitive tempo (SCT) since the first SCT scale using careful test-construction procedures was published in 2009.

Method: MEDLINE (PubMed), Embase, PsychINFO, and Web of Science databases were searched from September 2009 through December 2019. Articles reporting on reliability (internal consistency, test-retest, and interrater reliability), structural validity (an aspect of construct validity focused on items' convergent and discriminant validity), concurrent and longitudinal external validity, invariance, or intervention/experimental findings were included.

Entrustment Decision Making: Extending Miller's Pyramid.

The iconic Miller's pyramid, proposed in 1989, characterizes 4 levels of assessment in medical education ("knows," "knows how," "shows how," "does"). The frame work has created a worldwide awareness of the need to have different assessment approaches for different expected outcomes of education and training. At the time, Miller stressed the innovative use of simulation techniques, geared at the third level ("shows how"); however, the "does" level, assessment in the workplace, remained a largely uncharted area.

Oxidative phosphorylation in creatine transporter deficiency.

X-linked creatine transporter deficiency (CTD) is one of the three types of cerebral creatine deficiency disorders. CTD arises from pathogenic variants in the X-linked gene SLC6A8. We report the first phosphorus ( P) MRS study of patients with CTD, where both phosphocreatine and total creatine concentrations were found to be markedly reduced.

Response to Placebo in Fragile X Syndrome Clinical Trials: An Initial Analysis.

Fragile X syndrome (FXS) is the leading cause of inherited intellectual disability and autism spectrum disorder. Individuals with FXS often present with a wide range of cognitive deficits and problem behaviors. Educational, behavioral and pharmacological interventions are used to manage these and other complex issues affecting individuals with FXS.

Persistent, refractory, and biphasic anaphylaxis: A multidisciplinary Delphi study.

Background: The use of inconsistent definitions for anaphylaxis outcomes limits our understanding of the natural history and epidemiology of anaphylaxis, hindering clinical practice and research efforts.

Objective: Our aim was to develop consensus definitions for clinically relevant anaphylaxis outcomes by utilizing a multidisciplinary group of clinical and research experts in anaphylaxis.

Methods: Using Delphi methodology, we developed agenda topics and drafted questions to review during monthly conference calls.

Tissue-based Gene Expression as Potential Biomarkers for IBD Course.

Inflammatory bowel diseases (IBDs) are highly heterogeneous in disease phenotype, behavior, and response to therapy. Diagnostic and therapeutic decisions in IBD are based primarily on clinical and endoscopic severity and histopathologic analysis of intestinal biopsies. With this approach, however, only a minority of patients experience durable remission.

Factor Structure of the Aberrant Behavior Checklist in Individuals with Fragile X Syndrome: Clarifications and Future Guidance.

The Aberrant Behavior Checklist (ABC) is a standardized rating scale used for assessing problematic behavior of individuals with developmental disabilities. It has five subscales: Irritability, Social Withdrawal, Stereotypic Behavior, Hyperactivity, and Inappropriate Speech. A previous study in individuals with fragile X syndrome (FXS) reported six factors, with the Social Withdrawal factor bifurcating into Socially Unresponsive and Social Avoidance factors, suggesting a different factor structure in people with FXS.

The thrombin-inflammation axis in cancer progression.

The last half century of cancer research has seen an explosion in our understanding of the complex interplay between cancer cells and host-derived factors critical for cancer progression. Two important host-derived arms that are part of this complex interplay are the inflammatory immune compartment and the hemostatic system. Chronic pathological inflammation is a major factor in the development of multiple common malignancies, including adenocarcinomas of the colon, pancreas, prostate and breast.

Liver fibrosis is driven by protease-activated receptor-1 expressed by hepatic stellate cells in experimental chronic liver injury.

Background: Blood coagulation protease activity is proposed to drive hepatic fibrosis through activation of protease-activated receptors (PARs). Whole-body PAR-1 deficiency reduces experimental hepatic fibrosis, and studies suggest a potential contribution by PAR-1 expressed by hepatic stellate cells. However, owing to a lack of specific tools, the cell-specific role of PAR-1 in experimental hepatic fibrosis has never been formally investigated.

Feasibility of Surgeon-Delivered Audit and Feedback Incorporating Peer Surgical Coaching to Reduce Fistula Incidence following Cleft Palate Repair: A Pilot Trial.

Background: Improving surgeons' technical performance may reduce their frequency of postoperative complications. The authors conducted a pilot trial to evaluate the feasibility of a surgeon-delivered audit and feedback intervention incorporating peer surgical coaching on technical performance among surgeons performing cleft palate repair, in advance of a future effectiveness trial.

Methods: A nonrandomized, two-arm, unblinded pilot trial enrolled surgeons performing cleft palate repair.

Hydroxyurea Dose Escalation for Sickle Cell Anemia in Sub-Saharan Africa.

Background: Hydroxyurea has proven safety, feasibility, and efficacy in children with sickle cell anemia in sub-Saharan Africa, with studies showing a reduced incidence of vaso-occlusive events and reduced mortality. Dosing standards remain undetermined, however, and whether escalation to the maximum tolerated dose confers clinical benefits that outweigh treatment-related toxic effects is unknown.

Methods: In a randomized, double-blind trial, we compared hydroxyurea at a fixed dose (approximately 20 mg per kilogram of body weight per day) with dose escalation (approximately 30 mg per kilogram per day).