The Spectrum of Colonization in the Gastrointestinal Tract of Pediatric and Adolescent Patients.

organisms are rare, gram-positive, sugar-fermenting cocci, identifiable in tissues only by histologic examination or molecular testing. Since its discovery, the pathogenicity and relevance of in the human gastrointestinal tract has remained ill-defined. A recent literature review of 66 reported examples demonstrated the potential for severe complications such as emphysematous gastritis and gastric perforation.

Epithelial NAD depletion drives mitochondrial dysfunction and contributes to intestinal inflammation.

Introduction: We have previously demonstrated that a pathologic downregulation of peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC1α) within the intestinal epithelium contributes to the pathogenesis of inflammatory bowel disease (IBD). However, the mechanism underlying downregulation of PGC1α expression and activity during IBD is not yet clear.

Methods: Mice (male; C57Bl/6, /+; mice, and ) were subjected to experimental colitis and treated with nicotinamide riboside.

TP53 mutation prevalence in normal airway epithelium as a biomarker for lung cancer risk.

Background: There is a need for biomarkers that improve accuracy compared with current demographic risk indices to detect individuals at the highest lung cancer risk. Improved risk determination will enable more effective lung cancer screening and better stratification of lung nodules into high or low-risk category. We previously reported discovery of a biomarker for lung cancer risk characterized by increased prevalence of TP53 somatic mutations in airway epithelial cells (AEC).

Studying the Epithelial Effects of Intestinal Inflammation In Vitro on Established Murine Colonoids.

The intestinal epithelium plays an essential role in human health, providing a barrier between the host and the external environment. This highly dynamic cell layer provides the first line of defense between microbial and immune populations and helps to modulate the intestinal immune response. Disruption of the epithelial barrier is a hallmark of inflammatory bowel disease (IBD) and is of interest for therapeutic targeting.

Biosimilars for Pediatric Patients With Inflammatory Bowel Disease: Pediatric Gastroenterology Clinical Practice Survey.

Background: Biosimilars are biological agents that have been demonstrated to have similar safety and efficacy profiles as the originator. The objective of this study was to evaluate the perspectives of pediatric gastroenterologists in the United States (U.S.

Microcystin-LR aerosol induces inflammatory responses in healthy human primary airway epithelium.

Harmful algal blooms plague bodies of freshwater globally. These blooms are often composed of outgrowths of cyanobacteria capable of producing the heptapeptide Microcystin-LR (MC-LR) which is a well-known hepatotoxin. Recently, MC-LR has been detected in aerosols generated from lake water.

Pediatric endoscopy across multiple clinical settings: Efficiency and adverse events.

Background: Endoscopic procedures are becoming increasingly important for the diagnosis and treatment of gastrointestinal disorders during childhood, and have evolved from a more infrequent inpatient procedure in the operating room to a routine outpatient procedure conducted in multiple care settings. Demand for these procedures is rapidly increasing and thus there is a need to perform them in an efficient manner. However, there are little data comparing the efficiency of pediatric endoscopic procedures in diverse clinical environments.

The need for comprehensive multidisciplinary programs, complex interventions, and precision medicine for bicuspid aortic valve disease.

Patients with bicuspid aortic valves commonly require an intervention on their valve and/or aorta. Because of their heterogeneous presentations, recommendations for imaging surveillance and surgery timing are highly individualized. Critical points in care include time of diagnosis, transition from adolescent to adult medicine, and surgery referral.

Advancing NGS quality control to enable measurement of actionable mutations in circulating tumor DNA.

The primary objective of the FDA-led Sequencing and Quality Control Phase 2 (SEQC2) project is to develop standard analysis protocols and quality control metrics for use in DNA testing to enhance scientific research and precision medicine. This study reports a targeted next-generation sequencing (NGS) method that will enable more accurate detection of actionable mutations in circulating tumor DNA (ctDNA) clinical specimens. To accomplish this, a synthetic internal standard spike-in was designed for each actionable mutation target, suitable for use in NGS following hybrid capture enrichment and unique molecular index (UMI) or non-UMI library preparation.

Cyclic GMP-AMP synthase contributes to epithelial homeostasis in intestinal inflammation via Beclin-1-mediated autophagy.

Inflammatory bowel disease (IBD) represents a set of idiopathic and chronic inflammatory diseases of the gastrointestinal tract. Central to the pathogenesis of IBD is a dysregulation of normal intestinal epithelial homeostasis. cGAS is a DNA-sensing receptor demonstrated to promote autophagy, a mechanism that removes dysfunctional cellular components.

P046 Tofacitinib Induced Resolution of Severe Colitis and Reactive Atypia in an Adolescent Patient With IBD.

Tofacitinib is an anti-JAK/STAT small molecule approved for treatment of adults (but not children and adolescents) with moderate to severe ulcerative colitis. Data is limited in children and teens although two major centers have shown efficacy as both mono- and dual - combination therapy using tofacitinib in pediatric patients refractory to anti-TNF agents. We present a 16-year-old female diagnosed with inflammatory ileocolonic Crohn's disease without upper gastrointestinal involvement after presenting with several months of abdominal pain, diarrhea, and unintentional weight loss.

Association of Fecal Calprotectin With Endoscopic and Histologic Activity in Pediatric Inflammatory Bowel Disease.

Unlabelled: Fecal calprotectin (FC) is a noninvasive marker of intestinal inflammation used for screening and ongoing monitoring of inflammatory bowel disease (IBD); it is unclear the association of specific FC values with disease activity. The aim of our study was to examine the association of FC values with endoscopic and histologic severity.

Methods: We performed a retrospective chart review of patients who had FC done between 30 days and 1 day before colonoscopy at our institution.

Cross-oncopanel study reveals high sensitivity and accuracy with overall analytical performance depending on genomic regions.

Background: Targeted sequencing using oncopanels requires comprehensive assessments of accuracy and detection sensitivity to ensure analytical validity. By employing reference materials characterized by the U.S.

Platelet-T cell aggregates in lung cancer patients: Implications for thrombosis.

Platelet-leukocyte aggregates (PLAs) are associated with increased thrombosis risk. The influence of PLA formation is especially important for cancer patients, since thrombosis accounts for approximately 10% of cancer-associated deaths. Our objective was to characterize and quantify PLAs in whole blood samples from lung cancer patients compared to healthy volunteers with the intent to analyze PLA formation in the context of lung cancer-associated thrombosis.

Applications of a Specialty Bicuspid Aortic Valve Program: Clinical Continuity and Translational Collaboration.

Bicuspid aortic valve (BAV) is a common congenital heart diagnosis and is associated with aortopathy. Current guidelines for aortic resection have been validated but are based on aortic diameter, which is insufficient to predict acute aortic events. Clinical and translational collaboration is necessary to identify biomarkers that can individualize the timing of prophylactic surgery for BAV aortopathy.

Predictors of Left Ventricular Dysfunction After Surgery for Degenerative Mitral Regurgitation.

Background: This study was performed to determine whether strain can supplement the ability of left ventricular (LV) ejection fraction (LVEF) to predict postoperative ventricular dysfunction in patients undergoing mitral valve surgery for degenerative mitral regurgitation (DMR).

Methods: From 2004 to 2017, 520 patients with an LVEF of 60% or more underwent mitral valve surgery (98% repair) for DMR. All patients had preoperative, predischarge, and follow-up (mean, 5.

Technical advance in targeted NGS analysis enables identification of lung cancer risk-associated low frequency TP53, PIK3CA, and BRAF mutations in airway epithelial cells.

Background: Standardized Nucleic Acid Quantification for SEQuencing (SNAQ-SEQ) is a novel method that utilizes synthetic DNA internal standards spiked into each sample prior to next generation sequencing (NGS) library preparation. This method was applied to analysis of normal appearing airway epithelial cells (AEC) obtained by bronchoscopy in an effort to define a somatic mutation field effect associated with lung cancer risk. There is a need for biomarkers that reliably detect those at highest lung cancer risk, thereby enabling more effective screening by annual low dose CT.

Circulating Lactonase Activity but Not Protein Level of PON-1 Predicts Adverse Outcomes in Subjects with Chronic Kidney Disease.

The burden of cardiovascular disease and death in chronic kidney disease (CKD) outpaces that of the other diseases and is not adequately described by traditional risk factors alone. Diminished activity of paraoxonase (PON)-1 is associated with increased oxidant stress, a common feature underlying the pathogenesis of CKD. We aimed to assess the prognostic value of circulating PON-1 protein and PON lactonase activity on adverse clinical outcomes across various stages and etiologies of CKD.

Case Report of an Awake Craniotomy in a Patient With Eisenmenger Syndrome.

We present a detailed report of an awake craniotomy for recurrent third ventricular colloid cyst in a patient with severe pulmonary arterial hypertension in the setting of Eisenmenger syndrome, performed 6 weeks after we managed the same patient for a more conservative procedure. This patient has a high risk of perioperative mortality and may be particularly susceptible to perioperative hemodynamic changes or fluid shifts. The risks of general anesthesia induction and emergence must be balanced against the risks inherent in an awake craniotomy on a per case basis.

RNAseq analysis of bronchial epithelial cells to identify COPD-associated genes and SNPs.

Background: There is a need for more powerful methods to identify low-effect SNPs that contribute to hereditary COPD pathogenesis. We hypothesized that SNPs contributing to COPD risk through cis-regulatory effects are enriched in genes comprised by bronchial epithelial cell (BEC) expression patterns associated with COPD.

Methods: To test this hypothesis, normal BEC specimens were obtained by bronchoscopy from 60 subjects: 30 subjects with COPD defined by spirometry (FEV1/FVC < 0.

A lung cancer risk classifier comprising genome maintenance genes measured in normal bronchial epithelial cells.

Background: Annual low dose CT (LDCT) screening of individuals at high demographic risk reduces lung cancer mortality by more than 20%. However, subjects selected for screening based on demographic criteria typically have less than a 10% lifetime risk for lung cancer. Thus, there is need for a biomarker that better stratifies subjects for LDCT screening.

Haplotype and diplotype analyses of variation in ERCC5 transcription cis-regulation in normal bronchial epithelial cells.

Excision repair cross-complementation group 5 (ERCC5) gene plays an important role in nucleotide excision repair, and dysregulation of ERCC5 is associated with increased lung cancer risk. Haplotype and diplotype analyses were conducted in normal bronchial epithelial cells (NBEC) to better understand mechanisms responsible for interindividual variation in transcript abundance regulation of ERCC5 We determined genotypes at putative ERCC5 cis-regulatory SNPs (cis-rSNP) rs751402 and rs2296147, and marker SNPs rs1047768 and rs17655. ERCC5 allele-specific transcript abundance was assessed by a recently developed targeted sequencing method.