A National Survey of the Training and Practice Patterns of Practicing Pediatric Advanced Endoscopists in the United States.

BACKGROUND AND AIMS: Pediatric advanced endoscopy consists primarily of endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS) and is becoming more common in pediatrics. This study aims to characterize the current landscape of pediatric advanced endoscopy training and practice by directly surveying independently practicing pediatric advanced endoscopists (PAEs). We also aim to ascertain expert opinion on competency in pediatric ERCP and EUS. METHODS: A 66-question REDCap survey and a 73-question Qualtrics survey were distributed to members of the ERCP Special Interest Group of North American Society of Pediatric Gastroenterology, Hepatology, and Nutrition. Respondents currently performing ERCP or EUS independently in children were included. Statistical analysis was performed using Mann-Whitney U test. RESULTS: Of 41 PAEs surveyed, 38 (92.7%) responded and 27 independent practitioners were included. Thirteen respondents performed EUS. PAEs who completed an advanced endoscopy fellowship (AEF) were more comfortable performing American Society for Gastrointestinal Endoscopy grade 3 or grade 4 ERCPs ( P < 0.0008) and felt more prepared to practice EUS independently than other trainees. Expert opinion of PAEs felt a threshold of 200 procedures was needed to attain competency in either ERCP or EUS. Pediatric duodenoscope exposure improved comfort in performing ERCP in children <10 kg ( P = 0.009). CONCLUSIONS: Training of pediatric gastroenterologists in ERCP and EUS are highly variable, though the skills attained are similar. AEF-trained specialists reported greater training volumes and felt more prepared to practice independently than those who did not. Competency thresholds determined by expert PAEs for ERCP and EUS agree with American Society for Gastrointestinal Endoscopy guidelines for adult advanced endoscopy trainees.

A critical review of bile acids and their receptors in hepatic encephalopathy.

Hepatic encephalopathy describes an array of neurological complications that arise due to liver insufficiency. The pathogenesis of hepatic encephalopathy shares a longstanding association with hyperammonemia and inflammation, and recently, aberrant bile acid signaling has been implicated in the development of key features of hepatic encephalopathy. These key features include neuronal dysfunction, neuroinflammation and blood-brain barrier permeability. This review summarizes the findings of recent studies demonstrating a role for bile acids in the pathogenesis of hepatic encephalopathy via one of three main bile acid receptors and speculates on the possible downstream consequences of aberrant bile acid signaling.

Leptin Enhances Hepatic Fibrosis and Inflammation in a Mouse Model of Cholestasis.

Leptin is an adipokine with roles in food intake and energy metabolism through its actions on neurons in the hypothalamus. The role of leptin in obesity and cardiovascular disorders is well documented. However, its influence on liver conditions such as cholestasis is poorly understood. The effects of exogenous leptin and leptin-neutralizing antibody on biliary hyperplasia, hepatic fibrosis, and inflammation in the multidrug resistance protein 2 knockout (Mdr2KO) mouse model of cholestasis were assessed by quantifying markers specific for cholangiocytes, activated hepatic stellate cells (HSCs), and cytokines. Serum and hepatic leptin were increased in Mdr2KO mice compared with FVB/NJ (FVBN) controls, and exogenous leptin enhanced biliary hyperplasia and liver fibrosis in Mdr2KO and FVBN mice. Leptin administration increased hepatic expression of C-C motif chemokine ligand 2 and IL-6 in Mdr2KO mice. In contrast, leptin-neutralizing antibody reduced intrahepatic bile duct mass and decreased HSC activation in Mdr2KO mice compared with FVBN controls. Sex-related differences were noted, with female Mdr2KO mice having more leptin than males. In cholangiocytes and LX2 cells in vitro, leptin increased phosphorylated Akt and stimulated cell proliferation. Leptin receptor siRNA and inhibitors of Akt phosphorylation impaired leptin-induced cell proliferation and proinflammatory cytokines. The current data suggest that leptin is abnormally increased in cholestatic mice, and excess leptin increases ductular reaction, hepatic fibrosis, and inflammation via leptin receptor-mediated phosphorylation of Akt in cholangiocytes and HSCs.

Severe Acute Respiratory Syndrome Coronavirus-2 Infection in Children With Liver Transplant and Native Liver Disease: An International Observational Registry Study.

OBJECTIVE: Increased mortality risk because of severe acute respiratory syndrome coronavirus-2 (SARS-CoV2) infection in adults with native liver disease (LD) and liver transplant (LT) is associated with advanced age and comorbid conditions. We aim to report outcomes for children with LD and LT enrolled in the NASPGHAN/SPLIT SARS-CoV2 registry. METHODS: In this multicenter observational cohort study, we collected data from 91 patients <21 years (LD 44, LT 47) with laboratory-confirmed SARS-CoV2 infection between April 21 and September 17, 2020. RESULTS: Patients with LD were more likely to require admission (70% vs 43% LT, P = 0.007) and pediatric intensive care unit (PICU) management (32% vs 4% LT, P = 0.001). Seven LD patients required mechanical ventilation (MV) and 2 patients died; no patients in the LT cohort died or required MV. Four LD patients presented in pediatric acute liver failure (PALF), 2 with concurrent multisystem inflammatory syndrome in children (MIS-C); all recovered without LT. Two LD patients had MIS-C alone and 1 patient died. Bivariable logistic-regression analysis found that patients with nonalcoholic fatty LD (NAFLD) (odds ratio [OR] 5.6, P = 0.02) and LD (OR 6.1, P = 0.01, vs LT) had higher odds of severe disease (PICU, vasopressor support, MV, renal replacement therapy or death). CONCLUSIONS: Although not directly comparable, LT recipients had lower odds of severe SARS-CoV2 infection (vs LD), despite immunosuppression burden. NAFLD patients reported to the registry had higher odds of severe SARS-CoV2 disease. Future controlled studies are needed to evaluate effective treatments and further stratify LD and LT patients with SARS-CoV2 infection.

Multiorgan Metabolomics and Lipidomics Provide New Insights Into Fat Infiltration in the Liver, Muscle Wasting, and Liver-Muscle Crosstalk Following Burn Injury.

Burn injury mediated hypermetabolic syndrome leads to increased mortality among severe burn victims, due to liver failure and muscle wasting. Metabolic changes may persist up to 2 years following the injury. Thus, understanding the underlying mechanisms of the pathology is crucially important to develop appropriate therapeutic approaches. We present detailed metabolomic and lipidomic analyses of the liver and muscle tissues in a rat model with a 30% body surface area burn injury located at the dorsal skin. Three hundred and thirty-eight of 1587 detected metabolites and lipids in the liver and 119 of 1504 in the muscle tissue exhibited statistically significant alterations. We observed excessive accumulation of triacylglycerols, decreased levels of S-adenosylmethionine, increased levels of glutamine and xenobiotics in the liver tissue. Additionally, the levels of gluconeogenesis, glycolysis, and tricarboxylic acid cycle metabolites are generally decreased in the liver. On the other hand, burn injury muscle tissue exhibits increased levels of acyl-carnitines, alpha-hydroxyisovalerate, ophthalmate, alpha-hydroxybutyrate, and decreased levels of reduced glutathione. The results of this preliminary study provide compelling observations that liver and muscle tissues undergo distinctly different changes during hypermetabolism, possibly reflecting liver-muscle crosstalk. The liver and muscle tissues might be exacerbating each other's metabolic pathologies, via excessive utilization of certain metabolites produced by each other.

Two cases of adenodermatofibroma.

Dermatofibromas (DF) are common skin lesions composed of a dermal proliferation of fibroblasts and histiocytes. Among the variants of DFs, adenodermatofibroma are characterized by a dense proliferation of fibroblasts and histiocytes admixed with entrapped dilated glandular structures. We report two additional cases of adenodermatofibromas, review the literature, theorize on the histopathogenesis of this variant, and suggest that there are different patterns among adenodermatofibromas, from primarily cystic to primarily glandular.

Paradoxical modulation of influenza by intranasal administration of non-replicating adenovirus particles.

Respiratory mucosal infection by airborne microbes is a common event that occurs every day. We report here that intranasal administration of non-replicating adenovirus (Ad) particles to mice could either confer rapid protection against influenza virus (IFV) challenge independent of adaptive immunity, or exacerbate influenza by triggering rapid death. The life-or-death outcome hinges on the time interval between Ad administration and IFV challenge in conjunction with specific mouse/IFV strains. Intranasal instillation of Ad particles 1-47 days prior to IFV challenge conferred rapid protection against influenza in Balb/c mice whereas exposure to Ad 39 days prior to challenge with a specific IFV strain or 1 day post-challenge with that IFV strain induced rapid death in C57BL/6 mice. Notably, consecutive administrations of Ad prior to IFV challenge conferred a synergy in triggering a potent anti-influenza state; even a detrimental Ad exposure 39 days before challenge with the deadly IFV strain was reversed to a beneficial one by subsequent Ad boosts. Results revealed an intricate relationship between infection and innate immunity that is a linchpin around which effects revolve from protective immunity to collateral damage. It is urgent to repeat the experiments with an expanded scope for characterizing the status that defines susceptibility or resistance to IFV infection and subsequently reveal the underlying mechanisms. Whether broad heterologous protective effects induced by AdE and adaptive immunity elicited by vaccination could confer synergy during mitigation of a pandemic remains to be seen.

Chronic diarrhea.

Chronic diarrhea is a complex and common problem faced by primary care clinicians. Its causes can range from the common and relatively benign excessive juice consumption to the more alarming inflammatory bowel disease (IBD). This paper will review the definition and etiology of chronic diarrhea and aims to provide a simple approach to its diagnosis and management including when, if appropriate, to refer to GI specialist.

Concentration of polychlorinated biphenyls in serum from New Jersey biomonitoring study: 2016-2018.

The first statewide New Jersey Biomonitoring (NJBM) of serum polychlorinated biphenyls (PCBs) was conducted from 2016 to 2018. Forty ortho-substituted PCBs were measured in serum samples collected from 920 NJ residents in compliance with the CDC method. The lipid adjusted geometric mean (GM) of ∑40PCB concentration for all the 920 measured subjects was 65.5 ng/g lipid (95% CIs: 56.9-75.4 ng/g lipid). Age stratified serum concentration showed that the lowest GM (33.3 ng/g lipid) was observed in the 20-39 years age group (n = 282), followed by a concentration of 76.05 ng/g lipid (n = 382) in the 40-59 years age group, and the highest GM (168.4 ng/g lipid) was found in the 60-74 years age group (n = 256). A survey regression model revealed that ∑40PCBs was significantly associated with age, moderately associated with geographic region, and not significantly associated with sex. The comparison of serum PCB levels in NJBM with the sequential National Health and Nutrition Examination Survey (NHANES) data suggested that the serum PCBs in NJ adults declined 52-59% at all age groups over the last decade. Positive Matrix Factorization (PMF) suggests that ongoing and recent exposure to lower molecular weight PCBs contributes about 15% to total serum PCB levels and more in younger subjects, while higher molecular weight PCBs contribute 52% of the total serum PCB levels and more in older subjects.

Prevalence of Abnormal Ultrasound Findings in Asymptomatic Posterior Tibial Tendons.

BACKGROUND: Posterior tibial tendon dysfunction (PTTD) is a pathological condition that can cause failure of the posterior tibial tendon (PTT). Initially, patients with PTTD are often asymptomatic, making early identification and treatment challenging. Certain ultrasound (US) characteristics have been implicated in the presence of tendinopathy, but their frequency has yet to be assessed in the PTT. The purpose of this study was to identify and report on the frequency of incidental, or potentially early subclinical, tendinopathic US characteristics in asymptomatic PTTs. METHODS: Following institutional review board approval, 150 participants underwent a bilateral-comprehensive US assessment. The resulting images were reviewed and assessed to identify the presence of abnormalities demonstrated to represent tendinopathy. RESULTS: Overall, 266 tendons were assessed and 128 (48.1%) were determined to have at least one tendinopathic trait. Specifically, 51 (19.2%) had circumferential fluid, 69 (25.9%) had noncircumferential fluid, 22 (8.3%) had thickening, 31 (11.7%) had heterogenicity, 19 (7.1%) had hyperemia, and 2 (0.8%) had calcification. Additionally, Caucasian participants were found to be nearly 3 times more likely to have tendinopathic findings when compared with African American participants. CONCLUSION: Sixty-seven percent of participants and 48.1% of PTTs evaluated had at least one tendinopathic feature identified on US. The prevalence rates of these findings, observed in participants, were as follows: noncircumferential fluid, circumferential fluid, heterogenicity, and thickening. Knowing the frequency of these traits may help clinicians to identify subclinical tendinopathy in the PTT before it progresses to PTTD. LEVEL OF EVIDENCE: Level IV, case series.

Occupational Contact Dermatitis: Common Occupational Allergens.

The prevalence of occupational contact dermatitis is estimated to be between 6.7% and 10.6% and can lead to missed work and job loss. Although treatment may provide temporary relief, identifying the culprit allergen may help the clinician counsel on how to avoid or reduce exposure. Some of the most common high-risk occupations for allergic contact dermatitis include agricultural workers, construction workers, health care workers, hairdressers, mechanics, and machinists. In this article, we discuss the common occupational exposures of these high-risk professions, and summarize the common culprit allergens.

Overexpression of NEIL3 associated with altered genome and poor survival in selected types of human cancer.

Base excision repair, which is initiated by the DNA N-glycosylase proteins, is the frontline for repairing potentially mutagenic DNA base damage. Several base excision repair genes are deregulated in cancer and affect cellular outcomes to chemotherapy and carcinogenesis. Endonuclease VIII-like 3 (NEIL3) is a DNA glycosylase protein that is involved in oxidative and interstrand crosslink DNA damage repair. Our previous work has showed that NEIL3 is required to maintain replication fork integrity. It is unknown whether NEIL3 overexpression could contribute to cancer phenotypes, and its prognostic value and use as potential drug target remain unexplored. Our analysis of cancer genomics data sets reveals that NEIL3 frequently undergoes overexpression in several cancers. Furthermore, patients who exhibited NEIL3 overexpression with pancreatic adenocarcinoma, lung adenocarcinoma, lower grade glioma, kidney renal clear cell carcinoma, and kidney papillary cell carcinoma had worse overall survival. Importantly, NEIL3 overexpressed tumors accumulate mutation and chromosomal variations. Furthermore, NEIL3 overexpressed tumors exhibit simultaneous overexpression of homologous recombination genes (BRCA1/2) and mismatch repair genes (MSH2/MSH6). However, NEIL3 overexpression is negatively correlated with tumor overexpressing nucleotide excision repair genes (XPA, XPC, ERCC1/2). Our results suggest that NEIL3 might be a potential prognosis marker for high-risk patients, and/or an attractive therapeutic target for selected cancers.

Wernicke's Encephalopathy Presenting as Sensorineural Hearing Loss.

Sleeve gastrectomy is a restrictive-type weight loss surgery that can result in nutritional deficiencies, such as vitamin B1 (thiamine) deficiency. Although Wernicke's encephalopathy is a known complication following bariatric surgery, bilateral sensorineural hearing loss is a rare presenting symptom of this condition. We present a case of a patient two months postoperative following a sleeve gastrectomy whose chief complaint was hearing loss. While initial laboratory evaluation of her complaint showed elevated inflammatory markers, prompting an autoimmune workup, ultimately the diagnosis of Wernicke's encephalopathy was confirmed by a low thiamine level and magnetic resonance imaging findings. A correction of the patient's thiamine deficiency led to an improvement of her symptoms.

Occupationally Induced Allergic Contact Dermatitis to Methylchloroisothiazolinone/Methylisothiazolinone Among Water Bottle Plant Workers.

BACKGROUND: Methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) allergy has increased for the last decade, mostly not only because of high concentrations in cosmetics but also because of its use as a biocide in industrial settings. OBJECTIVE: We report an outbreak of allergic contact dermatitis in 8 workers at a water bottling plant secondary to excess levels of MCI/MI in the cooling system, found to be at levels 5 times the manufacturer's recommendations. METHODS: Of 15 workers in the plastic bottle manufacturing area, 8 developed dermatitis, and 4 were referred for patch testing using a 100-allergen panel applied and interpreted in the standardized method according to the North American Contact Dermatitis Group. RESULTS: Four workers had a positive reaction to MCI/MI. An investigation at the plant revealed that the concentration of MCI/MI was 365 ppm. The manufacturer's recommended level was 48 ppm. The cooling system was subsequently flushed, and biocide levels decreased to recommended levels. Afterward, all the affected workers experienced clearance of their allergic contact dermatitis. CONCLUSIONS: Occupational sensitization to MCI/MI is on the rise, in this instance, because of excess levels in the cooling system. Our findings demonstrate the continued need for awareness of the allergenicity of this preservative in the occupational setting.

Measuring methane emissions from abandoned and active oil and gas wells in West Virginia.

Recent studies have reported methane (CH4) emissions from abandoned and active oil and gas infrastructure across the United States, where measured emissions show regional variability. To investigate similar phenomena in West Virginia, we measure and characterize emissions from abandoned and active conventional oil and gas wells. In addition, we reconcile divergent regional CH4 emissions estimates by comparing our West Virginia emissions estimates with those from other states in the United States. We find the CH4 emission factors from 112 plugged and 147 unplugged wells in West Virginia are 0.1 g CH4 h-1 and 3.2 g CH4 h-1, respectively. The highest emitting unplugged abandoned wells in WV are those most recently abandoned, with the mean emission of wells abandoned between 1993 and 2015 of 16 g CH4 h-1 compared to the mean of those abandoned before 1993 of 3 × 10-3 g CH4 h-1. Using field observations at a historic mining area as a proxy for state-wide drilling activity in the late 19th/early 20th century, we estimate the number of abandoned wells in WV at between 60,000 and 760,000 wells. Methane emission factors from active conventional wells were estimated at 138 g CH4 h-1. We did not find an emission pattern relating to age of wells or operator for active wells, however, the CH4 emission factor for active conventional wells was 7.5 times larger than the emission factor used by the EPA for conventional oil and gas wells. Our results suggest that well emission factors for active and abandoned wells can vary within the same geologic formation and may be affected by differences in state regulations. Therefore, accounting for state-level variations is critical for accuracy in greenhouse gas emissions inventories, which are used to guide emissions reduction strategies.

Normal Ultrasonographic Parameters of the Posterior Tibial, Peroneal, and Achilles Tendons.

Tendinopathy of the foot and ankle is common and can lead to pain or functional limitations. The most frequently affected tendons in the foot and ankle are the posterior tibial, peroneal, and Achilles. We used ultrasound to determine normal values for these tendons. From 2015 to 2016, a prospective, standardized bilateral lower extremity ultrasound examination protocol was performed by a musculoskeletal ultrasonographer of the 4 tendons and above and below the malleoli as appropriate. A total of 199 patients with 398 extremities were identified, consented, and participated in the study. Most tendons were normally distributed. The average size of the tendons was as follows: Achilles 5.0 mm (range 2.8-11.2 mm); peroneus long above the malleolus 2.1 mm (range 0.7-3.6 mm), below the malleolus 2.9 mm (range 0.8-6.3 mm); peroneus brevis above the malleolus 1.2 cm (range 0.3-4.0 mm), below the malleolus 1.3 mm (range 0.5-4.8 mm); posterior tibial tendon above the malleoli 3.7 mm (range 1.9-8.1 mm), below the malleolus 4.6 cm (range 1.8-11.8 mm). Standard deviations and distribution curves were similarly calculated for each tendon. This baseline data can assist clinicians in their diagnostic ability with ultrasound. Given its low cost, lack of ionizing radiation and dynamic ability along with an improved understanding of normative data it may become an increasingly used diagnostic modality. Levels of Evidence: Level II: Diagnostic.