Intraductal papillary mucinous neoplasm in a neonate with congenital hyperinsulinism and a de novo germline SKIL gene mutation.

A 3 day old infant with persistent severe hypoglycemia was found to have a cystic pancreatic tumor. Cessation of glucose infusion led to severe hypoglycemia. Pancreaticoduodenectomy was performed and revealed an intraductal papillary mucinous neoplasm (IPMN) with high-grade dysplasia. Sequencing of the IPMN revealed a KRAS gene mutation not present in surrounding normal tissues. Deep sequencing of the patient's blood for KRAS mutations showed no evidence of mosaicism. Whole exome sequencing of the blood of the patient and both parents revealed a de novo germline SKIL mutation in the child that was not present in either parent. This suggests a possible role for SKIL in the pathogenesis of pancreatic tumors.

The Association of Weight With Surgical Morbidity in Infants Undergoing Enterostomy Reversal: A Study of the NSQIP-Pediatrics Database.

INTRODUCTION: Optimal criteria and timing for enterostomy closure (EC) in neonates is largely based on clinical progression and adequate weight, with most institutions using 2.0-2.5 kg as the minimum acceptable weight. It is unclear how the current weight cutoff affects post-operative morbidity. AIM: To determine how infant weight at the time of EC influences 30-day complications. METHODS: Infants weighing ≤4000 g who underwent EC were identified in the 2012-2019 ACS NSQIP-P database. Demographics, comorbidities, and 30-day outcomes were assessed using univariate analysis. Multivariable logistic regression controlling for ASA score, nutritional support, and ventilator support was used to estimate the independent association of weight on risk of 30-day complications. RESULTS: A total of 1692 neonates from the NSQIP-P database during the years 2012-2019 met inclusion criteria. Neonates weighing <2.5 kg were significantly more likely to have a younger gestational age, require ventilator support, and have concurrent comorbidities. Major morbidity, a composite outcome of the individual postoperative complications, was observed in 283 (16.7%) infants. ASA classifications 4 and 5, dependence on nutritional support, and ventilator support were independently associated with increased risk of 30-day complications. With respect to weight, we found no significant difference in major morbidity between infants weighing <2.5 kg and infants weighing ≥2.5 kg. CONCLUSION: Despite using a robust, national dataset, we could find no evidence that a defined weight cut-off was associated with a reduction in major morbidity, indicating that weight should not be a priority factor when determining eligibility for neonatal EC. LEVEL OF EVIDENCE: III.

Effects of tall man lettering on the visual behaviour of critical care nurses while identifying syringe drug labels: a randomised in situ simulation.

BACKGROUND: Patients in intensive care units are prone to the occurrence of medication errors. Look-alike, sound-alike drugs with similar drug names can lead to medication errors and therefore endanger patient safety. Capitalisation of distinct text parts in drug names might facilitate differentiation of medication labels. The aim of this study was to test whether the use of such 'tall man' lettering (TML) reduces the error rate and to examine effects on the visual attention of critical care nurses while identifying syringe labels. METHODS: This was a prospective, randomised in situ simulation conducted at the University Hospital Zurich, Zurich, Switzerland. Under observation by eye tracking, 30 nurses were given 10 successive tasks involving the presentation of a drug name and its selection from a dedicated set of 10 labelled syringes that included look-alike and sound-alike drug names, half of which had TML-coded labels.Error rate as well as dwell time, fixation count, fixation duration and revisits were analysed using a linear mixed-effects model analysis to compare TML-coded with non-TML-coded labels. RESULTS: TML coding of syringe labels led to a significant decrease in the error rate (from 5.3% (8 of 150 in non-TML-coded sets) to 0.7% (1 of 150 in TML-coded sets), p<0.05). Eye tracking further showed that TML affects visual attention, resulting in longer dwell time (p<0.01), more and longer fixations (p<0.05 and p<0.01, respectively) on the drug name as well as more frequent revisits (p<0.01) compared with non-TML-coded labels. Detailed analysis revealed that these effects were stronger for labels using TML in the mid-to-end position of the drug name. CONCLUSIONS: TML in drug names changes visual attention while identifying syringe labels and supports critical care nurses in preventing medication errors.

Bile salts increase epithelial cell proliferation through HuR-induced c-Myc expression.

BACKGROUND: Bile salts increase intestinal mucosal proliferation through an increase in c-Myc, a transcription factor that controls the expression of numerous translation regulatory proteins. HuR is an RNA-binding protein that regulates translation of target mRNAs. RNA-binding proteins can control mRNA stability by binding to AU- and U-rich elements located in the 3'-untranslated regions (3'-UTRs) of target mRNAs. AIM: To determine how bile salt-induced c-Myc stimulates enterocyte proliferation. METHODS: Enterocyte proliferation was measured both in vivo using C57Bl6 mice and in vitro using IEC-6 cells after taurodeoxycholate (TDCA) supplementation. HuR and c-Myc protein expression was determined by immunoblot. c-Myc mRNA expression was determined by PCR. HuR expression was inhibited using specific small interfering RNA. HuR binding to c-Myc mRNA was determined by immunoprecipitation. RESULTS: TDCA increased enterocyte proliferation in vivo and in vitro. TDCA stimulates translocation of HuR from the nucleus to the cytoplasm. Cytoplasmic HuR regulates c-Myc translation by HuR binding to the 3'-UTR of c-Myc mRNA. Increased TDCA-induced c-Myc increases enterocyte proliferation. CONCLUSIONS: Bile salts have beneficial effects on the intestinal epithelial mucosa, which are important in maintaining intestinal mucosal integrity and function. These data further support an important beneficial role of bile salts in regulation of mucosal growth and repair. Decreased enterocyte exposure to luminal bile salts, as occurs during critical illness, liver failure, starvation, and intestinal injury, may have a detrimental effect on mucosal integrity.

Magnetic Appendix: An Uncommon Indication for Appendectomy.

Foreign object ingestions are a common occurrence in pediatrics, often necessitating endoscopic or surgical intervention. The ingestion of multiple magnets poses an increased risk for serious complications. Our article presents a case of a five-year-old boy who swallowed two pennies and four magnets. The latter failed to pass spontaneously and were lodged in the appendiceal orifice resulting in a challenging and unsuccessful endoscopic retrieval and hence required laparoscopic exploration, appendectomy, and partial cecal resection.

Deoxycholic acid causes DNA damage while inducing apoptotic resistance through NF-κB activation in benign Barrett's epithelial cells.

Gastroesophageal reflux is associated with adenocarcinoma in Barrett's esophagus, but the incidence of this tumor is rising, despite widespread use of acid-suppressing medications. This suggests that refluxed material other than acid might contribute to carcinogenesis. We looked for potentially carcinogenetic effects of two bile acids, deoxycholic acid (DCA) and ursodeoxycholic acid (UDCA), on Barrett's epithelial cells in vitro and in vivo. We exposed Barrett's (BAR-T) cells to DCA or UDCA and studied the generation of reactive oxygen/nitrogen species (ROS/RNS); expression of phosphorylated H2AX (a marker of DNA damage), phosphorylated IkBα, and phosphorylated p65 (activated NF-κB pathway proteins); and apoptosis. During endoscopy in patients, we took biopsy specimens of Barrett's mucosa before and after esophageal perfusion with DCA or UDCA and assessed DNA damage and NF-κB activation. Exposure to DCA, but not UDCA, resulted in ROS/RNS production, DNA damage, and NF-κB activation but did not increase the rate of apoptosis in BAR-T cells. Pretreatment with N-acetyl-l-cysteine (a ROS scavenger) prevented DNA damage after DCA exposure, and DCA did induce apoptosis in cells treated with NF-κB inhibitors (BAY 11-7085 or AdIκB superrepressor). DNA damage and NF-κB activation were detected in biopsy specimens of Barrett's mucosa taken after esophageal perfusion with DCA, but not UDCA. These data show that, in Barrett's epithelial cells, DCA induces ROS/RNS production, which causes genotoxic injury, and simultaneously induces activation of the NF-κB pathway, which enables cells with DNA damage to resist apoptosis. We have demonstrated molecular mechanisms whereby bile reflux might contribute to carcinogenesis in Barrett's esophagus.

Acid and bile salt-induced CDX2 expression differs in esophageal squamous cells from patients with and without Barrett's esophagus.

BACKGROUND & AIMS: It is not clear why only a minority of patients with gastroesophageal reflux disease (GERD) develop Barrett's esophagus. We hypothesized that differences among individuals in molecular pathways activated when esophageal squamous epithelium is exposed to reflux underlie the development of Barrett's metaplasia. METHODS: We used esophageal squamous cell lines from patients who had GERD with Barrett's esophagus (normal esophageal squamous [NES]-B3T and NES-B10T) and without Barrett's esophagus (NES-G2T and NES-G4T) to study effects of acid and bile salts on expression of the CDX2 gene. Bay 11-705, Ad5 inhibitor kappaB(IkappaB)alpha-SR, and site-directed mutagenesis were used to explore effects of nuclear factor-kappaB (NF-kappaB) inhibition on CDX2 promoter activity; DNA binding of the NF-kappaB subunits p50 and p65 was assessed by chromatin immune-precipitation. RESULTS: Acid and bile salts increased CDX2 messenger RNA (mRNA), protein, and promoter activity in NES-B3T and NES-B10T cells, but not in NES-G2T or NES-G4T cells. Inhibition of NF-kappaB abolished the increase in CDX2 promoter activity. Increased CDX2 promoter activity was associated with nuclear translocation of p50, which bound to the promoter. We found CDX2 mRNA in 7 of 10 esophageal squamous biopsy specimens from patients with Barrett's esophagus, but in only 1 of 10 such specimens from patients who had GERD without Barrett's esophagus. CONCLUSIONS: Acid and bile salts induce CDX2 mRNA and protein expression in esophageal squamous cells from patients with Barrett's esophagus, but not from GERD patients without Barrett's esophagus. We speculate that these differences in acid- and bile salt-induced activation of molecular pathways may underlie the development of Barrett's metaplasia.

Sphingosine-1-phosphate regulates the expression of adherens junction protein E-cadherin and enhances intestinal epithelial cell barrier function.

BACKGROUND: The regulation of intestinal barrier permeability is important in the maintenance of normal intestinal physiology. Sphingosine-1-phosphate (S1P) has been shown to play a pivotal role in enhancing barrier function in several non-intestinal tissues. The current study determined whether S1P regulated function of the intestinal epithelial barrier by altering expression of E-cadherin, an important protein in adherens junctions. METHODS: Studies were performed upon cultured differentiated IECs (IEC-Cdx2L1 line) using standard techniques. RESULTS: S1P treatment significantly increased levels of E-cadherin protein and mRNA in intestinal epithelial cells (IECs) and also led to E-cadherin localizing strongly to the cell-cell border. S1P also improved the barrier function as indicated by a decrease in 14C-mannitol paracellular permeability and an increase in transepithelial electrical resistance (TEER) in vitro. CONCLUSIONS: These results indicate that S1P increases levels of E-cadherin, both in cellular amounts and at the cell-cell junctions, and leads to improved barrier integrity in cultured intestinal epithelial cells.

Superior Mesenteric Artery Stenosis Due to Disseminated Tuberculosis in a Pediatric Patient.

Disseminated tuberculosis (TB) associated with mesenteric arteritis has not been established in children. We present the case of an 8-year-old woman who presented with TB and superior mesenteric artery stenosis. Although rare, large vessel involvement from Takayasu arteritis can occur in TB. Evaluation for mesenteric vessel involvement should be considered in pediatric patients presenting with widely disseminated TB and abdominal pain.

Cutaneous ciliated cyst: a case report with focus on mullerian heterotopia and comparison with eccrine sweat glands.

Cutaneous ciliated cyst is an exceedingly rare, benign lesion most commonly found in the dermis or subcutis of the lower extremities of young female patients in their second and third decades. The pathogenesis of the cyst is unknown. We report a cutaneous ciliated cyst in the lower extremity of a 13-year-old female patient. On histologic examination, clusters of eccrine sweat glands were observed adjacent to the cyst. Upon comparison of the immunohistochemical profile of the cutaneous ciliated cyst and the eccrine sweat glands, they appeared almost completely unrelated. The histologic, immunohistochemical, and ultrastructural findings of this case and the literature provide evidence in favor of the Mullerian heterotopia theory.