Ileal transposition:A non-restrictive bariatric surgical procedure that reduces body fat and increases ingestion-related energy expenditure

Background: Ileal Transposition (IT) was developed as a model to study body weight reduction without the restrictive or malabsorptive aspects of other bariatric surgeries, but the exact mechanisms of the alterations in body weight after IT are not completely understood. Objective: To provide a detailed description of the surgical procedure of IT, and describe its effect on energy balance parameters. Methods: Adult male Lewis rats underwent either IT (IT+) or sham (IT-) surgery. Following surgery body weight and energy intake were monitored. After attaining weight stability (> 30 days), energy expenditure and its components were assessed using indirect calorimetry at a day of fasting, limited intake, and ad libitum intake. At the end of the study body composition analysis was performed. Results: IT+ resulted in transiently reduced energy intake, increased ingestion-related energy expenditure (IEE) and decreased body and adipose tissue weight when compared to IT-. At weight stability, neither energy budget (i.e., energy intake - energy expenditure), nor energy efficiency was different in IT+ rats compared to IT-. Conclusion: Our data show that the primary cause of weight reduction following IT+ is a transient reduction in energy intake. If the increased IEE is related to a higher level of satiety, compensatory feeding to bridge body weight difference between IT+ and IT- rats is less likely to occur

Necrotizing Enterocolitis Associated with Congenital Heart Disease:a Different Entity?

Background: Necrotizing enterocolitis (NEC) predominantly occurs in preterm infants (PT-NEC). In term neonates, NEC occurs more frequently when a congenital heart disease is present (CHDNEC). Our aim was to evaluate differences and similarities in disease characteristics of PT-NEC versus CHD-NEC.Methods: In this retrospective case-control study we identified all CHD infants who developed NEC Bell's stage &gt;= 2 in our center from 2004 to 2014. We randomly selected (1:2 ratio) PT-NEC infants from the same period. Biochemical and clinical variables were retrieved from patient files.Results: We found 18 CHD-NEC infants and selected 36 PT-NEC infants (gestational age 28.3 [25-35.6] weeks vs. 38.6 [31.7-40.7] weeks). Postnatal age at onset was significantly lower in CHD-NEC patients (4 [2-24] vs. 11 [4-41] days, p &lt;0.001). Lowest pH levels were lower (7.21 [7.01-7.47] vs. 7.27 [6.68-7.39], p = 0.02), and highest CRP levels were higher (112.5 mg/L [5.0-425.0] vs. 66.0 [52-189.0], p = 0.05) in PT-NEC vs. CHD-NEC. Anatomic localisation of the disease differed: the colon was significantly more often involved in CHD-NEC versus PT-NEC (86% vs. 33%, p = 0.03). Mortality caused by NEC was not different (22% vs. 11%, p = 0.47).Conclusion: While outcome of NEC in both groups is similar, the predominant NEC localisation differed between CHD-NEC and PT-NEC patients. This suggests that both variants of the disease have a different underlying pathophysiological mechanism that predisposes different intestinal regions to develop NEC.Type of Study: Retrospective Case-Control Study. (C) 2018 Elsevier Inc. All rights reserved.</p

Long-Term Neurodevelopmental Outcomes in Children with Biliary Atresia

Objective: To assess long-term neurodevelopmental outcomes in school-aged children with biliary atresia. Study design: All Dutch children (6-12 years of age) diagnosed with biliary atresia were invited to participate in this study. We used validated neurodevelopmental tests to assess motor skills and cognition, and questionnaires to assess behavior. Scores were compared with the Dutch norm population, by means of 1-sample tests. Results are given as number and percentage or mean ± SD. Results: We included 46 children, with a median age of 11 years (range, 6-13 years); 36 children had undergone a liver transplantation (78%). Twelve children (26%) received special education (vs 2.4% in the norm population; P <.01). Motor outcomes were significantly affected compared with the norm population (P <.01), with 25% normal (vs 85%), 25% borderline (vs 10%), and 50% low scores (vs 5%). Total IQ was lower in patients with biliary atresia, compared with the norm population (91 ± 18 vs 100 ± 15; P <.01). There were no significant differences in test scores between children with native liver and after liver transplantation. Conclusions: School-aged children with biliary atresia show neurodevelopmental impairments compared with the norm population, especially in motor skills. Our data strongly warrant evaluation of neurodevelopmental intervention programs to assess whether long-term outcomes could be improved

Gut Microbiota Composition of Biliary Atresia Patients Before Kasai Portoenterostomy Associates With Long-term Outcome

BACKGROUND AND AIMS: Biliary atresia (BA) is a cholestatic, fibro-obliterative cholangiopathy of unknown etiology. BA is primarily treated by a surgical approach, i.e. the Kasai portoenterostomy (KPE), to obtain clearance of jaundice (COJ). The gut microbiota (GM) composition has been associated with the course of several cholestatic liver diseases. It is largely unknown, however, whether GM composition associates with the outcome of KPE. We compared the GM composition of BA patients and controls and assessed if GM composition before KPE was related to COJ after KPE. METHODS: We compared feces of term born BA patients before KPE and controls (patients undergoing inguinal hernia repair) by 16S rRNA sequencing. Composition and alpha diversity of the GM were compared between BA and controls before KPE and after KPE, between patients with COJ vs. without COJ (total serum bilirubin < or ≥ 20 μmol/L < 6mo post-KPE). RESULTS: Alpha diversity was comparable between BA (n = 12, age 1.6[1.3-1.8]mo) and controls (n = 6, age 2.0[1.4-2.1]mo; P = 0.22). Compared to controls, BA patients had lower abundances of Bifidobacteriaceae (β=-1.98, P < 0.001) and Lachnospiraceae (β=-1.84, P = 0.007), and higher abundances of Streptococcus (β=1.13, P = 0.003). The alpha diversity prior to KPE correlated negatively with COJ (R = -0.63, P = 0.03). Lower alpha diversity pre-KPE was associated with COJ [+] (βlogit = -0.64, P = 0.04). We observed greater abundances of genus Acinetobacter (β=1.27, P = 0.03) and family Clostridiaceae (β=1.45, P = 0.03) and lower abundances of the family Enterobacteriaceae, (genera Klebsiella (β=-1.21, P = 0.01), Salmonella (β=-1.57, P = 0.02)) in COJ [+] vs. COJ [-]. CONCLUSIONS: The gut microbiota of biliary atresia patients prior to Kasai portoenterostomy associates with outcome, clearance of jaundice, suggestive of predictive and mechanistic roles of the gut microbiota composition in bile homeostasis

A critical role of hepatic GABA in the metabolic dysfunction and hyperphagia of obesity

Hepatic lipid accumulation is a hallmark of type II diabetes (T2D) associated with hyperinsulinemia, insulin resistance, and hyperphagia. Hepatic synthesis of GABA, catalyzed by GABA-transaminase (GABA-T), is upregulated in obese mice. To assess the role of hepatic GABA production in obesity-induced metabolic and energy dysregulation, we treated mice with two pharmacologic GABA-T inhibitors and knocked down hepatic GABA-T expression using an antisense oligonucleotide. Hepatic GABA-T inhibition and knockdown decreased basal hyperinsulinemia and hyperglycemia and improved glucose intolerance. GABA-T knockdown improved insulin sensitivity assessed by hyperinsulinemic-euglycemic clamps in obese mice. Hepatic GABA-T knockdown also decreased food intake and induced weight loss without altering energy expenditure in obese mice. Data from people with obesity support the notion that hepatic GABA production and transport are associated with serum insulin, homeostatic model assessment for insulin resistance (HOMA-IR), T2D, and BMI. These results support a key role for hepatocyte GABA production in the dysfunctional glucoregulation and feeding behavior associated with obesity

Hepatocyte membrane potential regulates serum insulin and insulin sensitivity by altering hepatic GABA release

Hepatic lipid accumulation in obesity correlates with the severity of hyperinsulinemia and systemic insulin resistance. Obesity-induced hepatocellular lipid accumulation results in hepatocyte depolarization. We have established that hepatocyte depolarization depresses hepatic afferent vagal nerve firing, increases GABA release from liver slices, and causes hyperinsulinemia. Preventing hepatic GABA release or eliminating the ability of the liver to communicate to the hepatic vagal nerve ameliorates the hyperinsulinemia and insulin resistance associated with diet-induced obesity. In people with obesity, hepatic expression of GABA transporters is associated with glucose infusion and disposal rates during a hyperinsulinemic euglycemic clamp. Single-nucleotide polymorphisms in hepatic GABA re-uptake transporters are associated with an increased incidence of type 2 diabetes mellitus. Herein, we identify GABA as a neuro-hepatokine that is dysregulated in obesity and whose release can be manipulated to mute or exacerbate the glucoregulatory dysfunction common to obesity

HPV type-specific distribution among family members and linen in households of cutaneous wart patients

Background Common and plantar warts are caused by human papillomaviruses (HPV). Mode of transmission of wart HPVs within families is largely unknown. Objective To demonstrate similarity of HPV type(s) among wart cases, family members and household linen. Methods In a cross-sectional study, swabs taken from 123 warts and foreheads of 62 index patients and 157 family members and from 58 kitchen towels and 59 bathroom mats were tested for DNA of 23 cutaneous wart-associated HPV types. Generalized estimating equations (GEE) were used to estimate the chance of detecting the same HPV type as was found in the index patients on the family contacts and on the kitchen towels and bathroom mats. Results HPV1, HPV2, HPV27 and HPV57 were the most prevalent types in the warts of the index patients. Altogether, 60 (42.3%) of the 142 family members without warts had HPV DNA on their foreheads. When HPV1 and HPV2 were found in the warts, these types were also frequently (>50%) found on the foreheads of index patients and their family members, as well as on the kitchen towels and the bathroom mats. HPV27 and HPV57 were less frequently found (<25%) on foreheads and linen. No associations were found for age, sex and site of HPV DNA presence. Conclusion Dissemination of skin wart-causing HPV types, from wart cases to household contacts and linen, such as kitchen towels and bathroom mats, is more likely for HPV1 and HPV2 than for HPV27 and HPV57. The role of towels and bathroom mats in HPV transmission deserves further investigation.Dermatology-oncolog

Decreasing Trends in Intestinal Resection and Re-Resection in Crohn's Disease A Nationwide Cohort Study:A Nationwide Cohort Study

OBJECTIVE: To assess time trends in intestinal resection and re-resection in Crohn's disease (CD) patients.SUMMARY OF BACKGROUND DATA: CD treatment has changed considerably over the past decades. The effect of these advances on the necessity of intestinal resections and the risk of re-resection is unclear.METHODS: In this nationwide cohort study, adult CD patients with ileocolonic, small bowel, colon, or rectum resections between 1991 and 2015 were included. Data were retrieved from the Dutch nationwide network and registry of histopathology and cytopathology (PALGA). Time trends were analyzed with a broken stick model and Cox proportional hazard model with smoothing splines.RESULTS: The identified cohort comprised 8172 CD patients (3293/4879 male/female) in whom 10,315 intestinal resections were performed. The annual intestinal resection rate decreased nonlinearly from 22.7/100,000 CD patients (1991) to 2.5/100,000 (2015). A significantly steeper decrease was observed before 1999 (slope -1.56) as compared to subsequent years (slope -0.41) (P &lt; 0.001). Analogous trends were observed for ileocolonic, small bowel, and colon resections. Overall cumulative risk of re-resection was 10.9% at 5 years, 18.6% at 10 years, and 28.3% at 20 years after intestinal resection. The hazard for intestinal re-resection showed a nonlinear decreasing trend, with hazard ratio 0.39 (95% confidence interval 0.36-0.44) in 2000 and hazard ratio 0.25 (95% confidence interval 0.18-0.34) in 2015 as compared to 1991.CONCLUSION: Over the past 25 years, intestinal resection rate has decreased significantly for ileocolonic, small bowel, and colonic CD. In addition, current postoperative CD patients are at 75% lower risk of intestinal re-resection.This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0.</p

Analysis of urinary oligosaccharides in lysosomal storage disorders by capillary high-performance anion-exchange chromatography–mass spectrometry

Many lysosomal storage diseases are characterized by an increased urinary excretion of glycoconjugates and oligosaccharides that are characteristic for the underlying enzymatic defect. Here, we have used capillary high-performance anion-exchange chromatography (HPAEC) hyphenated to mass spectrometry to analyze free oligosaccharides from urine samples of patients suffering from the lysosomal storage disorders fucosidosis, α-mannosidosis, GM1-gangliosidosis, GM2-gangliosidosis, and sialidosis. Glycan fingerprints were registered, and the patterns of accumulated oligosaccharides were found to reflect the specific blockages of the catabolic pathway. Our analytical approach allowed structural analysis of the excreted oligosaccharides and revealed several previously unpublished oligosaccharides. In conclusion, using online coupling of HPAEC with mass spectrometric detection, our study provides characteristic urinary oligosaccharide fingerprints with diagnostic potential for lysosomal storage disorders

Surgical Outcome of Children with a Malignant Liver Tumour in The Netherlands:A Retrospective Consecutive Cohort Study

INTRODUCTION: Six to eight children are diagnosed with a malignant liver tumour yearly in the Netherlands. The majority of these tumours are hepatoblastoma (HB) and hepatocellular carcinoma (HCC), for which radical resection, often in combination with chemotherapy, is the only curative treatment option. We investigated the surgical outcome of children with a malignant liver tumour in a consecutive cohort in the Netherlands. METHODS: In this nationwide, retrospective observational study, all patients (age &lt; 18 years) diagnosed with a malignant liver tumour, who underwent partial liver resection or orthotopic liver transplantation (OLT) between January 2014 and April 2021, were included. Children with a malignant liver tumour who were not eligible for surgery were excluded from the analysis. Data regarding tumour characteristics, diagnostics, treatment, complications and survival were collected. Outcomes included major complications (Clavien-Dindo ≥ 3a) within 90 days and disease-free survival. The results of the HB group were compared to those of a historical HB cohort. RESULTS: Twenty-six children were analysed, of whom fourteen (54%) with HB (median age 21.5 months), ten (38%) with HCC (median age 140 months) and one with sarcoma and a CNSET. Thirteen children with HB (93%) and three children with HCC (30%) received neoadjuvant chemotherapy. Partial hepatic resection was possible in 19 patients (12 HB, 6 HCC, and 1 sarcoma), whilst 7 children required OLT (2 HB, 4 HCC, and 1 CNSET). Radical resection (R0, margin ≥ 1.0 mm) was obtained in 24 out of 26 patients, with recurrence only in the patient with CNSET. The mean follow-up was 39.7 months (HB 40 months, HCC 40 months). Major complications occurred in 9 out of 26 patients (35% in all, 4 of 14, 29% for HB). There was no 30- or 90-day mortality, with disease-free survival after surgery of 100% for HB and 80% for HCC, respectively. Results showed a tendency towards a better outcome compared to the historic cohort, but numbers were too small to reach significance. CONCLUSION: Survival after surgical treatment for malignant liver tumours in the Netherlands is excellent. Severe surgical complications arise in one-third of patients, but most resolve without long-term sequelae and have no impact on long-term survival