Development of pancreatic diseases during long-term follow-up after acute pancreatitis:a post-hoc analysis of a prospective multicenter cohort

Background and Aim: More insight into the incidence of and factors associated with progression following a first episode of acute pancreatitis (AP) would offer opportunities for improvements in disease management and patient counseling. Methods: A long-term post hoc analysis of a prospective cohort of patients with AP (2008–2015) was performed. Primary endpoints were recurrent acute pancreatitis (RAP), chronic pancreatitis (CP), and pancreatic cancer. Cumulative incidence calculations and risk analyses were performed. Results: Overall, 1184 patients with a median follow-up of 9 years (IQR: 7–11) were included. RAP and CP occurred in 301 patients (25%) and 72 patients (6%), with the highest incidences observed for alcoholic pancreatitis (40% and 22%). Pancreatic cancer was diagnosed in 14 patients (1%). Predictive factors for RAP were alcoholic and idiopathic pancreatitis (OR 2.70, 95% CI 1.51–4.82 and OR 2.06, 95% CI 1.40–3.02), and no pancreatic interventions (OR 1.82, 95% CI 1.10–3.01). Non-biliary etiology (alcohol: OR 5.24, 95% CI 1.94–14.16, idiopathic: OR 4.57, 95% CI 2.05–10.16, and other: OR 2.97, 95% CI 1.11–7.94), RAP (OR 4.93, 95% CI 2.84–8.58), prior pancreatic interventions (OR 3.10, 95% CI 1.20–8.02), smoking (OR 2.33, 95% CI 1.14–4.78), and male sex (OR 2.06, 95% CI 1.05–4.05) were independently associated with CP. Conclusion: Disease progression was observed in a quarter of pancreatitis patients. We identified several risk factors that may be helpful to devise personalized strategies with the intention to reduce the impact of disease progression in patients with AP.</p

Consensus on the definition of colorectal anastomotic leakage: A modified Delphi study

BACKGROUND: Despite the emerging knowledge about colorectal anastomotic leakage (CAL) through the increasing number of clinical and experimental studies, there is no generally accepted definition of CAL. Because of the wide variety of definitions used in literature, comparison of study outcomes and quality of care is complicated. AIM: To reach consensus on the definition of CAL using a modified Delphi method. METHODS: The RAND/UCLA appropriateness method was used. The expert panel consisted of international colorectal surgeons and researchers who had published three or more articles about CAL. The consensus process consisted of two online distributed questionnaires and a third round with a recommendation. In the questionnaires participants were asked to rate the appropriateness of statements using a 1-9 Likert scale. Consensus was defined as a panel median between 1-3 or 7-9 without disagreement. In the final round a recommendation was formed regarding the definition of CAL and the expert panel was asked if they agreed or disagreed. RESULTS: Twenty-three authors participated in the first round and twenty-one finished the second round. After two rounds consensus was reached on 37 items (80%) in nine different categories. The International Study Group of Rectal Cancer definition is the most frequently advised general definition by our panel. Consensus was reached regarding the clinical symptoms of CAL, which serum markers contributes to the suspicion of CAL, which radiological and perioperative findings should be considered as CAL, which grading system is appropriate and if there should be a range of postoperative days in the definition. Eventually, 19 experts completed all three rounds of which 16 (84%) agreed with our final recommendations for the definition of CAL. CONCLUSION: A consensus-based recommendation for the definition of CAL was formed using our modified Delphi method that can be widely incorporated in the field

The influence of nitrous oxide on hearing

Obesity is associated with chronic low-grade systemic inflammation. Bariatric surgery has been shown to reduce this inflammation. Here, the effect of a nonsurgical bariatric technique, the duodenal-jejunal bypass liner (DJBL), on systemic inflammation was investigated. Seventeen obese patients with type 2 diabetes were treated with the DJBL for 6 months. Plasma C-reactive protein (CRP), myeloperoxidase (MPO), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-alpha) were determined prior to and during DJBL treatment. Three months after initiation of DJBL treatment, TNF-alpha levels had increased from 1.8 +/- 0.1 to 2.1 +/- 0.1 pg/mL, whereas IL-6 increased from 2.7 +/- 0.3 to 4.0 +/- 0.5 pg/mL (both p <0.05). CRP and MPO also increased, though the differences were not significant. After 6 months, the levels of all parameters were similar to baseline levels (CRP, 4.2 +/- 0.6 mg/L; TNF-alpha, 2.0 +/- 0.1 pg/mL; IL-6, 3.5 +/- 0.5 pg/mL; MPO, 53.6 +/- ng/mL; all p = ns compared to baseline). In the current study, 6 months of endoscopic DJBL treatment did not lead to decreased systemic inflammation

Metabolic improvement in obese patients after duodenal–jejunal exclusion is associated with intestinal microbiota composition changes

Background: Intestinal microbiota have been suggested to play an important role in the pathogenesis of obesity and type 2 diabetes. Bariatric surgery improves both conditions and has been associated with changes in intestinal microbiota composition. We investigated the effect of a nonsurgical bariatric technique on intestinal microbiota composition in relation to metabolic improvement. Methods: Seventeen patients with obesity and type 2 diabetes were treated with the nonsurgical duodenal–jejunal bypass liner, which excludes the proximal 60 cm small intestine from food. Fecal samples as well as metabolic parameters reflecting obesity and type 2 diabetes were obtained from the patients at baseline, after 6 months with the device in situ, and 6 months after explantation. Results: After 6 months of treatment, both obesity and type 2 diabetes had improved with a decrease in weight from 106.1 [99.4–123.5] to 97.4 [89.4–114.0] kg and a decrease in HbA 1c from 8.5% [7.6–9.2] to 7.2% [6.3–8.1] (both p < 0.05). This was paralleled by an increased abundance of typical small intestinal bacteria such as Proteobacteria, Veillonella, and Lactobacillus spp. in feces. After removal of the duodenal–jejunal bypass liner, fecal microbiota composition was similar to that observed at baseline, despite persistent weight loss. Conclusion: Improvement of obesity and type 2 diabetes after exclusion of the proximal 60 cm small intestine by treatment with a nonsurgical duodenal–jejunal bypass liner may be promoted by changes in fecal microbiota composition. </p

Endoscopic duodenal-jejunal bypass liner rapidly improves type 2 diabetes.

Bariatric procedures excluding the proximal small intestine improve glycemic control in type 2 diabetes within days. To gain insight into the mediators involved, we investigated factors regulating glucose homeostasis in patients with type 2 diabetes treated with the novel endoscopic duodenal-jejunal bypass liner (DJBL). Seventeen obese patients (BMI 30-50 kg/m(2)) with type 2 diabetes received the DJBL for 24 weeks. Body weight and type 2 diabetes parameters, including HbA(1c) and plasma levels of glucose, insulin, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and glucagon, were analyzed after a standard meal before, during, and 1 week after DJBL treatment. At 24 weeks after implantation, patients had lost 12.7 +/- 1.3 kg (p <0.01), while HbA(1c) had improved from 8.4 +/- 0.2 to 7.0 +/- 0.2 % (p <0.01). Both fasting glucose levels and the postprandial glucose response were decreased at 1 week after implantation and remained decreased at 24 weeks (baseline vs. week 1 vs. week 24: 11.6 +/- 0.5 vs. 9.0 +/- 0.5 vs. 8.6 +/- 0.5 mmol/L and 1,999 +/- 85 vs. 1,536 +/- 51 vs. 1,538 +/- 72 mmol/L/min, both p <0.01). In parallel, the glucagon response decreased (23,762 +/- 4,732 vs. 15,989 +/- 3,193 vs. 13,1207 +/- 1,946 pg/mL/min, p <0.05) and the GLP-1 response increased (4,440 +/- 249 vs. 6,407 +/- 480 vs. 6,008 +/- 429 pmol/L/min, p <0.01). The GIP response was decreased at week 24 (baseline-115,272 +/- 10,971 vs. week 24-88,499 +/- 10,971 pg/mL/min, p <0.05). Insulin levels did not change significantly. Glycemic control was still improved 1 week after explantation. The data indicate DJBL to be a promising treatment for obesity and type 2 diabetes, causing rapid improvement of glycemic control paralleled by changes in gut hormones

Complement alternative pathway activation in human nonalcoholic steatohepatitis

The innate immune system plays a major role in the pathogenesis of nonalcoholic steatohepatitis (NASH). Recently we reported complement activation in human NASH. However, it remained unclear whether the alternative pathway of complement, which amplifies C3 activation and which is frequently associated with pathological complement activation leading to disease, was involved. Here, alternative pathway components were investigated in liver biopsies of obese subjects with healthy livers (n = 10) or with NASH (n = 12) using quantitative PCR, Western blotting, and immunofluorescence staining. Properdin accumulated in areas where neutrophils surrounded steatotic hepatocytes, and colocalized with the C3 activation product C3c. C3 activation status as expressed by the C3c/native C3 ratio was 2.6-fold higher (p<0.01) in subjects with NASH despite reduced native C3 concentrations (0.94+/-0.12 vs. 0.57+/-0.09; p<0.01). Hepatic properdin levels positively correlated with levels of C3c (rs = 0.69; p<0.05) and C3c/C3 activation ratio (rs = 0.59; p<0.05). C3c, C3 activation status (C3c/C3 ratio) and properdin levels increased with higher lobular inflammation scores as determined according to the Kleiner classification (C3c: p<0.01, C3c/C3 ratio: p<0.05, properdin: p<0.05). Hepatic mRNA expression of factor B and factor D did not differ between subjects with healthy livers and subjects with NASH (factor B: 1.00+/-0.19 vs. 0.71+/-0.07, p = 0.26; factor D: 1.00+/-0.21 vs. 0.66+/-0.14, p = 0.29;). Hepatic mRNA and protein levels of Decay Accelerating Factor tended to be increased in subjects with NASH (mRNA: 1.00+/-0.14 vs. 2.37+/-0.72; p = 0.22; protein: 0.51+/-0.11 vs. 1.97+/-0.67; p = 0.28). In contrast, factor H mRNA was downregulated in patients with NASH (1.00+/-0.09 vs. 0.71+/-0.06; p<0.05) and a similar trend was observed with hepatic protein levels (1.12+/-0.16 vs. 0.78+/-0.07; p = 0.08). Collectively, these data suggest a role for alternative pathway activation in driving hepatic inflammation in NASH. Therefore, alternative pathway factors may be considered attractive targets for treating NASH by inhibiting complement activation

Non-alcoholic steatohepatitis: A non-invasive diagnosis by analysis of exhaled breath.

BACKGROUND & AIMS: Histological evaluation of a liver biopsy is the current gold standard to diagnose non-alcoholic steatohepatitis (NASH), but the procedure to obtain biopsies is associated with morbidity and high costs. Hence, only subjects at high risk are biopsied, leading to underestimation of NASH prevalence and undertreatment. Since analysis of volatile organic compounds in breath has been shown to accurately identify subjects with other chronic inflammatory diseases, we investigated its potential as a noninvasive tool to diagnose NASH. METHODS: Wedge-shaped liver biopsies from 65 subjects (BMI 24.8-64.3 kg/m(2)) were obtained during surgery and histologically evaluated. The profile of volatile organic compounds in pre-operative breath samples was analyzed by gas chromatography-mass spectrometry and related to liver histology scores and plasma parameters of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). RESULTS: Three exhaled compounds were sufficient to distinguish subjects with (n=39) and without NASH (n=26), with an area under the ROC curve of 0.77. The negative and positive predictive values were 82% and 81%. In contrast, elevated ALT levels or increased AST/ALT ratios both showed negative predictive values of 43%, and positive predictive values of 88% and 70%, respectively. The breath test reduced the hypothetical percentage of undiagnosed NASH patients from 67-79% to 10%, and of misdiagnosed subjects from 49-51% to 18%. CONCLUSION: Analysis of volatile organic compounds in exhaled air is a promising method to indicate NASH presence and absence. In comparison to plasma transaminase levels, the breath test significantly reduced the percentage of missed NASH patients and the number of unnecessarily biopsied subjects

How to use the ADI-R for classifying autism spectrum disorders? Psychometric properties of criteria from the literature in 1,204 Dutch children

Contains fulltext : 125717.pdf (publisher's version ) (Closed access)The algorithm of the Autism Diagnostic Interview-Revised provides criteria for autism versus non-autism according to DSM-IV. Criteria for the broader autism spectrum disorders are needed. This study investigated the validity of seven sets of criteria from the literature, in 1,204 Dutch children (aged 3-18 years) with and without mental retardation. The original criteria (Rutter et al. in ADI-R Autism Diagnostic Interview Revised. Manual. Western Psychological Services, Los Angeles, 2003) well discriminated ASD from non-ASD in MR. All other criteria (IMGSAC in Am Soc Hum Genet 69:570-581 2001; Sung et al. in Am J Hum Genet 76: 68-81, 2005; Risi et al. in J Am Acad Child Adolesc Psychiatry 45: 1094-1103, 2006) were sensitive at the cost of specificity, bearing the risk of overinclusiveness. In the group without MR, clinicians should decide whether sensitivity or specificity is aimed for, to choose the appropriate criteria. Including the Autism Diagnostic Observation Schedule revised algorithms in the classification, the specificity increases, at the cost of sensitivity. This study adds to a more valid judgment on which criteria to use for specific objectives