A core outcome set for appendicitis: A consensus approach utilizing modified Delphi methodology.

BACKGROUND: Appendicitis is one of the most common pathologies encountered by general and acute care surgeons. The current literature is inconsistent, as it is fraught with outcome heterogeneity, especially in the area of nonoperative management. We sought to develop a core outcome set (COS) for future appendicitis studies to facilitate outcome standardization and future data pooling. METHODS: A modified Delphi study was conducted after identification of content experts in the field of appendicitis using both the Eastern Association for the Surgery of Trauma (EAST) landmark appendicitis articles and consensus from the EAST ad hoc COS taskforce on appendicitis. The study incorporated three rounds. Round 1 utilized free text outcome suggestions, then in rounds 2 and 3 the suggests were scored using a Likert scale of 1 to 9 with 1 to 3 denoting a less important outcome, 4 to 6 denoting an important but noncritical outcome, and 7 to 9 denoting a critically important outcome. Core outcome status consensus was defined a priori as >70% of scores 7 to 9 and <15% of scores 1 to 3. RESULTS: Seventeen panelists initially agreed to participate in the study with 16 completing the process (94%). Thirty-two unique potential outcomes were initially suggested in round 1 and 10 (31%) met consensus with one outcome meeting exclusion at the end of round 2. At completion of round 3, a total of 17 (53%) outcomes achieved COS consensus. CONCLUSION: An international panel of 16 appendicitis experts achieved consensus on 17 core outcomes that should be incorporated into future appendicitis studies as a minimum set of standardized outcomes to help frame future cohort-based studies on appendicitis. LEVEL OF EVIDENCE: Diagnostic Test or Criteria; Level V.

Roux-en-Y versus one-anastomosis gastric bypass (RYSA study): weight loss, metabolic improvements, and nutrition at 1 year after surgery, a multicenter randomized controlled trial.

OBJECTIVE: Although it has been suggested that one-anastomosis gastric bypass (OAGB) is metabolically superior to the "gold standard," i.e., Roux-en-Y gastric bypass (RYGB), there is little robust evidence to prove it. Because this result may arise from the typically longer length of bypassed intestine in OAGB, here, the authors standardized the bypass length in RYGB and OAGB and compared weight loss and metabolic outcomes in a randomized controlled trial. METHODS: The authors randomized 121 bariatric patients to RYGB (n = 61) or OAGB (n = 60) in two Finnish University Hospitals and measured weight; body composition; metabolic features (insulin sensitivity, lipids, inflammation, nutrition); and comorbidities before and 6 and 12 months after the operation. RESULTS: Total weight loss was similar in RYGB and OAGB at 6 months (mean: 21.2% [95% CI: 19.4-23.0] vs. 22.8% [95% CI: 21.5-24.1], p = 0.136) and 12 months (25.4% [95% CI: 23.4-27.5] vs. 26.1% [95% CI: 24.2-28.9], p = 0.635). Insulin sensitivity, lipids, and inflammation improved similarly between the groups (p > 0.05). Remission of type 2 diabetes and hypercholesterolemia was marked and similar (p > 0.05) but the use of antihypertensive medications was lower (p = 0.037) and hypertension tended to improve more (p = 0.053) with RYGB versus OAGB at 12 months. Higher rates of vitamin D-25 deficiency (p < 0.05) and lower D-25 levels were observed with OAGB versus RYGB throughout the follow-up (p < 0.001). No differences in adverse effects were observed. CONCLUSIONS: RYGB and OAGB were comparable in weight loss, metabolic improvement, remission of diabetes and hypercholesterolemia, and nutrition at 1-year follow-up. Vitamin D-25 deficiency was more prevalent with OAGB, whereas reduction in antihypertensive medications and hypertension was greater with RYGB. There is no need to change the current practices of RYGB in favor of OAGB.

Inhibition of HSD17B13 protects against liver fibrosis by inhibition of pyrimidine catabolism in nonalcoholic steatohepatitis.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, in which prognosis is determined by liver fibrosis. A common variant in hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13, rs72613567-A) is associated with a reduced risk of fibrosis in NAFLD, but the underlying mechanism(s) remains unclear. We investigated the effects of this variant in the human liver and in Hsd17b13 knockdown in mice by using a state-of-the-art metabolomics approach. We demonstrate that protection against liver fibrosis conferred by the HSD17B13 rs72613567-A variant in humans and by the Hsd17b13 knockdown in mice is associated with decreased pyrimidine catabolism at the level of dihydropyrimidine dehydrogenase. Furthermore, we show that hepatic pyrimidines are depleted in two distinct mouse models of NAFLD and that inhibition of pyrimidine catabolism by gimeracil phenocopies the HSD17B13-induced protection against liver fibrosis. Our data suggest pyrimidine catabolism as a therapeutic target against the development of liver fibrosis in NAFLD.

Obesity Modifies the Performance of Fibrosis Biomarkers in Nonalcoholic Fatty Liver Disease.

CONTEXT: Guidelines recommend blood-based fibrosis biomarkers to identify advanced nonalcoholic fatty liver disease (NAFLD), which is particularly prevalent in patients with obesity. OBJECTIVE: To study whether the degree of obesity affects the performance of liver fibrosis biomarkers in NAFLD. DESIGN: Cross-sectional cohort study comparing simple fibrosis scores [Fibrosis-4 Index (FIB-4); NAFLD Fibrosis Score (NFS); aspartate aminotransferase to platelet ratio index; BARD (body mass index, aspartate-to-alanine aminotransferase ratio, diabetes); Hepamet Fibrosis Score (HFS)] and newer scores incorporating neo-epitope biomarkers PRO-C3 (ADAPT, FIBC3) or cytokeratin 18 (MACK-3). SETTING: Tertiary referral center. PATIENTS: We recruited overweight/obese patients from endocrinology (n = 307) and hepatology (n = 71) clinics undergoing a liver biopsy [median body mass index (BMI) 40.3 (interquartile range 36.0-44.7) kg/m2]. Additionally, we studied 859 less obese patients with biopsy-proven NAFLD to derive BMI-adjusted cutoffs for NFS. MAIN OUTCOME MEASURES: Biomarker area under the receiver operating characteristic (AUROC), sensitivity, specificity, and predictive values to identify histological stage ≥F3 fibrosis or nonalcoholic steatohepatitis with ≥F2 fibrosis [fibrotic nonalcoholic steatohepatitis (NASH)]. RESULTS: The scores with an AUROC ≥0.85 to identify ≥F3 fibrosis were ADAPT, FIB-4, FIBC3, and HFS. For fibrotic NASH, the best predictors were MACK-3 and ADAPT. The specificities of NFS, BARD, and FIBC3 deteriorated as a function of BMI. We derived and validated new cutoffs for NFS to rule in/out ≥F3 fibrosis in groups with BMIs <30.0, 30.0 to 39.9, and ≥40.0 kg/m2. This optimized its performance at all levels of BMI. Sequentially combining FIB-4 with ADAPT or FIBC3 increased specificity to diagnose ≥F3 fibrosis. CONCLUSIONS: In obese patients, the best-performing fibrosis biomarkers are ADAPT and the inexpensive FIB-4, which are unaffected by BMI. The widely used NFS loses specificity in obese individuals, which may be corrected with BMI-adjusted cutoffs.

Distinct contributions of metabolic dysfunction and genetic risk factors in the pathogenesis of non-alcoholic fatty liver disease.

BACKGROUND & AIMS: There is substantial inter-individual variability in the risk of non-alcoholic fatty liver disease (NAFLD). Part of which is explained by insulin resistance (IR) ('MetComp') and part by common modifiers of genetic risk ('GenComp'). We examined how IR on the one hand and genetic risk on the other contribute to the pathogenesis of NAFLD. METHODS: We studied 846 individuals: 492 were obese patients with liver histology and 354 were individuals who underwent intrahepatic triglyceride measurement by proton magnetic resonance spectroscopy. A genetic risk score was calculated using the number of risk alleles in PNPLA3, TM6SF2, MBOAT7, HSD17B13 and MARC1. Substrate concentrations were assessed by serum NMR metabolomics. In subsets of participants, non-esterified fatty acids (NEFAs) and their flux were assessed by D5-glycerol and hyperinsulinemic-euglycemic clamp (n = 41), and hepatic de novo lipogenesis (DNL) was measured by D2O (n = 61). RESULTS: We found that substrate surplus (increased concentrations of 28 serum metabolites including glucose, glycolytic intermediates, and amino acids; increased NEFAs and their flux; increased DNL) characterized the 'MetComp'. In contrast, the 'GenComp' was not accompanied by any substrate excess but was characterized by an increased hepatic mitochondrial redox state, as determined by serum ß-hydroxybutyrate/acetoacetate ratio, and inhibition of hepatic pathways dependent on tricarboxylic acid cycle activity, such as DNL. Serum ß-hydroxybutyrate/acetoacetate ratio correlated strongly with all histological features of NAFLD. IR and hepatic mitochondrial redox state conferred additive increases in histological features of NAFLD. CONCLUSIONS: These data show that the mechanisms underlying 'Metabolic' and 'Genetic' components of NAFLD are fundamentally different. These findings may have implications with respect to the diagnosis and treatment of NAFLD. LAY SUMMARY: The pathogenesis of non-alcoholic fatty liver disease can be explained in part by a metabolic component, including obesity, and in part by a genetic component. Herein, we demonstrate that the mechanisms underlying these components are fundamentally different: the metabolic component is characterized by hepatic oversupply of substrates, such as sugars, lipids and amino acids. In contrast, the genetic component is characterized by impaired hepatic mitochondrial function, making the liver less able to metabolize these substrates.

Defining Global Benchmarks in Elective Secondary Bariatric Surgery Comprising Conversional, Revisional, and Reversal Procedures.

OBJECTIVE: To define "best possible" outcomes for secondary bariatric surgery (BS). BACKGROUND: Management of poor response and of long-term complications after BS is complex and under-investigated. Indications and types of reoperations vary widely and postoperative complication rates are higher compared to primary BS. METHODS: Out of 44,884 BS performed in 18 high-volume centers from 4 continents between 06/2013-05/2019, 5,349 (12%) secondary BS cases were identified. Twenty-one outcome benchmarks were established in low-risk patients, defined as the 75th percentile of the median outcome values of centers. Benchmark cases had no previous laparotomy, diabetes, sleep apnea, cardiopathy, renal insufficiency, inflammatory bowel disease, immunosuppression, thromboembolic events, BMI> 50 kg/m2 or age> 65 years. RESULTS: The benchmark cohort included 3143 cases, mainly females (85%), aged 43.8 ±â€Š10 years, 8.4 ±â€Š5.3 years after primary BS, with a BMI 35.2 ±â€Š7 kg/m2. Main indications were insufficient weight loss (43%) and gastro-esophageal reflux disease/dysphagia (25%). 90-days postoperatively, 14.6% of benchmark patients presented ≥1 complication, mortality was 0.06% (n = 2). Significantly higher morbidity was observed in non-benchmark cases (OR 1.37) and after conversional/reversal or revisional procedures with gastrointestinal suture/stapling (OR 1.84). Benchmark cutoffs for conversional BS were ≤4.5% re-intervention, ≤8.3% re-operation 90-days postoperatively. At 2-years (IQR 1-3) 15.6% of benchmark patients required a reoperation. CONCLUSION: Secondary BS is safe, although postoperative morbidity exceeds the established benchmarks for primary BS. The excess morbidity is due to an increased risk of gastrointestinal leakage and higher need for intensive care. The considerable rate of tertiary BS warrants expertise and future research to optimize the management of non-success after BS.

Association of complicated appendicitis on the risk of later in vitro fertilization treatment requirement and ectopic pregnancy: a nationwide cohort study.

INTRODUCTION: A population-based register study utilizing three Finnish National Registers was carried out to determine whether uncomplicated appendicitis, complicated appendicitis and appendectomy without appendicitis are associated with a subsequent risk of requiring in vitro fertilization (IVF) treatment or a risk of ectopic pregnancy among reproductive-age women. MATERIAL AND METHODS: A total of 23 997 women who underwent appendectomy for uncomplicated or complicated appendicitis or for nonspecific abdominal pain or who had nonspecific abdominal pain without surgical procedures between 2000 and 2012 were included in the study. The later risks of IVF treatment requirement and ectopic pregnancy were assessed after uncomplicated appendicitis, complicated appendicitis and appendectomy without appendicitis. Women with nonspecific abdominal pain without surgical procedures served as the reference group. RESULTS: The rates of later IVF treatment after uncomplicated appendicitis, complicated appendicitis and appendectomy without appendicitis were low (2.1%, 2.5% and 2.3%, respectively; p = 0.681). Neither appendicitis nor appendectomy was associated with the risk of requiring IVF treatment. The rate of ectopic pregnancy after uncomplicated and complicated appendicitis was very low (0.8%). Women with uncomplicated appendicitis had a significantly lower risk of ectopic pregnancy compared with patients with nonspecific abdominal pain. CONCLUSIONS: Appendicitis, whether complicated or uncomplicated, and appendectomy without appendicitis does not increase the risk of requiring later IVF treatment or the risk of ectopic pregnancy.

Assessment of Lifestyle Factors Helps to Identify Liver Fibrosis Due to Non-Alcoholic Fatty Liver Disease in Obesity.

Only some individuals with obesity develop liver fibrosis due to non-alcoholic fatty liver disease (NAFLD-fibrosis). We determined whether detailed assessment of lifestyle factors in addition to physical, biochemical and genetic factors helps in identification of these patients. A total of 100 patients with obesity (mean BMI 40.0 ± 0.6 kg/m2) referred for bariatric surgery at the Helsinki University Hospital underwent a liver biopsy to evaluate liver histology. Physical activity was determined by accelerometer recordings and by the Modifiable Activity Questionnaire, diet by the FINRISK Food Frequency Questionnaire, and other lifestyle factors, such as sleep patterns and smoking, by face-to-face interviews. Physical and biochemical parameters and genetic risk score (GRS based on variants in PNPLA3, TM6SF2, MBOAT7 and HSD17B13) were measured. Of all participants 49% had NAFLD-fibrosis. Independent predictors of NAFLD-fibrosis were low moderate-to-vigorous physical activity, high red meat intake, low carbohydrate intake, smoking, HbA1c, triglycerides and GRS. A model including these factors (areas under the receiver operating characteristics curve (AUROC) 0.90 (95% CI 0.84-0.96)) identified NAFLD-fibrosis significantly more accurately than a model including all but lifestyle factors (AUROC 0.82 (95% CI 0.73-0.91)) or models including lifestyle, physical and biochemical, or genetic factors alone. Assessment of lifestyle parameters in addition to physical, biochemical and genetic factors helps to identify obese patients with NAFLD-fibrosis.

The PNPLA3-I148M Variant Confers an Antiatherogenic Lipid Profile in Insulin-resistant Patients.

CONTEXT: The I148M (rs738409-G) variant in PNPLA3 increases liver fat content but may be protective against cardiovascular disease. Insulin resistance (IR) amplifies the effect of PNPLA3-I148M on liver fat. OBJECTIVE: To study whether PNPLA3-I148M confers an antihyperlipidemic effect in insulin-resistant patients. DESIGN: Cross-sectional study comparing the impact of PNPLA3-I148M on plasma lipids and lipoproteins in 2 cohorts, both divided into groups based on rs738409-G allele carrier status and median HOMA-IR. SETTING: Tertiary referral center. PATIENTS: A total of 298 obese patients who underwent a liver biopsy during bariatric surgery (bariatric cohort: age 49 ±â€…9 years, body mass index [BMI] 43.2 ±â€…6.8 kg/m2), and 345 less obese volunteers in whom liver fat was measured by proton magnetic resonance spectroscopy (nonbariatric cohort: age 45 ±â€…14 years, BMI 29.7 ±â€…5.7 kg/m2). MAIN OUTCOME MEASURES: Nuclear magnetic resonance profiling of plasma lipids, lipoprotein particle subclasses and their composition. RESULTS: In both cohorts, individuals carrying the PNPLA3-I148M variant had significantly higher liver fat content than noncarriers. In insulin-resistant and homozygous carriers, PNPLA3-I148M exerted a distinct antihyperlipidemic effect with decreased very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) particles and their constituents, and increased high-density lipoprotein particles and their constituents, compared with noncarriers. VLDL particles were smaller and LDL particles larger in PNPLA3-I148M carriers. These changes were geometrically opposite to those due to IR. PNPLA3-I148M did not have a measurable effect in patients with lower IR, and its effect was smaller albeit still significant in the less obese than in the obese cohort. CONCLUSIONS: PNPLA3-I148M confers an antiatherogenic plasma lipid profile particularly in insulin-resistant individuals.

Effect of Laparoscopic Sleeve Gastrectomy vs Roux-en-Y Gastric Bypass on Weight Loss and Quality of Life at 7 Years in Patients With Morbid Obesity: The SLEEVEPASS Randomized Clinical Trial.

Importance: Laparoscopic sleeve gastrectomy (LSG) is currently the predominant bariatric procedure, although long-term weight loss and quality-of-life (QoL) outcomes compared with laparoscopic Roux-en-Y gastric bypass (LRYGB) are lacking. Objective: To determine weight loss equivalence of LSG and LRYGB at 7 years in patients with morbid obesity, with special reference to long-term QoL. Design, Setting, and Participants: The SLEEVE vs byPASS (SLEEVEPASS) multicenter, multisurgeon, open-label, randomized clinical equivalence trial was conducted between March 10, 2008, and June 2, 2010, in Finland. The trial enrolled 240 patients with morbid obesity aged 18 to 60 years who were randomized to undergo either LSG or LRYGB with a 7-year follow-up (last follow-up, September 26, 2017). Analysis was conducted on an intention-to-treat basis. Statistical analysis was performed from June 4, 2018, to November 8, 2019. Interventions: Laparoscopic sleeve gastrectomy (n = 121) or LRYGB (n = 119). Main Outcomes and Measures: The primary end point was percentage excess weight loss (%EWL) at 5 years. Secondary predefined follow-up time points were 7, 10, 15, and 20 years, with included 7-year secondary end points of QoL and morbidity. Disease-specific QoL (DSQoL; Moorehead-Ardelt Quality of Life questionnaire [range of scores, -3 to 3 points, where a higher score indicates better QoL]) and general health-related QoL (HRQoL; 15D questionnaire [0-1 scale for all 15 dimensions, with 1 indicating full health and 0 indicating death]) were measured preoperatively and at 1, 3, 5, and 7 years postoperatively concurrently with weight loss. Results: Of 240 patients (167 women [69.6%]; mean [SD] age, 48.4 [9.4] years; mean [SD] baseline body mass index, 45.9 [6.0]), 182 (75.8%) completed the 7-year follow-up. The mean %EWL was 47% (95% CI, 43%-50%) after LSG and 55% (95% CI, 52%-59%) after LRYGB (difference, 8.7 percentage units [95% CI, 3.5-13.9 percentage units]). The mean (SD) DSQoL total score at 7 years was 0.50 (1.14) after LSG and 0.49 (1.06) after LRYGB (P = .63), and the median HRQoL total score was 0.88 (interquartile range [IQR], 0.78-0.95) after LSG and 0.87 (IQR, 0.78-0.95) after LRYGB (P = .37). Greater weight loss was associated with better DSQoL (r = 0.26; P < .001). At 7 years, mean (SD) DSQoL scores improved significantly compared with baseline (LSG, 0.50 [1.14] vs 0.10 [0.94]; and LRYGB, 0.49 [1.06] vs 0.12 [1.12]; P < .001), unlike median HRQoL scores (LSG, 0.88 [IQR, 0.78-0.95] vs 0.87 [IQR, 0.78-0.90]; and LRYGB, 0.87 [IQR, 0.78-0.92] vs 0.85 [IQR, 0.77-0.91]; P = .07). The overall morbidity rate was 24.0% (29 of 121) for LSG and 28.6% (34 of 119) for LRYGB (P = .42). Conclusions and Relevance: This study found that LSG and LRYGB were not equivalent in %EWL at 7 years. Laparoscopic Roux-en-Y gastric bypass resulted in greater weight loss than LSG, but the difference was not clinically relevant based on the prespecified equivalence margins. There was no difference in long-term QoL between the procedures. Bariatric surgery was associated with significant long-term DSQoL improvement, and greater weight loss was associated with better DSQoL. Trial Registration: ClinicalTrials.gov Identifier: NCT00793143.

The PNPLA3-I148M variant increases polyunsaturated triglycerides in human adipose tissue.

BACKGROUND & AIMS: The I148M variant in PNPLA3 is the major genetic risk factor for non-alcoholic fatty liver disease (NAFLD). The liver is enriched with polyunsaturated triglycerides (PUFA-TGs) in PNPLA3-I148M carriers. Gene expression data indicate that PNPLA3 is liver-specific in humans, but whether it functions in adipose tissue (AT) is unknown. We investigated whether PNPLA3-I148M modifies AT metabolism in human NAFLD. METHODS: Profiling of the AT lipidome and fasting serum non-esterified fatty acid (NEFA) composition was conducted in 125 volunteers (PNPLA3148MM/MI , n = 63; PNPLA3148II , n = 62). AT fatty acid composition was determined in 50 volunteers homozygous for the variant (PNPLA3148MM , n = 25) or lacking the variant (PNPLA3148II , n = 25). Whole-body insulin sensitivity of lipolysis was determined using [2 H5 ]glycerol, and PNPLA3 mRNA and protein levels were measured in subcutaneous AT and liver biopsies in a subset of the volunteers. RESULTS: PUFA-TGs were significantly increased in AT in carriers versus non-carriers of PNPLA3-I148M. The variant did not alter the rate of lipolysis or the composition of fasting serum NEFAs. PNPLA3 mRNA was 33-fold higher in the liver than in AT (P < .0001). In contrast, PNPLA3 protein levels per tissue protein were three-fold higher in AT than the liver (P < .0001) and nine-fold higher when related to whole-body AT and liver tissue masses (P < .0001). CONCLUSIONS: Contrary to previous assumptions, PNPLA3 is highly abundant in AT. PNPLA3-I148M locally remodels AT TGs to become polyunsaturated as it does in the liver, without affecting lipolysis or composition of serum NEFAs. Changes in AT metabolism do not contribute to NAFLD in PNPLA3-I148M carriers.

Hydroxysteroid 17-ß dehydrogenase 13 variant increases phospholipids and protects against fibrosis in nonalcoholic fatty liver disease.

Carriers of the hydroxysteroid 17-ß dehydrogenase 13 (HSD17B13) gene variant (rs72613567:TA) have a reduced risk of NASH and cirrhosis but not steatosis. We determined its effect on liver histology, lipidome, and transcriptome using ultra performance liquid chromatography-mass spectrometry and RNA-seq. In carriers and noncarriers of the gene variant, we also measured pathways of hepatic fatty acids (de novo lipogenesis [DNL] and adipose tissue lipolysis [ATL] using 2H2O and 2H-glycerol) and insulin sensitivity using 3H-glucose and euglycemic-hyperinsulinemic clamp) and plasma cytokines. Carriers and noncarriers had similar age, sex and BMI. Fibrosis was significantly less frequent while phospholipids, but not other lipids, were enriched in the liver in carriers compared with noncarriers. Expression of 274 genes was altered in carriers compared with noncarriers, consisting predominantly of downregulated inflammation-related gene sets. Plasma IL-6 concentrations were lower, but DNL, ATL and hepatic insulin sensitivity were similar between the groups. In conclusion, carriers of the HSD17B13 variant have decreased fibrosis and expression of inflammation-related genes but increased phospholipids in the liver. These changes are not secondary to steatosis, DNL, ATL, or hepatic insulin sensitivity. The increase in phospholipids and decrease in fibrosis are opposite to features of choline-deficient models of liver disease and suggest HSD17B13 as an attractive therapeutic target.

Bile Reflux is a Common Finding in the Gastric Pouch After One Anastomosis Gastric Bypass.

INTRODUCTION: Data on postoperative bile reflux after one anastomosis gastric bypass (OAGB) is lacking. Bile reflux scintigraphy (BRS) has been shown to be a reliable non-invasive tool to assess bile reflux after OAGB. We set out to study bile reflux after OAGB with BRS and endoscopy in a prospective series (RYSA Trial). METHODS: Forty patients (29 women) underwent OAGB between November 2016 and December 2018. Symptoms were reported and upper gastrointestinal endoscopy (UGE) was done preoperatively. Six months after OAGB, bile reflux was assessed in UGE findings and as tracer activity found in gastric tube and esophagus in BRS (follow-up rate 95%). RESULTS: Twenty-six patients (68.4%) had no bile reflux in BRS. Twelve patients (31.6%) had bile reflux in the gastric pouch in BRS and one of them (2.6%) had bile reflux also in the esophagus 6 months postoperatively. Mean bile reflux activity in the gastric pouch was 5.2% (1-21%) of total activity. De novo findings suggestive of bile reflux (esophagitis, stomal ulcer, foveolar inflammation of gastric pouch) were found for 15 patients (39.5%) in postoperative UGE. BRS and UGE findings were significantly associated (P = 0.022). Eight patients experienced de novo reflux symptoms at 6 months, that were significantly associated with BRS and de novo UGE findings postoperatively (P = 0.033 and 0.0005, respectively). CONCLUSION: Postoperative bile reflux in the gastric pouch after OAGB is a common finding in scintigraphy and endoscopy. The long-term effects of bile exposure will be analyzed in future reports after a longer follow-up. TRIAL REGISTRATION: Clinical Trials Identifier NCT02882685.

Performance of imaging studies in patients with suspected appendicitis after stratification with adult appendicitis score.

BACKGROUND: Diagnostic scoring is used to stratify patients with suspected appendicitis into three groups: high, intermediate, and low probability of appendicitis. The stratification can be used for selective imaging to avoid the harms of radiation without compromising diagnostic accuracy. The aim was to study how stratification by Adult Appendicitis Score affects diagnostic performance of imaging studies. METHODS: Analysis of 822 patients who underwent diagnostic imaging for suspected appendicitis was made. Adult Appendicitis Score was used to stratify patients into groups of high, intermediate, and low probability of appendicitis. Diagnostic performance of computed tomography (CT) and ultrasound (US) was compared between these patient groups. RESULTS: After scoring, pre-test probability of appendicitis ranged from 9-16% in low probability group to 75-79% in high probability group in patients who underwent US or CT. Post-test probability of appendicitis after positive CT was 99, 91, and 75% in high probability, intermediate probability and low probability groups, respectively, p < 0.001. After positive US the respective probabilities were 95, 91 and 42%, p < 0.001. CONCLUSION: Diagnostic imaging has limited value in patients with low probability of appendicitis according to Adult Appendicitis Score.

Laparoscopic Surgery or Conservative Treatment for Appendiceal Abscess in Adults? A Randomized Controlled Trial.

OBJECTIVE: We hypothesized that immediate laparoscopic surgery for appendiceal abscess would result in faster recovery than conservative treatment. BACKGROUND: On the basis of the retrospective studies, conservative management of appendiceal abscess is recommended as a first line treatment, but some controversy exists. METHODS: Sixty adult patients diagnosed with appendiceal abscess were randomly assigned to either laparoscopic surgery (n = 30) or conservative treatment (n = 30). Hospital stay, recurrences, additional interventions, and complications within 60 days from randomization were recorded. RESULTS: There was no difference in hospital stay: 4 days (interquartile range: 3-5 days) in the laparoscopy group versus 5 days (3-8) in the conservative group, P = 0.105. Patients in the laparoscopy group had 10% risk for bowel resection and 13% risk for incomplete appendectomy. There were significantly fewer patients with unplanned readmissions in the laparoscopy group: 1 (3%) versus 8 (27%), P = 0.026. Additional interventions were required in 2 (7%) patients in the laparoscopy group (percutaneous drainage) and in 9 (30%) patients in the conservative group (surgery), P = 0.042. Recurrent abscesses and failure to respond to conservative treatment were the main reasons for additional interventions. Open surgery was required in 3 (10%) patients in the laparoscopy group and in 4 (13%) patients in the conservative group. Postoperative complications occurred in 3 patients in laparoscopic group versus 2 patients in the conservative group. The rate of uneventful recovery was 90% in the laparoscopy group versus 50% in the conservative group, P = 0.002. CONCLUSIONS: Laparoscopic surgery in experienced hands is safe and feasible first-line treatment for appendiceal abscess. It is associated with fewer readmissions and fewer additional interventions than conservative treatment with comparable hospital stay.

High admission C-reactive protein level and longer in-hospital delay to surgery are associated with increased risk of complicated appendicitis.

PURPOSE: Debate on the effect of in-hospital delay on the risk of perforation in appendicitis persists, and the results from previous studies are controversial. The aims of this study were to present the effect of in-hospital delay on the risk of perforation in appendicitis and to assess the utility of C-reactive protein (CRP) measurement in detecting the patients with complicated appendicitis. METHODS: Prospectively collected data of 389 adult patients who underwent surgery for acute appendicitis were analyzed in order to find the most accurate method for recognizing the pre-hospital perforations. The effect of in-hospital delay on the further risk of perforation in patients with not yet perforated acute appendicitis was then analyzed. RESULTS: Out of 389 patients with appendicitis, 91 patients (23.4 %) had complicated appendicitis, 23 with abscess, and 68 with free perforation. Admission CRP level of 99 mg/l or higher was 90.3 % specific for complicated appendicitis. In patients with admission CRP less than 99 mg/l, the incidence of perforation doubled from 9.5 to 18.9 % when the in-hospital delay increased from less than 6 h to more than 12 h. CONCLUSIONS: Complicated appendicitis can be identified with a high CRP level on admission. Delaying surgery can increase the risk of perforation.

A new adult appendicitis score improves diagnostic accuracy of acute appendicitis--a prospective study.

BACKGROUND: The aim of the study was to construct a new scoring system for more accurate diagnostics of acute appendicitis. Applying the new score into clinical practice could reduce the need of potentially harmful diagnostic imaging. METHODS: This prospective study enrolled 829 adults presenting with clinical suspicion of appendicitis, including 392 (47%) patients with appendicitis. The collected data included clinical findings and symptoms together with laboratory tests (white cell count, neutrophil count and C-reactive protein), and the timing of the onset of symptoms. The score was constructed by logistic regression analysis using multiple imputations for missing values. Performance of the constructed score in patients with complete data (n = 725) was compared with Alvarado score and Appendicitis inflammatory response score. RESULTS: 343 (47%) of patients with complete data had appendicitis. 199 (58%) patients with appendicitis had score value at least 16 and were classified as high probability group with 93% specificity.Patients with score below 11 were classified as low probability of appendicitis. Only 4% of patients with appendicitis had a score below 11, and none of them had complicated appendicitis. In contrast, 207 (54%) of non-appendicitis patients had score below 11. There were no cases with complicated appendicitis in the low probability group. The area under ROC curve was significantly larger with the new score 0.882 (95% CI 0.858-0.906) compared with AUC of Alvarado score 0.790 (0.758-0.823) and Appendicitis inflammatory response score 0.810 (0.779-0.840). CONCLUSIONS: The new diagnostic score is fast and accurate in categorizing patients with suspected appendicitis, and roughly halves the need of diagnostic imaging.