Risk factors for anastomotic leakage in colonic procedures within an ERAS-protocol. A retrospective cohort study from the Swedish part of the international ERAS-database.

BACKGROUND: Research on anastomotic leakage (AL) in colonic procedures within an Enhanced Recovery After Surgery (ERAS) protocol has not yet been conducted. The aim of this study was to identify risk factors for AL after colonic surgery. METHODS: The study included all consecutively recorded patients operated with colonic resection surgery in the Swedish part of the international ERAS® Interactive Audit System (EIAS) between September 2009 and June 2022. The cohort was analyzed and evaluated regarding risk factors for AL. RESULTS: Altogether 10,632 patients were included, 10,219 were without AL and 413 (3.9%) were with AL. After adjusted analysis, male sex (4.6% AL), OR: 1.49; 95% CI (1.16-1.90), obesity (4.8% AL), OR: 1.62; 95% CI (1.18-2.24), previous surgery (4.4% AL), OR: 1.45; 95% CI (1.14-1.86), open surgery (4.4% AL), OR: 1.36; 95% CI (1.02-1.83), anastomosis between small bowel and rectum (13.1% AL), OR: 3.97; 95% CI (2.23-7.10), stapled anastomosis (5.3% AL), OR: 2.46; 95% CI (1.79-3.38), inhalation anesthesia (4.2% AL), OR: 1.80; 95% CI (1.26-2.57), and conversion to open surgery (5.5% AL), OR 1.49; 95% CI (1.02-2.19) were significant risk factors for AL. Although pre and intraoperative compliance to the ERAS-protocol was similar, excess of fluids day 0 was an independent predictor for AL. CONCLUSION: Male sex, obesity, previous surgery, open surgery, stapled anastomotic technique, anastomosis between small bowel and rectum, inhalation anesthesia, conversion to open surgery, and among ERAS interventions, excess of fluids day 0, were significant risk factors for AL.

Plasma bile acids in association with Crohn's disease.

BACKGROUND: In addition to facilitating lipid digestions, bile acids (BA) are signalling molecules acting on receptors on immune cells and along the gastrointestinal (GI) tract. The aim of this study was to assess if altered bile acid profiles in plasma are associated with Crohn's disease (CD). METHOD: This cross-sectional study included individuals (aged ≥18 years) referred for colonoscopy at a tertiary centre in Stockholm between 2016 and 2019. All participants received bowel preparation, completed a lifestyle questionnaire and provided blood samples for analysis. During colonoscopy, severity of disease was graded, and biopsies were taken from colonic mucosa. In the current substudy, 88 individuals with CD and 88 age-matched controls were selected for analysis of BA in plasma with ultra performance liquid chromatography (UPLC). Linear regression models were then used to compare mean bile acid concentrations and concentration ratios between CD and controls. RESULTS: Individuals with CD had lower plasma concentrations of the majority of secondary BA compared to controls, in total CD/CC ratio 0.60 (SE 0.12), p = 0.001. The most prominent observations were lower levels of deoxycolic acid derivates and lithocolic acid derivates among participants with CD. Moreover, plasma concentration for secondary BA among participants with active CD was significantly lower compared to those with CD in remission, CD active/CD remission ratio 0.65 (SE 0.11), p < 0.002. CONCLUSION: Crohn's disease may be associated with altered plasma bile acid composition. The significance of colonic bacterial diversity in this context needs to be investigated in further studies.

It is known that Crohn's disease is associated with dysbiosis in the gut microbiota and that primary bile acids are transformed to secondary bile acids by bacterial enzymes in the gut before reabsorbed and transported back to the liver.In this cross-sectional study, Crohn's disease was associated with lower concentrations of secondary bile acids in blood plasmaThe findings should encourage further studies the role of the gut microbiome and bile acid metabolism in development of Crohn's disease and bile acid profile as a biomarker for bowel inflammation.

Evaluation of plasma Short chain fatty acid levels as markers for Inflammatory bowel disease.

BACKGROUND: Specific variations of short chain fatty acids in fecal samples have been shown for patients with inflammatory bowel disease. The aim of this study was to assess if Crohn's disease and ulcerative colitis are associated with altered concentrations of short chain fatty acids also in blood plasma. METHOD: Between 2016-2019, Swedish adults referred to a tertiary center for colonoscopy were asked to participate in a cross-sectional study. Individuals with Crohn's disease or ulcerative colitis as well as individuals with no findings on the colonoscopy (defined as clean colon) were included in the study. Data on colonoscopy findings, blood samples (including haemoglobin, C-reactive protein and short chain fatty acid analysis) as well as a validated lifestyle questionnaire including 277 questions were collected from all participants. Linear regression was used to compare mean concentrations of short chain fatty acids between Crohn's disease, ulcerative colitis and clean colon. RESULTS: The cohort consisted of 132 individuals with Crohn's disease, 119 with ulcerative colitis and 205 with clean colon. In the crude model, succinic acid was significantly lower (p < 0.05) among patients with Crohn's disease (mean 3.00 µM SE 0.10) and ulcerative colitis (mean 3.13 µM SE 0.10) in comparison to clean colon (mean 3.41 µM SE 0.08), however when adjusting for sex, age and diet the results did not remain statistically significant. No differences in plasma concentration of the other measured short chain fatty acids were detected. CONCLUSION: Crohn's disease and ulcerative colitis are not associated with altered short chain fatty acid concentrations in plasma. Further research is needed to confirm or refute our findings.

In this cross-sectional study including individuals with inflammatory bowel disease and healthy subjects we found no association between Crohn's disease and ulcerative colitis and short chain fatty acid concentrations in plasma.

Effect of age on quality of life after gastric bypass: data from the Scandinavian Obesity Surgery Registry.

BACKGROUND: Whether patients aged 60 years or older should be recommended bariatric surgery is still controversial. OBJECTIVE: To assess the effect of age on health-related quality of life (QoL) over time after gastric bypass. SETTING: Data from the Swedish national registry for bariatric surgery. METHODS: Data of 57,215 patients undergoing gastric bypass were retrieved from the Scandinavian Obesity Surgery Register with a follow-up rate at 1,2, and 5 years at 89%, 69%, and 59%, respectively. Patients were divided into 5-years age intervals. Odds ratios for the relative mean changes in QoL were compared by logistic regression. RESULTS: Preoperatively, patients aged 60 years or older scored better on mental aspects (Mental Component Summary score, MCS) of RAND-36 (Short Form Health Survey (higher values better)) as well as OP (Obesity related Problem scale (lower values better)) better than the entire cohort of patients (MCS: mean [95% CI], 46.2 [45.5-46.9] versus 43.5 [43.4-43.7], respectively; OP: mean [95% CI], 55.3 [54.0-56.6] versus 64.1 [63.9-64.4], respectively), whereas the Physical Component Summary (PCS) scores of patients aged 60 years or older were lower (mean [95% CI], 32.3 [31.7-32.8] for the ≥60-yr cohort versus 36.4 [36.2-36.5] for the entire cohort; P < .001 for all). In all age groups, MCS was improved at 1 and 2 years but decreased to baseline at 5 years. The postoperative improvements in PCS and OP were sustained in all age groups. Although the relative increases for PCS and OP in patients aged ≥60 years were somewhat lower compared with the entire cohort at 5 years, the values were well above baseline levels (mean [95% CI], 41.0 [40.0-42.0] versus 32.3 [31.7-32.8] and 22.2 [20.3-24.0] versus 55.3 [54.0-56.6], respectively; P < .001). CONCLUSION: Mental QoL is transiently improved after bariatric surgery without marked differences between age groups. However, patients aged ≥60 years report pronounced and sustained improvements in physical and obesity-specific QoL 5 years postoperatively. These observations support previous studies that older patients should not be denied bariatric surgery from a risk-benefit perspective, solely based on age.

Delivery mode and risk of gastrointestinal disease in the offspring.

INTRODUCTION: The global increase of individuals born by cesarean section with reported levels up to 20% of all deliveries, makes it important to study cesarean section and possible associations that can increase risk of subsequent diseases in children. The aim of the study was to evaluate if cesarean section is associated with increased risk of gastrointestinal disease later in life in a large population-based cohort. MATERIAL AND METHODS: In this national population-based cohort study including all full-term individuals registered in the Medical Birth Register in Sweden between 1990 and 2000, type of delivery (exposure) was collected from the Medical Birth Register. The study population was followed until 2017 with regards to the outcomes: inflammatory bowel disease (Crohn's disease or ulcerative colitis), appendicitis, cholecystitis, or diverticulitis registered in the Swedish National Patient Register. Cox proportional-hazards models compared disease-free survival time between exposed and unexposed. RESULTS: The final study population consisted of 1 102 468 individuals of whom 11.6% were delivered by cesarean section and 88.4% were vaginally delivered. In univariate analysis, cesarean section was associated with Crohn's disease (hazard ratio [HR] 1.13, 95% confidence interval [CI] 1.02-1.25), diverticulosis (HR 1.57, 95% CI 1.13-2.18), and cholecystitis (HR 1.16, 95% CI 1.05-1.28). However, the increased risk only remained for Crohn's disease after adjustment for confounders (HR 1.14, 95% CI 1.02-1.27). No associations between delivery mode and appendicitis, ulcerative colitis, cholecystitis, or diverticulosis were found in the multivariate analysis. CONCLUSIONS: Cesarean section is associated with Crohn's disease later in life, but no other association between delivery mode and gastrointestinal disorders later in life could be found.

Guidelines for Perioperative Care in Elective Abdominal and Pelvic Surgery at Primary and Secondary Hospitals in Low-Middle-Income Countries (LMIC's): Enhanced Recovery After Surgery (ERAS) Society Recommendation.

BACKGROUND: This is the first Enhanced Recovery After Surgery (ERAS®) Society guideline for primary and secondary hospitals in low-middle-income countries (LMIC's) for elective abdominal and gynecologic care. METHODS: The ERAS LMIC Guidelines group was established by the ERAS® Society in collaboration with different representatives of perioperative care from LMIC's. The group consisted of seven members from the ERAS® Society and eight members from LMIC's. An updated systematic literature search and evaluation of evidence from previous ERAS® guidelines was performed by the leading authors of the Colorectal (2018) and Gynecologic (2019) surgery guidelines (Gustafsson et al in World J Surg 43:6592-695, Nelson et al in Int J Gynecol Cancer 29(4):651-668). Meta-analyses randomized controlled trials (RCTs), prospective and retrospective cohort studies from both HIC's and LMIC's were considered for each perioperative item. The members in the LMIC group then applied the current evidence and adapted the recommendations for each intervention as well as identifying possible new items relevant to LMIC's. The Grading of Recommendations, Assessment, Development and Evaluation system (GRADE) methodology was used to determine the quality of the published evidence. The strength of the recommendations was based on importance of the problem, quality of evidence, balance between desirable and undesirable effects, acceptability to key stakeholders, cost of implementation and specifically the feasibility of implementing in LMIC's and determined through discussions and consensus. RESULTS: In addition to previously described ERAS® Society interventions, the following items were included, revised or discussed: the Surgical Safety Checklist (SSC), preoperative routine human immunodeficiency virus (HIV) testing in countries with a high prevalence of HIV/AIDS (CD4 and viral load for those patients that are HIV positive), delirium screening and prevention, COVID 19 screening, VTE prophylaxis, immuno-nutrition, prehabilitation, minimally invasive surgery (MIS) and a standardized postoperative monitoring guideline. CONCLUSIONS: These guidelines are seen as a starting point to address the urgent need to improve perioperative care and to effect data-driven, evidence-based care in LMIC's.

Childhood appendicitis and future risk of inflammatory bowel disease - A nationwide cohort study in Sweden 1973-2017.

AIM: The aim of this study was to investigate the association between juvenile appendicitis, treated conservatively or with appendectomy, and adult risk of inflammatory bowel disease (IBD), either ulcerative colitis (UC) or Crohn's disease (CD). We used nationwide population data from more than 100,000 individuals followed for over four decades. METHOD: All Swedish patients discharged with a diagnosis of appendicitis before the age of 16 years between 1973 to 1996 were identified. Everyone diagnosed with appendicitis was matched to an individual in the general population without a history of juvenile appendicitis (unexposed) of similar age, sex and region of residence. The study population was retrospectively followed until 2017 for any development of UC or CD. Cox proportional-hazards models compared disease-free survival time between exposed and unexposed individuals, also analysing the impact of treatment (conservative treatment versus appendectomy). RESULTS: The final cohort consisted of 52,391 individuals exposed to appendicitis (1,674,629 person years) and 51,415 unexposed individuals (1,638,888 person years). Childhood appendicitis with appendectomy was associated with a significantly lower risk of adult IBD [adjusted hazard ratio (aHR) 0.48 (0.42-0.55)], UC [aHR 0.30 (0.25-0.36)] and CD [aHR 0.82 (0.68-0.97)]. Those treated conservatively had a lower risk of adult UC [aHR 0.29 (0.12-0.69)] but not CD [aHR 1.12 (0.61-2.06)] compared with unexposed individuals. CONCLUSION: Juvenile appendicitis treated with appendectomy was associated with a decreased risk of adult IBD, both UC and CD. Those treated conservatively instead of with surgery had a lower risk of UC only. Our findings warrant more research on the role of the appendix and gut microbiota in the pathogenesis of IBD.

Learning by doing: an observational study of the learning curve for ultrasonic fundus-first dissection in elective cholecystectomy.

BACKGROUND: Surgical safety and patient-related outcomes are important considerations when introducing new surgical techniques. Studies about the learning curves for different surgical procedures are sparse. The aim of this observational study was to evaluate the learning curve for ultrasonic fundus-first (FF) dissection in elective laparoscopic cholecystectomy (LC). METHODS: The study was conducted at eight hospitals in Sweden between 2017 and 2019. The primary endpoint was dissection time, with secondary endpoints being intra- and postoperative complication rates and the surgeon's self-assessed performance level. Participating surgeons (n = 16) were residents or specialists who performed LC individually but who had no previous experience in ultrasonic FF dissection. Each surgeon performed fifteen procedures. Video recordings from five of the procedures were analysed by two external surgeons. Patient characteristics and data on complications were retrieved from the Swedish Registry of Gallstone Surgery and Endoscopic Retrograde Cholangiopancreatography (GallRiks). RESULTS: Dissection time decreased as experience increased (p = 0.001). Surgeons with limited experience showed more rapid progress. The overall complication rate was 14 (5.8%), including 3 (1.3%) potentially technique-related complications. Video assessment scores showed no correlation with the number of procedures performed. The self-assessed performance level was rated lower when the operation was more complicated (p < 0.001). CONCLUSIONS: Our results show that dissection time decreased with increasing experience. Most surgeons identified both favourable and unfavourable aspects of the ultrasonic FF technique. The ultrasonic device is considered well suited for gallbladder surgery, but most participating surgeons preferred to dissect the gallbladder the traditional way, beginning in the triangle of Calot. Nevertheless, LC with ultrasonic FF dissection can be considered easy to learn with a low complication rate during the initial learning curve, for both residents and specialists.

The risk of inflammatory bowel disease after bariatric surgery.

BACKGROUND: The association between bariatric surgery and new onset of inflammatory bowel disease has so far only been sparsely studied and with conflicting results. OBJECTIVES: To investigate the association between bariatric surgery and inflammatory bowel disease in a large population-based cohort. SETTING: Nationwide in Sweden. METHODS: This population-based retrospective cohort study included Swedish individuals registered in the Scandinavian Obesity Surgery Registry who underwent primary Roux-en-Y gastric bypass or sleeve gastrectomy during 2007-2018. Ten control individuals from the general population were matched according to age, sex, and region of residence at time of exposure. The study population was followed until 2019 with regard to the development of inflammatory bowel disease. Cox proportional hazards models were used to compare disease-free survival time between subgroups and control individuals for each outcome. RESULTS: The final cohort consisted of 64,188 exposed individuals with a total follow-up of 346,860 person-years and 634,530 controls with total follow-up of 3,444,186 person-years. Individuals who underwent Roux-en-Y-gastric bypass had an increased risk of later development of Crohn's disease (hazard ratio [HR] 1.8, 95% CI 1.5-2.2) and unclassified inflammatory bowel disease (HR 2.7, 95% CI 2.0-3.7) but not ulcerative colitis (HR .9, 95% CI .8-1.1) compared with control individuals, whereas individuals who underwent sleeve gastrectomy had an increased risk of ulcerative colitis (HR 1.8, 95% CI 1.1-3.1) but not Crohn's disease (HR .8, 95% CI .3-2.1) and unclassified inflammatory bowel disease (HR 2.5, 95% CI .8-7.8). CONCLUSIONS: Roux-en-Y gastric bypass was associated with increased risk of Crohn's disease and unclassified inflammatory bowel disease, whereas sleeve gastrectomy was associated with increased risk of ulcerative colitis only.

Guidelines for Perioperative Care in Bariatric Surgery: Enhanced Recovery After Surgery (ERAS) Society Recommendations: A 2021 Update.

BACKGROUND: This is the second updated Enhanced Recovery After Surgery (ERAS®) Society guideline, presenting a consensus for optimal perioperative care in bariatric surgery and providing recommendations for each ERAS item within the ERAS® protocol. METHODS: A principal literature search was performed utilizing the Pubmed, EMBASE, Cochrane databases and ClinicalTrials.gov through December 2020, with particular attention paid to meta-analyses, randomized controlled trials and large prospective cohort studies. Selected studies were examined, reviewed and graded according to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. After critical appraisal of these studies, the group of authors reached consensus regarding recommendations. RESULTS: The quality of evidence for many ERAS interventions remains relatively low in a bariatric setting and evidence-based practices may need to be extrapolated from other surgeries. CONCLUSION: A comprehensive, updated evidence-based consensus was reached and is presented in this review by the ERAS® Society.

Impact of Age on Obesity-related Comorbidity After Gastric Bypass: A Cohort Study From the Scandinavian Obesity Surgery Registry (SOReg).

OBJECTIVE: To evaluate the resolution of obesity-related comorbidities after gastric bypass in relation to age. SUMMARY BACKGROUND DATA: Previous studies have shown that age >60 years is associated with a significant, but small, increased risk of complications after gastric bypass. The effect in terms of improvement of obesity-related comorbidities in this group of patients is not studied. METHODS: Data on 57,215 patients operated with primary gastric bypass between May 2007 and December 2018 was extracted from the Scandinavian Obesity Surgery Registry. Odds ratio and 95% confidence interval for resolution of comorbidities in 5-years age groups at 1, 2, and 5 years postoperatively was calculated by logistic regression with the entire cohort of patients as reference. Resolution was defined as no longer in need for pharmacological (or continuous positive airway pressure) treatment. RESULTS: Follow-up rates in all eligible patients were 89%, 69%, and 59% at 1, 2, and 5 years, respectively, and 64% in patients >60 years at 5 years. At baseline, the prevalence of most comorbidities was higher in patients above 60 years. In this group of patients, the preoperative prevalence of diabetes, hypertension, dyslipidemia and obstructive sleep apnea syndrome was reduced at 5years by 45%, 10%, 24%, and 62%, respectively. Compared to all patients, the odds ratio (95% confidence interval) for resolution of these comorbidities in patients above 60 years at five years were 0.70 (0.57-0.86) 0.45 (0.37-0.53), 0.80 (0.63-1.01), and 0.54 (0.40-0.72). CONCLUSIONS: Although to somewhat lower rates compared to younger patients, marked and sustained improvements in obesity-related comorbidities are seen after gastric bypass in patients >60 years. This, together with the finding that bariatric surgery is safe in this group of patients, suggests that age should not be considered an exclusion criterion by itself.

Short-term outcome in robotic vs laparoscopic and open rectal tumor surgery within an ERAS protocol: a retrospective cohort study from the Swedish ERAS database.

BACKGROUND: Advantages of robotic technique over laparoscopic technique in rectal tumor surgery have yet to be proven. Large multicenter, register-based cohort studies within an optimized perioperative care protocol are lacking. The aim of this retrospective cohort study was to compare short-term outcomes in robotic, laparoscopic and open rectal tumor resections, while also determining compliance to the enhanced recovery after surgery (ERAS)®Society Guidelines. METHODS: All patients scheduled for rectal tumor resection and consecutively recorded in the Swedish part of the international ERAS® Interactive Audit System between January 1, 2010 to February 27, 2020, were included (N = 3125). Primary outcomes were postoperative complications and length of stay (LOS) and secondary outcomes compliance to the ERAS protocol, conversion to open surgery, symptoms delaying discharge and reoperations. Uni- and multivariate comparisons were used. RESULTS: Robotic surgery (N = 827) had a similar rate of postoperative complications (Clavien-Dindo grades 1-5), 35.9% compared to open surgery (N = 1429) 40.9% (OR 1.15, 95% CI (0.93, 1.41)) and laparoscopic surgery (N = 869) 31.2% (OR 0.88, 95% CI (0.71, 1.08)). LOS was longer in the open group, median 9 days (IRR 1.35, 95% CI (1.27, 1.44)) and laparoscopic group, 7 days (IRR 1.14, 95% CI (1.07, 1.21)) compared to the robotic group, 6 days. Pre- and intraoperative compliance to the ERAS protocol were similar between groups. CONCLUSIONS: In this multicenter cohort study, robotic surgery was associated with shorter LOS compared to both laparoscopic and open surgery and had lower conversion rates vs laparoscopic surgery. The rate of complications was similar between groups.

Validity of Routinely Collected Swedish Data in the International Enhanced Recovery After Surgery (ERAS) Database.

BACKGROUND: This study aims to assess patient coverage, validity and data quality in the Swedish part of the International Enhanced Recovery After Surgery (ERAS) Interactive Audit System (EIAS). METHOD: All Swedish ERAS centers that recorded colorectal surgery data in EIAS between January 1, 2017, and December 31, 2017, were included (N = 12). Information registered in EIAS was compared with data from electronic medical records at each hospital to assess the overall coverage of EIAS. Twenty random-selected patients from each of the contributing centers were assessed for accuracy for a set of clinically relevant variables. All patients admitted to the contributing centers were included for the assessment of rate of missing on a selection of key clinical variables. RESULTS: Eight hospitals provided complete information for the evaluation, while four hospitals only allowed assessment of coverage and missing data. The eight hospitals had an overall coverage of 98.8% in EIAS (n = 1301) and the four 86.7% (n = 811). The average agreement for the assessed postoperative outcome variables was 96.5%. The accuracy was excellent for 'length of hospital stay,' 'reoperation,' and 'any complications,' but lower for other types of complications. Only a few variables had more than 5% missing data, and missingness was associated with hospital type and size. CONCLUSION: This validation of the Swedish part of the international ERAS database suggests high patient coverage in EIAS and high agreement and limited missingness in clinically relevant variables. This validation approach or a modified version can be used for continued validation of the International ERAS database.

Risk Factors for Anastomotic Leakage in Patients with Rectal Tumors Undergoing Anterior Resection within an ERAS Protocol: Results from the Swedish ERAS Database.

BACKGROUND: Research on risk factors for anastomotic leakage (AL) alone within an Enhanced Recovery After Surgery (ERAS) protocol has not yet been conducted. The aim of this study was to identify risk factors for AL and study short-term outcome after AL in patients operated with anterior resection (AR). METHODS: All prospectively and consecutively recorded patients operated with AR in the Swedish part of the international ERAS® Interactive Audit System (EIAS) between January 2010 and February 2020 were included. The cohort was evaluated regarding risk factors for AL and short-term outcomes, including uni- and multivariate analysis. Pre-, intra- and postoperative compliance to ERAS®Society guidelines was calculated and evaluated. RESULTS: Altogether 1900 patients were included, 155 (8.2%) with AL and 1745 without AL. Male gender, obesity, peritoneal contamination, year of surgery 2016-2020, duration of primary surgery and age remained significant predictors for AL in multivariate analysis. There was no significant difference in overall pre- and intraoperative compliance to ERAS®Society guidelines between groups. Only preadmission patient education remained as a significant ERAS variable associated with less AL. AL was associated with longer length of stay (LOS), higher morbidity rate and higher rate of reoperations. CONCLUSION: Male gender, obesity, peritoneal contamination, duration of surgery, surgery later in study period, age and preadmission patient education were associated with AL in patients operated on with AR. Overall pre- and intraoperative compliance to the ERAS protocol was high in both groups and not associated with AL.

Childhood appendectomy and adult mental disorders: A population-based cohort study.

BACKGROUND: Recent studies suggest that disruption of the colonic microbiota homeostasis is associated with low-grade systemic inflammation and mental disorders. The cecal appendix may influence the homeostasis of the colonic microbiota. In this large population-based study, we investigated whether early removal of the appendix is associated with an increased risk of mental disorders later in life. MATERIALS AND METHODS: All Swedish individuals born between 1973 and 1992 (N = 1,937,488) were included and followed prospectively until December 31, 2016 for any psychiatric International Classification of Disease diagnosis from age 14 or later in life. The main exposure was defined as having a history of appendectomy before age 14 (N = 44,259); the second exposure, appendicitis before age 14 but without appendectomy (N = 1,542), and the third exposure studied was a history of hernia surgery before age 14 (N = 35,523). Control groups for each respective exposure were all unexposed individuals in the study population. RESULTS: Individuals exposed to appendectomy before age 14 had a 19% increased risk of depressive disorder (adjusted hazard ratio [aHR] = 1.19; 95% confidence interval [95% CI]: 1.15-1.23), 27% increased risk of bipolar affective disorder (aHR = 1.27; 95% CI: 1.17-1.37), and a 20% increased risk of an anxiety disorder (aHR = 1.20; 95% CI: 1.16-1.23) compared to individuals unexposed to childhood appendectomy. We found no association between appendectomy and increased risk of obsessive-compulsive disorder and schizophrenia and there was no association between appendicitis without appendectomy and mental disorders. The association between childhood hernia surgery and mental disorders later in life was small but significant. CONCLUSION: Childhood appendectomy, but not appendicitis without appendectomy, was associated with a significantly increased risk of mood and anxiety disorders in adulthood.

Ezetimibe in Combination With Simvastatin Reduces Remnant Cholesterol Without Affecting Biliary Lipid Concentrations in Gallstone Patients.

Background In randomized trials (SHARP [Study of Heart and Renal Protection], IMPROVE -IT [Improved Reduction of Outcomes: Vytorin Efficacy International Trial]), combination of statin and ezetimibe resulted in additional reduction of cardiovascular events. The reduction was greater in patients with type 2 diabetes mellitus (T2 DM ), where elevated remnant cholesterol and high cardiovascular disease risk is characteristic. To evaluate possible causes behind these results, 40 patients eligible for cholecystectomy, randomized to simvastatin, ezetimibe, combined treatment (simvastatin+ezetimibe), or placebo treatment during 4 weeks before surgery, were studied. Methods and Results Fasting blood samples were taken before treatment start and at the end (just before surgery). Bile samples and liver biopsies were collected during surgery. Hepatic gene expression levels were assessed with qPCR . Lipoprotein, apolipoprotein levels, and content of cholesterol, cholesteryl ester, and triglycerides were measured after lipoprotein fractionation. Lipoprotein subclasses were analyzed by nuclear magnetic resonance. Apolipoprotein affinity for human arterial proteoglycans ( PG ) was measured. Biomarkers of cholesterol biosynthesis and intestinal absorption and bile lipid composition were analyzed using mass spectrometry. Combined treatment caused a statistically significant decrease in plasma remnant particles and apolipoprotein B (ApoB)/lipoprotein content of cholesterol, cholesteryl esters, and triglycerides. All treatments reduced ApoB-lipoprotein PG binding. Simvastatin and combined treatment modified the composition of lipoproteins. Changes in biomarkers of cholesterol synthesis and absorption and bile acid synthesis were as expected. No adverse events were found. Conclusions Combined treatment caused atheroprotective changes on ApoB-lipoproteins, remnant particles, bile components, and in ApoB-lipoprotein affinity for arterial PG . These effects might explain the decrease of cardiovascular events seen in the SHARP and IMPROVE - IT trials. Clinical Trial Registration URL : www.clinicaltrialsregister.eu . Unique identifier: 2006-004839-30).