Ernica Clinical Consensus Statements on Total Colonic and Intestinal Aganglionosis.

BACKGROUND: Hirschsprung disease is a congenital intestinal motility disorder characterized by an absence of enteric ganglion cells. Total colonic aganglionosis and near total or total intestinal aganglionosis, defined as absence of ganglion cells in the entire colon and with variable length of small bowel involved, are life-threatening conditions which affect less than 10 % of all patients with Hirschsprung disease. The aim of this project was to develop clinical consensus statements within ERNICA, the European Reference Network for rare congenital digestive diseases, on four major topics: Surgical treatment of total colonic aganglionosis, surgical treatment of total intestinal aganglionosis, management of poor bowel function in total colonic and/or intestinal aganglionosis and long-term management in total colonic and or intestinal aganglionosis. METHODS: A multidisciplinary panel of representatives from ERNICA centers was invited to participate. Literature was searched, using specified search terms, in Medline (ALL), Embase and Google Scholar. Abstracts were screened and full text publications were selected. The panel was divided in four groups that extracted data from the full text publications and suggested draft statements for each of the major topics. A modified Delphi process was used to refine and agree on the statements. RESULTS: The consensus statement was conducted by a multidisciplinary panel of 24 participants from 10 European countries, 45 statements reached consensus after 3 Delphi-rounds. The availability of high-quality clinical evidence was limited, and most statements were based on expert opinion. Another 25 statements did not reach consensus. CONCLUSIONS: Total colonic and total intestinal aganglionosis are rare variants of Hirschsprung disease, with very limited availability of high-quality clinical evidence. This consensus statement provides statements on the surgical treatment, management of poor bowel function and long-term management for these rare patients. The expert panel agreed that patients benefit from multidisciplinary and personalized care, preferably in an expert center. TYPE OF STUDY: Clinical consensus statement. LEVEL OF EVIDENCE: 3a.

Validation of the Clavien-Madadi Classification for Unexpected Events in Pediatric Surgery: A Collaborative ERNICA Project.

BACKGROUND: The Clavien-Madadi classification is a novel instrument for the assessment and grading of unexpected events in pediatric surgery, based on the Clavien-Dindo classification. The system has been adjusted to better fit the pediatric population in a prospective single-center study. There is a need now to validate the Clavien-Madadi classification within an international expert network. METHODS: A pediatric surgical working group created 19 case scenarios with unexpected events in a multi-staged process. Those were circulated within the European Reference Network of Inherited and Congenital Anomalies (ERNICA) and surgeons were instructed to rate the scenarios according to the Clavien-Madadi vs. Clavien-Dindo classification. RESULTS: 59 surgeons from 12 European countries completed the questionnaire. Based on ratings of the case scenarios, the Clavien-Madadi classification showed significantly superior agreement rates of the respondents (85.9% vs 76.2%; p < 0.05) and was less frequently considered inaccurate for rating the pediatric population compared to Clavien-Dindo (2.1% vs 11.1%; p = 0.05). Fleiss' kappa analysis showed slightly higher strength of agreement using the Clavien-Madadi classification (0.74 vs 0.69). Additionally, intraclass correlation coefficient was slightly higher for the Clavien-Madadi compared to the Clavien-Dindo classification (ICCjust 0.93 vs 0.89; ICCunjust 0.93 vs 0.89). More pediatric surgeons preferred the Clavien-Madadi classification for the case scenarios (43.0% vs 11.8%; p = 0.002) and advantages of the Clavien-Madadi were confirmed by 81.4% of the surgeons. CONCLUSION: The Clavien-Madadi classification is an accurate and reliable instrument for the grading of unexpected events in pediatric surgery. We therefore recommend its application in clinical and academic pediatric surgical practice. LEVEL OF EVIDENCE: III.

Functional and Health-Related Quality of Life Outcomes into Adulthood for Females Surgically Treated for Anorectal Malformation.

BACKGROUND: Controlled outcomes into adulthood for females with anorectal malformation (ARM) are still scantily studied. The primary aim was to investigate bowel function, bladder function and health-related quality of life (HRQoL) in females operated for ARM. METHODS: A cross-sectional questionnaire-based observational study was performed including females treated for ARM at our institution between 1994 and 2017. The bowel function was assessed with bowel function score (BFS) and urinary tract function with lower urinary tract symptoms (LUTS) questionnaires. HRQoL was investigated with validated age-dependent questionnaires. Patient characteristics were retrospectively retrieved from the medical records and descriptive statistics were used for analysis. HRQoL outcomes were compared with normative data whilst bowel and bladder function outcomes were compared to age-matched female controls. RESULTS: Forty-four (41.5 %) of 106 females responded to the questionnaires. Ten of 29 patients (34.5 %) aged 4-17 years and 4 of 14 patients (28.6%) aged ≥18 years, reported a well-preserved bowel function (BFS≥17). Constipation issues decreased with age. BFS was similar in patients with perineal and vestibular fistulas. Thirty-six (83.7%) of the patients had at least one LUTS. No adult patients had issues with involuntary urinary leakage. Adults scored significantly (p = 0.004) lower than normative data regarding HRQoL, while children and adolescents scored comparably to norm data. CONCLUSIONS: Only 28.6 % of the adult patients reported a well-preserved bowel function, similar to the proportion reported by children 4-17 years of age. Adult patients appear to have a diminished HRQoL, however the correlation with BFS was weak. LEVEL OF EVIDENCE: III.

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.

Bridging the Gap: A Systematic Review on Reporting Baseline Characteristics, Process, and Outcome Parameters in Rectosigmoid Hirschsprung's Disease.

The variation in standardized, well-defined parameters in Hirschsprung's disease (HSCR) research hinders overarching comparisons and complicates evaluations of care quality across healthcare settings. This review addresses the significant variability observed in these parameters as reported in recent publications. The goal is to compile a list of commonly described baseline characteristics, process and outcome measures, and to investigate disparities in their utilization and definitions. A systematic review of literature on the primary care process for HSCR was performed according to PRISMA guidelines. Relevant literature published between 2015 and 2021 was obtained by combining the search term "Hirschsprung's disease" with "treatment outcome," "complications," "mortality," "morbidity," and "survival" in Medline, Embase, and the Cochrane Library. We extracted study characteristics, reported process and outcome parameters, and patient and disease characteristics. We extracted 1,026 parameters from 200 publications and categorized these into patient characteristics (n = 226), treatment and care process characteristics (n = 199), and outcomes (n = 601). A total of 116 parameters were reported in more than 5% of publications. The most frequently reported characteristics were sex (88%), age at the time of surgery (66%), postoperative Hirschsprung-associated enterocolitis (64%), type of repair (57%), fecal incontinence (54%), and extent of aganglionosis (51%). This review underscores the pronounced variation in reported parameters within HSCR studies, highlighting the necessity for consistent, well-defined measures and reporting systems to foster improved data interpretability. Moreover, it advocates for the use of these findings in the development of a Core Indicator Set, complementing the recently developed Core Outcome Set. This will facilitate quality assessments across pediatric surgical centers throughout Europe.

Fertility in patients with Hirschsprung's disease: population-based cohort study.

BACKGROUND: The aim of this study was to assess fertility in patients treated for Hirschsprung's disease. METHODS: This was a nationwide, population-based cohort study, including all patients with Hirschsprung's disease registered in the Swedish National Patient Register between 1964 and 2004. Five age- and sex-matched controls per patient were randomly selected by Statistics Sweden. Outcome data were retrieved from the Multi-Generation Register, and the Swedish National Patient Register. Study exposure was Hirschsprung's disease and the primary outcome was fertility, defined as having one or more children. Individuals with chromosomal anomalies were excluded. RESULTS: The study cohort comprised 597 patients with Hirschsprung's disease (143 female) and 2969 controls (714 female). The mean(s.d.) age at follow-up was 29.6(10.0) years for patients and 29.8(10.1) years for the controls. A total of 191 (32.0 per cent) patients compared with 1072 (36.1 per cent) controls had one or more children (P = 0.061). The analysis showed that fewer female patients with Hirschsprung's disease had a child (29.4 versus 38.7 per cent, P = 0.037), they were older when they gave birth to their first child (28.1 versus 26.4 years, P = 0.033), and they had fewer children. Of the female patients with Hirschsprung's disease, 19 (45.2 per cent) had only one child, compared with 79 (28.6 per cent) of the female control group (P = 0.047). No difference was noted in the male group in this regard. CONCLUSION: Female patients with Hirschsprung's disease were less likely to have a child, had fewer children, and were older when they gave birth to their first child compared with the controls, indicating impaired fertility. There was no significant difference between male patients with Hirschsprung's disease and controls.

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.

Prevalence of Beckwith Wiedemann Syndrome and Risk of Embryonal Tumors in Children Born with Omphalocele.

AIM OF THE STUDY: Children with omphalocele have an increased prevalence of Beckwith Wiedemann syndrome (BWS) and thus a suspected increased risk of developing embryonal tumors, e.g. Wilms tumor, hepatoblastoma, neuroblastoma and rhabdomyosarcoma. The aim of this study was to examine the prevalence of BWS and the risk of embryonal tumors amongst patients born with omphalocele. METHODS: A population-based cohort was used, including all children born in Sweden 1/1 1997-31/12 2016. Patients with omphalocele were identified through the Swedish National Patient Register and the Swedish Medical Birth Register. For each case of omphalocele ten age and sex matched individuals unexposed for omphalocele were randomly selected for comparison. Data on BWS and embryonal tumors were collected from the Swedish National Patient Register and the Swedish National Cancer Register. MAIN RESULTS: Out of 207 cases of omphalocele, 15 (7.2%) were diagnosed with BWS. None of the children with omphalocele had yet developed any kind of embryonal tumor (median follow-up time 8 years). None of the 2070 controls were diagnosed with BWS but 3 (0.1%) of them had developed embryonal tumors during a median follow-up time of 10 years. CONCLUSIONS: In this study the prevalence of BWS amongst children born with omphalocele is in the lower range of previously reported figures. Also, the prevalence of embryonal tumors amongst children with BWS is lower than expected and the risk of embryonal tumors in children with omphalocele and BWS might not be as high as previously stated. This must be taken into consideration when counseling parents prenatally. TYPE OF STUDY: National register cohort study. LEVEL OF EVIDENCE: II.

Postoperative complications and myocardial injury in patients receiving air or oxygen. Prospective, randomised and pilot study.

BACKGROUND: Supplementary oxygen is administered during anaesthesia to increase oxygen delivery and prevent hypoxia. Recent studies have questioned this routine. In this pilot study, our main aim was to investigate if 21% oxygen compared to ≥50% reduces the risk of postoperative complications and myocardial injury. METHODS: In this pragmatic, multicentre, single-blind study, patients undergoing vascular surgery were randomised to receive a fraction of inspired oxygen (Fi O2 ) ≥ 0.50 and oxygen saturation determined by pulse oximetry (SpO2 ) ≥ 98% (group H) or Fi O2 of 0.21 and SpO2 > 90% (group N) oxygen perioperatively. The primary outcome was a composite outcome of major pre-defined postoperative complications assessed at 30 days. Myocardial injury was determined by serial troponin measurements. Data were analysed using generalised estimating equation, Mann-Whitney U test or chi-squared test, as appropriate. RESULTS: The 191 patients were randomised, and per-protocol principle was used for analyses. At 30-day follow-up, 43 out of 94 patients (46%) had a postoperative complication in group H and 36 out of 90 patients (40%) in group N, p = .46. New myocardial injury was seen in 27% versus 22% in Groups H and N respectively (p = .41). No differences in other outcomes were observed between the groups. Twelve patients (13%) in Group N had SpO2 < 90%, six recovered spontaneously and six required supplemental oxygen. At 1-year follow-up, one patient in group H had died. CONCLUSION: In this pilot study, postoperative complications were similar between the groups in patients randomised to Fi O2 of 0.21 or ≥0.50 and no difference was found in the incidence of new myocardial injury. Larger, prospective adequately powered studies are needed.

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.

The Neuroimmune Response to Surgery - An Exploratory Study of Trauma-Induced Changes in Innate Immunity and Heart Rate Variability.

Surgery triggers a systemic inflammatory response that ultimately impacts the brain and associates with long-term cognitive impairment. Adequate regulation of this immune surge is pivotal for a successful surgical recovery. We explored the temporal immune response in a surgical cohort and its associations with neuroimmune regulatory pathways and cognition, in keeping with the growing body of evidence pointing towards the brain as a regulator of peripheral inflammation. Brain-to-immune communication acts through cellular, humoral and neural pathways. In this context, the vagal nerve and the cholinergic anti-inflammatory pathway (CAP) have been shown to modify peripheral immune cell activity in both acute and chronic inflammatory conditions. However, the relevance of neuroimmune regulatory mechanisms following a surgical trauma is not yet elucidated. Twenty-five male patients undergoing elective laparoscopic abdominal surgery were included in this observational prospective study. Serial blood samples with extensive immune characterization, assessments of heart rate variability (HRV) and cognitive tests were performed before surgery and continuing up to 6 months post-surgery. Temporal immune responses revealed biphasic reaction patterns with most pronounced changes at 5 hours after skin incision and 14 days following surgery. Estimations of cardiac vagal nerve activity through HRV recordings revealed great individual variations depending on the pre-operative HRV baseline. A principal component analysis displayed distinct differences in systemic inflammatory biomarker trajectories primarily based on pre-operative HRV, with potiential consequences for long-term surgical outcomes. In conclusion, individual pre-operative HRV generates differential response patterns that associate with distinct inflammatory trajectories following surgery. Long-term surgical outcomes need to be examined further in larger studies with mixed gender cohorts.

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.

The Karolinska NeuroCOVID study protocol: Neurocognitive impairment, biomarkers and advanced imaging in critical care survivors.

BACKGROUND: This is the study plan of the Karolinska NeuroCOVID study, a study of neurocognitive impairment after severe COVID-19, relating post-intensive care unit (ICU) cognitive and neurological deficits to biofluid markers and MRI. The COVID-19 pandemic has posed enormous health challenges to individuals and health-care systems worldwide. An emerging feature of severe COVID-19 is that of temporary and extended neurocognitive impairment, exhibiting a myriad of symptoms and signs. The causes of this symptomatology have not yet been fully elucidated. METHODS: In this study, we aim to investigate patients treated for severe COVID-19 in the ICU, as to describe and relate serum-, plasma- and cerebrospinal fluid-borne molecular and cellular biomarkers of immune activity, coagulopathy, cerebral damage, neuronal inflammation, and degeneration, to the temporal development of structural and functional changes within the brain as evident by serial MRI and extensive cognitive assessments at 3-12 months after ICU discharge. RESULTS: To date, we have performed 51 3-month follow-up MRIs in the ICU survivors. Of these, two patients (~4%) have had incidental findings on brain MRI findings requiring activation of the Incidental Findings Management Plan. Furthermore, the neuropsychological and neurological examinations have so far revealed varying and mixed patterns. Several patients expressed cognitive and/or mental concerns and fatigue, complaints closely related to brain fog. CONCLUSION: The study goal is to gain a better understanding of the pathological mechanisms and neurological consequences of this new disease, with a special emphasis on neurodegenerative and neuroinflammatory processes, in order to identify targets of intervention and rehabilitation.

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.

Omphalocele: national current birth prevalence and survival.

PURPOSE: The increase in prenatal diagnosis together with the high rates of associated anomalies in omphalocele has led to increased rates of termination of pregnancies. The aim of this study was to examine the national Swedish birth prevalence and survival rates among these patients. METHODS: This study is based on a nationwide population-based cohort of all children born in Sweden between 1/1/1997 and 31/12/2016. All omphalocele cases were identified though the Swedish National Patient Register and the Swedish Medical Birth Register. Outcome of malformations and deaths were retrieved from the Swedish Birth Defects Register and the Swedish Causes of Death Register. RESULTS: The study included 207 cases of omphalocele (42% females). The birth prevalence for omphalocele was 1/10,000 live births. About 62% of the cases had associated malformations and/or genetic disorders; most common was ventricular septal defect. The mortality within the first year was 13%. The rate of termination of pregnancy was 59%. CONCLUSION: The national birth prevalence for omphalocele in Sweden is 1/10,000 newborn, with high termination rates. Over half of the pregnancies with prenatally diagnosed omphalocele will be terminated. Among those who continue the pregnancy, 1-year survival rates are high. TYPE OF STUDY: National register study LEVEL OF EVIDENCE: III.

National birth prevalence, associated anomalies and mortality for gastroschisis in Sweden.

AIM: An increased incidence has been reported for the congenital abdominal wall defect gastroschisis. The reason for this increasing trend is not known, nor the aetiology. The aim of this study was to examine the national birth prevalence in Sweden, the termination rate, associated anomalies and the mortality of gastroschisis within the cohort. METHODS: A nationwide, population-based descriptive study of children born with gastroschisis in Sweden between 1/1 1997 and 31/12 2016 was conducted. The cohort was collected from the Swedish Medical Birth Register and the Swedish National Patient Register. Several other national registers were then interlinked to identify outcome data. RESULTS: The study included 361 cases of gastroschisis, 54% female. The birth prevalence was 1.52 in 10,000 live births. The termination rate was 21%. The mortality within the cohort was 4.4% with a 1-year mortality of 3.9%. Most frequent associated anomalies were gastrointestinal (11.4%), musculoskeletal (9.8%) and cardiovascular anomalies (7.9%). CONCLUSION: During the 20-year study period, a stable birth prevalence of 1.52 per 10 000 live births was seen in Sweden. The mortality was low, 4.4%, but the termination of pregnancies was high, 21%. Almost one-third had associated congenital anomalies where gastrointestinal anomalies were the most common.

Evaluation of Bowel Function, Urinary Tract Function, and Quality of Life after Transanal Endorectal Pull-Through Surgery for Hirschsprung's Disease.

INTRODUCTION: The objective of this study is to determine short-term complications and evaluate long-term bowel function, lower urinary tract symptoms, and quality of life (QoL) in patients treated for Hirschsprung's disease (HSCR) with transanal endorectal pull-though (TERPT) compared with healthy controls. MATERIALS AND METHODS: This cross-sectional case-control study included 30 HSCR patients treated with TERPT in 2006 to 2014 at Karolinska University Hospital, and 30 healthy controls matched for age and gender. Data on short-term complications were compiled from medical records and classified according to Clavien-Dindo. Bowel function and QoL were evaluated with the validated questionnaires bowel function score and KIDSCREEN-52. Lower urinary tract symptoms were evaluated through an 8-item lower urinary tract symptoms (LUTS) questionnaire. RESULTS: Six (20%) patients had a short-term postoperative complication according to Clavien-Dindo, with insufficient pain management being the most common complication. The median age at follow-up was 7 years (range = 4-11). Median bowel function score was significantly lower in HSCR patients than in controls, 14 versus 19 (p < 0.001). Twenty-one of the HSCR patients reported impaired bowel function compared with two of the controls (p < 0.001). The overall prevalence of LUTS was 11 (38%) in the HSCR patients compared with seven (23%) in the controls (p = 0.751). HSCR patients reported a slightly lower QoL in the KIDSCREEN domain "financial resources" compared with controls (p = 0.008). CONCLUSION: According to Clavien-Dindo, short-term postoperative complications occurred in 20% of the patients. Impaired bowel function persists throughout childhood for most HSCR patients. The prevalence of LUTS and QoL is not affected in HSCR patients compared with controls.

Clinical characteristics and validation of diagnosis in individuals with Hirschsprung disease and inflammatory bowel disease.

BACKGROUND/PURPOSE: Hirschsprung disease has previously been reported to be associated with inflammatory bowel disease (IBD). The aim was to clinically confirm the diagnosis and to describe characteristics among individuals with both conditions in a national populationbased cohort. METHODS: Nationwide, population-based cohort study, including all individuals with a Hirschsprung disease diagnosis and an IBD diagnosis registered between 1964 and 2016, in which clinical data were collected from the medical records of 18 validated cases with both Hirschsprung disease and IBD. The medical record of each individual in the study cohort was reviewed for age at IBD diagnosis, type of aganglionosis, type of surgical treatment, subtype of IBD, and treatment for IBD. RESULTS: Median age at follow up was 34 years (range 19-66), and 3 of 18 indivduals (17%) were females. Median age at first diagnosis of IBD was 21 years (range 10-46). Six patients had ulcerative colitis, ten had Crohn's disease and two had unclassified IBD. Most of the patients had pharmacological treatment for IBD and 5 (28%) individuals had surgical treatment. CONCLUSION: Hirschsprung disease and IBD was clinically confirmed in 18 cases. Age at IBD onset and subtype of IBD is similar to IBD patients without Hirschsprung disease. Five individuals had undergone surgical treatment for IBD.

Association between cerebrospinal fluid biomarkers of neuronal injury or amyloidosis and cognitive decline after major surgery.

BACKGROUND: Postoperative neurocognitive decline is a frequent complication in adult patients undergoing major surgery with increased risk for morbidity and mortality. The mechanisms behind cognitive decline after anaesthesia and surgery are not known. We studied the association between CSF and blood biomarkers of neuronal injury or brain amyloidosis and long-term changes in neurocognitive function. METHODS: In patients undergoing major orthopaedic surgery (knee or hip replacement), blood and CSF samples were obtained before surgery and then at 4, 8, 24, 32, and 48 h after skin incision through an indwelling spinal catheter. CSF and blood concentrations of total tau (T-tau), neurofilament light, neurone-specific enolase and amyloid ß (Aß1-42) were measured. Neurocognitive function was assessed using the International Study of Postoperative Cognitive Dysfunction (ISPOCD) test battery 1-2 weeks before surgery, at discharge from the hospital (2-5 days after surgery), and at 3 months after surgery. RESULTS: CSF and blood concentrations of T-tau, neurone-specific enolase, and Aß1-42 increased after surgery. A similar increase in serum neurofilament light was seen with no overall changes in CSF concentrations. There were no differences between patients having a poor or good late postoperative neurocognitive outcome with respect to these biomarkers of neuronal injury and Aß1-42. CONCLUSIONS: The findings of the present explorative study showed that major orthopaedic surgery causes a release of CSF markers of neural injury and brain amyloidosis, suggesting neuronal damage or stress. We were unable to detect an association between the magnitude of biomarker changes and long-term postoperative neurocognitive dysfunction.

The overall risk of malignancies is not increased in patients with Hirschsprung disease.

PURPOSE: Hirschsprung disease (HSCR) has previously been associated with increased risk of medullary thyroid cancer. The aim of this study was to assess the overall risk of malignancies in patients with Hirschsprung disease in a population-based cohort. METHODS: This was a nationwide, population-based cohort study. The study exposure was HSCR and the study outcome was malignancy. The cohort included all individuals with HSCR registered in the Swedish National Patient Register between 1964 and 2013 and ten age- and sex-matched controls per patient, randomly selected from the Population Register. Data were linked with the Swedish National Cancer Register to identify individuals with malignancy diagnosis. RESULTS: The cohort comprised 739 individuals with HSCR (565 male) and 7390 controls (5650 male). Median age of the cohort was 19 years (range 2-49). In total nine (1.2%) individuals in the exposed cohort were diagnosed with malignancies compared to 57 (0.8%) in the non-exposed cohort (p = 0.195). Median age at malignancy diagnosis was 3 years (range 0-46) in the exposed group, compared to 23 (range 0-42), p = 0.132. No cases with medullary carcinoma of the thyroid were found in this cohort. CONCLUSIONS: There was no significant difference in risk of malignancies in the exposed group compared to the unexposed group.