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.

Dynamic Compression Therapy for Pectus Carinatum in Children and Adolescents: Factors for Success.

BACKGROUND: Pectus carinatum (PC) is a congenital chest wall deformity. In childhood, it is increasingly treated with dynamic compression therapy. Factors for success for dynamic brace therapy are relatively unknown. METHODS: Between 2013 and 2020, 740 patients treated with the Dynamic Compression System (DCS), were studied. This included the effect of age, gender, pectus height, symmetry and pectus rigidity on treatment time and symptoms with linear multiple regression analyses. RESULTS: Carinatum height and high pressure of initial correction at the start of treatment were associated with a prolonged duration of treatment. For each cm increase in carinatum height, the total treatment duration increased with 1.9 months (p-value= 0.002, 95% CI: 0.70-3.13). An initial correction pressure of ≥7.6 pounds per square inch (psi), increased the treatment duration with 3.5 months (p-value 0.006, 95% CI: 1.04-6.01) compared to an initial correction pressure of ≤5.0 psi. A high initial pressure of correction of ≥7.6 psi increased the odds of having somatic symptoms with 1.19 (p-value= 0.012, 95% CI: 1.04-1.45) and psychosocial symptoms with 1.13 (p-value= 0.04, 95% CI: 1.01-1.27) compared to a low initial pressure of correction of ≤5.0 psi. An initial pressure of correction of 5.1-7.5 psi increased the odds of having somatic symptoms with 1.14 (p-value 0.046, 95% CI: 1.00-1.29) compared to an initial pressure of correction of ≤5.0 psi. Patients with asymmetric chests were more likely to abandon therapy CONCLUSIONS: High carinatum height and high initial pressure of correction are associated with prolonged bracing treatment and a higher failure rate. LEVEL OF EVIDENCE: III.

Determining the Correct Resection Level in Patients with Hirschsprung Disease Using Contrast Enema and Full Thickness Biopsies: Can the Diagnostic Accuracy be Improved by Examining Submucosal Nerve Fiber Thickness?

BACKGROUND: Intraoperative resection level in patients with Hirschsprung disease (HD) is determined by contrast enema, surgeon's intraoperative judgement and full thickness biopsy (FTB) identifying ganglia. This study aims to evaluate diagnostic accuracy of contrast enema and FTB in determination of resection level and whether this can be improved by measuring submucosal nerve fiber diameter. METHODS: We retrospectively analyzed contrast enema and intraoperative FTBs obtained in our center, determining diagnostic accuracy for level of resection. Gold standard was pathological examination of resection specimen. Secondly, we matched transition zone pull-through (TZPT) patients with non-TZPT patients, based on age and length of resected bowel, to blindly compare nerve fibers diameters between two groups using group comparison. RESULTS: From 2000-2021, 209 patients underwent HD surgery of whom 180 patients (138 males; median age at surgery: 13 weeks) with 18 TZPTs (10%) were included. Positive predictive value of contrast enema was 65.1%. No caliber change was found in patients with total colon aganglionosis (TCA). Negative predictive value of surgeon's intraoperative judgement and FTB in determining resection level was 79.0% and 90.0% (91.2% single-stage, 84.4% two-stage surgery) respectively. Mean nerve fiber diameter in TZPT was 25.01 µm (SD= 5.63) and in non-TZPT 24.35 µm (SD= 6.75) (p = 0.813). CONCLUSION: Determination of resection level with combination of contrast enema, surgeon's intraoperative judgement and FTB results in sufficient diagnostic accuracy in patients with HD. If no caliber change is seen with contrast enema, TCA should be considered. Resection level or transition zone cannot be determined by assessment of submucosal nerve fiber diameter in FTB. TYPE OF STUDY: clinical research paper.

Familial Experience With Hirschsprung's Disease Improves the Patient's Ability to Cope.

Introduction: Familial occurrence of Hirschsprung's disease may have a positive effect on patients' ability to cope with the disease. The aim was to compare long-term bowel function and generic quality of life between patients with familial and non-familial Hirschsprung's disease. Methods: This was a nationwide, cross-sectional study in which we included all 830 Hirschsprung patients of 8 years and older who had undergone surgery between 1957 and 2015. We excluded patients with a permanent stoma, intellectual disability, or an unknown or foreign address. We requested patients to complete the validated pediatric or adult Defecation and Fecal Continence questionnaire and the Child Health Questionnaire Child Form-87, or the World Health Organization Quality of Life-100 Assessment Instrument. Results: We analyzed 336 Hirschsprung patients, 15.8% of whom were familial cases and 84.2% were non-familial cases. After adjusting for aganglionic length, sex, and age, patients with familial Hirschsprung's disease were twice more likely to suffer from constipation (OR = 2.47, 95% CI, 1.21-5.05, p = 0.013). The quality of life of the pediatric patients was comparable, but in adult patients the energy/fatigue, thinking/learning/concentration, and work capacity facets showed better scores in the familial patients with Hirschsprung's disease of the rectosigmoid (p = 0.029, p = 0.024, p = 0.036, respectively). Conclusions: Different facets of generic quality of life are better in adult patients with familial Hirschsprung's disease of the rectosigmoid. It seems that familial experience with the disease influences patients' coping abilities positively.

Hypothermic Machine Perfusion as a National Standard Preservation Method for Deceased Donor Kidneys.

BACKGROUND: Recently, continuous nonoxygenated hypothermic machine perfusion (HMP) has been implemented as standard preservation method for deceased donor kidneys in the Netherlands. This study was designed to assess the effect of the implementation of HMP on early outcomes after transplantation. METHODS: Kidneys donated in the Netherlands in 2016 and 2017 were intended to be preserved by HMP. A historical cohort (2010-2014) preserved by static cold storage was chosen as the control group. Primary outcome was delayed graft function (DGF). Additional analyses were performed on safety, graft function, and survival up until 2 y after transplantation. RESULTS: Data were collected on 2493 kidneys. Analyses showed significantly more donation after circulatory death, preemptive transplantation, and retransplants in the project cohort. Of the 681 kidneys that were transplanted during the project, 81% were preserved by HMP. No kidneys were discarded due to HMP-related complications. DGF occurred in 38.2% of the project cohort versus 43.7% of the historical cohort (P < 0.001), with a significantly shorter duration within the project cohort (7 versus 9 d, P = 0.003). Multivariate regression analysis showed an odds ratio of 0.69 (95% confidence interval, 0.553-0.855) for the risk of DGF when using HMP compared with cold storage (P = 0.001). There was no significant difference in kidney function, graft survival, and recipient survival up until 2 y posttransplantation. CONCLUSIONS: This study showed that HMP as a standard preservation method for deceased donor kidneys is safe and feasible. HMP was associated with a significant reduction of DGF.

Functional Outcomes After Surgery for Total Colonic, Long-Segment, Versus Rectosigmoid Segment Hirschsprung Disease.

OBJECTIVES: Knowledge on long-term outcomes in patients with Hirschsprung disease is progressing. Nevertheless, differences in outcomes according to aganglionic lengths are unclear. We compared long-term bowel function and generic quality of life in Hirschsprung patients with total colonic or long-segment versus rectosigmoid aganglionosis. METHODS: In this nationwide, cross-sectional study participants with proven Hirschsprung disease received the Defecation and Fecal Continence questionnaire, and the Child Health Questionnaire Child Form-87, or the WHO Quality of Life-100. We excluded deceased patients, patients who were younger than 8 years, lived abroad, had a permanent enterostomy, or were intellectually impaired. RESULTS: The study population (n = 334) was operated for rectosigmoid (83.9%), long-segment (8.7%), or total colonic aganglionosis (7.5%). Fecal incontinence in general was not significantly different between the three groups, but liquid fecal incontinence was significantly associated with total colonic aganglionosis (odds ratio [OR] = 6.00, 95% confidence interval [CI] 2.07-17.38, P = 0.001). Regarding constipation, patients with total colonic or long-segment aganglionosis were less likely to suffer from constipation than the rectosigmoid group (OR = 0.21, 95% CI, 0.05-0.91, P = 0.038 and OR = 0.11, 95% CI, 0.01-0.83, P = 0.032). Quality of life was comparable between the three groups, except for a lower physical score in children with total colonic aganglionosis (P = 0.016). CONCLUSIONS: Over time Hirschsprung patients with total colonic or long-segment aganglionosis do not suffer from worse fecal incontinence in general. A difference in stool consistency may underlie the association between liquid fecal incontinence and total colonic aganglionosis and constipation in patients with rectosigmoid aganglionosis. Despite these differences, generic quality of life is comparable on reaching adulthood.

International Core Outcome Set for Acute Simple Appendicitis in Children: Results of a Systematic Review, Delphi Study, and Focus Croups With Young People.

OBJECTIVE: To develop an international core outcome set (COS), a minimal collection of outcomes that should be measured and reported in all future clinical trials evaluating treatments of acute simple appendicitis in children. SUMMARY OF BACKGROUND DATA: A previous systematic review identified 115 outcomes in 60 trials and systematic reviews evaluating treatments for children with appendicitis, suggesting the need for a COS. METHODS: The development process consisted of 4 phases: (1) an updated systematic review identifying all previously reported outcomes, (2) a 2-stage international Delphi study in which parents with their children and surgeons rated these outcomes for inclusion in the COS, (3) focus groups with young people to identify missing outcomes, and (4) international expert meetings to ratify the final COS. RESULTS: The systematic review identified 129 outcomes which were mapped to 43 unique outcome terms for the Delphi survey. The first-round included 137 parents (8 countries) and 245 surgeons (10 countries), the second-round response rates were 61% and 85% respectively, with 10 outcomes emerging with consensus. After 2 young peoples' focus groups, 2 additional outcomes were added to the final COS (12): mortality, bowel obstruction, intraabdominal abscess, recurrent appendicitis, complicated appendicitis, return to baseline health, readmission, reoperation, unplanned appendectomy, adverse events related to treatment, major and minor complications. CONCLUSION: An evidence-informed COS based on international consensus, including patients and parents has been developed. This COS is recommended for all future studies evaluating treatment ofsimple appendicitis in children, to reduce heterogeneity between studies and facilitate data synthesis and evidence-based decision-making.

Comparison of intra- and extra-corporeal laparoscopic hernia repair in children: A systematic review and pooled data-analysis.

BACKGROUND: Laparoscopic surgery is increasingly used to repair paediatric inguinal hernias and can be divided into intra- or extra-corporeal closing techniques. No statement regarding the superiority of one of the two techniques can be made. This study aims to provide evidence supporting the superiority of intra- or extra-corporeal suturing technique. METHODS: A systematic literature search was conducted using PubMed, Embase, MEDLINE, and Cochrane Library databases. Randomised controlled trials and prospective studies comparing different laparoscopic techniques were eligible for inclusion. Data were pooled using a random-effects model, comparing single-port extra-peritoneal closure to intra-peritoneal purse string suture closing. Primary outcome was recurrence rate. Secondary outcomes were duration of surgery (min), peri­ and post-operative complications (i.e. injury of spermatic vessels or spermatic cord, tuba lesions, bleeding and apnoea, haematoma/scrotal oedema, hydrocele, wound infection, iatrogenic ascent of the testis and testicular atrophy), contralateral patent processus vaginalis (CPPV) rate, post-operative pain, length of hospital stay and cosmetic appearance of the wound. RESULTS: Fifteen studies (n = 3680 patients, age range 0.5-12 years, follow-up range 3-10 months) were included is this systematic review. Intra-corporeal hernia repair was performed in 738 children and extra-corporeal repair was performed in 2942 children. A pooled data analysis could only be performed for the single port extra-corporeal closing technique and the three port intra-corporeal closing technique. We found that recurrence rate was lower in the single-port extra-corporeal closing technique compared to the intra-corporeal purse suture closing technique (0.6% vs 5.5%, 95% CI 0.107 (0.024-0.477); p < 0.001). Operation time was shorter for extra-corporeal unilateral and bilateral inguinal hernia repair compared with intra-corporeal approach, but no pooled data analysis could be performed. Due to the presence of substantial heterogeneity, it was not possible to assess other outcome measures. CONCLUSION: Single-port extra-corporeal closure seems to result in less recurrent hernias and a shorter operative time compared to intra-corporeal purse suture closing technique. No difference regarding peri­ and post-operative complications could be found and no statements regarding the length of hospital admission, post-operative pain and cosmetics could be made due to substantial heterogeneity. LEVEL OF EVIDENCE: Level II.

Left Ventricular Geometrical Changes in Severely Obese Adolescents: Prevalence, Determinants, and Clinical Implications.

Left ventricular hypertrophy (LVH) is independently associated with a higher risk of cardiovascular morbidity and mortality in adults. Adiposity is a risk factor for LVH, independent of blood pressure. Potential causes of this nonhemodynamic pathogenesis identified in adults include adverse body fat distribution, insulin resistance, dyslipidemia, and obstructive sleep apnea syndrome (OSA). In severely obese adolescents, the determinants of obesity-induced changes in left ventricular structure are poorly characterized. Cardiac ultrasonographic, demographic, anthropometric, and comorbidity-related data were prospectively collected in adolescents with severe obesity refractory to conservative treatment who presented for surgical therapy. Differences between adolescents with LVH and without LVH were evaluated using independent samples t, chi-square, or Fisher's exact test. Multivariable linear regression analysis was performed to evaluate associations with left ventricular structural changes, corrected for body mass index (BMI) z score. Forty-three patients entered analysis, of whom 24 (55.8%) showed LVH. The most common geometrical change was eccentric LVH (eLVH), occurring in 21 subjects (48.8%). Demographic and anthropometric variables did not differ between patients with and without LVH. Independent of BMI z score, left ventricular mass index was significantly associated with apnea-hypopnea index (AHI) (regression parameter B = 0.8; 95% CI 0.3 to 1.2). Interventricular septum thickness (IVST) was significantly associated with HOMA-IR values (B = 0.1; 95% CI 0.04 to 0.2), HDL-cholesterol (B = - 1.2; 95% CI - 2.2 to 0.1), and triglyceride levels (B = 0.5; 95% CI 0.001 to 0.9). LVH, especially eLVH, is highly prevalent amongst severely obese adolescents. Adverse changes in cardiac structure, increased IVST in particular, are independently associated with several nonhemodynamic comorbidities that are common in this population, namely OSA, insulin resistance, and dyslipidemia.

Obstructive sleep apnea in obese adolescents referred for bariatric surgery: association with metabolic and cardiovascular variables.

BACKGROUND: obstructive sleep apnea syndrome (OSA) is a well-described disease entity in adults, with a higher prevalence in severely obese individuals, while at the same time associated with several comorbidities independently of BMI. Literature regarding OSA in severely obese adolescents is qualitatively and quantitatively limited, possibly resulting in suboptimal diagnosis and treatment. METHODS: polysomnographic, demographic, anthropometric, and comorbidity-related data were prospectively collected in 56 adolescents with morbid obesity refractory to conservative treatment who presented for surgical therapy. Differences between adolescents with no/mild (apnea-hypopnea index (AHI) 0-4.9) and moderate/severe OSA (AHI ≥ 5.0) were evaluated using independent-samples t, chi-square or Fisher's exact tests. Multivariable linear regression analysis was performed to evaluate the association of several variables with AHI, corrected for BMI z-score. RESULTS: of the 53 included subjects, 48 (90.6%) showed some degree of sleep disordered breathing and 20 (37.7%) had moderate/severe OSA. Patients with moderate/severe OSA had on average a higher neck circumference (42.4 versus 40.1 cm, p = 0.008), higher BMI z-score (3.7 versus 3.4, p = 0.003), higher plasma triglyceride level (2.2 versus 1.5 mmol/L, p = 0.012), and lower IGF (29.6 versus 40.2 mmol/L, p = 0.010) than those with no/mild OSA. BMI z-score and plasma triglyceride levels were independently related to AHI. CONCLUSIONS: OSA is highly prevalent amongst morbidly obese adolescents and is strongly associated with BMI z-score. Elevated plasma triglyceride levels are associated with AHI, independent of BMI z-score.

Sternocostal instability after Ravitch repair in adolescents; 3 case-reports and a review of surgical techniques in the literature.

Ravitch repair is a common surgical procedure to correct chest wall deformities. In this procedure, a subperichondreal cartilage resection of the deformed parasternal cartilage, and if necessary a repositioning of the sternum, is performed. Insufficient regeneration of the resected cartilage may result in sternocostal instability or even floating sternum. This rare complication presents with symptoms of pain and exercise intolerance. METHODS: We describe sternocostal instability in 3 adolescent patients after the Ravitch procedure for pectus carinatum and reviewed the literature on this topic. RESULTS: Our patients suffered different degrees of instability. In all cases, we eventually achieved a satisfactory outcome. There is little literature on sternocostal instability. It is a rare complication, mainly occurring after reoperation by damaging the perichondrium. CONCLUSIONS: Malunion of costal cartilage is a rare complication of open pectus repair. To achieve the best regeneration and stability of the sternum, less extended resection of cartilage should be performed and the number of cartilages resected should be limited. The perichondrium must be kept intact. Autologous grafts, growth-enhancing materials, and metal or bioabsorbable struts may contribute to stabilization and regeneration of the cartilage.

Correlation of Preoperative State Anxiety and Pain Six Weeks After Surgical Correction of Pectus Excavatum.

BACKGROUND: Pain is a major concern in the early postoperative phase after correction of pectus excavatum. Most studies only focus on pain management in the first days after surgery and describe methods to alleviate the pain immediately postoperatively. The severity of postoperative pain may be influenced by anxiety. So far, few studies have looked into the relationship between anxiety and postoperative pain after pectus excavatum correction. OBJECTIVES: This study aimed to investigate the correlation between preoperative anxiety and late postoperative pain scores. METHODS: This was a prospective cohort study. Anxiety was assessed with the State and Trait Anxiety Inventory questionnaire. Visual analogue scale (VAS) for pain scores assessed the pain at rest and activity. Anxiety was measured before surgery and pain scores six weeks after surgery. A hierarchical linear regression analysis was performed to investigate the correlation between baseline anxiety and pain measurements six weeks after surgery. RESULTS: In this study, 136 patients were included. State anxiety was not associated with postoperative pain (mean of pain on activity and in rest), only with pain on activity after six weeks. Age and sex were not effect modifiers in any of the models. Relevant confounding factors, although not significant, consisted of trait, sex, minor complications, epidural duration, major complications, and the number of stabilizer plates. The explained variance of state anxiety on VAS for pain scores was minimum after 6 weeks. CONCLUSIONS: Preoperative anxiety does not appear to influence postoperative pain after PE correction.

Impact of Cold Ischemia Time on Outcomes of Deceased Donor Kidney Transplantation: An Analysis of a National Registry.

BACKGROUND: Cold ischemia time (CIT) is known to impact kidney graft survival rates. We compare the impact of CIT on graft failure and mortality in circulatory death versus brain death donor kidneys and how it relates to donor age. METHODS: We used the prospective Dutch Organ Transplantation Registry to include 2153 adult recipients of brain death (n = 1266) and circulatory death (n = 887) donor kidneys after static cold storage from transplants performed between 2005 and 2012. CIT was modeled nonlinearly with splines. Associations and interactions between CIT, donor type, donor age, 5-year (death-censored) graft survival, and mortality were evaluated. RESULTS: The median CIT was 16.2 hours (interquartile range 12.8-20), ranging from 3.4 to 44.7 hours for brain death and 4.7 to 46.6 hours for circulatory death donor kidneys. At >12 hours of CIT, we observed an increased risk of graft failure in kidneys donated after circulatory death versus after brain death. This risk rose significantly at >22 hours of CIT (hazard ratio 1.45; 95% confidence interval, 1.01-2.49; P = 0.043). Kidneys that came from 60-year-old circulatory death donors demonstrated elevated hazard risk at 19 hours of CIT, a shorter timeline than that for kidneys that came from brain death donors of the same age (hazard ratio 1.33; 95% confidence interval, 1.00-1.78; P = 0.045). The additional harmful effects of increased CIT in kidneys from circulatory-death donors were also found for death-censored graft failure but did not affect mortality rates in any significant way. CONCLUSIONS: The findings support the hypothesis that prolonged cold ischemia is more harmful for circulatory death donor kidneys that have already been subjected to a permissible period of warm ischemia. Efforts should be made to reduce CIT, especially for older circulatory death donor kidneys.

Abdominal Wall Pain or Irritable Bowel Syndrome: Validation of a Pediatric Questionnaire.

OBJECTIVES: A questionnaire study demonstrated that some adult patients who were diagnosed with irritable bowel syndrome (IBS) were in fact having an abdominal wall pain syndrome, such as anterior cutaneous nerve entrapment syndrome (ACNES). The aim of the present study was to investigate whether a pediatric version of this questionnaire was useful in diagnosing abdominal wall pain syndromes in children with chronic abdominal pain (CAP). METHODS: An 18-item questionnaire was tested in 3 groups of children with CAP: group 1, children who underwent surgery for ACNES (n = 42); group 2, children who were found to have ACNES after an outpatient analysis (n = 57); and group 3, children diagnosed with IBS (n = 53). Qualities including internal consistency (Cronbach α), cut-off points and a ROC-curve were calculated using standard statistical analysis. RESULTS: Questionnaire response rates in the three populations of CAP children ranged from 69% to 92%. When comparing ACNES and IBS groups, 17 of 18 questions were discriminative (P < 0.01, Cronbach α 0.74). Total questionnaire scores ranged from 0 (IBS likely) to 17 points (ACNES likely). A median 13-point score (range 8-17) was found in both ACNES groups. In contrast, a median 8-point score was calculated in children with IBS (range 3-13, P < 0.01). Using an 11-point cut-off score, a child with CAP was diagnosed with ACNES with 86% sensitivity and 89% specificity. A ROC curve with an AUC of 0.94 was obtained. CONCLUSIONS: A 17-item questionnaire showed good diagnostic test properties and may aid in distinguishing ACNES from IBS in pediatric populations with chronic abdominal pain.

Establishing a core outcome set for treatment of uncomplicated appendicitis in children: study protocol for an international Delphi survey.

INTRODUCTION: Appendicitis is a global disease affecting roughly 1 in every 12 people in the world, with the highest incidence between ages 10 and 19 years. To date, a wide variety of health outcomes have been reported in randomised controlled trials and meta-analyses evaluating treatments for appendicitis. This is especially the case in studies comparing non-operative treatment with operative treatment. A set of standard outcomes, to be reported in all future trials, is needed to allow for adequate comparison and interpretation of clinical trial results and to make data pooling possible. This protocol describes the development of such a global core outcome set (COS) to allow unified reporting of treatment interventions in children with acute uncomplicated appendicitis. METHODS AND ANALYSIS: We use current international standard methodology for the development and reporting of this COS. Its development consists of three phases: (1) an update of the most recent systematic review on outcomes reported in uncomplicated paediatric appendicitis research to identify additional outcomes, (2) a three-step global Delphi study to identify a set of core outcomes for which there is consensus between parents and (paediatric) surgeons and (3) an expert meeting to finalise the COS and its definitions. Children and young people will be involved through their parents during phase 2 and will be engaged directly using a customised face-to-face approach. ETHICS AND DISSEMINATION: The medical research ethics committee of the Academic Medical Center Amsterdam has approved the study. Each participating country/research group will ascertain ethics board approval. Electronic informed consent will be obtained from all participants. Results will be presented in peer-reviewed academic journals and at (international) conferences. TRIAL REGISTRATION NUMBER: COMET registration: 1119.

Early cost-utility estimation of the surgical correction of pectus excavatum with the Nuss bar.

OBJECTIVES: The surgical correction of pectus excavatum (PE) with a Nuss bar provides satisfactory outcomes, but its cost-effectiveness is yet unproven. We prospectively analysed early outcomes and costs for Nuss bar placement. METHODS: Fifty-four patients aged 16 years or older (6 females and 48 males; mean age, 17.9 years; range 16.0-29.4 years) with a PE filled out a Short Form-36 Health Survey (SF-6D) preoperatively and 1 year after a Nuss procedure. Costs included professional fees and fees for the operating room, materials and hospital care. Changes in the responses to the SF-36 or its domains were compared using the Wilcoxon signed rank test and the utility test results were calculated preoperatively and postoperatively from the SF-6D. The quality-adjusted life years (QALYs) were calculated from the results of these tests. RESULTS: Significant improvements in physical functioning, social functioning, mental health and health transition (all P < 0.05) were noted. The other SF-36 subgroups showed improvement; however, the improvement was not significant. The SF-6D utility showed improvement from 0.76 preoperatively to 0.79 at the 1-year follow-up (P = 0.096). The mean direct costs were €8805. The 1-year discounted QALY gain was 0.03. The estimated cost-utility ratio was €293 500 per QALY gained. CONCLUSIONS: Despite a significant improvement in many domains of the SF-36, the results of the SF-6D cost-utility analysis showed only a small improvement in cost-effectiveness (> €80 000/QALY) for patients with PE 1 year after Nuss bar placement. Based on this discrepancy, general health outcome measurements as the basis for cost-utility analysis in patients with PE may not be the best way forward.

Euthanasia through living organ donation: Ethical, legal, and medical challenges.

Euthanasia is categorically prohibited in almost all countries throughout the world. In Belgium and the Netherlands, combining euthanasia and subsequent organ donation in a so-called donation after circulatory-death (DCD) procedure is feasible on legal and medical grounds, and is increasingly gaining social and ethical acceptance. However, heart transplantation after DCD is currently not performed in Belgium and the Netherlands after euthanasia due to concerns surrounding the prolonged warm ischemia time associated with DCD and its effect on subsequent heart function. A number of patients who undergo euthanasia explicitly express their wish to donate their organs in a "living organ donation" procedure, which then causes death. Assuming that euthanasia is permitted, as expressed in Dutch and Belgian legislation, this exploratory article addresses whether it is legally and ethically sound to donate organs, especially the heart, as a living donor and to perform euthanasia in the same procedure in a patient who fulfills the due diligence requirements for euthanasia. Organ donation euthanasia (ODE) would then cause death by the associated surgical procedure, and in addition would improve the quality of the other donated organs, a procedure that would fully respect the patient's autonomy.

Clinical recovery in children with uncomplicated appendicitis undergoing non-operative treatment: secondary analysis of a prospective cohort study.

Non-operative treatment of uncomplicated appendicitis in children is gaining ground. Pending definitive evidence regarding its effectiveness, there is a call to evaluate clinical recovery after non-operative treatment. In this study, we analyzed data collected during initial admission of a multicenter prospective cohort in which children, 7-17 year, were treated non-operatively for uncomplicated appendicitis. During admission clinical parameters (pain and gastro-intestinal symptoms), inflammation parameters and sequential abdominal ultrasound were recorded. In total, 45 children were included, 42(93%) were discharged without the need for appendectomy; median [IQR] pain scores on admission were 5 [4-7], decreasing to 2 [0-3] after 1 day of treatment. Initially, 28/42 (67%) reported nausea and 19/42 (45%) vomiting; after 1 day, this was 3/42 (7%) and 1/42 (2%), respectively. White blood cell count declined from a median [IQR] of 12.9 [10.7-16.7] 10E9/L on admission to 7.0 [5.8-9.9] 10E9/L on day 1. Median [IQR] C-reactive protein levels increased from 27.5 [9-69] mg/L on admission to 48 [22-80] mg/L on day 1, declining to 21.5 [11-42] mg/L on day 2. Follow-up ultrasound showed no signs of complicated appendicitis in any of the patients.Conclusion: Clinical symptoms resolved in most children after 1 day of non-operative treatment. This suggests that non-operative treatment is a viable alternative to appendectomy regarding clinical recovery.Trail registration: NCT01356641 What is Known: • Non-operative treatment of uncomplicated appendicitis in children is safe and its use around the world is gaining ground, however high quality evidence from adequately designed randomized trials is still lacking. • Concerns have been raised regarding the potentially prolonged clinical recovery associated with non-operative treatment. What is New: • Most clinical symptoms resolve after 1 day of non-operative treatment in the majority of children.

Diagnostic characteristics of anterior cutaneous nerve entrapment syndrome in childhood.

Some children suffering from chronic abdominal pain may have an abdominal wall entity such as anterior cutaneous nerve entrapment syndrome. This syndrome is largely suspected on a combination of findings at history and physical examination. The aim is to obtain clues in history and physical examinations in a selected population of children with anterior cutaneous nerve entrapment syndrome. We analyzed all children with abdominal pain visiting our hospital between January 2013 and January 2015. A total of 71 cases were identified (median age 15 years, range 8-17, 77% female). Pain was severe (median 8, range 6-9), stabbing/burning (84%), superficial (88%), aggravated by physical activity (91%), and always in one abdominal area (97%). Hypo-/hyperesthesia (87%) or a positive pinch test (89%) was often found at the skin overlying the painful spot. Increased pain was reported by 97% when the abdominal muscles were tensed (Carnett test). A single anterior rectus sheath block is successful in almost all patients (97%). CONCLUSION: A combination of typical findings in history and physical examination allows for diagnosing childhood ACNES. What is Known: • Anterior cutaneous nerve entrapment syndrome (ACNES) is often overlooked in chronic abdominal pain. • Pediatric literature on diagnostic work up for ACNES is poor. What is New: • Two third reported treatment delay due to misdiagnosis as functional abdominal pain. • Medical history and physical examination revealed neuropathic pain characteristic in up to 90% of the cases.