15 Years of Vacuum Bell Therapy for Pectus Excavatum: Long-term Outcomes and Influencing Factors.

BACKGROUND: Long-term results and factors affecting outcomes of vacuum bell therapy for pectus excavatum are relatively unknown. METHODS: We conducted a retrospective study on patients (<18y) treated with vacuum bell therapy between May 2008 and October 2021. Primary outcome was treatment success; secondary outcomes were analysis of daily time spent on treatment, treatment duration, complications, long-term follow-up, treatment for patients awaiting a Nuss procedure, treatment for female patients, and factors affecting outcomes. RESULTS: Of 259 patients treated with vacuum bell therapy, 18.9% (n = 49/259) were still being treated, 17.4% (n = 45/259) were lost to follow-up and 63.7% (n = 165/259) completed treatment, with a 52.1% (n = 86/165) success rate. Median follow-up was 64.0 months (interquartile range 48.0-87.0). More time spent daily on vacuum bell therapy, total treatment duration, and overnight use led to a higher success rate (P = 0.002, P < 0.001, P < 0.001 resp.). Complications (22.8%, n = 59/259) were minor, recurrence occurred in 2.3% (n = 2/86) of patients. Of the patients treated while awaiting a Nuss procedure, 26.7% (n = 4/15) no longer required the Nuss procedure. Breast growth made 39.3% (n = 11/28) of female patients quit treatment. Deeper deformities (P = 0.02, P = 0.009), flexible chest wall (P = 0.007) and symptomatic pectus excavatum (P = 0.02) resulted in lower success rates. CONCLUSIONS: Vacuum bell therapy is successful in up to 52.1% of patients. Overnight vacuum bell use and treatment while awaiting a Nuss procedure should be encouraged. Older patients with a stiff chest wall can be successfully treated with prolonged treatment. For female patients watchful waiting or early treatment, to prevent challenges during breast growth, is preferred. LEVEL OF EVIDENCE: Level II.

Iodinated Contrast Induced Hypothyroidism in the Infant After Enteral Contrast Enema: A Case Report and Systematic Review.

Background: Excessive iodine intake triggers the Wolff-Chaikoff effect resulting in downregulation of thyroid hormone synthesis to prevent hyperthyroidism. Failure to escape the Wolff-Chaikoff effect can be seen especially in (premature born) infants and may result in prolonged iodine induced hypothyroidism. We describe a rare case of a preterm infant who developed severe iodinated contrast induced hypothyroidism after the use and prolonged stasis of enteral iodinated contrast media (ICM). In addition a systematic literature search was performed to evaluate all available data on this complication. Methods: A systematic literature search was performed in PubMed and Embase. Studies describing the effect of enteral ICM on thyroid function were considered eligible. The primary outcome was to determine the frequency of contrast induced hypothyroidism in infants after administration of enteral ICM. Results: The premature infant in our center developed severe iodinated contrast induced hypothyroidism after enteral ICM. In total, only two studies met our eligibility data, reporting eight patients. Out of these eight patients, four premature infants developed a contrast induced hypothyroidism after enteral administration of ICM. Conclusion: Data on severity, length and frequency of contrast induced hypothyroidism after exposure to enteral ICM is very scarce. The herein reported case and literature search illustrate the potential severity of the complication and underline the necessity of future studies on this topic. We recommend standardized monitoring of thyroid function after exposure to enteral ICM in newborns to prevent delayed diagnosis of severe contrast induced hypothyroidism until evidence based recommendations can be made.

Non-Invasive Assessment of Metabolic Dysfunction-Associated Steatotic Liver Disease in Adolescents with Severe Obesity; Patient Characteristics and Association with Leptin-A Cross-Sectional Overview of Baseline Data from a RCT.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common liver disease in adolescents with obesity. Nonetheless, the guidelines for screening and managing this disease are contradictory. The purpose of this study is to non-invasively assess the prevalence, patient characteristics, and potential associated factors of MASLD in this demographic. Methods: This study used baseline data from an RCT in adolescents eligible for bariatric surgery. MASLD was determined by measuring the hepatorenal index (HRI) with ultrasonography, blood liver tests, and the fatty liver index (FLI). Results: A total of 56 adolescents enrolled in the analyses; the majority were female n = 44 (79%); the mean age was 15.75 (±1.01) years; the average body mass index (BMI) was 44.08 (±5.16) kg/m2. In 35 (62.5%) of the patients, the HRI was abnormal. This group had a higher waist/hip ratio, elevated liver biochemistry, and significantly lower leptin levels (mean difference = -46.35, 95% CI -76.72, -15.99) compared to the group with a normal HRI. In 32 (55.2%) of the patients, ALT levels were elevated and the FLI was abnormal in all (100%) participants. Linear regression analysis indicated associations between the HRI and typical anthropometric and metabolic measurements; and an inverse association between HRI and leptin B = -0.003 (95% CI -0.005, -0.00), independently of sex- and age-adjusted BMI. Conclusions: MASLD is highly prevalent in adolescents with severe obesity. However, the prevalence strongly depends on which tool is used, namely the HRI (62.5%), alanine transaminase levels (55.2%), and FLI (100%). Our findings suggest that leptin may be a valuable biomarker in supporting the diagnosis of MASLD.

The Diagnostic Accuracy of Serum Alpha-Fetoprotein Levels in Follow-up for Recurrence of Sacrococcygeal Teratoma; a Nationwide Review of SCT Cases in the Netherlands.

BACKGROUND: Serum alpha-fetoprotein (AFP) is often used as tumour marker for recurrent sacrococcygeal teratoma (SCT). We aimed to assess the normal dynamics of serum AFP levels after initial resection and diagnostic accuracy of serum AFP levels the follow-up for recurrence in SCT. METHODS: This retrospective study included 57 patients treated for SCT in the six pediatric surgical centers in the Netherlands from 1980 to 2018. MAIN RESULTS: 57 patients were included in the study of whom 19 children developed 20 recurrences at a median of 14.0 months after initial resection. No significant difference was found in serum AFP level dynamics between the recurrence and non-recurrence group after initial resection (p = 0.950). Serum AFP levels did not significantly increase before recurrence (p = 0.106) compared to serum AFP levels of children without recurrence at the same time. However, serum AFP levels did significantly increase in malignant recurrences (n = 7) (p = 0.03) compared to patients without recurrence. A cut-off value of 55 µg/L was found to be predictive for recurrent SCT with an Area Under the Curve (AUC) of 0.636 with sensitivity of 50% and specificity of 100%. CONCLUSION: Dynamics of serum AFP levels are not different between patients with and without recurrence after initial resection of SCT. Serum AFP levels are not predictive for mature or immature recurrent SCT and normal AFP levels do not rule out recurrent SCT. However, serum AFP levels exceeding 55 µg/L can indicate recurrent SCT, especially malignant recurrences.

Intercostal Nerve Cryoablation or Epidural Analgesia for Multimodal Pain Management after the Nuss Procedure: A Cohort Study.

BACKGROUND: Nuss procedure for pectus excavatum is a minimally invasive, but painful procedure. Recently, intercostal nerve cryoablation has been introduced as a pain management technique. MATERIALS AND METHODS: In this cohort study, we compared the efficacy of multimodal pain management strategies in children undergoing a Nuss procedure. The effectiveness of intercostal nerve cryoablation combined with patient-controlled systemic opioid analgesia (PCA) was compared with continuous epidural analgesia (CEA) combined with PCA. The study was conducted between January 2019 and July 2022. Primary outcome was length of stay (LOS), and secondary outcomes were operation room time, postoperative pain, opioid consumption, and gabapentin use. RESULTS: Sixty-six consecutive patients were included, 33 patients in each group. The cryoablation group exhibited lower Numeric Rating Scale (NRS) pain scores on postoperative day 1 and 2 (p = 0.002, p = 0.001) and a shorter LOS (3 vs. 6 days (p < 0.001). Cryoablation resulted in less patients requiring opioids at discharge (30.3 vs. 97.0%; p < 0.001) and 1 week after surgery (6.1 vs. 45.4%; p < 0.001)). In the CEA group, gabapentin use was more prevalent (78.8 vs. 18.2%; p < 0.001) and the operation room time was shorter (119.4 vs. 135.0 minutes; p < .010). No neuropathic pain was reported. CONCLUSIONS: Intercostal nerve cryoablation is a superior analgesic method compared with CEA, with reduced LOS, opioid use, and NRS pain scores. The prophylactic use of gabapentin is redundant.

Weight Loss and Glycemic Control After Bariatric Surgery in Adolescents With Severe Obesity: A Randomized Controlled Trial.

PURPOSE: Bariatric surgery is regarded as a valuable treatment option for adolescents with severe obesity. However, high-quality evidence of its superiority over prolonged conservative treatment with multidisciplinary lifestyle intervention (MLI) is limited. This study investigated the efficacy and safety of bariatric surgery in adolescents without sufficient weight loss after MLI for severe obesity. METHODS: A two-group randomized controlled trial was designed to assess one-year health effects of bariatric surgery in adolescents with severe obesity. The participants were referred by pediatricians after completing MLI without sufficient effects. Eligible for participation were adolescents aged 14-16 years with severe obesity (age- and sex-adjusted body mass index (BMI) using the International Obesity Task Force cutoffs: BMI ≥40 kg/m2, or ≥35 kg/m2 in combination with comorbidity). Participants were assigned to MLI combined with laparoscopic adjustable gastric banding (n = 29) versus only MLI (n = 30). Participants were included from 2011 to 2019. Main outcomes were weight change and sex- and age-specific BMI loss. Additionaly, glucose metabolism, blood pressure and lipid profile were analysed. RESULTS: 53 patients completed the 12-months follow-up (89.8%). Mean (±standard deviation [SD]) weight loss in the surgery group was 11.2 ± 7.8% after 12 months, compared to a weight gain of 1.7 ± 8.1% in the control group. The fasting insulin, insulin resistance score and lipid profile improved significantly in the surgery group. DISCUSSION: Bariatric surgery was associated with substantial weight loss and improvements in glucose and lipid metabolism after 12 months compared to conservative treatment in adolescents with severe obesity.

Trends in Simple and Complex Appendicitis in Children and the Potential Correlation to Common Viral Pathogens-A Retrospective Cohort Study between 2010 and 2019 in The Netherlands.

The aim of this study was to evaluate the annual, seasonal and monthly trends in children with simple and complex appendicitis and their correlation to common viral pathogens in the Netherlands. A consecutive multicenter retrospective cohort study was performed between 2010 and 2019 including children (<18 years) surgically treated for appendicitis. The primary outcome was the distribution of children with simple and complex appendicitis per year, season and month. Relevant seasonal variation was defined as ≥5%. The secondary outcome was a positive correlation of the number of patients with simple and complex appendicitis to common viral pathogens (data anonymously provided by the Dutch Working Group on Clinical Virology from the Dutch Society for Clinical Microbiology (NVMM)). In total, 896 patients were included: N = 524 (58%) patients with simple and N = 372 (42%) with complex appendicitis. Of the children aged 0-5 years, 81% had complex appendicitis, versus 38% in 6-18 years (p < 0.001). An overall decline was demonstrated for both simple and complex appendicitis between 2010 and 2019. No seasonal variation was found for simple appendicitis. For complex appendicitis, the highest number of patients was found in spring, and lowest in summer (N = 372, spring 28.2 ± 5.1% versus summer 21.0 ± 5.8%, p = 0.011), but the variance was regarded as not relevant (<5% from baseline). A positive correlation was found between complex appendicitis with Adenovirus 40.41 (R = 0.356, 95%CI 0.045-0.604, p = 0.026) and simple appendicitis with Adenovirus NON 40.41 (R = 0.332, 95%CI 0.019-0.586, p = 0.039), but these correlations did not remain significant after a Bonferroni correction (p < 0.003). In conclusion, we found no relevant seasonal variation for simple or complex appendicitis, nor positive correlation with common viral pathogens.

Prognostic accuracy of factors associated with poor outcome in prenatally diagnosed sacrococcygeal teratoma: A systematic review and meta-analysis.

Several factors associated with poor outcome in patients with prenatally diagnosed sacrococcygeal teratoma (SCT) have been found. However, the prognostic accuracy of these factors has not been well established. Therefore, we aimed to systematically review the prognostic accuracy of factors associated with poor outcome in these patients. We queried Search Premier, COCHRANE Library, EMCARE, EMBASE, PubMed, ScienceDirect, and Web of Science databases to identify studies regarding patients with prenatally diagnosed SCT. Poor outcome was defined as termination of pregnancy (TOP), intrauterine fetal death (IUFD), or perinatal death. We estimated the odds ratio of factors associated with poor outcome. Eleven studies (447 patients) were included. Overall mortality, including TOP, was 34.9%. Factors associated with poor outcome in fetuses with prenatally diagnosed SCT were cardiomegaly, hypervascular tumor, solid tumor morphology, fetal hydrops, and placentomegaly. A tumor volume to fetal weight ratio (TFR) of >0.12 before a gestational age of 24 weeks is predictive of poor outcome. The prognostic accuracy of factors associated with poor outcome in fetuses prenatally diagnosed with SCT seems promising. Factors associated with cardiac failure such as cardiomegaly, hypervascular tumor, solid tumor morphology, fetal hydrops, placentomegaly, and TFR >0.12 were found to be predictive of poor outcome.

Implementing Contralateral Surgical Exploration during Hernia Repair in Children with Unilateral Inguinal Hernia: A Dutch Qualitative Study.

A total of 10-15% of children undergoing unilateral inguinal hernia repair develop a metachronous contralateral inguinal hernia (MCIH) that necessitates second anesthesia and surgery. Contralateral exploration can be performed to prevent MCIH development. This study investigates (1) factors that promote or hinder the adoption and (de-)implementation of contralateral groin exploration in children ≤ 6 months undergoing unilateral hernia repair and (2) strategies to overcome these barriers. A qualitative interview study was conducted using 14 semi-structured interviews and two focus groups involving healthcare professionals, stakeholders involved from a patients' perspective and stakeholders at the organizational/policy level. The results show that the effectiveness of surgical treatment and stakeholders' motivation and attitudes towards the intervention were reported as barriers for implementation, whereas patient and family outcomes and experience and strategies to overcome these barriers were identified as facilitating factors for future implementation. This study is unique in its contributions towards insights into facilitators and barriers for (de-)implementation of contralateral groin exploration in children with a unilateral inguinal hernia. In case the HERNIIA trial shows that contralateral exploration is beneficial for specific patient and family outcomes or a subgroup of children, the results of this study can help in the decision-making process as to whether contralateral exploration should be performed or not.

The Prevalence and Clinical Impact of Transition Zone Anastomosis in Hirschsprung Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Hirschsprung disease (HD) is characterized by absent neuronal innervation of the distal colonic bowel wall and is surgically treated by removing the affected bowel segment via pull-through surgery (PT). Incomplete removal of the affected segment is called transition zone anastomosis (TZA). The current systematic review aims to provide a comprehensive overview of the prevalence and clinical impact of TZA. METHODS: Pubmed, Embase, Cinahl, and Web of Sciences were searched (last search: October 2020), and studies describing histopathological examination for TZA in patients with HD were included. Data were synthesized into aggregated Event Rates (ER) of TZA using random-effects meta-analysis. The clinical impact was defined in terms of obstructive defecation problems, enterocolitis, soiling, incontinence, and the need for additional surgical procedures. The quality of studies was assessed using the Newcastle-Ottawa Scale. KEY RESULTS: This systematic review included 34 studies, representing 2207 patients. After excluding series composed of only patients undergoing redo PT, the prevalence was 9% (ER = 0.09, 95% CI = 0.05-0.14, p < 0.001, I2 = 86%). TZA occurred more often after operation techniques other than Duhamel (X2 = 19.21, p = <0.001). Patients with TZA often had obstructive defecation problems (62%), enterocolitis (38%), soiling (28%), and fecal incontinence (24%) in follow-up periods ranging from 6 months to 13 years. Patients with TZA more often had persistent obstructive symptoms (X2 = 7.26, p = 0.007). CONCLUSIONS AND INFERENCES: TZA is associated with obstructive defecation problems and redo PT and is thus necessary to prevent.

Should primary anastomosis be considered more? A retrospective analysis of anastomotic complications in young children.

Objective: Little is known about intestinal anastomotic leakage and stenosis in young children (≤3 years of age). The purpose of this study is to answer the following questions: (1) what is the incidence of anastomotic stenosis and leakage in infants? (2) which surgical diseases entail the highest incidence of anastomotic stenosis and leakage? (3) what are perioperative factors associated with anastomotic stenosis and leakage? Methods: Patients who underwent an intestinal anastomosis during primary abdominal surgery in our tertiary referral centre between 1998 and 2018 were retrospectively included. Both general incidence and incidence per disease of anastomotic complications were determined. Technical risk factors (location and type of anastomosis, mode of suturing, and suture resorption time) were evaluated by multivariate Cox regression for anastomotic stenosis. Gender and American Society of Anaesthesiology (ASA) score of ≥III were evaluated by χ2 test for anastomotic leakage. Results: In total, 477 patients underwent an anastomosis. The most prominent diseases are intestinal atresia (30%), Hirschsprung's disease (29%), and necrotizing enterocolitis (14%). Anastomotic stenosis developed in 7% (34/468) of the patients with highest occurrence in necrotizing enterocolitis (14%, 9/65). Colonic anastomosis was associated with an increased risk of anastomotic stenosis (hazard ratio (HR) =3.6, 95% CI 1.8 to 7.5). No technical features (type of anastomosis, suture resorption time and mode of suturing) were significantly associated with stenosis development. Anastomotic leakage developed in 5% (22/477) of the patients, with the highest occurrence in patients with intestinal atresia (6%, 9/143). An ASA score of ≥III (p=0.03) and male gender (p=0.03) were significantly associated with anastomotic leakage. Conclusions: Both anastomotic stenosis and leakage are major surgical complications. Identifying more patient specific factors can result in better treatment selection, which should not solely be based on the type of disease.

Diagnostic accuracy of ultrasonography to distinguish thyroglossal duct cysts from dermoid cysts in children with a midline neck swelling.

INTRODUCTION: Midline neck swellings are very common in children and mostly caused by thyroglossal duct cysts (TGDCs) or dermoid cysts (DCs). Since DCs can undergo simple excision, whilst TGDCs demand more thorough resection via Sistrunk procedure, it is important to differentiate between both pre-operatively. Previous studies have suggested an ultrasound-score (SIST) based on presence of septae, wall irregularity and solid components could do so. This study aims to evaluate the diagnostic accuracy of this score. METHODS: All patients (≤18 years) undergoing surgery between 2006 and 2018 for a midline neck mass at our tertiary centre with a histopathological diagnosis of TGDC or DC were retrospectively included. The pre-operative ultrasound was evaluated by an experienced radiologist and the SIST as well as location, tract, echogenicity, margin and multilocularity were scored. RESULTS: We included 97 children, of whom 67 (69 %) with TGDCs. The SIST showed a sensitivity of 37 %, specificity of 97 %, a positive predictive value of 96 % and a negative predictive value of 35 % for the SIST-score in detecting TGDCs, which resulted in an AUC of 0.67. In addition, internal echogenicity (P < 0.01) and margin definition (P < 0.01) were significantly associated to TGDC diagnosis whilst location and multilocularity were deemed insignificant following Bonferroni correction. CONCLUSION: We conclude that the SIST-score seems very capable to rule in TGDC. However, the SIST-score is far from making a clear distinction between DC and TGDCs preoperatively. The addition of other ultrasound variables, such as margin definition and echogenicity, might increase the diagnostic accuracy and demands further research.

Children with an Anorectal Malformation Going to Primary School: The Parent's Perspective.

BACKGROUND: Continence problems occur often in children with anorectal malformations (ARM). The aim of this study was to evaluate parental experiences with toilet facilities at Dutch primary schools and their experience with how schools deal with ARM children. METHODS: This survey was developed in collaboration with the national patient advocacy group (PAG). Recruitment for participation was conducted by the PAG (email listing and social media) and one expertise center for ARM. Participants were parents of school-attending ARM children aged 3 to 12 years. RESULTS: Sixty-one participants (31.9%) responded to the survey. The median age of the children was 7.0 years (IQR 5.0-9.0). Schools were often located in a village (63.9%) and encompassed 100-500 children (77.0%). In total, 14 parents (23.0%) experienced difficulties in finding a primary school. Experiences with the school were described as solely positive (37.7%), solely negative (9.8%), positive and negative (34.4%), and neither positive nor negative (16.4%). Regarding school toilet facilities, 65.6% of the toilets were reported clean and 78.7% were easily accessible. CONCLUSIONS: About 25% of parents reported difficulties in enrolling their children into primary school, and 45% reported negative experiences. This highlights the need for improved guidance and the optimization of education in schools when dealing with ARM children.

Impact of Presence, Level, and Closure of a Stoma on Growth in Young Children: A Retrospective Cohort Study.

INTRODUCTION: A stoma will cause nutrients loss which could result in impaired growth. Impaired growth can negatively impact long-term development. This study aims to evaluate: (1) the effect of stomas on growth comparing small bowel stoma versus colostomy and (2) if early closure (within 6 weeks), proximal small bowel stoma (within 50 cm of Treitz), major small bowel resection (≥ 30 cm), or adequate sodium supplementation (urinary level ≤ 30 mmol/L) influences growth. METHODS: Young children (≤ 3 years) treated with stomas between 1998 and 2018 were retrospectively identified. Growth was measured with weight-for-age Z-scores. Malnourishment was defined using the World Health Organization's definition. Comparison between changes in Z-scores at creation, closure, and a year following closure was done by Friedman's test with post hoc Wilcoxon's signed rank test or Wilcoxon's rank-sum test when necessary. RESULTS: In the presence of a stoma in 172 children, 61% showed growth decline. Severe malnourishment was seen at the time of stoma closure in 51% of the patients treated by small bowel stoma and 16% of those treated by colostomy. Within a year following stoma closure, 67% showed a positive growth trend. Having a proximal small bowel stoma and undergoing major small bowel resection led to significantly lower Z-scores at closure. Adequate sodium supplementation and early closure did not lead to significant changes in Z-scores. CONCLUSION: Stomas have a negative impact on growth in the majority of children. This impact might be decreased by preventing small bowel stomas when possible, specifically proximal stomas, and limiting small bowel resection. Since stoma closure is essential in reversing the negative effect on growth, we opt that early closure might result in an early shift to catch-up growth.

Diagnosing Hirschsprung Disease in Children Younger than 6 Months of Age: Insights in Incidence of Complications of Rectal Suction Biopsy and Other Final Diagnoses.

BACKGROUND: The gold standard for diagnosing Hirschsprung disease (HD) in patients younger than 6 months is pathological examination of rectal suction biopsy (RSB). The aim of this study was to gain insight into the following: (1) complications following RSB, (2) final diagnosis of patients referred for RSB, and (3) factors associated with HD. METHODS: Patients suspected of HD referred for RSB at our center were analyzed retrospectively. Severity of complications of RSB was assessed using Clavien-Dindo (CD) grading. Factors associated with HD were tested using multivariate logistic regression analysis. RESULTS: From 2000 to 2021, 371 patients underwent RSB because of infrequent defecation, at a median age of 44 days. Three patients developed ongoing rectal bleeding (0.8%) graded CD1. Most frequent final diagnoses were: HD (n = 151, 40.7%), functional constipation (n = 113, 31%), idiopathic meconium ileus (n = 11, 3%), and food intolerance (n = 11, 3%). Associated factors for HD were male sex (odds ratio [OR], 3.19; confidence interval [CI], 1.56-6.53), presence of syndrome (OR, 7.18; CI, 1.63-31.69), younger age at time of RSB (OR, 0.98; CI, 0.85-0.98), meconium passage for more than 48 hours (OR, 3.15; CI, 1.51-6.56), distended abdomen (OR, 2.09; CI, 1.07-4.07), bilious vomiting (OR, 6.39; CI, 3.28-12.47), and failure to thrive (OR, 8.46; CI, 2.11-34.02) (model R 2 = 0.566). CONCLUSION: RSB is a safe procedure with few and only minor complications. In the majority of patients referred for RSB under the age of 6 months, HD was found followed by a functional cause for the defecation problems. RSB should be obtained on a low threshold in all patients under the age of 6 months with the suspicion of HD.

Extracellular histone release by renal cells after warm and cold ischemic kidney injury: Studies in an ex-vivo porcine kidney perfusion model.

Extracellular histones are cytotoxic molecules involved in experimental acute kidney injury. In patients receiving a renal transplant from donors after circulatory death, who suffer from additional warm ischemia, worse graft outcome is associated with higher machine perfusate extracellular histone H3 concentrations. We now investigated temperature-dependent extracellular histone release in an ex vivo porcine renal perfusion model, and subsequently studied histone release in the absence and presence of non-anticoagulant heparin. Seven pairs of ischemically damaged porcine kidneys were machine perfused at 4°C (cold ischemia) or 28°C (warm ischemia). Perfusate histone H3 concentration was higher after warm as compared to cold ischemia (median (IQR) = 0.48 (0.20-0.83) µg/mL vs. 0.02 (0.00-0.06) µg/mL; p = .045, respectively). Employing immune-electron microscopy (EM), histone containing cytoplasmic protrusions of tubular and endothelial cells were found after warm ischemic injury. Furthermore, abundant histone localization was detected in debris surrounding severely damaged glomerular cells, in a "buck shot" pattern. In vitro, histones were cytotoxic to endothelial and kidney epithelial cells in a temperature-dependent manner. In a separate ex vivo experiment, addition of heparin did not change the total histone H3 levels observed in the perfusate but revealed a continuous increase in the level of a lower molecular weight histone H3 variant. Our findings show that ischemically damaged kidneys release more extracellular histones in warm ischemia, which by EM was due to histone release by renal cells. Blocking of histone-mediated damage during transplantation may be beneficial in prevention of renal injury.

Management and outcome of high-risk neuroendocrine tumors of the appendix in children; A systematic review.

This study systematically reviewed the literature to investigate the value of secondary surgery for children with a high-risk neuroendocrine tumor (NET) of appendix. A systematic search was performed in PubMed, Embase and Web of Science. All randomized controlled trials, cohort studies, and case series reporting on the management and outcomes of patients (<20 years) with a histopathologically proven NET of the appendix were eligible for inclusion. Two authors independently selected eligible articles, assessed risk of bias, and extracted data. The outcomes of patients with a high-risk NET treated with secondary surgery were compared to those treated without secondary surgery. Primary outcomes were recurrence rate and disease-free survival. The literature search yielded 667 articles, of which 29 were included. These studies reported on 1112 patients, of whom 145 (13%) had high-risk NET. Heterogeneity between studies was large and risk of bias was serious in 26 and moderate in three studies. Secondary surgery after primary appendectomy was performed in 64 of 145 patients (44%). Length of follow-up ranged between 0 and 612 months. In both treatment groups no recurrences were reported, and thus disease-free survival was 100%. Based on current literature, the value of secondary surgery for pediatric high-risk NET of the appendix may be questioned. However, evidence is scarce, of low-quality, and heterogeneity between studies is large. Large international studies with adequate follow-up are needed to generate high-quality evidence on this topic.

Systematic Review of Definitions and Outcome Measures for Postoperative Ileus and Return of Bowel Function after Abdominal Surgery in Children.

This review aims to objectify which definitions and outcome measures are used for the return of bowel function and postoperative ileus in children. PubMed and Embase were systematically searched from inception to December 17, 2020. Prospective studies conducted in children (aged 0-18 years) undergoing gastrointestinal surgery which reported on definitions and/or outcome measures for post-operative ileus or return of bowel function were evaluated. Definitions and outcome measures were extracted. From 4,027 references, 71 articles were included. From the 17 articles mentioning postoperative ileus, 8 (47%) provided a definition. In total, 34 outcome measures were used and 12 were unique. "Abdominal distension" was the most reported (41%) measure. In 41%, the outcome measures only described the return of gastric motility, while 18% described the return of intestinal motility. The return of bowel function was mentioned in 67 articles, none provided a definition. In total, 133 outcome measures were used and 37 were unique. Time to oral intake was the most reported (14%) measure. In 49%, the outcome measures only described the return of gastric motility, while 10% described the return of intestinal motility. High variation in definitions and outcome measures has limited the generalizability of research into postoperative bowel function in children. Without standardization, it will be impossible to compare research results and evaluate treatments. In children, the return of gastric motility seemingly should get more focus compared to adults. Therefore, we believe that a definition of postoperative ileus with an accompanying core outcome set, developed by a multidisciplinary team, specifically for children is required.

Perioperative Hypoxemia and Postoperative Respiratory Events in Infants with Hypertrophic Pyloric Stenosis.

BACKGROUND: Normalization of metabolic alkalosis is an important pillar in the treatment of infantile hypertrophic pyloric stenosis (IHPS) because uncorrected metabolic alkalosis may lead to perioperative respiratory events. However, the evidence on the incidence of respiratory events is limited. We aimed to study the incidence of peroperative hypoxemia and postoperative respiratory events in infants undergoing pyloromyotomy and the potential role of metabolic alkalosis. MATERIALS AND METHODS: We retrospectively reviewed all patients undergoing pyloromyotomy between 2007 and 2017. All infants received intravenous fluids preoperatively to correct metabolic abnormalities close to normal. We assessed the incidence of perioperative hypoxemia (defined as oxygen saturation [SpO2] < 90% for > 1min) and postoperative respiratory events. Additionally, the incidence of difficult intubations was evaluated. We performed a multivariate logistic regression analysis to evaluate the association between admission or preoperative serum pH values, bicarbonate or chloride, and peri- and postoperative hypoxemia or respiratory events. RESULTS: Of 406 included infants, 208 (51%) developed 1 or more episodes of hypoxemia during the perioperative period, of whom 130 (32%) experienced it during induction, 43 (11%) intraoperatively, and 112 (28%) during emergence. About 7.5% of the infants had a difficult intubation and 17 required more than 3 attempts by a pediatric anesthesiologist. Three patients developed respiratory insufficiency and 95 postoperative respiratory events were noticed. We did not find a clinically meaningful association between laboratory values reflecting metabolic alkalosis and respiratory events. CONCLUSIONS: IHPS frequently leads to peri- and postoperative hypoxemia or respiratory events and high incidence of difficult tracheal intubations. Preoperative pH, bicarbonate, and chloride were bad predictors of respiratory events.

Enhanced Th17 responses in the appendix of children with complex compared to simple appendicitis are associated with microbial dysbiosis.

Introduction: Appendicitis is one of the most common causes of acute abdominal surgery in children. The clinical course of appendicitis ranges from simple to complex appendicitis. The mechanisms underlying the heterogeneity of appendicitis in children remain largely unclear. Dysregulated T cell responses play an important role in several inflammatory diseases of the intestine, but the extend of T cell dysregulation in appendicitis in children is less well known. Methods: To characterize appendiceal T cells in simple and complex appendicitis we performed in-depth immunophenotyping of appendiceal-derived T cells by flow cytometry and correlated this to appendiceal-derived microbiota analyses of the same patient. Results: Appendix samples of twenty children with appendicitis (n = 8 simple, n = 12 complex) were collected. T cells in complex appendicitis displayed an increased differentiated phenotype compared to simple appendicitis, including a loss of both CD27 and CD28 by CD4+ T cells and to a lesser extent by CD8+ T cells. Frequencies of phenotypic tissue-resident memory CD69+CD4+ T cells and CD69+CD8+ T cells were decreased in children with complex compared to simple appendicitis, indicating disruption of local tissue-resident immune responses. In line with the increased differentiated phenotype, cytokine production of in particular IL-17A by CD4+ T cells was increased in children with complex compared to simple appendicitis. Furthermore, frequencies of IL-17A+ CD4+ T cells correlated with a dysregulation of the appendiceal microbiota in children with complex appendicitis. Conclusion: In conclusion, disruption of local T cell responses, and enhanced pro-inflammatory Th17 responses correlating to changes in the appendiceal microbiota were observed in children with complex compared to simple appendicitis. Further studies are needed to decipher the role of a dysregulated network of microbiota and Th17 cells in the development of complex appendicitis in children.