Comparative histological analysis of spleens in pediatric patients with hemolytic anemias: Insights into the pathophysiological mechanisms of spleen destruction in sickle cell anemia.

While sickle cell anemia (SCA) and hereditary spherocytosis (HS) share common features of increased spleen erythrophagocytosis due to increased red blood cell (RBC) turnover, SCA is specifically characterized by susceptibility to infections. In this study, histological lesions in the spleens of pediatric patients with SCA were analyzed, in close correlation with past clinical history and comparatively to HS, healthy and transfused ß-thalassemia patients (TDT). An evaluation of red pulp elementary lesions (red pulp fibrosis, iron deposition, number of Gandy-Gamna, and RBC trapping) combined into a severity score was established, as well as B-cell follicles analysis. Quantification on digitalized slides of iron deposition, RBC trapping, and red pulp fibrosis was additionally performed. Spleens from 22 children with SCA, eight with HS, eight with TDT, and three healthy controls (HC) were analyzed. Median age at splenectomy was not different between SCA and HS patients, 6.05 years (range: 4.5-16.0) versus 4.75 (range: 2.2-9.5). Marked heterogeneity was found in SCA spleens in contrast to other conditions. Contrary to previous reports, B-cell follicles were generally preserved in SCA. While RBC trapping was significantly increased in both SCA and HS (compared to TDT and HC), quantitative fibrosis and overall red pulp severity score were significantly increased in SCA spleens compared to other conditions. Moreover, there was an inverse correlation between quantitative fibrosis and number of B-cell follicles, linking these two compartments as well as spleen fibrosis to infectious susceptibility in SCA, potentially through impaired red pulp macrophage scavenging and B-cell subpopulations defects.

Intraperitoneal insufflation of carbon dioxide rescues intestinal damage in an experimental murine model of colitis.

OBJECTIVES: Necrotizing enterocolitis (NEC) is a severe neonatal surgical condition, associated with a prolonged pro-inflammatory state, leading to high mortality and morbidity rates. Carbon dioxide (CO2 ) insufflation during laparoscopy may have an anti-inflammatory effect. We aimed to evaluate the effects of CO2 -insufflation on experimental colitis. METHODS: Acute colitis was induced in 6-week-old Balb/c mice by the administration of 2%-dextran sulfate-sodium (DSS) during 7 days (n = 45). On Day 4, two groups received intraperitoneal insufflation (duration: 30 mn, pressure: 5 mmHg) of CO2 ("DSS+CO2 ") or air ("DSS+air"). A group received no insufflation ("DSS"). Groups were compared for clinical severity using the disease activity index (DAI-body weight loss, stool consistency, and bleeding), histological severity (histopathological activity index, colon length, and ulcerations), colonic mucosecretion, and inflammation. RESULTS: DAI was significantly decreased in DSS+CO2 group, compared to DSS (p < 0.0001) or DSS+air (p < 0.0001) groups. Colon length was increased in DSS+CO2 treated mice compared to DSS (p = 0.0002). The histopathological activity index was lower in DSS+CO2 (vs. DSS, p = 0.0059/vs. DSS+air, p = 0.0389), with decreased ulcerations (3.77 vs. 10.7, p = 0.0306), and persistent mucosecretion with increased mucin-secreting cells. CONCLUSIONS: CO2 -insufflation attenuates DSS-induced colitis and improves both clinical and histological scores. Laparoscopy with CO2 insufflation represents a therapeutic anti-inflammatory strategy for NEC.

Complications after Heller myotomy in children: a national multicenter study on the impact of prior endoscopic dilatation and identification of risk factors.

BACKGROUND: Although esophageal achalasia has been historically treated by Heller myotomy, endoscopic esophageal dilatations are nowadays often the first-line treatment in children. The aim was to assess whether performing an endoscopic dilatation before a Heller myotomy is associated with higher risks of esophageal perforation in children. METHODS: A retrospective multicentric study was performed, including children that underwent a Heller myotomy (2000-2022, 10 centers). Two groups were compared based on the history of previous dilatation before myotomy. Outcomes esophageal perforation (intra-operative or secondary) and post-operative complications requiring surgery (Clavien-Dindo III). Statistics Comparisons using contingency tables or Kruskal-Wallis when appropriate. Statistical significance: p-value < 0.05. RESULTS: A Heller myotomy was performed in 77 children (median age: 11.8 years), with prior endoscopic dilatation in 53% (n = 41). A laparoscopic approach was used in 90%, with associated fundoplication in 95%. Esophageal perforation occurred in 19% of children (n = 15), including 12 patients with intra-operative mucosal tear and 3 with post-operative complications related to an unnoticed esophageal perforation. Previous endoscopic dilatation did not increase the risk of esophageal perforation (22% vs 17%, OR: 1.4, 95%CI: 0.43-4.69). Post-operative complications occurred in 8% (n = 6), with similar rates regardless of prior endoscopic dilatation. Intra-operative mucosal tear was the only risk factor for post-operative complications, increasing the risk of complications from 5 to 25% (OR: 6.89, 95%CI: 1.38-31.87). CONCLUSIONS: Prior endoscopic dilatations did not increase the risk of esophageal perforation or postoperative complications of Heller myotomy in this cohort of children with achalasia. Mucosal tear was identified as a risk factor for post-operative complications.

Early splenectomy in a large cohort of children with sickle cell anemia: risks and consequences.

In children with sickle cell anemia (SCA), early splenic complications can require splenectomy, but the benefit-to-risk ratio and the age at which splenectomy may be safely performed remain unclear. To address this question, we analyzed the rate of post-splenectomy events in children with SCA splenectomized between 2000-2018 at the Robert Debré University Hospital, Paris, France. A total of 188 children underwent splenectomy, including 101 (11.9%) from our newborn cohort and 87 referred to our center. Median (Q1-Q3) age at splenectomy was 4.1 years (range 2.5-7.3 years), with 123 (65.4%) and 65 (34.6%) children splenectomized at ≥3 years of age or <3 years of age, respectively. Median postsplenectomy follow-up was 5.9 years (range 2.7-9.2 years) yielding 1192.6 patient-years (PY) of observation. Indications for splenectomy were mainly acute splenic sequestration (101 [53.7%]) and hypersplenism (75 [39.9%]). All patients received penicillin prophylaxis; 98.3% received 23-valent polysaccharic pneumococcal (PPV-23) vaccination, and 91.9% a median number of 4 (range 3-4) pneumococcal conjugate vaccine shots prior to splenectomy. Overall incidence of invasive bacterial infection and thrombo-embolic events were 0.005 / PY (no pneumococcal infections) and 0.003 / PY, respectively, regardless of age at splenectomy. There was an increased proportion of children with cerebral vasculopathy in children splenectomized <3 years of age (0.037 / PY vs. 0.011 / PY; P<0.01). A significantly greater proportion of splenectomized than non-splenectomized children were treated with hydroxycarbamide (77.2% vs. 50.1%; P<0.01), suggesting a more severe phenotype in children who present spleen complications. If indicated, splenectomy should not be delayed in children, provided recommended pneumococcal prophylaxis is available. Spleen complications in childhood may serve as a marker of severity.

Usefulness of routine early œsophagogram after primary repair of œsophageal atresia: a multicenter study.

BACKGROUND: Advances in surgical and neonatal care have led to improved survival of patients with œsophageal atresia (OA) over time. Morbidity remains significant, with one-third of patients being affected by a postoperative complication. Several aspects of management are not consensual, such as the use of œsophagogram before starting oral feeding. METHODS: We conducted a multicenter retrospective study, including all children with OA that underwent a primary anastomosis in the first days of life, between 2012 and 2018 in five French centers, to determine the usefulness of postoperative œsophagogram during the 10 days after early primary repair of OA to diagnose the anastomotic leak and congenital œsophageal stenosis. RESULTS: Among 225 included children, 90 (40%) had a routine œsophagogram and 25 (11%) had an anastomotic leak, clinically diagnosed before the scheduled œsophagogram in 24/25 (96%) children at median postoperative day 4. Ten patients had associated congenital œsophageal stenosis diagnosed on the œsophagogram in only 30% of cases. CONCLUSION: Early œsophagogram is rarely useful in the diagnosis of an anastomotic leak, which is clinically diagnosed before performing an œsophagogram in the majority of cases. The need for a postoperative œsophagogram should be evaluated on a case-by-case basis. IMPACT: Early œsophagogram is not helpful in the diagnosis of an anastomotic leak in the majority of cases. An anastomotic leak is most often diagnosed clinically before performing an œsophagogram. Early postoperative œsophagogram could be helpful for the diagnosis of congenital œsophageal stenosis. However, dysphagia occurs later and early diagnosis of congenital œsophageal stenosis has no impact on the management and outcome of asymptomatic children. Indication of postoperative œsophagogram has to be evaluated on a case-by-case basis.

Jejunal Feeding by Gastrojejunal Tube in Pediatric Refractory Gastroesophageal Reflux Disease.

OBJECTIVES: The objective of this study is to determine whether jejunal nutrition by gastrojejunal tube (GJT) could be a therapeutic option for refractory gastroesophageal reflux disease (GERD), avoiding further antireflux surgery. METHODS: A monocentric retrospective study was conducted for all children <18 years who underwent GJT placement to treat GERD. We collected data at the first GJT placement, 5 months after last GJT withdrawal, and at the end of the follow-up (June 2021). RESULTS: Among 46 GERD patients with 86 GJT, 32 (69.6%) and 30 (65.2%) avoided antireflux surgery 5 and 28 months, respectively, after the definitive GJT removal. Five months after GJT removal, discharge from hospital, transition to gastric nutrition, GERD complications, and treatment were significantly improved. Median age and weight at the first GJT placement were 7 months and 6.8 kg. Patients had digestive comorbidities or complicated GERD in 69.6% and 76.1% patients, respectively. The median duration of jejunal nutrition using GJT was 64.5 days. GJT had to be removed in 63 (75.9%) cases for technical problems. CONCLUSIONS: Jejunal nutrition by GJT could be an alternative to antireflux surgery avoiding sustainably antireflux surgery in most of complicated GERD patients. The high frequency of mechanical complications raises that these devices should be technically improved.

Predicting the risk of respiratory distress in newborns with congenital pulmonary malformations.

OBJECTIVES: Most children with prenatally diagnosed congenital pulmonary malformations (CPMs) are asymptomatic at birth. We aimed to develop a parsimonious prognostic model for predicting the risk of neonatal respiratory distress (NRD) in preterm and term infants with CPM, based on the prenatal attributes of the malformation. METHODS: MALFPULM is a prospective population-based nationally representative cohort including 436 pregnant women. The main predictive variable was the CPM volume ratio (CVR) measured at diagnosis (CVR first) and the highest CVR measured (CVR max). Separate models were estimated for preterm and term infants and were validated by bootstrapping. RESULTS: In total, 67 of the 383 neonates studied (17%) had NRD. For infants born at term (>37 weeks, n=351), the most parsimonious model included CVR max as the only predictive variable (receiver operating characteristic (ROC) curve area: 0.70±0.04, negative predictive value: 0.91). The probability of NRD increased linearly with increasing CVR max and remained below 10% for CVR max <0.4. In preterm infants (n=32), both CVR max and gestational age were important predictors of the risk of NRD (ROC: 0.85±0.07). Models based on CVR first had a similar predictive ability. CONCLUSIONS: Predictive models based exclusively on CVR measurements had a high negative predictive value in infants born at term. Our study results could contribute to the individualised general risk assessment to guide decisions about the need for newborns with prenatally diagnosed CPM to be delivered at specialised centres.

Intraoperative cerebral oxygen saturation and neurological outcomes following surgical management of necrotizing enterocolitis: Predictive factors of neurological complications following neonatal necrotizing enterocolitis: Predictive factors of neurological complications following neonatal necrotizing enterocolitis.

BACKGROUND: The goal of the present study was to investigate intraoperative factors associated with major neurological complications at 1 year following surgery for necrotizing enterocolitis. MATERIAL AND METHODS: The study consisted of a retrospective review of medical charts of patients operated for over one calendar year in one institution. Data collected included demographic data, cardiac resuscitation at birth, Bell classification, antibiotics usage, time of day of surgery, surgical technique, surgical duration, type of ventilation, intraoperative vasoactive agents, and albumin use, nadir cerebral saturation, the decrease in cerebral saturation from baseline, the time period when cerebral saturation was at least 20% below baseline, and the mean arterial pressure at nadir cerebral saturation. Reported follow-up complications were assessed during formal neonatologist consultation and additional imaging exploration as needed. Analyses included descriptive statistics, and univariable and multivariable statistics. RESULTS: The study included 32 patients with no prior clinical neurological complications, of which 25 had normal cerebral imaging. Severe neurological complications occurred in nine patients at 1 year: Intraventricular hemorrhage (N = 2) and Periventricular leukomalacia (N = 7). However, preoperative cerebral imaging was lacking in seven patients. Consequently, the observed neurological complications at 1 year might be present before the surgery. Multivariable analysis found the decrease in cerebral saturation ≥36% from baseline as the only factor associated with the occurrence of those complications. CONCLUSION: Intraoperative decrease of cerebral oxygen saturation below ≥36% from baseline is associated with severe neurological complications in neonates undergoing surgery for necrotizing enterocolitis.

Risk Factors of Early Mortality and Morbidity in Esophageal Atresia with Distal Tracheoesophageal Fistula: A Population-Based Cohort Study.

OBJECTIVE: To identify the risk factors for early mortality and morbidity in a population with distal esophageal atresia (EA)-tracheoesophageal fistula. STUDY DESIGN: Cohort study from a national register. Main outcomes and measures included early mortality, hospital length of stay (LoS), need for nutritional support at 1 year of age as a proxy measure of morbidity, and complications during the first year of life. RESULTS: In total, 1008 patients with a lower esophageal fistula were included from January 1, 2008, to December 31, 2014. The survival rate at 3 months was 94.9%. The cumulative hospital LoS was 31.0 (17.0-64.0) days. Multivariate analysis showed that intrahospital mortality at 3 months was associated with low birth weight (OR 0.52, 95% CI [0.38-0.72], P < .001), associated cardiac abnormalities (OR 6.09 [1.96-18.89], P = .002), and prenatal diagnosis (OR 2.96 [1.08-8.08], P = .034). LoS was associated with low birth weight (-0.225 ± 0.035, P < .001), associated malformations (0.082 ± 0.118, P < .001), surgical difficulties (0.270 ± 0.107, P < .001), and complications (0.535 ± 0.099, P < .001) during the first year of life. Predictive factors for dependency on nutrition support at 1 year of age were complications before 1 year (OR 3.28 [1.23-8.76], P < .02) and initial hospital LoS (OR 1.96 [1.15-3.33], P < .01). CONCLUSIONS: EA has a low rate of early mortality, but morbidity is high during the first year of life. Identifying factors associated with morbidity may help to improve neonatal care of this population.

Concomitant gastrostomy tube insertion during laparoscopic Nissen fundoplication for gastro-esophageal reflux disease: analysis of risk factors for fundoplication failure.

BACKGROUND: Laparoscopic Nissen fundoplication (LNF) and gastrostomy tube (GT) placement may be performed concomitantly in children with gastro-esophageal reflux disease (GERD) and failure to thrive. We aimed to evaluate the rate and risk factors for LNF failure in children undergoing concomitant LNF/GT. METHODS: A retrospective multi-institutional cohort study was conducted, reviewing patients that underwent LNF (2005-2014). Data collected included patient demographics, comorbidities, and type of GT (laparoscopy- or endoscopy-assisted). The primary outcome measure was LNF failure. Data was compared using contingency tables or Mann-Whitney tests, when appropriate. An exploratory analysis by Kaplan-Meier survival and Cox proportional hazards analysis was performed to determine predictors of time to LNF failure after LNF/GT. RESULTS: Of 189 children that underwent LNF, 99 (52%) had a concomitant GT (55% laparoscopy-, 45% endoscopy-assisted). LNF failed in 15% after LNF/GT and in 17% after LNF alone (p = 0.84), at a median age of 23 months (IQR 8-41). Using univariate analysis, we found that a younger age at the time of surgery (p = 0.05), prematurity (p = 0.0018), esophageal atresia (p = 0.01), and endoscopy-assisted GT (p = 0.02) were potential predictors of LNF failure after LNF/GT. After multivariate regression analysis, prematurity (p = 0.007) remained significantly associated with LNF failure after LNF/GT. No predictive factors for LNF failure after LNF alone were identified. CONCLUSIONS: Concomitant GT insertion and LNF is a common practice, as half of the children that undergo LNF also received GT insertion. Children born preterm or with esophageal atresia comprise a fragile population at high-risk of LNF failure after LNF/GT. Prospective, multicentric studies are needed to evaluate the best GT technique to use in children undergoing LNF.

The role of a pediatric tertiary care center in avoiding collateral damage for children with acute appendicitis during the COVID-19 outbreak.

PURPOSE: To evaluate the impact of the COVID-19 pandemic-related lockdown on management and outcomes of children with acute appendicitis. METHODS: A retrospective cohort study was conducted, including children treated for acute appendicitis (January 20th-May 11th, 2020). The data regarding the severity of appendicitis and outcome were collected and compared for two time periods, before and after the nationwide lockdown (March 17th, 2020). RESULTS: The number of cases of acute appendicitis increased by 77% during the lockdown (n = 39 vs. n = 69, p = 0.03). During the lockdown, children treated for appendicitis were older (11.1 vs. 8.9 years, p = 0.003), and were more likely to live more than 5 km away from our institution (77% vs. 52%, p = 0.017). Less children had previously consulted a general practitioner (15% vs. 33%, p = 0.028), whereas more children were transferred from other hospitals (52% vs. 31%, p = 0.043). There was no difference in terms of length of hospital stay, rate of postoperative intra-abdominal abscess, ER visits, and readmissions between both periods. Three children (4%) were diagnosed with COVID-19 and appendicitis. CONCLUSIONS: Despite an increase in the number of children with appendicitis managed at our hospital during the COVID-19-related lockdown, management, and outcome remained similar. Although our pediatric center was strongly affected by this pandemic, maintaining our prior practice strategies for acute appendicitis avoided the occurrence of collateral damage for those children.

Mowat Wilson syndrome and Hirschsprung disease: a retrospective study on functional outcomes.

AIM OF THE STUDY: Mowat Wilson syndrome (MWS) is a complex genetic disorder due to mutation or deletion of the ZEB2 gene (ZFHX1B), including multiple clinical features. Hirschsprung disease is associated with this syndrome with a prevalence between 43 and 57%. The aim of this study was to demonstrate the severe outcomes and the high complication rates in children with MWS, focusing on their complicated follow-up. METHODS: A retrospective comparative study was conducted on patients referred to Robert-Debré Children's Hospital for MWS from 2003 to 2018. Multidisciplinary follow-up was carried out by surgeons, geneticists, gastroenterologists, and neurologists. Data regarding patient characteristics, surgical management, postoperative complications, and functional outcomes were collected. RESULTS: Over this period of 15 years, 23 patients were diagnosed with MWS. Hirschsprung disease was associated with 10 of them (43%). Of these cases, two patients had recto-sigmoïd aganglionosis (20%), three had aganglionic segment extension to the left colic angle (30%), two to the right colic angle (20%), and three to the whole colon (30%). The median follow-up was 8.5 years (2 months-15 years). All patients had seizures and intellectual disability. Six children (60%) presented with cardiac defects. At the last follow-up, three patients still had a stoma diversion and 7 (70%) were fed orally. One patient died during the first months. Eight (80%) of these children required a second surgery due to complications. At the last follow-up, three patients reported episodes of abdominal bloating (42%), one recurrent treated constipation (14.3%), and one soiling (14.3%). Genetic analysis identified three patients with heterozygous deletions, three with codon mutations, and three with frameshift mutations. CONCLUSIONS: MWS associated with Hirschsprung disease has a high rate of immediate surgical complications but some patients may achieve bowel function comparable with non-syndromic HD patients. A multidisciplinary follow-up is required for these patients. LEVEL OF EVIDENCE: Retrospective observational single cohort study, Level 3.

Predictors of the Performance of Early Antireflux Surgery in Esophageal Atresia.

OBJECTIVE: To identify predictors of and factors associated with the performance of antireflux surgery during the first year of life in children born with esophageal atresia. STUDY DESIGN: All patients were included in a French registry for esophageal atresia. All 38 multidisciplinary French centers completed questionnaires about perinatal characteristics and one-year outcome for children born with esophageal atresia. RESULTS: Of 835 infants with esophageal atresia born in France from 2010 to 2014, 682 patients, excluding those with long-gap esophageal atresia, were included. Three patients had type I, 669 had type III, and 10 had type IV esophageal atresia. Fifty-three children (7.8%) received fundoplication during the first year of life. The median age at the time of the end-to-end esophageal anastomosis was 1.1 day (range 0-15). Multivariate analysis identified three perioperative factors that predicted the need for early antireflux surgery: anastomotic tension (P = .004), associated malformations (P = .019), and low birth weight (P = .018). Six other factors, measured during the first year of life, were associated with the need for antireflux surgery: gastroesophageal reflux (P < .001), anastomotic stricture (P < .001), gastrostomy (P < .001), acute life-threatening event (P = .002), respiratory complications (P = .045), and poor nutritional status (P < .001). CONCLUSIONS: Gastroesophageal reflux disease, low birth weight, poor nutrition, and surgical anastomosis difficulties predicted the performance of antireflux surgery in the first year of life in infants with esophageal atresia.

[Pulmonary glial heterotopia: Unique lesion in an infant with anencephalic twin]. / Hétérotopie gliale pulmonaire : une lésion exceptionnelle chez un nourrisson avec un jumeau anencéphale.

Pulmonary glial heterotopia is an extremely rare entity whose pathophysiology remains unclear. We report for the first time one case of pulmonary glial heterotopia occured in a one-month baby free from any malformation. She has the particularity of being born from monozygotic monochorionic twin pregnancy where her anencephalic exencephalic sister suffered a medical termination of pregnancy. She presented neonatal respiratory distress, which recurred one month later. Chest X-ray revealed bilateral cystic pulmonary lesions mainly located in the right lung. Given the suspicion of congenital cystic adenomatoid malformation (CCAM), she underwent an upper and a lower right lung lobectomy at four months old. The pathological study found a multi-cystic lesion consisted of well-differentiated and poorly cellular glial tissue sometimes lined by bronchic epithelium. There was no pathological evidence for a CCAM. The evolution was favorable after surgery with an infant who was well five months later. This is one of the very few cases where the disease did not lead to rapid death in utero or during the perinatal period. This suggests that effective management by surgery could be a decisive factor in the survival of these patients.

Routine multi detector computed tomography evaluation of tracheal impairment compared to laryngo-tracheal endoscopy in children with vascular ring.

PURPOSE: The aim of this study is to compare free-breathing routine multi detector computed tomography (MDCT) and laryngo-tracheal (LT) flexible endoscopy in the evaluation of tracheal impairment in children with vascular ring (VR). MATERIALS AND METHODS: We performed a retrospective and monocentric study of all patients with VR from 1997 to 2014. Clinical data included: initial symptoms, type of surgery and clinical outcome. MDCT were blindly reviewed by two radiologists in consensus, independently of LT endoscopy results. Radiologic and endoscopic results were reviewed according to four criteria: percentage of tracheal narrowing, distance of the compression from carina, presence of bronchial compression and signs of tracheomalacia (TM). Concordance was evaluated for each criterion with a Spearman coefficient. RESULTS: From 1997 to 2016, 21 patients with a vascular ring were operated on, among which 57% by thoracoscopy: double aortic arch (n = 14), Neuhauser anomaly (n = 4) and Right aorta + aberrant right subclavian artery (n = 3). 90% of them presented with respiratory symptoms among which 43% of stridor. Chest X-ray was suggestive of VR in 87% of the cases. MDCT images and LT endoscopy results were available and analyzed for nine patients. Concordance (Spearman correlation coefficient) was excellent for percentage and level of tracheal narrowing (1) and good for TM (0.79). CONCLUSION: Free breathing routine MDCT is a reliable exam compared to LT endoscopy in the evaluation of tracheal impairment in children with VR. In case of respiratory symptoms (except stridor) and suggestive chest X-ray of VR, endoscopy could be avoided and routine MDCT alone performed.