Long-term follow-up after retrosternal ileocolic esophagoplasty in two cases of long-gap esophageal atresia: why it is still a valid option as a rescue strategy

IntroductionEsophageal replacement surgery in children is sometimes necessary for long-gap esophageal atresia. Ileocolic esophagoplasty in the retrosternal space can serve as a good alternative technique in case of hostile posterior mediastinum. We present two cases of successful ileocolic transposition performed at 6 months of age.MethodsEsophageal replacement was performed through a midline laparotomy incision associated with a left cervical approach. The ileocolic transplant was pediculized on the right superior colic artery after ligating the right colic and ileocolic vessels. A retrosternal tunnel was created, and the ileocolic transplant pulled through it to reach the cervical region. Proximally, esophageal-ileal anastomosis and, distally, colonic–gastric anastomosis were performed. Ileocolic continuity was repaired.ResultsThere were no early postoperative complications. In both cases, the patients presented oral feeding difficulties during the first 6 postoperative months. Thereafter, full oral feeding was achieved, and both patients were clinically asymptomatic during the following 18 and 20 years, respectively, with satisfactory oral radiological assessments, showing no redundancy or inappropriate growth of the graft and no anastomotic stricture. Currently, these patients do not complain of dysphagia, pathological reflux, or respiratory symptoms.ConclusionWhen native esophagus preservation in long-gap esophageal atresia is estimated unfeasible, ileocolic transposition in the retrosternal space might be considered a good and safe option, particularly in those difficult cases after multiple previous surgical attempts and mediastinitis. This technique is putatively associated with a beneficial anti-reflux effect, thanks to the presence of the ileocecal valve, in preventing cervical peptic esophagitis. Long-term follow-up confirms that the transposed colon in the retrosternal space did not suffer any abnormal modification in size and growth

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life

Liver abscesses in the Western pediatric population.

Liver abscesses are rare in the Western pediatric population and data on predisposing factors and etiology are scarce. We aimed to describe predisposing factors, microbiological characteristics, and treatment. Retrospective analysis of children admitted to two tertiary care hospitals in Belgium from 1 January 1996 to 31 December 2019. We analyzed clinical features, predisposing factors, imaging characteristics, microbiological data, treatment, and outcome in children with a liver abscess and compared these data with the literature. We collected 24 cases with a male to female ratio of 1.4 and a median age of 3.2 years at time of diagnosis. Survival was 95.8%. Invasive culture specimens were obtained in 83.3% and showed growth of bacteria in 55%. Parenteral antibiotics were administered before invasive culture sampling in 80%. Liver abscesses were cryptogenic in four (16.7%) patients. Hepatobiliary disease was the most prevalent predisposing factor (n = 6; 25%), followed by recent antineoplastic therapy for malignancies (n = 5; 20.8%), intra-abdominal surgical pathology (n = 4; 16.7%) and umbilical venous catheters (n = 2; 8.3%). In two patients there was a parasitic origin (n = 2; 8.3%) and in one it was caused by Bartonellosis. There was no diagnosis of chronic granulomatous disease (CGD) in our cohort. Pediatric liver abscesses have a favorable outcome in the developed world. Whenever feasible, invasive abscess culture specimens should be obtained. In patients presenting with a cryptogenic liver abscess or atypical disease course, immunological workup should be ensured

L’everolimus comme traitement de deuxième/troisième ligne dans l’hépatite auto-immune pédiatrique

Objectifs : L’hépatite auto-immune (HAI) est une maladie inflammatoire chronique qui peut mener à la cirrhose chez les patients réfractaires au traitement conventionnel. Les traitements de seconde ligne actuels ont une efficacité variable et un niveau de recommandation faible. Dans ce contexte, l’utilisation des inhibiteurs du mammalian target of rapamycin (mTOR) s’est récemment développée dans l’HAI réfractaire au traitement. L'everolimus a montré des résultats prometteurs dans une série limitée chez l'adulte, mais aucun rapport n’a été publié dans l’HAI pédiatrique à ce jour. L’objectif de notre travail était de partager notre expérience de l’everolimus comme thérapie de deuxième ou de troisième ligne dans l’HAI pédiatrique. Méthodes : Les patients âgés de 0 à 18 ans atteints d’HAI et non transplantés ayant reçu de l’everolimus entre 2014 et 2021 ont été identifiés rétrospectivement dans la base de données d’hépatologie pédiatrique des Cliniques Universitaires Saint-Luc (Bruxelles, Belgique). Tous les patients ont été soumis à un dosage régulier des taux plasmatiques d’everolimus afin d’éviter la toxicité et d’évaluer la compliance thérapeutique. Une attention particulière a été portée à la survenue d’effets secondaires cliniques et biochimiques attribuables à l’everolimus. Résultats : Six patients atteints d’HAI ont été traités par everolimus dans notre centre pour une durée comprise entre 8 et 48 mois (médiane 28 mois). Aucun effet secondaire n’a été rapporté lorsque les taux plasmatiques d’everolimus se situaient dans les normes thérapeutiques. Les transaminases hépatiques se sont améliorées chez 5/6 patients à l’instauration de l’everolimus et ont diminué significativement à la fin du suivi (p<0.05). Aucun patient n’est entré en rémission biochimique au sens strict au cours du suivi et 3/6 patients ont admis avoir une compliance suboptimale au traitement. Conclusions : Nos données préliminaires présentent l’everolimus comme une option thérapeutique de deuxième/troisième ligne sans risque en cas d’HAI réfractaire. Bien qu’une amélioration des transaminases hépatiques ait été observée dans notre cohorte, des études prospectives seront nécessaires afin de déterminer si l’everolimus peut induire une rémission clinique et biochimique au long cours

Anti-GPVI (HY101) activates platelets in a multicolor flow cytometry panel

The platelet transmembrane receptor GPVI can be assessed together with other platelet membrane markers in a whole blood multicolor flow cytometry panel. The advantage of combining multiple antibodies in a single tube is the possibility of distinguishing multiple platelet subgroups. In this short communication, we describe an activation problem encountered with anti-GPVI, clone HY101. Activation of platelets was seen after the addition of anti-GPVI in a flow cytometry panel, highlighted by the expression of the activation markers CD62P, PAC-1, CD63, and CD107a. This was also confirmed by platelet aggregation studies

Predictive factors of response to non-transplant treatment strategies in progressive familial intrahepatic cholestasis type II

Purpose: Progressive familial intrahepatic cholestasis type II (PFIC-II) is a defect of bile salt exporter protein (BSEP) at the canalicular surface of the hepatocytes. The defect of BSEP leads to progressive liver injury and eventually cirrhosis. Thetreatment for PFIC-II includes liver transplantation (LT), UrsoDeoxyCholic Acid (UDCA) and biliary diversion (BD). There are no predictive factors to assess the responsiveness of patients to non-transplant modalities. Methods: Retrospective analysis of 33 PFIC-II patients was done. Diagnostic criteria were compatible clinical presentation with either confirmatory genetic analysis or the absence of BSEP on immuno-histochemistry. The need for LT was taken as a poor outcome while maintenance on non-LT treatment was as good. The UDCA and BD response was assessed on the following parameters. Normalisation Remission of clinical manifestations, normal liver enzymes and serum bile acids. Time to normalization (TTN) - Duration from start of UDCA or BD until biochemical normalization Duration of normalization (DOR) - Duration of time for which normalization was sustained Results: 33 PFIC-II children included, LT (n=20) and non-LT (n=13) groups comparable in terms of age and sex. The two groups differed significanty for the age at first presentation, history of neonatal jaundice & ALT levels. 4 of 5 (80%) with homozygous mutations needed a LT. BSEP staining positive was seen only in 6 and canalicular in 3. 1/6 with cytoplasmic staining needed LT. 7/33 responded to UDCA, 3 of these transiently and 4 with ongoing response. The mean TTN was 16.7 +/- 3.3 months and there was no significant difference between the transient and sustained responders. The mean DOR in the sustained responders is 41.2+/-9.4 months while in the transient responders it was 70+/-7.5 months. Conclusions: 30% of PFIC - II patients achieve normalization with non-LT treatment, while disease progress may not be affected. Prognostic factors identified for good response to non-LT management in PFIC-II are age at presentation >1 year, no neonatal jaundice, high ALT, absence of homozygous mutation and presence of BSEP on immuno-histochemistry. The trial with UDCA to assess response should be minimum 2 years. The response that is seen may not be permanent. (Table Presented)

The use of prothrombin complex concentrate in chronic liver disease: A review of the literature

Patients with chronic liver disease (CLD) and cirrhosis present a rebalanced hemostatic system in the three phases of haemostasis. This balance is however unstable and can easily tip towards bleeding or thrombosis. Management of both spontaneous bleeding and bleeding during invasive procedures remains a challenge in this patient population. Transfusion of blood products can result in circulatory overload and thereby worsen portal hypertension. As an alternative to fresh frozen plasma (FFP), prothrombin complex concentrates (PCC) may have merit in patients with liver disease because of their low volume. The impact of PCC in in-vitro spiking experiments of cirrhotic plasma is promising, but also warrants cautious use in light of thromboembolic risk. The majority of existing studies carried-out in CLD patients are retrospective or do not have an adequate control arm. A prospective study (the PROTON trial) was set up in 2013 to investigate the utility of PCC in patients undergoing liver transplantation. However, the study has never recruited the planned number of patients. Robust data on PCC safety in CLD is also required. The limited existing evidence does not seem to indicate an excessive thromboembolic risk. Currently, the utilisation of PCC in CLD cannot be routinely recommended but can provide an option for carefully selected cases in which other measures were not sufficient to control bleeding and after delicately weighing risks and benefits

Activity of the alpha-1 antitrypsin deficiency registry in Belgium

A Belgian alpha-1-antitrypsin (AAT) deficiency registry has been established in 2003. Currently 55 patients are included. At the same time, a working group has been set up for publishing national guidelines. In 2014, several Belgian patients founded Alpha-1 Global. We hope that the integrated activities of all the stakeholders involved in AAT deficiency will permit a high quality care for all patients suffering from this disabling disease.peerreview_statement: The publishing and review policy for this title is described in its Aims & Scope. aims_and_scope_url: http://www.tandfonline.com/action/journalInformation?show=aimsScope&journalCode=icop20status: publishe

Deoxyguanosine kinase deficiency and recurrent spontaneous pneumothorax: a case report

Abstract Background Deoxyguanosine kinase deficiency is mainly manifested by hepatic and neurological damage, hence it belongs to the hepatocerebral form of mitochondrial deoxyribonucleic acid depletion syndrome. The association between deoxyguanosine kinase deficiency and recurrent spontaneous pneumothorax has not currently been reported. Case presentation A 12-year-old Russian boy with deoxyguanosine kinase deficiency, a recipient of a liver transplant with amyotrophy secondary to his mitochondriopathy, presented with recurrent spontaneous bilateral pneumothorax refractory to drainage and surgery. Conclusion To our knowledge, this is the first documented case of deoxyguanosine kinase deficiency associated with recurrent spontaneous pneumothorax, which could be considered a late complication of deoxyguanosine kinase deficiency. At this point, this is only an association and further studies and research need to be performed to help confirm the pathogenesis of this association

Cystic fibrosis and alpha-1 antitrypsin deficiency: case report and review of literature

Background: This case report describes a child born with both cystic fibrosis (CF) and alpha-1 antitrypsin deficiency (A1ATD). Both are autosomal recessive inherited diseases, mainly affecting the lungs and the liver. The combination of both diseases together is rare and may lead to a fulminant disease with limited life span. To the best of our knowledge, no case has been reported of a patient born with both diseases. Case presentation: After an uneventful pregnancy, a male baby was born with meconium ileus. The suspected diagnosis of CF was confirmed based on the sweat test and genetic analysis. The child developed persisting cholestasis, too severe to be likely caused by CF alone and indicating an associated problem. The diagnosis of A1ATD was established based on clinical suspicion (persisting cholestasis), decreased serum alpha-1 antitrypsin and genetic analysis. Supportive therapy was started, however the boy evolved to rapidly progressive liver disease leading to liver failure which necessitated an infant liver transplantation. Conclusions: This case illustrates the complexity of care in case of two severe inherited diseases as well as post solid organ transplant care