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Brieuc Van Nieuwenhuyse1, Dimitri Van der Linden1,2, Olga Chatzis2, Cédric Lood3,4, Jeroen Wagemans3, Rob Lavigne4, Catherine de Magnée5, Étienne Sokal1,6, Hector Rodriguez-Villalobos7, Sarah Djebara8, Maya Merabishvili9, Patrick Soentjens8, Jean-Paul Pirnay9. 1Institute of Experimental and Clinical Research's Pediatric department, UCLouvain, Brussels, Belgium; 2Pediatric Infectious Diseases, General Pediatrics Department, Cliniques universitaires Saint-Luc, Brussels, Belgium; 3Department of Biosystems, Laboratory of Gene Technology, KULeuven, Leuven, Belgium; 4Department of Microbial and Molecular Systems, Centre of Microbial and Plant Genetics, KULeuven, Leuven, Belgium; 5Pediatric and Transplantation Surgery, Cliniques universitaires Saint-Luc, Brussels, Belgium; 6Pediatric Hepatology and Gastro-enterology, Cliniques universitaires Saint-Luc, Brussels, Belgium; 7Department of Microbiology, Cliniques universitaires Saint-Luc, Brussels, Belgium; 8Center for Infectious Diseases, Queen Astrid Military Hospital, Brussels, Belgium; 9Laboratory for Molecular and Cellular Technology, Queen Astrid Military Hospital, Brussels, Belgium A 14-month old boy undergoes a first liver transplantation (LT) (Day 0), from an ABO-incompatible living donor. On D+20, we detect a fecal carriage of an extensively drug-resistant (XDR) Pseudomonas aeruginosa (Pa) strain. Besides intermediate susceptibility to aztreonam and colistin and susceptibility to gentamycin, the strain is resistant to all other antibiotics. On D+53, the child enters a severe septic state due to a bacteremia with the same Pa strain. New antibiogram suggests a resistance to colistin. Liver bilomas' drainage material is cultured and grows the same Pa strain. Admission to the pediatric intensive care unit and adjunction of intravenous (IV) aztreonam, gentamycin, and colistin led to no improvement on the microbiological or clinical levels during the next four days. By collaborating with Queen Astrid Military Hospital (Bru

Safety of reducing antibiotic use in children with febrile neutropenia: A systematic review

To the Editor: Primary hyperoxaluria type 1 (PH1) is associated with hepatic overproduction of oxalate. Kidneys gradually become unable to eliminate excess oxalate, leading to systemic oxalosis (SO) with deposits in organs.1 When kidney transplantation (KT) becomes necessary, this oxalate load can lead to oxalate nephropathy recurrence. We report the potential interest of 18-fluorodeoxyglucose positron emission computed tomography (18-FDG-PET/CT) as a tool to assess SO in PH1 patients. Signed informed consent was obtained. [...]

Congenital exocrine pancreatic insufficiency is a rare condition. In a vast majority of patients, exocrine dysfunction occurs as part of a multisystemic disease, the most prevalent being cystic fibrosis and Shwachman-Bodian-Diamond syndrome. Recent fundamental studies have increased our understanding of the pathophysiology of these diseases. Exocrine pancreatic dysfunction should be considered in children with failure to thrive and fatty stools. Treatment is mainly supportive and consists of pancreatic enzyme replacement and liposoluble vitamins supplementation.

Hepatic capillariasis is a neglected, but serious, hepatic disease with a worldwide distribution caused by the nematode Calodium hepaticum.1–4 The nematode has a monoxenous life cycle and can infect any mammalian liver but mainly affects rodents, while humans are an accidental host.1,3,4 Infection occurs after ingestion of embryonated eggs from contaminated soil. The larvae hatch in the intestine, migrate, mature, and mate in the liver parenchyma, with hundreds unembryonated eggs laid.1,5 The eggs remain viable in the liver and are released into the environment after death of the host.3,4 In the soil, the eggs reach the infective stage.3,5 Poor sanitation and living conditions predispose to infection.1,5 There is a higher incidence in children attributable to higher soil-to-hand-to-mouth contact. Pica is an additional risk, particularly when presenting as geophagia.1 A 3-year-old Afghan girl born in Belgium and living in an asylum seeker center was referred for persistent high fever and abdominal pain. A history of pica was present. Pallor, weakness, and hepatomegaly were observed on clinical examination. Blood tests revealed elevated C-reactive protein (151 mg/L), ALT (360 IU/L), AST (207 IU/L), IgM levels (13.05 g/L), microcytic anemia (8.3 g/dL), and eosinophilia (12,750/µL). Stool cultures were negative. Abdominal ultrasound examination showed hepatosplenomegaly with ascites. FibroScan revealed minor fibrosis with a stage F1. Serology for Fasciola hepatica and Toxocara canis was positive. Liver biopsy revealed adult nematodes and eggs. The child was treated with triclabendazole (10 mg/kg/day) for 2 days then albendazole (50 mg/kg/day) and methylprednisolone (1 mg/kg/day) for 5 days. She responded well. Twenty days after treatment, she presented with a relapse. A review of the liver biopsy identified the diagnostic features of C. hepaticum (Fig. 1). This diagnosis was confirmed by PCR on the liver tissue. The positive Fasciola and Toxocara serologic tests were de

Post-operative bacterial infections are a leading cause of mortality and morbidity after ongoing liver transplantation. Bacteria causing these infections in the hospital setting can exhibit high degrees of resistance to multiple types of antibiotics, which leads to major therapeutic hurdles. Alternate ways of treating these antibiotic-resistant infections are thus urgently needed. Phage therapy is one of them and consists in using selected bacteriophage viruses - viruses who specifically prey on bacteria, naturally found in various environmental samples - as bactericidal agents in replacement or in combination with antibiotics. The use of phage therapy raises various research questions to further characterize what determines therapeutic success or failure. In this work, we report the story of a toddler who suffered from extensively drug-resistant Pseudomonas aeruginosa sepsis after liver transplantation. He was treated by a bacteriophage-antibiotic intravenous combination therapy for 86 days. This salvage therapy was well tolerated, without antibody-mediated phage neutralization. It was associated with objective clinical and microbiological improvement, eventually allowing for liver retransplantation and complete resolution of all infections. Clear in vitro phage-antibiotic synergies were observed. The occurrence of bacterial phage resistance did not result in therapeutic failure, possibly due to phage-induced virulence tradeoffs, which we investigated in different experimental models.

Schools have been a point of attention during the pandemic, and their closure one of the mitigating measures taken. A better understanding of the dynamics of the transmission of SARS-CoV-2 in elementary education is essential to advise decisionmakers. We conducted an uncontrolled non-interventional prospective study in Belgian French-speaking schools to describe the role of attending asymptomatic children and school staff in the spread of COVID-19 and to estimate the transmission to others. Each participant from selected schools was tested for SARS-CoV-2 using a polymerase chain reaction (PCR) analysis on saliva sample, on a weekly basis, during six consecutive visits. In accordance with recommendations in force at the time, symptomatic individuals were excluded from school, but per the study protocol, being that participants were blinded to PCR results, asymptomatic participants were maintained at school. Among 11 selected schools, 932 pupils and 242 school staff were included between January and May 2021. Overall, 6449 saliva samples were collected, of which 44 came back positive. Most positive samples came from isolated cases. We observed that asymptomatic positive children remaining at school did not lead to increasing numbers of cases or clusters. However, we conducted our study during a period of low prevalence in Belgium. It would be interesting to conduct the same analysis during a high prevalence period.

Although most invasive meningococcal disease (IMD) cases are sporadic without identified transmission links, outbreaks can occur. We report three cases caused by meningococcus B (MenB) at a Belgian nursery school over 9 months. The first two cases of IMD occurred in spring and summer 2018 in healthy children (aged 3-5 years) attending the same classroom. Chemoprophylaxis was given to close contacts of both cases following regional guidelines. The third case, a healthy child of similar age in the same class as a sibling of one case, developed disease in late 2018. Microbiological analyses revealed MenB with identical finetype clonal complex 269 for Case 1 and 3 (unavailable for Case 2). Antimicrobial susceptibility testing revealed no antibiotic resistance. Following Case 3, after multidisciplinary discussion, chemoprophylaxis and 4CMenB (Bexsero) vaccination were offered to close contacts. In the 12-month follow-up of Case 3, no additional cases were reported by the school. IMD outbreaks are difficult to manage and generate public anxiety, particularly in the case of an ongoing cluster, despite contact tracing and management. This outbreak resulted in the addition of MenB vaccination to close contacts in Wallonian regional guidelines, highlighting the potential need and added value of vaccination in outbreak management.

Introduction: After liver transplant (LT), hyperglycemia (HG) is a common complication and is associated to an unfavorable prognosis, a persistent diabetes onset and an increased cardiovascular event. However, in pediatric LT, incidence of HG, its occurrence, persistence, and predispositions remain understudied. Objectives: Therefore, the objectives of our study were the characterization and evolution of hyperglycemia in children with LT and the analysis of their glycemic profile. Methods: We collected 7-years data about 195 children with LT in Brussels to characterize hyperglycemia and associated risk factors in multivariate analyses, and we followed five children with LT during the most critical moment of HG to analyze their glycemic profile. Hyperglycemia was defined as a glycemia exceeded 200 mg/dL, for at least two measurements separated by 24 hours, outside the day of LT. Results: Our retrospective study showed that 24% of LT children presented hyperglycemia and its onset was between 0 and 14 days after transplant. Multivariate analysis showed that children with LT who benefited of steroids (OR 2,51) for a graft rejection and/or had a virus infection (OR 2,05) were more at risk to develop hyperglycemia. Glucose sensors showed that HG was present in the post-prandial afternoon for all LT children. Conclusions: Our study shows that children with LT were more at risk of developing hyperglycemia when they required the use of steroids or when they had a viral infection, and that the measurement of blood glucose during the first month posttransplantand in the post-prandial period is essential to detect glycemic abnormalities.

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Background: In DRC, childhood undernutrition remains a serious public health concern. Internationally recommended infant and young child feeding (IYCF) practices may improve child nutritional status. This study aimed to describe IYCF practices, factors associated with inappropriate complementary feeding, and infant’s nutritional status. Methods: A community-based cross-sectional study including 1,009 mother-infant pair was conducted in August 2019 in 32 health areas (16 in rural health zone and 16 in urban one) of South Kivu, Democratic Republic of Congo (DRC), among mothers who had infants under 24 months of age. Infant’s nutritional status was assessed using WHO Anthro plus software. To describe IYCF practices, we used the indicators recommended by the WHO. To study the factors associated with inappropriate complementary feeding practices, we performed univariable and multiple logistic regression analyzes. The data was analyzed in SPSS version 25. Results: The prevalence of early initiation of breastfeeding and exclusive breastfeeding up to 6 months of age was 73.7% and 42.2% respectively. Of the 746 infants aged 6–23.9 months, 246 (32.3%) received appropriate complementary feeding. Of the 997 infants who had valid anthropometric parameters, 416 (41.7%) were well-nourished, 374 (37.5%) were undernourished and 207 (20.8%) were overweight. Multivariable logistic regression analysis revealed that residence in rural area [Adjusted Odds Ratio (AOR): 2.38 (95% Confidence Interval (CI): 1.49, 3.78)], nonattendance at postnatal care (AOR 1.63; 95% CI 1.12, 2.96), low household socioeconomic (AOR 1.72; 95% CI 1.14, 2.59) and low maternal education (AOR 1.83; 95% CI 1.20, 2.77) were factors associated with inappropriate complementary feeding. Mothers with inappropriate complementary feeding practices were 6.88 times more likely to have undernourished infants than their counterparts (AOR 6.88; 95% CI 1.24, 18.37). Conclusion: Findings from this study provide strong evidence

Quadriceps muscle weakness and reduced exercise tolerance are prevalent and associated with a worse prognosis in patients with cystic fibrosis (CF). The one-minute sit-to-stand test (1STST) has been proposed to evaluate functional exercise capacity and quadriceps strength. The aim of the study was to verify the relationship between the 1STST and the maximal isometric voluntary contraction of the quadriceps (MVCQ) evaluated by the dynamometer in stable patients with CF and to evaluate the impact of intravenous (IV) antibiotherapy. Dynamometer and 1STST were performed in stable patients with CF at a routine visit, the admission and the discharge of an IV antibiotherapy. Patients wore an activity monitor during 72 h during IV treatment. 51 stable patients with CF at a routine visit and 30 treated with IV antibiotherapy were recruited. In stable patients, the 1STST was reduced to a mean of 2101 nxkg (657-SD), representing a median of 79% (7; 142-min; max)) of the predicted values (%PV) as well as the MVCQ to 78.64 N-m (23.21; 170.34), representing 57%PV (26). The 1STST was correlated to MVCQ (r = 0.536; p < 0.0001) and lung function (r = 0.508; p = 0.0001). Over the IV antibiotherapy course, the 1STST improves significantly like lung function and body mass index while a positive trend for MVCQ was observed. The gain of 1STST was correlated to the change in MVCQ (r = 0.441; p = 0.02) and was significantly higher in hospitalized patients versus home therapy. The 1STST is a good alternative to the dynamometer to evaluate and assess muscular weakness for the routine visit and IV antibiotherapy.

Autosomal recessive polycystic kidney disease (ARPKD) is a rare monogenic disorder characterized by early onset fibrocystic hepatorenal changes. Previous reports have documented pronounced phenotypic variability even among siblings in terms of patient survival. The underlying causes for this clinical variability are incompletely understood. We present the longitudinal clinical courses of 35 sibling pairs included in the ARPKD registry study ARegPKD, encompassing data on primary manifestation, prenatal and perinatal findings, genetic testing, and family history, including kidney function, liver involvement, and radiological findings. We identified 70 siblings from 35 families with a median age of 0.7 (interquartile range 0.1-6.0) years at initial diagnosis and a median follow-up time of 3.5 (0.2-6.2) years. Data on variants were available for 37 patients from 21 families. There were 8 patients from 7 families who required kidney replacement therapy (KRT) during follow-up. For 44 patients from 26 families, antihypertensive therapy was documented. Furthermore, 37 patients from 24 families had signs of portal hypertension with 9 patients from 6 families having substantial hepatic complications. Interestingly, pronounced variability in the clinical course of functional kidney disease was documented in only 3 sibling pairs. In 17 of 20 families of our cohort of neonatal survivors, siblings had only minor differences of kidney function at a comparable age. In patients surviving the neonatal period, our longitudinal follow-up of 70 ARPKD siblings from 35 families revealed comparable clinical courses of kidney and liver diseases in most families. The data suggest a strong impact of the underlying genotype.

Bowed legs and failure to thrive in children must be thoroughly investigated. Rickets results from deficient mineralization at the growth plate and can lead to bone deformation. The leading cause is vitamin D deficiency, but in rare cases, rickets can be caused by abnormalities of phospho-calcic metabolism, either primary (inherited) or secondary.

Chronic kidney disease (CKD) in children is a pro-inflammatory condition leading to a high morbidity and mortality. Accumulation of organic metabolic waste products, coined as uraemic toxins, parallels kidney function decline. Several of these uraemic toxins are protein-bound (PBUT) and gut-derived. Gut dysbiosis is a hallmark of CKD, resulting in a state of increased proteolytic fermentation that might be counteracted by dietary fibre. Data on fibre intake in children with CKD are lacking. We aimed to assess dietary fibre intake in a paediatric CKD cohort and define its relationship with PBUT concentrations. In this multi-centre, cross-sectional observational study, 61 non-dialysis CKD patients (9 ± 5 years) were included. Dietary fibre intake was assessed through the use of 24-h recalls or 3-day food records and coupled to total and free levels of 4 PBUTs (indoxyl sulfate (IxS), p-cresyl sulfate (pCS), p-cresyl glucuronide (pCG) and indole acetic acid (IAA). In general, fibre intake was low, especially in advanced CKD: 10 ± 6 g/day/BSA in CKD 4-5 versus 14 ± 7 in CKD 1-3 (p = 0.017). Lower concentrations of both total (p = 0.036) and free (p = 0.036) pCG were observed in the group with highest fibre intake, independent of kidney function. Fibre intake in paediatric CKD is low and is even worse in advanced CKD stages. Current dietary fibre recommendations for healthy children are not being achieved. Dietary management of CKD is complex in which too restrictive diets carry the risk of nutritional deficiencies. The relation of fibre intake with PBUTs remains unclear and needs further investigation. Graphical abstract.

Si l’hydronéphrose anténatale (HNA) est la malformation congénitale la plus fréquente, sa prise en charge est cependant controversée surtout en ce qui concerne le bilan à réaliser et l’intérêt d’une prophylaxie. Des études récentes remettent en doute l’indication systématique d’une cystographie à la recherche d’un reflux associé tout comme le bénéfice de l’antibioprophylaxie sur la survenue d’infection urinaire. Une approche moins agressive est discutée tenant compte essentiellement des données échographiques obtenues en postnatal. Nous proposons un algorithme de prise en charge tenant compte de ces données.

X-linked hypophosphatemia (XLH) is the most common genetic form of hypophosphatemic rickets and osteomalacia. In this disease, mutations in the PHEX gene lead to elevated levels of the hormone fibroblast growth factor 23 (FGF23), resulting in renal phosphate wasting and impaired skeletal and dental mineralization. Recently,international guidelines for the diagnosis and treatment of this condition have been published. However, more specific recommendations are needed to provide guidance at the national level, considering resource availability and health economic aspects. A national multidisciplinary group of Belgian experts convened to discuss translation of international best available evidence into locally feasible consensus recommendations.Patients with XLH may present to a wide array of primary, secondary and tertiary care physicians, among whom awareness of the disease should be raised. XLH has a very broad differential-diagnosis for which clinical features, biochemical and genetic testing in centers of expertise are recommended. Optimal care requires a multidisciplinary approach, guided by an expert in metabolic bone diseases and involving (according to the individual patient’s needs) pediatric and adult medical specialties and paramedical caregivers, including but not limited to general practitioners, dentists, radiologists and orthopedic surgeons. In children with severe or refractory symptoms, FGF23 inhibition using burosumab may provide superior outcomes compared to conventional medical therapy with phosphate supplements and active vitamin D analogues. Burosumab has also demonstrated promising results in adults on certain clinical outcomes such as pseudofractures. In summary, this work outlines recommendations for clinicians and policymakers, with a vision for improving the diagnostic and therapeutic landscape for XLH patients in Belgium.

The COVID-19 pandemic has proven to be a challenge in regard to the clinical presentation, prevention, diagnosis, and management of SARS-CoV-2 infection among children who are candidates for and recipients of SOT. By providing scenarios and frequently asked questions encountered in routine clinical practice, this document provides expert opinion and summarizes the available data regarding the prevention, diagnosis, and management of SARS-CoV-2 infection among pediatric SOT candidates and recipients and highlights ongoing knowledge gaps requiring further study. Currently available data are still lacking in the pediatric SOT population, but data have emerged in both the adult SOT and general pediatric population regarding the approach to COVID-19. The document provides expert opinion regarding prevention, diagnosis, and management of SARS-CoV-2 infection among pediatric SOT candidates and recipients.

Imbalanced colonic microbial metabolism plays a pivotal role in generating protein-bound uraemic toxins (PBUTs), which accumulate with deteriorating kidney function and contribute to the uraemic burden of children with chronic kidney disease (CKD). Dietary choices impact the gut microbiome and metabolism. The aim of this study was to investigate the relation between dietary fibre and gut-derived PBUTs in paediatric CKD. Sixty-one (44 male) CKD children (9 ± 5 years)were prospectively followed for two years. Dietary fibre intake was evaluated by either 24-h recalls (73%) or 3-day food records (27%) at the same time of blood sampling for assessment of total and free serum levels of different PBUTs using liquid chromatography. We used linear mixed models to assess associations between fibre intake and PBUT levels. We found an inverse association between increase in fibre consumption (g/day) and serum concentrations of free indoxyl sulfate (-3.1% (-5.9%; -0.3%) (p = 0.035)), free p-cresyl sulfate (-2.5% (-4.7%; -0.3%) (p = 0.034)), total indole acetic acid (IAA) (-1.6% (-3.0%; -0.3%) (p = 0.020)), free IAA (-6.6% (-9.3%; -3.7%) (p < 0.001)), total serum p-cresyl glucuronide (pCG) (-3.0% (-5.6%; -0.5%) (p = 0.021)) and free pCG levels (-3.3% (-5.8%; -0.8%) (p = 0.010)). The observed associations between dietary fibre intake and the investigated PBUTs highlight potential benefits of fibre intake for the paediatric CKD population. The present observational findings should inform and guide adaptations of dietary prescriptions in children with CKD.

Actinobacillus actinomycetemcomitans is a Gram-negative coccobacillus responsible for blood culture-negative endocarditis. This type of endocarditis is difficult to diagnose because of its insidious evolution and variability of symptoms. Moreover, valvular vegetation may be challenging to detect by echocardiography, especially in children with congenital heart disease. 18F-fluorodeoxyglucose positron emission tomography is frequently used as an additional diagnostic tool for infectious endocarditis in adult patients, and has proved efficient, especially for prosthetic valves. However, its value has been rarely described for the diagnosis of infectious endocarditis in children with congenital heart disease. The authors report the case of an 11-year-old boy with congenital aortic stenosis, who developed severe anemia, thrombocytopenia, hepatosplenomegaly, acute kidney injury, and biological signs of inflammation, with only very mild fever. Renal biopsy revealed the presence of crescentic glomerulonephritis. Transthoracic and transoesophageal echocardiography did not show any vegetation. An 18F-fluorodeoxyglucose positron emission tomography was performed and revealed abnormal 18F-FDG uptake in the area of the aortic valve, supporting the hypothesis of infectious endocarditis. The patient underwent cardiac surgery for the reparation of the aortic stenosis and calcified vegetation was found and resected from the aortic valve. One blood culture yielded Actinobacillus actinomycetemcomitans after 20 days. However, the PCR for the 16S rRNA gene on the resected vegetation was negative. He was treated with 4 weeks of parenteral antibiotics. Follow-up showed the resolution of the clinical and biological abnormalities within a few days. Blood culture-negative endocarditis should be considered in a child with multiorgan manifestations, such as thrombocytopenia, hepatosplenomegaly, and glomerulonephritis. Because echocardiography may not show valvular vegetation, especially in ch

Background: Suboptimal child nutrition remains the main factor underlying child undernutrition in Democratic Republic of Congo (DRC). This study aimed to assess the prevalence of minimum acceptable diet and associated factors among children aged 6–23 months old. Methods: Community-based cross-sectional study including 742 mothers with children aged 6–23 months old was conducted in 2 Health Zones of South Kivu, Eastern DRC. WHO indicators of Infant and Young Child Feeding (IYCF) regarding complementary feeding practices were used. Logistic regression analysis was used to quantify the association between sociodemographic indicators and adequate minimum acceptable diet for both univariate and multivariate analysis. Results: Overall, 33% of infants had minimum acceptable diet. After controlling for a wide range of covariates, residence urban area (AOR 2.39; 95% CI 1.43, 3.85), attendance postnatal care (AOR 1.68; 95% CI 1.12, 2.97), education status of mother (AOR 1.83; 95% CI 1.20, 2.77) and household socioeconomic status (AOR 1.72; 95% CI 1.14, 2.59) were factors positively associated with minimum acceptable diet. Conclusion: Actions targeting these factors are expected to improve infant feeding practices in South Kivu.

Vitamin D toxicity is associated with accidental overdoses due to manufacturing or intake errors and its secondary hypercalcemia can result in severe morbidity. Although patients with cystic fibrosis are potentially at increased risk for this intoxication as prescription of vitamin D preparations is a common practice in this population, the frequency of such events is currently unknown. We performed a retrospective analysis of all the files of cystic fibrosis patients followed at the Cliniques universitaires Saint-Luc over a 10-year period, recording 25(OH)- and 1,25(OH)2vitamin D levels as well as demographic data, lung function tests, Pseudomonas aeruginosa infection and results from pharmacological analysis of magistral liposoluble vitamins preparations. A total of 244 patients were included in the study. 13 patients (5%) had serum vitamin D levels corresponding to vitamin D overdose. Patients who had experienced an overdose were more likely to be F508del homozygous or suffer from exocrine pancreatic insufficiency. 2 patients developed significant hypercalcemia necessitating monitoring and hospitalization. Errors in the preparation of magistral liposoluble vitamin pills were identified in several intoxicated patients. Retrospective assessment of the dosing errors with the local pharmacists showed that trituration and dosing errors were their most frequent causes.

Epstein-Barr virus-associated smooth pulmonary tumor is a rare condition that mostly affects immunosuppressed patients. This case describes a young boy with a history of kidney transplantation who presented recurrent pneumonia. Multiple endobronchial soft tissue tumors affecting both right and left bronchial tree were found and partially removed by bronchoscopy. Immunohistologic analysis demonstrated Epstein-Barr virus-associated smooth pulmonary tumor. Immunosuppressive therapy was changed from tacrolimus to sirolimus. A few months later, new right upper lobe and inferior left lobe tumors were found. Recurrent left lower lobe pneumonia prompted lobectomy. In the present case, complete resection and change of immunosuppressive treatment were effective.

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Background: Over the last decade, advances in genetic techniques have resulted in the identification of rare hereditary disorders of renal magnesium and salt handling. Nevertheless, approximately 20% of all patients with tubulopathy lack a genetic diagnosis. Methods: We performed whole-exome and -genome sequencing of a patient cohort with a novel, inherited, salt-losing tubulopathy; hypomagnesemia; and dilated cardiomyopathy. We also conducted subsequent in vitro functional analyses of identified variants of RRAGD, a gene that encodes a small Rag guanosine triphosphatase (GTPase). Results: In eight children from unrelated families with a tubulopathy characterized by hypomagnesemia, hypokalemia, salt wasting, and nephrocalcinosis, we identified heterozygous missense variants in RRAGD that mostly occurred de novo. Six of these patients also had dilated cardiomyopathy and three underwent heart transplantation. We identified a heterozygous variant in RRAGD that segregated with the phenotype in eight members of a large family with similar kidney manifestations. The GTPase RagD, encoded by RRAGD, plays a role in mediating amino acid signaling to the mechanistic target of rapamycin complex 1 (mTORC1). RagD expression along the mammalian nephron included the thick ascending limb and the distal convoluted tubule. The identified RRAGD variants were shown to induce a constitutive activation of mTOR signaling in vitro. Conclusions: Our findings establish a novel disease, which we call autosomal dominant kidney hypomagnesemia (ADKH-RRAGD), that combines an electrolyte-losing tubulopathy and dilated cardiomyopathy. The condition is caused by variants in the RRAGD gene, which encodes Rag GTPase D; these variants lead to an activation of mTOR signaling, suggesting a critical role of Rag GTPase D for renal electrolyte handling and cardiac function.

Pierre Robin sequence is a congenital disorder classically characterized by retrognathia, glossoptosis and upper airway obstruction with or without cleft palate. This condition affects neonates and can cause serious respiratory and feeding difficulties requiring prompt intervention. Currently there are no standardized management algorithms for neonates with Pierre Robin sequence and management of the condition remains a challenge. Assuring adequate breathing and feeding should always be the first point of concern. Early diagnosis, sequential planning of treatment, adequate monitoring and multidisciplinary approach are essential for infants referred with Pierre Robin sequence. We discuss here the full scope of the disease and the various management options.

Phage therapy (PT) shows promising potential in managing biofilm infections, which include refractory orthopedic infections. We report the case of a 13-year-old girl who developed chronic polymicrobial biofilm infection of a pelvic bone allograft after Ewing's sarcoma resection surgery. Chronic infection by Clostridium hathewayi, Proteus mirabilis and Finegoldia magna was worsened by methicillin-susceptible Staphylococcus aureus exhibiting an inducible Macrolides-Lincosamides-Streptogramin B resistance phenotype (iMLSB). After failure of conventional conservative treatment, combination of in situ anti-S. aureus PT with surgical debridement and intravenous antibiotic therapy led to marked clinical and microbiological improvement, yet failed to prevent a recurrence of infection on the midterm. This eventually led to surgical graft replacement. Multiple factors can explain this midterm failure, among which incomplete coverage of the polymicrobial infection by PT. Indeed, no phage therapy against C. hathewayi, P. mirabilis or F. magna could be administered. Phage-antibiotic interactions were investigated using OmniLog® technology. Our results suggest that phage-antibiotic interactions should not be considered "unconditionally synergistic", and should be assessed on a case-by-case basis. Specific pharmacodynamics of phages and antibiotics might explain these differences. More than two years after final graft replacement, the patient remains cured of her sarcoma and no further infections occurred.

[This corrects the article DOI: 10.3389/fendo.2021.641543.].

Autosomal recessive polycystic kidney disease (ARPKD) is a severe disease of early childhood that is clinically characterized by fibrocystic changes of the kidneys and the liver. The main cause of ARPKD are variants in the PKHD1 gene encoding the large transmembrane protein fibrocystin. The mechanisms underlying the observed clinical heterogeneity in ARPKD remain incompletely understood, partly due to the fact that genotype-phenotype correlations have been limited to the association of biallelic null variants in PKHD1 with the most severe phenotypes. In this observational study we analyzed a deep clinical dataset of 304 patients with ARPKD from two independent cohorts and identified novel genotype-phenotype correlations during childhood and adolescence. Biallelic null variants frequently show severe courses. Additionally, our data suggest that the affected region in PKHD1 is important in determining the phenotype. Patients with two missense variants affecting amino acids 709-1837 of fibrocystin or a missense variant in this region and a null variant less frequently developed chronic kidney failure, and patients with missense variants affecting amino acids 1838-2624 showed better hepatic outcome. Variants affecting amino acids 2625-4074 of fibrocystin were associated with poorer hepatic outcome. Thus, our data expand the understanding of genotype-phenotype correlations in pediatric ARPKD patients and can lay the foundation for more precise and personalized counselling and treatment approaches.

Cornelia de Lange syndrome is a rare autosomal dominant or X-linked developmental disorder characterized by characteristic facial dysmorphism, intellectual disability, growth retardation, upper limb and multiorgan anomalies. Causative mutations have been identified in five genes coding for the cohesion complex structure components or regulatory elements. Among them, RAD21 is associated with a milder phenotype. Very few RAD21 intragenic mutations have been identified so far. Thus, any new patient is a valuable tool to delineate the associated phenotype. We discuss a new patient with RAD21 confirmed molecular diagnosis and compare his clinical features to those of previously described patients carrying different RAD21 intragenic mutations.

Primary hyperoxaluria type 1 (PH1) is an autosomal recessive disease caused by the functional defect of alanine-glyoxylate aminotransferase that results in the overproduction of oxalate. It can be devastating especially for kidneys, leading to end-stage renal disease (ESRD) during the first 2 to 3 decades of life in most patients. Consequently, many PH1 patients need kidney transplantation. However, because PH1 is caused by a liver enzyme deficiency, the only cure of the metabolic defect is liver transplantation. Thus, current transplant strategies to treat PH1 patients with ESRD include dual liver-kidney transplantation. However, the morbidity and mortality associated with liver transplantation make these strategies far from optimal. Fortunately, a therapeutic revolution is looming. Indeed, innovative drugs are being currently tested in clinical trials, and preliminary data show impressive efficacy to reduce the hepatic overproduction of oxalate. Hopefully, with these therapies, liver transplantation will no longer be necessary. However, some patients with progressing renal disease or those who will be diagnosed with PH1 at an advanced stage of chronic kidney disease will ultimately need kidney transplantation. Here we review the current knowledge on this subject and discuss the future of kidney transplant management in PH1 patients in the era of novel therapies.

Abnormal connections between the esophagus and low respiratory tract can result from embryological defects in foregut development. Beyond well-known malformations, including tracheo-esophageal fistula and laryngo-tracheo-esophageal cleft, rarer anomalies have also been reported, including communicating bronchopulmonary foregut malformations and tracheal atresia. Herein, we describe a case of what we have called "esophageal trachea," which, to our knowledge, has yet to be reported. A full-term neonate was born in our institution presenting with a foregut malformation involving both the middle esophagus and the distal trachea, which were found to be longitudinally merged into a common segment, 3 cm in length, located just above the carina and consisted of esophageal tissue without cartilaginous rings. At birth, the esophagus and trachea were surgically separated via right thoracotomy, the common segment kept on the tracheal side only, creating a residual long-gap esophageal atresia. The resulting severe tracheomalacia was treated via simultaneous posterior splinting of such diseased segment using an autologous pericardium patch, as well as by anterior aortopexy. Terminal esophagostomy and gastrostomy were created at that stage due to the long distance between esophageal segments. Between ages 18 and 24 months, the patient underwent native esophageal reconstruction using a multistage traction-and-growth surgical strategy that combined Kimura extra-thoracic esophageal elongations at the upper esophagus and Foker external traction at the distal esophagus. Ten months after esophageal reconstruction, prolonged, refractory, and severe tracheomalacia was further treated via anterior external stenting using a semitubular ringed Gore-Tex® prosthesis, through simultaneous median sternotomy and tracheoscopy. Currently, 2 years after the last surgery, respiratory stabilization, and full oral feeding were stably achieved. Multidisciplinary management was crucial for assuring lifes

Lung clearance index (LCI) in the early years was associated with LCI during adolescence in children with cystic fibrosis. Pre-school LCI may help to identify children in whom treatment could be intensified.

BACKGROUND: In Belgium, COVID-19 epidemy began on February 4, 2020 with a peak on April 10, 2020. Patients with cystic fibrosis (CF) followed in the Cliniques universitaires Saint-Luc were rapidly isolated before the government lockdown. METHODS: After the peak of the epidemy, we measured anti-SARS-CoV-2 IgM and IgG antibodies in 149 patients and collected clinical data. RESULTS: Only 3 asymptomatic patients presented IgG against the virus. In one patient hospitalized for COVID-19 (positive molecular testing), we did not detect any anti-SARS-CoV-2 antibodies, as in thirty-five other symptomatic patients considered as possible cases. CONCLUSIONS: Even if respiratory symptoms linked to CF are frequent and compatible with COVID-19, anti-SARS-CoV-2 IgG antibodies were detected only in 3 asymptomatic patients. This reassuring study concerning the risk of COVID-19 in patients with CF illustrates the difficulty to distinguish COVID-19 symptoms from respiratory exacerbations and the need of generalized molecular testing to make a precise diagnosis.

La tuberculose (TB) fait partie du top 10 des maladies mortelles dans le monde. La TB abdominale est difficile à diagnostiquer car ses symptômes sont insidieux. Les formes les plus fréquentes chez l’enfant sont la TB péritonéale et la TB ganglionnaire. Le diagnostic repose sur l’anamnèse, l’imagerie, la culture microbiologique et l’histologie. La polymerase chain reaction (PCR) confirme le diagnostic plus rapidement que la culture. Le traitement consiste en une quadrithérapie de 2 mois, suivie d’une bithérapie de 4 mois. Cet article décrit les différentes méthodes d’exploration permettant d’étayer le diagnostic de TB abdominale., [How I explore … abdominal tuberculosis in children ?] Tuberculosis (TB) is one of the top 10 causes of death worldwide. Abdominal TB is an uncommon presentation of TB and is challenging to diagnose due to its insidious onset. The most common forms in children are peritonitis and lymphadenitis. Diagnosis is based on radiological and histopathological findings. Specific PCR amplification confirms the diagnosis quicker than conventional cultures. The treatment includes a 6-month therapy and a close follow-up. This article describes the different methods allowing to confirm the diagnosis of abdominal TB.

BACKGROUND : Undernutrition predisposes children to a greater incidence and duration of diarrhea. No review and meta-analysis have yet been conducted to assess effectiveness of probiotics and synbiotics in undernourished children. AIMS : To assess the effectiveness of probiotics and synbiotics on diarrhea in undernourished children. METHODS : Randomized, double-blind, placebo-controlled trials evaluating the effects of probiotics and synbiotics on diarrhea in undernourished children were searched from 1990 to May 2020. Recommendations of the Cochrane Handbook and the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement were followed. RESULTS : The systematic review identified 15 trials with 6986 patients. The meta-analysis revealed that treatment with probiotic or synbiotic reduced significantly both the duration of diarrhea [Weighted mean difference (WMD) = −1.05 day, 95% CI (−1.98, −0.11)] and the hospital stay duration [Standard mean difference (SMD) = −2.87 days, 95% CI (−5.33, −0.42)], especially in specific patient subsets. In both groups, similar rates of vomiting and nutritional recovery were observed. No probiotics or synbiotics-related adverse effects were reported. Subgroup analyses showed that probiotic and synbiotic treatment were more effective in reducing risk of diarrhea in outpatients [Risk ratio (RR) = 0.86, 95%CI (0.75–0.98)]. CONCLUSION : This meta-analysis supports the potential beneficial roles of probiotics and synbiotics on diarrhea in undernourished children.

Background Obesity is a chronic disease with limited treatment options in pediatric patients. Liraglutide may be useful for weight management in adolescents with obesity. Methods In this randomized, double-blind trial, which consisted of a 56-week treatment period and a 26-week follow-up period, we enrolled adolescents (12 to <18 years of age) with obesity and a poor response to lifestyle therapy alone. Participants were randomly assigned (1:1) to receive either liraglutide (3.0 mg) or placebo subcutaneously once daily, in addition to lifestyle therapy. The primary end point was the change from baseline in the body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) standard-deviation score at week 56. Results A total of 125 participants were assigned to the liraglutide group and 126 to the placebo group. Liraglutide was superior to placebo with regard to the change from baseline in the BMI standard-deviation score at week 56 (estimated difference, −0.22; 95% confidence interval [CI], −0.37 to −0.08; P=0.002). A reduction in BMI of at least 5% was observed in 51 of 113 participants in the liraglutide group and in 20 of 105 participants in the placebo group (estimated percentage, 43.3% vs. 18.7%), and a reduction in BMI of at least 10% was observed in 33 and 9, respectively (estimated percentage, 26.1% vs. 8.1%). A greater reduction was observed with liraglutide than with placebo for BMI (estimated difference, −4.64 percentage points) and for body weight (estimated difference, −4.50 kg [for absolute change] and −5.01 percentage points [for relative change]). After discontinuation, a greater increase in the BMI standard-deviation score was observed with liraglutide than with placebo (estimated difference, 0.15; 95% CI, 0.07 to 0.23). More participants in the liraglutide group than in the placebo group had gastrointestinal adverse events (81 of 125 [64.8%] vs. 46 of 126 [36.5%]) and adverse events that led to discontinuation of the t