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Background & Aims: Primary sclerosing cholangitis (PSC) is a rare progressive liver disease associated with inflammatory bowel disease (IBD). It is usually diagnosed in adults but can also present in children. Data on long-term outcomes of pediatric PSC are limited. Our aim was to study the natural history of pediatric PSC in Sweden. Methods: This is a cohort study, including all children (<18 years), diagnosed with PSC between January 2000 and December 2015 at the Pediatric Liver Unit at Karolinska University Hospital, Stockholm. Patients were followed until liver transplantation, death or last date of follow-up (August 2021). Results: We identified 124 children with a median age of 14 (1.9-17.8) years at PSC diagnosis. Sixty percent were boys, 93% had IBD. Median follow-up time was 13 years (5.7-21.6). Overall event-free survival in the cohort was 91% (95% CI 0.84-0.95) at 5 years and 77% (95% CI 0.68-0.84) at 10 years after diagnosis. Autoimmune hepatitis (AIH) was present in 31% (n = 39). Portal hypertension developed in 13% (n = 16), biliary complications in 24% (n = 30), cholangiocarcinoma (CCA) in 0.8% (n = 1), while 13% (n = 16) underwent liver transplantation and three patients died. Transplant-free survival was 91% after 10 years. Individuals with a high SCOPE index at diagnosis had a 2.3-fold increased risk of requiring liver transplantation (hazard ratio 2.35, 95% CI 1.18-4.66, c-statistics = 0.70). Patients with an additional diagnosis of autoimmune hepatitis had slightly higher risk of reaching transplantation during follow-up (hazard ratio 2.85, 95% CI 1.06-7.67, p = 0.038). Conclusions: Children diagnosed with PSC have a good prognosis during the first decade after diagnosis. A high SCOPE index at diagnosis was associated with a less favorable outcome. Impact and implications: Data on long-term outcome in pediatric primary sclerosing cholangitis bridging over to adulthood is limited. There is a great need among children with primary sclerosing cholangitis and their parents for more knowledge about the natural history of this disease and what they can expect from the future. We hope that the data presented in this study may help counsel health professionals, young individuals and families affected by this disease.
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Empagliflozin has been successfully repurposed for treating neutropenia and neutrophil dysfunction in patients with glycogen storage disease type 1b (GSD 1b), however, data in infants are missing. We report on efficacy and safety of empagliflozin in infants with GSD 1b. This is an international retrospective case series on 21 GSD 1b infants treated with empagliflozin (total treatment time 20.6 years). Before starting empagliflozin (at a median age of 8.1 months with a median dose of 0.3 mg/kg/day) 12 patients had clinical signs and symptoms of neutrophil dysfunction. Six of these previously symptomatic patients had no further neutropenia/neutrophil dysfunction-associated findings on empagliflozin. Eight patients had no signs and symptoms of neutropenia/neutrophil dysfunction before start and during empagliflozin treatment. One previously asymptomatic individual with a horseshoe kidney developed a central line infection with pyelonephritis and urosepsis during empagliflozin treatment. Of the 10 patients who were treated with G-CSF before starting empagliflozin, this was stopped in four and decreased in another four. Eleven individuals were never treated with G-CSF. While in 17 patients glucose homeostasis remained stable on empagliflozin, four showed glucose homeostasis instability in the introductory phase. In 17 patients, no other side effects were reported, while genital (n = 2) or oral (n = 1) candidiasis and skin infection (n = 1) were reported in the remaining four. Empagliflozin had a good effect on neutropenia/neutrophil dysfunction-related signs and symptoms and a favourable safety profile in infants with GSD 1b and therefore qualifies for further exploration as first line treatment.
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Compostos Benzidrílicos , Glucosídeos , Doença de Depósito de Glicogênio Tipo I , Neutropenia , Neutrófilos , Humanos , Doença de Depósito de Glicogênio Tipo I/tratamento farmacológico , Doença de Depósito de Glicogênio Tipo I/complicações , Neutropenia/tratamento farmacológico , Masculino , Feminino , Lactente , Compostos Benzidrílicos/uso terapêutico , Compostos Benzidrílicos/administração & dosagem , Estudos Retrospectivos , Neutrófilos/efeitos dos fármacos , Glucosídeos/uso terapêutico , Glucosídeos/farmacologia , Glucosídeos/administração & dosagem , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Resultado do Tratamento , Fator Estimulador de Colônias de Granulócitos/uso terapêuticoRESUMO
BACKGROUND: Oral cholic acid therapy is an effective therapy in children with primary bile acid synthesis deficiencies. Most reported patients with this treatment have 3ß-hydroxy-Δ5-C27-steroid oxidoreductase deficiency. The aim of the study was the evaluation of cholic acid therapy in a cohort of patients with the rarer Δ4-3-oxosteroid 5ß-reductase (Δ4-3-oxo-R) deficiency. METHODS: Sixteen patients with Δ4-3-oxo-R deficiency confirmed by AKR1D1 gene sequencing who received oral cholic acid were retrospectively analyzed. RESULTS: First symptoms were reported early in life (median 2 months of age), with 14 and 3 patients having cholestatic jaundice and severe bleeding respectively. Fifteen patients received ursodeoxycholic acid before diagnosis, with partial improvement in 8 patients. Four patients had liver failure at the time of cholic acid initiation. All 16 patients received cholic acid from a median age of 8.1 months (range 3.1-159) and serum liver tests normalized in all within 6-12 months of treatment. After a median cholic acid therapy of 4.5 years (range 1.1-24), all patients were alive with their native liver. Median daily cholic acid dose at last follow-up was 8.3 mg/kg of body weight. All patients, but one, had normal physical examination and all had normal serum liver tests. Fibrosis, evaluated using liver biopsy (n = 4) or liver elastography (n = 9), had stabilized or improved. Cholic acid therapy enabled a 12-fold decrease of 3-oxo-∆4 derivatives in urine. Patients had normal growth and quality of life. The treatment was well tolerated without serious adverse events and signs of hepatotoxicity. CONCLUSIONS: Oral cholic acid therapy is a safe and effective treatment for patients with Δ4-3-oxo-R deficiency.
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Ácidos e Sais Biliares , Doenças Metabólicas , Criança , Humanos , Ácido Cólico/uso terapêutico , Estudos Retrospectivos , Qualidade de Vida , Doenças Metabólicas/tratamento farmacológico , Oxirredutases/genéticaRESUMO
INTRODUCTION: Portal vein obstruction (PVO) consists of anastomotic stenosis and thrombosis, which occurs due to a progression of the former. The aim of this large-scale international study is to assess the prevalence, current management practices and efficacy of treatment in patients with PVO. METHODS AND ANALYSIS: The Portal vein Obstruction Revascularisation Therapy After Liver transplantation registry will facilitate an international, retrospective, multicentre, observational study, with 25 centres around the world already actively involved. Paediatric patients (aged <18 years) with a diagnosed PVO between 1 January 2001 and 1 January 2021 after liver transplantation will be eligible for inclusion. The primary endpoints are the prevalence of PVO, primary and secondary patency after PVO intervention and current management practices. Secondary endpoints are patient and graft survival, severe complications of PVO and technical success of revascularisation techniques. ETHICS AND DISSEMINATION: Medical Ethics Review Board of the University Medical Center Groningen has approved the study (METc 2021/072). The results of this study will be disseminated via peer-reviewed publications and scientific presentations at national and international conferences. TRIAL REGISTRATION NUMBER: Netherlands Trial Register (NL9261).
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Hepatopatias , Transplante de Fígado , Doenças Vasculares , Humanos , Criança , Transplante de Fígado/efeitos adversos , Veia Porta , Estudos Retrospectivos , Prevalência , Doenças Vasculares/epidemiologia , Doenças Vasculares/etiologia , Doenças Vasculares/cirurgia , Sistema de Registros , Estudos Observacionais como Assunto , Estudos Multicêntricos como AssuntoRESUMO
BACKGROUND: Maintaining a good nutritional status during the hematopoietic cell transplantation (HCT) procedure is challenging in the pediatric population. METHODS: In a multicentric retrospective study, we compared the outcome of nutritional status and HCT-related parameters in 227 pediatric patients during and after HCT between 2005 and 2015. 112 patients received a gastrostomy before the start of HCT (GS group), and 115 did not receive a gastrostomy (NGS). Data collection was performed at HCT, 3, 6, and 12 months post-HCT. RESULTS: At time point of HCT the Standard Deviation Score (SDS) of weight was 0.17 in the NGS group, and 0.71 in the GS group (p = .01) Patients in the NGS group lost more weight during the first 3 months after HCT than patients in the GS group. At 12 months, patients in the NGS remained at a lower weight, while patients in the GS group slightly increased their weight. There were no differences between the groups in the incidence of acute graft-versus-host-disease (GvHD), overall survival, and non-relapse mortality. However, the number of febrile episodes requiring intravenous treatment with antibiotics, was higher in the GS group as compared to the NGS group, during the first 3 months post-HCT (p < .001). CONCLUSIONS: Our results indicate that gastrostomy can be utilized in children undergoing HCT without any negative effects on mortality. Therefore, the use of a gastrostomy appears to be a safe option to maintain a good nutritional status during the HCT procedure.
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Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Humanos , Criança , Estudos Retrospectivos , Estudos de Casos e Controles , Gastrostomia , Análise de Sobrevida , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doença Enxerto-Hospedeiro/etiologia , Condicionamento Pré-Transplante/métodosRESUMO
Not all children with obesity carry a similar risk of non-alcoholic fatty liver disease (NAFLD). We investigated the effect of obesity severity, metabolic risk parameters, and obesity treatment outcome on later risk of NAFLD in paediatric obesity. We conducted a nested case-control study of children and adolescents enrolled in the Swedish Childhood Obesity Treatment Register (BORIS) (2001-2016). NAFLD was ascertained from the National Patient Register. Five controls per case were matched by sex and age at index date and at the obesity treatment initiation. Seventy-six pairs (n cases = 76, n controls = 241) were included in the analysis (29% females, mean age at obesity treatment initiation was 10.8 ± 3.07 years). Mean age of NAFLD diagnosis was 14.2 ± 3.07 years. The risk for NAFLD increased with severe obesity (odds ratio [OR]: 3.15, 95% confidence interval [CI]: 1.69-5.89), impaired fasting glucose (OR: 5.29, 95% CI: 1.40-20.06), high triglycerides (OR: 2.33, 95% CI: 1.22-4.43) and weight gain (OR: 4.67, 95% CI: 1.51-14.49 per body mass index standard deviation score [BMI SDS] unit). Relative weight loss of at least 0.25 BMI SDS units reduced NAFLD risk independently of other risk factors (OR: 0.09, 95% CI: 0.01-0.56). Severe obesity, impaired fasting glucose and high triglycerides are risk factors for future NAFLD in paediatric obesity. Successful obesity treatment almost eliminates the risk for NAFLD independently of obesity severity, IFG and high triglycerides.
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Hepatopatia Gordurosa não Alcoólica , Obesidade Infantil , Adolescente , Índice de Massa Corporal , Estudos de Casos e Controles , Criança , Feminino , Humanos , Masculino , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/etiologia , Obesidade Infantil/complicações , Obesidade Infantil/epidemiologia , Fatores de Proteção , Fatores de Risco , Suécia/epidemiologiaRESUMO
OBJECTIVES: A descriptive and comparative study of gastric histological aspects according to the updated Sydney classification (USC), obtained from Helicobacter pylori-positive versus H pylori-negative children referred for upper gastrointestinal endoscopy. METHODS: The Prisma method was used to perform a systematic review and meta-analysis. Selection criteria were based on following key words USC, H pylori, children, endoscopy, or biopsy. Publication biases were assessed according to the Newcastle-Ottawa Scale, and a meta-regression analysis was done. The study was registered on the PROSPERO platform. RESULTS: Between 1994 and 2017, 1238 references were found; 97 studies were retained for the systematic review with a total number of 25,867 children; 75 studies were selected for the meta-analysis concerning 5990 H pylori-infected and 17,782 uninfected children.H pylori-positive versus H pylori-negative children, according to the USC, showed significantly higher relative risk for gastric antral and corpus chronic inflammation, presence of neutrophils, and of lymphoid follicles, and gastric mucosa atrophy, whereas, intestinal metaplasia showed a significantly higher RR only in antral biopsies. The meta-regression analysis showed that H pylori-positive versus H pylori-negative children had significantly higher risk only for corpus activity according to age, recurrent abdominal pain, and geographical area of low H pylori prevalence. CONCLUSIONS: H pylori infection in children was associated with higher relative risk for gastric antral and corpus chronic inflammation, presence of neutrophils, lymphoid follicles, and rare gastric mucosa atrophy, whereas, rare intestinal metaplasia was only significantly higher in the antral area.
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Gastrite , Infecções por Helicobacter , Helicobacter pylori , Biópsia , Criança , Mucosa Gástrica , Gastrite/complicações , Gastrite/diagnóstico , Gastrite/epidemiologia , Gastroscopia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/epidemiologia , Humanos , Metaplasia/patologiaRESUMO
Portal hypertension (PHT) in children may be caused by many different liver and vascular diseases and can lead to life threatening complications such as splenomegaly with thrombocytopenia. The treatment of choice for symptomatic splenomegaly is Partial Splenic Embolization (PSE) which is effective but painful, and therefore not offered to children younger than 10 years of age at the Karolinska University Hospital in Stockholm. Percutaneous microwave ablation (MWA) is a well-established method in adults for the treatment of tumors in the liver and other organs. It has been used for the treatment of secondary splenomegaly in adults, but to the best of our knowledge MWA for treatment of pediatric splenomegaly has not been studied. We present a successful case report of MWA of the spleen in a young boy with splenomegaly and thrombocytopenia due to liver cirrhosis and PHT.
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Hipertensão Portal , Esplenomegalia , Criança , Humanos , Masculino , Micro-Ondas , Baço/diagnóstico por imagem , Baço/cirurgia , Esplenomegalia/diagnóstico por imagem , Esplenomegalia/etiologia , Esplenomegalia/cirurgia , Resultado do TratamentoRESUMO
PHA in the paediatric population is an extremely rare and aggressive malignant soft tissue neoplasm, with less than 50 cases published worldwide. The prognosis is dismal. If the tumour is unresectable, one treatment option is LT. In this article, the current available literature is reviewed and additionally, three cases of paediatric patients with PHA who underwent LT at Karolinska University Hospital, Sweden, are presented. Based on the literature and our own experience, there is undoubtedly possible good outcome of LT due to PHA. On the contrary, no patients have survived PHA without LT. PHA in paediatric patients should be recommended to LT in selected patients. Effect of modern adjuvant chemo and RT should be evaluated further based on international registry for such rare cases of PHA.
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Hemangiossarcoma/cirurgia , Neoplasias Hepáticas/cirurgia , Transplante de Fígado , Pré-Escolar , Feminino , Hemangiossarcoma/diagnóstico , Humanos , Lactente , Neoplasias Hepáticas/diagnósticoRESUMO
BACKGROUND: Childhood obesity increases the risk of non-alcoholic fatty liver disease marked by elevated alanine aminotransferase (ALT). This study investigated the prevalence of increased ALT in children and adolescents with obesity, and its associations with sex, age, degree of obesity, and metabolic parameters. METHODS: Individuals between 5 and 17.99 years of age enrolled in the Swedish Childhood Obesity Treatment Register (BORIS) before March 2020 were included. Mildly increased ALT was defined by ALT 27-51 U/L (males) and 23-43 U/L (females), while markedly increased ALT by levels above. Multiple logistic regression models were used for statistical analysis. RESULTS: Among 11,776 individuals (age 11.0 ± 3.3 years, 53.5% males), the prevalence of mildly and markedly increased ALT were 37.9 and 10.6%, respectively. A sex-age interaction was found, where increasing age strengthened the odds of markedly increased ALT in males (OR, 99% CI: 1.34, 1.29-1.4 for each year) while the corresponding pattern in females with was minuscule (1.09, 1.02-1.10). Compared to class I obesity, class II and III obesity had greater odds ratios for mildly increased ALT (class II obesity OR, 99% CI: 1.51, 1.35-1.70; class III obesity OR, 99% CI: 2.17, 1.66-2.61) and for markedly increased ALT (class II obesity OR, 99% CI: 1.82, 1.51-2.20; class III obesity OR, 99% CI 3.38, 2.71-4.23). Dyslipidemia was associated with both mildly and markedly increased ALT, all p < 0.001. Prevalence of impaired fasting glucose was 19.1% in normal ALT group, 20.4% in mildly increased ALT group, and 29.0% in markedly increased ALT group. CONCLUSIONS: The risk of markedly increased ALT increased exponentially with age among boys, but not among girls. Higher degree of obesity was observed in individuals with mildly and markedly increased ALT. Further, metabolic derangements were more prevalent among individuals with mildly and markedly increased ALT.
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Hepatopatia Gordurosa não Alcoólica , Adolescente , Alanina Transaminase , Índice de Massa Corporal , Criança , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Masculino , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/etiologia , PrevalênciaRESUMO
BACKGROUND: No previous paediatric study has evaluated the frequency of diagnostic disagreement between clinical standard histopathological assessment (CSHA) and retrospective, independent, histopathological assessment (RIHA) of gastrointestinal Graft-Versus-Host Disease (GI-GVHD) METHODS: In a retrospective cohort study, based on gastrointestinal biopsies collected from allogeneic HSCT-treated children (<18 years) with symptom-based GI-GVHD, we evaluated; disagreement of histopathology-based GI-GVHD diagnosis in CSHA vs RIHA, and potential clinical consequences of differences between the assessments. The CSHA-based diagnoses were retrieved from histopathology reports. The RIHA was performed by one pathologist, blinded to the CSHA outcomes and based on the minimal criteria for histopathology-based GI-GVHD diagnosis by the NIH 2014. RESULTS: Seventy children with 92 endoscopic occasions (including 22 re-endoscopies) were enrolled. GI-GVHD was observed in 73% (67/92) of the endoscopies in the RIHA and in 54% (50/92) in the CSHA (P = .014). The RIHA confirmed 94% (47/50) with GI-GVHD and 52% (22/42) with non-GI-GVHD diagnoses, established in the CSHA. Disagreement, that is endoscopic occasions with GI-GVHD solely detected in RIHA or detection of GI-GVHD in CSHA but not in RIHA, was observed in 20/42 (48%) and 3/50 (6%), respectively (McNemar's test, P = .0008). The risk of a subsequent re-endoscopy was higher in endoscopic occasions with GI-GVHD detected in RIHA but not in CSHA vs if non-GI-GVHD were detected in both readings (P = .005). CONCLUSION: Our results suggest that in children with symptom-based GI-GVHD without histopathological confirmation in CSHA, a second, NIH 2014 based histopathological assessment should be considered before performing a re-endoscopy.
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Gastroenteropatias/diagnóstico , Trato Gastrointestinal/patologia , Doença Enxerto-Hospedeiro/diagnóstico , Transplante de Células-Tronco Hematopoéticas , Biópsia , Criança , Diagnóstico Diferencial , Endoscopia Gastrointestinal , Feminino , Gastroenteropatias/imunologia , Doença Enxerto-Hospedeiro/imunologia , Humanos , Masculino , Estudos Retrospectivos , SuéciaRESUMO
OBJECTIVES: The aim of the study was to assess clinical presentation, endoscopic findings, antibiotic susceptibility and treatment success of Helicobacter pylori (H. pylori) infected pediatric patients. METHODS: Between 2013 and 2016, 23 pediatric hospitals from 17 countries prospectively submitted data on consecutive H. pylori-infected (culture positive) patients to the EuroPedHP-Registry. RESULTS: Of 1333 patients recruited (55.1% girls, median age 12.6 years), 1168 (87.6%) were therapy naïve (group A) and 165 (12.4%) had failed treatment (group B). Patients resided in North/Western (29.6%), Southern (34.1%) and Eastern Europe (23.0%), or Israel/Turkey (13.4%). Main indications for endoscopy were abdominal pain or dyspepsia (81.2%, 1078/1328). Antral nodularity was reported in 77.8% (1031/1326) of patients, gastric or duodenal ulcers and erosions in 5.1% and 12.8%, respectively. Primary resistance to clarithromycin (CLA) and metronidazole (MET) occurred in 25% and 21%, respectively, and increased after failed therapy. Bacterial strains were fully susceptible in 60.5% of group A, but in only 27.4% of group B. Primary CLA resistance was higher in Southern and Eastern Europe (adjusted odds ratio [ORadj]â=â3.44, 95% confidence interval [CI] 2.22-5.32, Pâ<â0.001 and 2.62, 95% CI: 1.63-4.22, Pâ<â0.001, respectively) compared with Northern/Western Europe. Children born outside Europe showed higher primary MET resistance (ORadjâ=â3.81, 95% CI: 2.25-6.45, Pâ<â0.001). Treatment success in group A reached only 79.8% (568/712) with 7 to 14 days triple therapy tailored to antibiotic susceptibility. CONCLUSIONS: Peptic ulcers are rare in dyspeptic H. pylori-infected children. Primary resistance to CLA and MET is markedly dependent on geographical regions of birth and residence. The ongoing survey will show whether implementation of the updated ESPGHAN/NASPGHAN guidelines will improve the eradication success.
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Infecções por Helicobacter , Helicobacter pylori , Amoxicilina/uso terapêutico , Antibacterianos/uso terapêutico , Criança , Claritromicina/uso terapêutico , Quimioterapia Combinada , Europa (Continente) , Feminino , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/epidemiologia , Humanos , Israel/epidemiologia , Masculino , Metronidazol/uso terapêutico , Sistema de Registros , TurquiaRESUMO
Endoscopy with histopathological assessment is an established practice to confirm gastrointestinal graft-versus-host disease (GI-GVHD). However, the clinical relevance of this approach in children is incompletely evaluated. In a retrospective cohort study, we investigated the frequency of treatment changes in response to histopathological findings in all children (<18 years) in Sweden who underwent endoscopy for suspected GI-GVHD (2000-2013) after receiving hematopoietic stem cell transplantation. Sixty-eight children with ninety-one endoscopic occasions were enrolled. At the time of endoscopy, anti-GI-GVHD treatment was ongoing in 71% (65/91). In 18% (12/65) with ongoing treatment, no histopathological evidence of GI-GVHD or another cause to justify anti-GI-GVHD treatment was found. In 48% (44/91), endoscopy with histopathological assessment led to changes in the treatment regimen. Re-endoscopy was more frequent among those with treatment changes, versus unchanged treatment, 39% (17/44) and 13% (6/47), respectively (P = .007). Histopathological findings generating treatment changes were as follows: GI-GVHD in 68% (30/44), normal histology in 25% (11/44), and an alternative diagnosis in 7% (3/44). In conclusion, this study supports that endoscopy with histopathological assessment should be considered in all children with suspected GI-GVHD.
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Gastroenteropatias , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Criança , Endoscopia , Gastroenteropatias/diagnóstico , Gastroenteropatias/etiologia , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Estudos Retrospectivos , SuéciaRESUMO
The international liver glycogen storage disease (GSD) priority setting partnership (IGSDPSP) was established to identify the top research priorities in this area. The multiphase methodology followed the principles of the James Lind Alliance (JLA) guidebook. An international scoping survey in seven languages was distributed to patients, carers, and healthcare professionals to gather uncertainties, which were consolidated into summary questions. The existing literature was reviewed to ensure that the summary questions had not yet been answered. A second survey asked responders to prioritize these summary questions. A final shortlist of 22 questions was discussed during an international multi-stakeholder workshop, and a consensus was reached on the top 11 priorities using an adapted nominal group technique.In the first survey, a total of 1388 questions were identified from 763 responders from 58 countries. These original uncertainties were refined into 72 summary questions for a second prioritization survey. In total 562 responders from 58 countries answered the second survey. From the second survey, the top 10 for patients, carers and healthcare professionals was identified and this shortlist of 22 questions was taken to the final workshop. During the final workshop, participants identified the worldwide top 11 research priorities for liver GSD. In addition, a top three research priorities per liver GSD subtype was identified.This unique priority setting partnership is the first international, multilingual priority setting partnership focusing on ultra-rare diseases. This process provides a valuable resource for researchers and funding agencies to foster interdisciplinary and transnational research projects with a clear benefit for patients.
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Doença de Depósito de Glicogênio , Prioridades em Saúde , Inquéritos Epidemiológicos , Participação do Paciente , Pesquisa Biomédica , Cuidadores , Consenso , Comportamento Cooperativo , Pessoal de Saúde , Humanos , Fígado/metabolismo , Reino UnidoRESUMO
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disorder in children and has the potential to progress to advanced fibrosis/cirrhosis, end-stage liver disease and hepatocellular carcinoma. However, the natural history of the condition is poorly understood and there are no approved treatments. The European Paediatric Non-Alcoholic Fatty Liver Disease Registry (EU-PNAFLD) is a multi-centre registry of paediatric NAFLD that will serve as a prospective, observational, natural history study and provide a tractable back-bone to support recruitment into subsequent interventional trials. Collection of samples into a bio-repository will facilitate translational studies, including genome sequencing and metabolomics. EU-PNAFLD will work closely alongside the existing adult European NAFLD Registry to obtain data on clinical outcomes after 20-30â¯years. Through an international, well-characterised large-scale cohort, EU-PNAFLD will address the key questions in paediatric NAFLD and benefit patients with the condition.
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Hepatopatia Gordurosa não Alcoólica/metabolismo , Sistema de Registros , Adolescente , Biomarcadores/metabolismo , Carcinoma Hepatocelular , Criança , Pré-Escolar , Progressão da Doença , Europa (Continente) , Humanos , Lactente , Fígado/diagnóstico por imagem , Fígado/patologia , Cirrose Hepática , Neoplasias Hepáticas , Metabolômica , Hepatopatia Gordurosa não Alcoólica/genética , Estudos Prospectivos , Sequenciamento Completo do GenomaAssuntos
Infecções por Helicobacter , Helicobacter pylori/isolamento & purificação , Guias de Prática Clínica como Assunto , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Peso Corporal , Criança , Esquema de Medicação , Quimioterapia Combinada , Europa (Continente) , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/tratamento farmacológico , Humanos , América do Norte , Inibidores da Bomba de Prótons/administração & dosagem , Inibidores da Bomba de Prótons/uso terapêuticoRESUMO
OBJECTIVES: Gastrointestinal graft-versus-host disease (GI-GVHD) is a potentially life-threatening complication after hematopoietic stem cell transplantation. Symptoms indicating GI-GVHD motivates endoscopy with biopsy sampling and histopathological confirmation. Optimal extent of endoscopy in children is, however, presently unknown. Therefore, we aimed to evaluate whether biopsies from the rectosigmoid area versus the rest of the colon/ileocolon with or without biopsies from simultaneous upper endoscopy, were equally reliable for detection of GI-GVHD and relevant differential diagnoses. METHODS: Retrospective multicenter study based on histopathological re-evaluation of biopsies and hospital record data, collected from children with suspected GI-GVHD. RESULTS: Forty-four children with 51 endoscopic occasions (81 procedures) were included. Thirty-nine of 51 (76.5%) were diagnosed as GI-GVHD, 14 (27.4%) received a differential diagnosis and 7 (13.7%) had normal histology findings. Comorbidity, that is, simultaneous detection of a differential diagnosis and GI-GVHD, was observed in 9 (23.1%) cases. Cytomegalovirus infection was the most frequent differential diagnosis, 6 of 7 were detected in biopsies from rectosigmoid and esophagogastroduodenal areas. Sensitivity for detection of GI-GVHD in biopsies collected from rectosigmoid-ileocolonic-, rectosigmoid-, or esophagogastroduodenal areas were 97.4%, 84.6%, 83.3%, respectively, and 97.4% when the latter 2 were merged. The difference, nondetected GI-GVHD in the rectosigmoid area versus detected elsewhere in the GI tract, was statistically significant (Pâ=â0.03). CONCLUSIONS: Biopsies collected from the rectosigmoid area solely were not optimal for detection of pediatric GI-GVHD. When biopsy sampling from rectosigmoid and upper GI tract areas was combined, the sensitivity for GI-GVHD was, however, equally high as for ileocolonoscopy or full upper and lower endoscopy.
Assuntos
Biópsia/métodos , Endoscopia Gastrointestinal/métodos , Trato Gastrointestinal/patologia , Doença Enxerto-Hospedeiro/diagnóstico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Adolescente , Criança , Pré-Escolar , Infecções por Citomegalovirus/diagnóstico , Diagnóstico Diferencial , Feminino , Doença Enxerto-Hospedeiro/patologia , Humanos , Masculino , Estudos Retrospectivos , Sensibilidade e Especificidade , SuéciaRESUMO
BACKGROUND: Because of the changing epidemiology of Helicobacter pylori infection and low efficacy of currently recommended therapies, an update of the European Society for Paediatric Gastroenterology Hepatology and Nutrition/North American Society for Pediatric Gastroenterology, Hepatology and Nutrition recommendations for the diagnosis and management of H pylori infection in children and adolescents is required. METHODS: A systematic review of the literature (time period: 2009-2014) was performed. Representatives of both societies evaluated the quality of evidence using GRADE (Grading of Recommendation Assessment, Development, and Evaluation) to formulate recommendations, which were voted upon and finalized using a Delphi process and face-to-face meeting. RESULTS: The consensus group recommended that invasive diagnostic testing for H pylori be performed only when treatment will be offered if tests are positive. To reach the aim of a 90% eradication rate with initial therapy, antibiotics should be tailored according to susceptibility testing. Therapy should be administered for 14 days, emphasizing strict adherence. Clarithromycin-containing regimens should be restricted to children infected with susceptible strains. When antibiotic susceptibility profiles are not known, high-dose triple therapy with proton pump inhibitor, amoxicillin, and metronidazole for 14 days or bismuth-based quadruple therapy is recommended. Success of therapy should be monitored after 4 to 8 weeks by reliable noninvasive tests. CONCLUSIONS: The primary goal of clinical investigation is to identify the cause of upper gastrointestinal symptoms rather than H pylori infection. Therefore, we recommend against a test and treat strategy. Decreasing eradication rates with previously recommended treatments call for changes to first-line therapies and broader availability of culture or molecular-based testing to tailor treatment to the individual child.
Assuntos
Antiácidos/uso terapêutico , Antibacterianos/uso terapêutico , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/isolamento & purificação , Inibidores da Bomba de Prótons/uso terapêutico , Adolescente , Criança , Técnica Delphi , Esquema de Medicação , Farmacorresistência Bacteriana , Quimioterapia Combinada , HumanosRESUMO
UNLABELLED: The goal of first-line Helicobacter pylori therapy is to reach an eradication rate of 90% to avoid further investigations, antibiotic use, and spreading of resistant strains. AIM: To evaluate the eradication rate of high-dose sequential therapy in treatment-naïve children and to assess factors associated with failure. METHODS: Prospective data assessed in a registry from nine European centers between October 2009 and December 2011. Children with biopsy-proven Helicobacter pylori infection were prescribed 5 days of esomeprazole and amoxicillin, followed by 5 days of esomeprazole, clarithromycin, and metronidazole according to bodyweight. Eradication was assessed after 8-12 weeks. Primary endpoint was the eradication rate in children who received at least one dose and had follow-up data. Multivariate analysis evaluated potential factors for treatment success including sex, age, center, migrant status, antibiotic resistance, and adherence to therapy. RESULTS: Follow-up was available in 209 of 232 patients (age range 3.1-17.9 years, 118 females). Primary resistance occurred for clarithromycin in 30 of 209 (14.4%), for metronidazole in 32 (15.3%), for both antibiotics in 7 (3.3%), and culture failed in 6 (2.9%). Eradication was achieved in 168 of 209 children (80.4%, 95% CI 75.02-85.78), in 85.8% with no resistance, 72.6% with single resistance, and 28.6% with double resistance. Independent factors affecting eradication rate included resistance to clarithromycin (adjusted ORs 0.27 (0.09-0.84), p = .024), to metronidazole (0.25 (0.009-0.72), p = .010) or to both (0.04 (0.01-0.35), p = .004), and intake of ≤ 90% of prescribed drugs (0.03 (0.01-0.18), p < .001). CONCLUSION: A high-dose 10-day sequential therapy cannot be recommended in treatment-naïve children.