RESUMO
Echinococcus granulosus larvae can cause cystic echinococcosis (CE, also known as hydatid disease) in humans. The latent phase of hydatid disease lasts for years as a result of the slow growth of the cysts, which only become symptomatic when they are large. Therefore, CE is seldomly seen in very young children. Here we present a 4-year-old boy with two giant asymptomatic abdominal cysts. Ultrasound was inconclusive in regard to the nature of the cysts and serology for echinococcosis was negative, rendering CE improbable also in view of the young age. Nevertheless, in the absence of other conclusive explanations, the patient was started on albendazole. A subsequent diagnostic percutaneous puncture with direct microscopy of cyst fluid revealed parasitological evidence of echinococcosis. This case report shows that CE can present with giant cysts also at very young age and should be considered as a possible diagnosis in all children with giant abdominal cysts.
Assuntos
Albendazol , Equinococose , Echinococcus granulosus , Humanos , Masculino , Pré-Escolar , Equinococose/diagnóstico , Equinococose/parasitologia , Animais , Echinococcus granulosus/isolamento & purificação , Albendazol/uso terapêutico , Ultrassonografia , Cistos/diagnóstico , Cistos/parasitologia , Cistos/diagnóstico por imagem , Abdome/diagnóstico por imagemRESUMO
RATIONALE: Lipoprotein lipase (LPL) deficiency, a rare inherited metabolic disorder, is characterized by high triglyceride (TG) levels and life-threatening acute pancreatitis. Current treatment for pediatric patients involves a lifelong severely fat-restricted diet, posing adherence challenges. Volanesorsen, an EMA-approved RNA therapy for adults, effectively reduces TG levels by decreasing the production of apolipoprotein C-III. This 96-week observational open-label study explores Volanesorsen's safety and efficacy in a 13-year-old female with LPL deficiency. METHODS: The patient, with a history of severe TG elevations, 53 hospital admissions, and life-threatening recurrent pancreatitis despite dietary restrictions, received weekly subcutaneous Volanesorsen injections. We designed a protocol for this investigator-initiated study, primarily focusing on changes in fasting TG levels and hospital admissions. RESULTS: While the injections caused occasional pain and swelling, no other adverse events were observed. TG levels decreased during treatment, with more measurements below the pancreatitis risk threshold compared to pre-treatment. No hospital admissions occurred in the initial 14 months of treatment, contrasting with 21 admissions in the 96 weeks before. In the past 10 months, two pancreatitis episodes may have been linked to dietary noncompliance. Dietary restrictions were relaxed, increasing fat intake by 65% compared to baseline. While not fully reflected in the PedsQL, both parents and the patient narratively reported an improved quality of life. CONCLUSION: This study demonstrates, for the first time, that Volanesorsen is tolerated in a pediatric patient with severe LPL deficiency and effectively lowers TG levels, preventing life-threatening complications. This warrants consideration for expanded access in this population.
Assuntos
Hiperlipoproteinemia Tipo I , Oligonucleotídeos , Pancreatite , Triglicerídeos , Humanos , Feminino , Adolescente , Hiperlipoproteinemia Tipo I/tratamento farmacológico , Hiperlipoproteinemia Tipo I/genética , Pancreatite/tratamento farmacológico , Triglicerídeos/sangue , Lipase Lipoproteica/genética , Lipase Lipoproteica/deficiência , Resultado do Tratamento , Apolipoproteína C-IIIRESUMO
OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in children. Roughly a quarter of paediatric patients with NAFLD develop nonalcoholic steatohepatitis and fibrosis. Here, we evaluated the diagnostic accuracy of previously published noninvasive fibrosis scores to predict liver fibrosis in a large European cohort of paediatric patients with NAFLD. METHODS: The 457 patients with biopsy-proven NAFLD from 10 specialized centers were included. We assessed diagnostic accuracy for the prediction of any (F ≥ 1), moderate (F ≥ 2) or advanced (F ≥ 3) fibrosis for the AST/platelet ratio (APRI), Fibrosis 4 score (FIB-4), paediatric NAFLD fibrosis score (PNFS) and paediatric NAFLD fibrosis index (PNFI). RESULTS: Patients covered the full spectrum of fibrosis (F0: n = 103; F1: n = 230; F2: n = 78; F3: n = 44; F4: n = 2). None of the scores were able to accurately distinguish the presence of any fibrosis from no fibrosis. For the detection of moderate fibrosis, area under the receiver operating characteristic curve (AUROC) were: APRI: 0.697, FIB-4: 0.663, PNFI: 0.515, PNFS: 0.665, while for detection of advanced fibrosis AUROCs were: APRI: 0.759, FIB-4: 0.611, PNFI: 0.521, PNFS: 0.712. Fibrosis scores showed no diagnostic benefit over using ALT ≤ 50/ > 50 IU/L as a cut-off. CONCLUSIONS: Established fibrosis scores lack diagnostic accuracy to replace liver biopsy for staging of fibrosis, giving similar results as compared to using ALT alone. New diagnostic tools are needed for Noninvasive risk-stratification in paediatric NAFLD.
Assuntos
Hepatopatia Gordurosa não Alcoólica , Humanos , Criança , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/patologia , Contagem de Plaquetas , Aspartato Aminotransferases , Alanina Transaminase , Índice de Gravidade de Doença , Cirrose Hepática/diagnóstico , Cirrose Hepática/etiologia , Cirrose Hepática/patologia , Curva ROC , Biópsia , Fígado/patologiaRESUMO
The principal limitations of the terms NAFLD and NASH are the reliance on exclusionary confounder terms and the use of potentially stigmatising language. This study set out to determine if content experts and patient advocates were in favor of a change in nomenclature and/or definition. A modified Delphi process was led by three large pan-national liver associations. The consensus was defined a priori as a supermajority (67%) vote. An independent committee of experts external to the nomenclature process made the final recommendation on the acronym and its diagnostic criteria. A total of 236 panelists from 56 countries participated in 4 online surveys and 2 hybrid meetings. Response rates across the 4 survey rounds were 87%, 83%, 83%, and 78%, respectively. Seventy-four percent of respondents felt that the current nomenclature was sufficiently flawed to consider a name change. The terms "nonalcoholic" and "fatty" were felt to be stigmatising by 61% and 66% of respondents, respectively. Steatotic liver disease was chosen as an overarching term to encompass the various aetiologies of steatosis. The term steatohepatitis was felt to be an important pathophysiological concept that should be retained. The name chosen to replace NAFLD was metabolic dysfunction-associated steatotic liver disease. There was consensus to change the definition to include the presence of at least 1 of 5 cardiometabolic risk factors. Those with no metabolic parameters and no known cause were deemed to have cryptogenic steatotic liver disease. A new category, outside pure metabolic dysfunction-associated steatotic liver disease, termed metabolic and alcohol related/associated liver disease (MetALD), was selected to describe those with metabolic dysfunction-associated steatotic liver disease, who consume greater amounts of alcohol per week (140-350 g/wk and 210-420 g/wk for females and males, respectively). The new nomenclature and diagnostic criteria are widely supported and nonstigmatising, and can improve awareness and patient identification.
Assuntos
Hepatopatia Gordurosa não Alcoólica , Feminino , Masculino , Humanos , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Técnica Delphi , Etanol , Fatores de Risco Cardiometabólico , Consenso , HepatomegaliaRESUMO
The principal limitations of the terms NAFLD and NASH are the reliance on exclusionary confounder terms and the use of potentially stigmatising language. This study set out to determine if content experts and patient advocates were in favor of a change in nomenclature and/or definition. A modified Delphi process was led by three large pan-national liver associations. The consensus was defined a priori as a supermajority (67%) vote. An independent committee of experts external to the nomenclature process made the final recommendation on the acronym and its diagnostic criteria. A total of 236 panelists from 56 countries participated in 4 online surveys and 2 hybrid meetings. Response rates across the 4 survey rounds were 87%, 83%, 83%, and 78%, respectively. Seventy-four percent of respondents felt that the current nomenclature was sufficiently flawed to consider a name change. The terms "nonalcoholic" and "fatty" were felt to be stigmatising by 61% and 66% of respondents, respectively. Steatotic liver disease was chosen as an overarching term to encompass the various aetiologies of steatosis. The term steatohepatitis was felt to be an important pathophysiological concept that should be retained. The name chosen to replace NAFLD was metabolic dysfunction-associated steatotic liver disease. There was consensus to change the definition to include the presence of at least 1 of 5 cardiometabolic risk factors. Those with no metabolic parameters and no known cause were deemed to have cryptogenic steatotic liver disease. A new category, outside pure metabolic dysfunction-associated steatotic liver disease, termed metabolic and alcohol related/associated liver disease (MetALD), was selected to describe those with metabolic dysfunction-associated steatotic liver disease, who consume greater amounts of alcohol per week (140-350 g/wk and 210-420 g/wk for females and males, respectively). The new nomenclature and diagnostic criteria are widely supported and nonstigmatising, and can improve awareness and patient identification.
Assuntos
Hepatopatia Gordurosa não Alcoólica , Masculino , Feminino , Humanos , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Técnica Delphi , Hepatomegalia , Inquéritos e QuestionáriosRESUMO
The principal limitations of the terms NAFLD and NASH are the reliance on exclusionary confounder terms and the use of potentially stigmatising language. This study set out to determine if content experts and patient advocates were in favour of a change in nomenclature and/or definition. A modified Delphi process was led by three large pan-national liver associations. The consensus was defined a priori as a supermajority (67%) vote. An independent committee of experts external to the nomenclature process made the final recommendation on the acronym and its diagnostic criteria. A total of 236 panellists from 56 countries participated in 4 online surveys and 2 hybrid meetings. Response rates across the 4 survey rounds were 87%, 83%, 83%, and 78%, respectively. Seventy-four percent of respondents felt that the current nomenclature was sufficiently flawed to consider a name change. The terms "nonalcoholic" and "fatty" were felt to be stigmatising by 61% and 66% of respondents, respectively. Steatotic liver disease was chosen as an overarching term to encompass the various aetiologies of steatosis. The term steatohepatitis was felt to be an important pathophysiological concept that should be retained. The name chosen to replace NAFLD was metabolic dysfunction-associated steatotic liver disease (MASLD). There was consensus to change the definition to include the presence of at least 1 of 5 cardiometabolic risk factors. Those with no metabolic parameters and no known cause were deemed to have cryptogenic steatotic liver disease. A new category, outside pure metabolic dysfunction-associated steatotic liver disease, termed metabolic and alcohol related/associated liver disease (MetALD), was selected to describe those with metabolic dysfunction-associated steatotic liver disease, who consume greater amounts of alcohol per week (140-350 g/wk and 210-420 g/wk for females and males, respectively). The new nomenclature and diagnostic criteria are widely supported and non-stigmatising, and can improve awareness and patient identification.
Assuntos
Hepatopatia Gordurosa não Alcoólica , Feminino , Masculino , Humanos , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Técnica Delphi , Etanol , Consenso , HepatomegaliaRESUMO
OBJECTIVES: Currently, there is no consensus on how to score Crohn disease (CD) activity assessed by intestinal ultrasound (IUS) in children. This study aimed to design an easy-to-use IUS score for disease activity in pediatric CD. METHODS: Children undergoing ileo-colonoscopy for CD assessment underwent IUS the day before ileo-colonoscopy, assessed with simple endoscopic score for CD (SES-CD). IUS features were compared to the SES-CD on segmental level. Multiple regression analyses, separately for terminal ileum (TI) and colon, were done to assess predictors of disease activity and to develop a model. RESULTS: In 74 CD patients (median 15 years, 48% female), 67 TI and 364 colon segments were assessed. Based on receiver operating characteristics curves, bowel wall thickness (BWT) was categorized into low [1 point: 2-3 mm (TI) and 1.6-2 mm (colon)], medium [2 points: 3.0-3.7 mm (TI) and 2.0-2.7 mm (colon)], and high [3 points: >3.7 mm (TI) and >2.7 mm (colon)]. In TI, only BWT was retained in the model [high BWT: odds ratio (OR) 11.50, P < 0.001]. In colon, BWT (high BWT: OR 8.63, P < 0.001) and mesenteric fat (1 point: OR 3.02, P < 0.001) were independent predictors. A pediatric Crohn disease IUS score (PCD-US) cut-off of 1 resulted in a sensitivity of 82% (95% confidence interval, CI: 65%-93%) and 85% (95% CI: 80%-89%) and a cut-off of 3 in a specificity of 88% (72%-97%) and 92% (87%-96%) for TI and colon, respectively. Inter-observer agreement was moderate for TI and colon ( K : 0.42, K : 0.49, respectively). CONCLUSIONS: The PCD-US score is an easy-to-use and reliable score to detect or rule out CD activity on segmental level in children. External validation is needed before applying this score in clinical practice.
Assuntos
Doença de Crohn , Humanos , Criança , Feminino , Masculino , Doença de Crohn/diagnóstico por imagem , Colo/diagnóstico por imagem , Colonoscopia , Íleo/diagnóstico por imagem , Índice de Gravidade de DoençaRESUMO
BACKGROUND: There is currently no consensus on the definition of an abnormal intestinal ultrasound (IUS) for children with ulcerative colitis (UC). This cross-sectional study aimed to externally validate and compare 2 existing IUS indices in children with UC. METHODS: Children undergoing colonoscopy for UC assessment underwent IUS the day before colonoscopy, assessed with the Mayo endoscopic subscore. The UC-IUS index and the Civitelli index were compared with the Mayo endoscopic score in the ascending, transverse, and descending colon. The area under the receiver-operating characteristic curve for detecting a Mayo endoscopic score ≥2 of both scores was compared and sensitivity and specificity were calculated. RESULTS: A total of 35 UC patients were included (median age 15 years, 39% female). The area under the receiver-operating characteristic curve was higher for the UC-IUS index in the ascending colon (0.82 [95% confidence interval (CI), 0.67-0.97] vs 0.76 [95% CI, 0.59-0.93]; P = .046) and transverse colon (0.88 [95% CI, 0.76-1.00] vs 0.77 [95% CI, 0.60-0.93]; P = .01). In the descending colon, there was no difference (0.84 [95% CI, 0.70-0.99] vs 0.84 [95% CI, 0.70-0.98]). The optimal cutoff for the UC-IUS was <1 point to rule out a Mayo endoscopic score ≥2 (sensitivity: 88%, 100%, and 90% in the ascending, transverse, and descending colon, respectively) and a Mayo endoscopic score ≥2 could be detected using a cutoff of >1 (specificity: 84%, 83%, and 87%, respectively). For the Civitelli index, in our cohort, the optimal cutoff was <1 to rule out a Mayo endoscopic score ≥2 (sensitivity 75%, 65%, and 80%, respectively) and a cutoff >1 to detect a Mayo endoscopic score ≥2 (specificity 89%, 89%, and 93%, respectively). CONCLUSIONS: In this cohort, the UC-IUS index performed better than the Civitelli index. The UC-IUS index had both a high sensitivity and specificity in this cohort, when using 1 point as cutoff for a Mayo endoscopic score ≥2.
In this prospective study, we validated and compared 2 intestinal ultrasound indices to score pediatric ulcerative colitis: the UC-IUS index and the Civitelli index. In our cohort, the UC-IUS index was more accurate.
Assuntos
Colite Ulcerativa , Humanos , Feminino , Criança , Adolescente , Masculino , Colite Ulcerativa/diagnóstico por imagem , Estudos Transversais , Mucosa Intestinal , Colonoscopia , Intestinos/diagnóstico por imagem , Índice de Gravidade de DoençaRESUMO
Genome-wide association studies in adults have identified variants in hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13) and mitochondrial amidoxime reducing component 1 (MTARC1) as protective against nonalcoholic fatty liver disease (NAFLD). We aimed to test their association with pediatric NAFLD liver histology and investigate their function using metabolomics. A total of 1450 children (729 with NAFLD, 399 with liver histology) were genotyped for rs72613567T>TA in HSD17B13, rs2642438G>A in MTARC1, and rs738409C>G in patatin-like phospholipase domain-containing protein 3 (PNPLA3). Genotype-histology associations were tested using ordinal regression. Untargeted hepatic proteomics and plasma lipidomics were performed in a subset of children. We found rs72613567T>TA in HSD17B13 to be associated with lower odds of NAFLD diagnosis (odds ratio, 0.7; 95% confidence interval, 0.6-0.9) and a lower grade of portal inflammation (p < 0.001). rs2642438G>A in MTARC1 was associated with a lower grade of hepatic steatosis (p = 0.02). Proteomics found reduced expression of HSD17B13 in carriers of the protective -TA allele. MTARC1 levels were unaffected by genotype. Both variants were associated with down-regulation of fibrogenic pathways. HSD17B13 perturbs plasma phosphatidylcholines and triglycerides. In silico modeling suggested p.Ala165Thr disrupts the stability and metal binding of MTARC1. Conclusion: Both HSD17B13 and MTARC1 variants are associated with less severe pediatric NAFLD. These results provide further evidence for shared genetic mechanisms between pediatric and adult NAFLD.
Assuntos
17-Hidroxiesteroide Desidrogenases , Proteínas Mitocondriais , Hepatopatia Gordurosa não Alcoólica , Oxirredutases , 17-Hidroxiesteroide Desidrogenases/genética , Criança , Estudo de Associação Genômica Ampla , Humanos , Hidroxiesteroides , Proteínas Mitocondriais/genética , Hepatopatia Gordurosa não Alcoólica/genética , Oxirredutases/genética , OximasRESUMO
OBJECTIVES: Training healthcare physicians to perform intestinal ultrasound (IUS) during outpatient visits with equal accuracy as radiologists could improve clinical management of IBD patients. We aimed to assess whether a healthcare-physician can be trained to perform IUS, with equal accuracy compared with experienced radiologists in children with iBD, and to assess inter-observer agreement. METHODS: Consecutive children, 6 to 18âyears with IBD or suspicion of IBD, who underwent ileo-colonoscopy were enrolled. iUS was performed independently by a trained healthcare-physician and a radiologist in 1 visit. Training existed of an international training curriculum for IUS. Operators were blinded for each other's IUS, and for the ileocolonoscopy. Difference in accuracy of IUS by the healthcare-physician and radiologist was assessed using areas under the ROC curve (AUROC). Inter-observer variability was assessed in terminal ileum (TI), transverse colon (TC) and descending-colon (DC), for disease activity (ie, bowel wall thickness [BWT] >2âmm with hyperaemia or fat-proliferation, or BWT >3âmm). RESULTS: We included 73 patients (median age 15, interquartile range [IQR]:13-17, 37 [51%] female, 43 [58%] with Crohn disease). AUROC ranged between 0.71 and 0.81 for the healthcare-physician and between 0.67 and 0.79 for radiologist (Pâ >â0.05). Inter-observer agreement for disease activity per segment was moderate (K: 0.58 [SE: 0.09], 0.49 [SE: 0.12], 0.52 [SE: 0.11] respectively for TI, TC, and DC). CONCLUSIONS: A healthcare- physician can be trained to perform IUS in children with IBD with comparable diagnostic accuracy as experienced radiologists. The interobserver agreement is moderate. Our findings support the usage of IUS in clinical management of children with IBD.
Assuntos
Doenças Inflamatórias Intestinais , Médicos , Adolescente , Criança , Atenção à Saúde , Feminino , Humanos , Doenças Inflamatórias Intestinais/diagnóstico por imagem , Intestinos/diagnóstico por imagem , Masculino , UltrassonografiaRESUMO
OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) is an increasingly common condition in children characterised by insulin resistance and altered lipid metabolism. Affected patients are at increased risk of cardiovascular disease (CVD) and children with NAFLD are likely to be at risk of premature cardiac events. Evaluation of the plasma lipid profile of children with NAFLD offers the opportunity to investigate these perturbations and understand how closely they mimic the changes seen in adults with cardiometabolic disease. METHODS: We performed untargeted liquid chromatography-mass spectrometry (LC-MS) plasma lipidomics on 287 children: 19 lean controls, 146 from an obese cohort, and 122 NAFLD cases who had undergone liver biopsy. Associations between lipid species and liver histology were assessed using regression adjusted for age and sex. Results were then replicated using data from 9500 adults with metabolic phenotyping. RESULTS: More severe paediatric NAFLD was associated with lower levels of long chain, polyunsaturated phosphatidylcholines (pC) and triglycerides (TG). Similar trends in pC and TG chain length and saturation were seen in adults with hepatic steatosis; however, many of the specific lipids associated with NAFLD differed between children and adults. Five lipids replicated in adults (including PC(36:4)) have been directly linked to death and cardiometabolic disease, as well as indirectly via genetic variants. CONCLUSION: These findings suggest that, whilst similar pathways of lipid metabolism are perturbed in paediatric NAFLD as in cardiometabolic disease in adults, the specific lipid signature in children is different.
Assuntos
Doenças Cardiovasculares , Hepatopatia Gordurosa não Alcoólica , Adulto , Doenças Cardiovasculares/etiologia , Criança , Estudos Transversais , Humanos , Lipidômica , Fígado/patologia , Hepatopatia Gordurosa não Alcoólica/patologia , TriglicerídeosRESUMO
To determine the perception of children with inflammatory bowel disease (IBD) regarding monitoring tests, we first compared the reported discomfort and patient perspective during gastro-intestinal (GI)-endoscopy, magnetic resonance entrography (MRE), and ultrasound (US) and, in a second comparison, patient preference on non-invasive tests (venipuncture, sampling stool and US). A cross-sectional study in children 8-18 years undergoing an US, MRE, and GI-endoscopy for diagnosis or follow-up of IBD. After each procedure, the children filled out the Discomfort during research procedures questionnaire (DISCO-RC). Items of the DISCO-RC are as follows: nervousness, annoyance, pain, fright, boredom, and tiredness. Answers range from "not" (= 0 points) to "extremely" (= 4 points) (range total score: 0-24). Differences between the procedures were assessed with Friedman test, with subsequent Wilcoxon signed-rank test. The children were also asked which non-invasive test they preferred not to undergo regularly (venipuncture, stool-sampling, or US). Answers were analyzed with χ2-test. Forty-nine patients (27 (55%) female, median age 15 (range 9-17)) were included. The children reported to be most nervous, frightened, and tired after GI-endoscopy (median: 1, 1, 2 points, respectively), equally annoyed by MRE and GI-endoscopy (median 1 point), and equally bored by MRE and US. GI-endoscopy was ranked as most discomfortable, followed by MRE and US (total DISCO-RC scores: 7 vs. 5 vs. 2, p < 0.001). Most of the children preferred not to sample stool or perform venipuncture regularly (n = 20 (41%, both) (p < 0.001)).Conclusion: Our results suggest that the children with IBD report low discomfort after US, MRE, and GI-endoscopy. US is preferred as a monitoring tool, also among non-invasive monitoring tests. GI-endoscopy was most discomfortable. What is Known: ⢠Children with inflammatory bowel disease need to be monitored frequently for disease activity. ⢠Adult studies - including a systematic review - on acceptability of monitoring tools among IBD patients showed mixed results. What is New: ⢠Children in our study ranked gastro-intestinal endoscopy as most discomfortable, followed by MRE and US. ⢠With regard to non-invasive monitoring, most children preferred not to sample stool or perform venipuncture regularly, and preferred US.
Assuntos
Doenças Inflamatórias Intestinais , Adolescente , Adulto , Criança , Estudos Transversais , Feminino , Humanos , Doenças Inflamatórias Intestinais/diagnóstico , Imageamento por Ressonância Magnética/métodos , Percepção , Ultrassonografia/métodosRESUMO
BACKGROUND: Fecal calprotectin (FC) is a biomarker for inflammation in inflammatory bowel disease (IBD). Interpretation of results can be complicated because of the use of different assays to determine FC. GOALS: To assess the agreement between 2 different assays for determining FC in patients with IBD. METHODS: Samples from adults and children with IBD were tested with 2 assays: (1) EliA 2 Calprotectin and (2) EK-Cal. Samples were uniformly tested on the same day. Interassay variability was displayed in a Bland-Altman plot. The difference in categorization of the FC result (1: 0 to 250 mg/kg, 2: 250 to 500 mg/kg, 3: >500 mg/kg) was assessed with the linear weighted κ for adults and children separately. RESULTS: A total of 171 patients [mean age: 33 (range: 7 to 81); 92 (54%) female; 117 (68%) Crohn's disease; 53 (31%) ulcerative colitis] were included. Median (interquartile ranges) FC levels were 281 mg/kg (70 to 971) (EK-Cal) and 159 mg/kg (31 to 778) (EliA 2), and the mean delta FC was 89 mg/kg. In the adult population, there was substantial agreement between the 2 assays (κ: 0.72; SE: 0.06; 95% confidence interval, 0.60-0.83) and for pediatric patients, the agreement was almost perfect (κ: 0.83; SE: 0.06; 95% confidence interval: 0.70-0.95). Five of 171 patients (all aged ≥17 y and all with colonic disease) had a difference of 2 categories (1 vs. 3) between assays. Interassay variability was the highest in category 3. CONCLUSIONS: The agreement between the EliA 2 and EK-Cal assay in this cohort of IBD patients is substantial to almost perfect. Interassay variability is higher in the highest FC category.
Assuntos
Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Adulto , Biomarcadores , Criança , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/diagnóstico , Doença de Crohn/tratamento farmacológico , Fezes , Feminino , Humanos , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Complexo Antígeno L1 LeucocitárioRESUMO
Intestinal ultrasound (IUS) is increasingly used and promulgated as a noninvasive monitoring tool for children with inflammatory bowel disease because other diagnostic modalities such as colonoscopy and magnetic resonance imaging cause significant stress in the pediatric population. The most important parameters of inflammation that can be assessed using IUS are bowel wall thickness and hyperemia of the bowel wall. Research has shown that IUS has the potential to be a valuable additional point-of-care tool to guide treatment choice and to monitor and predict treatment response, although evidence of its accuracy and value in clinical practice is still limited. This review gives an update and overview of the current evidence on the use and accuracy of IUS in children with inflammatory bowel disease.
Assuntos
Doenças Inflamatórias Intestinais , Criança , Colonoscopia , Humanos , Doenças Inflamatórias Intestinais/diagnóstico por imagem , Intestinos/diagnóstico por imagem , Imageamento por Ressonância Magnética , Ultrassonografia/métodosRESUMO
BACKGROUND: Survivors of childhood, adolescent and young adult (CAYA) cancer may develop treatment-induced chronic liver disease. Surveillance guidelines can improve survivors' health outcomes. However, current recommendations vary, leading to uncertainty about optimal screening. The International Late Effects of Childhood Cancer Guideline Harmonization Group has developed recommendations for the surveillance of late hepatotoxicity after CAYA cancer. METHODS: Evidence-based methods based on the GRADE framework were used in guideline development. A multidisciplinary guideline panel performed systematic literature reviews, developed evidence summaries, appraised the evidence, and formulated recommendations on the basis of evidence, clinical judgement, and consideration of benefits versus the harms of the surveillance while allowing for flexibility in implementation across different health care systems. RESULTS: The guideline strongly recommends a physical examination and measurement of serum liver enzyme concentrations (ALT, AST, gGT, ALP) once at entry into long-term follow-up for survivors treated with radiotherapy potentially exposing the liver (moderate- to high-quality evidence). For survivors treated with busulfan, thioguanine, mercaptopurine, methotrexate, dactinomycin, hematopoietic stem cell transplantation (HSCT), or hepatic surgery, or with a history of chronic viral hepatitis or sinusoidal obstruction syndrome, similar surveillance for late hepatotoxicity once at entry into LTFU is reasonable (low-quality evidence/expert opinion, moderate recommendation). For survivors who have undergone HSCT and/or received multiple red blood cell transfusions, surveillance for iron overload with serum ferritin is strongly recommended once at long-term follow-up entry. CONCLUSIONS: These evidence-based, internationally-harmonized recommendations for the surveillance of late hepatic toxicity in cancer survivors can inform clinical care and guide future research of health outcomes for CAYA cancer survivors.
Assuntos
Sobreviventes de Câncer , Hepatopatias/diagnóstico , Hepatopatias/etiologia , Neoplasias/terapia , Lesões por Radiação/diagnóstico , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Humanos , Programas de Rastreamento/métodos , Neoplasias/mortalidade , Lesões por Radiação/etiologiaRESUMO
BACKGROUND AND AIMS: Recurrent primary sclerosing cholangitis (rPSC) following liver transplant (LT) has a negative impact on graft and patient survival; little is known about risk factors for rPSC or disease course in children. APPROACH AND RESULTS: We retrospectively evaluated risk factors for rPSC in 140 children from the Pediatric PSC Consortium, a multicenter international registry. Recipients underwent LT for PSC and had >90 days of follow-up. The primary outcome, rPSC, was defined using Graziadei criteria. Median follow-up after LT was 3 years (interquartile range 1.1-6.1). rPSC occurred in 36 children, representing 10% and 27% of the subjects at 2 years and 5 years following LT, respectively. Subjects with rPSC were younger at LT (12.9 vs. 16.2 years), had faster progression from PSC diagnosis to LT (2.5 vs. 4.1 years), and had higher alanine aminotransferase (112 vs. 66 IU/L) at LT (all P < 0.01). Inflammatory bowel disease was more prevalent in the rPSC group (86% vs. 66%; P = 0.025). After LT, rPSC subjects had more episodes of biopsy-proved acute rejection (mean 3 vs. 1; P < 0.001), and higher prevalence of steroid-refractory rejection (41% vs. 20%; P = 0.04). In those with rPSC, 43% developed complications of portal hypertension, were relisted for LT, or died within 2 years of the diagnosis. Mortality was higher in the rPSC group (11.1% vs. 2.9%; P = 0.05). CONCLUSIONS: The incidence of rPSC in this cohort was higher than previously reported, and was associated with increased morbidity and mortality. Patients with rPSC appeared to have a more aggressive, immune-reactive phenotype. These findings underscore the need to understand the immune mechanisms of rPSC, to lay the foundation for developing new therapies and improve outcomes in this challenging population.
Assuntos
Colangite Esclerosante/cirurgia , Rejeição de Enxerto/epidemiologia , Hipertensão Portal/epidemiologia , Transplante de Fígado , Adolescente , Fatores Etários , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Criança , Colangite Esclerosante/sangue , Colangite Esclerosante/epidemiologia , Progressão da Doença , Resistência a Medicamentos , Feminino , Glucocorticoides/uso terapêutico , Rejeição de Enxerto/tratamento farmacológico , Rejeição de Enxerto/patologia , Sobrevivência de Enxerto , Humanos , Hipertensão Portal/fisiopatologia , Doenças Inflamatórias Intestinais/epidemiologia , Internacionalidade , Masculino , Recidiva , Sistema de Registros , Fatores de Risco , Fatores de Tempo , gama-Glutamiltransferase/sangueRESUMO
BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease in children. Even at young age, it can progress to liver fibrosis. Given the drawbacks of liver biopsy, there is a need for non-invasive methods to accurately stage liver fibrosis in this age group. In this systematic review, we evaluate the diagnostic accuracy of non-invasive methods for staging liver fibrosis in children with NAFLD. METHODS: We searched MEDLINE, Embase, Web of Science and the Cochrane Library, for studies that evaluated the performance of a blood-based biomarker, prediction score or imaging technique in staging liver fibrosis in children with NAFLD, using liver biopsy as the reference standard. RESULTS: Twenty studies with a total of 1787 NAFLD subjects were included, which evaluated three prediction scores, five simple biomarkers, two combined biomarkers and six imaging techniques. Most studies lacked validation. Substantial heterogeneity of studies and limited available study data precluded a meta-analysis of the few fibrosis tests evaluated in more than one study. The most consistent accuracy data were found for transient elastography by FibroScan®, ELF test and ultrasound elastography, with an area under the receiver operating characteristics curve varying between 0.92 and 1.00 for detecting significant fibrosis. CONCLUSION: Due to the lack of validation, the accuracy and clinical utility of non-invasive fibrosis tests in children with NAFLD remains uncertain. As studies have solely been performed in tertiary care settings, accuracy data cannot directly be translated to screening populations.
Assuntos
Técnicas de Imagem por Elasticidade , Hepatopatia Gordurosa não Alcoólica , Biópsia , Criança , Humanos , Fígado/diagnóstico por imagem , Fígado/patologia , Cirrose Hepática/diagnóstico , Cirrose Hepática/patologia , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/patologia , Curva ROCRESUMO
BACKGROUND: Historically, US in the paediatric setting has mostly been the domain of radiologists. However, in the last decade, there has been an uptake of non-radiologist point-of-care US. OBJECTIVE: To gain an overview of abdominal non-radiologist point-of-care US in paediatrics. MATERIALS AND METHODS: We conducted a scoping review regarding the uses of abdominal non-radiologist point-of-care US, quality of examinations and training, patient perspective, financial costs and legal consequences following the use of non-radiologist point-of-care US. We conducted an advanced search of the following databases: Medline, Embase and Web of Science Conference Proceedings. We included published original research studies describing abdominal non-radiologist point-of-care US in children. We limited studies to English-language articles from Western countries. RESULTS: We found a total of 5,092 publications and selected 106 publications for inclusion: 39 studies and 51 case reports or case series on the state-of-art of abdominal non-radiologist point-of-care US, 14 on training of non-radiologists, and 1 each on possible harms following non-radiologist point-of-care US and patient satisfaction. According to included studies, non-radiologist point-of-care US is increasingly used, but no standardised training guidelines exist. We found no studies regarding the financial consequences of non-radiologist point-of-care US. CONCLUSION: This scoping review supports the further development of non-radiologist point-of-care US and underlines the need for consensus on who can do which examination after which level of training among US performers. More research is needed on training non-radiologists and on the costs-to-benefits of non-radiologist point-of-care US.
Assuntos
Pediatria , Sistemas Automatizados de Assistência Junto ao Leito , Abdome/diagnóstico por imagem , Criança , Humanos , Radiologistas , UltrassonografiaRESUMO
BACKGROUND & AIMS: Primary sclerosing cholangitis (PSC) is a rare bile duct disease strongly associated with inflammatory bowel disease (IBD). Whole-exome sequencing (WES) has contributed to understanding the molecular basis of very early-onset IBD, but rare protein-altering genetic variants have not been identified for early-onset PSC. We performed WES in patients diagnosed with PSC ≤ 12 years to investigate the contribution of rare genetic variants to early-onset PSC. METHODS: In this multicentre study, WES was performed on 87 DNA samples from 29 patient-parent trios with early-onset PSC. We selected rare (minor allele frequency < 2%) coding and splice-site variants that matched recessive (homozygous and compound heterozygous variants) and dominant (de novo) inheritance in the index patients. Variant pathogenicity was predicted by an in-house developed algorithm (GAVIN), and PSC-relevant variants were selected using gene expression data and gene function. RESULTS: In 22 of 29 trios we identified at least 1 possibly pathogenic variant. We prioritized 36 genes, harbouring a total of 54 variants with predicted pathogenic effects. In 18 genes, we identified 36 compound heterozygous variants, whereas in the other 18 genes we identified 18 de novo variants. Twelve of 36 candidate risk genes are known to play a role in transmembrane transport, adaptive and innate immunity, and epithelial barrier function. CONCLUSIONS: The 36 candidate genes for early-onset PSC need further verification in other patient cohorts and evaluation of gene function before a causal role can be attributed to its variants.