Background: Slow gastrointestinal (GI) transit occurs in moderate-to-severe malnutrition. Mechanisms underlying malnutrition-associated dysmotility remain unknown, partially due to lack of animal models. This study sought to characterize GI dysmotility in mouse models of malnutrition. Methods: Neonatal mice were malnourished by timed maternal separation. Alternatively, low-protein, low-fat diet was administered to dams, with malnourished neonates tested at two weeks or weaned to the same chow and tested as young adults. We determined total GI transit time by carmine red gavage, colonic motility by rectal bead latency, and both gastric emptying and small bowel motility with fluorescein isothiocyanate-conjugated dextran. We assessed histology with light microscopy, ex vivo contractility and permeability with force-transduction and Ussing chamber studies, and gut microbiota composition by 16S rDNA sequencing. Key Results: Both models of neonatal malnutrition and young adult malnourished males but not females exhibited moderate growth faltering, stunting, and grossly abnormal stomachs. Progression of fluorescent dye was impaired in both neonatal models of malnutrition, whereas gastric emptying was delayed only in maternally separated pups and malnourished young adult females. Malnourished young adult males but not females had atrophic GI mucosa, exaggerated intestinal contractile responses, and increased gut barrier permeability. These sex-specific abnormalities were associated with altered gut microbial communities. Conclusions & Inferences: Multiple models of early-life malnutrition exhibit delayed upper GI transit. Malnutrition affects young adult males more profoundly than females. These models will facilitate future studies to identify mechanisms underlying malnutrition-induced pathophysiology and sex-specific regulatory effects.
Purpose of review Biliary atresia (BA) is the leading cause of chronic liver disease and the most common indication for pediatric liver transplantation. The use of ultrasound (US) and related techniques continues to evolve to help diagnose BA as well as potentially to help predict outcomes after treatment with the Kasai portoenterostomy (KP). Recent findings There are no US findings that are definitive for BA; however, signs which are consistent with BA include gallbladder abnormalities, the triangular cord sign, presence of hepatic subcapsular flow, and hilar lymphadenopathy. Elastography techniques to measure liver stiffness may also increase the diagnostic accuracy of detecting BA, particularly in older infants or without other US findings. In addition, both US and elastography are still being studied as potential methods to predict outcomes after KP such as the development of portal hypertension and the need for liver transplant. Summary US findings in the diagnosis of BA are well characterized. Future studies will help determine the utility of elastography in diagnosing BA, as well as both US and elastography in monitoring and predicting disease outcomes after KP.
Complications of cirrhotic portal hypertension (PHTN) in children are broad and include clinical manifestations ranging from variceal hemorrhage, hepatic encephalopathy (HE), ascites, spontaneous bacterial peritonitis (SBP), and hepatorenal syndrome (HRS) to less common conditions such as hepatopulmonary syndrome, portopulmonary hypertension, and cirrhotic cardiomyopathy. The approaches to the diagnosis and management of these complications have become standard of practice in adults with cirrhosis with many guidance statements available. However, there is limited literature on the diagnosis and management of these complications of PHTN in children with much of the current guidance available focused on variceal hemorrhage. The aim of this review is to summarize the current literature in adults who experience these complications of cirrhotic PHTN beyond variceal hemorrhage and present the available literature in children, with a focus on diagnosis, management, and liver transplant decision making in children with cirrhosis who develop ascites, SBP, HRS, HE, and cardiopulmonary complications.
Background & Aims: Biliary atresia (BA) is the commonest single etiology indication for liver replacement in children. As timely access to liver transplantation (LT) remains challenging for small BA children (with prolonged waiting time being associated with clinical deterioration leading to both preventable pre- and post-transplant morbidity and mortality), the care pathway of BA children in need of LT was analyzed—from diagnosis to LT—with particular attention to referral patterns, timing of referral, waiting list dynamics and need for medical assistance before LT. Methods: International multicentric retrospective study. Intent-to-transplant study analyzing BA children who had indication for LT early in life (aged < 3 years at the time of assessment), over the last 5 years (2016–2020). Clinical and laboratory data of 219 BA children were collected from 8 transplant centers (6 in Europe and 2 in USA). Results: 39 patients underwent primary transplants. Children who underwent Kasai in a specialist -but not transplant- center were older at time of referral and at transplant. At assessment for LT, the vast majority of children already were experiencing complication of cirrhosis, and the majority of children needed medical assistance (nutritional support, hospitalization, transfusion of albumin or blood) while waiting for transplantation. Severe worsening of the clinical condition led to the need for requesting a priority status (i.e., Peld Score exception or similar) for timely graft allocation for 76 children, overall (35%). Conclusions: As LT currently results in BA patient survival exceeding 95% in many expert LT centers, the paradigm for BA management optimization and survival have currently shifted to the pre-LT management. The creation of networks dedicated to the timely referral to a pediatric transplant center and possibly centralization of care should be considered, in combination with implementing all different graft type surgeries in specialist centers (including split and living donor LTs) to achieve timely LT in this vulnerable population.
A 15-year old Hispanic male with asthma presented with 1-week of hematemesis, melena, and 1month 10 lb weight loss. His hemoglobin was 7.7 g/dL, and he received a red blood cell transfusion and intravenous acid blockade medication. His white blood cells, platelets, electrolytes, albumin, and international normalized ratio were normal. Initial endoscopic features showed focal ecchymoses, diffuse mucosal nodularity, and oozing; however, specimen pathology lacked significant abnormalities. Abdominal CT and PET scan demonstrated gastric wall thickening, nodularity, and hypermetabolic activity, respectively. Oncology recommended full-thickness biopsies to better evaluate for malignancy. Repeat endoscopy with surgical laparoscopic mucosal resection and wedge biopsies revealed a markedly thickened muscular wall and chronic inflammation (Fig. 1). Workup for malignancies, infections, rheumatologic or autoinflammatory disorders was negative. Subsequent esophagogastroduodenoscopy and lacrimal duct specimens were obtained to perform additional diagnostic tissue staining and were Congo red positive with birefringence via polarized light, consistent with amyloid deposition (Fig. 2). LC-MS/MS confirmed AL (lambda)-type amyloid deposition. Pulmonary function tests and echocardiogram were normal.Amyloidosis is a group of hereditary or acquired diseases marked by systemic or localized amyloid deposition leading to progressive organ dysfunction (1). An accumulation of abnormal proteins occurs in immunoglobulin light chain (AL) amyloidosis and aging-associated amyloidosis (1,2). Conversely, an excess of normal proteins occurs in systemic (AA) amyloidosis or ß2-microglobulin amyloidosis (1). Gastrointestinal manifestations of amyloidosis include dysmotility, malabsorption, and bleeding (2). Previous case reports described adult amyloidosis patients with gastrointestinal involvement presenting with hematemesis (3,4). We report a rare pediatric case of systemic AL amyloidosis presenting with upper gastrointestinal bleeding.
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