Background Malnutrition underlies 45% of under-5 deaths globally. Severe acute malnutrition (SAM) is the most serious form of undernutrition, characterized by wasting with or without edema. Mortality remains high (10%–40%) among children requiring hospitalization for complicated SAM. Objectives We aimed to systematically document the factors independently associated with inpatient mortality in children with SAM. Methods Embase, Ovid MEDINE, the Cochrane Library, and clinicaltrials.gov were searched for articles published between January 2000 and January 2020, using a prespecified protocol. Eligible studies included children aged ≤59 mo hospitalized with SAM and used multivariable analysis to assess the baseline factors independently associated with inpatient mortality. Random-effects meta-analysis, stratified by the stated measure of effect, was used where >20% of studies included the same factor in analyses. Results Twenty-eight of 1432 studies fulfilled inclusion criteria: 19 studies included all children with SAM and 9 included specific subgroups of children with SAM. All 19 main studies were from 8 countries across Africa, with a median of 400 children/study. The mean inpatient mortality was 15.7% (95% CI: 10.4%, 21.0%) and HIV prevalence ranged from 2.1% to 51%. Nine factors were included in the meta-analysis, stratified by HR and OR. HIV infection (HR: 4.32; 95% CI: 2.31, 8.08), weight-for-height z score (WHZ) (OR: 0.44; 95% CI: 0.24, 0.80), diarrhea (HR: 2.84; 95% CI: 1.40, 5.75), pneumonia (HR: 1.89; 95% CI: 1.19, 3.02), presence of shock (HR: 3.67; 95% CI: 2.24, 6.03), and lack of appetite (HR: 2.16; 95% CI: 1.48, 3.16) were associated with increased mortality, whereas child age and sex were not. The association between edema and mortality was difficult to ascertain from the available studies. Conclusions HIV infection, diarrhea, pneumonia, shock, lack of appetite, and lower WHZ are independent predictors of inpatient mortality in children with SAM. These factors may help to risk-stratify children being hospitalized with complicated SAM. This systematic review/meta-analysis protocol was registered at www.crd.york.ac.uk/prospero as CRD42019152267.

Hepatic encephalopathy (HE) encompasses a spectrum of neuropsychiatric disorders related to liver failure. The development of HE can have a profound impact on mortality as well as quality of life for patients and carers. Ammonia is central in the disease process contributing to alteration in neurotransmission, oxidative stress, and cerebral edema and astrocyte swelling in acute liver failure. Inflammation in the presence of ammonia coactively worsens HE. Inflammation can result from hyperammonemic responses, endotoxemia, innate immune dysfunction or concurrent infection. This review summarizes the current processes implicated in the pathogenesis of HE, as well as current and potential treatments. Treatments currently focus on reducing inflammation and/or blood ammonia levels and provide varying degrees of success. Optimization of current treatments and initial testing of novel therapies will provide the basis of improvement of care in the near future.

Nutritional recovery and hospital readmission following inpatient management of complicated severe acute malnutrition (SAM) are poorly characterised. We aimed to ascertain patterns and factors associated with hospital readmission, nutritional recovery and morbidity, in children discharged from hospital following management of complicated SAM in Zambia and Zimbabwe over 52-weeks posthospitalization.Multivariable Fine-Gray subdistribution hazard models, with death and loss to follow-up as competing risks, were used to identify factors associated with hospital readmission; negative binomial regression to assess time to hospitalisation and ordinal logistic regression to model factors associated with nutritional recovery.A total of 649 children (53% male, median age 18.2 months) were discharged to continue community nutritional rehabilitation. All-cause hospital readmission was 15.4% (95% CI 12.7, 18.6) over 52 weeks. Independent risk factors for time to readmission were cerebral palsy (adjusted subhazard ratio (aSHR): 2.96, 95% CI 1.56, 5.61) and nonoedematous SAM (aSHR: 1.64, 95%CI 1.03, 2.64). Unit increases in height-for-age Z-score (HAZ) (aSHR: 0.82, 95% CI 0.71, 0.95) and enrolment in Zambia (aSHR: 0.52, 95% CI 0.28, 0.97) were associated with reduced subhazard of time to readmission. Young age, SAM at discharge, nonoedematous SAM and cerebral palsy were associated with poor nutritional recovery throughout follow-up.Collectively, nonoedematous SAM, ongoing SAM at discharge, cerebral palsy and low HAZ are independent risk factors for readmission and poor nutritional recovery following complicated SAM. Children with these high-risk features should be prioritised for additional convalescent care to improve long-term outcomes.