Legume-supplemented feed for children hospitalised with severe malnutrition: a phase II trial.

Children hospitalised with severe malnutrition have high mortality and readmission rates post-discharge. Current milk-based formulations target restoring ponderal growth but not the modification of gut barrier integrity or microbiome which increases the risk of gram-negative sepsis and poor outcomes. We propose that legume-based feeds rich in fermentable carbohydrates will promote better gut health and improve overall outcomes. We conducted an open-label phase II trial at Mbale and Soroti Regional Referral Hospitals, Uganda, involving 160 children aged 6 months to 5 years with severe malnutrition (mid-upper arm circumference (MUAC) < 11·5 cm and/or nutritional oedema). Children were randomised to a lactose-free, chickpea-enriched legume paste feed (LF) (n 80) v. WHO standard F75/F100 feeds (n 80). Co-primary outcomes were change in MUAC and mortality to day 90. Secondary outcomes included weight gain (> 5 g/kg/d), de novo development of diarrhoea, time to diarrhoea and oedema resolution. Day 90 MUAC increase was marginally lower in LF v. WHO arm (1·1 cm (interquartile range (IQR) 1·1) v. 1·4 cm (IQR 1·40), P = 0·09); day 90 mortality was similar (11/80 (13·8 %) v. 12/80 (15 %), respectively, OR 0·91 (95 % CI 0·40, 2·07), P = 0·83). There were no differences in any of the other secondary outcomes. Owing to initial poor palatability of the LF, ten children switched to WHO feeds. Per-protocol analysis indicated a trend to lower day 90 mortality and readmission rates in the LF (6/60 (10 %) and 2/60(3 %)) v. WHO feeds (12/71(17·5 %) and 4/71(6 %)). Further refinement of LF and clinical trials are warranted, given the poor outcomes in children with severe malnutrition.

Predicting the risk of mortality during hospitalization in sick severely malnourished children using daily evaluation of key clinical warning signs.

BACKGROUND: Despite adherence to WHO guidelines, inpatient mortality among sick children admitted to hospital with complicated severe acute malnutrition (SAM) remains unacceptably high. Several studies have examined risk factors present at admission for mortality. However, risks may evolve during admission with medical and nutritional treatment or deterioration. Currently, no specific guidance exists for assessing daily treatment response. This study aimed to determine the prognostic value of monitoring clinical signs on a daily basis for assessing mortality risk during hospitalization in children with SAM. METHODS: This is a secondary analysis of data from a randomized trial (NCT02246296) among 843 hospitalized children with SAM. Daily clinical signs were prospectively collected during ward rounds. Multivariable extended Cox regression using backward feature selection was performed to identify daily clinical warning signs (CWS) associated with time to death within the first 21 days of hospitalization. Predictive models were subsequently developed, and their prognostic performance evaluated using Harrell's concordance index (C-index) and time-dependent area under the curve (tAUC). RESULTS: Inpatient case fatality ratio was 16.3% (n=127). The presence of the following CWS during daily assessment were found to be independent predictors of inpatient mortality: symptomatic hypoglycemia, reduced consciousness, chest indrawing, not able to complete feeds, nutritional edema, diarrhea, and fever. Daily risk scores computed using these 7 CWS together with MUAC<10.5cm at admission as additional CWS predict survival outcome of children with SAM with a C-index of 0.81 (95% CI 0.77-0.86). Moreover, counting signs among the top 5 CWS (reduced consciousness, symptomatic hypoglycemia, chest indrawing, not able to complete foods, and MUAC<10.5cm) provided a simpler tool with similar prognostic performance (C-index of 0.79; 95% CI 0.74-0.84). Having 1 or 2 of these CWS on any day during hospitalization was associated with a 3 or 11-fold increased mortality risk compared with no signs, respectively. CONCLUSIONS: This study provides evidence for structured monitoring of daily CWS as recommended clinical practice as it improves prediction of inpatient mortality among sick children with complicated SAM. We propose a simple counting-tool to guide healthcare workers to assess treatment response for these children. TRIAL REGISTRATION: NCT02246296.

Early management of hypokalaemia in severely malnourished children under five could help to reduce deaths in developing countries.

AIM: This study evaluated the factors associated with hypokalaemia and their outcomes, in severely malnourished children under 5 years of age. METHODS: We focused on 407 severely malnourished children under five who were admitted to the Dhaka Hospital, International Centre for Diarrhoeal Disease Research, Bangladesh, from April 2011 to June 2012. The cases were 139 with hypokalaemia, and the comparisons were 268 without hypokalaemia. RESULTS: Cases were older than the comparisons, with a poor socio-economic status and a higher death rate of 12% vs 7%. They were more likely to present with a history of measles, diarrhoea, lethargy, lower pulse rates, hyponatraemia, metabolic acidosis, hypocalcaemia, hypomagnesaemia, higher height or length, severe underweight, severe wasting and leucocytosis on admission. At discharge, cases had lower potassium levels and a higher proportion had persistent hypokalaemia. Cases received longer treatment with ampicillin and micronutrients. After adjusting for confounders, hypokalaemia was independently associated with poor socio-economic status, diarrhoea, lower pulse rates, hypocalcaemia, metabolic acidosis and leucocytosis. CONCLUSION: Identifying simple clinical signs, like diarrhoea and lower pulse rates, and laboratory parameters, such as hypocalcaemia and metabolic acidosis, may enable the early management of hypokalaemia in severely malnourished children under 5 years. This could reduce morbidity and mortality.

Socio-demographic risk factors for severe malnutrition in children aged under five among various birth cohorts in Bangladesh.

Tackling malnutrition is a major health priority for a developing country like Bangladesh. This study explored the differences in prevalence of having only one form, and multiple forms, of severe malnutrition (stunting, wasting and underweight) among under-5 children in Bangladesh, and aimed to identify the important factors affecting these. Data were extracted from the Bangladesh Demographic Health Surveys conducted in 2007, 2011 and 2014. The outcome measures were 'only one form' and 'multiple forms' of severe malnutrition in children aged under 5 years. A Chi-squared test was performed to find the association of outcome variables with selected socio-demographic factors and logistic regression models were applied to identify risk factors. A total of 19,874 children aged under 5 years were included in the analysis. The overall proportion with one form of severe child malnutrition was approximately 12%, and the proportion with multiple forms was 8%. Age, mother's education, father's occupation, mother currently working, watching television, source of water, solid waste used in cooking, intimate partner violence (IPV), wealth index, urban/rural place of residence and birth cohort were found to be significant factors for both having only one and having multiple forms of severe child malnutrition. Children with an uneducated mother of poor socioeconomic class had a higher risk of severe malnutrition. Children of fathers with a professional occupation were at lower risk of having multiple forms of severe malnutrition. The proportions of children aged under 5 years with one or multiple forms of severe malnutrition were shown to be high in Bangladesh. The prevention of malnutrition in the country should be seen as a significant public health issue and given top priority.

Severe Malnutrition and Anemia Are Associated with Severe COVID in Infants.

BACKGROUND: COVID-19 is uncommon and less severe in children than adults. It is thought that infants may be at higher risk for severe disease than older children. There is a paucity of literature on infants with COVID, particularly those with severe disease. OBJECTIVE: We describe demographic, epidemiologic, clinical, radiological, laboratory features and outcomes of infants with confirmed SARS-CoV-2 infection admitted to a tertiary care teaching hospital in Pune, India. METHODOLOGY: Infants who tested positive for SARS-CoV-2 and were admitted between 1 April 2020 and 7 August 2020 were included in the study. RESULTS: A total of 13 infants were admitted during the study period. The median age was 8 months (IQR 6) and nine were male. Common presenting features were fever (n = 8, 62%), poor feeding, irritability, and runny nose (n = 3, 23%). Comorbidities noted were severe acute malnutrition (SAM) in three cases (23%) and nutritional megaloblastic anemia, iron deficiency anemia, sickle thalassemia and renal calculi in one case (8%) each. There was a history of low birth weight in two cases (15%). Pallor was noted in three cases (23%), SAM in three cases (23%) and tachypnea and respiratory distress in four cases (30%). Severe anemia, thrombocytopenia, elevated ferritin, abnormal procalcitonin, abnormal C Reactive Protein and deranged D-dimer was noted in three cases (23%) each. Neutrophil-lymphocyte ratio was normal in all cases. Three infants (43%) had evidence of pneumonia on the chest radiograph, of which one had adult respiratory distress syndrome (ARDS) like pattern, one infant had cardiomegaly and perihilar infiltrates. Hydroxychloroquine and azithromycin were given to five patients (38%), Intravenous Immunoglobulin and methylprednisolone were administered to one patient (8%). One infant died of ARDS with multi-organ dysfunction with refractory shock and hemophagocytic lymphohistiocytosis. CONCLUSION: SAM and anemia may be associated with severe COVID in infants.

Survival status and mortality predictors among severely malnourished under 5 years of age children admitted to Minia University maternity and children hospital.

BACKGROUND: Though effective treatment programs for severely malnourished children are available, mortality rate among children with acute malnutrition continue to rise and little is known about its long-term outcomes and potential predictors of its in-hospital and post-discharge mortality. The aim of this study was to assess the survival status and predictors for mortality in severely malnourished children admitted to Minia University Maternity and Children Hospital. METHODS: A retrospective cohort study which included 135 children under 5 years of age who were admitted to the nutrition rehabilitation ward with severe acute malnutrition (SAM) during the period from January to December 2018. Data were collected from the inpatient's hospital records and the children's parents/guardians were interviewed using a detailed structured questionnaire that inquired about demographic and socioeconomic variables. The logistic and Cox regressions were used to assess the factors associated with the SAM's mortality. RESULTS: A total of 135 children were enrolled into the study. Death rate during hospitalization was 9.6%. The survival rate at the end of the fourth week of admission was 82.4%. There were 6.7% post-discharge deaths among 104 alive discharged children which occurred within 8 weeks after discharge. The adjusted HRs (95% CIs) for total SAM deaths were 1.57 (1.10-2.99) in children < 12 vs ≥ 12 months old; 4.79 (2.23-6.10) in those with WAZ < -3SD, 2.99 (1.16-4.66) in those with edema at admission and 3.44 (1.07-9.86) in children with complications. The respective ORs (95%CIs) for in-hospital SAM deaths in the same groups of children were 2.64 (1.22-6.43), 8.10 (2.16-11.67), 3.04 (1.70-6.06) and 3.71 (1.59-6.78). The main predictor for the SAM's post-discharge mortality was illiteracy of mothers; the adjusted HR (95%CI) was 7.10 (1.58-31.93; p = 0.01). CONCLUSIONS: Age, WAZ, edema and complications at admission were predictors for both in-hospital and total SAM mortality, while mother's education contributed to the early post-discharge mortality. The identification of predictors for mortality is an important preliminary step for interventions aiming to reduce morbidity and mortality.

Treatment outcomes of severe acute malnutrition and predictors of recovery in under-five children treated within outpatient therapeutic programs in Ethiopia: a systematic review and meta-analysis.

BACKGROUND: Severe acute malnutrition affects around 17 million under-five children in the world, of which the highest burden is accounted by Sub-Saharan Africa where Ethiopia is found. Though there are few individual, inconsistent and inconclusive studies, there is no nationally representative study on treatment outcomes of SAM in outpatient therapeutic feeding programs of Ethiopia. This study aimed at estimating the pooled treatment outcomes and predictors of recovery rate among under- five children with SAM in Ethiopia. METHODS: Electronic databases (PubMed, Medline (EBSCOhost), EMBASE (Elsevier), CINAHL (EBSCOhost), web of science, Scopus, Science Direct and Food Science and Technology Abstracts (FSTA)), and grey literature sources (Google scholar, Mednar, World Cat and google) were used to retrieve articles. The random effect model was used to estimate the pooled treatment outcomes. Hazard ratios were used to determine the predictors of recovery rate. Cochran's Q, I2, and univariate Meta regression were done for heterogeneity. Begg's & Egger's tests were used for publication bias. RESULTS: Nineteen articles with a total number of 23,395 under-five children with SAM were used for this meta-analysis. The pooled recovery, death, defaulter and non-recovery rates were 70% (95% CI: 64, 76), 2% (95% CI: 1, 2), 10% (95%CI: 7, 12), 15% (95% CI: 10, 20), respectively. Diarrhea (HR = 0.8, 95% CI: 0.75, 0.94), no edema (HR = 0.41, 95% CI: 0.33, 0.50) and amoxicillin (HR = 1.81, 95% CI: 1.18, 2.44) were independent predictors of recovery rate of children with SAM in Ethiopia. Publication year was found to be the potential source of heterogeneity between included studies. CONCLUSION: The treatment outcomes of children with SAM from outpatient therapeutic feeding programs of Ethiopia are lower than the sphere guidelines, WHO and national recommendations. Diarrhea and no edema antagonized the recovery rate of children, while amoxicillin enhanced the recovery rate of children from SAM. Community health workers need to be trained. Especial attention should be given while treating children with diarrhea and severe wasting. Community mobilization is also recommended to improve community awareness about the therapeutic foods.

Myocardial and haemodynamic responses to two fluid regimens in African children with severe malnutrition and hypovolaemic shock (AFRIM study).

BACKGROUND: Fluid therapy in severely malnourished children is hypothesized to be deleterious owing to compromised cardiac function. We evaluated World Health Organization (WHO) fluid resuscitation guidelines for hypovolaemic shock using myocardial and haemodynamic function and safety endpoints. METHODS: A prospective observational study of two sequential fluid management strategies was conducted at two East African hospitals. Eligible participants were severely malnourished children, aged 6-60 months, with hypovolaemic shock secondary to gastroenteritis. Group 1 received up to two boluses of 15 ml/kg/h of Ringer's lactate (RL) prior to rehydration as per WHO guidelines. Group 2 received rehydration only (10 ml/kg/h of RL) up to a maximum of 5 h. Comprehensive clinical, haemodynamic and echocardiographic data were collected from admission to day 28. RESULTS: Twenty children were enrolled (11 in group 1 and 9 in group 2), including 15 children (75%) with kwashiorkor, 8 (40%) with elevated brain natriuretic peptide >300 pg/ml, and 9 (45%) with markedly elevated median systemic vascular resistance index (SVRI) >1600 dscm-5/m2 indicative of severe hypovolaemia. Echocardiographic evidence of fluid-responsiveness (FR) was heterogeneous in group 1, with both increased and decreased stroke volume and myocardial fractional shortening. In group 2, these variables were more homogenous and typical of FR. Median SVRI marginally decreased post fluid administration (both groups) but remained high at 24 h. Mortality at 48 h and to day 28, respectively, was 36% (4 deaths) and 81.8% (9 deaths) in group 1 and 44% (4 deaths) and 55.6% (5 deaths) in group 2. We observed no pulmonary oedema or congestive cardiac failure on or during admission; most deaths were unrelated to fluid interventions or echocardiographic findings of response to fluids. CONCLUSION: Baseline and cardiac response to fluid resuscitation do not indicate an effect of compromised cardiac function on response to fluid loading or that fluid overload is common in severely malnourished children with hypovolaemic shock. Endocrine response to shock and persistently high SVRI post fluid-therapy resuscitation may indicate a need for further research investigating enhanced fluid volumes to adequately correct volume deficit. The adverse outcomes are concerning, but appear to be unrelated to immediate fluid management.

Pulmonary rehabilitation after lung transplantation with severe complications: A case report.

This case study describes a 59-year-old male with a body mass index of 14.4 kg/m2 and a diagnosis of interstitial lung disease, pneumoconiosis, and severe pulmonary hypertension who received a bilateral lung transplant in a hospital in mainland China. Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) was initiated before the lung transplant; in addition, an emergency thoracotomy was performed three hours afterwards due to uncontrolled bleeding. VA-ECMO was weaned 34 hours later, but weaning from the ventilator failed multiple times due to bilateral pneumothorax, weak neuromuscular drive, and muscle strength. A full, personalized rehabilitation program was initiated with the help of a respiratory therapy team and the physician, drawing on the American Thoracic Society/European Respiratory Society Statement on Pulmonary Rehabilitation. This included nutrition support, draining air from the chest pleural cavity, aggressive bronchial-hygiene therapy, a weaning plan, breathing and physical exercises, and psychological support. Eighty-one days after the tracheotomy, the patient was successfully weaned, decannulated, and discharged. A careful, ongoing evaluation and a personalized program assisted with weaning this difficult patient.

Effect of a food supplementation and psychosocial stimulation trial for severely malnourished children on the level of maternal depressive symptoms in Bangladesh.

BACKGROUND: Maternal depression is associated with poor child development and growth in low-income countries. This paper evaluates the effect of a community-based trial providing psychosocial stimulation and food supplements to severely malnourished children on maternal depressive symptoms in Bangladesh. METHODS: Severely underweight (weight-for-age Z-score < -3) hospitalized children aged 6-24 months (n = 507), were randomly assigned to: psychosocial stimulation (PS), food supplementation (FS), PS+FS, clinic control (CC) and hospital control (CH) at discharge. PS included play sessions with children and parental counselling to mothers during fortnightly follow-up visit at community clinics, conducted by trained play leaders for 6 months. FS involved cereal-based supplements (150-300 kcal/day) for 3 months. All groups received medical care, micronutrient supplements and growth monitoring. We used Bayley scales, Home Observation for Measurement of Environment (HOME) inventory and a parenting questionnaire to assess child development, home stimulation and mothers' child-rearing practices, respectively. We assessed mothers' depressive symptoms using a modified version of Centre for Epidemiologic Studies Depression Scale at baseline and at 6 months post intervention. RESULTS: Maternal depressive symptoms were significantly lower in the CH group at baseline (P = 0.014). After 6 months of intervention there was no significant effect of intervention after adjusting for baseline scores and all possible confounders. Maternal depressive symptoms were higher among poorer (P = 0.06), older (P = 0.057) and less educated (P = 0.019) mothers, who were housewives (P = 0.053), and whose husbands had more unstable jobs (P = 0.058). At 6 months post intervention, children's cognitive (P = 0.045) and motor (P = 0.075) development, HOME (P = 0.012) and mother's parenting score (P = 0.057) were higher among mothers with lower depressive symptoms. CONCLUSION: The study did not show a significant effect of the intervention on the level of maternal depressive symptoms. Interventions with higher intensity and/or of longer duration focusing directly on maternal psychosocial functioning are probably needed to reduce maternal depressive symptoms.

Severe hypoglycemia with reduced liver volume as an indicator of end-stage malnutrition in patients with anorexia nervosa: a retrospective observational study.

BACKGROUND: Hypophosphatemia due to excessive carbohydrate administration is considered the primary pathogenesis of refeeding syndrome. However, its association with liver injury and hypoglycemia, often seen in severe malnutrition before re-nutrition, remains unclear. Autophagy reportedly occurs in the liver of patients with severe malnutrition. This study aimed to clarify the pathophysiology of liver injury and hypoglycemia by focusing on liver volume. METHODS: Forty-eight patients with anorexia nervosa with a body mass index (BMI) of < 13 kg/m2 were included (median BMI: 10.51 kg/m2 on admission). Liver volume was measured in 36 patients who underwent abdominal computed tomography (CT), and the "estimated liver weight/ideal body weight" was used as the liver volume index. Seventeen blood test items were analyzed during the first 60 days. RESULTS: Liver volume significantly decreased when abdominal CTs were conducted shortly before or after hypoglycemia compared to when the scans were performed during periods without hypoglycemia. Five patients with severe hypoglycemia on days 13-18 after admission had a very low nutritional intake; of them, four showed a marked decrease in liver volume. Severe hypoglycemia was accompanied by low serum triglycerides and liver dysfunction. Patients experiencing hypoglycemia of blood glucose levels < 55 mg/dL (< 3.05 mmol/L) (32 patients; median lowest BMI: 9.45 kg/m2) exhibited significantly poorer blood findings for most of the 17 items, except serum phosphorus and potassium, than did those not experiencing hypoglycemia (16 patients; median lowest BMI: 11.2 kg/m2). All patients with a poor prognosis belonged to the hypoglycemia group. Empirically, initiating re-nutrition at 500 kcal/day (20-25 kcal/kg/day), increasing to 700-800 kcal/day after a week, and then gradually escalating can reduce serious complications following severe hypoglycemia. CONCLUSIONS: Liver volume reduction accompanied by hypoglycemia, low serum triglyceride levels, and liver dysfunction occurs when the body's stored energy sources are depleted and external nutritional intake is inadequate, suggesting that the liver was consumed as a last resort to obtain energy essential for daily survival. This pathophysiology, distinct from refeeding syndrome, indicates the terminal stage of malnutrition and is a risk factor for complications and poor prognosis. In treatment, extremely low nutrient levels should be avoided.

This study aimed to clarify the pathophysiology of severe malnutrition in patients with anorexia nervosa by focusing on liver volume. The small size of the liver was almost always accompanied by hypoglycemia within a week. In several cases, extremely low nutritional intake, continued for approximately 2 weeks after admission, resulted in severe hypoglycemia and a marked decrease in liver volume. The 32 patients with hypoglycemia presented worse blood test items related to liver function, nutrition, and blood cell count compared to the 16 patients without such a condition. All cases with poor prognosis were in the hypoglycemia group. These findings suggest that severe hypoglycemia with decreased liver volume indicates the end stage of malnutrition. Liver volume reduction is considered a reflection of the liver's consumption of itself as a last resort for energy procurement for daily survival when the body's stored energy sources are depleted, and external nutritional intake is insufficient. When managing such patients, extremely low nutritional administration should be avoided.

Impact of Malnutrition on the Outcomes in Patients Admitted with Heart Failure.

Background: Heart failure, a major public health concern, significantly contributes to hospital admissions. This study evaluates the impact of malnutrition on both patient and hospital outcomes in heart failure admissions, with a specific focus on variations in outcomes based on the severity of malnutrition. Methods: Utilizing the National Inpatient Sample (NIS) database, this retrospective cohort study included adult patients admitted with a principal diagnosis of heart failure. Malnutrition was identified using the well-validated ICD 10 codes. We compared outcomes between patients with and without malnutrition, focusing on mortality, length of stay (LOS), hospital charges, cardiac arrest, and cardiogenic shock. Results: Out of 1,110,085 heart failure patients, 36,522 (3.29%) were malnourished. Malnourished patients exhibited significantly higher adjusted in-hospital mortality rates (aOR 3.32; 95% CI 3.03-3.64), longer LOS (mean increase of 4.67 days; p < 0.001), and higher hospital charges (mean increase of USD 77,416.9; p < 0.01). Increased rates of cardiac arrest (aOR 2.39; 95% CI 1.99-2.86; p < 0.001) and cardiogenic shock (aOR 3.74; 95% CI 3.40-4.12; p < 0.001) were also noted in malnourished patients. Severely malnourished patients faced worse outcomes compared to those with mild to moderate malnutrition. Conclusions: Heart failure patients with malnutrition experience higher mortality rates, longer hospital stays, increased hospitalization charges, and greater complication rates, including cardiac arrest and cardiogenic shock, compared to non-malnourished patients. Outcomes deteriorate with the increasing severity of malnutrition. Timely and individualized nutritional interventions may significantly improve outcomes for heart failure admissions.

Correlation between blood pressure and mortality in older critically ill patients: Insights from a large intensive care unit database.

OBJECTIVES: The study aimed to investigate the relationship between blood pressure (BP) levels and mortality among critically ill older adults in the intensive care unit (ICU), establish optimal BP target for this population, and assess the mediating effect of severe malnutrition on BP-related mortality. METHODS: Data were extracted from the Medical Information Mart for Intensive Care IV version 2.2 database, focusing on critically ill patients aged 80 years and older. The analysis included various BP parameters, such as systolic BP (SBP), diastolic BP (DBP), and mean arterial pressure (MAP). RESULTS: The study cohort comprised 14,660 critically ill patients, of whom 1558 (10.6 %) experienced ICU mortality and 2493 (17.0 %) experienced in-hospital mortality. Lower BP levels (SBP ≤ 112 mmHg; DBP ≤ 53 mmHg; MAP ≤65 mmHg), were associated with an increased risk of both ICU and in-hospital mortality. Notably, only reduced SBP levels were linked to a higher risk of 1-year mortality, with an adjusted hazard ratio 1.13 (95 % confidence interval 1.05 to 1.23). Additionally, severe malnutrition was identified as a mediator in the relationship between low BP levels and ICU mortality, with BP levels positively correlated with prognostic nutritional indexes. CONCLUSION: Among critically ill older adults, lower BP levels are significantly associated with higher risks of ICU and in-hospital mortality, while reduced SBP levels are linked to 1-year mortality. These findings emphasize the importance of assessing nutritional status in older ICU patients with low BP levels to potentially mitigate mortality risk.

Hepatic mitochondrial and peroxisomal alterations in acutely ill malnourished Malawian children: A postmortem cohort study.

Objectives: To describe and compare liver mitochondrial and peroxisomal histopathology by nutritional status in children who died following hospitalization for acute illness in Malawi. Methods: Liver tissue was collected using Minimally Invasive Tissue Sampling from eleven children under-five years old who died during hospitalization and were either non-wasted (n = 4), severely wasted (n = 4) or had edematous malnutrition (n = 3). Histology was assessed on hematoxylin and eosin stained slides. Mitochondrial and peroxisomal ultrastructural features were characterized using electron microscopy (EM) and immunofluorescence (IF). Results: Hepatic steatosis was present in 50 % of non-wasted and severely wasted children and all children with edematous malnutrition. Edematous malnutrition was associated with 56 % and 45 % fewer mitochondria than severe wasting (p < 0.001) and no wasting (p = 0.006), respectively, and abnormal mitochondrial morphology compared to severe wasting (p = 0.002) and no wasting (p = 0.035). Peroxisomal abundance was reduced in edematous malnutrition compared to severe wasting (p = 0.005), but did not differ from no-wasting. Conclusion: Edematous malnutrition is associated with reduced abundance and altered morphology of hepatic mitochondria and peroxisomes. Interventions targeting improvements in hepatic metabolic function may be beneficial in improving metabolism and reducing mortality in children with severe malnutrition, particularly in those with nutritional edema.

Micronutrient status in children aged 6-59 months with severe wasting and/or nutritional edema: implications for nutritional rehabilitation formulations.

Undernutrition remains a global struggle and is associated with almost 45% of deaths in children younger than 5 years. Despite advances in management of severe wasting (though less so for nutritional edema), full and sustained recovery remains elusive. Children with severe wasting and/or nutritional edema (also commonly referred to as severe acute malnutrition and part of the umbrella term "severe malnutrition") continue to have a high mortality rate. This suggests a likely multifactorial etiology that may include micronutrient deficiency. Micronutrients are currently provided in therapeutic foods at levels based on expert opinion, with few supportive studies of high quality having been conducted. This narrative review looks at the knowledge base on micronutrient deficiencies in children aged 6-59 months who have severe wasting and/or nutritional edema, in addition to highlighting areas where further research is warranted (See "Future Directions" section).

Inflammation: the driver of poor outcomes among children with severe acute malnutrition?

Severe acute malnutrition (SAM) is the most life-threatening form of undernutrition and underlies at least 10% of all deaths among children younger than 5 years in low-income countries. SAM is a complex, multisystem disease, with physiological perturbations observed in conjunction with the loss of lean mass, including structural and functional changes in many organ systems. Despite the high mortality burden, predominantly due to infections, the underlying pathogenic pathways remain poorly understood. Intestinal and systemic inflammation is heightened in children with SAM. Chronic inflammation and its consequent immunomodulation may explain the increased morbidity and mortality from infections in children with SAM, both during hospitalization and in the longer term after discharge. Recognition of the role of inflammation in SAM is critical in considering new therapeutic targets in this disease, which has not seen a transformational approach to treatment for several decades. This review highlights the central role of inflammation in the wide-ranging pathophysiology of SAM, as well as identifying potential interventions that have biological plausibility based on evidence from other inflammatory syndromes.

Incidence of tuberculosis and its predictors among under-five children with severe acute malnutrition in North Shoa, Amhara region, Ethiopia: a retrospective follow-up study.

Introduction: Although tuberculosis (TB) is one of the significant public health challenges in severely malnourished children throughout the globe, it is a severe issue for countries such as Ethiopia, with significant resource limitations. Few studies have examined the incidence of tuberculosis and its predictors among children under five years of age with severe acute malnutrition in developing countries, and there is a paucity of data. This study aimed to estimate the incidence of tuberculosis and its predictors among under-five children with severe acute malnutrition (SAM) in North Shoa, Amhara region, Ethiopia. Methods: An institution-based retrospective follow-up study was conducted between January 20, 2017, and June 20, 2019. The sample size was calculated using STATA, which yields a total of 345 charts that were selected with systematic random sampling. Data entry was performed using Epi-data version 4.2 and analyzed with STATA 14. Kaplan-Meier survival curves were computed. Cox proportional hazard models were fitted to detect the determinants of tuberculosis. The hazard ratio with a 95% confidence interval was subsequently calculated. Variables with p-values < 0.05 were considered statistically significant. Results: The incidence rate of tuberculosis among children under five years of age with SAM was 4.6 per 100 person-day observations (95% CI: 3.29, 8.9). Predictors of TB were a history of contact with known TB cases [AHR: 1.4 (95% CI: 1.00, 2.8], HIV/AIDS [AHR: 3.71 (95% CI: 2.10, 8.71)], baseline pneumonia [AHR: 2.10 (1.76,12)], not supplying zinc at baseline [AHR: 3.1 (1.91, 4.70)], and failed appetite taste at the diagnosis of SAM [AHR: 2.4 (1.35, 3.82)]. Conclusions: In this study, the incidence rate of TB was high. Not supplying zinc at baseline, failed appetite taste at the diagnosis of SAM, history of contact with known TB cases, and baseline pneumonia were significant predictors of TB. Prioritizing regular TB screenings, nutritional support, and zinc supplementation for under-five children with SAM should be implemented to reduce the risk of TB.

Death in severely malnourished hospitalized children presenting with diarrhea and vomiting.

INTRODUCTION: There is lack of data on outcomes of severely malnourished children who are hospitalized with concomitant diarrhea and vomiting. We sought to evaluate outcomes of such children. METHODOLOGY: In this retrospective chart review, we used electronic databases to evaluate children aged 0-59 months and admitted to the Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh, with diarrhea and severe malnutrition between April 2011 and August 2012. Outcomes of children with and without vomiting were compared. The primary outcome was death. A probability of ≤ 0.05 was considered statistically significant. RESULTS: Out of 306 enrolled children, 51 (17%) had vomiting and 255 (83%) did not have vomiting. A total of 31 (10%) children died, 12 (24%) of them had vomiting and 19 (8%) did not have vomiting. Death was significantly higher in severely malnourished diarrheal children with vomiting (12/51 (24%)) compared to those without vomiting (19/255 (8%)) (Relative risk [RR] 2.73, 95% confidence interval [CI] 1.61-4.64; p < 0.001). We used Log linear bi-nominal regression after adjusting for potential confounders such as metabolic acidosis and hypoglycemia, and found that vomiting was significantly associated with deaths in severely malnourished diarrheal children (RR 1∙89, 95% CI 1.01-1.33; p = 0.05). CONCLUSIONS: Our analysis showed that children with diarrhea and severe malnutrition who had vomiting during hospitalization were at a higher risk of death compared to those without vomiting. The results underscore the importance of prompt identification and management of vomiting to reduce deaths in such children.

Prevalence and correlates of severe under-5 child anthropometric failure measured by the composite index of severe anthropometric failure in Bangladesh.

Background: Although Bangladesh has made noticeable progress in reducing the prevalence of stunting, wasting, and being underweight among under-5 children, it has not been very successful in reducing overall severe anthropometric failure (SAF) among them. Therefore, the study aims to identify the prevalence and risk factors of SAF measured by the Composite Index of Severe Anthropometric Failure (CISAF) among under-5 children in Bangladesh. Methods: Data was drawn from a cross-sectional Bangladesh Demographic Health Survey (BDHS) conducted in 2017-2018. A bivariate analysis (Chi-square test) and logistic regression analysis were used to estimate the unadjusted, and age and sex-adjusted prevalence of SAF. Odds ratio (OR) and confidence interval (CI) were assessed using logistic regression analysis to identify the various risk factor of SAF. Results: The overall adjusted prevalence of under-5 child SAF was 11.3% (95% CI: 10.6-12.0) and it was highly prevalent among children of uneducated mothers (adjusted, 22%, 95% CI: 17.3-26.8). The key factors associated with SAF were children in the age group 24-35 months (OR: 2.43, 95% CI: 1.83-3.23), children born with low birth weight (OR: 3.14, 95% CI: 2.24-4.97), children of underweight mothers (OR: 1.82, 95% CI: 1.44-2.29), children of parents with no formal education (OR: 2.28, 95% CI: 1.56-3.31) and children from lower socio-economic status (OR: 2.25, 95% CI: 1.55-3.26). Conclusion: Prioritizing and ensuring context-specific interventions addressing individual, community, public policy, and environment level risk factors from policy level to implementation to reduce structural and intermediary determinants of under-5 SAF.