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.

Childhood growth during recovery from acute illness in Africa and South Asia: a secondary analysis of the childhood acute illness and nutrition (CHAIN) prospective cohort.

Background: Growth faltering is well-recognized during acute childhood illness and growth acceleration during convalescence, with or without nutritional therapy, may occur. However, there are limited recent data on growth after hospitalization in low- and middle-income countries. Methods: We evaluated growth following hospitalization among children aged 2-23 months in sub-Saharan Africa and South Asia. Between November 2016 and January 2019, children were recruited at hospital admission and classified as: not-wasted (NW), moderately-wasted (MW), severely-wasted (SW), or having nutritional oedema (NO). We describe earlier (discharge to 45-days) and later (45- to 180-days) changes in length-for-age [LAZ], weight-for-age [WAZ], mid-upper arm circumference [MUACZ], weight-for-length [WLZ] z-scores, and clinical, nutritional, and socioeconomic correlates. Findings: We included 2472 children who survived to 180-days post-discharge: NW, 960 (39%); MW, 572 (23%); SW, 682 (28%); and NO, 258 (10%). During 180-days, LAZ decreased in NW (-0.27 [-0.36, -0.19]) and MW (-0.23 [-0.34, -0.11]). However, all groups increased WAZ (NW, 0.21 [95% CI: 0.11, 0.32]; MW, 0.57 [0.44, 0.71]; SW, 1.0 [0.88, 1.1] and NO, 1.3 [1.1, 1.5]) with greatest gains in the first 45-days. Of children underweight (<-2 WAZ) at discharge, 66% remained underweight at 180-days. Lower WAZ post-discharge was associated with age-inappropriate nutrition, adverse caregiver characteristics, small size at birth, severe or moderate anaemia, and chronic conditions, while lower LAZ was additionally associated with household-level exposures but not with chronic medical conditions. Interpretation: Underweight and poor linear growth mostly persisted after an acute illness. Beyond short-term nutritional supplementation, improving linear growth post-discharge may require broader individual and family support. Funding: Bill & Melinda Gates FoundationOPP1131320; National Institute for Health ResearchNIHR201813.

Determinants of Undernutrition among Children Admitted to a Pediatric Hospital in Port Sudan, Sudan.

Severe acute undernutrition (SAU) is still a crucial global health issue in the 0-59 months population, increasing the risk of mortality as well as of long-term consequences. In Sudan, 3.3 million children suffered from acute malnutrition between 2018 and 2019. This study was planned to evaluate, in the area of Port Sudan, the prevalence of acute undernutrition after the COVID-19 pandemic and to identify the most important factors favoring the development of acute undernutrition. The available clinical records of all the under-five children (n = 1012) admitted to the Port Sudan Emergency Pediatric Hospital from 1 February 2021 to 31 January 2022 were analyzed. The presence of wasting and kwashiorkor was assessed and children were categorized according to age, gender, place of residence, main reason for hospitalization, and underlying comorbidities. Acute undernutrition was evidenced in 493 (48.7%) children. Of them, only 16 (3.2%) were diagnosed with kwashiorkor. Children with SAU had a higher prevalence of acute gastroenteritis (p < 0.05) and parasitosis (p < 0.05). Infants aged 0-6 months were those with the lowest risk of undernutrition, whereas those aged 7-12 months were those with the greater risk. In these patients, multivariate analysis revealed that SAU and MAU were 2.5 times (OR 2.51; 95% CI, 1.79-3.55) and 5.5 times (OR 5.56; 95% CI, 2.59-18.7) higher. This study shows that the area of Port Sudan is still suffering from an alarming prevalence of severe wasting and the risk of developing acute undernutrition seems strictly related to the introduction of complementary feeding and tends to reduce with increasing age. Measures already in place to prevent acute malnutrition should be reinforced with improvement of mother education on child feeding.

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).

Vegan Diet in Dermatology: A Review.

Diet is known to play a role in the development of skin disorders. While a vegan diet is frequently described as a risk factor for skin disease secondary to nutritional deficiency, this risk may be overestimated. This review aims to debunk myths and provide information on skin disorders and inflammatory skin conditions that have associations with specific nutritional deficiencies in the context of a vegan diet. A literature search was performed for each nutrient and inflammatory skin disease using the PubMed/MEDLINE database and public health website pages concerning a vegan diet. The literature has individual cases reporting skin disease due to deficiencies in vitamin B2 and vitamin A in patients following a vegan diet. The recommended daily amounts of nutrients and vitamins can be fulfilled on a vegan diet. Vegan diets also avoid food groups such as dairy and other animal-based products, which holds benefits in inflammatory skin diseases including acne, psoriasis, hidradenitis suppurativa, and atopic dermatitis. Overall, the risk of skin disease secondary to nutritional deficiency in patients following a vegan diet is very low and likely over-emphasized. A well-balanced and conscientiously planned vegan diet can adequately provide the necessary amounts of proteins, vitamins, and minerals to support skin health.

Coma With Hyperammonemia in a Patient With Kwashiorkor.

We describe a case of coma-related hyperammonemia in a woman presenting with severe edematous malnutrition (Kwashiorkor-like), without underlying hepatic disease. Our main hypothesis is that the patient developed a functional urea cycle disorder, due to the inability to synthesize N-acetylglutamate which is the activator of the first enzymes (carbamoyl phosphate synthetase) of urea cycle, in a context of severe deficiency of essential amino acids and of acetyl-CoA. Severe hyperammonemia is a medical emergency exposing to the risk of cerebral edema. Urgent treatment should interrupt protein intake, stimulate protein anabolism, and remove ammonia from the blood using renal replacement therapy and ammonia scavengers. Hyperammonemia should be searched in case of unexplained coma, even among patients without hepatic disorder, in particular among young patients. Hyperammonemia should also be searched among patients with severe protein-calorie malnutrition.

Community-based management of acute malnutrition for infants under 6 months of age is safe and effective: analysis of operational data.

OBJECTIVE: To assess the effectiveness of outpatient management with ready-to-use and supplementary foods for infants under 6 months (u6m) of age who were unable to be treated as inpatients due to social and economic barriers. DESIGN: Review of operational acute malnutrition treatment records. SETTING: Twenty-one outpatient therapeutic feeding clinics in rural Malawi. PARTICIPANTS: Infants u6m with acute malnutrition treated as outpatients because of barriers to inpatient treatment. The comparison group consisted of acutely malnourished children 6-9 months of age who were being treated at the same time in the same location in the context of two different randomised clinical trials. RESULTS: A total of 323 infants u6m were treated for acute malnutrition (130 severe and 193 moderate). A total of 357 infants 6-9 months old with acute malnutrition (seventy-four severe and 283 moderate) were included as contemporaneous controls. Among infants u6m with severe acute malnutrition, 98 (75·4 %) achieved nutritional recovery; in comparison, 56 (75·7 %) of those with severe acute malnutrition 6-9 months old recovered. Among infants u6m with moderate acute malnutrition, 157 (81·3 %) recovered; in comparison, 241 (85·2 %) of those aged 6-9 months recovered. CONCLUSIONS: In a rural Malawian population of infants u6m who had generally already stopped exclusive breast-feeding and were now acutely malnourished, treatment with therapeutic or supplementary foods under the community management of acute malnutrition model was safe and effective. In settings where social and financial factors make hospital admission challenging, consideration should be given to lowering the recommended age of ready-to-use therapeutic and supplementary foods to infants u6m.

Protein malnutrition in BALB/C mice: A model mimicking clinical scenario of marasmic-kwashiorkor malnutrition.

Protein malnutrition continues to be a major global issue. A stable animal model to address protein malnutrition and its effect on various disease conditions is necessary. In the present study, we have formulated and standardized a low protein diet (LPD) to develop a protein malnutrition model using Balb/C mice. Healthy male Balb/C mice were weaned and exposed to LPD combinations while another group exposed to normal diet (18% protein). Animal survival, change in body weight, body mass index (BMI), biochemical parameters, antioxidant status, and liver histopathology were used to confirm the development of malnourished mice model (marasmic-kwashiorkor). Mice receiving 10% protein diet showed moderate weight gain, higher BMI, and no mortality compared to the 6% protein group. The former group showed remarkable differences in BMI, biochemical and antioxidant parameters. Further, histopathological changes against the normal group at weeks 20 and 30 confirmed the development of protein malnutrition in mice on 10% protein diet. The study confirms the development of a stable, economical, reproducible, and clinically relevant protein malnutrition model using the formulated 10% protein diet. Further, the model can be used for short and long-term studies to investigate the pathophysiology of malnutrition in any disease/condition.

Prognostic Significance of Serum Biochemistry Profile in Children With Severe Acute Malnutrition.

Background Malnutrition is a condition caused by defective nutrition in which either deficiency or excess of energy, protein, or micronutrients cause any measurable adverse effects on tissues/body form (body shape, size, composition), function, and clinical outcome. Children with a weight-for-height below -3 standard deviations (SD) of the mean based on the WHO standards have a high risk of death exceeding nine-fold that of children with a weight-for-height above 1 SD. In severe acute malnutrition (SAM) liver function tests, renal function tests, and serum electrolytes are deranged but their correlation with the prognosis is not well defined. So, there was a need for a study to know the prognostic significance. For this purpose, the current study was conducted in the pediatric ward of Uttar Pradesh University of Medical Sciences (UPUMS), Saifai, UP, India. Method This is an observational cross-sectional study conducted in the Department of Pediatrics, UPUMS (Saifai, UP, India) from January 2018 to July 2019 after approval from the institutional ethical committee. We enrolled 100 children with SAM who fulfilled the inclusion criterion after obtaining proper and well-informed consent. Result We studied children aged six to 59 months. The mean age of admitted patients in our study was nearly 24 months (24.18 months). The median age that was most common at the time of admission is nearly 1 year (13 months). In our study relation of serum sodium and serum potassium with the survival of SAM was found statistically significant. Conclusion Severe acute malnutrition is both a medical and social disorder. The risk of mortality increases as the severity of malnutrition increases. High-risk cases can be identified and can be treated aggressively and on a priority basis. Serum electrolyte disturbances in SAM are one of the most important predictors of the severity.

A multi-country, prospective cohort study to evaluate the economic implications of relapse among children recovered from severe acute malnutrition: a study protocol.

BACKGROUND: Community-based management of acute malnutrition (CMAM) is an effective intervention at recovering children from severe acute malnutrition (SAM) and preventing mortality. However, there is growing evidence that for many children recovery is not sustained post-discharge. This study will assess the economic implications of relapse by calculating the average cost of treating a case of SAM that relapses after initial CMAM treatment compared to the cost of a case that remains recovered for 6 months post-discharge. METHODS: This protocol outlines the methods for a cost-efficiency analysis to assess cost per episode of treatment for acute malnutrition for children enrolled in CMAM programs for initial SAM treatment in Mali, Somalia and South Sudan. Cost data will be collected and analyzed on a monthly basis for each CMAM service component (outpatient treatment program for SAM, supplementary feeding program for moderate acute malnutrition, and inpatient stabilization care for SAM with medical complications). Financial data will be extracted from expenditure records from institutional accounting systems where possible. Where these are not present, cost data will be collected via interview and review of financial documents. Staff time allocation interviews will be conducted. This data will be applied to quantify personnel costs, to apportion costs that are shared between programs and to exclude staff time spent on research activities. DISCUSSION: This study will provide the first estimates to address the limited evidence on the economic implications of SAM relapse in CMAM programs. Data from this economic analysis will help raise awareness and provide actionable data for the global nutrition community to address the financial burden of relapse. Estimating the cost of relapse in three countries representing different geographic and operational contexts will help in generalizing these results. TRIAL REGISTRATION: Registration # IORG0007116, Date of registration: 06/09/2020. This study is not registered as a clinical trial as it is observational research and does not include an intervention. The study has received the required ethical approvals as outlined in the declarations.

Subclinical Kwashiorkor in Adults: A New Age Paradigm.

Childhood protein-energy undernutrition (PEU) is a well-recognized problem and therefore a lot of work has been done to identify and manage paediatric PEU. Though there have been several reports of low protein consumption in adults from developing countries, PEU and its subtle forms (subclinical PEU) are not yet recognized as adult disorders. Physicians and public perception do not favour easy recognition and action. In this review, the authors provide a scoping review of the existing literature on this entity providing insights into its recognition, pathogenesis and management. Adult subclinical PEU is an enormous under-recognized challenge that can have detrimental consequences if not recognized and corrected in time. PEU has grave health and economic impact on the patient and society. Therefore, it is important to recognize subclinical PEU and prevent its progression to full-blown form.

A multi-country, prospective cohort study to measure rate and risk of relapse among children recovered from severe acute malnutrition in Mali, Somalia, and South Sudan: a study protocol.

BACKGROUND: The Community-Based Management of Acute Malnutrition (CMAM) model transformed the treatment of severe acute malnutrition (SAM) by shifting treatment from inpatient facilities to the community. Evidence shows that while CMAM programs are effective in the initial recovery from SAM, recovery is not sustained for some children requiring them to receive treatment repeatedly. This indicates a potential gap in the model, yet little evidence is available on the incidence of relapse, the determinants of the phenomena, or its financial implications on program delivery. METHODS: This study is a multi-country prospective cohort study following "post-SAM" children (defined as children following anthropometric recovery from SAM through treatment in CMAM) and matched community controls (defined as children not previously experiencing acute malnutrition (AM)) monthly for six months. The aim is to assess the burden and determinants of relapse to SAM. This study design enables the quantification of relapse among post-SAM children, but also to determine the relative risk for, and excess burden of, AM between post-SAM children and their matched community controls. Individual -, household-, and community-level information will be analyzed to identify potential risk-factors for relapse, with a focus on associations between water, sanitation, and hygiene (WASH) related exposures, and post-discharge outcomes. The study combines a microbiological assessment of post-SAM children's drinking water, food, stool via rectal swabs, dried blood spots (DBS), and assess for indicators of enteric pathogens and immune function, to explore different exposures and potential associations with treatment and post-treatment outcomes. DISCUSSION: This study is the first of its kind to systematically track children after recovery from SAM in CMAM programs using uniform methods across multiple countries. The design allows the use of results to: 1) facilitate understandings of the burden of relapse; 2) identify risk factors for relapse and 3) elucidate financial costs associated with relapse in CMAM programs. This protocol's publication aims to support similar studies and evaluations of CMAM programs and provides opportunities for comparability of an evidence-based set of indicators for relapse to SAM.

Risk of Chronic Disease after an Episode of Marasmus, Kwashiorkor or Mixed-Type Severe Acute Malnutrition in the Democratic Republic of Congo: The Lwiro Follow-Up Study.

Background: Long-term impact of different forms of severe acute malnutrition (SAM) in childhood on the emergence of noncommunicable diseases (NCDs) is poorly known. Aim: To explore the association between subtypes of SAM during childhood, NCDs, and cardiovascular risk factors (CVRFs) in young adults 11 to 30 years after post-SAM nutritional rehabilitation. Methods: In this follow-up study, we investigated 524 adults (mean age 22 years) treated for SAM during childhood in eastern Democratic Republic of the Congo (DRC) between 1988 and 2007. Among them, 142 had a history of marasmus, 175 of kwashiorkor, and 207 had mixed-form SAM. These participants were compared to 407 aged- and sex-matched control adults living in the same community without a history of SAM. Our outcomes of interest were cardiometabolic risk markers for NCDs. Logistic and linear regressions models were sued to estimate the association between subtype of SAM in childhood and risk of NCDs. Results: Compared to unexposed, former mixed-type SAM participants had a higher adjusted ORs of metabolic syndrome [2.68 (1.18; 8.07)], central obesity [1.89 (1.11; 3.21)] and low HDL-C (High-density lipoprotein cholesterol) [1.52 (1.08; 2.62)]. However, there was no difference between groups in terms of diabetes, high blood pressure, elevated LDL-C (low-density lipoprotein cholesterol) and hyper TG (hypertriglyceridemia) and overweightness. Former mixed-type SAM participants had higher mean fasting glucose [3.38 mg/dL (0.92; 7.7)], reduced muscle strength [−3.47 kg (−5.82; −1.11)] and smaller hip circumference [−2.27 cm (−4.24; −0.31)] compared to non-exposed. Regardless of subtypes, SAM-exposed participants had higher HbA1c than unexposed (p < 0.001). Those with a history of kwashiorkor had cardiometabolic and nutritional parameters almost superimposable to those of unexposed. Conclusion: The association between childhood SAM, prevalence of NCDs and their CVRFs in adulthood varies according to SAM subtypes, those with mixed form being most at risk. Multicenter studies on larger cohorts of older participants are needed to elucidate the impact of SAM subtypes on NCDs risk.

Refeeding Syndrome Developed in a Patient With Kwashiorkor Can Mimic Findings of Mitochondrial Disorder.

Kwashiorkor is a serious nutritional disease. The 7-month-old male patient presented with severe metabolic acidosis and elevated liver enzymes. His condition was similar to fatty acid oxidation defect. He was taken to the hospital on the previous day with complaints of poor sucking and difficulty breathing. Treatment of upper respiratory tract infection was provided and then he returned to his home. He was cyanotic in bed after 12 hours. The patient, who was taken to the hospital unconscious and not fed for 12 hours, was not given any food orally in the first health center. Until laboratory tests are done, only iv electrolyte and a fluid containing dextrose were given. When the laboratory results were found to be significantly pathological, he was urgently referred to our hospital 4 hours after the admission. The content of the iv treatment applied at the time of referral was not clearly written. Low electrolytes, uric acid, liver enzymes, urea and creatinine elevation were detected at an outer center. Ketosis, lactic acidosis and dibasic aciduria were detected in urine organic acid analysis. He was diagnosed with Kwashiorkor and refeeding syndrome according to the clinical and laboratory findings. His complaints improved with appropriate treatment.

Case report: Cystic fibrosis with kwashiorkor: A rare presentation in the era of universal newborn screening.

Background: Universal newborn screening changed the way medical providers think about the presentation of cystic fibrosis (CF). Before implementation of universal screening, it was common for children with CF to present with failure to thrive, nutritional deficiencies, and recurrent infections. Now, nearly all cases of CF are diagnosed by newborn screening shortly after birth before significant symptoms develop. Therefore, providers often do not consider this illness in the setting of a normal newborn screen. Newborn screening significantly decreases the risk of complications in early childhood, yet definitive testing should be pursued if a patient with negative newborn screening presents with symptoms consistent with CF, including severe failure to thrive, metabolic alkalosis due to significant salt losses, or recurrent respiratory infections. Case presentation: We present a case of a 6-month-old infant male with kwashiorkor, severe edema, multiple vitamin deficiencies, hematemesis secondary to coagulopathy, and diffuse erythematous rash, all secondary to severe pancreatic insufficiency. His first newborn screen had an immunoreactive trypsinogen (IRT) value below the state cut-off value, so additional testing was not performed, and his growth trajectory appeared reassuring. He was ultimately diagnosed with CF by genetic testing and confirmatory sweat chloride testing, in the setting of his parents being known CF carriers and his severe presentation being clinically consistent with CF. Acutely, management with supplemental albumin, furosemide, potassium, and vitamin K was initiated to correct the presenting hypoalbuminemia, edema, and coagulopathy. Later, pancreatic enzyme supplementation and additional vitamins and minerals were added to manage ongoing deficiencies from pancreatic insufficiency. With appropriate treatment, his vitamin deficiencies and edema resolved, and his growth improved. Conclusion: Due to universal newborn screening, symptomatic presentation of CF is rare and presentation with kwashiorkor is extremely rare in resource-rich communities. The diagnosis of CF was delayed in our patient because of a normal newborn screen and falsely reassuring growth, which after diagnosis was determined to be secondary to severe edematous malnutrition. This case highlights that newborn screening is a useful but imperfect tool. Clinicians should continue to have suspicion for CF in the right clinical context, even in the setting of normal newborn screen results.

Educational Case: Understanding Kwashiorkor and Marasmus: Disease Mechanisms and Pathologic Consequences.

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, seehttp://journals.sagepub.com/doi/10.1177/2374289517715040.1.

Kwashiorkor on the south shore.

Kwashiorkor syndrome is a form of severe protein-energy malnutrition characterized by protein deficiency and bilateral extremity swelling. Worldwide, most affected regions include Southeast Asia, South Africa and Central America; it is rare in developed countries such as the USA. We report a case of profound kwashiorkor in a 38-year-old male with an underlying psychiatric disorder and restricted diet who presented with extensive abdominal distention and systemic findings indicative of protein malnutrition.