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Background: Poor nutrition status is common among hospitalized children and children in low-income countries and may be associated with increased susceptibility to edema and infections. We hypothesized that poor nutrition status, established with a suboptimal composition of parenteral nutrition (PN), predisposes to endotoxemia-induced edema, oxidative stress, and dysregulated immune responses., Methods: Using a 2 × 2 factorial design, 3-day-old piglets (n = 40) were given either optimal or suboptimal composition of PN for 7 days and then infused with either saline or lipopolysaccharide (LPS) for 9 hours to induce an acute-phase reaction. Abdominal tissue edema and blood markers of immunity, inflammation, and oxidative stress were assessed., Results: Piglets receiving suboptimal nutrition showed signs of malnutrition with restricted growth, signs of inflammation (elevated C-reactive protein [CRP], interleukin-6, and serum amyloid A levels), oxidative stress (lower erythrocyte glutathione/hemoglobin and α-tocopherol/cholesterol ratios), and liver dysfunction (increased liver weight and blood bilirubin levels). Perirenal edema was more excessive in malnourished LPS-infused animals, relative to healthy LPS-infused control animals (P < .01). Malnutrition reduced the inflammatory response to LPS (lower CRP, tumor necrosis factor-α, haptoglobin, and neutrophil to lymphocyte ratio) but did not influence LPS-induced oxidative stress markers., Conclusions: We conclude that endotoxemia and malnutrition in combination lead to acute-phase hyporesponsiveness and perirenal edema in piglets. This finding may have implications for pediatric patients that suffer from malnutrition, as their response to bacterial infections may differ substantially from patients of normal nutrition status., (© 2019 American Society for Parenteral and Enteral Nutrition.)

Background: The WHO recommended criteria for diagnosis of sever acute malnutrition (SAM) are weight-for-height/length Z-score (WHZ) of <- 3Z of the WHO 2006 standards, a mid-upper-arm circumference (MUAC) of < 115 mm, nutritional oedema or any combination of these parameters. A move to eliminate WHZ as a diagnostic criterion has been made on the assertion that children with a low WHZ are healthy, that MUAC is a "superior" prognostic indicator of mortality and that adding WHZ to the assessment does not improve the prediction of death. Our objective was to examine the literature comparing the risk of death of SAM children admitted by WHZ or MUAC criteria., Methods: We conducted a systematic search for reports which examined the relationship of WHZ and MUAC to mortality for children less than 60 months. The WHZ, MUAC, outcome and programmatic variables were abstracted from the reports and examined. Individual study's case fatality rates were compared by chi-squared analysis and random effects meta-analyses for combined data., Results: Twenty-one datasets were reviewed. All the patient studies had an ascertainment bias. Most were inadequate because they had insufficient deaths, used obsolete standards, combined oedematous and non-oedematous subjects, did not report the proportion of children with both deficits or the deaths occurred remotely after anthropometry. The meta-analyses showed that the mortality risks for children who have SAM by MUAC < 115 mm only and those with SAM by WHZ < -3Z only are not different., Conclusions: As the diagnostic criteria identify different children, this analysis does not support the abandonment of WHZ as an important independent diagnostic criterion for the diagnosis of SAM. Failure to identify such children will result in their being denied treatment and unnecessary deaths from SAM.

Background: Severe acute malnutrition (SAM) is diagnosed when the weight-for-height Z-score (WHZ) is <-3Z of the WHO 2006 standards, or a mid-upper-arm circumference (MUAC) of < 115 mm or there is nutritional oedema. Although there has been a move to eliminate WHZ as a diagnostic criterion we have shown that children with a low WHZ have at least as high a mortality risk as those with a low MUAC. Here we take the estimated case fatality rates and published case-loads to estimate the proportion of total SAM related deaths occurring in children that would be excluded from treatment with a MUAC-only policy., Methods: The effect of varying case-load and mortality rates on the proportion of all deaths that would occur in admitted children was examined. We used the same calculations to estimate the proportion of all SAM-related deaths that would be excluded with a MUAC-only policy in 48 countries with very different relative case loads for SAM by only MUAC, only WHZ and children with both deficits. The case fatality rates (CFR) are taken from simulations, empirical data and the literature., Results: The relative number of cases of SAM by MUAC alone, WHZ alone and those with both criteria have a dominant effect on the proportion of all SAM-related deaths that would occur in children excluded from treatment by a MUAC-only program. Many countries, particularly in the Sahel, West Africa and South East Asia would fail to identify the majority of SAM-related deaths if a MUAC only program were to be implemented. Globally, the estimated minimum number of deaths that would occur among children excluded from treatment in our analyses is 300,000 annually., Conclusions: The number, proportion or attributable fraction of children excluded from treatment with any change of current policy are the correct indicators to guide policy change. CRFs alone should not be used to guide policy in choosing whether or not to drop WHZ as a diagnostic for SAM. All the criteria for diagnosis of malnutrition need to be retained. It is critical that methods are found to identify those children with a low WHZ, but not a low MUAC, in the community so that they will not remain undetected.

Background: According to WHO childhood severe acute malnutrition (SAM) is diagnosed when the weight-for-height Z-score (WHZ) is <-3Z of the WHO 2006 standards, the mid-upper-arm circumference (MUAC) is < 115 mm, there is nutritional oedema or any combination of these parameters. Recently there has been a move to eliminate WHZ as a diagnostic criterion on the assertion that children meeting the WHZ criterion are healthy, that MUAC is universally a superior prognostic indicator of mortality and that adding WHZ to the assessment does not improve the prediction; these assertions have lead to a controversy concerning the role of WHZ in the diagnosis of SAM., Methods: We examined the mortality experience of 76,887 6-60 month old severely malnourished children admitted for treatment to in-patient, out-patient or supplementary feeding facilities in 18 African countries, of whom 3588 died. They were divided into 7 different diagnostic categories for analysis of mortality rates by comparison of case fatality rates, relative risk of death and meta-analysis of the difference between children admitted using MUAC and WHZ criteria., Results: The mortality rate was higher in those children fulfilling the WHO 2006 WHZ criterion than the MUAC criterion. This was the case for younger as well as older children and in all regions except for marasmic children in East Africa. Those fulfilling both criteria had a higher mortality. Nutritional oedema increased the risk of death. Having oedema and a low WHZ dramatically increased the mortality rate whereas addition of the MUAC criterion to either oedema-alone or oedema plus a low WHZ did not further increase the mortality rate. The data were subject to extreme confounding giving Simpson's paradox, which reversed the apparent mortality rates when children fulfilling both WHZ and MUAC criteria were included in the estimation of the risk of death of those fulfilling either the WHZ or MUAC criteria alone., Conclusions: Children with a low WHZ, but a MUAC above the SAM cut-off point are at high risk of death. Simpson's paradox due to confounding from oedema and mathematical coupling may make previous statistical analyses which failed to distinguish the diagnostic groups an unreliable guide to policy. WHZ needs to be retained as an independent criterion for diagnosis of SAM and methods found to identify those children with a low WHZ, but not a low MUAC, in the community.

The various types of oedema in man are considered in relation to Starling's hypothesis of fluid movement from capillaries, with the main emphasis on nutritional oedema and the nephrotic syndrome in children. It is concluded that each condition has sufficient anomalous findings to render Starling's hypothesis untenable. The finding that the endothelial glycocalyx is key to control of fluid movement from and into the capillaries calls for complete revision of our understanding of oedema formation. The factors so far known to affect the function of the glycocalyx are reviewed. As these depend upon sulphated proteoglycans and other glycosaminoglycans, the argument is advanced that the same abnormalities will extend to the interstitial space and that kwashiorkor is fundamentally related to a defect in sulphur metabolism which can explain all the clinical features of the condition, including the formation of oedema.

Background: Poor nutrition status is common among hospitalized children and children in low-income countries and may be associated with increased susceptibility to edema and infections. We hypothesized that poor nutrition status, established with a suboptimal composition of parenteral nutrition (PN), predisposes to endotoxemia-induced edema, oxidative stress, and dysregulated immune responses.Methods: Using a 2 × 2 factorial design, 3-day-old piglets (n = 40) were given either optimal or suboptimal composition of PN for 7 days and then infused with either saline or lipopolysaccharide (LPS) for 9 hours to induce an acute-phase reaction. Abdominal tissue edema and blood markers of immunity, inflammation, and oxidative stress were assessed.Results: Piglets receiving suboptimal nutrition showed signs of malnutrition with restricted growth, signs of inflammation (elevated C-reactive protein [CRP], interleukin-6, and serum amyloid A levels), oxidative stress (lower erythrocyte glutathione/hemoglobin and α-tocopherol/cholesterol ratios), and liver dysfunction (increased liver weight and blood bilirubin levels). Perirenal edema was more excessive in malnourished LPS-infused animals, relative to healthy LPS-infused control animals (P < .01). Malnutrition reduced the inflammatory response to LPS (lower CRP, tumor necrosis factor-α, haptoglobin, and neutrophil to lymphocyte ratio) but did not influence LPS-induced oxidative stress markers.Conclusions: We conclude that endotoxemia and malnutrition in combination lead to acute-phase hyporesponsiveness and perirenal edema in piglets. This finding may have implications for pediatric patients that suffer from malnutrition, as their response to bacterial infections may differ substantially from patients of normal nutrition status. [ABSTRACT FROM AUTHOR]

Objectives: This study aims to describe the mortality risk of children in the community who had severe acute malnutrition (SAM) defined by either a mid-upper arm circumference (MUAC) <115mm, a low weight-for-height Z-score (WHZ) <-3 or both criteria. Methods: We pooled individual-level data from children aged 6–59 months enrolled in 3 community-based studies in the Democratic Republic of the Congo (DRC), Senegal and Nepal. We estimate the mortality hazard using Cox proportional hazard models in groups defined by either anthropometric indicator. Results: In total, we had 49,001 time points provided by 15,060 children available for analysis, summing to a total of 143,512 person-months. We found an increasing death rate with a deteriorating nutritional status for all anthropometrical indicators. Children identified as SAM only by a low MUAC (<115mm) and those identified only by a low WHZ (Z-score <-3) had a similar mortality hazard which was about 4 times higher than those without an anthropometric deficit. Having both a low MUAC and a low WHZ was associated with an 8 times higher hazard of dying compared to children within the normal range. The 2 indicators identified a different set of children; the proportion of children identified by both indicators independently ranged from 7% in the DRC cohort, to 35% and 37% in the Senegal and the Nepal cohort respectively. Conclusion: In the light of an increasing popularity of using MUAC as the sole indicator to identify SAM children, we show that children who have a low WHZ, but a MUAC above the cut-off would be omitted from diagnosis and treatment despite having a similar risk of death. [ABSTRACT FROM AUTHOR]

The various types of oedema in man are considered in relation to Starling's hypothesis of fluid movement from capillaries, with the main emphasis on nutritional oedema and the nephrotic syndrome in children. It is concluded that each condition has sufficient anomalous findings to render Starling's hypothesis untenable. The finding that the endothelial glycocalyx is key to control of fluid movement from and into the capillaries calls for complete revision of our understanding of oedema formation. The factors so far known to affect the function of the glycocalyx are reviewed. As these depend upon sulphated proteoglycans and other glycosaminoglycans, the argument is advanced that the same abnormalities will extend to the interstitial space and that kwashiorkor is fundamentally related to a defect in sulphur metabolism which can explain all the clinical features of the condition, including the formation of oedema. [ABSTRACT FROM AUTHOR]