Trends in underweight, stunting, and wasting prevalence and inequality among children under three in Indian states, 1993-2016.

Child undernutrition remains high in India with far-reaching consequences for child health and development. Anthropometry reflects undernutrition. We examined the state-level trends in underweight, stunting, and wasting prevalence and inequality by living standards using four rounds of the National Family Health Surveys in 26 states in India, conducted in 1992-1993, 1998-1999, 2005-2006, and 2015-2016. The average annual reduction (AAR) for underweight ranged from 0.04 percentage points (pp) (95% CI - 0.12, 0.20) in Haryana to 1.05 pp (95% CI 0.88, 1.22) in West Bengal for underweight; 0.35 pp (95% CI 0.11, 0.59) in Manipur to 1.47 (95% CI 1.19, 1.75) in Himachal Pradesh for stunting; and - 0.65 pp (95% CI - 0.77, - 0.52) in Haryana to 0.36 pp (95% CI 0.22, 0.51) in Bihar & Jharkhand for wasting. We find that change in the pp difference between children with the poorest and richest household living standards varied by states: statistically significant decline (increase) was observed in 5 (3) states for underweight, 5 (4) states for stunting, and 2 (1) states for wasting. Prevalence of poor anthropometric outcomes as well as disparities by states and living standards remain a problem in India.

Metabolic reprogramming and epigenetic changes of vital organs in SARS-CoV-2-induced systemic toxicity.

Extrapulmonary manifestations of COVID-19 are associated with a much higher mortality rate than pulmonary manifestations. However, little is known about the pathogenesis of systemic complications of COVID-19. Here, we create a murine model of SARS-CoV-2-induced severe systemic toxicity and multiorgan involvement by expressing the human ACE2 transgene in multiple tissues via viral delivery, followed by systemic administration of SARS-CoV-2. The animals develop a profound phenotype within 7 days with severe weight loss, morbidity, and failure to thrive. We demonstrate that there is metabolic suppression of oxidative phosphorylation and the tricarboxylic acid (TCA) cycle in multiple organs with neutrophilia, lymphopenia, and splenic atrophy, mirroring human COVID-19 phenotypes. Animals had a significantly lower heart rate, and electron microscopy demonstrated myofibrillar disarray and myocardial edema, a common pathogenic cardiac phenotype in human COVID-19. We performed metabolomic profiling of peripheral blood and identified a panel of TCA cycle metabolites that served as biomarkers of depressed oxidative phosphorylation. Finally, we observed that SARS-CoV-2 induces epigenetic changes of DNA methylation, which affects expression of immune response genes and could, in part, contribute to COVID-19 pathogenesis. Our model suggests that SARS-CoV-2-induced metabolic reprogramming and epigenetic changes in internal organs could contribute to systemic toxicity and lethality in COVID-19.

Characterizing the contribution of high temperatures to child undernourishment in Sub-Saharan Africa.

Despite improvements to global economic conditions, child undernourishment has increased in recent years, with approximately 7.5% of children suffering from wasting. Climate change is expected to worsen food insecurity and increase potential threats to nutrition, particularly in low-income and lower-middle income countries where the majority of undernourished children live. We combine anthropometric data for 192,000 children from 30 countries in Sub-Saharan Africa with historical climate data to directly estimate the effect of temperature on key malnutrition outcomes. We first document a strong negative relationship between child weight and average temperature across regions. We then exploit variation in weather conditions to statistically identify the effects of increased temperatures over multiple time scales on child nutrition. Increased temperatures in the month of survey, year leading up to survey and child lifetime lead to meaningful declines in acute measures of child nutrition. We find that the lifetime-scale effects explain most of the region-level negative relationship between weight and temperature, indicating that high temperatures may be a constraint on child nutrition. We use CMIP5 local temperature projections to project the impact of future warming, and find substantial increases in malnutrition depending on location: western Africa would see a 37% increase in the prevalence of wasting by 2100, and central and eastern Africa 25%.

Protein energy-wasting associated with nephrotic syndrome - the comparison of metabolic pattern in severe nephrosis to different stages of chronic kidney disease.

BACKGROUND: Nephrotic syndrome (NS) is associated with a hypercatabolic state expressed as an exacerbated degradation of muscle mass. However, the clinical significance of this phenomenon has not yet been investigated. The aim of the study was to evaluate the nutritional status of patients with severe NS (defined as nephrotic range proteinuria with hypoalbuminemia ≤2.5 g/dL) and estimated glomerular filtration rate (eGFR) ≥45 mL/min/1.73 m2 in comparison to patients in different stages of chronic kidney disease (CKD). METHODS: Twenty men with severe NS (NS group) and 40 men without proteinuria similar in term of serum creatinine (control group) were included into the study. A retrospective cohort of 40 men with CKD stage G4 (PreD group) and 20 haemodialysis men (HD group) were added to the analysis after matching for age, height and weight using propensity score matching. The bioimpedance spectroscopy and biochemical nutritional markers were evaluated. RESULTS: Nephrotic patients had a significantly lower lean tissue mass (LTM; p = 0.035) and index (a quotient of LTM over height squared, LTI; p = 0.068), with an expected deficiency of LTM by 3.2 kg, and LTI by 0.9 kg/m2 when compared to the control group. A significant lean tissue deficit (defined as LTI below the lower limit of the reference range by 1.0 kg/m2) was observed in 12.5% of patients in the control group in comparison to 31.7% with advanced CKD (PreD+HD; p = 0.032) and 50% with NS (p = 0.003). NS group presented with higher phosphorus (p = 0.029), uric acid (p = 0.002) and blood urea (p = 0.049) than the control group. Blood urea was strongly negatively correlated with LTM in NS (r = - 0.64, p = 0.002). Nine nephrotic patients (45%) were identified as hypercatabolic based on severe hyperphosphatemia (> 5.0 mg/dL) and/or hyperuricemia (> 8.0 mg/dL), and were characterized by higher blood urea and lower prealbumin, as well as LTM lower by 5.6 kg than in less catabolic individuals. CONCLUSIONS: In term of lean tissue amount, NS group was more similar to advanced CKD than to the control group. We concluded that specific metabolic pattern with elevated phosphorus, uric acid and blood urea, and lean tissue deficiency may be defined as protein-energy wasting associated with nephrotic syndrome (neph-PEW).

TGF-ß Pathway Inhibition Protects the Diaphragm From Sepsis-Induced Wasting and Weakness in Rat.

Sepsis is a frequent complication in patients in intensive care units (ICU). Diaphragm weakness, one of the most common symptoms observed, can lead to weaning problems during mechanical ventilation. Over the last couple of years, members of the transforming growth factor (TGF) ß family, such as myostatin, activin A, and TGF-ß1, have been reported to strongly trigger the activation of protein breakdown involved in muscle wasting. The aim of this study was to investigate the effect of TGF-ß inhibitor LY364947 on the diaphragm during chronic sepsis.Rats were separated into four groups exposed to different experimental conditions: Control group, Septic group, Septic group with inhibitor from day 0 (LY D0), and Septic group with inhibitor from day 1 (LY D1). Sepsis was induced in rats by cecal ligation and puncture, and carried out for 7 days.Chronic sepsis was responsible for a decrease in body weight, food intake and diaphragm's mass. The inhibitor was able to abolish diaphragm wasting only in the LY D1 group. Similarly, LY364947 had a beneficial effect on the diaphragm contraction only for the LY D1 group. SMAD3 was over-expressed and phosphorylated within rats in the Septic group; however, this effect was reversed by LY364947. Calpain-1 and -2 as well as MAFbx were over-expressed within individuals in the Septic group. Yet, calpain-1 and MAFbx expressions were decreased by LY364947.With this work, we demonstrate for the first time that the inhibition of TGF-ß pathway during chronic sepsis protects the diaphragm from wasting and weakness as early as one day post infection. This could lead to more efficient treatment and care for septic patients in ICU.

Diarrhoeal children with concurrent severe wasting and stunting compared to severe wasting or severe stunting.

OBJECTIVE: Children with both severe wasting and severe stunting (SWSS) represent an extreme form of malnutrition and are prone to develop severe infection. The study aims to demonstrate clinical features and aetiology of diarrhoea among children with SWSS compared to those with either severe wasting (SW) or severe stunting (SS), which may help in early identification of high-risk children. METHODS: Data were extracted from the database of the diarrhoeal disease surveillance system (DDSS) of Dhaka Hospital, icddr,b from 2008 to 2017. Among 14 403 under-five diarrhoeal children, 149 had concurrent SWSS (WLZ/WHZ ˂-3 with LAZ/HAZ ˂-3), 795 had SW (WLZ/WHZ ˂-3 but LAZ/HAZ ≥-3) alone, and 1000 had only SS (LAZ/HAZ ˂-3 but WLZ/WHZ ≥-3). RESULTS: In logistic regression analysis after adjusting for potential confounders, dehydrating diarrhoea and slum dwelling were independently associated with SWSS vs. SW (P < 0.05). When compared with SS, dehydration and maternal illiteracy were independently associated with SWSS (P < 0.05). In comparison with SW or SS, SWSS less often included infection with rotavirus (P < 0.05). Dehydration was independently associated with SW vs. SS after adjusting for potential confounders (P < 0.05). CONCLUSION: Children with SWSS more often presented with dehydrating diarrhoea (69%) than children who had either SW (55%) or SS (43%). However, SWSS patients less frequently presented with rotavirus-associated diarrhoeal illnesses. This result underscores the importance of early detection and prompt management of dehydrating diarrhoea in children with concomitant severe wasting and severe stunting to reduce morbidity and mortality in these children, especially in poor settings.

OBJECTIF: Les enfants souffrant à la fois d'émaciation sévère et de retard de croissance sévère (ESRCS) représentent une forme extrême de malnutrition et sont susceptibles de développer des infections graves. L'étude vise à démontrer les caractéristiques cliniques et l'étiologie de la diarrhée chez les enfants atteints d'ESRCS par rapport à ceux souffrant d'émaciation sévère ou de retard de croissance sévère, ce qui pourrait aider à identifier rapidement les enfants à haut risque. MÉTHODES: Les données ont été extraites de la base de données du système de surveillance des maladies diarrhéiques (SSMD) de l'hôpital de Dhaka, icddr,b de 2008 à 2017. Parmi les 14.403 enfants de moins de cinq ans atteints de diarrhée, 149 avaient une ESRCS concomitants (WLZ/WHZ ˂-3 avec LAZ/HAZ ˂-3), 795 avaient une ES seule (WLZ/WHZ ˂-3 mais LAZ/HAZ ≥-3) et 1000 avaient un RCS seul (LAZ/HAZ ˂-3 mais WLZ/WHZ ≥-3). RÉSULTATS: Dans l'analyse de régression logistique, après ajustement des facteurs de confusion potentiels, la diarrhée déshydratante et l'habitation dans les bidonvilles étaient associées indépendamment à l'ESRCS par rapport à l'ES (P < 0,05). Par rapport au RCS, la déshydratation et l'analphabétisme de la mère ont été associés indépendamment à l'ESRCS (P < 0,05). Par rapport à l'ES ou au RCS, l'ESRCS incluait moins souvent l'infection par un rotavirus (P < 0,05). La déshydratation a été associée indépendamment à l'ES comparé au RCS après ajustement pour les facteurs de confusion potentiels (P < 0,05). CONCLUSION: Les enfants ayant une ESRCS présentent plus souvent une diarrhée déshydratante (69%) que ceux ayant soit une ES (55%) ou un RCS (43%). Cependant, les enfants atteints d'ESRCS présentaient moins fréquemment des maladies diarrhéiques associées à un rotavirus. Ce résultat souligne l'importance d'une détection précoce et d'une prise en charge rapide de la diarrhée déshydratante chez les enfants présentant une émaciation et un retard de croissance sévères concomitants, afin de réduire la morbidité et la mortalité chez ces enfants, en particulier dans les milieux pauvres.

Muscle wasting in the critically ill patient: how to minimise subsequent disability.

Muscle wasting in critically ill patients is the most common complication associated with critical care. It has significant effects on physical and psychological health, mortality and quality of life. It is most severe in the first few days of illness and in the most critically unwell patients, with muscle loss estimated to occur at 2-3% per day. This muscle loss is likely a result of a reduction in protein synthesis relative to muscle breakdown, resulting in altered protein homeostasis. The associated weakness is associated with in an increase in both short- and long-term mortality and morbidity, with these detrimental effects demonstrated up to 5 years post discharge. This article highlights the significant impact that muscle wasting has on critically ill patients' outcomes, how this can be reduced, and how this might change in the future.

A Practical Approach to Nutrition, Protein-Energy Wasting, Sarcopenia, and Cachexia in Patients with Chronic Kidney Disease.

Objectives of Review: Protein-energy wasting (PEW) is a state of disordered catabolism resulting from metabolic and nutritional derangements in chronic disease states. Patients with chronic kidney disease (CKD), and end-stage renal disease (ESRD) in particular, have muscle wasting, sarcopenia, and cachexia that contribute to frailty and morbidity. Moreover, reverse epidemiology findings have strongly linked PEW with mortality in CKD and ESRD. Updated Findings: The malnutrition-inflammation score (KALANTAR Score) provides a useful tool to predict nutritional risk. A stronger focus on renal nutrition in renal patients is needed to attenuate cachexia and muscle loss. Malnutrition is a far greater threat in patients with renal disease than obesity, which means dietary counseling needs to be tailored to reflect this observation. The need to achieve optimal caloric intake is compounded by the need to limit excess protein intake in CKD, resulting in the need for energy supplementation to avoid PEW. Preventing PEW is the most pressing clinical concern in CKD/ESRD. Other nutritional issues to reckon in renal disease include the need to normalize serum bicarbonate to manage acidosis, uric acid control, and phosphorous control in CKD and ESRD. Exercise maybe beneficial, but further work is needed to prove a conclusive benefit via a randomized trial. Summary: PEW prevention is an integral part of renal nutrition and is of paramount importance given the obesity paradox. Integrative approaches by physicians and dieticians are needed to take a holistic view of a patient's diet beyond just control of particular laboratory parameters.

Body composition of children with moderate and severe undernutrition and after treatment: a narrative review.

BACKGROUND: Until recently, undernourished children were usually assessed using simple anthropometric measurements, which provide global assessments of nutritional status. There is increasing interest in obtaining more direct data on body composition to assess the effects of undernutrition on fat-free mass (FFM) and its constituents, such as muscle and organs, and on fat mass (FM) and its regional distribution. MAIN TEXT: Recent studies show that severe-acute undernutrition, categorised as 'wasting', is associated with major deficits in both FFM and FM that may persist in the long-term. Fat distribution appears more central, but this is more associated with the loss of peripheral fat than with the elevation of central fat. Chronic undernutrition, categorised as 'stunting', is associated with deficits in FFM and in specific components, such as organ size. However, the magnitude of these deficits is reduced, or - in some cases - disappears, after adjustment for height. This suggests that FFM is largely reduced in proportion to linear growth. Stunted children vary in their FM - in some cases remaining thin throughout childhood, but in other cases developing higher levels of FM. The causes of this heterogeneity remain unclear. Several different pathways may underlie longitudinal associations between early stunting and later body composition. Importantly, recent studies suggest that short children are not at risk of excess fat deposition in the short term when given nutritional supplementation. CONCLUSION: The short- and long-term functional significance of FFM and FM for survival, physical capacity and non-communicable disease risk means that both tissues merit further attention in research on child undernutrition.

Differences in lung function between children with sickle cell anaemia from West Africa and Europe.

INTRODUCTION: Lung function abnormalities are common in sickle cell anaemia (SCA) but data from sub-Saharan Africa are limited. We hypothesised that children with SCA from West Africa had worse lung function than their counterparts from Europe. METHODS: This prospective cross-sectional study evaluated spirometry and anthropometry in black African individuals with SCA (haemoglobin phenotype SS) aged 6-18 years from Nigeria and the UK, when clinically stable. Age-matched controls were also included in Nigeria to validate the Global Lung Initiative spirometry reference values. RESULTS: Nigerian SCA patients (n=154) had significant reductions in both FEV1 and FVC of ~1 z-score compared with local controls (n=364) and ~0.5 z-scores compared with the UK patients (n=101). Wasting (body mass index z-score<-2) had a prevalence of 27% in Nigerian patients and 7% in the UK ones (p<0.001). Among children with SCA, being resident in Nigeria (OR 2.4, 95% CI 1.1 to 4.9), wasting (OR 2.3, 95% CI 1.1 to 5.0) and each additional year of age (OR 1.2, 95% CI 1.1 to 1.4) were independently associated with increased risk of restrictive spirometry (FVC z-score<-1.64+FEV1/FVC≥-1.64). CONCLUSIONS: This study showed that chronic respiratory impairment is more severe in children with SCA from West Africa than Europe. Our findings suggest the utility of implementing respiratory assessment in African children with SCA to early identify those with chronic lung injury, eligible for closer follow-up and more aggressive therapies.

Kidney cachexia or protein-energy wasting in chronic kidney disease: facts and numbers.

BACKGROUND: Weight loss and homeostatic disturbances of both energy and protein balances are characteristics of several illnesses including cancer, heart failure, and chronic kidney disease (CKD). Different definitions have been used to describe this deleterious process. The term protein-energy wasting (PEW) has been proposed for CKD patients by the International Society of Renal Nutrition and Metabolism. METHODS: We searched the publication in Medline from February 2008 to September 2018 using PEW or cachexia in their title. RESULTS: Since its inception, the term PEW has been exceptionally successful, highlighted by 327 original publications referenced in PubMed over 10 years. Using this classification, several studies have confirmed that PEW is among the strongest predictors of mortality in CKD patients [hazard ratio of 3.03; confidence interval of 1.69-5.26 in 1068 haemodialysis patients and 1.40 (1.04-1.89) in 1487 non-dialysed patients across PEW stages 0 to 4]. Based on this classification, prevalence of PEW is 28% to 54% among 16 434 adults undergoing maintenance dialysis. PEW prevalence increases when renal function declines, that is, from <2% in CKD stages 1-2 to 11-54% in CKD stages 3-5. A more general definition of cachexia for all chronic diseases proposed by the Society on Sarcopenia, Cachexia and Wasting Disorders was also published concurrently. In the CKD area, we found 180 publications using 'cachexia' underlining that some confusion or overlap may exist. The definitions of PEW and cachexia are somewhat similar, and the main difference is that a loss of body weight >5% is a mandatory criterion for cachexia but supportive for PEW. CONCLUSIONS: The recent understanding of cachexia physiopathology during CKD progression suggests that PEW and cachexia are closely related and that PEW corresponds the initial state of a continuous process that leads to cachexia, implicating the same metabolic pathways as in other chronic diseases. Despite the success of the definition of PEW, using a more uniform term such as 'kidney disease cachexia' could be more helpful to design future research through collaborative groups of researchers with focus on cachexia.

Hemojuvelin is a novel suppressor for Duchenne muscular dystrophy and age-related muscle wasting.

BACKGROUND: Muscle wasting occurs in response to various physiological and pathological conditions, including ageing and Duchenne muscular dystrophy (DMD). Transforming growth factor-ß1 (TGF-ß1) contributes to muscle pathogenesis in elderly people and DMD patients; inhibition of TGF-ß1 signalling is a promising therapeutic strategy for muscle-wasting disorders. Hemojuvelin (HJV or Hjv as the murine homologue) is a membrane-bound protein that is highly expressed in skeletal muscle, heart, and liver. In hepatic cells, Hjv acts as a coreceptor for bone morphogenetic protein, a TGF-ß subfamily member. The aim of this study was to investigate whether Hjv plays an essential role in muscle physiological and pathophysiological processes by acting as a coreceptor for TGF-ß1 signalling. METHODS: Conventional and conditional Hjv knockout mice as well as mdx and aged mice transfected with Hjv overexpression vector were used to study the role of Hjv in muscle physiology and pathophysiology. qRT-PCR, western blotting, and immunohistochemistry examinations were conducted to evaluate gene, protein, and structural changes in vivo and in vitro. Exercise endurance was determined using treadmill running test, and muscle force was detected by an isometric transducer. RNA interference, immunoprecipitation, and dual-luciferase reporter assays were utilized to explore the mechanism by which Hjv regulates TGF-ß1 signalling in skeletal muscle. RESULTS: Conventional and conditional Hjv knockout mice displayed muscle atrophy, fibrosis, reduced running endurance, and muscle force. HJV was significantly down-regulated in the muscles of DMD patients (n = 3, mean age: 11.7 ± 5.7 years) and mdx mice as well as in those of aged humans (n = 10, 20% women, mean age: 75.1 ± 9.5 years) and mice. Overexpression of Hjv rescued dystrophic and age-related muscle wasting. Unlike its function in hepatic cells, the bone morphogenetic protein downstream phosphorylated p-Smad1/5/8 signalling pathway was unchanged, but TGF-ß1, TGF-ß receptor II (TßRII), and p-Smad2/3 expression were increased in Hjv-deficient muscles. Mechanistically, loss of Hjv promoted activation of Smad3 signalling induced by TGF-ß1, whereas Hjv overexpression inhibited TGF-ß1/Smad3 signalling by directly interacting with TßRII on the muscle membrane. CONCLUSIONS: Our findings identify an unrecognized role of HJV in skeletal muscle by regulating TGF-ß1/Smad3 signalling as a coreceptor for TßRII. Unlike the TGF-ß1/Smad3 pathway, HJV could be a reliable drug target as its expression is not widespread. Novel therapeutic strategies could potentially be devised to interfere only with the muscle function of HJV to treat DMD and age-related muscle wasting.

Stunting, wasting and breast-feeding as correlates of body composition in Cambodian children at 6 and 15 months of age.

The study aimed at assessing stunting, wasting and breast-feeding as correlates of body composition in Cambodian children. As part of a nutrition trial (ISRCTN19918531), fat mass (FM) and fat-free mass (FFM) were measured using 2H dilution at 6 and 15 months of age. Of 419 infants enrolled, 98 % were breastfed, 15 % stunted and 4 % wasted at 6 months. At 15 months, 78 % were breastfed, 24 % stunted and 11 % wasted. Those not breastfed had lower FMI at 6 months but not at 15 months. Stunted children had lower FM at 6 months and lower FFM at 6 and 15 months compared with children with length-for-age z ≥0. Stunting was not associated with height-adjusted indexes fat mass index (FMI) or fat-free mass index (FFMI). Wasted children had lower FM, FFM, FMI and FFMI at 6 and 15 months compared with children with weight-for-length z (WLZ) ≥0. Generally, FFM and FFMI deficits increased with age, whereas FM and FMI deficits decreased, reflecting interactions between age and WLZ. For example, the FFM deficits were -0·99 (95 % CI -1·26, -0·72) kg at 6 months and -1·44 (95 % CI -1·69; -1·19) kg at 15 months (interaction, P<0·05), while the FMI deficits were -2·12 (95 % CI -2·53, -1·72) kg/m2 at 6 months and -1·32 (95 % CI -1·77, -0·87) kg/m2 at 15 months (interaction, P<0·05). This indicates that undernourished children preserve body fat at the detriment of fat-free tissue, which may have long-term consequences for health and working capacity.

Dietary inflammatory index and parameters of diet quality in normal weight and obese patients undergoing hemodialysis.

OBJECTIVE: Better nutritional reserves are proposed as a mechanism for the protective role of obesity in hemodialysis. Little is known about the quality of diet as a major contributor to nutritional status, specifically body mass index and obesity. The aim of this study was to assess dietary inflammatory index (DII®) score and other parameters of diet in normal-weight and obese patients undergoing hemodialysis to understand whether there is a benefit for obese patients. METHODS: This cross-sectional study included 85 hemodialysis patients (44 obese and 41 normal-weight). Four-day 24-h dietary recalls and anthropometric measurements were collected. DII, energy-adjusted DII (E-DII), dietary energy density (DED), mean adequacy ratio (MAR), and malnutrition inflammation score (MIS) were calculated. RESULTS: Median E-DII score (1 [0.29-1.47] versus 0.42 [0.12-1.27]; P = 0.047) was higher and DII score (1.18 [0.03-2.26] versus 1.79 [0.47-2.49]; P = 0.046) was lower in the obese group. Obese patients had higher DED (1.52 ± 0.23 versus 1.43 ± 0.28; P = 0.034) and lower MIS (6.3 ± 2.5 versus 10.5 ± 3.1; P < 0.001) compared with the normal weight group. There was no significant difference in MAR between groups (P = 0.358). E-DII had significant positive correlation with weight (r = 0.226; P = 0.037), triceps skinfold thickness (r = 0.239; P = 0.035), and DED (r = 0.227; P = 0.036). MAR had significant negative correlation with MIS (r = -0.287; P = 0.008). CONCLUSIONS: Observed higher diet inflammatory potential and energy density and lower wasting in the obese group, along with similar adequacy of nutrients intake between groups, indicates that lower wasting, but not other indicators of nutritional status, are involved in better prognosis of obese patients with hemodialysis. Further studies are required to assess the potential dietary factors involved in determining wasting in advanced kidney failure.

Implications of low muscle mass across the continuum of care: a narrative review.

Abnormalities in body composition can occur at any body weight. Low muscle mass is a predictor of poor morbidity and mortality and occurs in several populations. This narrative review provides an overview of the importance of low muscle mass on health outcomes for patients in inpatient, outpatient and long-term care clinical settings. A one-year glimpse at publications that showcases the rapidly growing research of body composition in clinical settings is included. Low muscle mass is associated with outcomes such as higher surgical and post-operative complications, longer length of hospital stay, lower physical function, poorer quality of life and shorter survival. As such, the potential clinical benefits of preventing and reversing this condition are likely to impact patient outcomes and resource utilization/health care costs. Clinically viable tools to measure body composition are needed for routine screening and intervention. Future research studies should elucidate the effectiveness of multimodal interventions to counteract low muscle mass for optimal patient outcomes across the healthcare continuum. Key messages Low muscle mass is associated with several negative outcomes across the healthcare continuum. Techniques to identify and counteract low muscle mass in clinical settings are needed.

Chronic hyponatremia in a patient with renal salt wasting and without cerebral disease: relationship between RSW, risk of fractures and cognitive impairment.

Renal salt wasting syndrome (RSW) is defined as a renal loss of sodium leading to hyponatremia and a decrease in extracellular fluid volume (ECV). Differentiation of this disorder from the syndrome of inappropriate antidiuretic hormone secretion (SIADH), a common cause of hyponatremia, can be difficult because both can present with hyponatremia and concentrated urine with natriuresis. Our clinical case about a 78-year-old woman with a recent fracture of the right femur not only confirms that this syndrome can occur in patients without intracranial pathologies (CT documented), but depicts how the hyponatremia caused by RSW can show a chronic, oscillating course. This is an interesting point of view because it suggests to us to consider RSW in the differential diagnosis of patients with chronic hyponatremia.

Factors associated with wasting among children under five years old in South Asia: Implications for action.

South Asia continues to carry the greatest share and number of wasted children worldwide. Understanding the determinants of wasting is important as policymakers renew efforts to tackle this persistent public health and development problem. Using data from national surveys in Bangladesh, India, the Maldives, Nepal, Pakistan and Afghanistan, this analysis explores factors associated with wasting among children aged 0 to 59 months (n = 252,797). We conducted multivariate mixed logistic regression and backwards stepwise methods to identify parsimonious models for each country separately (all p values <0.05). Younger children (0 to 5 months), and those whose mothers had a low body mass index (<18.5 kg/m2) had greater odds of being wasted in all countries. Later birth order, being male, maternal illiteracy, short maternal stature, lack of improved water source, and household poverty were also associated with wasting in various countries, but not systematically in all. Seasonality was also not consistently associated with wasting in the final models. These findings suggest that pre-conception (adolescence), pregnancy and early postpartum, represent windows of opportunity for tackling child wasting, not only stunting. Our analysis suggests that the underlying determinants of wasting and stunting in South Asia are similar, but not universal across geographies. Cost-effective interventions to prevent both stunting and wasting, and to treat severe wasting, need to be scaled up urgently. Separating these two manifestations of child undernutrition in conceptual and programmatic terms may unnecessarily impair progress to reach the Sustainable Development Goals targets aimed at addressing both child stunting and wasting.

Systemic SMAD7 Gene Therapy Increases Striated Muscle Mass and Enhances Exercise Capacity in a Dose-Dependent Manner.

Striated muscle wasting occurs with a variety of disease indications, contributing to mortality and compromising life quality. Recent studies indicate that the recombinant adeno-associated virus (serotype 6) Smad7 gene therapeutic, AVGN7, enhances skeletal and cardiac muscle mass and prevents cancer-induced wasting of both tissues. This is accomplished by attenuating ActRIIb intracellular signaling and, as a result, the physiological actions of myostatin and other ActRIIb ligands. AVGN7 also enhances isolated skeletal muscle twitch force, but is unknown to improve systemic muscle function similarly, especially exercise capacity. A 2-month-long dose-escalation study was therefore conducted using 5 × 1011, 1 × 1012, and 5 × 1012 vg/mouse and different tests of systemic muscle function. Body mass, skeletal muscle mass, heart mass, and forelimb grip strength were all increased in a dose-dependent manner, as was the fiber cross-sectional area of tibialis anterior muscles. Maximal oxygen consumption (VO2max), a measure of metabolic rate, was similarly enhanced during forced treadmill running, and although the total distance traveled was only elevated by the highest dose, all doses reduced the energy expenditure rate compared to control mice injected with an empty vector. Such improvements in VO2max are consistent with physiological cardiac hypertrophy, which is highly beneficial and a normal adaptive response to exercise. This was particularly evident at the lowest dose tested, which had minimal significant effects on skeletal muscle mass and/or function, but increased heart weight and exercise capacity. These results together suggest that AVGN7 enhances striated muscle mass and systemic muscle function. They also define minimally effective and optimal doses for future preclinical trials and toxicology studies and in turn will aid in establishing dose ranges for clinical trials.