Cachectic muscle wasting in acute myeloid leukaemia: a sleeping giant with dire clinical consequences.

Acute myeloid leukaemia (AML) is a haematological malignancy with poor survival odds, particularly in the older (>65 years) population, in whom it is most prevalent. Treatment consists of induction and consolidation chemotherapy to remit the cancer followed by potentially curative haematopoietic cell transplantation. These intense treatments are debilitating and increase the risk of mortality. Patient stratification is used to mitigate this risk and considers a variety of factors, including body mass, to determine whether a patient is suitable for any or all treatment options. Skeletal muscle mass, the primary constituent of the body lean mass, may be a better predictor of patient suitability for, and outcomes of, AML treatment. Yet skeletal muscle is compromised by a variety of factors associated with AML and its clinical treatment consistent with cachexia, a life-threatening body wasting syndrome. Cachectic muscle wasting is associated with both cancer and anticancer chemotherapy. Although not traditionally associated with haematological cancers, cachexia is observed in AML and can have dire consequences. In this review, we discuss the importance of addressing skeletal muscle mass and cachexia within the AML clinical landscape in view of improving survivability of this disease.

Therapeutic Implications of miRNAs for Muscle-Wasting Conditions.

MicroRNAs (miRNAs) are small, non-coding RNA molecules that are mainly involved in translational repression by binding to specific messenger RNAs. Recently, miRNAs have emerged as biomarkers, relevant for a multitude of pathophysiological conditions, and cells can selectively sort miRNAs into extracellular vesicles for paracrine and endocrine effects. In the overall context of muscle-wasting conditions, a multitude of miRNAs has been implied as being responsible for the typical dysregulation of anabolic and catabolic pathways. In general, chronic muscle disorders are associated with the main characteristic of a substantial loss in muscle mass. Muscular dystrophies (MDs) are a group of genetic diseases that cause muscle weakness and degeneration. Typically, MDs are caused by mutations in those genes responsible for upholding the integrity of muscle structure and function. Recently, the dysregulation of miRNA levels in such pathological conditions has been reported. This revelation is imperative for both MDs and other muscle-wasting conditions, such as sarcopenia and cancer cachexia. The expression levels of miRNAs have immense potential for use as potential diagnostic, prognostic and therapeutic biomarkers. Understanding the role of miRNAs in muscle-wasting conditions may lead to the development of novel strategies for the improvement of patient management.

The Clinical Value of Nutritional Care before and during Active Cancer Treatment.

Malnutrition and muscle wasting are frequently reported in cancer patients, either linked to the tumor itself or caused by oncologic therapies. Understanding the value of nutritional care during cancer treatment remains crucial. In fact, cancer-associated sarcopenia plays a key role in determining higher rates of morbidity, mortality, treatment-induced toxicities, prolonged hospitalizations and reduced adherence to anticancer treatment, worsening quality of life and survival. Planning baseline screening to intercept nutritional troubles earlier, organizing timely reassessments, and providing adequate counselling and dietary support, healthcare professional may positively interfere with this process and improve patients' overall outcomes during the whole disease course. Several screening tools have been proposed for this purpose. Nutritional Risk Screening (NRS), Mini Nutritional Assessment (MNA), Patient Generated Subjective Global Assessment (PG-SGA) are the most common studied. Interestingly, second-level tools including skeletal muscle index (SMI) and bioelectric impedance analysis (BIA) provide a more precise assessment of body composition, even if they are more complex. However, nutritional assessment is not currently used in clinical practice and procedures must be standardized in order to improve the efficacy of standard chemotherapy, targeted agents or even checkpoint inhibitors that is potentially linked with the patients' nutritional status. In the present review, we will discuss about malnutrition and the importance of an early nutritional assessment during chemotherapy and treatment with novel checkpoint inhibitors, in order to prevent treatment-induced toxicities and to improve survival outcomes.

The clinical relevance and mechanism of skeletal muscle wasting.

Skeletal muscle wasting occurs in both chronic and acute diseases. Increasing evidence has shown this debilitating process is associated with short- and long-term outcomes in critical, cancer and surgical patients. Both muscle quantity and quality, as reflected by the area and density of a given range of attenuation in CT scan, impact the patient prognosis. In addition, ultrasound and bioelectrical impedance analysis (BIA) are also widely used in the assessment of body composition due to their bedside viability and no radioactivity. Mechanism researches have revealed complicated pathways are involved in muscle wasting, which include altered IGF1-Akt-FoxO signaling, elevated levels of myostatin and activin A, activation of NF-κB pathway and glucocorticoid effects. Particularly, central nervous system (CNS) has been proven to participate in regulating muscle wasting in various conditions, such as infection and tumor. Several promising therapeutic agents have been under developing in the treatment of muscle atrophy, such as myostatin antagonist, ghrelin analog, non-steroidal selective androgen receptor modulators (SARMs). Notably, nutritional therapy is still the fundamental support in combating muscle wasting. However, the optimizing and tailored nutrition regimen relies on accurate metabolism measurement and large clinical trials in the future. Here, we will discuss the current understanding of muscle wasting and potential treatment in clinical practice.

Relapse and regression to severe wasting in children under 5 years: A theoretical framework.

Systematic reviews have highlighted that repeated severe wasting after receiving treatment is likely to be common, but standardised measurement is needed urgently. The Council of Research & Technical Advice for Acute Malnutrition (CORTASAM) released recommendations on standard measurement of relapse (wasting within 6 months after exiting treatment as per recommended discharge criteria), regression (wasting within 6 months after exiting treatment before reaching recommended discharge criteria) and reoccurrence (wasting after 6 months of exit from treatment as per recommended discharge criteria). We provide a theoretical framework of post-treatment relapse and regression to severe wasting to guide discussions, risk factor analyses, and development and evaluations of interventions. This framework highlights that there are factors that may impact risk of relapse and regression in addition to the impact of contextual factors associated with incidence and reoccurrence of severe wasting more generally. Factors hypothesised to be associated with relapse and regression relate specifically to the nutrition and health status of the child on admission to, during and exit from treatment and treatment interventions, platforms and approaches as well as type of exit from treatment (e.g., before reaching recommended criteria). These factors influence whether children reach full recovery, and poorer nutritional and immunological status at exit from treatment are more proximate determinants of risk of severe wasting after treatment, although post-treatment interventions may modify risks. The evidence base for many of these factors is weak. Our framework can guide research to improve our understanding of risks of relapse and regression and how to prevent them and inform programmes on what data to collect to evaluate relapse. Implementation research is needed to operationalise results in programmes and reduce post-treatment severe wasting at scale.

Regular exercise and branched-chain amino acids prevent ischemic acute kidney injury-related muscle wasting in mice.

Acute kidney injury (AKI) causes glucose and protein metabolism abnormalities that result in muscle wasting, thereby affecting the long-term prognosis of critical illness survivors. Here, we examined whether early intervention with treadmill exercise and branched-chain amino acids (BCAA) can prevent AKI-related muscle wasting and reduced physical performance in mice. Unilateral 15 min ischemia-reperfusion injury was induced in contralateral nephrectomized mice, and muscle histological and physiological changes were assessed and compared with those of pair-fed control mice, since AKI causes severe anorexia. Mice exercised for 30 min each day and received oral BCAA for 7 days after AKI insult. By day 7, ischemic AKI significantly decreased wet weight, myofiber cross-sectional area, and central mitochondrial volume density of the anterior tibialis muscle, and significantly reduced maximal exercise time. Regular exercise and BCAA prevented AKI-related muscle wasting and low physical performance by suppressing myostatin and atrogin-1 mRNA upregulation, and restoring reduced phosphorylated Akt and PGC-1α mRNA expression in the muscle. Ischemic AKI induces muscle wasting by accelerating muscle protein degradation and reducing protein synthesis; however, we found that regular exercise and BCAA prevented AKI-related muscle wasting without worsening kidney damage, suggesting that early rehabilitation with nutritional support could prevent AKI-related muscle wasting.

Factors associated with moderate wasting among marginalized 6 to 23-month aged children in Bangladesh: Findings of the Suchana program baseline survey data.

Suchana-a large-scale, 7-year nutrition program that started in 2015-is being implemented in 250,000 households in the marginalized segment in north-east Bangladesh, with the aim of improving childhood nutrition status. Untreated childhood moderate wasting may develop to severe wasting, which is associated with a 10-fold higher risk of mortality compared to children of normal weight relative to height/length. Identifying the diverse, age-specific risk factors for moderate wasting may help such programs to formulate tailored interventions to prevent and treat childhood malnutrition in rural communities. The objective of this study was to identify the age-specific factors associated with moderate wasting among 6‒23-month-old children in beneficiary households. Cross-sectional data on 4,400 children was collected through systematic sampling between November 2016 and February 2017 using the Suchana beneficiary list. In total, 8.1% of 6‒11 month-olds and 10.3% of 12‒23 month-olds suffered moderate wasting; 12‒23-month-olds had a 1.3-fold higher risk of moderate wasting than 6‒11-month-olds. Our results of logistic regression models suggest that larger household size, higher maternal body mass index (BMI), and maternal food consumption status more than usual during the recent pregnancy were associated with a reduced risk of moderate wasting among 6‒11-month-olds. Higher maternal BMI, normal maternal food consumption status during last pregnancy, being female and maternal knowledge on diarrheal management, were associated with a reduced risk of moderate wasting among 12‒23-month-olds. In conclusion, beyond maternal BMI and maternal food consumption status during the last pregnancy, the factors associated with moderate wasting among 6‒23-month-olds in the poorest households in Bangladesh are age-specific.

Concurrently wasted and stunted 6-59 months children admitted to the outpatient therapeutic feeding programme in Karamoja, Uganda: Prevalence, characteristics, treatment outcomes and response.

This study assessed the prevalence of concurrently wasted and stunted (WaSt) children, their characteristics, treatment outcomes and response; and factors associated with time to recovery among children aged 6-59 months admitted to Outpatient Therapeutic Care (OTC) in Karamoja, Uganda. We conducted a retrospective cohort study with data from January 2016 to October 2017 for children admitted to nine OTCs in Karamoja. We defined wasted, stunted and underweight as 2.0 Z-scores below the median per WHO growth standards and < 12.5 cm for low Mid-Upper Arm Circumference (MUAC). WaSt was defined as concurrently wasted and stunted. Out of 788 eligible children included in the analysis; 48.7% (95% CI; 45.2-52.2) had WaSt. WaSt was common among males; 56.3% (95% CI; 51.3-61.3). Median age was 18 months in WaSt versus 12 months in non-WaSt children (p < 0.001). All WaSt children were underweight; and more severely wasted than non-WaSt children. During recovery, WaSt children gained weight more rapidly than non-WaSt children (2.2g/kg/day vs. 1.7g/kg/day). WaSt children had lower recovery rate (58.0% vs. 65.4%; p = 0.037). The difference in median time of recovery between WaSt and non-WaSt children (63 days vs. 56 days; p = 0.465) was not significant. Factors associated with time to recovery were children aged 24-59 months (aHR = 1.30; 95% CI;1.07-1.57;), children with MUAC 10.5-11.4 cm (aHR = 2.03; 95% CI; 1.55-2.66), MUAC ≥ 11.5 cm at admission (aHR = 3.31; 95% CI; 2.17-5.02) and living in Moroto (aHR = 3.34; 95% CI; 2.60-4.30) and Nakapiripirit (aHR = 1.95; 95% CI; 1.51-2.53) districts. The magnitude of children with WaSt in OTC shows that existing therapeutic feeding protocols could be used to detect and treat WaSt children. Further research is needed to identify and address the factors associated with sub-optimal recovery in WaSt children for effective OTC programming in Karamoja.

Role of Optimized Plant Protein Combinations as a Low-Cost Alternative to Dairy Ingredients in Foods for Prevention and Treatment of Moderate Acute Malnutrition and Severe Acute Malnutrition.

Tackling the global burden of acute malnutrition in children remains a major public health challenge and is essential for achieving sustainable development. Despite having effective treatment options, most wasted children go untreated; treatment coverage for severe acute malnutrition (SAM) children is only about 20%. Milk is currently an essential component of effective SAM treatment, incorporated into ready-to-use therapeutic food (RUTF). Reaching the untreated children, as well as preventing SAM, requires investment in innovative and cost-efficient approaches. To date, attempts to replace or remove milk from RUTF have been either unsuccessful or unpersuasive. This is likely because milk provides the highest protein quality and density of all typical RUTF ingredients. However, alternative protein sources could provide cost savings. Alternative protein sources, especially plant-based protein alternatives, have had shown more promising progress for the treatment of children with moderate acute malnutrition. Acknowledging that cost is a major barrier to the scale-up of treatment of acute malnutrition and that alternative protein sources are a practical means to reduce cost, continued research focusing on alternative proteins is necessary.

Metabolic aspects of muscle wasting during critical illness.

PURPOSE OF REVIEW: Skeletal muscle wasting during critical illness is the result of disturbed metabolism. No proven effective interventions targeting skeletal muscle mass and function during critical illness currently exist. This review summarizes recent advances regarding the complexity of metabolic factors involved and the challenge of establishing the clinical effects of metabolic interventions targeting the muscle. RECENT FINDINGS: Although the catabolic state is limited to the acute phase of critical illness, its subsequent impact on muscle mass and function persists long after ICU discharge. Immobilization, inflammation and disturbed muscle energy and nutrient metabolism are key drivers of muscle protein loss. Current research focuses on the effects of enhanced protein provision, specific substrate delivery and physical exercise. Whilst some interventions have been successful at improving muscle mass, these effects do not always carry over into muscle function or strength. SUMMARY: Increased understanding of metabolic derangements during critical illness provides new potential targets for treatment. The potential of dietary protein to attenuate the muscle protein catabolic state has yet to be established in clinical trials. Basic research should focus on ways to further improve the anabolic potential of nutrition by unravelling mechanisms that regulate anabolic and catabolic pathways and energy metabolism.

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.

Human muscle-derived CLEC14A-positive cells regenerate muscle independent of PAX7.

Skeletal muscle stem cells, called satellite cells and defined by the transcription factor PAX7, are responsible for postnatal muscle growth, homeostasis and regeneration. Attempts to utilize the regenerative potential of muscle stem cells for therapeutic purposes so far failed. We previously established the existence of human PAX7-positive cell colonies with high regenerative potential. We now identified PAX7-negative human muscle-derived cell colonies also positive for the myogenic markers desmin and MYF5. These include cells from a patient with a homozygous PAX7 c.86-1G > A mutation (PAX7null). Single cell and bulk transcriptome analysis show high intra- and inter-donor heterogeneity and reveal the endothelial cell marker CLEC14A to be highly expressed in PAX7null cells. All PAX7-negative cell populations, including PAX7null, form myofibers after transplantation into mice, and regenerate muscle after reinjury. Transplanted PAX7neg cells repopulate the satellite cell niche where they re-express PAX7, or, strikingly, CLEC14A. In conclusion, transplanted human cells do not depend on PAX7 for muscle regeneration.

Novel molecular targets of muscle wasting in cancer patients.

PURPOSE OF REVIEW: Cancer-associated muscle wasting affects many patients and leads to reduced patient function, decreased quality of life and poor responses to surgical and oncological treatments. Despite advancements in the understanding of its pathophysiology, no current treatment or accepted strategy for successful management exists. In this review, we provide an update on potential novel therapeutic targets in cancer cachexia. RECENT FINDINGS: Recent research has focused on molecular mechanisms underlying cancer-associated muscle wasting, allowing identification of potential therapeutic targets and the development of several promising drugs. However, due to the multifactorial and patient-specific pathogenesis of cachexia, the demonstration of a measurable and meaningful clinical effect in randomized controlled trials has proven difficult. Potential novel targets such as circulating macrophage inhibitory cytokine 1/growth differentiation factor 15 and ZRT/IRT-like protein 14 have shown relevance in animal models, but their therapeutic manipulation has yet to be translated to patients. Increasing evidence has suggested that a single therapy may not be successful and a targeted, multimodal approach is required. SUMMARY: The management of cancer-associated muscle wasting is complex. Future clinical trials should focus on early multimodal therapeutic interventions involving targeted therapies, with careful deliberation of chosen nutritional and functional outcomes.

Recent developments in the field of cachexia, sarcopenia, and muscle wasting: highlights from the 11th Cachexia Conference.

This article highlights the updates from preclinical and clinical studies into the field of wasting disorders that were presented at the 11th Cachexia Conference held in Maastricht, the Netherlands, in December 2018. Herein, we summarize the biological and clinical significance of different markers and new diagnostic tools and cut-offs for the detection of skeletal muscle wasting, including micro-RNAs, siRNAs, epigenetic targets, the ubiquitin-proteasome system, mammalian target of rapamycin signalling, news in body composition analysis including the D3-creatine dilution method, and electrocardiography that was modified to enable segmental impedance spectroscopy. Of particular interest were the beneficial effects of BIO101 on muscle cell differentiation, hypertrophy of myofibers associated with mammalian target of rapamycin pathways activation, and the effect of metal ion transporter ZIP14 loss that reduces cancer-induced cachexia. The potential of anti-ZIP14 antibodies and zinc chelation as anti-cachexia therapy should be tested in patients with cancer cachexia. Big randomized studies were presented such as RePOWER (observational study of patients with primary mitochondrial myopathy), STRAMBO (influence of physical performance assessed as score and clinical testing), MMPOWER (treatment of elamipretide in subjects with primary mitochondrial myopathy), FORCE (examined differences in relative dose intensity and moderate and severe chemotherapy-associated toxicities between a strength training intervention and a control group), and SPRINTT (effectiveness of exercise training in healthy aging). Effective treatments were urothelin A, rapamycin analogue treatment, epigenetic factor BRD 4 and epigenetic protein BET, and the gut pathobiont Klebsiella oxytoca. Clinical studies that investigated novel approaches, including urolithin A, the role of gut microbiota, metal ion transporter ZIP14, lysophosphatidylcholine and lysophosphatidylethanolamine, and BIO101, were described. It remains a fact, however, that effective treatments of cachexia and wasting disorders are urgently needed in order to improve patients' quality of life and their survival.

The associations of fat tissue and muscle mass indices with all-cause mortality in patients undergoing hemodialysis.

Protein-energy wasting, which involves loss of fat and muscle mass, is prevalent and is associated with mortality in hemodialysis (HD) patients. We investigated the associations of fat tissue and muscle mass indices with all-cause mortality in HD patients. The study included 162 patients undergoing HD. The fat tissue index (FTI) and skeletal muscle mass index (SMI), which represent respective tissue masses normalized to height squared, were measured by bioimpedance analysis after dialysis. Patients were divided into the following four groups according to the medians of FTI and SMI values: group 1 (G1), lower FTI and lower SMI; G2, higher FTI and lower SMI; G3, lower FTI and higher SMI; and G4, higher FTI and higher SMI. The associations of the FTI, SMI, and body mass index (BMI) with all-cause mortality were evaluated. During a median follow-up of 2.5 years, 29 patients died. The 5-year survival rates were 48.6%, 76.1%, 95.7%, and 87.4% in the G1, G2, G3, and G4 groups, respectively (P = 0.0002). The adjusted hazard ratio values were 0.34 (95% confidence interval [CI] 0.10-0.95, P = 0.040) for G2 vs. G1, 0.13 (95%CI 0.01-0.69, P = 0.013) for G3 vs. G1, and 0.25 (95%CI 0.07-0.72, P = 0.0092) for G4 vs. G1, respectively. With regard to model discrimination, on adding both FTI and SMI to a model with established risk factors, the C-index increased significantly when compared with the value for a model with BMI (0.763 vs. 0.740, P = 0.016). Higher FTI and/or higher SMI values were independently associated with reduced risks of all-cause mortality in HD patients. Moreover, the combination of the FTI and SMI may more accurately predict all-cause mortality when compared with BMI. Therefore, these body composition indicators should be evaluated simultaneously in this population.

Effectiveness of NGO-government partnership to prevent and treat child wasting in urban India.

This study reviews the performance of a community-based nutrition programme in preventing and treating wasting without complications among children under age three in urban informal settlements of India. Implemented by a non-profit organization, with national (Integrated Child Development Services [ICDS]) and city-level (Municipal Corporation of Greater Mumbai [MCGM]) government partners, the programme screened 7,759 children between May 2014 and April 2015. During this period, the programme admitted 705 moderately wasted and 189 severely wasted children into the treatment group and 6,820 not wasted children into the prevention group. Both prevention and treatment groups received growth monitoring, referrals to public health facilities, and home-based counselling (if <6 months) by community health workers. Treatment groups received additional home-based counselling and access to medical screenings. Severely wasted children also received access to ready-to-use therapeutic food. The study assessed default rates, wasting status, and average weight gain 3 months after admission. Factors associated with growth faltering in the prevention group were explored using logistic regression. Default rates for the severely wasted, moderately wasted, and prevention group were 12.7%, 20.4%, and 22.1%, respectively. Recovery rate was 42.4% for the severely wasted and 61.3% for the moderately wasted. For the moderately wasted, mean weight gain was 2.1 g/kg/day, 95% confidence interval (CI) [1.6, 2.6], and 4.5 g/kg/day for the severely wasted, 95% CI [3.1, 5.9]. Among prevention group children, 3.6% faltered into wasting-3.2% into moderate and 0.4% into severe. The paper gives insights into ways in which ICDS and MCGM can successfully integrate large-scale community-based acute malnutrition programming.

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.

Community management of acute malnutrition (CMAM) programme in Pakistan effectively treats children with uncomplicated severe wasting.

Severe wasting is the most widespread form of severe acute malnutrition, affecting an estimated 17 million children globally. This analysis assesses the effectiveness of Pakistan's community management of acute malnutrition (CMAM) programme. We conducted a retrospective case series analysis of 32,458 children aged 6-59 months who were admitted to the programme with a mid-upper arm circumference (MUAC) < 115 mm (January 1-December 31, 2014). We found that at admission, 59.6% of the children were girls and 87.4% were in the age group 6-23 months old. While in the programme, 120 children (0.4%) died, 3,456 (10.6%) defaulted, and 28,882 (89.0%) were discharged after a mean length of stay of 69.3 ± 25.7 days. Children's mean weight gain while in the programme was 3.2 ± 2.7 g/kg body weight/day. At discharge, 28,499 children (98.7% of discharged) had recovered (MUAC ≥ 125 mm). The odds of death were significantly higher among children with weight-for-height (WHZ) < -3 and/or height-for-age (HAZ) < -2 at admission. The odds of recovery on the basis of MUAC ≥125 mm were higher among children with HAZ ≥ -2 at admission. The odds of recovery on the basis of WHZ ≥ -2 were significantly higher among children with WHZ ≥ -3 and/or HAZ < -2 at admission. Pakistan's CMAM programme is effective in achieving good survival and recovery rates. Population-level impact could be increased by giving priority to children 6-23 months old and children with multiple anthropometric failure and by scaling up CMAM in the provinces and areas where the risk, prevalence, and/or burden of severe acute malnutrition is highest.

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.