Photobiomodulation therapy moderates cancer cachexia-associated muscle wasting through activating PI3K/AKT/FoxO3a pathway.

Cancer cachexia-associated muscle wasting as a multifactorial wasting syndrome, is an important factor affecting the long-term survival rate of tumor patients. Photobiomodulation therapy (PBMT) has emerged as a promising tool to cure and prevent many diseases. However, the effect of PBMT on skeletal muscle atrophy during cancer progression has not been fully demonstrated yet. Here, we found PBMT alleviated the atrophy of myotube diameter induced by cancer cells in vitro, and prevented cancer-associated muscle atrophy in mice bearing tumor. Mechanistically, the alleviation of muscle wasting by PBMT was found to be involved in inhibiting E3 ubiquitin ligases MAFbx and MuRF-1. In addition, transcriptomic analysis using RNA-seq and GSEA revealed that PI3K/AKT pathway might be involved in PBMT-prevented muscle cachexia. Next, we showed the protective effect of PBMT against muscle cachexia was totally blocked by AKT inhibitor in vitro and in vivo. Moreover, PBMT-activated AKT promoted FoxO3a phosphorylation and thus inhibiting the nucleus entry of FoxO3a. Lastly, in cisplatin-treated muscle cachexia model, PBMT had also been shown to ameliorate muscle atrophy through enhancing PI3K/AKT pathway to suppress MAFbx and MuRF-1 expression. These novel findings revealed that PBMT could be a promising therapeutic approach in treating muscle cachexia induced by cancer.

Trends in social determinants of inequality in child undernutrition from the Ethiopian Demographic and Health Surveys, 2005-2016.

BACKGROUND: While child undernutrition has been eliminated in some middle-income countries, it remains highly prevalent in sub-Sahara African (SSA) and South Asian regions, and is disproportionately concentrated among the poor. In this study, we estimated trends in child undernutrition by social determinants and related risks from wealth inequality in Ethiopia, from 2005 to 2016. METHOD: We analyzed data from three consecutive surveys (2005, 2011, and 2016) from the Ethiopian Demographic and Health Survey. First, we estimated trends in the prevalence of childhood undernutrition variables (stunting, underweight, and wasting) and social determinants (household wealth status, education level, place of residence, and administrative regions). Then we assessed evidence of undernutrition by wealth-related inequality with concentration curves (visual) and concentration indeces (quantitative). A multilevel mixed-effect Poisson regression model was used to identify predictors of undernutrition variables expressed as covariate-adjusted rate ratios, with 95% confidence intervals (RRs, 95%CI). RESULT: A total of 23,934 mother-child pairs were obtained from the three surveys. The average prevalence decreased by 12.4 percentage points for stunting (from 50.8 to 38.4%, P<0.01), 9.5 percentage points for underweight (33.2% to23.7%, P<0.01), and 2.1 percentage points for wasting (12.2% to10.1%, P<0.01). There was persistent and statistically evidence of wealth inequality in stunting, underweight, and wasting (concentration indeces of -0.2 to -0.04, all P values <0.05). Stunting, underweight, and wasting variables were associated with male sex of the child (RR 0.94, 0.95, 0.85, all P-values <0.01) recent diarrhea (RR 1.18, 1.27, 1.37, all P-values <0.01), secondary education status of the mother (RR 0.66, 0.57, 0.61, all P-values < 0.057), increasing wealth index (richest) (RR 0.73, 0.70, 0.50, all P-values < 0.05), and having no toilet facility (RR 1.16, 1.22, 1.18, all P-values < 0.05). CONCLUSION: Despite the decreased burden of stunting and underweight, the prevalence of wasting remained relatively unchanged in Ethiopia from 2005 to 2016. Moreover, wealth-related inequality in child undernutrition increased for most of the child undernutrition indicators during this period. Social determinants of child undernutrition warrant urgent implementation of strategies to reduce their health impacts in SSA.

CT-based screening of sarcopenia and its role in cachexia syndrome in pancreatic cancer.

Since computed tomography (CT) is a part of standard diagnostic protocol in pancreatic ductal adenocarcinoma (PDAC), we have evaluated the value of CT for sarcopenia screening in patients with PDAC, intending to expand the diagnostic value of tomographic studies. In our study, we included 177 patients with available CT images. Two groups were formed: Group 1 consisted of 117 patients with PDAC in various locations and stages and Group 2, or the control group, consisted of 60 "nominally healthy" patients with other somatic non-oncological diseases. The body mass index (BMI) was defined as a ratio of patient's weight to the square of their height (kg/m2). CT-based body composition analysis was performed using commercially available software with evaluation of sarcopenia using skeletal muscle index (SMI, cm2/m2). Based on the SMI values, sarcopenia was found in 67.5% of patients (79 out of 117) in the first patient group. It was found more frequently in males (42 out of 56; 75%) than in females (37 out of 61; 60.6%). Additionally, we observed a decrease in muscle mass (hidden sarcopenia) in 79.7% in patients with a normal BMI. Even in overweight patients, sarcopenia was found in 50% (sarcopenic obesity). In patients with reduced BMI sarcopenia was found in all cases (100%). Statistically significant difference of SMI between two groups was revealed for both sexes (p = 0,0001), with no significant difference between groups in BMI. BMI is an inaccurate value for the assessment of body composition as it does not reflect in the details the human body structure. As SMI may correlate with the prognosis, decreased muscle mass- especially "hidden" sarcopenia or sarcopenic obesity- should be reported. The use of CT-based evaluation of sarcopenia and sarcopenic obesity will allow for a better treatment response assessment in patients with cancer cachexia.

Protective effects of hachimijiogan (HJG), a Japanese Kampo medicine, on cancer cachectic muscle wasting in mice.

Myogenesis is required to generate skeletal muscle tissue and to maintain skeletal muscle mass. Decreased myogenesis under various pathogenic conditions results in muscular atrophy. Through a small screening of Japanese traditional (Kampo) medicines, hachimijiogan (HJG) was shown to promote the myogenic differentiation of C2C12 myoblasts through the upregulation of myogenin. In tumor-bearing cancer-cachectic mice, HJG was also found to have a protective effect against cancer-cachectic muscle wasting. This effect was significant when HJG was administered in combination with aerobic exercise by treadmill running. Moreover, HJG ameliorated the cellular atrophy of C2C12 myotubes induced by treatment with conditioned medium derived from a colon-26 cancer cell culture. In addition, HJG suppressed H2O2-dependent myotube atrophy, suggesting that HJG could reverse the atrophic phenotypes by eliminating reactive oxygen species.

Prevalence and factors associated with undernutrition among children under the age of five years in Benin.

BACKGROUND: Benin ranks as one of the countries in the world with an alarmingly high prevalence of stunting, wasting, and underweight in children under five years. However, limited studies have examined the factors associated with the prevalence of these undernutrition indicators among children under five years in the country. This study aimed to fill this research gap by examining the prevalence rates and factors associated with stunting, wasting, and underweight among this specific population of interest. METHODS: This quantitative study utilised data from the most recent Benin Demographic and Health Survey (BDHS) conducted in 2017-18. The survey employed a nationally representative cross-sectional design and utilised a two-stage stratified cluster sampling technique to select participants. The study included a sample of 13,589 children under the age of five years. The main analytical approach employed was binary logistic regression, which was used to explore the associations between undernutrition (the combined outcome variable representing stunting, wasting, and underweight) and various socio-demographic factors. RESULTS: The combined prevalence of stunting, wasting, and underweight among children under five years in Benin during the 2017-18 survey period was 14.95%. Several factors were significantly associated with these indicators of undernutrition, including female gender (AOR = 0.71, 95% CI = 0.59-0.85), birth weight of 4.1 kg and over (AOR = 0.26, 95% CI = 0.14-0.48), multiple births (AOR = 3.22, 95% CI = 2.11-4.91), and a child's experience of diarrhoea (AOR = 1.76, 95% CI = 1.40-2.20). Furthermore, the prevalence of these undernutrition indicators was higher among children whose mothers had lower levels of education (AOR = 0.82, 95% CI = 0.01-0.42) and were unmarried (AOR = 0.67, 95% CI = 0.49-0.93). CONCLUSIONS: This present study confirms that undernutrition rates are elevated in Benin and are closely linked to perinatal factors such as birth weights and multiple births, postnatal health conditions including diarrheal episodes, and socio-demographic determinants such as a child's gender, maternal education level, and marital status. Therefore, there is the need to consider specific modifiable factors, such as low birth weight, episodes of child diarrhoea, and maternal education as priority targets for child nutrition interventions in Benin.

Is There a Need to "Modernize" and "Simplify" the Diagnostic Criteria of Protein-Energy Wasting?

Protein energy wasting(PEW) is a term that most nephrologists used to define nutritional disorders in patients with acute kidney injury and chronic kidney disease. Although this nomenclature is well implemented in the field of nephrology, the use of other terms such as cachexia or malnutritionin the majority of chronic diseases can induce confusion regarding the definition and interpretation of these terms. There is ample evidence in the literature that the pathways involved in cachexia/malnutrition and PEW are common. However, in kidney diseases, there are pathophysiological conditions such as accumulation of uremic toxins, and the use of dialysis, which may induce a phenotypic specificity justifying the original term PEW. In light of the latest epidemiologic studies, the criteria for PEW used in 2008 probably need to be updated. The objective of this review is to summarize the main mechanisms involved in cachexia/malnutrition and PEW. We discuss the need to modernize and simplify the current definition and diagnostic criteria of PEW. We consider the interest of proposing a specific nomenclature of PEW for children and elderly patients with kidney diseases.

Sea star wasting syndrome reaches the high Antarctic: Two recent outbreaks in McMurdo Sound.

Sea star wasting syndrome (SSWS) can cause widespread mortality in starfish populations as well as long-lasting changes to benthic community structure and dynamics. SSWS symptoms have been documented in numerous species and locations around the world, but to date there is only one record of SSWS from the Antarctic and this outbreak was associated with volcanically-driven high temperature anomalies. Here we report outbreaks of SSWS-like symptoms that affected ~30% of individuals of Odontaster validus at two different sites in McMurdo Sound, Antarctica in 2019 and 2022. Unlike many SSWS events in other parts of the world, these outbreaks were not associated with anomalously warm temperatures. Instead, we suggest they may have been triggered by high nutrient input events on a local scale. Although the exact cause of these outbreaks is not known, these findings are of great concern because of the keystone role of O. validus and the slow recovery rate of Antarctic benthic ecosystems to environmental stressors.

Disease-related malnutrition with inflammation and cachexia.

In 2010, the definition of cachexia was jointly developed by the European Society for Clinical Nutrition and Metabolism (ESPEN) Special Interest Groups (SIG) "Cachexia-anorexia in chronic wasting diseases" and "Nutrition in geriatrics". Cachexia was considered as a synonym of disease-related malnutrition (DRM) with inflammation by the ESPEN guidelines on definitions and terminology of clinical nutrition. Starting from these concepts and taking into account the available evidence the SIG "Cachexia-anorexia in chronic wasting diseases" conducted several meetings throughout 2020-2022 to discuss the similarities and differences between cachexia and DRM, the role of inflammation in DRM, and how it can be assessed. Moreover, in line with the Global Leadership Initiative on Malnutrition (GLIM) framework, in the future the SIG proposes to develop a prediction score to quantify the individual and combined effect(s) of multiple muscle and fat catabolic mechanisms, reduced food intake or assimilation and inflammation, which variably contribute to the cachectic/malnourished phenotype. This DRM/cachexia risk prediction score could consider the factors related to the direct mechanisms of muscle catabolism separately from those related to the reduction of nutrient intake and assimilation. Novel perspectives in the field of DRM with inflammation and cachexia were identified and described in the report.

Two decades of change in sea star abundance at a subtidal site in Puget Sound, Washington.

Long-term datasets can reveal otherwise undetectable ecological trends, illuminating the historical context of contemporary ecosystem states. We used two decades (1997-2019) of scientific trawling data from a subtidal, benthic site in Puget Sound, Washington, USA to test for gradual trends and sudden shifts in total sea star abundance across 11 species. We specifically assessed whether this community responded to the sea star wasting disease (SSWD) epizootic, which began in 2013. We sampled at depths of 10, 25, 50 and 70 m near Port Madison, WA, and obtained long-term water temperature data. To account for species-level differences in SSWD susceptibility, we divided our sea star abundance data into two categories, depending on the extent to which the species is susceptible to SSWD, then conducted parallel analyses for high-susceptibility and moderate-susceptibility species. The abundance of high-susceptibility sea stars declined in 2014 across depths. In contrast, the abundance of moderate-susceptibility species trended downward throughout the years at the deepest depths- 50 and 70 m-and suddenly declined in 2006 across depths. Water temperature was positively correlated with the abundance of moderate-susceptibility species, and uncorrelated with high-susceptibility sea star abundance. The reported emergence of SSWD in Washington State in the summer of 2014 provides a plausible explanation for the subsequent decline in abundance of high-susceptibility species. However, no long-term stressors or mortality events affecting sea stars were reported in Washington State prior to these years, leaving the declines we observed in moderate-susceptibility species preceding the 2013-2015 SSWD epizootic unexplained. These results suggest that the subtidal sea star community in Port Madison is dynamic, and emphasizes the value of long-term datasets for evaluating patterns of change.

Tumor loss-of-function mutations in STK11/LKB1 induce cachexia.

Cancer cachexia (CC), a wasting syndrome of muscle and adipose tissue resulting in weight loss, is observed in 50% of patients with solid tumors. Management of CC is limited by the absence of biomarkers and knowledge of molecules that drive its phenotype. To identify such molecules, we injected 54 human non-small cell lung cancer (NSCLC) lines into immunodeficient mice, 17 of which produced an unambiguous phenotype of cachexia or non-cachexia. Whole-exome sequencing revealed that 8 of 10 cachexia lines, but none of the non-cachexia lines, possessed mutations in serine/threonine kinase 11 (STK11/LKB1), a regulator of nutrient sensor AMPK. Silencing of STK11/LKB1 in human NSCLC and murine colorectal carcinoma lines conferred a cachexia phenotype after cell transplantation into immunodeficient (human NSCLC) and immunocompetent (murine colorectal carcinoma) models. This host wasting was associated with an alteration in the immune cell repertoire of the tumor microenvironments that led to increases in local mRNA expression and serum levels of CC-associated cytokines. Mutational analysis of circulating tumor DNA from patients with NSCLC identified 89% concordance between STK11/LKB1 mutations and weight loss at cancer diagnosis. The current data provide evidence that tumor STK11/LKB1 loss of function is a driver of CC, simultaneously serving as a genetic biomarker for this wasting syndrome.

Emerging Mechanisms of Skeletal Muscle Homeostasis and Cachexia: The SUMO Perspective.

Mobility is an intrinsic feature of the animal kingdom that stimulates evolutionary processes and determines the biological success of animals. Skeletal muscle is the primary driver of voluntary movements. Besides, skeletal muscles have an immense impact on regulating glucose, amino acid, and lipid homeostasis. Muscle atrophy/wasting conditions are accompanied by a drastic effect on muscle function and disrupt steady-state muscle physiology. Cachexia is a complex multifactorial muscle wasting syndrome characterized by extreme loss of skeletal muscle mass, resulting in a dramatic decrease in life quality and reported mortality in more than 30% of patients with advanced cancers. The lack of directed treatments to prevent or relieve muscle loss indicates our inadequate knowledge of molecular mechanisms involved in muscle cell organization and the molecular etiology of cancer-induced cachexia (CIC). This review highlights the latest knowledge of regulatory mechanisms involved in maintaining muscle function and their deregulation in wasting syndromes, particularly in cachexia. Recently, protein posttranslational modification by the small ubiquitin-like modifier (SUMO) has emerged as a key regulatory mechanism of protein function with implications for different aspects of cell physiology and diseases. We also review an atypical association of SUMO-mediated pathways in this context and deliberate on potential treatment strategies to alleviate muscle atrophy.

Progressive development of melanoma-induced cachexia differentially impacts organ systems in mice.

Cachexia is a systemic wasting syndrome that increases cancer-associated mortality. How cachexia progressively and differentially impacts distinct tissues is largely unknown. Here, we find that the heart and skeletal muscle undergo wasting at early stages and are the tissues transcriptionally most impacted by cachexia. We also identify general and organ-specific transcriptional changes that indicate functional derangement by cachexia even in tissues that do not undergo wasting, such as the brain. Secreted factors constitute a top category of cancer-regulated genes in host tissues, and these changes include upregulation of the angiotensin-converting enzyme (ACE). ACE inhibition with the drug lisinopril improves muscle force and partially impedes cachexia-induced transcriptional changes, although wasting is not prevented, suggesting that cancer-induced host-secreted factors can regulate tissue function during cachexia. Altogether, by defining prevalent and temporal and tissue-specific responses to cachexia, this resource highlights biomarkers and possible targets for general and tissue-tailored anti-cachexia therapies.

How Can Nutrition Research Better Reflect the Relationship Between Wasting and Stunting in Children? Learnings from the Wasting and Stunting Project.

Childhood wasting and stunting affect large numbers of children globally. Both are important risk factors for illness and death yet, despite the fact that these conditions can share common risk factors and are often seen in the same child, they are commonly portrayed as relatively distinct manifestations of undernutrition. In 2014, the Wasting and Stunting project was launched by the Emergency Nutrition Network. Its aim was to better understand the complex relationship and associations between wasting and stunting and examine whether current separations that were apparent in approaches to policy, financing, and programs were justified or useful. Based on the project's work, this article aims to bring a wasting and stunting lens to how research is designed and financed in order for the nutrition community to better understand, prevent, and treat child undernutrition. Discussion of lessons learnt focuses on the synergy and temporal relationships between children's weight loss and linear growth faltering, the proximal and distal factors that drive diverse forms of undernutrition, and identifying and targeting people most at risk. Supporting progress in all these areas requires research collaborations across interest groups that highlight the value of research that moves beyond a focus on single forms of undernutrition, and ensures that there is equal attention given to wasting as to other forms of malnutrition, wherever it is present.

Phytochemicals: A potential therapeutic intervention for the prevention and treatment of cachexia.

Cachexia, a multifactorial and often irreversible wasting syndrome, is often associated with the final phase of several chronic disorders. Although cachexia is characterized by skeletal muscle wasting and adipose tissue loss, it is a syndrome affecting different organs, which ultimately results in systemic complications and impaired quality of life. The pathogenesis and underlying molecular mechanisms of cachexia are not fully understood, and currently there are no effective standard treatments or approved drug therapies to completely reverse cachexia. Moreover, adequate nutritional interventions alone cannot significantly improve cachexia. Other approaches to ameliorate cachexia are urgently needed, and thus, the role of medicinal plants has received considerable importance in this respect due to their beneficial health properties. Increasing evidence indicates great potential of medicinal plants and their phytochemicals as an alternative and promising treatment strategy to reduce the symptoms of many diseases including cachexia. This article reviews the current status of cachexia, the molecular mechanisms of primary events driving cachexia, and state-of-the-art knowledge that reports the preventive and therapeutic activities of multiple families of phytochemical compounds and their pharmacological mode of action, which may hold promise as an alternative treatment modality for the management of cachexia. Based on our review of various in vitro and in vivo models of cachexia, we would conclude that phytochemicals may have therapeutic potential to attenuate cachexia, although clinical trials are required to unequivocally confirm this premise.

Wasting syndrome and associated factors in hospitalized older people.

Wasting syndrome (WS) is characterized by clinically important unintentional weight loss >5 % in six to 12 months. This syndrome is responsible for a significant portion of hospitalizations throughout the world and is an important indicator of serious diseases, especially in individuals with 60 years of age or older. The aim of the present study was to investigate WS and associated factors in hospitalized older people. An observational cross-sectional study was developed at a university hospital in Brazil with male and female patients ≥60 years of age. WS was considered in the occurrence of unintentional weight loss of 10 % in 12 months, 7.5 % in six months or >5 % in three months. Data were collected on sociodemographic, clinical, lifestyle, nutritional and biochemical characteristics. This study received approval from the local institutional review board and all participants signed a statement of informed consent. The sample was composed of 178 older people with a mean age of 70.0 ± 8.0 years. The prevalence of WS was 45.5 %. WS was associated with the following clinical variables: conservative CKD (p = 0.007), dysphagia (p = 0.035), dementia (p = 0.017), anorexia (p < 0.001), fatigue (p = 0.001), functional dependence (measured using the Barthel Index) (p = 0.001) and medications that cause malabsorption (p = 0.020); the following nutritional variables: body mass index (p < 0.001), low calf circumference (p < 0.001), low muscle strength (p = 0.001), low muscle mass (p < 0.001) and undernourishment or risk of malnutrition (evaluated using the Mini Nutritional Assessment); and the following biochemical variables: high CRP (p = 0.027), hypoalbuminemia (p = 0.005) and anemia (p < 0.001). The prevalence of WS was high among the hospitalized older people in the present sample and was associated with clinical and biochemical aspects as well as all nutritional variables analyzed. In contrast, lifestyle and sociodemographic characteristics were not associated with wasting syndrome.

A preponderance of gastrointestinal cancer patients transition into cachexia syndrome.

BACKGROUND: Cancer cachexia is frequently documented by self-reported, single time-point weight histories. This approach lacks the granularity needed to fully elucidate the progression of cachexia syndrome. This study aimed to longitudinally assess body weight changes pre- and post-cancer diagnosis in gastrointestinal (GI) cancer patients. METHODS: Body weights and relevant clinical data recorded in the electronic health record 12 months pre- and post-GI cancer (colorectal, gastroesophageal, hepatobiliary and pancreatic) diagnosis were extracted. Weight loss was categorized by the International Consensus Definition for cachexia. RESULTS: A total of 879 patients were included in the final cohort including patients diagnosed with colorectal (n = 317), hepatocellular (n = 185), biliary (n = 72), pancreatic (n = 186) or gastroesophageal (n = 119) cancer. Stage of disease was equally distributed. Patients without cachexia at diagnosis (n = 608) remained weight stable during the 12 months pre-diagnosis (+0.5 ± 0.5% body weight; P = 0.99). Patients with cachexia at diagnosis (n = 271) remained weight stable 6 to 12 months prior to diagnosis (+0.4 ± 0.8%; P > 0.9999) and lost 8.7 ± 0.6% (P < 0.0001) within the 6 months pre-diagnosis. Patients without cachexia at diagnosis lost more weight post-diagnosis (6.3 ± 0.6%) than patients with cachexia at diagnosis (4.7 ± 1.0%; P = 0.01). Pre-diagnosis weight trajectories did not differ between primary malignancies or stage of disease in patients without or with cachexia at diagnosis (all P ≥ 0.05). Post-diagnosis weight trajectories did differ by primary malignancy (P ≤ 0.0002) and stage (P < 0.0001). In both patients without and with cachexia at diagnosis, colorectal patients lost the least amount of weight post-diagnosis and gastroesophageal patients lost the most amount of weight post-diagnosis. Stage 4 patients without or with cachexia at diagnosis lost the most weight post-diagnosis (P ≤ 0.0003). Regardless of cachexia status at diagnosis, patients lost more weight when treated with systemic therapy (7.1 ± 0.7%; P < 0.0001; n = 419) or radiation therapy (8.4 ± 1.4%; P = 0.02; n = 116) compared to those who did not. Patients who did not have surgery lost more weight post-diagnosis (7.6 ± 1.1%; P < 0.0001; n = 355) compared to those who did have surgery. By 12 months post-diagnosis, 83% of the surviving GI cancer patients in this cohort had transitioned into cachexia syndrome. CONCLUSIONS: Significant weight loss in patients with GI cancer cachexia at diagnosis initiates at least 6 months prior to diagnosis, and most patients will transition into cachexia syndrome post-diagnosis, regardless of pre-diagnosis weight change and stage of disease. These findings punctuate the importance of weight surveillance in cancer detection and earlier palliative interventions post-diagnosis in the GI cancer patient population.

Fever of Unknown Origin, Wasting Syndrome and Bone Marrow Involvement: A Leprosy Case Report.

Mycobacterium leprae, the etiologic agent of leprosy, is an acid-fast-staining and slow-growing bacilli that infect macrophages and Schwann cells individually or through forming globi. The clinical presentation of leprosy is broad and depends on the host immune response. We report a case of a 42-year-old Brazilian man presenting with fever of unknown origin (FUO), anemia, wasting syndrome, and neuropathy. The diagnosis of lepromatous leprosy was made after an extensive investigation revealed the presence of M. leprae in the bone marrow. Bone marrow involvement in leprosy is rare and some authors believe the presence of M. leprae in the bone marrow can act as a reservoir of the disease facilitating future relapses. It is important to investigate bone marrow involvement in leprosy, especially when the patient presents with cytopenias and positive epidemiologic history.

A Prospective, Cohort Study of the Effect of Acute and Chronic Malnutrition on Length of Stay in Children Having Surgery in Rwanda.

BACKGROUND: Malnutrition is common in pediatric surgical patients, but there are little data from low-income countries that estimate the association of malnutrition with surgical outcomes. We aimed to determine the prevalence of malnutrition and its association with length of stay (LOS) among pediatric surgical patients in Kigali, Rwanda. METHODS: We conducted a prospective observational cohort study. We enrolled surgical patients between 1 month and 15 years of age. We measured the association of acute malnutrition (wasting) and chronic malnutrition (stunting) with postoperative LOS using log-gamma regression to account for the skewed LOS distribution. Adjustment was made for sex, age, elective versus emergency surgery, household income, and American Society of Anesthesiologists (ASA) classification. RESULTS: Of 593 children, 124 children (21.2%) had acute malnutrition (wasting) with 39 (6.6%) severely wasted. A total of 160 (26.9%) children had chronic malnutrition (stunting), with 81 (13.7%) severely stunted. Median (interquartile range [IQR]) LOS after surgery was 2 (1-5) days for children with mild/no wasting, 6 (2.5-12.5) days for children with moderate wasting, and 6 (2-15) days with severe wasting. Median (IQR) LOS after surgery was 2 (1-6) days for children with mild/no stunting, 3 (1-3) days for children with moderate stunting, and 5 (2.3-11.8) days with severe stunting malnutrition. After adjustment for confounders, the moderate wasting was associated with increased LOS, with ratio of means (RoM), 1.6; 95% confidence interval [CI], 1.3-2.0; P < .0001. Severe wasting was not associated with increased LOS (RoM, 1.3; 95% CI, 0.9-1.7; P = .12). Severe, but not moderate, stunting was associated with increased LOS (RoM, 1.9; 1.5-2.4; P < .0001). CONCLUSIONS: Malnutrition is prevalent in >20% of children presenting for surgery and associated with increased LOS after surgery, even after accounting for individual and family-level confounders. Although some aspects of malnutrition may relate to the surgical condition, severe malnutrition may represent a modifiable social risk factor that could be targeted to improve postoperative outcomes and resource use. Severely stunted children should be identified as at risk of having delayed recovery after surgery.

Wasting condition as a marker for severe disease in pediatric Crohn's disease.

ABSTRACT: Several studies have shown an association between sarcopenia and clinical outcomes in patients with Crohn's disease (CD). However, studies have shown different results, and the association between prognosis and wasting conditions in pediatric patients with CD is uncertain. In this study, we evaluated the clinical significance of wasting in pediatric CD patients.We retrospectively analyzed data on wasting syndrome in patients diagnosed with CD at the Pediatric Department of Gachon University Gil Medical Center between January 1995 and January 2018.Of 105 patients diagnosed with CD, 39.0% were classified into the wasting group (weight-for-age z-score ≤-1) and 61.0% into the nonwasting group (weight-for-age z-score >-1). Height-for-age and body mass index-for-age z-scores at the time of diagnosis were significantly associated with wasting (P < .001 and P < .001, respectively). Additionally, wasting was significantly associated with low levels of hemoglobin (P < .001), high levels of inflammatory markers, including C-reactive protein (P = .005) and erythrocyte sedimentation rate (P = .04), and a smaller surface area of the gluteus maximus muscle (P < .001). Interestingly, since the site of CD involvement and other markers for nutrition did not correlate with wasting syndrome, wasting appears to be a marker for the severity of pediatric CD. Lastly, the wasting group tended to have a greater use of biologic therapy after first-line therapy failed to improve wasting syndrome.Wasting syndrome, including sarcopenia, can serve as a marker for the severity of pediatric CD.

Interdisciplinary management of FGF23-related phosphate wasting syndromes: a Consensus Statement on the evaluation, diagnosis and care of patients with X-linked hypophosphataemia.

X-linked hypophosphataemia (XLH) is the most frequent cause of hypophosphataemia-associated rickets of genetic origin and is associated with high levels of the phosphaturic hormone fibroblast growth factor 23 (FGF23). In addition to rickets and osteomalacia, patients with XLH have a heavy disease burden with enthesopathies, osteoarthritis, pseudofractures and dental complications, all of which contribute to reduced quality of life. This Consensus Statement presents the outcomes of a working group of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases, and provides robust clinical evidence on management in XLH, with an emphasis on patients' experiences and needs. During growth, conventional treatment with phosphate supplements and active vitamin D metabolites (such as calcitriol) improves growth, ameliorates leg deformities and dental manifestations, and reduces pain. The continuation of conventional treatment in symptom-free adults is still debated. A novel therapeutic approach is the monoclonal anti-FGF23 antibody burosumab. Although promising, further studies are required to clarify its long-term efficacy, particularly in adults. Given the diversity of symptoms and complications, an interdisciplinary approach to management is of paramount importance. The focus of treatment should be not only on the physical manifestations and challenges associated with XLH and other FGF23-mediated hypophosphataemia syndromes, but also on the major psychological and social impact of the disease.