Comparison of bioelectrical impedance analysis and computed tomography for the assessment of muscle mass in patients with gastric cancer.

BACKGROUND: Low muscle mass was significantly correlated with poor clinical outcomes in cancer patients. This study aimed to compare the differences between bioelectrical impedance analysis (BIA) and computed tomography (CT) in measuring skeletal muscle mass and detecting low muscle mass in patients with gastric cancer (GC). METHOD: This cross-sectional study included a total of 302 consecutive patients diagnosed with GC at our institution from October 2021 to March 2023. CT images were analyzed at the L3 level to obtain the cross-sectional area of skeletal muscle, which was subsequently used for calculating whole-body skeletal muscle mass via the Shen equation and skeletal muscle tissue density. BIA was utilized to measure skeletal muscle mass using the manufacturer's proprietary algorithms. Skeletal muscle mass (kg) was divided by height squared (m2) to obtain skeletal muscle index (SMI, kg/m2). Pearson's correlation coefficient was performed to assess the correlation between SMI measured by BIA and CT. The agreement between the two methods was assessed using Bland-Altman analyses. The clinically acceptable agreement was defined as the 95% limits of agreement (LOA) for the percentage bias falling within ± 10%. The area under the receiver operating characteristic curve (AUC) was used to evaluate the performance of BIA in identifying low muscle mass. RESULTS: A total of 59 patients (19.5%) were identified as having low muscle mass based on CT analysis, whereas only 19 patients (6.3%) met the criteria for low muscle mass according to BIA analysis. BIA-measured SMI showed a strong positive correlation with CT-measured SMI in all patients (r = 0.715, P < 0.001). With Bland-Altman analysis, there was a significant mean bias of 1.18 ± 0.96 kg/m2 (95% CI 1.07-1.29, P < 0.001) between SMI measured by BIA and CT. The 95% LOA for the percentage bias ranged from -7.98 to 33.92%, which exceeded the clinically acceptable range of ± 10%. A significant difference was observed in the mean bias of SMI measured by BIA and CT between patients with and without GLIM malnutrition (1.42 ± 0.91 kg/m2 versus 0.98 ± 0.96 kg/m2, P < 0.001). The cut-off values for BIA-measured SMI in identifying low muscle mass using CT as the reference were 10.11 kg/m2 for males and 8.71 kg/m2 for females (male: AUC = 0.840, 95% CI: 0.772-0.908; female: AUC = 0.721, 95% CI: 0.598-0.843). CONCLUSIONS: Despite a significant correlation, the values of skeletal muscle mass obtained BIA and CT cannot be used interchangeably. The BIA method may overestimate skeletal muscle mass in GC patients compared to CT, especially among those with GLIM malnutrition, leading to an underestimation of low muscle mass prevalence.

Associations among Preoperative Malnutrition, Muscle Loss, and Postoperative Walking Ability in Intertrochanteric Fractures: A Retrospective Study.

Sarcopenia and malnutrition are increasing in older adults and are reported risk factors for functional impairment after hip fracture surgery. This study aimed to investigate the associations between skeletal muscle mass loss, malnutrition, and postoperative walking ability in patients with hip fracture. We retrospectively reviewed patients who underwent intertrochanteric fracture surgery at our institute. The psoas muscle index, controlling nutritional status score, and functional ambulation category (FAC) were used to evaluate skeletal muscle mass, nutritional status, and walking ability, respectively. Six months after surgery, walking ability was assessed as either "gait disturbance" or "independent gait". Multivariate binomial logistic regression analysis, with skeletal muscle mass, nutritional status, and other factors, was used to predict the risk of being assigned to the gait disturbance group. This study included 95 patients (mean age, 85.2 years; 70 women). Sixty-six patients had low skeletal muscle mass, 35 suffered from malnutrition, and 28 had both. Malnutrition and low skeletal muscle mass were significantly associated with postoperative gait disturbance (FAC < 3). Preoperative low skeletal muscle mass and malnutrition were risk factors for postoperative poor walking ability. Further preventive interventions focusing on skeletal muscle mass and nutritional status are required.

Substantial Loss of Skeletal Muscle Mass Occurs After Femoral Fragility Fracture.

BACKGROUND: Femoral fragility fractures in older adults can result in devastating loss of physical function and independence. Skeletal muscle atrophy likely contributes to disability. The purpose of this study was to characterize the change in skeletal muscle mass, investigate the relationship with malnutrition and physical function, and identify risk factors for skeletal muscle loss. METHODS: Adults ≥65 years of age who were treated with operative fixation of an isolated femoral fragility fracture were enrolled in this multicenter, prospective observational study. Skeletal muscle mass was assessed within 72 hours of admission using multifrequency bioelectrical impedance analysis, which was repeated at 6 weeks, 3 months, and 6 months. Sarcopenia was defined by sex-specific cutoffs for the appendicular skeletal muscle mass index. The Mini Nutritional Assessment was used to measure nutritional status at the time of injury. Physical function was measured using the Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function domain. Linear mixed models were used to evaluate changes in skeletal muscle mass and PROMIS Physical Function scores over time and to evaluate factors associated with skeletal muscle mass changes. RESULTS: Ninety participants (74% female) with a mean age of 77.6 ± 9.0 years were enrolled. At the time of injury, 30 (33%) were sarcopenic and 44 (49%) were at risk for malnutrition or had malnutrition. Older age was associated with lower skeletal muscle mass (age of ≥75 versus <75 years: least squares mean [and standard error], -3.3 ± 1.6 kg; p = 0.042). From the time of injury to 6 weeks, participants lost an average of 2.4 kg (9%) of skeletal muscle mass (95% confidence interval [CI] = ‒3.0 to ‒1.8 kg; p < 0.001). This early loss did not recover by 6 months (1.8 kg persistent loss compared with baseline [95% CI = ‒2.5 to ‒1.1 kg]; p < 0.001). Participants with normal nutritional status lost more skeletal muscle mass from baseline to 6 weeks after injury compared with those with malnutrition (1.3 kg more loss [standard error, 0.6 kg]; p = 0.036). A 1-kg decrease in skeletal muscle mass was associated with an 8-point decrease in the PROMIS Physical Function (model parameter estimate, 0.12 [standard error, 0.04]; p = 0.002). CONCLUSIONS: We found that older adults with femoral fragility fractures lost substantial skeletal muscle mass and physical function. Participants with adequate baseline nutrition actually lost more muscle mass than those who were malnourished, indicating that future investigations of interventions to prevent muscle loss should focus on older adults regardless of nutritional status. LEVEL OF EVIDENCE: Prognostic Level II . See Instructions for Authors for a complete description of levels of evidence.

Association between nutritional status and platelet-to-lymphocyte ratio in patients with hepatocellular carcinoma undergoing transcatheter arterial chemoembolization.

Introduction: Introduction: nutritional status and platelet-to-lymphocyte ratio (PLR) have been found to be associated with prognosis in patients with hepatocellular carcinoma (HCC) undergoing transcatheter arterial chemoembolization (TACE). Objectives: to evaluate the association between nutritional status and PLR in patients with HCC undergoing TACE. Methods: a total of 152 HCC patients received TACE were enrolled. The nutritional status was evaluated by Patient-Generated Subjective Global Assessment (PG-SGA). Patients with PG-SGA A and PG-SGA (B or C) were classified as the well-nourished and malnourished groups. Results: according to the PG-SGA, 130 (85.5 %) patients were malnourished. The median PLR was significantly different between well-nourished and malnourished groups (p = 0.008). A positive correlation was found between PLR and PG-SGA score (r = -0.265, p = 0.001). The optimal PLR cutoff value was 102.165 to predict malnutrition, with a sensitivity of 65.4 %, specificity of 72.7 %, and an area under the curve (AUC) of 0.677 (95 % confidence interval (CI): 0.550-0.804; p = 0.008). A logistic stepwise regression model showed that the PLR was associated with nutritional status in Model 1 without adjustment, as well as if adjusted by age, sex, type of TACE (c-TACE/DEB-TACE) and Child-Pugh stage (odds ratio, 0.190; 95 % CI: 0.062-0.582; p = 0.004). Conclusions: nutritional status measured by PG-SGA was significantly associated with PLR in patients with HCC undergoing TACE.

Introducción: Introducción: se ha encontrado que el estado nutricional y el índice plaquetas-linfocitos (PLR) se asocian con el pronóstico en pacientes con carcinoma hepatocelular (CHC) sometidos a quimioembolización transarterial (TACE). Objetivos: evaluar la asociación entre el estado nutricional y la PLR en pacientes con CHC sometidos a TACE. Métodos: se evaluaron 152 pacientes con CHC que recibieron TACE. El estado nutricional fue evaluado por Evaluación Global Subjetiva Generada por el Paciente (PG-SGA). Los pacientes con PG-SGA A y PG-SGA (B o C) se clasificaron como los grupos bien nutridos y desnutridos. Resultados: según la PG-SGA, 130 (85,5 %) pacientes estaban desnutridos. La mediana de PLR fue significativamente diferente entre los grupos bien nutridos y desnutridos (p = 0,008). Se encontró una correlación positiva entre PLR y la puntuación PG-SGA (r = -0,265, p = 0,001). El valor de corte óptimo de PLR fue de 102,165 para predecir la malnutrición, con una sensibilidad del 65,4 %, una especificidad del 72,7 % y un área bajo la curva (AUC) de 0,677 (intervalo de confianza [IC] del 95 %: 0,550-0,804; p = 0,008). Un modelo de regresión logística escalonada mostró que el PLR se asoció con el estado nutricional en el Modelo 1 sin ajuste, así como cuando se ajustó por edad, sexo, tipo de TACE (c-TACE/DEB-TACE) y etapa Child-Pugh (odds ratio, 0,190; IC 95 %: 0,062-0,582; p = 0,004). Conclusiones: el estado nutricional medido por PG-SGA se asoció significativamente con PLR en pacientes con CHC sometidos a TACE.

Preoperative nutritional evaluation of prostate cancer patients undergoing laparoscopic radical prostatectomy.

BACKGROUND AND OBJECTIVE: Prostate cancer (PCa) is one of the most common malignant tumors in men. Geriatric Nutritional Risk Index (GNRI) is an objective index for evaluating nutritional status of elderly people over 65 years old. The aim of the current study was to explore the correlation and predictive value between GNRI and postoperative recovery and complications in PCa patients undergoing laparoscopic radical prostatectomy (LRP). METHODS: Taking 98 as the GNRI boundary value, 96 PCa patients (aged≥65 y) undergoing LRP in the Department of Urology, Affiliated Hospital of North Sichuan Medical College from January 2018 to December 2020 were grouped into malnutrition group (MNg, 34 patients, 35.4%) and normal nutrition group (NNg, 62 patients, 64.6%). Basic information, laboratory examination indexes, operation conditions, postoperative complications and postoperative recovery indexes of patients were recorded and retrospectively analyzed. Clavien-Dindo Classification System (CDCS) was used to assess postoperative complications. T-test was used to analyze differences between the two groups. ROC curve was generated to determine the predictive value of GNRI for postoperative complications. RESULTS: Percentage of complications was significantly higher in MNg group compared with that in NNg group (P < 0.01). The average grade based on CDCS was significantly lower in NNg group compared with that in MNg group (P < 0.01). Body weight, Body Mass Index (BMI), preoperative hemoglobin value (HGB), serum albumin (ALB) values of MNg and NNg were significantly positively correlated with GNRI (P<0.01). Incidence and severity of postoperative complications of MNg patients were significantly higher compared with those of NNg patients (P<0.05). Average hospitalization cost of MNg patients was higher in MNg patients compared with that of NNg patients (P<0.05). Duration of post-anesthesia care unit (PACU), duration of antibiotic use and duration of indwelling drainage tube were longer in MNg patients compared with those in NNg patients (P<0.05). Furthermore, volume of indwelling drainage tube was higher in MNg patients compared with that in NNg patients (P<0.05). CONCLUSION: GNRI is an effective and reliable tool for evaluation of preoperative nutritional status of prostate cancer patients. The findings showed that GNRI is correlated with postoperative recovery and complications, and is an effective predictive marker.

Chitosan oligosaccharide attenuates endoplasmic reticulum stress-associated intestinal apoptosis via the Akt/mTOR pathway.

Endoplasmic reticulum stress (ERS) and apoptosis are widely considered as essential factors associated with intestinal disorders, whereas nutritional therapeutic approaches targeting ERS may control disease activity. Thus, we focus on the potential benefit of chitosan oligosaccharide (COS) on repressing ERS and ERS-induced apoptosis. In this study, we used the ERS model with tunicamycin (TM)-induced IPEC-J2 cells in vitro and nutrient deprivation-induced ERS in piglets to evaluate the protective mechanism of COS against ERS and ERS-induced apoptosis. The results showed that cells were characterized by activation of the unfolded protein response (UPR) and increased epithelial apoptosis upon exposure to TM. However, these changes were significantly attenuated by COS and the expressions of Akt and mTORC1 were inhibited. Furthermore, a specific inhibitor of mTOR confirmed the suppression of Akt and reduced the activation of the UPR and apoptosis. In vivo, COS protected against nutrient deprivation-induced ERS in the jejunum of piglets, in which the overexpression of the UPR and apoptosis was rescued. Consistently, COS attenuated nutrient deprivation-induced disruption of intestinal barrier integrity and functional capacity. Together, we provided the first evidence that COS could protect against intestinal apoptosis through alleviating severe ERS, which may be related to the inhibition of the Akt/mTOR signaling pathway.

Features Associated With Weight Loss and Growth Stunting for Young Children During Cancer Therapy.

Features associated with malnutrition are poorly elucidated in pediatric cancer care. We aimed to better understand characteristics associated with weight-for-height (WHZ) and height-for-age (HAZ) changes for infants and young children during cancer treatment. This retrospective study included 434 patients diagnosed <3 years old from 2007 to 2015 at a large pediatric cancer center. Patients starting treatment outside our center, those with relapsed or secondary malignancies, or with inaccurate information were excluded. Abstracted weights and heights for a 24-month period after treatment initiation were converted to sex-specific and age-specific z scores. Although not statistically different at baseline, patients with hematologic malignancies gained weight over time, while other tumor types did not. Higher treatment intensity and younger age at diagnosis increased odds of clinically significant weight loss. Older children had higher HAZ at diagnosis and HAZ also significantly decreased over time for all examined risk factors, which is distinctly different from patterns in WHZ over time. In conclusion, WHZ and HAZ are affected differently by cancer treatment in infants and young children. We identify key risk factors for weight loss and growth stunting which will be necessary to develop prospective trials to examine anthropometric, biochemical, and patient recorded outcomes around nutrition.

Plasmodium chabaudi Infection Alters Intestinal Morphology and Mucosal Innate Immunity in Moderately Malnourished Mice.

Plasmodium falciparum is a protozoan parasite which causes malarial disease in humans. Infections commonly occur in sub-Saharan Africa, a region with high rates of inadequate nutrient consumption resulting in malnutrition. The complex relationship between malaria and malnutrition and their effects on gut immunity and physiology are poorly understood. Here, we investigated the effect of malaria infection in the guts of moderately malnourished mice. We utilized a well-established low protein diet that is deficient in zinc and iron to induce moderate malnutrition and investigated mucosal tissue phenotype, permeability, and innate immune response in the gut. We observed that the infected moderately malnourished mice had lower parasite burden at the peak of infection, but damaged mucosal epithelial cells and high levels of FITC-Dextran concentration in the blood serum, indicating increased intestinal permeability. The small intestine in the moderately malnourished mice were also shorter after infection with malaria. This was accompanied with lower numbers of CD11b+ macrophages, CD11b+CD11c+ myeloid cells, and CD11c+ dendritic cells in large intestine. Despite the lower number of innate immune cells, macrophages in the moderately malnourished mice were highly activated as determined by MHCII expression and increased IFNγ production in the small intestine. Thus, our data suggest that malaria infection may exacerbate some of the abnormalities in the gut induced by moderate malnutrition.

Extracellular vesicles isolated from milk can improve gut barrier dysfunction induced by malnutrition.

Malnutrition impacts approximately 50 million children worldwide and is linked to 45% of global mortality in children below the age of five. Severe acute malnutrition (SAM) is associated with intestinal barrier breakdown and epithelial atrophy. Extracellular vesicles including exosomes (EVs; 30-150 nm) can travel to distant target cells through biofluids including milk. Since milk-derived EVs are known to induce intestinal stem cell proliferation, this study aimed to examine their potential efficacy in improving malnutrition-induced atrophy of intestinal mucosa and barrier dysfunction. Mice were fed either a control (18%) or a low protein (1%) diet for 14 days to induce malnutrition. From day 10 to 14, they received either bovine milk EVs or control gavage and were sacrificed on day 15, 4 h after a Fluorescein Isothiocyanate (FITC) dose. Tissue and blood were collected for histological and epithelial barrier function analyses. Mice fed low protein diet developed intestinal villus atrophy and barrier dysfunction. Despite continued low protein diet feeding, milk EV treatment improved intestinal permeability, intestinal architecture and cellular proliferation. Our results suggest that EVs enriched from milk should be further explored as a valuable adjuvant therapy to standard clinical management of malnourished children with high risk of morbidity and mortality.

Application of four nutritional risk indexes in perioperative management for esophageal cancer patients.

PURPOSE: The Prognostic Nutritional Index (PNI), Nutritional Risk Index (NRI), Geriatric Nutritional Risk Index (GNRI), and Controlling Nutritional Status (CONUT) score were devised for quantifying nutritional risk. This study evaluated their properties in detecting compromised nutrition and guiding perioperative management of esophageal cancer patients. METHODS: A prospective institutional database of esophageal cancer patients was reviewed and analyzed. Compromised nutritional status was defined as PNI < 50, NRI < 97.5, GNRI < 92, or CONUT score ≥ 4, respectively. The malnutrition diagnosis consensus established by the European Society of Clinical Nutrition and Metabolism (ESPEN 2015) was selected as reference. Multivariable logistic regression and receiver operating characteristic curve analysis were used. External validation was conducted. RESULTS: After reviewing the 212-patient database, 192 patients were finally included. Among the four nutritional indexes, the GNRI < 92 showed highest sensitivity (72.0%), specificity (78.9%), and consistency (AUC 0.754, 95% CI 0.672-0.836) with malnutrition diagnosed by ESPEN 2015. The GNRI < 92 showed comparable performance with ESPEN 2015 in recognizing decreased fat mass, fat-free mass, and skeletal muscle mass (all P < 0.01). Both the GNRI < 92 and ESPEN 2015 showed good property in predicting major complications, infectious complications, overall complications and delayed hospital discharge (all P < 0.01), better than PNI < 50, NRI < 97.5, and CONUT score ≥ 4. Regarding the external validation, a retrospective analysis of 155 esophageal cancer patients confirmed the better performance of GNRI < 92 in predicting perioperative morbidities than other 3 nutritional indexes. CONCLUSION: The GNRI was optimal in perioperative management of esophageal cancer patients among the four nutritional indexes and was an appropriate alternative to ESPEN 2015 for simplifying nutritional assessment.

Comprehensive miRNA and DNA Microarray Analyses Reveal the Response of Hepatic miR-203 and Its Target Gene to Protein Malnutrition in Rats.

Adequate protein nutrition is essential for good health. Effects of protein malnutrition in animals have been widely studied at the mRNA level with the development of DNA microarray technology. Although microRNAs (miRNAs) have attracted attention for their function in regulating gene expression and have been studied in several disciplines, fewer studies have clarified the effects of protein malnutrition on miRNA alterations. The present study aimed to elucidate the relationship between protein malnutrition and miRNAs. Six-week old Wistar male rats were fed a control diet (20% casein) or a low-protein diet (5% casein) for two weeks, and their livers were subjected to both DNA microarray and miRNA array analysis. miR-203 was downregulated and its putative target Hadhb (hydroxyacyl-CoA dehydrogenase ß subunit), known to regulate ß-oxidation of fatty acids, was upregulated by the low-protein diet. In an in vitro experiment, miR-203 or its inhibitor were transfected in HepG2 cells, and the pattern of Hadhb expression was opposite to that of miR-203 expression. In addition, to clarifying the hepatic miRNA profile in response to protein malnutrition, these results showed that a low-protein diet increased Hadhb expression through downregulation of miR-203 and induced ß-oxidation of fatty acids.

Weight loss, malnutrition, and cachexia in COVID-19: facts and numbers.

Patients with COVID-19 disease are prone to develop significant weight loss and clinical cachexia. Three reports with altogether 589 patients that reported on weight loss and cachexia in COVID-19 were identified. Disease severity of patients and the timing of the assessment during the disease course in these patients were variable-65 patients (11%) were intensive care treated at the time of assessment, and 183 (31%) were cared for in sub-intensive or intermediate care structures. The frequency of weight loss ≥5% (that defines cachexia) was 37% (range 29-52%). Correlates of weight loss occurrence were reported to be raised C-reactive protein levels, impaired renal function status, and longer duration of COVID-19 disease. Underweight status by WHO criteria (BMI < 18.5 kg/m2 ) was only observed in 4% of patients analysing data from seven studies with 6661 patients. Cachexia assessment in COVID-19 needs assessment of weight loss. COVID-19 associated cachexia is understood to affect muscle and fat tissue as is also seen in many other chronic illness-associated forms of cachexia. There are many factors that can contribute to body wasting in COVID-19, and they include loss of appetite and taste, fever and inflammation, immobilization, as well as general malnutrition, catabolic-anabolic imbalance, endocrine dysfunction, and organ-specific complications of COVID-19 disease such as cardiac and renal dysfunction. Treatment of COVID-19 patients should include a focus on nutritional support and rehabilitative exercise whenever possible. Specific anti-cachectic therapies for COVID-19 do not exist, but constitute a high medical need to prevent long-term disability due to acute COVID-19 disease.

Measurement of body mass by bioelectrical impedance analysis and computed tomography in cancer patients with malnutrition - a cross-sectional observational study.

Malnutrition and cachexia affects the majority of cancer patients and significantly worsens their quality of life and prognosis. However, the diagnostic criteria of malnutrition and cachexia remain a topic under constant debate. To overcome this hurdle, diagnostic tools to objectively detect and quantify the loss of muscle and fat mass are needed. Computed tomography (CT)-based measurement is currently considered the golden standard. Bioelectrical impedance analysis (BIA) is an economical, non-invasive tool but it is seen controversial in patients with cancer and malnutrition because of possible estimation errors.BIA and CT-based analysis of body mass compartments were performed 172 times in 118 cancer patients, within the nutrition program of our institution. Prevalence of malnutrition was determined according to the global leadership initiative on malnutrition criteria. Data obtained for muscle and fat mass from both BIA and CT were correlated using Pearson's ρ. All analyses were performed with an explorative significance level of 5%.45.7% of the cohort were classified as "malnourished." No significant differences were observed between the 2 groups regarding demographic data. Median body mass index, Karnofsky performance status, and nutritional risk score were lower in the malnourished group. Values for muscle and fat mass by BIA and CT were significantly lower in malnourished patients. Correlation of the measured parameters were highly significant between CT-based and BIA measurement. In the overall cohort, correlation of measured muscle mass values by CT and BIA was significant with Pearson's ρ = 0.794 (P < .01). Looking at patients without malnutrition only, Pearson's ρ was 0.754 (P < .01). The correlation of measured fat mass values was equally significant, with Pearson's ρ of 0.748 (P < .01) in the overall cohort and 0.771 (P < .01) in patients with malnutrition.To our knowledge, this is the first study comparing BIA to CT-based body mass analysis in a large cohort of cancer patients with malnutrition. The results suggest that BIA is a valid diagnostic tool for the assessment of muscle and fat mass, even in patients with malnutrition, and could be implemented for the early detection and short-term follow-up of malnutrition and cachexia.

Histone Deacetylase Activity and the Renin-Angiotensin-Aldosterone System: Key Elements in Cardiorenal Alterations Provoked by Chronic Malnutrition in Male Adult Rats.

BACKGROUND/AIMS: Chronic malnutrition (M) affects >1 billion people worldwide. Epidemiological data point to long-term renal and cardiovascular outcomes (e.g. arterial hypertension, cardiorenal syndromes). The renin-angiotensin-aldosterone system (RAAS) has been implicated in the physiopathology of these disturbances, but M-induced alterations in RAAS-modulated renal Na+ handling and their cardiovascular repercussions are not known. Moreover, altered tissue-specific histone deacetylases (HDAC) results in arterial hypertension and the use of sodium Valproate (Val; a HDAC inhibitor) reduces blood pressure. However, there are no reports regarding the renal and cardiovascular effects of HDAC inhibition in M, or on the signaling pathways involved. The central aim of our study has been to investigate whether alterations in the HDAC/RAAS axis underpin alterations in active Na+ transport in the kidney and heart, and affects blood pressure. METHODS: Male rats aged 28 days were given either a control (C) or a multideficient diet (Regional Basic Diet, RBD), which mimics alimentary habits from developing countries. Subgroups received Losartan (Los), a blocker of type 1 Angiotensin II receptors. When the rats reached 70 days, new subgroups received Val until they were 90 days of age. Homogenates and enriched plasma membrane fractions from renal cortex corticis and cardiomyocytes were obtained by differential centrifugation of the tissues. The activity of renal and cardiac deacetylases was assayed by measuring - after incubation with the membranes - the amount of deacetylated lysines in a substrate containing an acetylated lysine side chain. Protein kinases activities were measured following the incorporation of the γ-phosphoryl group of [γ-32P]ATP into Ser/Thr residues of histone type III-S. The activity of Na+-transporting ATPases (kidney and heart) was quantified by measuring the release of Pi from ATP that was sensitive to ouabain ((Na++K+)ATPase), or sensitive to furosemide (Na+-ATPase). Tail-cuff plethysmography was used to measure systolic blood pressure and heart rate. RESULTS: M provoked HDAC downregulation, which was reversed by Los and Val, either alone or in combination, with selective upregulation of protein kinases C and A (PKC, PKA) in renal cortex corticis, but not in left ventricle cardiomyocytes. The 2 kinases were strongly inhibited by Los and Val in both organs. Malnourished rats developed elevated systolic arterial pressure (SAP) and heart rate (HR) at 70 days of age; Los and Val restored the control SAP, but not HR. Functional and the above biochemical alterations were associated with the deregulation of renal and cardiac Na+-transporting ATPases. (Na++K+)ATPase activities were downregulated in M rats in both organs, and were further inhibited by the pharmacological treatments in the renal cortex corticis (C and M groups) and the left ventricle (only in C rats). No additional effect was found in cardiac (Na++K+)ATPase from M rats. Ouabain-resistant Na+-ATPase was upregulated in renal cortex corticis and downregulated in cardiomyocytes, returning to C values after administration of Los and Val. CONCLUSION: The HDAC/RAAS axis appears to be a key regulator of Na+-transporting ATPases in renal cortex corticis and cardiomyocytes via an appropriate balance of PKC and PKA activities. Modifications within the HDAC/RAAS axis provoked by chronic M - with repercussions in renal and cardiac Na+ transport - underpin alterations in bodily Na+ homeostasis that culminate with the onset of arterial hypertension and potential cardiorenal syndrome.

Geriatric nutritional risk index as a useful prognostic factor in second allogeneic hematopoietic stem cell transplantation.

Second allogeneic hematopoietic stem cell transplantation (allo-HSCT) has a low survival outcome and a high non-relapse mortality (NRM) rate which is a major obstacle to this treatment. We hypothesized that the status of malnourishment after first allo-HSCT as represented by the geriatric nutritional risk index (GNRI) could be used as a prognostic factor to determine the outcomes of second allo-HSCT. A total of 108 patients with a median age of 42 (range, 17-69) years, who received second allo-HSCT for disease recurrence after first allo-HSCT from our institution, were included in this study. Low GNRI had a significant impact on NRM at 2 years after second allo-HSCT: 56.9% in patients with GNRI ≤ 92 compared with 27.5% in patients with GNRI > 92 (P = 0.002). In multivariate analysis, GNRI of ≤ 92 was the only significant factor for NRM (hazard ratio [HR] 2.29, 95% confidence interval [CI] 1.15-4.56, P = 0.018). High-risk disease status at second allo-HSCT (HR 2.74, 95% CI 1.46-5.14, P = 0.002) and GNRI of ≤ 92 (HR 1.70, 95% CI 1.02-2.82, P = 0.042) were identified as significant factors for overall survival (OS). A score of 1 was assigned to each factor, and the OS rate at 2 years after second allo-HSCT decreased according to the score: 53.0% in patients with score 0, 32.3% with score 1, and 2.5% with score 2 (P < 0.001). In conclusion, GNRI could be a useful predictor for the outcomes of second allo-HSCT. A prospective study in other cohorts is warranted to validate the findings of our study.

A Brazilian regional basic diet-induced chronic malnutrition drives liver inflammation with higher ApoA-I activity in C57BL6J mice.

Malnutrition is still considered endemic in many developing countries. Malnutrition-enteric infections may cause lasting deleterious effects on lipid metabolism, especially in children living in poor settings. The regional basic diet (RBD), produced to mimic the Brazilian northeastern dietary characteristics (rich in carbohydrate and low in protein) has been used in experimental malnutrition models, but few studies have explored the effect of chronic RBD on liver function, a central organ involved in cholesterol metabolism. This study aimed to investigate whether RBD leads to liver inflammatory changes and altered reverse cholesterol metabolism in C57BL6/J mice compared to the control group, receiving a standard chow diet. To evaluate liver inflammation, ionized calcium-binding adapter protein-1 (IBA-1) positive cell counting, interleukin (IL)-1ß immunohistochemistry, and tumor necrosis factor (TNF)-α and IL-10 transcription levels were analyzed. In addition, we assessed reverse cholesterol transport by measuring liver apolipoprotein (Apo)E, ApoA-I, and lecithin-cholesterol acyltransferase (LCAT) by RT-PCR. Furthermore, serum alanine aminotransferase (ALT) was measured to assess liver function. RBD markedly impaired body weight gain compared with the control group (P<0.05). Higher hepatic TNF-α (P<0.0001) and IL-10 (P=0.001) mRNA levels were found in RBD-challenged mice, although without detectable non-alcoholic fatty liver disease. Marked IBA-1 immunolabeling and increased number of positive-IBA-1 cells were found in the undernourished group. No statistical difference in serum ALT was found. There was also a significant increase in ApoA mRNA expression in the undernourished group, but not ApoE and LCAT, compared with the control. Altogether our findings suggested that chronic RBD-induced malnutrition leads to liver inflammation with increased ApoA-I activity.

The gut microbiota attenuates muscle wasting by regulating energy metabolism in chemotherapy-induced malnutrition rats.

BACKGROUND: Malnutrition is a common clinical symptom in cancer patients after chemotherapy, which is characterized by muscle wasting and metabolic dysregulation. The regulation of muscle metabolism by gut microbiota has been studied recently. However, there is no direct convincing evidence proving that manipulating gut microbiota homeostasis could regulate muscle metabolic disorder caused by chemotherapy. Here, we investigate the potential role of gut microbiota in the regulation of the muscle metabolism in 5-fluorouracil (5-Fu)-induced malnutrition rat model. METHODS: Male Sprague-Dawley rats were randomly divided into two groups (n = 8/group): control group and 5-Fu group. In the 5-Fu group, rats received 5-Fu (40 mg/kg/day) by intraperitoneal injection for 4 days, and all rats were raised for 8 days. Nutritional status, muscle function, muscle metabolites, and gut microbiota were assessed. Fecal microbiota transplantation (FMT) was applied to explore the potential regulation of gut microbiota on muscle metabolism. RESULTS: 5-Fu-treated rats exhibited loss of body weight and food intake compared to control group. 5-Fu decreased the levels of total protein and albumin in serum, and significantly increased the levels of IL-6 and TNF-α in muscle tissue. Rats that received 5-Fu displayed concurrent reduction of muscle function and fiber size. Moreover, 5-Fu group showed a distinct profile of gut microbiota compared to control group, including the relative lower abundance of Firmicutes and a higher abundance of Proteobacteria and Verrucomicrobia. Fourteen differential muscle metabolites were identified between two groups, which were mainly related to glycolysis, amino acid metabolism, and TCA cycle pathway. Furthermore, fecal transplantation from healthy rats improved nutritional status and muscle function in 5-Fu-treated rats. Notably, FMT inhibited the inflammatory response in muscle, and reversed the changes of several differential muscle metabolites and energy metabolism in 5-Fu-treated rats. CONCLUSIONS: Our study demonstrated that gut microbiota played an important role in the regulation of muscle metabolism and promoting muscle energy production in 5-Fu-induced malnutrition rats, suggesting the potential attenuation of chemotherapy-induced muscle wasting by manipulating gut microbiota homeostasis.

Undernutrition combined with dietary mineral oil hastens depuration of stored dioxin and polychlorinated biphenyls in ewes. 1. Kinetics in blood, adipose tissue and faeces.

Food safety crises involving persistent organic pollutants [POPs, e.g. dioxins, polychlorinated biphenyls (PCBs), organochlorine pesticides] lead to systematic slaughter of livestock to prevent their entry into the food chain. Therefore, there is a need to develop strategies to depurate livestock moderately contaminated with POPs in order to reduce such economic and social damages. This study aimed to test a POPs depuration strategy based on undernutrition (37% of energy requirements) combined with mineral oil (10% in total dry matter intake) in nine non-lactating ewes contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and PCBs 126 and 153. In order to better understand the underlying mechanisms of the depuration process, POPs kinetics and body lipids dynamics were followed concomitantly over 57-day of depuration in POPs storage (adipose tissue, AT), central distribution (blood) and excretion (faeces) compartments. Faecal POPs concentrations in underfed and mineral oil supplemented ewes increased by 2.0 to 2.6-fold, but not proportionally to lipids concentration which increased by 6-fold, compared to the control ewes. Nonetheless, after 57 days of depuration in undernutrition and mineral oil supplementation, AT POPs concentrations were 1.5 to 1.6-fold higher while serum concentrations remained unchanged compared to the control ewes. This was concomitant with a decrease by 2.7-fold of the AT estimated lipids weight along the depuration period. This reduction of the volume of the storage compartment combined with the increase of POPs faecal excretion in underfed and mineral oil supplemented ewes led to a reduction by 1.5-fold of the PCB 126 AT burden, while no changes were observed for TCDD and PCB 153 burdens (vs. no change for PCB 126 and increases for TCDD and PCB 153 AT burdens in control ewes). The original approach of this study combining the fine description at once of POPs kinetic and of body lipids dynamic improved our understanding of POPs fate in the ruminant.

Undernutrition combined with dietary mineral oil hastens depuration of stored dioxin and polychlorinated biphenyls in ewes. 2. Tissue distribution, mass balance and body burden.

Food safety crises involving persistent organic pollutants (POPs) lead to systematic slaughter of livestock to prevent contaminants from entering the food chain. Therefore, there is a need to develop strategies to depurate livestock moderately contaminated with POPs to reduce economic and social damage. This study aimed to test undernutrition (37% of energy requirements) combined with mineral oil (10% in total dry matter intake) in nine non-lactating ewes contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and polychlorinated biphenyls (PCBs) 126 and 153 as a strategy to enhance the depuration of POPs through faecal excretion. To better understand the underlying mechanisms of the depuration process, lipophilic POPs and lipid fluxes were co-monitored in various body and excretion compartments. Body compartments (adipose tissues, muscle, liver and blood) and the total empty body were analyzed for lipids and POPs concentrations and burdens at slaughter, as well as excretion compartments (faeces and wool) collected during the depuration period. Decreases in empty body total and lipid weights were 6-fold higher in underfed and supplemented ewes compared to control ewes. In addition, over the depuration period undernutrition and supplementation treatment increased faecal TCDD, PCBs 126 and 153 excretions by 1.4- to 2.1-fold but tended to decrease wool PCB 153 excretion by 1.4-fold. This induced 2- to 3-fold higher decreases in the empty body POPs burdens for underfed and supplemented ewes. Nonetheless, when expressed relative to the calculated initial empty body burdens, burdens at slaughter decreased only slightly from 97%, 103% and 98% for control ewes to 92%, 97% and 94% for underfed and supplemented ones, for TCDD, PCBs 126 and 153, respectively. Fine descriptions at once of POPs kinetic (companion paper 1) and mass balance (companion paper 2), and of body lipid dynamics were very useful in improving our understanding of the fate of POPs in the ruminants.

Serum IGFBP2 Level Is a New Candidate Biomarker of Severe Malnutrition in Advanced Lung Cancer.

Objectives: This study aimed to analyze and evaluate serum insulin-like growth factor-binding protein 2 (IGFBP2) levels as a new biomarker of severe malnutrition in patients with advanced lung cancer.Design and methods: This prospective study involved 59 patients with advanced lung cancer. We detected serum IGFBP2 level by using enzyme-linked immunosorbent assay and analyzed its relationship to clinical characteristics, nutritional status, Glasgow prognostic score (GPS), and survival. Serum albumin and C-reactive protein (CRP) levels were measured, and nutritional status was assessed using Patient-Generated Subjective Global Assessment (PG-SGA). The best cutoff point value for serum IGFBP2 level was established using receiver operating characteristic analysis. Kaplan-Meier method was utilized to analyze the survival curves.Results: Serum IGFBP2 levels were elevated in patients with advanced lung cancer and severe malnutrition. The best cutoff value for serum IGFBP2 level was determined at 363 ng/ml, which could diagnose severe malnutrition with 73.3% sensitivity and 70.5% specificity and was found to be related to albumin, CRP, and GPS. Patients whose serum IGFBP2 levels were higher than 363 ng/ml had poor survival outcome.Conclusion: This study demonstrates the remarkably association between higher serum level of IGFBP2 and severe malnutrition, albumin, CRP, GPS, and survival. Hence, serum IGFBP2 level can be used as a potential biomarker for diagnosis of severe malnutrition in patients with advanced lung cancer.