Monocarboxylate Transporter 8 Deficiency: From Pathophysiological Understanding to Therapy Development.

Genetic defects in the thyroid hormone transporter monocarboxylate transporter 8 (MCT8) result in MCT8 deficiency. This disorder is characterized by a combination of severe intellectual and motor disability, caused by decreased cerebral thyroid hormone signalling, and a chronic thyrotoxic state in peripheral tissues, caused by exposure to elevated serum T3 concentrations. In particular, MCT8 plays a crucial role in the transport of thyroid hormone across the blood-brain-barrier. The life expectancy of patients with MCT8 deficiency is strongly impaired. Absence of head control and being underweight at a young age, which are considered proxies of the severity of the neurocognitive and peripheral phenotype, respectively, are associated with higher mortality rate. The thyroid hormone analogue triiodothyroacetic acid is able to effectively and safely ameliorate the peripheral thyrotoxicosis; its effect on the neurocognitive phenotype is currently under investigation. Other possible therapies are at a pre-clinical stage. This review provides an overview of the current understanding of the physiological role of MCT8 and the pathophysiology, key clinical characteristics and developing treatment options for MCT8 deficiency.

Independent of physical activity, volumetric muscle loss injury in a murine model impairs whole-body metabolism.

Volumetric muscle loss (VML) injuries result in a non-recoverable loss of muscle tissue and function due to trauma or surgery. Reductions in physical activity increase the risk of metabolic comorbidities over time, and it is likely that VML may reduce whole-body activity. However, these aspects remain uncharacterized following injury. Our goal was to characterize the impact of VML on whole-body physical activity and metabolism, and to further investigate possible muscle-specific metabolic changes. Adult male C57Bl/6J (n = 28) mice underwent a standardized VML injury to the posterior compartment of the hind limb, or served as injury naïve controls. Mice underwent longitudinal evaluation of whole-body physical activity and metabolism in specialized cages up to three times over the course of 8 weeks. At terminal time points of 4- and 8-weeks post-VML in vivo muscle function of the posterior compartment was evaluated. Additionally, the gastrocnemius muscle was collected to understand histological and biochemical changes in the muscle remaining after VML. The VML injury did not alter the physical activity of mice. However, there was a noted reduction in whole-body metabolism and diurnal fluctuations between lipid and carbohydrate oxidation were also reduced, largely driven by lower carbohydrate utilization during active hours. Following VML, muscle-specific changes indicate a decreased proportion of fast (i.e., type IIb and IIx) and a greater proportion of slow (i.e., type I and IIa) fibers. However, there were minimal changes in the capillarity and metabolic biochemical activity properties of the gastrocnemius muscle, suggesting a miss-match in capacity to support the physiologic needs of the fibers. These novel findings indicate that following VML, independent of changes in physical activity, there is whole-body diurnal metabolic inflexibility. Supporting future investigations into the chronic and overlooked co-morbidities of VML injury.

Cancer cachexia: molecular mechanism and pharmacological management.

Cancer cachexia often occurs in malignant tumors and is a multifactorial and complex symptom characterized by wasting of skeletal muscle and adipose tissue, resulting in weight loss, poor life quality and shorter survival. The pathogenic mechanism of cancer cachexia is complex, involving a variety of molecular substrates and signal pathways. Advancements in understanding the molecular mechanisms of cancer cachexia have provided a platform for the development of new targeted therapies. Although recent outcomes of early-phase trials have showed that several drugs presented an ideal curative effect, monotherapy cannot be entirely satisfactory in the treatment of cachexia-associated symptoms due to its complex and multifactorial pathogenesis. Therefore, the lack of definitive therapeutic strategies for cancer cachexia emphasizes the need to develop a better understanding of the underlying mechanisms. Increasing evidences show that the progression of cachexia is associated with metabolic alternations, which mainly include excessive energy expenditure, increased proteolysis and mitochondrial dysfunction. In this review, we provided an overview of the key mechanisms of cancer cachexia, with a major focus on muscle atrophy, adipose tissue wasting, anorexia and fatigue and updated the latest progress of pharmacological management of cancer cachexia, thereby further advancing the interventions that can counteract cancer cachexia.

Low skeletal muscle density combined with muscle dysfunction predicts adverse events after adult cardiovascular surgery.

BACKGROUND AND AIMS: Although muscle dysfunctions are widely known as a poor prognostic factor in patients with cardiovascular disease, no study has examined whether the addition of low skeletal muscle density (SMD) assessed by computed tomography (CT) to muscle dysfunctions is useful. This study examined whether SMDs can strengthen the predictive ability of muscle dysfunctions for adverse events in patients who underwent cardiovascular surgery. METHODS AND RESULTS: We retrospectively reviewed 853 patients aged ≥40 years who had preoperative CT for risk management purposes and who measured muscle dysfunctions (weakness: low grip strength and slowness: slow gait speed). Low SMD based on transverse abdominal CT images was defined as a mean Hounsfield unit of the psoas muscle <45. All definitions of muscle dysfunction (weakness only, slowness only, weakness or slowness, weakness and slowness), the addition of SMDs was shown to significantly improve the continuous net reclassification improvement and integrated discrimination improvement for adverse events in all analyses (p < 0.05). Low SMDs combined with each definition of muscle dysfunction had the highest risk of all-cause death (hazard ratio: lowest 3.666 to highest 6.002), and patients with neither low SMDs nor muscle dysfunction had the lowest risk of all-cause and cardiovascular-related events. CONCLUSION: The addition of SMDs consistently increased the predictive ability of muscle dysfunctions for adverse events. Our results suggest that when CT is performed for any clinical investigation, the addition of the organic assessment of skeletal muscle can strengthen the diagnostic accuracy of muscle wasting.

The association of muscle size, strength and exercise capacity with all-cause mortality in non-dialysis-dependent CKD patients.

BACKGROUND/OBJECTIVE: Patients with chronic kidney disease (CKD) are commonly reported to exhibit skeletal muscle wasting, reduced strength and exercise capacity. Evidence from patients with end-stage renal disease (ESRD) demonstrates these factors are associated with mortality, but it is unclear whether this relationship exists earlier in the illness. Our objective was to determine whether muscle size, strength or exercise capacity was associated with all-cause mortality, unscheduled hospital admissions or time to ESRD in patients not requiring dialysis. METHODS: This is a prospective cohort study of 89 patients with CKD stages 3b-5 not requiring renal replacement therapy with a mean follow-up period of 3.3 years in which the contribution of predictors of rectus femoris muscle size, muscle strength, exercise capacity to all-cause mortality rates, progression to ESRD and time to first hospitalization were investigated. RESULTS: Unadjusted analysis suggested each 1 cm2 increase in quadriceps muscle size (measured by ultrasonography cross-sectional area) was associated with a 38% reduced risk for death (p = .006), and a 10 m improvement on the incremental shuttle walk test was associated with a 3% reduced risk for death (p = .04). However, this relationship was not present in analysis adjusted for age, gender and eGFR. No association was seen between any factor for the development of ESRD or time to first hospitalization. CONCLUSION: These results suggest that in this small cohort, muscle size and exercise capacity are associated with mortality when considered alone, but this relationship was not present in adjusted analyses. Further investigation in a larger patient group is warranted.

Skeletal muscle loss phenotype in cirrhosis: A nationwide analysis of hospitalized patients.

BACKGROUND & AIMS: There are very limited data on the healthcare burden of muscle loss, the most frequent complication in hospitalized cirrhotics. We determined the healthcare impact of a muscle loss phenotype in hospitalized cirrhotics. METHODS: The Nationwide Inpatient Sample (NIS) database (years 2010-2014) was analyzed. Search terms included cirrhosis and its complications, and an expanded definition of a muscle loss phenotype that included all conditions associated with muscle loss. In-hospital mortality, length of stay (LOS), post-discharge disposition, co-morbidities and cost during admission were analyzed. Univariate and multivariate analyses were performed to identify associations between a muscle loss phenotype and outcomes. Impact of muscle loss in cirrhotics was compared to that in a random sample (2%) of general medical inpatients. RESULTS: A total of 162,694 hospitalizations for cirrhosis were reported, of which 18,261 (11.2%) included secondary diagnosis codes for a muscle loss phenotype. A diagnosis of muscle loss was associated with a significantly (p < 0.001 for all) higher mortality (19.3% vs 8.2%), LOS (14.2 ± 15.8 vs. 4.6 ± 6.9 days), and median hospital charge per admission ($21,400 vs. $8573) and a lower likelihood of discharge to home (30.1% vs. 60.2%). All evaluated outcomes were more severe in cirrhotics than general medical patients (n = 534,687). Multivariate regression analysis showed that a diagnosis of muscle loss independently increased mortality by 130%, LOS by 80% and direct cost of care by 119% (p < 0.001 for all). Alcohol use, female gender, malignancies and other organ dysfunction were independently associated with muscle loss. CONCLUSIONS: Muscle loss contributed to higher mortality, LOS, and direct healthcare costs in hospitalized cirrhotics.

Association between low muscle mass and survival in incurable cancer patients: A systematic review.

Current data suggest that low skeletal muscle mass provides prognostic information in patients with cancer and may even be considered a biomarker in research and clinical evaluations. The aim of this systematic review was to explore whether low muscle mass is associated with overall survival (OS) in patients with incurable cancer. A systematic search was conducted for published literature using PubMed/MEDLINE, Scopus, LILACS, and the Cochrane Library, with no restrictions on language or publication date, to examine whether low muscle mass is associated with OS in patients with incurable cancer. Eligible studies included low muscle mass evaluated using gold standard techniques (dual energy x-ray absorptiometry or computed tomography). The studies quality assessment was performed using the Newcastle-Ottawa Scale. Thirteen studies were included. The studies reported on 1959 patients between 54.3 (median) and 72.9 (mean) y of age; pancreatic cancer was the most common type of tumor. According to the survival curves and most of the multivariate analyses, there was no statistically significant association between loss of muscle mass and reduced OS. Four studies reported that overweight or obese patients with muscle mass depletion had significantly shorter OS. These results indicate that there is insufficient evidence to associate low muscle mass with OS in patients with incurable cancer. Further studies deploying other muscle measurement methods suggest that use of low muscle mass cutoff alone is still necessary in the pursuit of OS prediction in this population.

Association of loss of muscle mass with mortality in liver cirrhosis without or before liver transplantation: A systematic review and meta-analysis.

BACKGROUND: Liver cirrhosis is a risk factor for the loss of muscle mass, which is associated with numerous adverse health outcomes. This meta-analysis aimed to examine whether loss of muscle mass was a predictor of increased mortality in cirrhotic patients without or before liver transplantation. METHODS: Without language restriction, PubMed and Embase were searched for articles published from the earliest records to December 2018 investigating the influence of loss of muscle mass on survival of cirrhotic patients. Those who had undergone liver transplantation and had hepatocellular carcinoma were excluded. The main outcome was the hazard ratio (HR) for the association of mortality with loss of muscle mass, and the secondary outcome was the association of loss of muscle mass with Child-Pugh class and death caused by severe infection. RESULTS: The meta-analysis included 16 observational studies, comprising 4070 participants. The pooled crude and adjusted HRs for the association of mortality with loss of muscle mass were 2.05 (95% confidence interval [CI], 1.51-2.78) and 2.36 (95% CI, 1.61-3.46). Using Child-Pugh Class A as reference, the odds ratios (ORs) for the association of loss of muscle mass with Child-Pugh Class B and Class C were 1.68 (95% CI, 0.96-2.92) and 1.94 (95% CI, 0.66-5.65). Patients with loss of muscle mass were likely to have infection-related mortality (OR = 3.38, 95% CI, 0.61-18.88) but the association did not reach statistical significance. CONCLUSIONS: Loss of muscle mass is associated with mortality in cirrhotic patients without or before liver transplantation. Future studies should be conducted to explore whether exercise and nutritional supplementation can reverse muscle mass loss and improve long-term survival.

Clinical utility of bioimpedance analysis in liver cirrhosis.

BACKGROUND: The objective of the present study was to examine the impact of muscle mass depletion (MMD) as determined by data in bioimpedance analysis (BIA) in liver cirrhosis (LC) patients (n = 382, 204 in male and 178 in female) on survival and to validate the utility of cutoff values in BIA recommended from current recommendations. METHODS: Muscle mass depletion was defined as patients with skeletal muscle mass index (SMI) using BIA <7.0 cm2 /m2 for male and <5.7 cm2 /m2 for female based on current recommendations. We retrospectively examined variables related to the presence of MMD using univariate and multivariate analyses and investigated the impact of MMD on survival. RESULTS: A total of 135 patients (35.3%) had MMD. Subjects were predominantly Child-Pugh A (278/382, 72.8%). For the entire cohort, the 5-year cumulative survival rates were 59.8% in patients with MMD and 84.4% in patients without MMD (P < 0.0001). In the multivariate analysis for survival, MMD revealed to be a significant adverse predictor for survival and for most subgroup analyses, the differences between MMD group and non-MMD group in terms of survival reached significance. CONCLUSION: Muscle mass measurement using BIA may be helpful for LC patients and current recommendations were well verified in our analysis.

Lower Pectoralis Muscle Area Is Associated with a Worse Overall Survival in Non-Small Cell Lung Cancer.

BACKGROUND: Muscle wasting is a component of the diagnosis of cancer cachexia and has been associated with poor prognosis. However, recommended tools to measure sarcopenia are limited by poor sensitivity or the need to perform additional scans. We hypothesized that pectoralis muscle area (PMA) measured objectively on chest CT scan may be associated with overall survival (OS) in non-small cell lung cancer (NSCLC). METHODS: We evaluated 252 cases from a prospectively enrolling lung cancer cohort. Eligible cases had CT scans performed prior to the initiation of surgery, radiation, or chemotherapy. PMA was measured in a semi-automated fashion while blinded to characteristics of the tumor, lung, and patient outcomes. RESULTS: Men had a significantly greater PMA than women (37.59 vs. 26.19 cm2, P < 0.0001). In univariate analysis, PMA was associated with age and body mass index (BMI). A Cox proportional hazards model was constructed to account for confounders associated with survival. Lower pectoralis area (per cm2) at diagnosis was associated with an increased hazard of death of 2% (HRadj, 0.98; confidence interval, 0.96-0.99; P = 0.044) while adjusting for age, sex, smoking, chronic bronchitis, emphysema, histology, stage, chemotherapy, radiation, surgery, BMI, and ECOG performance status. CONCLUSIONS: Lower PMA measured from chest CT scans obtained at the time of diagnosis of NSCLC is associated with a worse OS. IMPACT: PMA may be a valuable CT biomarker for sarcopenia-associated lung cancer survival. Cancer Epidemiol Biomarkers Prev; 26(1); 38-43. ©2016 AACR SEE ALL THE ARTICLES IN THIS CEBP FOCUS SECTION, "THE OBESITY PARADOX IN CANCER EVIDENCE AND NEW DIRECTIONS".

Low muscle attenuation is a prognostic factor for survival in metastatic breast cancer patients treated with first line palliative chemotherapy.

BACKGROUND: Low muscle mass (LMM) and low muscle attenuation (LMA) reflect low muscle quantity and low muscle quality, respectively. Both are associated with a poor outcome in several types of solid malignancies. This study determined the association of skeletal muscle measures with overall survival (OS) and time to next treatment (TNT). PATIENTS AND METHODS: A skeletal muscle index (SMI) in cm2/m2 and muscle attenuation (MA) in Hounsfield units (HU) were measured using abdominal CT-images of 166 patients before start of first-line chemotherapy for metastatic breast cancer. Low muscle mass (SMI <41 cm2/m2), sarcopenic obesity (LMM and BMI ≥30 kg/m2) and low muscle attenuation (MA <41 HU and BMI <25 kg/m2 or MA <33 HU and BMI ≥25 kg/m2) were related to OS and TNT. RESULTS: The prevalence of LMM, sarcopenic obesity and LMA were 66.9%, 7.2% and 59.6% respectively. LMM and sarcopenic obesity showed no significant association with OS and TNT, whereas LMA was associated with both lower OS (HR 2.04, 95% CI 1.34-3.12, p = 0.001) and shorter TNT (HR 1.72, 95% CI 1.14-2.62, p = 0.010). Patients with LMA had a median OS and TNT of 15 and 8 months respectively, compared to 23 and 10 months in patients with normal MA. CONCLUSION: LMA is a prognostic factor for OS and TNT in metastatic breast cancer patients receiving first-line palliative chemotherapy, whereas LMM and sarcopenic obesity are not. Further research is needed to establish what impact LMA should have in daily clinical practice.

Loss of Muscle Mass During Chemotherapy Is Predictive for Poor Survival of Patients With Metastatic Colorectal Cancer.

PURPOSE: Low muscle mass is present in approximately 40% of patients with metastatic colorectal cancer (mCRC) and may be associated with poor outcome. We studied change in skeletal muscle during palliative chemotherapy in patients with mCRC and its association with treatment modifications and overall survival. PATIENTS AND METHODS: In 67 patients with mCRC (mean age ± standard deviation, 66.4 ± 10.6 years; 63% male), muscle area (square centimeters) was assessed using computed tomography scans of the third lumbar vertebra before and during palliative chemotherapy. Treatment modifications resulting from toxicity were evaluated, including delay, dose reduction, or termination of chemotherapy. Multiple regression analyses were performed for the association between change in muscle area and treatment modification and secondly overall survival. RESULTS: Muscle area of patients with mCRC decreased significantly during 3 months of chemotherapy by 6.1% (95% CI, -8.4 to -3.8; P < .001). Change in muscle area was not associated with treatment modifications. However, patients with muscle loss during treatment of 9% or more (lowest tertile) had significantly lower survival rates than patients with muscle loss of less than 9% (at 6 months, 33% v 69% of patients alive; at 1 year, 17% v 49% of patients alive; log-rank P = .001). Muscle loss of 9% or more remained independently associated with survival when adjusted for sex, age, baseline lactate dehydrogenase concentration, comorbidity, mono-organ or multiorgan metastases, treatment line, and tumor progression at first evaluation by computed tomography scan (hazard ratio, 4.47; 95% CI, 2.21 to 9.05; P < .001). CONCLUSION: Muscle area decreased significantly during chemotherapy and was independently associated with survival in patients with mCRC. Further clinical evaluation is required to determine whether nutritional interventions and exercise training may preserve muscle area and thereby improve outcome.

Skeletal Muscle Depletion Predicts the Prognosis of Patients with Advanced Pancreatic Cancer Undergoing Palliative Chemotherapy, Independent of Body Mass Index.

INTRODUCTION: Body composition has emerged as a prognostic factor in cancer patients. We investigated whether sarcopenia at diagnosis and loss of skeletal muscle during palliative chemotherapy were associated with survival in patients with pancreatic cancer. METHODS: We retrospectively reviewed the clinical outcomes of pancreatic cancer patients receiving palliative chemotherapy between 2003 and 2010. The cross-sectional area of skeletal muscle at L3 by computed tomography was analyzed with Rapidia 3D software. We defined sarcopenia as a skeletal muscle index (SMI)< 42.2 cm2/m2 (male) and < 33.9 cm2/m2 (female) using ROC curve. RESULTS: Among 484 patients, 103 (21.3%) patients were sarcopenic at diagnosis. Decrease in SMI during chemotherapy was observed in 156 (60.9%) male and 65 (40.6%) female patients. Decrease in body mass index (BMI) was observed in 149 patients (37.3%), with no gender difference. By multivariate analysis, sarcopenia (P< 0.001), decreasedBMI and SMI during chemotherapy (P = 0.002, P = 0.004, respectively) were poor prognostic factors for overall survival (OS). While the OS of male patients was affected with sarcopenia (P< 0.001) and decreased SMI (P = 0.001), the OS of female patients was influenced with overweight at diagnosis (P = 0.006), decreased BMI (P = 0.032) and decreased SMI (P = 0.014). Particularly, while the change of BMI during chemotherapy did not have impact on OS within the patients with maintained SMI (P = 0.750), decrease in SMI was associated with poor OS within the patients with maintained BMI (HR 1.502; P = 0.002). CONCLUSIONS: Sarcopenia at diagnosis and depletion of skeletal muscle, independent of BMI change, during chemotherapy were poor prognostic factors in advanced pancreatic cancer.

Prognostic value of muscle atrophy in cirrhosis using psoas muscle thickness on computed tomography.

BACKGROUND & AIMS: Waiting-list mortality in patients with cirrhosis and a relatively low MELD score is a matter of concern. The aim of this study was to determine whether a marker of muscle waste could improve prognostication. METHODS: A pre-MELD cohort (waiting time-based allocation; n=186) and a MELD-era cohort (n=376) were examined. At evaluation, transversal psoas muscle thickness (TPMT) was measured on a computed tomography (CT) image at the level of the umbilicus. In the pre-MELD cohort, TPMT/height (mm/m) and the MELD score were entered in univariate and multivariate models to predict mortality after registration. Applicability of pre-MELD findings was tested in the MELD-era. RESULTS: In the pre-MELD cohort, the MELD score and TPMT/height were significantly associated with mortality. The discrimination of a score combining MELD and TPMT/height (MELD-psoas) was 0.84 (95% CI, 0.62-0.95). In the MELD-era, TPTM/height was significantly associated with mortality, independent of the MELD and MELD-Na scores. There was a 15% increase in mortality risk per unit decrease in TPMT/height. The discrimination of MELD-psoas score (0.82; 95% CI, 0.64-0.93) was superior to that of the MELD score and similar to that of the MELD-Na score. In patients with refractory ascites, mortality was significantly higher when TPMT/height was <16.8 mm/m (42% vs. 9%, p=0.02). CONCLUSIONS: TPMP/height on CT at the level of the umbilicus, an objective marker of muscle waste, may be predictive of mortality in cirrhotic patients, independent of the MELD and MELD-Na scores. It may help to better assess the prognosis of patients with refractory ascites.

[Exome sequencing revealed Allan-Herndon-Dudley syndrome underlying multiple disabilities]. / Monivammaisuuden taustalla Allan-Herndon-Dudleyn oireyhtymä.

Normal function of the thyroid gland is the cornerstone of a child's mental development and physical growth. We describe a Finnish family, in which the diagnosis of three brothers became clear after investigations that lasted for more than 30 years. Two of the sons have already died. DNA analysis of the third one, a 16-year-old boy, revealed in exome sequencing of the complete X chromosome a mutation in the SLC16A2 gene, i.e. MCT8, coding for a thyroid hormone transport protein. Allan-Herndon-Dudley syndrome was thus shown to be the cause of multiple disabilities.

Combined influence of leisure-time physical activity and hip circumference on all-cause mortality.

UNLABELLED: Hip circumference has been shown to be inversely associated with mortality. Muscle atrophy in the gluteofemoral region may be a possible explanation and thus physical activity is likely to play an important role. OBJECTIVE: To estimate the combined effects of hip circumference and physical activity on mortality. DESIGN AND METHODS: From the Copenhagen City Heart Study, 3,358 men and 4,350 women aged 21 to 93 years without pre-existing diagnosis of diabetes, stroke, ischemic heart disease, or cancer in 1991-1994 and with complete information on the variables of interest were included in the analyses. The participants were followed to 2009 in the Danish Civil Registration System, with 1.3% loss to follow-up and 2,513 deaths. Hazard ratios (HR) were estimated for combinations of physical activity and hip circumference. RESULTS: Hip circumference was inversely associated with mortality irrespective of being physically active or not. However, being physically active seemed to counterbalance some of the adverse health effects of a small hip circumference; when comparing inactive to active, the excess mortality at the 25th percentile of hip circumference is 40% in men (HR = 1.40, 95% CI: 1.14-1.72) and 33% in women (HR = 1.33, CI: 1.10-1.62). These associations were observed after adjustment for waist circumference and weight change in the 6 months before the examination. CONCLUSION: Less effects of physical activity were found in individuals with greater hip circumferences. A small hip circumference appears hazardous to survival. However, being physically active may counterbalance some of the hazardous effects of a small hip circumference.

Recent progress in elucidating signalling proteolytic pathways in muscle wasting: potential clinical implications.

AIMS: Muscle wasting prevails with disuse (bedrest and immobilisation) and is associated with many diseases (cancer, sepsis, diabetes, kidney failure, trauma, etc.). This results first in prolonged hospitalisation with associated high health-care costs and second and ultimately in increased morbidity and mortality. The precise characterisation of the signalling pathways leading to muscle atrophy is therefore particularly relevant in clinical settings. DATA SYNTHESIS: Recent major papers have identified highly complex intricate pathways of signalling molecules, which induce the transcription of the muscle-specific ubiquitin protein ligases MAFbx/Atrogin-1 and MuRF1 that are overexpressed in nearly all muscle wasting diseases. These signalling pathways have been targeted with success in animal models of muscle wasting. In particular, these findings have revealed a finely tuned crosstalk between both anabolic and catabolic processes. CONCLUSIONS: Whether or not such strategies may be useful for blocking or at least limiting muscle wasting in weight losing and cachectic patients is becoming nowadays a very exciting clinical challenge.

Skeletal muscle mass abnormalities are associated with survival rates of institutionalized elderly nursing home residents.

BACKGROUND: Knowledge about the changes in skeletal muscle mass in nursing home residents is very limited. We hypothesized that such patients have different types of skeletal muscle mass abnormalities that may affect mortality rates. Therefore, the objective of this study was to evaluate the prevalence and extent of skeletal muscle mass decline, its different clinical phenotypes (sarcopenia, wasting/atrophy and cachexia) and the mortality rates associated with these abnormalities. METHODS: A retrospective chart-review study comprising 109 institutionalized nursing home residents. Body mass index, body fat mass, fat free mass, skeletal muscle mass and survival rates were assessed. RESULTS: Skeletal muscle mass abnormalities were found among 73 out of 109 (67.0%) patients and were more prevalent in males compared with females (97.8% and 43.8%, respectively, p<0.001). Most of these patients had muscle wasting/atrophy (51.4%) or sarcopenia (40.3%), and 9.7% suffered from cachexia. One third of the patients with abnorrmal skeletal muscle mass showed a moderate decline of skeletal muscle mass (34.7%) while the remainder (65.3%) had very low levels of skeletal muscle mass. Each group was characterized by typical medical conditions associated with skeletal muscle mass abnormality. A Kaplan-Meier survival plot of mortality showed only lower one-year survival rates in the group with sarcopenia (60%) and muscle atrophy or cachexia (53%), compared with elderly participants with a normal skeletal muscle mass (73%), (p<0.0001). There were no significant differences in 1-year mortality rates between patients with abnormal skeletal muscle mass (whether sarcopenia, cachexia or wasting). CONCLUSION: About two thirds of nursing home patients show skeletal muscle mass abnormalities, most within the range of very low skeletal muscle mass rather than moderately low skeletal muscle mass, that are associated with shorter survival rates, compared with normal skeletal muscle mass patients.

Postoperative loss of skeletal muscle mass, complications and quality of life in patients undergoing cardiac surgery.

OBJECTIVE: The objective of this study was to describe postoperative undernutrition in terms of postoperative losses of appendicular skeletal muscle mass (ASMM) with respect to complications, quality of life, readmission, and 1-y mortality after cardiac surgery. METHODS: Patients undergoing cardiac surgery were prospectively followed. ASMM was measured 2 wk before and 2 mo after surgery using dual-energy X-ray absorptiometry. ASMM consists of arm skeletal muscle mass (SMM) and leg SMM. The association between ≥5% of ASMM decrease and postoperative outcome was analyzed using the chi-square test. A similar approach was used to analyze arm SMM and leg SMM decreases separately. RESULTS: Twenty-nine patients were included (23 male, 34.5% ≥65 y old). Postoperatively, seven patients (24.1%) lost ≥5% ASMM. When analyzed separately, a ≥5% decrease in leg SMM was associated with a decrease in experienced vitality (odds ratio 13.0, 95% confidence interval 1.32-128.11, P = 0.03). In contrast, a ≥5% loss of arm SMM was associated with fewer in-hospital complications (odds ratio 0.20, 95% confidence interval 0.04-0.98, P = 0.04). These patients were characterized by a higher preoperative fat-free mass index (kilograms per meter squared; P = 0.01). CONCLUSIONS: The results suggest that a preoperatively higher fat-free mass index indicates better ability to cope with operative stress, resulting in fewer complications. In addition, postoperative loss of muscle mass was associated with decreased vitality. We advocate further research investigating the effect of preoperative and postoperative nutritional intervention combined with physical exercise programs to increase lean body mass and thereby improve postoperative recovery after cardiac surgery.

Frailty and chronic kidney disease: the Third National Health and Nutrition Evaluation Survey.

BACKGROUND: Frailty is common in the elderly and in persons with chronic diseases. Few studies have examined the association of frailty with chronic kidney disease. METHODS: We used data from the Third National Health and Nutrition Examination Survey to estimate the prevalence of frailty among persons with chronic kidney disease. We created a definition of frailty based on established validated criteria, modified to accommodate available data. We used logistic regression to determine whether and to what degree stages of chronic kidney disease were associated with frailty. We also examined factors that might mediate the association between frailty and chronic kidney disease. RESULTS: The overall prevalence of frailty was 2.8%. However, among persons with moderate to severe chronic kidney disease (estimated glomerular filtration rate < 45 mL/min/1.73 m2), 20.9% were frail. The odds of frailty were significantly increased among all stages of chronic kidney disease, even after adjustment for the residual effects of age, sex, race, and prevalent chronic diseases. The odds of frailty associated with chronic kidney disease were only marginally attenuated with additional adjustment for sarcopenia, anemia, acidosis, inflammation, vitamin D deficiency, hypertension, and cardiovascular disease. Frailty and chronic kidney disease were independently associated with mortality. CONCLUSION: Frailty is significantly associated with all stages of chronic kidney disease and particularly with moderate to severe chronic kidney disease. Potential mechanisms underlying the chronic kidney disease and frailty connection remain elusive.