Associations of pre-existing co-morbidities with skeletal muscle mass and radiodensity in patients with non-metastatic colorectal cancer.

BACKGROUND AND AIM: Co-morbidities and computerized tomography-measured muscle abnormalities are both common in cancer patients and independently adversely influence clinical outcomes. Muscle abnormalities are also evident in other diseases, such as diabetes and obesity. This study examined for the first time the association between co-morbidities and muscle abnormalities in patients diagnosed with colorectal cancer (CRC). METHODS: This cross-sectional study included 3051 non-metastatic patients with Stages I-III CRC. Muscle abnormalities, measured at diagnosis, were defined as low skeletal muscle mass index (SMI) or low skeletal muscle radiodensity (SMD) quantified using computerized tomography images using optimal stratification. Co-morbidities included in the Charlson index were ascertained. χ2 tests were used to compare the prevalence of co-morbidities by the presence or absence of each muscle abnormality. Logistic regressions were performed to evaluate which co-morbidities predicted muscle abnormalities adjusting for age, sex, body mass index, weight change, cancer stage, cancer site, race/ethnicity, and smoking. RESULTS: Mean age was 63 years; 50% of patients were male. The prevalence of low SMI and low SMD were 43.1% and 30.2%, respectively. Co-morbidities examined were more prevalent in patients with low SMD than in those with normal SMD, and most remained independent predictors of low SMD after adjustment for covariates. Co-morbidities associated with higher odds of low SMD included myocardial infarction [odds ratio (OR) = 1.77, P = 0.023], congestive heart failure (OR = 3.27, P < 0.001), peripheral vascular disease (OR = 2.15, P = 0.002), diabetes with or without complications (OR = 1.61, P = 0.008; OR = 1.46, P = 0.003, respectively), and renal disease (OR = 2.21, P < 0.001). By contrast, only diabetes with complications was associated with lower odds of low SMI (OR = 0.64, P = 0.007). CONCLUSIONS: Prevalence of muscle abnormalities was high in patients with non-metastatic CRC. Pre-existing co-morbidities were associated with low SMD, suggestive of a potential shared mechanism between fat infiltration into muscle and each of these co-morbidities.

Nonalcoholic fatty liver disease in spinal and bulbar muscular atrophy.

OBJECTIVE: To determine the prevalence and features of fatty liver disease in spinal and bulbar muscular atrophy (SBMA). METHODS: Two groups of participants with SBMA were evaluated. In the first group, 22 participants with SBMA underwent laboratory analysis and liver imaging. In the second group, 14 participants with SBMA were compared to 13 female carriers and 23 controls. Liver biopsies were done in 4 participants with SBMA. RESULTS: Evidence of fatty liver disease was detected by magnetic resonance spectroscopy in all participants with SBMA in the first group, with an average dome intrahepatic triacylglycerol of 27% (range 6%-66%, ref ≤5.5%). Liver dome magnetic resonance spectroscopy measurements were significantly increased in participants with SBMA in the second group relative to age- and sex-matched controls, with average disease and male control measurements of 17% and 3%, respectively. Liver biopsies were consistent with simple steatosis in 2 participants and nonalcoholic steatohepatitis in 2 others. CONCLUSIONS: We observed evidence of nonalcoholic liver disease in nearly all of the participants with SBMA evaluated. These observations expand the phenotypic spectrum of the disease and provide a potential biomarker that can be monitored in future studies.

Impact of Neuromuscular Electrical Stimulation (NMES) on 90-Day Episode Costs and Post-Acute Care Utilization in Total Knee Replacement Patients with Disuse Atrophy.

INTRODUCTION: This study evaluated differences in: 1) total episode payments, 2) probability of hospital readmission, 3) probability of inpatient rehab facility (IRF) and utilization, and 4) probability of skilled nursing care facility (SNF) utilization in patients who had disuse atrophy and underwent a total knee arthroplasty (TKA) and either did, or did not, receive preoperative home-based neuromuscular electrical stimulation (NMES) therapy. MATERIALS AND METHODS: We used the Medicare limited dataset for a 5% sample of beneficiaries from 2014 and 2015 to construct episodes-of-care for TKA (DRG-470) patients with disuse atrophy who underwent a TKA during the 30 days prior to hospital admission and 90 days post-discharge. Patients were stratified into those who either did or did not receive pre- and postoperative NMES therapy. An ordinary least square (OLS) model was used to estimate the impact of NMES on total episode. Linear probability models were used to estimate the impact of NMES on SNF or IRF utilization and readmission. RESULTS: A $3,274 reduction in episode payments for patients who used preoperative NMES versus those who did not (p<0.001) was demonstrated. The probability of readmission was 12.7% lower for those who used preoperative NMES therapy versus those who did not (p=0.609). The probability of utilizing IRF and SNF was 56.7% (p=0.061) and 46.4% (p=<0.001) lower for those who used pre- and postoperative NMES versus those who did not, respectively. CONCLUSION: Significant reduction in total episode payments and SNF utilization for TKA patients with disuse atrophy who had NMES therapy was demonstrated.

Towards a European Registry and Biorepository for Patients with Spinal and Bulbar Muscular Atrophy.

Pathomechanisms of spinal and bulbar muscular atrophy (SBMA) have been extensively investigated and are partially understood, but no effective treatment is currently available for this disabling disorder. Its rarity, the slow disease progression, and lack of sensitive-to-change outcome measures render design and conduction of clinical trials a challenging task. Therefore, it is fundamental to strengthen the network of clinical centers interested in SBMA for clinical trial readiness. We propose to create and maintain an International SBMA Registry where as many well-characterized patients as possible can be included, with the following aims: facilitate planning of clinical trials and recruitment of patients, define natural history of the disease, characterize epidemiology, develop standards of care, and inform the community of patients about research progresses and ongoing trials. We also aim at developing harmonized and coordinated biorepositories. The experience obtained during the last years in the field of other neuromuscular disorders and of Huntington disease offers valuable precedents.

Kidney function and sarcopenia in the United States general population: NHANES III.

BACKGROUND/AIMS: It is not known whether sarcopenia is associated with levels of kidney function in community-dwelling adults. METHODS: Subjects were adult Third National Health and Nutrition Examination Survey participants in whom bioimpedance was performed (n = 13,770). Class I sarcopenia was defined as a skeletal mass index of 1-2 standard deviations below and class II sarcopenia as < 2 standard deviations below young adult values. RESULTS: A monotonic association existed between increasing sarcopenia prevalence and declining glomerular filtration rate: > or = 90 ml/min/1.73 m2, 22.8% class I, 3.8% class II sarcopenia; 60-89 ml/min/1.73 m2, 33.6% class I, 5.3% class II sarcopenia, and < 60 ml/min/1.73 m2, 50.7% class I, 9.4% class II sarcopenia (p < 0.0001). This association dissipated when adjustment was made for older age and more comorbidity. Multivariate associations (p < 0.05) of sarcopenia and chronic kidney disease included: older age; low income-to-poverty ratio; overweight; lack of exercise; low carbohydrate, fat and protein intake; hypercalcemia; low 25-hydroxy-vitamin D3; higher diastolic blood pressure, and insulin resistance. CONCLUSION: Sarcopenia is common in community-dwelling adults with chronic kidney disease. Although causality cannot be assumed, several associations may be susceptible to intervention.

[Pathogenesis of "Leningrad" (blockade) hypertension (60-th anniversary of the Leningrad blockade)]. / Patogenez "leningradskoi" (blokadnoi) gipertonii (k 60-letiiu Leningradskoi blokady).

Leningrad (blockade) hypertension observed in survivors of the Leningrad blockade during the World War II is a unique form of hypertension initiated and maintained pathogenetically by disturbed neuroregulation resultant from a severe psychoemotional stress. Pathogenesis of Leningrad hypertension involves mechanisms playing a key role in pathogenesis of other forms of essential hypertension. A characteristic feature of this pathogenesis is interaction of the initial and key neurogenic factor with such hypertensive factors of alimentary-dystrophic genesis as lesions of the vascular wall secondary to marked hypoproteinemia and hypovolemia. Later, in addition to hypertension the patients developed atherosclerosis, nephrosclerosis and other diseases.

Founder effect in spinal and bulbar muscular atrophy (SBMA) in Scandinavia.

We haplotyped 13 Finnish, 10 Swedish, 12 Danish and 2 Norwegian SBMA (spinal and bulbar muscular atrophy, Kennedy disease) families with a total of 45 patients and 7 carriers for 17 microsatellite markers spanning a 25.2 cM region around the androgen receptor gene on chromosome Xq11-q12 in search of a genetic founder effect. In addition, the haplotypes of 50 Finnish, 20 Danish and 22 Swedish control males were examined. All the Scandinavian SBMA families shared the same 18 repeat allele for the intragenic GGC repeat, which was present in only 24% of the controls. Linkage disequilibrium was also seen for the closest microsatellite markers. In addition, extended haplotypes of the Finnish, Swedish and Danish SBMA families revealed country-specific common founder haplotypes, which over time became gradually shortened by recombinations. No common haplotype was found among the controls. The data suggest that the SBMA mutation was introduced into western Finland 20 generations ago. Haplotype analysis implies a common ancestor for the majority of Scandinavian SBMA patients.