These observations in a contemporary advanced ADHF cohort suggest that serum chloride levels at admission are independently and inversely associated with mortality. The prognostic value of serum sodium in ADHF was diminished compared with chloride.
prognosis. Systematic description of metabolite patterns in large numbers of HF patients has not been described. Methods: We analyzed plasma samples from 400 patients with chronic HF. All participants met Framingham criteria for HF and had a previous echocardiogram. Data on demographics, comorbid conditions, functional status (6 minute walk distance [6MWD]), and quality of life (Kansas City Cardiomyopathy Questionnaire [KCCQ]) were collected. A blood sample was obtained and aliquoted plasma stored at -70 OC. Eighty-six amino acids (AA), organic acids (OA) and acylcarnitines (AC) were quantified using targeted metabolomic profiling. Analytes with coefficient of variation!0.05 were considered non-variable and not analyzed further. Data was log transformed to maintain a symmetric distribution. Metabolite levels were tested for association with gender, race, HF type (HFrEF vs HFpEF), diabetes status, NYHA class, and 6MWD using linear regression. Multiple comparisons were accounted for by False Discovery Rate (FDR), with FDR!0.05 being considered significant. Results: The cohort was 50% African American, 50% female, 67% HFrEF, and had an average age of 70. There were significant differences in metabolite abundance by each characteristic examined, including race and gender. A strong pattern emerged for citric acid cycle intermediates and HF phenotype; one or more of these intermediates showed significant association with HF type, NYHA class, and 6MWD. Also of note was an increased abundance of short branched-chain AC among diabetics, which was not accompanied by the expected increase in corresponding branched-chain AA. Each of these associations persisted after adjustment for renal function. Conclusion: There are significant differences in plasma metabolomic profiles among HF patients. Metabolites vary by demographics and diabetes status, and citric acid cycle intermediates may be associated with disease severity/prognosis. Analysis in larger data sets is warranted.Introduction: Acute decompensated heart failure (ADHF) can be complicated by electrolyte abnormalities. While there is an abundance of knowledge regarding the clinical significance of serum sodium levels, to our knowledge, there are limited data regarding the prognostic significance of serum chloride levels in ADHF. Hypothesis: We hypothesize that lower serum chloride levels will be associated with long-term mortality after admission for ADHF. Methods: We reviewed 1,318 consecutive patients with established chronic heart failure, with implantable cardioverter defibrillators, admitted for ADHF to the Cleveland Clinic between 7/2008 and 12/2013 and also validated our findings in an independent ADHF cohort from the University of Pennslvania (N5876). All patients were followed for all-cause mortality. Cox-proportional hazards models were adjusted for admission sodium, blood urea nitrogen, length of stay, age, ischemic cardiomyopathy, beta-blocker use, renin-angiotensin system inhibitor use, and mineralocorticoid antagonist use. Results: In our cohort (median age...
Introduction: X‐linked myotubular myopathy (XLMTM), characterized by severe hypotonia, weakness, respiratory distress, and early mortality, is rare and natural history studies are few. Methods: RECENSUS is a multicenter chart review of male XLMTM patients characterizing disease burden and unmet medical needs. Data were collected between September 2014 and June 2016. Results: Analysis included 112 patients at six clinical sites. Most recent patient age recorded was ≤18 months for 40 patients and >18 months for 72 patients. Mean (SD) age at diagnosis was 3.7 (3.7) months and 54.3 (77.1) months, respectively. Mortality was 44% (64% ≤18 months; 32% >18 months). Premature delivery occurred in 34/110 (31%) births. Nearly all patients (90%) required respiratory support at birth. In the first year of life, patients underwent an average of 3.7 surgeries and spent 35% of the year in the hospital. Discussion: XLMTM is associated with high mortality, disease burden, and healthcare utilization. Muscle Nerve 57: 550–560, 2018
This study used a sex-linked dwarf mutant (SLD) chicken to evaluate growth-promoting and metabolic effects of recombinant human insulin-like growth factor-I (rhIGF-I) treatment. The SLD chicken is characterized by a 30% reduction in body weight and by high plasma GH levels, low plasma IGF-I and triodothyronine (T3) levels and very low GH binding on liver membranes, suggesting reduced functional GH receptors compared with normal chickens. The effects of a continuous s.c. infusion by osmotic mini-pump of 0.1 mg rhIGF-I/kg per day from 4 to 8 weeks of age on body weight, bone growth and body composition were investigated in female SLD and normal chicks. In addition, half of the birds received a dietary supplement of T3 (0.1 parts per million). Plasma levels of IGF-I, GH, T3, thyroxine and insulin were followed during the treatment. In normal chicks, rhIGF-I infusion had no effect on growth and little effect on plasma hormone levels except for a decrease in plasma insulin. In dwarf chicks, rhIGF-I infusion slightly increased body weight but had no effect on longitudinal bone growth. In addition, plasma GH levels were decreased and T3 levels remained lower than in normal chicks. Normal and dwarf chicks showed a decrease in abdominal fat after both IGF-I administration and T3 supplementation, the treatments having additive effects in dwarf chicks only. The combined rhIGF-I and T3 treatment restored a quasi-normal hormonal pattern in dwarf chicks, except for insulin which remained lower than in normal chicks. These results suggest that IGF-I in the chicken has no direct endocrine effect on statural growth.
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