Ubjects (`cases’) were identified consecutively from patients with untreated pulmonary TB which had been newly-diagnosed by 2 or more sputum smear samples positive for Acid Fast Bacilli (AFB) following World Health Organization (WHO) guidelines [30]. Exclusion criteria included age less than 18 years, prior treatment for TB, and known comorbidity with diabetes mellitus (DM), HIV, malignancy, lung disease other than TB, or 1485-00-3 site cardiac disease. Cases were followed during the first two months of treatment with a standard regimen of Isoniazid, Rifampin, Ethambutol, and Pyrazinamide as per the Bolivian National TB Control Program guidelines. We compared results to a control group of healthy volunteers (`controls’) drawn from community organizations within the same geographic region as cases. Both cases and controls were screened by serology for HIV and all were negative. Anlotinib baseline evaluations were performed on all subjects, including blood samples, appetite evaluation, height and weight measurements, and bioimpedance analysis. Cases had repeat evaluations at treatment days 30 and 60.Statistical EvaluationWe evaluated differences in demographics between cases and controls using simple t-tests. For comparisons between cases and controls for key measures (nutritional status and hormones), we used Generalized Estimating Equations in a univariate regression to adjust for the correlated covariance structure from repeated measures among cases [36]. Thus, p-values reported are more conservative than individual comparisons for every one of the cases and controls at each follow-up time. Pearson correlations were computed for appetite, BMI, and BF versus PYY, leptin, ghrelin, and resistin for cases at each time point (baseline, days 30 and 60). Reported p-values were adjusted for multiple comparisons using Sidak’s method [37]. Due to the exploratory nature of the correlations, unadjusted p-values were also examined. To evaluate the effects of “abnormal” hormone levels, multivariate regressions for changes in appetite, BF, and BMI during treatment were fit for extreme pre-treatment values of each hormone. Values in cases were categorized as above,Cachexia in TBbelow or within the 95 confidence interval of control values. These categories were then regressed on the amount of change observed in nutritional status, controlling for baseline nutritional status and using “within the 95 confidence interval of control values” as the reference group. For example, if the outcome was change in appetite from baseline to day 30, two predictors would be a 3-level categorical variable for PYY and the baseline appetite score. Only appetite changes from baseline to day 30 and BF and BMI changes from baseline to day 60 were included, as changes during other treatment intervals were not significant (Table 1).Appetite-Regulatory HormonesMean PYY was elevated at 164.6 pcg/ml in pre-treatment cases, approximately twice the plasma concentration of controls (Figure 1, Table 1). PYY concentrations decreased 45 from baseline during the first 30 days of treatment (p,0.0001) at which time they were not significantly different from control values. There was a non-significant 14 PYY decline from day 30 to 60 (Table 1, Figure 1). Baseline leptin was three-fold lower in cases than in controls (3.2 pcg/ml vs 9.9 pcg/ml, p,0.001) and increased significantly during each treatment interval (p = 0.004 baseline to day 30, p = 0.036 day 30 to 60). Even by day 60, leptin levels remained be.Ubjects (`cases’) were identified consecutively from patients with untreated pulmonary TB which had been newly-diagnosed by 2 or more sputum smear samples positive for Acid Fast Bacilli (AFB) following World Health Organization (WHO) guidelines [30]. Exclusion criteria included age less than 18 years, prior treatment for TB, and known comorbidity with diabetes mellitus (DM), HIV, malignancy, lung disease other than TB, or cardiac disease. Cases were followed during the first two months of treatment with a standard regimen of Isoniazid, Rifampin, Ethambutol, and Pyrazinamide as per the Bolivian National TB Control Program guidelines. We compared results to a control group of healthy volunteers (`controls’) drawn from community organizations within the same geographic region as cases. Both cases and controls were screened by serology for HIV and all were negative. Baseline evaluations were performed on all subjects, including blood samples, appetite evaluation, height and weight measurements, and bioimpedance analysis. Cases had repeat evaluations at treatment days 30 and 60.Statistical EvaluationWe evaluated differences in demographics between cases and controls using simple t-tests. For comparisons between cases and controls for key measures (nutritional status and hormones), we used Generalized Estimating Equations in a univariate regression to adjust for the correlated covariance structure from repeated measures among cases [36]. Thus, p-values reported are more conservative than individual comparisons for every one of the cases and controls at each follow-up time. Pearson correlations were computed for appetite, BMI, and BF versus PYY, leptin, ghrelin, and resistin for cases at each time point (baseline, days 30 and 60). Reported p-values were adjusted for multiple comparisons using Sidak’s method [37]. Due to the exploratory nature of the correlations, unadjusted p-values were also examined. To evaluate the effects of “abnormal” hormone levels, multivariate regressions for changes in appetite, BF, and BMI during treatment were fit for extreme pre-treatment values of each hormone. Values in cases were categorized as above,Cachexia in TBbelow or within the 95 confidence interval of control values. These categories were then regressed on the amount of change observed in nutritional status, controlling for baseline nutritional status and using “within the 95 confidence interval of control values” as the reference group. For example, if the outcome was change in appetite from baseline to day 30, two predictors would be a 3-level categorical variable for PYY and the baseline appetite score. Only appetite changes from baseline to day 30 and BF and BMI changes from baseline to day 60 were included, as changes during other treatment intervals were not significant (Table 1).Appetite-Regulatory HormonesMean PYY was elevated at 164.6 pcg/ml in pre-treatment cases, approximately twice the plasma concentration of controls (Figure 1, Table 1). PYY concentrations decreased 45 from baseline during the first 30 days of treatment (p,0.0001) at which time they were not significantly different from control values. There was a non-significant 14 PYY decline from day 30 to 60 (Table 1, Figure 1). Baseline leptin was three-fold lower in cases than in controls (3.2 pcg/ml vs 9.9 pcg/ml, p,0.001) and increased significantly during each treatment interval (p = 0.004 baseline to day 30, p = 0.036 day 30 to 60). Even by day 60, leptin levels remained be.
