Nutritional Indices Predict All Cause Mortality in Patients with Multi-/Rifampicin-Drug Resistant Tuberculosis.

Background: Multidrug- and rifampicin-resistant tuberculosis (MDR/RR-TB) with high mortality remains a public health crisis and health security threat. This study aimed to explore the predictive value of nutritional indices for all-cause mortality (ACM) in MDR/RR-TB patients. Methods: We retrospectively recruited MDR/RR-TB patients between January 2015 and December 2021, randomly assigning them to training and validation cohorts. Patients were divided into high nutritional risk groups (HNRGs) and low nutritional risk groups (LNRGs) based on the optimal cut-off value obtained from receiver operating characteristic (ROC) analyses of the hemoglobin-albumin-lymphocyte-platelet (HALP) score, prognostic nutritional index (PNI), and controlling nutritional status (CONUT) score. In the training cohort, Kaplan-Meier survival curves and Log rank tests were used to compare overall survival (OS) between the groups. Cox risk proportion regression analyses were used to explore the risk factors of ACM in patients with MDR/RR-TB. The predictive performance of ACM was assessed using area under the curve (AUC), sensitivity and specificity of ROC analyses. Results: A total of 524 MDR/RR-TB patients, with 255 in the training cohort and 269 in the validation cohort, were included. Survival analyses in the training cohort revealed significantly lower OS in the HNRGs compared to the LNRGs. After adjusting for covariates, multivariate analysis identified low HALP score, low PNI and high CONUT score were independent risk factors for ACM in MDR/RR-TB patients. ROC analyses demonstrated good predictive performance for ACM with AUCs of 0.765, 0.783, 0.807, and 0.811 for HALP score, PNI, CONUT score, and their combination, respectively. Similar results were observed in the validation set. Conclusion: HALP score, PNI, and CONUT scores could effectively predict ACM in patients with MDR/RR-TB. Hence, routine screening for malnutrition should be given more attention in clinical practice to identify MDR/RR-TB patients at higher risk of mortality and provide them with nutritional support to reduce mortality.

A Novel Inflammatory Indicator for Tuberculosis-Associated Obstructive Pulmonary Disease (TOPD): The Systemic Inflammatory Response Index (SIRI).

Background: The development of chronic obstructive pulmonary disease (COPD) following tuberculosis (TB) is known as tuberculosis-associated obstructive pulmonary disease (TOPD). This study aimed to explore the predictive value of inflammatory indicators for TOPD in TB patients. Methods: Data for this cross-sectional study were collected between January 2014 and January 2022 at Wuhan Jinyintan Hospital. The ratio of inflammatory indicators, including Systemic Inflammatory Response Index (SIRI), C-reactive protein-to-lymphocyte ratio (CLR), eosinophil count-to-lymphocyte count ratio (ELR), were calculated. Univariate and multivariate logistic regression analyses were conducted to explore the association between the ratio of inflammatory indicators and TOPD. Furthermore, the relationship between the ratio of inflammatory indicators and TOPD was investigated using propensity score matching (PSM) and receiver operating characteristic (ROC) curve analysis was performed to evaluate their predictive value for TOPD. Results: The present study included a total of 737 patients, of whom 83 participants (11.26%) had TOPD. Sixty-nine TOPD patients and 69 non-TOPD (NTOPD) patients were successfully matched. Univariate and multivariable logistics regression analysis, conducted before and after PSM, revealed that SIRI was independently significantly associated with an increased risk of TOPD. The area under curve (AUC) of SIRI were 0.702 and 0.668 before and after PSM, respectively. Additionally, patients were stratified into four different groups based on SIRI quartiles for further analysis. The prevalence of TOPD in TB patients showed an increase with higher SIRI values, both before and after PSM. Conclusion: Levels of inflammatory indicators were higher in TOPD patients when compared to NTOPD patients. SIRI may be a simple and useful inflammatory index for assessing TOPD, and TB patients with higher values of SIRI are more likely to be high-risk group for TOPD.

Bioequivalence of Recombinant Human Teriparatide Injection in Healthy Adult Female Subjects in the Fasting State.

A single-center, randomized, open, 2-period, self-crossover, single-dose trial was conducted to evaluate the bioequivalence of the test (T) and reference (R) preparations in healthy adult female subjects under fasting conditions. Seventy-six subjects were enrolled in the study, and subjects were randomly divided into 2 groups at a 1:1 ratio and were administered once per period, with a 4-day washout period. In each period, plasma drug concentrations, blood calcium changes, and antibodies were determined for pharmacokinetics, pharmacodynamics, and immunogenicity analysis, respectively, and adverse events were recorded for safety analysis. The 90% confidence intervals for the geometric mean ratios (T:R) of maximum plasma concentration, area under the plasma concentration-time curve from time 0 to the last measurable concentration, and area under the plasma concentration-time curve from time 0 to infinity were within the predefined bioequivalence criterion of 80%-125%, indicating bioequivalence between the T and R preparations under fasting conditions. Comparable serum calcium levels demonstrated pharmacodynamics similarity, and no differences were found in immunogenicity profiles. Additionally, the incidence of adverse reactions to the T preparation was 18.4% lower than that of the R preparation (31.6%). This study confirmed the bioequivalence of the T and R preparations under fasting conditions, along with comparable immunogenicity profiles and good safety.

The survival analysis of rifampicin/multidrug-resistant tuberculosis patients based on the levels of inflammatory biomarkers: a retrospective cohort study.

Purpose: The development of tuberculosis and inflammatory status are closely related. The aim of this study was to investigate the prognostic value of inflammatory biomarkers in patients with rifampicin/multidrug-resistant tuberculosis (RR/MDR-TB). Patients and methods: This study recruited 504 patients with RR/MDR-TB from Wuhan Jinyintan Hospital. A total of 348 RR/MDR patients from January 2017 to December 2019 were defined as training set, the rest of patients as validation set. The patients were divided into three-risk degrees according to the levels of inflammatory biomarkers (median, 85th percentile). Kaplan-Meier curve and log-rank test were used to assess survival differences among the groups. Cox proportion risk regression was used to identify risk factors for RR/MDR-TB mortality. Results: In training set, cox proportion risk regression analysis showed that high age (≥60 years) [OR (95%CI):1.053(1.03188-1.077)], smoking [OR (95%CI):2.206(1.191-4.085)], and bronchiectasia [OR (95%CI):2.867(1.548-5.311)] were prognostic factors for RR/MDR-TB patients. In addition, lower survival rates were observed in high CAR group [OR (95%CI):1.464(1.275-1.681)], high CPR group[OR (95%CI):1.268(1.101-1.459)], high CLR group[OR (95%CI):1.004(1.002-1.005)], high NLR group[OR (95%CI):1.103(1.069-1.139)], high PLR group[OR (95%CI):1.003(1.002-1.004)], and high MLR group[OR (95%CI):3.471(2.188-5.508)].Furthermore, AUCs of age, smoking, bronchiectasia, CAR, CPR, CLR, NLR, PLR, and MLR for predicting mortality in RR/MDR-TB patients were 0.697(95%CI:0.618-0.775), 0.603(95%CI:0.512-0.695), 0.629(95%CI:0.538-0.721), 0.748(95%CI:0.675-0.821, P<0.05), 0.754(95%CI:0.683-0.824, P<0.05), 0.759(95%CI:0.689-0.828, P<0.05), 0.789(95%CI:0.731-0.846, P<0.05), 0.740(95%CI:0.669-0.812, P<0.05), and 0.752(95%CI:0.685-0.819, P<0.05), respectively. Importantly, the AUC of predicting mortality of combination of six inflammatory biomarkers [0.823 (95%CI:0.769-0.876)] is higher than any single inflammatory biomarkers. Additionally, the similar results are also obtained in the validation set. Conclusion: Inflammatory biomarkers could predict the survival status of RR/MDR-TB patients. Therefore, more attention should be paid to the level of inflammatory biomarkers in clinical practice.

A Scoring System Based on Laboratory Parameters and Clinical Features to Predict Unfavorable Treatment Outcomes in Multidrug- and Rifampicin-Resistant Tuberculosis Patients.

Background: The growth of antibiotic resistance to Mycobacterium TB represents a major barrier to the goal of "Ending the global TB epidemics". This study aimed to develop and validate a simple clinical scoring system to predict the unfavorable treatment outcomes (UTO) in multidrug- and rifampicin-resistant tuberculosis (MDR/RR-TB) patients. Methods: A total of 333 MDR/RR-TB patients were recruited retrospectively. The clinical, radiological and laboratory features were gathered and selected by lasso regression. These variables with area under the receiver operating characteristic curve (AUC)>0.6 were subsequently submitted to multivariate logistic analysis. The binomial logistic model was used for establishing a scoring system based on the nomogram at the training set (N = 241). Then, another independent set was used to validate the scoring system (N = 92). Results: The new scoring system consists of age (8 points), education level (10 points), bronchiectasis (4 points), red blood cell distribution width-coefficient of variation (RDW-CV) (7 points), international normalized ratio (INR) (7 points), albumin to globulin ratio (AGR) (5 points), and C-reactive protein to prealbumin ratio (CPR) (6 points). The scoring system identifying UTO has a discriminatory power of 0.887 (95% CI=0.835-0.939) in the training set, and 0.805 (95% CI=0.714-0.896) in the validation set. In addition, the scoring system is used exclusively to predict the death of MDR/RR-TB and has shown excellent performance in both training and validation sets, with AUC of 0.930 (95% CI=0.872-0.989) and 0.872 (95% CI=0.778-0.967), respectively. Conclusion: This novel scoring system based on seven accessible predictors has exhibited good predictive performance in predicting UTO, especially in predicting death risk.

[Study on the Fritillaria cirrhosa seed germination and polyploid induction].

OBJECTIVE: In order to improving the existent breeds of Fritillaria cirrhosa, increasing its medicinal ingredients and enriching the resources of heredity breeding. METHODS: By using of low-temperature stratification treatment, the seed of Fritillaria cirrhosa completed its after-ripening of physiology and morphology. The induction treatment by different concentrations of colchicine solution and different treatment times for Fritillaria cirrhosa seeds were compared. RESULT: Detected the plant morphology and chromosome number, it is shown that the induced material obviously possessed the characteristics of polyploid. CONCLUSION: With the treatment of 30 mg/L GA3 for 32 h and stratification for 70 d, the seed germination rate of Fritillaria cirrhosa reached 67.0%. After treated with 0.1% colchicine solution for 48 h, the stratificationed mature seed showed polyploid inductivity of 85.7%.