Drug recommendation for optimization on treatment outcome for MDR/RR-TB based on a multi-center, large scale, retrospective cohort study in China.

OBJECTIVE: With the change in drug-resistant pattern, MDR/RR-TB was faced with underlying changes in regimens. A multi-center, large-scale, retrospective study performed aims to provide a recommendation of drug selection on optimization of outcome for the patients. METHOD: The study was conducted in six TB-specialized hospitals in China. Patients were included from 2018-2021 and followed up throughout the treatment. Using a multivarariable and propensity score-matched logistic regression analysis, we evaluated associations between outcomes and drug use, as well as clinical characteritics. RESULTS: Of 3112 patients, 74.29% had treatment sucess, 14.52% lost to follow-up, 9.67% failure, and 1.51% died. Treatment success was positively associated with Bedaquiline(Bdq), Linezolid(Lzd), and Cycloserin(Cs). Capreomycin(Cm) increased the risk of unfavorable outcomes. other drugs such as Amikacin(Amk) and clofazimine had no significant effect on outcomes. If isolates were susceptible to fluoroquinolones(FQs), FQs could decrease the risk of unfavorable outcomes. CONCLUSIONS: The recommendation order for the treatment of MDR/RR-TB is Bdq, Lzd, and Cs. FQs were decreased in use intensity. Injection drugs, whether Amk or Cm, are not recommended.

Primary tumor resection improves prognosis of unresectable carcinomas of the transverse colon including flexures with pulmonary metastasis: a cohort study.

PURPOSE: Studies of unresectable colorectal cancer pulmonary metastasis (CRPM) have rarely analyzed patient prognosis from the perspective of colonic subsites. This study aimed to evaluate the effects of primary tumor resection (PTR) on the prognosis of patients with unresectable pulmonary metastases of transverse colon cancer pulmonary metastasis (UTCPM), hepatic flexure cancer pulmonary metastasis (UHFPM), and splenic flexure cancer pulmonary metastasis (USFPM). METHODS: Patients were identified from the Surveillance, Epidemiology, and End Results database between 2000 and 2018. The Cox proportional hazards regression models were used to identify prognostic factors of overall survival (OS) and cause-specific survival (CSS). The Kaplan-Meier analyses and log-rank tests were conducted to assess the effectiveness of PTR on survival. RESULTS: This study included 1294 patients: 419 with UHFPM, 636 with UTCPM, and 239 with USFPM. Survival analysis for OS and CSS in the PTR groups, showed that there were no statistical differences in the the UHFPM, UTCPM, and USFPM patients. There were statistical differences in the UHFPM, UTCPM, and USFPM patients for OS and CSS. Three non-PTR subgroups showed significant statistical differences for OS and CSS. CONCLUSION: We confirmed the different survival rates of patients with UTCPM, UHFPM, and USFPM and proved for the first time that PTR could provide survival benefits for patients with unresectable CRPM from the perspective of the colonic subsites of the transverse colon, hepatic flexure, and splenic flexure.

Effects of Bedaquiline Combined with Fluoroquinolone and/or Clofazimine on QT Interval in Patients with Multidrug-Resistant Tuberculosis: a Retrospective Study.

With the application of bedaquiline (Bdq), the success rate of multidrug-resistant tuberculosis (MDR-TB) treatment has been significantly improved; however, the cardiac safety of the patients during treatment cannot be ignored. Hence, this study compared the effects of bedaquiline alone and bedaquiline combined with fluoroquinolones (FQs) and/or clofazimine (CFZ) on the QT interval. This single-center retrospective cohort study analyzed the clinical data of MDR-TB patients treated with bedaquiline for 24 weeks from January 2020 to May 2021 in Xi'an Chest Hospital and compared the changes in QTcF between the two groups. Eighty-five patients were included in the study and grouped by types of anti-TB drugs affecting the QT interval they used. Group A included bedaquiline (n = 33), and group B included bedaquiline in combination with fluoroquinolones and/or clofazimine (n = 52). Out of patients with available corrected QT interval by Fridericia's formula (QTcF) data, 2.4% (2/85) experienced a postbaseline QTcF of ≥500 ms, and 24.7% (21/85) had at least one change of QTcF of ≥60 ms from baseline. In group A, 9.1% (3/33) had at least one ΔQTcF of >60 ms, as did 34.6% (18/52) of group B. Multivariate Cox regression analysis showed that the adjusted risk of QT prolongation was 4.82 times higher in group B (95% confidence interval [CI], 1.406 to 16.488). Bedaquiline combined with other anti-TB drugs affecting QT interval significantly increased the incidence of grade 3 or 4 QT prolongation; however, no serious ventricular arrhythmia and permanent drug withdrawal occurred. The use of bedaquiline combined with fluoroquinolone and/or clofazimine is an independent risk factor affecting QT interval. IMPORTANCE Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis. The emergence of MDR-TB is caused by an organism that is resistant to at least isoniazid and rifampin and is currently considered the major challenge for the global control of TB. Bedaquiline is the first new TB drug in 50 years with a unique mechanism of action, strong anti-M. tuberculosis activity. Yet unexplained excess deaths in the bedaquiline arms have been found in some phase II clinical trials; thus, the FDA has issued a "boxed warning." However, the cardiac safety of the patients during treatment cannot be ignored. Accordingly, further investigations are needed to establish whether bedaquiline combined with clofazimine, fluoroquinolones, or anti-TB drugs affecting the QT interval in a long-course or short-course treatment increases the risk of QT prolongation.

Treatment Outcomes and Risk Factors of Multidrug-Resistant Tuberculosis Patients in Xi'an China, a Retrospective Cohort Study.

Background: Long-term regimens are widely used for multidrug-resistant tuberculosis (MDR-TB) in North-West China; however, risk factors associated with the treatment outcomes are not well known. Methods: This was a retrospective cohort study of MDR-TB patients treated with longer regimen in Xi'an from 2017 to 2019. Risk factors associated with the treatment outcome were analyzed using multiple logistic regression. Results: Of the 446 patients with MDR-TB included, 215 were cured, 84 completed treatment, 23 failed treatment, 108 were lost to follow-up, and 16 died. Unfavorable outcome risk factors were age >40 years (OR = 3.25, 95% CI = 2.12-4.98), male sex (OR = 2.53, 95% CI = 1.52-4.22), and re-treated tuberculosis (OR = 1.70, 95% CI = 1.11-2.61), whereas poor treatment outcome risk factors were age >40 years (OR = 5.51, 95% CI = 2.52-12.07), fluoroquinolones not used in the regimen (OR = 3.31, 95% CI = 1.45-7.51), and smear-positive (OR = 4.0, 95% CI = 1.47-10.8). Conclusion: In Xi'an, MDR-TB treatments with long-term regimens had low success rates, and age, sex, and tuberculosis treatment history were risk factors of MDR-TB treatment outcomes.

Alterations of the oral microbiome in patients treated with the Invisalign system or with fixed appliances.

INTRODUCTION: Although the Invisalign system has been used widely in recent years, the influences of this treatment on the oral microbiome and whether or not this influence is different from that of fixed appliances is still unknown. In this study, we investigated the changes in the oral microbiome in patients treated with the Invisalign system or with fixed appliances. METHODS: Fifteen subjects were enrolled, comprising 5 fixed appliance patients, 5 Invisalign patient, and 5 healthy controls. Saliva samples were collected, and high-throughput pyrosequencing was performed based on the 16S rRNA gene. RESULTS: Both fixed and Invisalign orthodontic treatments resulted in dysbiosis of the oral microbiome. Firmicutes and TM7 at the phyla level and Neisseria at the genus level displayed statistically significant differences between the 2 orthodontic groups. The effect of these changes with microbiome on oral health was inconsistent. The inferred microbial function of the Invisalign group suggested this group was more predisposed to periodontal diseases. CONCLUSION: The influence of the Invisalign system on the oral microbiome was no better for oral health compared with fixed appliances. The convenience of maintaining oral hygiene rather than changes in the oral microbiome may be the underlying reason for the performance of the Invisalign system on oral health.

[Protection of polysaccharides-2b from mudan cortex of Paeonia suffruticosa andr on diabetic cataract in rats].

OBJECTIVE: To observe the the protective effection of polysaccharides-2b of mudan cortex of Paeonia suffruticosa andr (PSM2b) on diabetic cataract. METHOD: The animal model of diabetic cataract in rats was induced by streptozotocin (STZ) and freund's adjuvant complete (CFA). The initial opacity occurrence time in lens was investigated with cranny lamp, and opacity degree of lens was compared too. The activities of glutathione peroxidase (GSH-pX), superoxide dismutase (SOD), catalase (CAT), the content of malonaldehyde (MDA) in serum and lens were detected. At the same time, the activities of Na(+) -K(+) -ATPase, the content of macromolecular weight protein and infusibility protein in lens were detected too. RESULT: The results examinated by cranny lamp showed that PSM2b could significantly postpone the occurrence and alleviate opacity degree of lens. Compared with model group, every treatment group of PSM2b could lower the level of MDA, high and middle dose groups could increase the levels of SOD, GSH-pX, CAT in serum and lens in evidence, and enhance the activity of Na(+) -K(+) -ATPase. These indexes present favorable positive correlation between dose and effect. CONCLUSION: All these results demonstrated that PSM2b had apparently protective effection on diabetic cataract in rats.

[Protection of polysaccharide ATPS-2 from Armillariella tabescens on immunological liver injury in mice induced by BCG plus LPS].

OBJECTIVE: To observe the effect of polysaccharide ATPS-2 from Armillariella tabescens on the immunological liver injury in mice induced by BCG plus LPS. METHOD: BCG and LPS were adopted to establish BCG plus LPS liver injury model in mice. The content of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and NO, the activity of superoxide dismutase (SOD) and malondiadehyde (MDA) content of liver homogenate in mice were measured by colorimetric method. The content of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), on serum were measured by enzyme linked immunosorbent assay (ELISA) , and T- and B-lymphocyte proliferation were measured by MTT. Index of liver, spleen and thymus were calculated after treatment. RESULT: Polysaccharide ATPS-2 from A. tabescens (25, 50, 100 mg x kg(-1)) could obviously reduce the high level of ALT, AST, NO and TNF-alpha, IL-1 on serum, inhibit the high level of MDA, increase the low activity of SOD in liver homogenate and enhance T-and B-lymphocyte proliferation, elevate the spleen, thymic index and decrease liver index of the mice to different extent. CONCLUSION: Polysaccharide ATPS-2 from A. tabescens had apparently protective effects in the immunological liver injury mice induced by BCG plus LPS.