BackgroundLimited treatment options of extensive drug-resistant tuberculosis (XDR-TB) have led to its high mortality worldwide. Relevant data about mortality of XDR-TB patients in literature are limited and likely underestimate the real situation in China, since the majority of patients with XDR-TB are lost to follow-up after discharge from TB hospitals. In this study, we sought to investigate the mortality and associated risk factors of Human Immunodeficiency Virus (HIV)-negative patients with XDR-TB in China.MethodsAll patients who were diagnosed with XDR-TB for the first time in four TB care centers across China between March 2013 and February 2015 were consecutively enrolled. Active tracking through contacting patients or family members by phone or home visit was conducted to obtain patients’ survival information by February 2017. Multivariable Cox regression models were used to evaluate factors associated with mortality.ResultsAmong 67 patients enrolled, the mean age was 48.7 (Standard Deviation [SD] = 16.7) years, and 51 (76%) were men. Fourteen patients (21%) were treatment naïve at diagnosis indicating primary transmission. 58 (86.8%) patients remained positive for sputum smear or culture when discharged. During a median follow-up period of 32 months, 20 deaths occurred, with an overall mortality of 128 per 1000 person-years. Among patients who were dead, the median survival was 5.4 months (interquartile range [IQR]: 2.2–17.8). Seventeen (85%) of them died at home, among whom the median interval from discharge to death was 8.4 months (IQR: 2.0–18.2). In Cox proportional hazards regression models, body mass index (BMI) < 18.5 kg/m2 (adjusted hazard ratio [aHR] = 4.5, 95% confidence interval [CI]: 1.3–15.7), smoking (aHR = 4.7, 95%CI:1.7–13.2), or a clinically significant comorbidity including heart, lung, liver, or renal disorders or auto-immune diseases (aHR = 3.5, 95%CI: 1.3–9.4), were factors independently associated with increased mortality.ConclusionOur study suggested an alarming situation of XDR-TB patients in China with a sizable proportion of newly transmitted cases, a high mortality rate, and a long period in community. This observation calls for urgent actions to improve XDR-TB case management in China, including providing regimens with high chances of cure and palliative care, and enhanced infection control measures.
Abstractα5β1 integrin is highly expressed in airway smooth muscle cells and mediate the adhesion of airway smooth muscle cells to fibronectin to regulate airway remodelling in asthma. This study aimed to investigate the effects of synthetic cyclic peptide *CRRETAWAC* on fibronectin‐induced cytokine secretion of airway smooth muscle cells and the underlying mechanism. Human airway smooth muscle cells were isolated and treated with fibronectin, IL‐13, *CRRETAWAC* peptide, α5β1 integrin‐blocking antibody, FAK inhibitor or p38 MAPK inhibitor. The transcription and secretion of eotaxin‐1 and RANTES were detected by real‐time PCR and ELISA, respectively. The phosphorylation of FAK and MAPKs including p38, ERK1/2 and JNK1/2 was detected by Western blot analysis. The transcription and secretion of eotaxin‐1 and RANTES increased in airway smooth muscle cells cultured in fibronectin‐coated plates. However, α5β1 integrin‐blocking antibody, *CRRETAWAC* peptide, FAK inhibitor or p38 MAPK inhibitor significantly reduced mRNA levels and the secretion of eotaxin‐1 and RANTES in airway smooth muscle cells cultured in fibronectin‐coated plates. In addition, the phosphorylation of FAK and p38 MAPK was significantly increased in airway smooth muscle cells cultured in fibronectin‐coated plates compared to the cells cultured in uncoated plates and was significantly reduced in airway smooth muscle cells treated with *CRRETAWAC* peptide. Fibronectin induces cytokine synthesis and secretion of airway smooth muscle cells. Peptide *CRRETAWAC* antagonizes fibronectin‐induced cytokine synthesis and secretion of airway smooth muscle cells via the inhibition of FAK and p38 MAPK, and is a potential agent for the therapy of asthma.
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