Activities of Biapenem against Mycobacterium tuberculosis in Macrophages and Mice.

OBJECTIVE: To assess the activities of biapenem against multidrug-resistant and extensively drug-resistant Mycobacterium tuberculosis. METHODS: Biapenem/clavulanate (BP/CL) was evaluated for in vitro activity against Mycobacterium tuberculosis (Mtb) multidrug-resistant (MDR) isolates, extensively drug-resistant (XDR) isolates, and the H37RV strain. BP/CL activity against the H37Rv strain was assessed in liquid cultures, in macrophages, and in mice.. RESULTS: BP/CL exhibited activity against MDR and XDR Mtb isolates in liquid cultures. BP/CL treatment significantly reduced the number of colony forming units (CFU) of Mtb within macrophages compared with control untreated infected macrophages. Notably, BP/CL synergized in pairwise combinations with protionamide, aminosalicylate, and capreomycin to achieve a fractional inhibitory concentration for each pairing of 0.375 in vitro. In a mouse tuberculosis infection model, the efficacy of a cocktail of levofloxacin + pyrazinamide + protionamide + aminosalicylate against Mtb increased when the cocktail was combined with BP/CL, achieving efficacy similar to that of the positive control treatment (isoniazid + rifampin + pyrazinamide) after 2 months of treatment. CONCLUSION: BP/CL may provide a new option to clinically treat MDR tuberculosis.

The volume threshold of 300 versus 100 ml/day for chest tube removal after pulmonary lobectomy: a meta-analysis.

OBJECTIVES: In this meta-analysis, we conducted a pooled analysis of clinical studies comparing the efficacy of a volume threshold of 300 ml/day before removing a chest tube (CT) versus 100 ml/day after a lobectomy. METHODS: According to the recommendations of the Cochrane Collaboration, we established a rigorous study protocol. We performed a systematic electronic search of PubMed, Embase, Cochrane Library, Web of Science databases, CNKI, the Wanfang database, CBMdisc and Google Scholar to identify articles to include in our meta-analysis. A literature search was performed using relevant keywords. A meta-analysis was performed using RevMan© software. RESULTS: Five studies, published between 2014 and 2015, including 615 patients (314 patients who had the CT removed when daily drainage was <300 ml and 301 patients who had the CT removed when daily drainage was <100 ml) met the selection criteria. From the available data, the patients using the volume threshold of 300 ml/day had a significantly decreased duration of drainage [MD = -44.07; 95% confidence interval (CI) -64.45 to -23.68; P < 0.0001] and hospital stay after operation (MD = -2.25; 95% CI -3.52 to -0.97; P = 0.0006) compared with patients using a volume threshold of 100 ml/day after a pulmonary lobectomy. However, no significant differences were observed in postoperative complications, such as pleural fluid reaccumulation [Odds ratio (OR) = 1.73; 95% CI = 0.74-4.07; P = 0.21] and atelectasis (OR = 0.97; 95% CI = 0.52-1.81; P = 0.93). Thoracentesis rates after removing the CT also showed no significant difference (OR = 1.53; 95% CI 0.55-4.22; P = 0.41). CONCLUSIONS: Our results showed that a higher volume threshold, up to 300 ml/day, is effective in reducing hospitalization times and duration of drainage in patients who undergo a lobectomy. Moreover, the volume threshold of 300 ml/day does not increase the occurrence of postoperative atelectasis, pleural fluid reaccumulation and thoracentesis rates. However, this review is limited by the methodological quality of the included trials, and additional studies according to the recommendations of Cochrane Library are appreciated.

Comparative beneficiary effects of immunotherapy against chemotherapy in patients with advanced NSCLC: Meta-analysis and systematic review.

Lung cancer is the most commonly diagnosed cancer among men and it is the third ranked in women. There are two major types of lung cancer, namely, small cell lung cancer (SCLC), which accounts for ~20% of the cases, and non-small cell lung cancer (NSCLC), which is the most common. Chemotherapy and chemoradiotherapy have been used as the first-line therapies but suffer from lack of efficacy and also of several toxic adverse effects. Immunotherapeutic approaches including tumor antigen vaccination, monoclonal antibodies targeting checkpoint pathways and also activated immune cells are being developed and have been shown to be effective in treating NSCLC. Despite their promise, efficacy of several immunotherapies has not been consistent. We undertook this meta-analysis study to analyze results from clinical trials that compared efficacy and safety of immunotherapies with placebo or chemotherapy/radiotherapy in improving overall survival (OS) and progression-free survival (PFS) of NSCLC patients. Various databases were searched to identify randomized clinical studies examining the efficacy and safety of antibody- and vaccine-based immunotherapies in NSCLC patients in comparison to chemotherapy or chemoradiotherapy or placebo. Effects on OS and PFS and also adverse events have been compared. In accordance with the selection criteria, a total of 13 studies with 3,513 patients in immunotherapy and 3,072 patients in chemotherapy/placebo, were selected. PFS (odds ratio 1.81, 95% CI 1.36, 2.42; P<0.0001) and OS (P<0.0001) are found to be greatly improved by immunotherapies. Immunotherapy of NSCLC patients was also found to prevent several adverse effects and to improve daily living ability of the patients. The present meta-analysis strongly suggests that immunotherapy improves OS and PFS of patients with NSCLC.

Comparison of Histological, Microbiological, and Molecular Methods in Diagnosis of Patients with TBLN Having Different Anti-TB Treatment Background.

OBJECTIVE: The influence of anti-tuberculosis (TB) treatment history on tuberculous lymphadenitis (TBLN) diagnosis is unclear. Therefore, this study aims to evaluate the diagnostic methods, including histology, microbiology, and molecular tests, used for TBLN. METHODS: In this study, suspected patients with TBLN and having different anti-TB treatment background were enrolled. All the samples were tested simultaneously by histology, Ziehl-Neelsen (ZN) staining, mycobacterial culture (culture), Xpert MTB/RIF (xpert), real-time PCR, and high-resolution melting curve PCR (HRM). Thereafter, the performance of these methods on samples with different anti-TB treatment background was assessed. RESULTS: In our study, 89 patients were prospectively included 82 patients with TBLN and 7 with other diseases. The overall sensitivities of Xpert, real-time PCR, histology, ZN staining, and culture were 86.6%, 69.5%, 58.5%, 43.9%, and 22.0%, respectively. The anti-TB treatment history revealed dramatic influences on the sensitivity of culture (P < 0.0001). In fact, the treatment that lasted over 3 months also influenced the sensitivity of Xpert (P < 0.05). However, the treatment history did not affect the performance of remaining tests (P > 0.05). For rifampicin drug susceptibility test (DST), the anti-TB treatment showed only significant influence on the success rate of culture DST (P = 0.001), but not on those of Xpert and HRM tests (P > 0.05). CONCLUSION: Other tests as well as culture should be considered for patients with TBLN having retreatment history or over 1-month treatment to avoid false negative results.

Vitamin D deficiency and the risk of tuberculosis: a meta-analysis.

BACKGROUND AND AIM: To conduct meta-analyses of all published studies on various aspects of association between vitamin D and tuberculosis (TB). METHODS: PubMed and Web of Knowledge were searched for all properly controlled studies on vitamin D and TB. Pooled odds ratio, mean difference or standardized mean difference, and its corresponding 95% confidence interval were calculated with the Cochrane Review Manager 5.3. RESULTS: A significantly lower vitamin D level was found in TB patients vs controls; vitamin D deficiency (VDD) was associated with an increased risk of TB, although such an association was lacking in the African population and in the human immunodeficiency virus-infected African population. A significantly lower vitamin D level was found in human immunodeficiency virus-TB-coinfected African patients receiving antiretroviral treatment who developed TB-associated immune reconstitution inflammatory syndrome vs those who did not develop TB-associated immune reconstitution inflammatory syndrome. VDD was associated with an increased risk of developing active TB in those subjects with latent TB infection and with an increased risk of tuberculin skin test conversion/TB infection conversion, and the trend toward a lower vitamin D level in active TB patients vs latent TB infection subjects did not reach statistical significance, indicating that VDD was more likely a risk factor than a consequence of TB. This concept was further strengthened by our result that anti-TB treatment did not affect vitamin D level in TB patients receiving the treatment. CONCLUSION: Our analyses revealed an association between vitamin D and TB. VDD is more likely a risk factor for TB than its consequence. More studies are needed to determine whether vitamin D supplementation is beneficial to TB prevention and treatment.

Physical activity and risk of lung cancer: a meta-analysis of prospective cohort studies.

BACKGROUND: Previous studies investigating the association of physical activity with risk of lung cancer reported conflicting results. In order to update and improve available evidence on any link, a meta-analysis was performed. METHOD: We searched the PubMed database for prospective cohort studies investigating the relation of physical activity with risk of lung cancer. The pooled relative risk (RR) with its 95% confidence intervals (95%CI) was used to assess the association. RESULTS: We included 14 prospective studies with a total of 1,644,305 participants, with 14,074 incident lung cancer cases documented during follow-up. Meta-analysis of all 14 studies suggested both high and medium levels of physical activity to be associated with decreased risk of lung cancer compared to the reference group with low level of physical activity (for high level, RR = 0.77, 95%CI 0.73-0.81, P < 0.001; for medium level, RR = 0.87, 95%CI 0.83-0.90, P < 0.001). Subgroup analyses by gender found obvious associations in both men and women. No publication bias was observed. CONCLUSION: Our findings suggest that high and medium levels of physical activity have a beneficial effect on lung cancer by reducing the overall risk of tumour development among both men and women.

[Clinical analysis of treating 174 cases with pulmonary tuberculosis by pneumonectomy].

OBJECTIVE: To evaluate the efficacy and indication of pneumonectomy in patients with pulmonary tuberculosis. METHODS: From January 1992 to the end of 2008, 174 patients with pulmonary tuberculosis underwent pneumonectomy. According to the classification of pulmonary tuberculosis, there were tuberculous destroyed lungs (n = 106), chronic fibro-cavernous pulmonary tuberculosis (n = 27), cavernous pulmonary tuberculosis with aspergilloma (n = 5), tuberculous tracheobronchial stenosis (n = 16), pulmonary tuberculosis with encapsulated empyema (n = 5), tuberculous empyema with broncho pleural fistula (n = 4) and massive hemoptysis (n = 11). RESULTS: The surgical approaches were pneumonectomy (n = 146), pleuropneumonectomy (n = 21), chlorine pneumonectomy (n = 3), pneumonectomy with thoracoplasty (n = 1) and pneumonectomy with tracheoplasty (n = 3). The overall clinical cure rate was 93.0%, the rate of complications 11.5% and the operative mortality 2.3%. There were 3 dead cases resulting from operations in six months. CONCLUSION: Tuberculosis chemotherapy is an important modality for pulmonary tuberculosis, but surgical therapy remains essential for some patients. Pneumonectomy may increase the cure rates of severe pulmonary and multiple drug resistant tuberculosis.

[Impact of TNM staging and treatment mode on the prognosis of non-small cell lung cancer].

OBJECTIVE: To study the impact of TNM staging and combined treatment mode on the survival of non-small cell lung cancer (NSCLC) patients. METHODS: From January 1997 to December 2002, 987 NSCLC patients were surgically treated in this hospital. Of those, 574 received combined modality therapy (surgery + chemotherapy/radiotherapy), while 413 underwent operation alone. Their clinicopathological data were retrospectively analyzed. RESULTS: The 1-, 3-, 5-, and 10-year overall survival rates were 87.7%, 57.5%, 54.6% and 54.5%, respectively, for the whole group, which were 90.6%, 57.5%, 54.3% and 54.1% for the combined therapy group versus 83.8%, 57.6%, 55.2% and 55.2% for the group treated by surgical resection alone. The 1-year survival rate of the combined therapy group was significantly higher than that of the surgical resection alone group (90.6% vs. 83.8%) (P<0.01). With regard to the T factor, 5-year survival rate of the combined therapy group (surgery + radiotherapy) was higher than that of surgery alone group, especially in T4 cases (43.6% vs. 12.7%), with a significant difference between them (P<0. 05). As for the N factor, the 1-year survival rate of NO patients in the combined therapy group (surgery + chemotherapy/radiotherapy) was significantly higher than that of surgery alone group (94.4%, 97.9% vs. 90.0%) (P<0.05). The 1-year survival rate of N1 patients in the combined therapy group (surgery + chemotherapy or + chemotherapy and radiotherapy) was 91.7% and 100% versus 82.9% in the surgery alone group (P<0.01); The 1- and 3-year survival rates of N2 patients in the combined modality therapy group (surgery + chemotherapy) were 82.1% and 37.3%, while those of the surgery alone group were 69.4% and 26.5%, respectively, with a significant difference (P<0.05, P<0.01). All the severity of primary tumor, distance of lymph node involvement, and distant tumor metastasis significantly worsen the prognosis of the patients. CONCLUSION: The prognosis in NSCLC patients treated with combined modality therapy (surgery + chemotherapy/radiotherapy) is better than that with surgery alone. The larger the original tumor and the farther the lymph node and tumor metastases, the worse the prognosis is for NSCLC patients.

[Relationship between vascular endothelial growth factor C expression level and lymph node metastasis in non small cell lung cancer].

OBJECTIVE: To investigate the relationship between vascular endothelial growth factor C (VEGF-C) expression level and lymph node metastasis in non small cell lung cancer (NSCLC). METHODS: Fifty-two NSCLC patients, 38 males and 14 females, aged (59+/-11) (29-77), were divided into 2 groups based on the pathological examination: lymph node metastasis positive group (n=25) and lymph node metastasis negative group (n=27). RT-PCR and immunohistochemistry were used to detect the mRNA and protein expression of VEGF-C in the tumor tissues and lymph nodes resected during operation. RESULTS: The VEGF-C mRNA expression level in the lung tumor tissue of the lymph node metastasis positive group was 0.273+/-0.179, significantly higher than that in the lymph node metastasis negative group (0.089+/-0.087, P<0.01). The VEGF-C mRNA expression level in the positive lymph node of the lymph node metastasis positive group was 0.207+/-0.174, significantly higher than that in the lymph node metastasis negative group (0.114+/-0.107, P<0.01), but not significantly different from that in the negative lymph nodes of the same group(0.196+/-0.186, P>0.05). The VEGF-C protein positive rate of the lung cancer tissues of the lymph node metastasis positive group was 93.3% (14/15), significantly higher than that of the lymph node metastasis negative group (6.7%, 1/15, P<0.01). The VEGF-C protein positive rate of the metastasis positive lymph noses was 80.4% (37/46), and all 52 metastasis negative lymph nodes were VEGF-C protein negative. CONCLUSION: VEGF-C mRNA and protein expression levels predict lymph node metastasis and can be useful predictors of lymph node metastasis in NSCLC.

[Expression of HDGF and its implication in stage I non-small cell lung cancer].

OBJECTIVE: To evaluate the expression of HDGF and its implication in patients who undergone radical resection for stage I non-small cell lung cancer. METHODS: Immunohistochemical technique was applied to detect the expression of HDGF in 118 lung cancer tissues and 30 normal lung tissues as control. At the same time, the expression of VEGF and Ki-67 labeling rate of the tumors was evaluated. RESULTS: HDGF expression was observed in all cases, and significantly higher than that in normal lung tissues (52.23 +/- 10.35 vs. 156.73 +/- 70.95, P < 0.01). Expresson of HDGF was closely related to histological classification, and the expression in adenocarcinoma was much stronger than that in squamous cell cancers (P = 0.001), but not related to other clinicopathological factors. VEGF expression was closely related to the expression of HDGF. HDGF expression in the VEGF high expression group was much higher than that in VEGF low expression group (171.77 +/- 81.07 vs. 142.81 +/- 59.84, P = 0.028). Ki-67 expression was also closely related to the expression of HDGF, the labeling rate of Ki-67 in high HDGF expression group was much higher than that in low HDGF expression group (30.49% +/- 7.88% vs. 17.80% +/- 5.63%, P = 0.001). Univariate analysis showed that the patients with high HDGF expression had a shorter overall survival than that with low HDGF expression (40.0% vs. 77.5%, P = 0.008), and multivariate Cox regression analysis showed that HDGF was a significantly independent predictive factors for patients with stage I NSCLC (RR = 1.011, P = 0.002). CONCLUSION: HDGF expression is upgraded in postoperative stage I non-small cell lung cancer patients. HDGF is a significantly independent predictive factor for patients with stage I NSCLC. HDGF may play an important role on carcinogenesis and development of stage I NSCLC through promoting cell proliferation and neoangiogenesis of the tumor.

Surgical treatment of complex malignant anterior mediastinal tumors invading the superior vena cava.

Determining the appropriate surgery-based treatment for complicated anterior mediastinal malignancies (CAMM), especially those invading the superior vena cava (SVC) and its branches, remains a challenge for general thoracic surgeons. In this report, we summarize our experience and lessons regarding this issue in order to discuss a reasonable strategy for diagnosis and treatment of CAMM. Between January 2001 and April 2003, 15 patients with CAMM invading the SVC and/or its branches with or without invasion of other neighboring organs were surgically treated in our institution by a single surgeon team. We collected clinical data from the medical charts and from surgeons' specific notes for complicated cases, and performed a comprehensive analysis. There were 9 patients with malignant thymoma. Thymic carcinoma, teratoma, embryonal carcinoma, Hodgkin's lymphoma, non-Hodgkin's lymphoma, and mixed teratoma with thymoma were diagnosed in 1 patient each. All procedures were performed via median sternotomy. Some angioplasty techniques were successfully used to resect and reconstruct the SVC. Ten of the 15 patients also underwent pulmonary resection due to involvement of pulmonary parenchyma. Four of the patients underwent perioperative chemotherapy. There were no perioperative deaths. Two patients suffered prolonged ventilation after surgery, and there were no other severe complications related to surgery. One patient died 10 months after surgery. The remaining 14 patients were still living and their progress is still monitored. As of August 2004, the median follow-up duration for all patients was 35 months, and the disease-free survival duration was 10-43 months. CAMM can be safely and completely resected via a median sternotomy, even if it has invaded other mediastinal structures. CAMM should be pathologically identified before initial treatment. A good outcome for patients with CAMM is possible if a suitable strategy combining accurate diagnosis and appropriate treatment, especially surgical resection, is established.

[Application of vascular surgery in the treatment of thoracic neoplasm].

OBJECTIVE: To investigate superior vena cava (SVC) and anonymous vein resection with prosthesis replacement for lung carcinoma and mediastinal tumor, and to assess the surgical procedure and prognosis. METHODS: Experimental research: Eighteen adult dogs were divided randomly into two groups. Group A (n = 9) underwent blocking of the SVC system, and Group B (n = 9) underwent SVC resection with prosthesis replacement. The SVC pressure and histological changes of brain tissue were measured and evaluated for group A. The histological changes of prosthesis were studied in group B. Clinical research: Fifty-six patients with thoracic neoplasm were studied, of which 42 were lung carcinoma and 14 were mediastinal tumor. Resection of primary lesions and metastatic lymph nodes with replacement of SVC system were performed for all patients. Long-term follow-up was performed. RESULTS: Experimental research: In Group A, the pressure of SVC was higher when both SVC and the azygous vein were blocked as compared to SVC blocking only (P < 0.05); hyperemia and edema of brain tissue were not observed in two-hour obstruction. The inner face of vascular prosthesis was covered with fibrin two months after operation in group B. Vascular endothelial cells were found to grow in it, and there was no thrombosis without anticoagulation. Clinical research revealed that there was no death associated with the operation and there was no early or late obstruction of SVC. The survival rates of the patients with lung carcinoma in 1, 3 and 5 years were 84.2% 40.9% and 38.9% respectively. The patients with mediastinal tumor were all alive except 1 patient who died of metastasis. CONCLUSIONS: Radical resection combined with prosthesis replacement of SVC system extends the indications of thoracic neoplasm resection and improve the long-term survival rate and living qualities of the patients. It may be recommended in the surgical treatment of thoracic tumor.