Heteronemin and tetrac derivatives suppress non-small cell lung cancer growth via ERK1/2 inhibition.

The most common cancer, lung cancer, causes deaths worldwide. Most lung cancer patients have non-small cell lung carcinomas (NSCLCs) with a poor prognosis. The chemotherapies frequently cause resistance therefore search for new effective drugs for NSCLC patients is an urgent and essential issue. Deaminated thyroxine, tetraiodothyroacetic acid (tetrac), and its nano-analogue (NDAT) exhibit antiproliferative properties in several types of cancers. On the other hand, the most abundant secondary metabolite in the sponge Hippospongia sp., heteronemin, shows effective cytotoxic activity against different types of cancer cells. In the current study, we investigated the anticancer effects of heteronemin against two NSCLC cell lines, A549 and H1299 cells in vitro. Combined treatment with heteronemin and tetrac derivatives synergistically inhibited cancer cell growth and significantly modulated the ERK1/2 and STAT3 pathways in A549 cells but only ERK1/2 in H1299 cells. The combination treatments induce apoptosis via the caspases pathway in A549 cells but promote cell cycle arrest via CCND1 and PCNA inhibition in H1299 cells. In summary, these results suggest that combined treatment with heteronemin and tetrac derivatives could suppress signal transduction pathways essential for NSCLC cell growth. The synergetic effects can be used potentially as a therapeutic procedure for NSCLC patients.

Recommendation for management of patients with their first episode of primary spontaneous pneumothorax, using video-assisted thoracoscopic surgery or conservative treatment.

International guidelines do not recommend surgery for the first episode of primary spontaneous pneumothorax (PSP), except in cases of persistent air leak, hemopneumothorax, bilateral pneumothorax, or occupations at risk. However, these recommendations have been challenged because of a significant reduction in the recurrence rate in emerging studies. We evaluated the rationale of recommendations by systematically reviewing RCTs and observational studies by using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) system. We searched articles in PubMed, EMBASE, and Cochrane databases up to August 15, 2020. The primary outcomes were the recurrence rate and complication rate. The secondary outcomes were hospital stay and drainage duration. Nine eligible studies with 1121 patients were retrieved and analyzed. The recurrence rate was lower in the VATS than in conservative treatment with moderate evidence (OR 0.13, 95% CI 0.09 to 0.19, P < 0.001, I2 = 0%). We did not find significant differences in complication rate (Peto OR 1.17, 95% CI 0.33 to 4.12, P = 0.80), hospital stay duration (MD - 0.48 days, 95% CI - 2.84 to 1.87, P = 0.69, very low evidence), and in drainage duration (MD - 3.99 days, 95% CI - 9.06 to 1.08, P = 0.12, very low evidence) between the two groups. Our results would suggest VATS treatment as a weak recommendation for patients with the first episode of PSP, based on our systematic review of the current evidence by using the GRADE system, indicating that different treatments will be appropriate for different patients and that patients' values and preferences should be incorporated through shared decision making.Trial REGISTRY: PROSPERO; No.: CRD42020162267.

Minimization of the complications associated with bar removal after the Nuss procedure in adults.

BACKGROUND: Pectus bar removal after Nuss repair is associated with the risk of major complications that are underreported. Of these, surgical bleeding is the main concern. Old age and placement of more than one bar are reported risk factors for pectus bar removal. In this study, we presented our experience regarding the modified skills required to minimize complications during bar removal, especially in adult patients. METHODS: Consecutive patients who underwent pectus bar removal as the final stage of Nuss repair between August 2014 and December 2018 were included. The patients were positioned in the supine position. The bar(s) was (were) removed from the left side via the bilateral approach using the previous surgical scars after full dissection of the ends of the bar lateral to the hinge point and after straightening the right end of the bar. Bleeding was carefully checked after removal. An elastic bandage was wrapped around the chest after wound closure to prevent wound hematoma/seroma formation. RESULTS: A total of 283 patients (260 male and 23 female), with a mean age of 22.8 ± 6.6 years at the time of the Nuss repair were included. The mean duration of pectus bar maintenance interval was 4.3 years (range: 1.9 to 9.8 years). A total of 200 patients (71%) had two bars. The mean estimated blood loss was 11.7 mL (range: 10 mL to 100 mL). Nine patients (3.1%) experienced complications, six had pneumothorax and three had wound hematoma. No major bleeding occurred. Adults and the use of more than one bar were not associated with a significantly higher rate of complications (P = 0.400 and P = 0.260, respectively). CONCLUSIONS: Adult patients and removal of multiple bars were not risk factors for complications in our cohort. Skill in preventing intraoperative mediastinal traction, carefully controlling bleeding, and reducing the effect of dead space around the wounds could minimize the risk of bleeding complications. A multicentric study or case accumulation is needed to further evaluate the risk factors of removal pectus bar(s).