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Osimertinib has favorable efficacy in patients with NSCLC harboring T790M, detected from ctDNA with unknown tumor mutation status, in whom disease had progressed during prior EGFR-TKI therapy.

Background: IBM Watson for Oncology (WFO) is a cognitive computing system helping physicians quickly identify key information in a patient's medical record, surface relevant evidence, and explore treatment options. This study assessed the possibility of using WFO for clinical treatment in lung cancer patients. Methods:We evaluated the level of agreement between WFO and multidisciplinary team (MDT) for lung cancer. From January to December 2018, newly diagnosed lung cancer cases in Chonnam National University Hwasun Hospital were retrospectively examined using WFO version 18.4 according to four treatment categories (surgery, radiotherapy, chemoradiotherapy, and palliative care). Treatment recommendations were considered concordant if the MDT recommendations were designated 'recommended' by WFO. Concordance between MDT and WFO was analyzed by Cohen's kappa value.Results: In total, 405 (male 340, female 65) cases with different histology (adenocarcinoma 157, squamous cell carcinoma 132, small cell carcinoma 94, others 22 cases) were enrolled. Concordance between MDT and WFO occurred in 92.4% (k=0.881, P<0.001) of all cases, and concordance differed according to clinical stages. The strength of agreement was very good in stage IV non-small cell lung carcinoma (NSCLC) (100%, k=1.000) and extensive disease small cell lung carcinoma (SCLC) (100%, k=1.000). In stage I NSCLC, the agreement strength was good (92.4%, k=0.855). The concordance was moderate in stage III NSCLC (80.8%, k=0.622) and relatively low in stage II NSCLC (83.3%, k=0.556) and limited disease SCLC (84.6%, k=0.435). There were discordant cases in surgery (7/57, 12.3%), radiotherapy (2/12, 16.7%), and chemoradiotherapy (15/129, 11.6%), but no discordance in metastatic disease patients.Conclusions: Treatment recommendations made by WFO and MDT were highly concordant for lung cancer cases especially in metastatic stage. However, WFO was just an assisting tool in stage I-III NSCLC and limited disease SCLC; so, patient-doctor relationship and shared decision making may be more important in this stage.

Osteoclasts are responsible for the bone erosion associated with rheumatoid arthritis (RA). The upregulation of the chemokines CCL19 and CCL21 and their receptor CCR7 has been linked to RA pathogenesis. The purpose of this study was to evaluate the effects of CCL19 and CCL21 on osteoclasts and to reveal their underlying mechanisms. The expression of CCL19, CCL21 and CCR7 was higher in RA patients than in osteoarthritis patients. In differentiating osteoclasts, tumor necrosis factor-α, interleukin-1β and lipopolysaccharide stimulated CCR7 expression. CCL19 and CCL21 promoted osteoclast migration and resorption activity. These effects were dependent on the presence of CCR7 and abolished by the inhibition of the Rho signaling pathway. CCL19 and CCL21 promoted bone resorption by osteoclasts in an in vivo mice calvarial model. These findings demonstrate for the first time that CCL19, CCL21 and CCR7 play important roles in bone destruction by increasing osteoclast migration and resorption activity. This study also suggests that the interaction of CCL19 and CCL21 with CCR7 is an effective strategic focus in developing therapeutics for alleviating inflammatory bone destruction.

BackgroundIdentification and understanding of the pathogens responsible for pleural infection is critical for appropriate antibiotic treatment. This study sought to determine the microbiological characteristics of pleural infection and to identify potential predictive factors associated with mortality.MethodsIn this retrospective study, we analyzed patient data from 421 cases of parapneumonic effusion. A total of 184 microorganisms were isolated from 164 patients, using two culture systems: a standard method and a method using pairs of aerobic and anaerobic blood culture bottles.ResultsThe most frequently isolated microorganisms were streptococci (31.5%), followed by staphylococci (23.4%), gram-negative bacteria (18.5%) and anaerobes (10.3%). Streptococci were the main microorganisms found in standard culture (41.9%) and community-acquired infections (52.2%), and were susceptible to all antimicrobial agents in drug sensitivity testing. Staphylococci were the most frequently isolated pathogens in blood cultures (30.8%) and hospital-acquired infections (38.3%), and were primarily multidrug-resistant (61.8%). In multivariate analysis, the following were significant predictive factors for 30-day mortality among the total population: CURB-65 ≥ 2 (aOR 5.549, 95% CI 2.296–13.407, p<0.001), structural lung disease (aOR 2.708, 95% CI 1.346–5.379, p = 0.004), PSI risk class IV-V (aOR 4.714, 95% CI 1.530–14.524, p = 0.007), no use of intrapleural fibrinolytics (aOR 3.062, 95% CI 1.102–8.511, p = 0.014), hospital-acquired infection (aOR 2.205, 95% CI 1.165–4.172, p = 0.015), age (aOR 0.964, 95% CI 0.935–0.994, p = 0.018), and SOFA score ≥2 (aOR 2.361, 95% CI 1.134–4.916, p = 0.022).ConclusionIn this study, common pathogens causing pleural infection were comparable to previous studies, and consisted of streptococci, staphylococci, and anaerobes. CURB-65 ≥2, structural lung disease, PSI risk class IV-V, no use of intrapleural fibrinolytics, hospital-acquired infection, older age, and SOFA score ≥ 2 are potential predictors of mortality in pleural infection.

Although various studies on predictive markers in the use of PD-1/PD-L1 inhibitors are in progress, only PD-L1 expression levels in tumor tissues are currently used. In the present study, we investigated whether baseline serum levels of IL-6 can predict the treatment response of patients with advanced non-small cell lung cancer (NSCLC) treated with PD-1/ PD-L1 inhibitors. In our cohort of 125 NSCLC patients, the objective response rate (ORR) and disease control rate (DCR) were significantly higher in those with low IL-6 (<13.1 pg/ml) than those with high IL-6 (ORR 33.9% vs. 11.1%, p=0.003; DCR 80.6% vs. 34.9%, p<0.001). The median progression-free survival was 6.3 months (95% confidence interval [CI], 3.9-8.7) in the low IL-6 group, significantly longer than in the high IL-6 group (1.9 months, 95% CI, 1.6-2.2, p<0.001). The median overall survival in the low IL-6 group was significantly longer than in the high IL-6 group (not reached vs. 7.4 months, 95% CI, 4.8-10.0). Thus, baseline serum IL-6 levels could be a potential biomarker for predicting the efficacy and survival benefit of PD-1/PD-L1 inhibitors in NSCLC.

Default from tuberculosis (TB) treatment could exacerbate the disease and result in the emergence of drug resistance. This study identified the risk factors for default from TB treatment in Korea. This single-center case–control study analyzed 46 default cases and 100 controls. Default was defined as interrupting treatment for 2 or more consecutive months. The reasons for default were mainly incorrect perception or information about TB (41.3%) and experience of adverse events due to TB drugs (41.3%). In univariate analysis, low income (< 2,000 US dollars/month, 88.1% vs. 68.4%, P = 0.015), absence of TB stigma (4.3% vs. 61.3%, P < 0.001), treatment by a non-pulmonologist (74.1% vs. 25.9%, P < 0.001), history of previous treatment (37.0% vs. 19.0%, P = 0.019), former defaulter (15.2% vs. 2.0%, P = 0.005), and combined extrapulmonary TB (54.3% vs. 34.0%, P = 0.020) were significant risk factors for default. In multivariate analysis, the absence of TB stigma (adjusted odd ratio [aOR]: 46.299, 95% confidence interval [CI]: 8.078–265.365, P < 0.001), treatment by a non-pulmonologist (aOR: 14.567, 95% CI: 3.260–65.089, P < 0.001), former defaulters (aOR: 33.226, 95% CI: 2.658–415.309, P = 0.007), and low income (aOR: 5.246, 95% CI: 1.249–22.029, P = 0.024) were independent predictors of default from TB treatment. In conclusion, patients with absence of disease stigma, treated by a non-pulmonologist, who were former defaulters, and with low income should be carefully monitored during TB treatment in Korea to avoid treatment default.