No abstract

Thymic epithelial tumors are the most common mediastinal tumors. Surgery is the mainstay of treatment and complete resection provides the best survival rate. However, advanced tumors often require multimodality treatment and thus we analyzed the prognostic potential of routine circulating biomarkers that might help to risk-stratify patients beyond tumor stage and histology. Preoperative values for white blood cell count (WBC), C-reactive protein (CRP) and lactate dehydrogenase (LDH) were analyzed in 220 thymic epithelial tumor patients operated between 1999 and 2018. Increased CRP levels (>1 mg/dl) were significantly more often measured in thymic carcinoma and neuroendocrine tumors when compared to thymoma. LDH serum activity was higher in thymic neuroendocrine tumors when compared to thymoma or thymic carcinoma. The median disease specific survival was significantly longer in thymoma cases than in thymic carcinoma and neuroendocrine tumors. Increased preoperative LDH level (>240 U/L) associated with shorter survival in thymus carcinoma (HR 4.76, p = 0.0299). In summary, higher CRP associated with carcinoma and neuroendocrine tumors, while LDH increased primarily in neuroendocrine tumors suggesting that biomarker analysis should be performed in a histology specific manner. Importantly, preoperative serum LDH might be a prognosticator in thymic carcinoma and may help to risk stratify surgically treated patients in multimodal treatment regimens.

Providing accurate utilization forecasts is key to maintaining optimal vaccine stocks in any health facility. Current approaches to vaccine utilization forecasting are based on often outdated population census data, and rely on weak, low-dimensional demand forecasting models. Further, these models provide very little insights into factors that influence vaccine utilization. Here, we built a state-of-the-art, machine learning model using novel, temporally and regionally relevant vaccine utilization data. This highly multidimensional machine learning approach accurately predicted bi-weekly vaccine utilization at the individual health facility level. Specifically, we achieved a forecasting fraction error of less than two for about 45% of regional health facilities in both the Tanzania regions analyzed. Our “random forest regressor” had an average forecasting fraction error that was almost 18 times less compared to the existing system. Importantly, using our model, we gleaned several key insights into factors underlying utilization forecasts. This work serves as an important starting point to reimagining predictive health systems in the developing world by leveraging the power of Artificial Intelligence and big data.

MAVS pathway by direct administration into the tumor. We performed the phase I dose escalation safety/tolerability and preliminary efficacy study of intra-tumoral and subcutaneous administration of HVJ-E in patients suffering from chemotherapy-resistant malignant pleural mesothelioma. Method: We performed the dose upward titration clinical study for checking the safety, drug tolerance, and preliminary efficacy of the intra-tumoral and subsequent subcutaneous administration of HVJ-E. We administrated HVJ-E to the patients 4 times per 2 weeks (the first was intra-tumoral, and residual 3 times were subcutaneous injection), and then washed out the drug from the body for 2 weeks. This cycle was repeated 2 times. We observed the patients for 8 weeks, and evaluated them by CTCAE, modified RECIST, and PERCIST. Result: Three patients were enrolled as a low-dose group, and three patients were enrolled as a high-dose group. There was no discontinuation of the administration due to the severe adverse events. Results; The mean disease duration from confirmed diagnosis to this trial was 2.27 years (0.6-4.5 years). We defined the primary endpoint as an assessment of dose limiting toxicity related with HVJ-E. Neither serious adverse events (SAE) nor DLT were observed during the observation period.The following symptoms were observed. Fever (83.3%), and the local symptoms at injection site, for example, rubor, swelling, or induration (100%) were observed, but the local relapse of mesothelioma at the injection site was not observed. It was confirmed that the intra-tumoral and subcutaneous administration of HVJ-E was safe for chemotherapyresistant pleural mesothelioma patients, because these AEs were transient and slight. The efficacy as a secondary endpoint was evaluated with modified RECIST, and PERCIST. DCR of low dose level cohort was 0% (0/3), because of PD, meanwhile, high dose level cohort indicated 100% (3/3). Consequently, the DCR of all cases who had treated with HVJ-E was 50% (3/6) by mRECIST, meanwhile, the DCR evaluated by PERCIST was 100%. Conclusion: It was suggested that HVJ-E was useful for disease control of advanced pleural mesothelioma patients without severe adverse events. Now we do the next step trial for malignant pleural mesothelioma and melanoma with high dose of HVJ-E.