Current status and challenges of immunotherapy in ALK rearranged NSCLC

Rearrangements of the anaplastic lymphoma kinase (ALK) gene account for 5-6% in non-small cell lung cancer (NSCLC). ALK rearranged NSCLC is sensitive to ALK tyrosine kinase inhibitors (TKIs) but prone to drug resistance. Meanwhile, ALK rearranged NSCLC has poor response to single immunotherapy. Here we mainly describe the immune escape mechanisms of ALK mutated NSCLC and the role of related biomarkers. Additionally, we collate and evaluate preclinical and clinical studies of novel immune combination regimens, and describe the prospects and perspectives for the in vivo application of novel immune technologies in patients with ALK rearranged NSCLC

The Naturally Occurring YMDD Mutation among Patients Chronically Infected HBV and Untreated with Lamivudine: A Systematic Review and Meta-Analysis

Background: Several recent reports have demonstrated that tyrosine (Y)-methionine (M)-aspartic acid (D)-aspartic acid (D) (YMDD) motif mutations can naturally occur in chronic HBV patients without antiviral treatment such as lamivudine therapy. This paper aims to assess the overall spontaneous incidence and related risk factors of YMDD-motif mutations among lamivudine-naïve chronic HBV carriers, so as to provide some clue for clinical treatment of hepatitis B. Methodology/Principal Findings: Chinese and English literatures were searched for studies reporting natural YMDD mutations among untreated chronic HBV patients from 2001 to 2010. The incidence estimates were summarized and analyzed by meta-analyses. Forty-seven eligible articles from eight countries were selected in this review (13 in English and 34 in Chinese). The pooled incidence of YMDD-motif mutation among untreated chronic HBV patients from eight countries was 12.21 % (95 % CI: 9.69%–14.95%). China had an incidence of 13.38 % (95 % CI: 10.90%–16.07%) and seven other countries had an incidence of 9.90 % (95 % CI: 3.28%–19.55%), respectively. Lamivudine therapy would increase the risk of mutations 5.23 times higher than the untreated patients. A higher HBV DNA copy number was associated with increased incidence of natural YMDD mutation. No significant difference was found in YMDD mutation incidence between groups of different gender, age, HBeAg status, patients ’ ALT (alanine aminotransferase) level, and between the groups of HBV genotype B and C. Conclusions: The YMDD-motif mutations can occur spontaneously with a relatively high incidence in CHB patient

Prevalence and trend of hepatitis C virus infection among blood donors in Chinese mainland: a systematic review and meta-analysis

<p>Abstract</p> <p>Background</p> <p>Blood transfusion is one of the most common transmission pathways of hepatitis C virus (HCV). This paper aims to provide a comprehensive and reliable tabulation of available data on the epidemiological characteristics and risk factors for HCV infection among blood donors in Chinese mainland, so as to help make prevention strategies and guide further research.</p> <p>Methods</p> <p>A systematic review was constructed based on the computerized literature database. Infection rates and 95% confidence intervals (95% CI) were calculated using the approximate normal distribution model. Odds ratios and 95% CI were calculated by fixed or random effects models. Data manipulation and statistical analyses were performed using STATA 10.0 and ArcGIS 9.3 was used for map construction.</p> <p>Results</p> <p>Two hundred and sixty-five studies met our inclusion criteria. The pooled prevalence of HCV infection among blood donors in Chinese mainland was 8.68% (95% CI: 8.01%-9.39%), and the epidemic was severer in North and Central China, especially in Henan and Hebei. While a significant lower rate was found in Yunnan. Notably, before 1998 the pooled prevalence of HCV infection was 12.87% (95%CI: 11.25%-14.56%) among blood donors, but decreased to 1.71% (95%CI: 1.43%-1.99%) after 1998. No significant difference was found in HCV infection rates between male and female blood donors, or among different blood type donors. The prevalence of HCV infection was found to increase with age. During 1994-1995, the prevalence rate reached the highest with a percentage of 15.78% (95%CI: 12.21%-19.75%), and showed a decreasing trend in the following years. A significant difference was found among groups with different blood donation types, Plasma donors had a relatively higher prevalence than whole blood donors of HCV infection (33.95% <it>vs </it>7.9%).</p> <p>Conclusions</p> <p>The prevalence of HCV infection has rapidly decreased since 1998 and kept a low level in recent years, but some provinces showed relatively higher prevalence than the general population. It is urgent to make efficient measures to prevent HCV secondary transmission and control chronic progress, and the key to reduce the HCV incidence among blood donors is to encourage true voluntary blood donors, strictly implement blood donation law, and avoid cross-infection.</p

Temporal trends of the association between ambient temperature and hospitalisations for cardiovascular diseases in Queensland, Australia from 1995 to 2016:A time-stratified case-crossover study

BackgroundIn the context of global warming, studies have turned to assess the temporal trend of the association between temperature and health outcomes, which can be used to reflect whether human beings have adapted to the local temperature. However, most studies have only focused on hot temperature and mortality. We aim to investigate the temporal variations in the association between ambient temperature and hospitalisations for cardiovascular diseases in Queensland, Australia from 1995 to 2016.Methods and findingsWe obtained data on 1,855,717 cardiovascular hospitalisations (mean age: 65.9 years, 42.7% female) from all 443 postal areas in Queensland, Australia between January 1, 1995 and December 31, 2016. Grid-level meteorological data were downloaded from scientific information for landowners. We used a time-stratified case-crossover design fitted with a conditional quasi-Poisson regression model and time-varying distributed lag nonlinear model (DLNM) to evaluate the association between temperature and cardiovascular hospitalisations and the temporal trends of the associations. Stratified analyses were performed in different age, sex, and climate zones. In all groups, relative risks (RRs) of cardiovascular hospitalisations associated with high temperatures (heat effects) increased, but cold effects showed a decreasing trend from 1995 to 2016. The increasing magnitude of heat effects was larger (p = 0.002) in men than in women and larger (p ConclusionThe impacts of cold temperatures on cardiovascular hospitalisations have decreased, but the impacts of high temperatures have increased in Queensland, Australia. The findings highlight that Queensland people have adapted to the impacts of cold temperatures, but not high temperatures. The burden of cardiovascular hospitalisations due to high temperatures is likely to increase in the context of global warming

Socioeconomic level and associations between heat exposure and all-cause and cause-specific hospitalization in 1,814 Brazilian cities:A nationwide case-crossover study

BackgroundHeat exposure, which will increase with global warming, has been linked to increased risk of a range of types of cause-specific hospitalizations. However, little is known about socioeconomic disparities in vulnerability to heat. We aimed to evaluate whether there were socioeconomic disparities in vulnerability to heat-related all-cause and cause-specific hospitalization among Brazilian cities.Methods and findingsWe collected daily hospitalization and weather data in the hot season (city-specific 4 adjacent hottest months each year) during 2000-2015 from 1,814 Brazilian cities covering 78.4% of the Brazilian population. A time-stratified case-crossover design modeled by quasi-Poisson regression and a distributed lag model was used to estimate city-specific heat-hospitalization association. Then meta-analysis was used to synthesize city-specific estimates according to different socioeconomic quartiles or levels. We included 49 million hospitalizations (58.5% female; median [interquartile range] age: 33.3 [19.8-55.7] years). For cities of lower middle income (LMI), upper middle income (UMI), and high income (HI) according to the World Bank's classification, every 5°C increase in daily mean temperature during the hot season was associated with a 5.1% (95% CI 4.4%-5.7%, P ConclusionsLess developed cities displayed stronger associations between heat exposure and all-cause hospitalizations and certain types of cause-specific hospitalizations in Brazil. This may exacerbate the existing geographical health and socioeconomic inequalities under a changing climate