Cellular immunotherapy combined with platinum-based chemotherapy prolongs survival for non-small cell lung cancer patients.

Platinum-based chemotherapy is the primary treatment option for advanced non-small cell lung cancer (NSCLC) patients without a driver gene mutation, but its efficacy is still modest. Through a potential synergistic effect, autologous cellular immunotherapy (CIT) composed of cytokine-induced killer (CIK), natural killer (NK), and T cells might enhance it. NK cells exhibited in vitro cytotoxicity toward lung cancer cells (A549 cells) following platinum therapy. Using flow cytometry, the expression of MICA, MICB, DR4, DR5, CD112, and CD155 on lung cancer cells was assessed. In this retrospective cohort study, there were included 102 previously untreated stage IIIB/IV NSCLC patients ineligible for tyrosine kinase inhibitor (TKI) target therapy who received either chemotherapy alone (n=75) or combination therapy (n=27). The cytotoxicity of NK cells for A549 cells was increased obviously and a time-dependent enhancement of this effect was also observed. After platinum therapy, the levels of MICA, MICB, DR4, DR5, CD112, and CD155 on the surface of A549 cells were increased. In the combination group, the median PFS was 8.3 months, compared to 5.5 months in the control group (p=0.042); the median overall survival was 18.00 months, compared to 13.67 months in the combined group (p=0.003). The combination group had no obvious immune-related adverse effects. The combination of NK cells with platinum showed synergistic anticancer effects. Combining the two strategies increased survival with minor adverse effects. Incorporating CIT into conventional chemotherapy regimens may improve NSCLC treatment. However, additional evidence will require multicenter randomized controlled trials.

Trends of Ten Leading Causes of Death in Head and Neck Squamous Cell Carcinoma.

OBJECTIVE: An understanding of the leading causes of death in patients with head and neck squamous cell carcinoma (HNSCC) would be helpful to inform doctors, patients, and healthcare providers on disease management. This study aimed to comprehensively study the leading causes of death in these survivors. METHODS: We investigated the trends of risk factors for major causes of death in patients with HNSCC. Causes of death in HNSCC were obtained from the Surveillance, Epidemiology, and End Results registries. We characterized trends in the 5-year cumulative mortality as well as risk factors associated with the ten leading causes of death. RESULTS: Among 48 297 deaths identified, the ten leading causes were as follows: HNSCC, heart disease, lung cancer, chronic obstructive pulmonary disease (COPD), cerebrovascular disease, pneumonia & influenza, accidents & adverse effects, esophagus cancer, chronic liver diseases, and septicemia. Non-HNSCC deaths surpassed HNSCC deaths 4 years after cancer diagnosis. There was a significant decline in the 5-year cumulative mortality from HNSCC, heart disease, lung cancer, COPD, cerebrovascular disease, and esophagus cancer. The risks of mortality from the ten leading causes varied with patient characteristics. CONCLUSION: Our findings provide a useful picture of mortality patterns in HNSCC survivors, which might help when planning personalized HNSCC care.

Correlation of circulating tumor DNA EGFR mutation levels with clinical outcomes in patients with advanced lung adenocarcinoma.

BACKGROUND: Circulating tumor DNA (ctDNA) is a promising biomarker for non-invasive epidermal growth factor receptor mutations (EGFRm) detection in lung cancer patients, but existing methods have limitations in sensitivity and availability. In this study, we used the ΔCt value (mutant cycle threshold [Ct] value-internal control Ct value) generated during the polymerase chain reaction (PCR) assay to convert super-amplification-refractory mutation system (superARMS) from a qualitative method to a semi-quantitative method named reformed-superARMS (R-superARMS), and evaluated its performance in detecting EGFRm in plasma ctDNA in patients with advanced lung adenocarcinoma. METHODS: A total of 41 pairs of tissues and plasma samples were obtained from lung adenocarcinoma patients who had known EGFRm in tumor tissue and were previously untreated. EGFRm in ctDNA was identified by using superARMS. Through making use of ΔCt value generated during the detection process of superARMS, we indirectly transform this qualitative detection method into a semi-quantitative PCR detection method, named R-superARMS. Both qualitative and quantitative analyses of the data were performed. Kaplan-Meier analysis was performed to estimate the progression-free survival (PFS) and overall survival (OS). Fisher exact test was used for categorical variables. RESULTS: The concordance rate of EGFRm in tumor tissues and matched plasma samples was 68.3% (28/41). At baseline, EGFRm-positive patients were divided into two groups according to the cut-off ΔCt value of EGFRm set at 8.11. A significant difference in the median OS (mOS) between the two groups was observed (EGFRm ΔCt ≤8.11 vs. >8.11: not reached vs. 11.0 months; log-rank P = 0.024). Patients were divided into mutation clearance (MC) group and mutation incomplete clearance (MIC) group according to whether the ΔCt value of EGFRm test turned negative after 1 month of treatment. We found that there was also a significant difference in mOS (not reached vs. 10.4 months; log-rank P = 0.021) between MC group and MIC group. Although there was no significant difference in PFS between the two groups, the two curves were separated and the PFS of MC group tended to be higher than the MIC group (not reached vs. 27.5 months; log-rank P = 0.088). Furthermore, EGFRm-positive patients were divided into two groups according to the cut-off of the changes in ΔCt value of EGFRm after 1 month of treatment, which was set at 4.89. A significant difference in the mOS between the two groups was observed (change value of ΔCt >4.89 vs. ≤4.89: not reached vs. 11.0 months; log-rank P = 0.014). CONCLUSIONS: Detecting EGFRm in ctDNA using R-superARMS can identify patients who are more likely sensitive to targeted therapy, reflect the molecular load of patients, and predict the therapeutic efficacy and clinical outcomes of patients.

Three-dimensional gait characteristics of patients after unilateral total knee arthroplasty.

ABSTRACT: The purpose of this study is to evaluate the gait characteristics of bilateral limbs after unilateral total knee arthroplasty (TKA) using three-dimensional (3D) dynamic capture technology.Forty-two patients who underwent TKA were selected from the Orthopedic Medical Center of The Second Hospital of Jilin University from November 2018 to May 2019. We used a 3D dynamic capture system to measure the gait characteristics of patients at 3 months after TKA. The data, including relative position and direction of different body parts, the force between feet and ground, spatial and temporal relationship of the lower limb muscles, were measured. Besides, the surface electromyogram signal and the force plate analog signal were also collected. The walking ability, knee 3D kinematic, and kinetic characteristics were analyzed by the Cortex software.Spatial and temporal parameters, including stride frequency, double support phase, single support phase, step length, step time, step width, stride length, gait cycle, velocity, were no significant difference in bilateral lower extremities (P > .05). The reaction force of hip, knee, and ankle joint in the operation side were less than that of the healthy side, but the difference was not statistically significant (P > .05). However, when compared with the healthy side, the hip joint in operation side had a larger maximum extension angle (P < .001), the knee joint in operation side had a larger maximum valgus angle and valgus activity (P < .05), and had a smaller tibial maximum internal rotation angle (P < .05). Besides, the surface electromyogram signals of tibialis anterior muscles were reduced (P < .05).3D gait analysis, as an objective and quantitative evaluation method, is a safe, effective, and reliable method for evaluating postoperative knee function. The data of gait analysis prove that TKA is a vital treatment to improve the function of patients with knee arthritis. Besides, gait analysis also showed that there were various kinematic and biomechanical abnormalities in the knee after TKA, which may be the reason why the surgical knee could not immediately return to normal level.

Rickettsia japonica and Novel Rickettsia Species in Ticks, China.

PCR amplification indicated the minimum infection rate of Rickettsia spp. was 0.66% in Haemaphysalis longicornis ticks collected from Shandong Province, China. Phylogenetic analysis based on the rrs, gltA, ompA, and ompB genes indicated that the ticks carried R. japonica, Candidatus Rickettsia longicornii, and a novel Rickettsia species related to R. canadensis.

Anaplasma species detected in Haemaphysalis longicornis tick from China.

Anaplasma are tick-borne obligatory intracellular bacteria, which infect humans and other animals. The Anaplasma species carried by ticks in China are not well studied. We collected 3145 questing Haemaphysalis longicornis ticks including 120 larvae, 2460 nymphs and 565 adults from vegetation in Jiaonan County, Shandong Province, China from 2013 to 2015. All ticks were examined for the presence of Anaplasma species by nested PCR amplification of the 16S rRNA gene. For further differentiation of A. capra from A. centrale, gltA and msp2 genes were sequenced for A. capra. Three Anaplasma species were detected in the nymph and/or adult ticks with the minimum infection rate of ticks as follows: 1.55% for A. bovis, 0.10% for A. phagocytophilum, and 0.03% for A. capra. These results indicated that the H. longicornis tick in Jiaonan County carried multiple Anaplasma species, which may be a challenge for public health in the studying area.

Screening for lung cancer using low-dose computed tomography: concerns about the application in low-risk individuals.

Low-dose computed tomography (LDCT) has been increasingly accepted as an efficient screening method for high-risk individuals to reduce lung cancer mortality. However, there remains a gap of knowledge in the practical implementation of screening on a larger scale, especially for low-risk individuals. The aim of this study is to initiate discussion through an evidence-based analysis and provide valuable suggestions on LDCT screening for lung cancer in clinical practice. Among previously published randomized controlled trials (RCTs), the National Lung Screening Trial (NLST) is the only one demonstrating positive results in a high-risk population of old age and heavy smokers. It is also shown that the potential harms include false-positive findings, radiation exposure etc., but its magnitude is uncertain. In the meantime, the current risk stratification system is inadequate, and is difficult to define selection criteria. Thus, the efficacy of LDCT in lung cancer screening needs to be confirmed in future trials, and the procedure should not be proposed to individuals without comparable risk to those in the NLST. Furthermore, there is a lack of evidence to support the expansion of LDCT screening to low-risk individuals. Therefore, recommendation of LDCT screening for these patients could be premature in clinical practice although some of them might be missed based on current definition of risk factors. Further studies and advances in risk assessment tools are urgently needed to address the concerns about lung cancer screening in order to improve the outcomes of lung cancer.

Association between Single Nucleotide Polymorphisms in XRCC3 and Radiation-Induced Adverse Effects on Normal Tissue: A Meta-Analysis.

The X-ray repair cross-complementing group 3 (XRCC3) protein plays an important role in the repair of DNA double-strand breaks. The relationship between XRCC3 polymorphisms and the risk of radiation-induced adverse effects on normal tissue remains inconclusive. Thus, we performed a meta-analysis to elucidate the association between XRCC3 polymorphisms and radiation-induced adverse effects on normal tissue. All eligible studies up to December 2014 were identified through a search of the PubMed, Embase and Web of Science databases. Seventeen studies involving 656 cases and 2193 controls were ultimately included in this meta-analysis. The pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were calculated to evaluate the association between XRCC3 polymorphisms and the risk of radiation-induced normal tissue adverse effects. We found that the XRCC3 p.Thr241Met (rs861539) polymorphism was significantly associated with early adverse effects induced by radiotherapy (OR = 1.99, 95%CI: 1.31-3.01, P = 0.001). A positive association lacking statistical significance with late adverse effects was also identified (OR = 1.28, 95%CI: 0.97-1.68, P = 0.08). In addition, the rs861539 polymorphism was significantly correlated with a higher risk of adverse effects induced by head and neck area irradiation (OR = 2.41, 95%CI: 1.49-3.89, p = 0.0003) and breast irradiation (OR = 1.41, 95%CI: 1.02-1.95, p = 0.04), whereas the correlation was not significant for lung irradiation or pelvic irradiation. Furthermore, XRCC3 rs1799794 polymorphism may have a protective effect against late adverse effects induced by radiotherapy (OR = 0.47, 95%CI: 0.26-0.86, P = 0.01). Well-designed large-scale clinical studies are required to further validate our results.