Combined influence of nutritional and inflammatory status and depressive symptoms on mortality among US cancer survivors: Findings from the NHANES.

BACKGROUND: Inflammation and nutrition and depression are interrelated, and both are related to changes in mortality rates. We investigated the association of nutritional and inflammation index or depressive symptoms with the risk of all-cause mortality or cause-specific mortality among cancer survivors. METHODS: A prospective cohort of a nationally representative sample of cancer survivors, aged 40 years or older (n = 2331; weighted population, 15 248 255; 67.6 ± 11.0 years; 50.6 % males), were recruited from the US National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018. Advanced lung cancer inflammation index (ALI) reflected inflammation and nutritional status and Patient Health Questionnaire 9 (PHQ-9) demonstrated depressive symptoms. The independent and joint associations of ALI and PHQ-9 score with mortality outcomes were examined among cancer survivors and Cox regression analysis based on weights was used to calculate the relative risk. RESULTS: We identified 605 all-cause deaths (cancer, 204; non-cancer, 401) over a median of 6.2 years of follow-up (15,385 person-years; interquartile range, 3.3-9.8 years). High ALI was observed to be consistently associated with lower risks of all-cause (hazard ratio [HR], 0.516; 95 % CI, 0.400-0.667) and non-cancer (HR, 0.414; 95 % CI, 0.291-0.588) mortality compared with low ALI in a series of adjusted models. Meanwhile, lower PHQ-9 score (0-4) was associated with lower risks of all-cause (HR, 0.686; 95 % CI, 0.521-0.903) and non-cancer (HR, 0.686; 95 % CI, 0.474-0.992) mortality compared with higher PHQ-9 score (≥10). Furthermore, joint analyses showed that high ALI was associated with a decreased risk of death among cancer survivors who were not depressive. Specifically, survivors with high ALI but not depressive symptoms had the lowest overall (HR, 0.404; 95 % CI, 0.228-0.715) risks. CONCLUSION: In this cohort study, we observed impact of nutritional and inflammatory status and depressive symptoms on mortality among cancer survivors, with the lowest risks of death from both all causes and non-cancer being noted among the combination of high level ALI with no depression.

Association between intake of the n-3 polyunsaturated fatty acid docosahexaenoic acid (n-3 PUFA DHA) and reduced risk of ovarian cancer: A systematic Mendelian Randomization study.

BACKGROUND & AIMS: Whether the intake of docosahexaenoic acid (DHA), an n-3 polyunsaturated fatty acid, is beneficial for ovarian cancer (OC) remains controversial and we hope to disentangle this puzzle using genetic data from large-scale populations in European and Asian. METHODS: We employed, for the first time, a systematic Mendelian randomization (MR) design to comprehensively evaluate the causal effect of plasma DHA levels, an objective biomarker of DHA intake, on OC risk in European and then verified the extrapolation of the results in the Asian. Data in the analysis included genetic association data obtained from large-scale genome-wide association studies with 13,499 individuals for plasma DHA measurements and 66,450 individuals for OC in the European population, and 1361 individuals for plasma DHA measurements and 61,457 individuals for OC in the Asian population. The causal relationship between DHA and OC was estimated using the inverse-variance weighted approach, together with extensive validation and sensitivity analyses to verify the main results. RESULTS: In the European population, MR evidence suggested a causal relationship between higher plasma DHA levels and lower OC risk (OR, 0.89 for OC per one-SD increment in DHA; 95% CI, 0.83 to 0.96; P = 0.003). Subgroup analysis by histological type of OC indicated that this observed association was stronger among endometrioid ovarian cancer (EOC) (OR, 0.82; 95% CI, 0.69 to 0.96; P = 0.014). A similar causal association of borderline significance was reached in the Asian replication set. The above results were consistently supported by a series of validation and sensitivity analyses. CONCLUSION: Our study provided robust genetic evidence for a protective association between plasma DHA levels and lower risk of OC, especially EOC, in the European population. These findings may inform prevention strategies and interventions directed towards DHA intake and OC.

Insight into the causality between basal metabolic rate and endometrial and ovarian cancers: Analysis utilizing systematic Mendelian randomization and genetic association data from over 331,000 UK biobank participants.

BACKGROUND: Observational studies have demonstrated that basal metabolic rate (BMR) is associated with the risk of endometrial cancer (EC) and ovarian cancer (OC). However, it is unclear whether these associations reflect a causal relationship. OBJECTIVE: To reveal the causality between BMR and EC and OC, we performed the first comprehensive two-sample Mendelian randomization (MR) analyses. METHODS: Genetic variants were used as proxies of BMR. GWAS summary statistics of BMR, EC and OC were obtained from the UK Biobank Consortium, Endometrial Cancer Association Consortium and Ovarian Cancer Association Consortium respectively. The inverse variance weighted method was employed as the main approach for MR analysis. A series of sensitivity analyses were implemented to validate the robustness and reliability of the results. RESULTS: BMR was significantly related to an increased risk of EC (ORSD  = 1.49; 95% CI: 1.29-1.72; p-Value < .001) and OC (ORSD  = 1.21; 95% CI: 1.08-1.35; p-Value < .001). Furthermore, the stratified analysis indicated that BMR was positively associated with endometrioid endometrial cancer (EEC) (ORSD  = 1.45; 95% CI, 1.23-1.70; p-Value < .001), clear cell ovarian cancer(CCOC) (ORSD  = 1.89; 95% CI:1.35-2.64; p-Value < .001) and endometrioid ovarian cancer risk (EOC) (ORSD  = 1.45; 95% CI: 1.12-1.88; p-Value = .005). However, there were no significant associations of BMR with invasive mucinous ovarian cancer (IMOC), high-grade serous ovarian cancer (HGSOC) and low-grade serous ovarian cancer (LGSOC). The robustness of the above results was further verified in sensitivity analyses. CONCLUSION: The MR study provided etiological evidence for the positive association of BMR with the risk of EC, EEC, OC, CCOC and EOC. But this study did not provide enough evidence suggesting the causal associations of BMR with IMOC, HGSOC and LGSOC.

Pain Incidence and Associated Risk Factors among Cancer Patients within 72 Hours after Surgery: A Large Retrospective Analysis.

BACKGROUND: A fundamental principle of pain management is to determine the distribution and causes of pain. However, relevant data among postoperative cancer patients based on a large amount of data remain sparse. OBJECTIVE: We aimed to investigate the incidence of postoperative pain in cancer patients and to explore the associated risk factors. METHODS: We retrospectively collected information on postoperative pain-evaluation records of cancer patients who underwent surgery between 1 January 2014 and 31 December 2019. Descriptive statistics were presented, and multinominal logistic regression analysis was performed to explore the risk factors associated with postoperative pain. RESULTS: Among the 11,383 patients included in the study, the incidence of mild/moderate to severe pain at the 24th hour after surgery was 74.9% and 18.3%, respectively. At the 48th and 72nd hour after surgery, the incidence of mild pain increased slightly, while the incidence of moderate to severe pain continued to decrease. Female patients experienced a higher risk of pain (ORs: 1.37-1.58). Undergoing endoscopic surgery was associated with a higher risk of pain (ORs: 1.40-1.56). Patients with surgical sites located in the respiratory system had a higher risk of pain compared to in the digestive system (ORs: 1.35-2.13), and other patients had a relatively lower risk of pain (ORs: 0.11-0.61). CONCLUSION: The majority of cancer patients experienced varying degrees of postoperative pain but may not receive adequate attention and timely treatment. Female, young age and endoscopic surgery were associated with increased pain risk, and effective identification of these high-risk groups had positive implications for enhanced postoperative pain management.

Postoperative Pain in Patients Undergoing Cancer Surgery and Intravenous Patient-Controlled Analgesia Use: The First and Second 24 h Experiences.

INTRODUCTION: Postoperative cancer pain imposes severe physical and psychological problems. We aimed to investigate the pain experiences of patients with cancer after surgery, analyze the impact of infusion volume by patient-controlled analgesia (PCA), and explore the variations between day 1 and day 2. METHODS: Data were retrospectively extracted from a large health data platform. Descriptive statistics were presented for the demographic and clinical profiles of patients. Multiple logistic regression analyses were performed to evaluate associations between intensity of pain and PCA use after adjustment for risk factors. RESULTS: Among 11,383 patients with cancer, the incidence of pain (moderate to severe pain) was 93.3% (18.3%) at the first 24 h after operation, while the respect values decreased to 91.1% and 9.5% at the second 24 h. Further, female patients consistently experienced higher risk of pain over the whole 48 h postoperatively. Surgical sites were related to pain risk, with the highest risk among the respiratory system (OR 2.077, 95% CI 1.392-3.100). High doses of continuous volume (OR 2.453, 95% CI 1.742-3.456) and total volume (OR 2.830, 95% CI 2.037-3.934) of infusions were related to 1-3-fold elevated pain risk. Additionally, the observed associations were mostly repeated and could be up to over 10 times when pain was evaluated with number of PCA pump compressions instead of Numerical Rating Scale (NRS). CONCLUSIONS: High risk of postoperative cancer pain, particularly among the high PCA dose group, could possibly indicate inadequate pain control, and presence of modifiable risk factors warrants more aggressive pain management strategies perioperatively.

Synergism between the metabolic syndrome components and cancer incidence: results from a prospective nested case-control study based on the China Health and Retirement Longitudinal Study (CHARLS).

OBJECTIVES: Synergism between the metabolic syndrome (MetSyn) components and cancer incidence still remains inconclusive. We aimed to investigate the unique or joint role of MetSyn components in cancer onset. DESIGN: We conducted a prospective nested case-control study based on the China Health and Retirement Longitudinal Study. SETTING: An ongoing national representative longitudinal study included follow-up survey of people aged 45 years and older and their partners living in private households in China. PARTICIPANTS: There were 17 708 individuals included at baseline. A total of 306 incident cancers was identified during the follow-up. For every case, we used incidence-density sampling to match three concurrent cancer-free controls by age, sex, and both duration and calendar time of follow-up. Exposure of interest was any MetSyn diagnosis at baseline. RESULTS: We observed elevation in cancer risk associated with MetSyn in a significant way when the number of MetSyn components was over three (OR: 1.88; 95% CI: 1.19 to 2.97), or when components contained any of elevated triglycerides (OR: 1.61; 95% CI: 1.05 to 2.48), reduced high-density lipoprotein (HDL) cholesterol (OR: 2.33; 95% CI: 1.40 to 3.86) or elevated blood pressure (OR: 1.65; 95% CI: 1.04 to 2.59) after consistent multiple adjustments in different models. The highest cancer risk was in the female reproductive system and breast cancer (OR: 4.22; 95% CI: 1.62 to 10.95) followed by digestive system (OR: 1.67; 95% CI: 1.11 to 2.53). Sensitivity analyses showed similar results after first follow-up was excluded. However, any unique MetSyn component was not associated with increased cancer risk. Interestingly, the reduced HDL was observed to be widely associated with over twofold increased risk of cancer, only when together with other MetSyn components. CONCLUSION: MetSyn components, in a collaborative manner rather than its unique component, were associated with elevated cancer risk. Not only obesity but even subtle metabolic disturbances may give rise to cancer.

Comparing Long-Term Survival Outcomes for Muscle-Invasive Bladder Cancer Patients Who Underwent with Radical Cystectomy and Bladder-Sparing Trimodality Therapy: A Multicentre Cohort Analysis.

Background: Although radical cystectomy (RC) is the clinical practice guideline-recommended treatment of muscle-invasive bladder cancer (MIBC), bladder-sparing trimodality therapy (TMT) has emerged as a valid treatment option. Findings comparing the survival outcomes for MIBC patients who underwent RC and TMT are inconclusive. Objective: We designed a large hospital-based multicohort study to compare the effectiveness of TMT with RC. Methods: Information on deaths was jointly retrieved from EMR (electronic medical record), cause of death registry, and chronic disease surveillance as well as study-specific questionnaire. To avoid the systematical difference between patients who received two modalities, RC-MIBC cohort was propensity score-matched to TMT-MIBC cohort, and the Cox proportional hazard regression was used to calculate the overall survival (OS) and disease-specific survival (DSS). Results: There were 891 MIBC patients treated with RC and another 891 MIBC patients who underwent with TMT in the propensity score matching. Comparable effectiveness between two modalities was observed for DSS (HR, 1.20; 95% confidence interval (CI), 0.94 to 1.49) and OS (HR, 1.17; 95% CI, 0.91 to 1.43) according to multiple adjustment after a median follow-up of approximately 9.3 years. However, a relatively higher mortality rate around 5 years after TMT treatment was found compared to RC (HR, 1.26; 95% CI, 1.01 to 1.53). The respective 5-year OS rates were 69% and 73% for TMT cohort and RC cohort, respectively. Conclusions: Our findings supported that MIBC patients with TMT yielded survival outcomes comparable to MIBC patients who underwent RC overall. Treatment options should be suggested considering patients' age and willingness.

Hormone replacement therapy in relation to the risk of colorectal cancer in women by BMI: a multicentre study with propensity score matching.

BACKGROUND: Epidemiological evidence about hormone replacement therapy and colorectal carcinogenesis by demographic and clinical traits remains unclear. We aimed to assess this postulated association in a large multicentre study and further explore the modification effect by BMI and others. METHODS: We retrospectively collected records of women diagnosed with colorectal cancer (CRC) at the age of 50 years and older during 2014-2017 and their HRT dispensing prior to CRC diagnosis in three tertiary hospitals in China. CRC cases were matched with controls at a ratio of 1:3 using nearest neighbour propensity scores matching to better control for the remaining imbalance between groups, which generated a total of 824 cases with 2472 controls. RESULTS: Our study confirmed the inversed association between colorectal cancer risk and hormone replacement therapy (OR, 0.62; 95% CI, 0.54-0.75), which was more prominent among women having multiple HRT dispenses (OR, 0.60; 95% CI, 0.52-0.76). Furthermore, significant associations were consistently observed for the short-term (OR, 0.69; 95% CI, 0.57-0.88), middle-term (OR, 0.51; 95% CI, 0.41-0.66), and long-term HRT users (OR, 0.70; 95% CI, 0.43-0.90). Estrogen-related regimen reduced CRC risk more than progestogen-only. We, for the first time, found that the modifying effect of BMI on HRT use and CRC risk was in different ways when BMI was categorized by a medium level of 27. CONCLUSION: Our findings mainly suggest that there might be a different mechanism for the reversed association between HRT and colorectal tumorigenesis by BMI level, providing thoughts on clinical treatment of CRC.

Clinical significance of serum IgM and IgG levels in COVID-19 patients in Hubei Province, China.

Background: There have been many studies about coronavirus disease 2019 (COVID-19), but the clinical significance of quantitative serum severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2)-specific IgM and IgG levels of COVID-19 patients have not been exhaustively analyzed. We aimed to investigate the time profiles of these IgM/IgG levels in COVID-19 patients and their correlations with clinical features. Methods: A multicenter clinical study was conducted from February 20 to March 5 2020. It involved 179 COVID-19 patients (108 males and 71 females) from five hospitals in Huangshi in Hubei Province, China. To detect SARS-CoV-2-specific IgM/IgG, quantitative antibody assays (two-step indirect immunoassays with direct chemiluminescence technology) based on the nucleocapsid protein (NP) and spike protein 1 (S1) were used. For normally distributed data, means were compared using the t-test, χ 2-test, or exact probability method. For categorical data, medians were compared using Mann-Whitney U test. Results: The median age was 57 (44-69) years (58 [38-69] for males and 57 [49-68] for females). The median duration of positive nucleic acid test was 22.32 (17.34-27.43) days. The mortality rate was relatively low (3/179, 1.68%). Serum SARS-CoV-2-specific IgG was detected around week 1 after illness onset, gradually increased until peaking in weeks 4 and 5, and then declined. Serum IgM peaked in weeks 2 and 3, then gradually declined and returned to its normal range by week 7 in all patients. Notably, children had milder respiratory symptoms with lower SARS-CoV-2-specific IgM/IgG levels. The duration of positive nucleic acid test in the chronic obstructive pulmonary disease (COPD) group was 30.36 (18.99-34.76) days, which was significantly longer than that in the non-COPD group (21.52 [16.75-26.51] days; P = 0.025). The peak serum SARS-CoV-2-specific IgG was significantly positively correlated with the duration of positive nucleic acid test. The incidence rate of severe and critical cases in the IgMhi group (using the median IgM level of 29.95 AU/mL as the cutoff for grouping) was about 38.0% (19/50), which was twice as much as that in the IgMlo group (18.4%; 9/49). The patients with positive chest imaging and lymphocytopenia (<1 × 109/L) had a higher SARS-CoV-2-specific IgM level. Conclusions: Quantitative SARS-CoV-2-specific IgM and IgG levels are helpful for the diagnosis, severity classification, and management of COVID-19 patients, and they should be monitored in each stage of this disease.

Risk of Death in Colorectal Cancer Patients with Multi-morbidities of Metabolic Syndrome: A Retrospective Multicohort Analysis.

PURPOSE: The prevalence of multi-morbidities with colorectal cancer (CRC) is known to be increasing. Particularly prognosis of CRC patients co-diagnosed with metabolic syndrome (MetSyn) was largely unknown. We aimed to examine the death risk of CRC patients according to the multiple MetSyn morbidities. MATERIALS AND METHODS: We identified CRC patients with MetSyn from the electronic medical records (EMR) systems in five independent hospitals during 2006-2011. Information on deaths was jointly retrieved from EMR, cause of death registry and chronic disease surveillance as well as study-specific questionnaire. Cox proportional hazards regression was used to calculate the overall and CRC-specific hazards ratios (HR) comparing MetSyn CRC cohort with reference CRC cohort. RESULTS: A total of 682 CRC patients in MetSyn CRC cohort were identified from 24 months before CRC diagnosis to 1 month after. During a median follow-up of 92 months, we totally observed 584 deaths from CRC, 245 being in MetSyn cohort and 339 in reference cohort. Overall, MetSyn CRC cohort had an elevated risk of CRC-specific mortality (HR, 1.49; 95% confidence interval [CI], 1.07 to 1.90) and overall mortality (HR, 1.43; 95% CI, 1.09 to 1.84) compared to reference cohort after multiple adjustment. Stratified analyses showed higher mortality risk among women (HR, 1.87; 95% CI, 1.04 to 2.27) and specific components of MetSyn. Notably, the number of MetSyn components was observed to be significantly related to CRC prognosis. CONCLUSION: Our findings supported that multi-morbidities of MetSyn associated with elevated death risk after CRC. MetSyn should be considered as an integrated medical condition more than its components in CRC prognostic management.

A novel prognostic biomarker for muscle invasive bladder urothelial carcinoma based on 11 DNA methylation signature.

Muscle-invasive bladder urothelial carcinoma (MIBC) is a highly invasive cancer, which leads to prevalent recurrence and poor prognosis. Exploring the association of DNA methylation and the prognosis of MIBC will thus be of important value in clinical management and treatment. Bumphunter method and adaptive lasso regression were used to explore the relationship between different methylation regions (DMRs) and the prognosis of MIBC. Next, we constructed a risk prognosis model and validated this model. Moreover, the performance of this risk model was examined by using time-dependent receiver operating characteristic curve (ROC). We identified 58,449 different methylation sites and 490 different methylation regions. Among them, 11 DMRs were associated with the prognosis of MIBC through rigorous screening. Through the linear combination of 11 DMRs, a putative marker was developed, which can distinguish the survival risk in both the training dataset (HR = 2.58, 95% CI = (1.64, 4.05)) and the verification dataset (HR = 2.77, 95% CI = (1.25, 6.15)). Relatively high predictive values were observed from this model for training dataset (AUC = 0.791) and verification dataset (AUC = 0.668). Stratified analysis showed that the association was independent of gender. A nomogram was additionally generated to predict 5-year survival probability containing risk score and pathological stage. Its performance was evaluated by applying calibration curve. The methylation signature risk model based on 11 DMRs may be a reliable prognostic signature for MIBC, which provides new insights into development of individualized therapy for MIBC.

Identifying Potential Prognostic Markers for Muscle-Invasive Bladder Urothelial Carcinoma by Weighted Gene Co-Expression Network Analysis.

Muscle-invasive bladder urothelial carcinoma (MIBC) is characterized as a genetic heterogeneous cancer with a high percentage of recurrence and worse prognosis. Identify the prognostic potentials of novel genes for muscle-invasive urothelial bladder cancer could at least provide important information for early detection and clinical treatment. Weighted gene co-expression network analysis (WGCNA) algorithm, a powerful systems biology approach, was utilized to extract co-expressed gene networks from mRNA expression dataset to construct transcriptional modules in MIBC samples, which was associated with demographic and clinical traits of MIBC patients. The potential prognostic markers of MIBC were screened out in the discovery dataset and verified in an independent external validation dataset. A total of 8 co-expression modules were detected through the WGCNA algorithm in the discovery datasets based on 401 MIBC samples. One transcriptional module enriched in cell development was observed to be correlated with the MIBC prognosis in the discovery datasets (HR = 1.48, 95%CI = 1.04-2.11) and independently verified in an external dataset (HR = 3.59, 95%CI = 1.09-11.79). High expression of hub genes including discoidin domain receptor tyrosine kinase 2 (DDR2), PDZ and LIM domain 3 (PDLIM3), zinc finger protein 521 (ZNF521), methionine sulfoxide reductase B3 (MSRB3) were significantly associated with the unfavorable survival of MIBC patients. We identified and validated four novel potential biomarkers associated with prognosis of MIBC patients by constructing genes co-expression networks. The discovery of these genetic markers may provide a new target for the development of MIBC chemotherapeutic drugs.

A Novel Biomarker Based on miRNA to Predict the Prognosis of Muscle-Invasive Bladder Urothelial Carcinoma.

Muscle-invasive bladder urothelial carcinoma (MIBC) is characteristic of high mortality and high recurrence. Distinguishing the prognostic risk of MIBC at the molecular level of miRNA expression is rarely performed and thus of great significance for the management and treatment of MIBC in clinics. Adaptive lasso Cox's proportional hazards model was used to explore the relationship between differential expression miRNAs (DEmiRNAs) and MIBC survival. Furthermore, we evaluated the epithelial-mesenchymal transition (EMT) score and immune infiltration abundance by exploring EMT signature genes and TIMER database, respectively. A total of 8 DEmiRNAs were detected to be associated with the survival rate of MIBC by using the lasso Cox algorithm. Through the linear combination of these 8 DEmiRNAs, we constructed a calculated marker, which could be used to distinguish the prognosis risk in both TCGA dataset (HR = 2.03, 95% CI = (1.47, 2.83)) and independent validation dataset (HR = 7.74, 95% CI = (1.05, 56.93)). Meanwhile, the constructed marker had reasonably high predictive values of the AUC (area under the curve) in the TCGA dataset and validation dataset being 0.73 and 0.63, respectively. In addition, we observed that the expression values of let-7c, miR-100, and miR-145 were associated with EMT score and the abundance of macrophage in tumor tissue as well. This newly identified risk score signature based on the combination of 8 miRNAs could significantly predict the prognostic risk of MIBC and might provide insight into immunotherapy and targeted therapy of MIBC.

The Relative Risk of Immune-Related Liver Dysfunction of PD-1/PD-L1 Inhibitors Versus Chemotherapy in Solid Tumors: A Meta-Analysis of Randomized Controlled Trials.

Background: Immune checkpoint inhibitors (ICIs) have made a significant breakthrough in the treatment of solid tumors; however, their use also generates unique immune-related adverse effects (irAEs). Here, we performed a systematic review and meta-analysis to assess the risk of immune-related liver dysfunction between in patients treated by programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors exclusively and chemotherapy. Methods: A comprehensive search of multiple databases identified eligible studies, including randomized controlled trials (RCTs) with PD-1/PD-L1 inhibitors exclusively and chemotherapy in patients with different solid tumors was carried out. The elevations of alanine aminotransferase (ALT) and aspartic aminotransferase (AST) were used to evaluate liver dysfunction. The relative risk (RR) and 95% confidence intervals (CI) were calculated and analyzed by Review Manager 5.3 and STATA version 12.0 statistical software. Results: After screening and eligibility assessment, a total of 5638 patients from 12 RCTs were included in our meta-analysis. In comparison with chemotherapy, patients treated with PD-1/PD-L1 inhibitors exclusively showed an increased incidence of all-grade ALT/AST elevations (ALT: RR, 1.52, 95% CI, 1.09-2.13; p = 0.01; AST: RR, 1.96, 95% CI, 1.37-2.81; p = 0.0002). Patients receiving PD-1 inhibitors showed the significantly higher risk of all-grade ALT/AST elevations incidence than those receiving chemotherapy (ALT: RR, 1.47; 95% CI, 1.05-2.07; p = 0.03; AST: RR, 1.90, 95% CI, 1.32-2.73; p = 0.0005). However, no significant difference was found between PD-L1 inhibitor and chemotherapy group. Moreover, for non-small cell lung cancer (NSCLC) and urothelial carcinoma (UC), patients treated with PD-1/PD-L1 inhibitors exclusively exhibited a significant higher risk of all-grade ALT elevation incidence (NSCLC: RR, 1.92; 95% CI, 1.23-3.02; p = 0.004; UC: RR, 3.36; 95% CI, 1.12-10.06, p = 0.03) and all-grade AST elevation incidence (NSCLC: RR, 2.37; 95% CI, 1.45-3.87, p = 0.0005; UC: RR, 4.47; 95% CI, 1.30-15.38, p = 0.02) than chemotherapy. Conclusions: The meta-analysis confirms that PD-1/PD-L1 inhibitors exclusive pose an increased risk of immune-related liver dysfunction than chemotherapy. PD-1/PD-L1 blockade in NSCLC and UC increase the risk of immune-related liver dysfunction, but not in melanoma (MM) and head-neck squamous cell carcinoma (HNSCC).

Efficacy and Safety of Direct Oral Anticoagulants for Risk of Cancer-Associated Venous Thromboembolism.

Efficacy and safety of direct oral anticoagulants (DOACs) for preventing primary and recurrent venous thromboembolism (VTE) in patients with cancer remain unclear. In this study, we conducted a systematic review to summarize the most up-to-date evidence from randomized controlled trials (RCTs). Our primary outcomes included the benefit outcome (VTE) and safety outcome (major bleeding). A random-effects model was used to pool the relative risks (RRs) for data syntheses. The Grading of Recommendations Assessment, Development and Evaluation tool was used to evaluate the quality of the entire body of evidence across studies. We included 11 RCTs with a total of 3741 patients with cancer for analyses. The DOACs were significantly related with a reduced risk of VTE when compared with non-DOACs: RR = 0.77, 95% confidence interval [CI]: 0.61-0.99, P = .04. Nonsignificant trend towards a higher risk of major bleeding was found in DOACs: RR = 1.28 95% CI: 0.81-2.02, P = .29. The quality of the entire body of evidence was graded as moderate for risk of VTE, and low for risk of major bleeding. To summarize, DOACs were found to have a favorable effect on risk of VTE but a nonsignificant higher risk of major bleeding compared with non-DOACs in patients with cancer. The safety effect of DOACs in patients with cancer requires further evaluation in adequately powered and designed studies.

Association of hormone replacement therapy with increased risk of meningioma in women: A hospital-based multicenter study with propensity score matching.

AIM: There is no consensus regarding the association between hormone replacement therapy (HRT) and risk of meningioma so far. We conducted the first study among Chinese female patients to investigate the influence of HRT use on the risk of meningioma. METHODS: We retrospectively collected records of diagnosis of meningioma for women aged 50 years and above during 2011-2016 and dispense of HRT prior to meningioma diagnosis in three tertiary hospitals in China. Meningioma cases were matched with controls at a ratio of 1:2 by using nearest neighbor propensity scores matching in order to balance the baseline characteristics between groups, which generated a total of 629 cases with 1258 controls. RESULTS: We observed prior use of HRT associated with increased risk of meningioma (odds ratio [OR], 1.2; 95% confidence interval [CI], 1.0-1.4) and the association was more prominent among women having multiple HRT dispenses and longer term exposure (OR, 1.3; 95% CI, 1.1-1.6), among those with combination therapy of estrogens and progestogens (OR, 1.3; 95% CI, 1.1-1.7) than monotherapy, and among progestogen users than estrogen users as for monotherapy. Furthermore, vaginal, subcutaneous implant seems to be associated with a higher risk of meningioma compared with oral administration although no significance had been reached. CONCLUSION: This case-control study provides evidence that hormone use for an HRT purpose might constitute the development and growth of meningioma as an independent risk factor, especially for combination therapy and/or long-term users, which supports that meningioma might be a hormone-sensitive tumor.

Prenatal and Postnatal Medical Conditions and the Risk of Brain Tumors in Children and Adolescents: An International Multicenter Case-Control Study.

BACKGROUND: Previous studies have evaluated the effect of medical diagnostic radiation on brain tumors. Recent cohort studies have reported an increased risk associated with exposure to head CT scans. METHODS: Information regarding medical conditions, including prenatal and postnatal exposure to medical diagnostic radiation, was obtained from CEFALO, a multicenter case-control study performed in Denmark, Norway, Sweden, and Switzerland through face-to-face interview. Eligible cases of childhood and adolescent brain tumors (CABT) were ages 7 to 19 years, diagnosed between January 1, 2004 and August 31, 2008, and living in the participating countries (n = 352). The cases were matched by age, sex, and region to 646 population-based controls. RESULTS: Prenatal exposure to medical diagnostic radiation and postnatal exposure to X-rays were not associated with CABTs. A higher risk estimate of CABTs, although not statistically significant, was found for exposure to head CT scan (OR, 1.86; 95% confidence interval, 0.82-4.22). The associations with head injury, febrile seizure, fever in the first 12 weeks, and general anesthesia were close to unity. CONCLUSIONS: Prenatal or postnatal medical conditions, including medical diagnostic radiation, were not associated with CABTs. On the basis of small numbers of exposed children, we observed a nonsignificant increased risk for CT scans of the head. IMPACT: We have presented additional evidence, suggesting that exposure to head CT scan may be associated with the occurrence of CABTs. Cancer Epidemiol Biomarkers Prev; 26(1); 110-5. ©2016 AACR.

Treatment of adolescent patients with class II division 1 malocclusion using Eruption guidance appliance: A comparative study with Twin-block and Activator-Headgear appliances.

The aim of this study was to evaluate the compliance and short-term effects of eruption guidance appliance (EGA) in adolescents with class II division 1 malocclusion in comparison with twin-block appliance (TBA) and activator-headgear appliance (A-HG). Dental records of 1886 patients were viewed in this retrospective study 129 patients treated with one of these three functional appliances were identified. 123 fulfilled the inclusion criteria and data were extracted from the dental records. Gender, age, compliance, overjet change at every visit, number of appliance breakages and number of emergency visits apart from appliance breakage were studied. The data were analyzed with Chi-square test, General Linear Model and Fisher scoring test. Results showed that 47 patients were treated with EGA, 38 patients with TBA and 38 patients with A-HG. Mean ages starting the treatment were slightly lower with EGA (11.5 years) than with TBA (12.3 years) and A-HG (11.8 years). Non-compliance was higher in the EGA group (31.9%) than TBA group (26.3%) and A-HG group (23.7%). Mean overjet reduction per month was 0.6 mm for EGA which was lower than TBA group (0.7 mm) and A-HG groups (0.7 mm).The number of emergency visits and appliance breakage were lower in EGA group. However, there was no statistically significant difference between the 3 groups regarding ages,compliance, mean overjet reduction, emergency visits and appliance breakage aspects. In conclusion, this study indicates that EGA is an alternative choice in the treatment of adolescent patients with class II division 1 malocclusion. However, long-term follow-up and cephalometric prospective study should be performed to continue our understanding more about the mechanisms of EGA and more definite conclusions can be made.