Tyrosine kinase inhibitors for radioiodine refractory differentiated thyroid cancer: A systematic review and meta-analysis.

BACKGROUND: The poor overall prognosis of radioiodine refractory thyroid cancer is an inevitable challenge in managing this disease. A series of trials have demonstrated the antitumor activity of tyrosine kinase inhibitors (TKIs) in radioiodine refractory differentiated thyroid cancer (RAIR-DTC). However, the available evidence cannot determine the optimal choice of TKI in RAIR-DTC. METHODS: This study searched PubMed, EMBASE, Cochrane databases, and the ClinicalTrials website. The Cochrane bias risk tool was used to assess the risk of bias, and to evaluate randomized clinical trials (RCT) of RAIR-DTC patients treated with the TKI system. Outcomes, including progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were reported. RESULTS: Seven studies involving 1310 patients with RAIR-DTC was conducted to compare the PFS and OS of various TKI monotherapies with placebo. The results showed that all TKI monotherapies had a statistically significant benefit in terms of PFS compared with placebo, with lenvatinib demonstrating the greatest benefit (hazard ratio [HR] 0.19, 95% credible interval [CrI] 0.14-0.25). In terms of OS, only apatinib (HR 0.42, 95% CrI 0.18-0.97) and anlotinib (HR 0.36, 95% CrI 0.18-0.73) showed statistically significant benefits compared with placebo. TKIs also had a higher incidence of AEs of grade 3 or higher compared with placebo. The findings suggest that lenvatinib may be the preferred TKI for the treatment of RAIR-DTC, although its high incidence of AEs should be considered. The results also indicate that TKI treatment may be similarly effective in RAIR-DTC patients with BRAF or RAS mutations and in those with papillary or follicular subtypes of the disease, regardless of prior TKI treatment. CONCLUSIONS: The results of this meta-analysis suggest that targeted therapy with TKIs may be beneficial for patients with radioiodine-refractory advanced or metastatic differentiated thyroid cancer. Among the TKIs analyzed, lenvatinib appeared to be the most effective at improving PFS, although it also had the highest incidence of AEs. Further research through direct randomized controlled trials is needed to determine the optimal choice of TKI for treating patients with RAIR-DTC. This study is beneficial for formulating patients' treatment plans and guides clinicians' decision-making.

BMI trajectories in late middle age, genetic risk, and the incident diabetes in older adults: evidence from a 26-year longitudinal study.

This study investigated the association between BMI trajectories in late middle age and incident diabetes in later years. A total of 11,441 participants aged 50-60 years from the Health and Retirement Study with at least two self-reported BMI records were included. Individual BMI trajectories representing average BMI changes per year were generated using multilevel modeling. Adjusted risk ratios (ARRs) and 95% confidence intervals (95% CIs) were calculated. Associations between BMI trajectories and diabetes risk in participants with different genetic risks were estimated for 5720 participants of European ancestry. BMI trajectories were significantly associated with diabetes risk in older age (slowly increasing vs. stable: ARR 1.31, 95% CI 1.12-1.54; rapidly increasing vs. stable: ARR 1.5, 95% CI 1.25-1.79). This association was strongest for normal-initial-BMI participants (slowly increasing: ARR 1.34, 95% CI 0.96-1.88; rapidly increasing: ARR 2.06, 95% CI 1.37-3.11). Participants with a higher genetic liability to diabetes and a rapidly increasing BMI trajectory had the highest risk for diabetes (ARR 2.15, 95% CI 1.67-2.76). These findings confirmed that BMI is the leading risk factor for diabetes and that although the normal BMI group has the lowest incidence rate for diabetes, people with normal BMI are most sensitive to changes in BMI.

Association between nut consumption and cancer risk: a meta-analysis.

This study aims to conduct a meta-analysis and dose-response analysis of the relationship between nut intake and cancer risk and mortality. Electronic databases were searched. A meta-analysis was conducted to calculate the pooled effect sizes (ESs) with the corresponding 95% CIs, and a dose-response analysis was performed. A random-effects model was used in the statistical analysis. Two independent reviewers completed the full-text screening, data extraction, and quality assessment. We included 17 articles in the present meta-analysis. Total nuts intake was revealed to be significantly associated with reduced cancer risk (ES: 0.9; 95% CI: 0.86-0.95; P < 0.001) and cancer mortality (ES: 0.88; 95% CI: 0.85-0.92, P < 0.001), especially lung cancer risk (ES: 0.86; 95% CI: 0.81-0.91, P < 0.001) and gastric cancer risk (ES: 0.79; 95% CI: 0.68-0.91, P = 0.001). Moreover, a 10 g/d increment of tree nuts consumption was associated with a 20% cancer mortality reduction (ES: 0.80; 95% CI: 0.71-0.89; P < 0.0001). Nuts intake is significantly associated with the reduction of cancer risk and mortality. Especially, nuts intake is significantly associated with reduced lung cancer risk and gastric cancer risk. Noticeably, a 10 g/d increase in tree nuts intake is related to a 20% reduction in overall cancer mortality.

Depression Trajectories, Genetic Risk, and Cognitive Performance in Older Adults: Multilevel Model with a 10-Year Longitudinal Cohort.

INTRODUCTION: Cognitive performance in older ages is strongly affected by individuals' genetic predispositions. We investigated whether depression trajectories were associated with subsequent cognitive performance independent of participants' genetic predispositions. METHODS: Participants from the Health and Retirement Study with European ancestry and aged over 50 were included in the analysis. Depressive symptoms were evaluated using the Center for Epidemiologic Studies Depression Scale, and the 6-year trajectories were fitted using latent class linear mixed models. Linear multilevel regression was applied to model the associations between depression trajectory and subsequent cognitive performance. Stratified analyses were performed to investigate these associations in participants with different genetic predispositions of cognitive performance and APOE ε4 allelic status. RESULTS: A total of 5,942 eligible participants were included in the study. Four depression trajectories were identified. Compared with the nondepression trajectory, all other depression trajectories were associated with worse cognitive performance (ß [95% CI]: mild-depression trajectory: -0.20 [-0.56, -0.06], p = 0.007; worsening-depression trajectory: -0.29 [-0.47, -0.12], p = 0.001; persistent-depression trajectory: -0.32 [-0.53, -0.13], p = 0.001). Although these associations were independent of participants' inherent genetic risk, the participants with a low polygenetic score for cognitive performance were more likely to have an enhanced association between depression trajectories and cognitive decline. Similar relationships were also found in APOE ε4 noncarriers. CONCLUSION: Among older participants with European ancestry, even a mild-depression trajectory was associated with worse cognitive performance. Early intervention in participants with any degree of depression might benefit regarding preventing cognitive performance decline.

Association between BMI trajectories in late-middle age and subsequent dementia risk in older age: a 26-year population-based cohort study.

BACKGROUND: The association between body mass index (BMI) and dementia risk differs depending on follow-up time and age at BMI measurement. The relationship between BMI trajectories in late-middle age (50-65 years old) and the risk of dementia in older age (> 65 years old) has not been revealed. METHODS: In the present study, participants from the Health and Retirement Study were included. BMI trajectories were constructed by combining BMI trend and variation information. The association between BMI trajectories at the age of 50-65 years and dementia risk after the age of 65 years was investigated. Participants with European ancestry and information on polygenic scores for cognitive performance were pooled to examine whether genetic predisposition could modify the association. RESULTS: A total of 10,847 participants were included in the main analyses. A declining BMI trend and high variation in late-middle age were associated with the highest subsequent dementia risk in older age compared with an ascending BMI trend and low variation (RR = 1.76, 95% CI = 1.45-2.13). Specifically, in stratified analyses on BMI trajectories and dementia risk based on each individual's mean BMI, the strongest association between a declining BMI trend with high variation and elevated dementia risk was observed in normal BMI group (RR = 2.66, 95% CI = 1.72-4.1). Similar associations were found when participants were stratified by their genetic performance for cognition function without interaction. CONCLUSIONS: A declining BMI trend and high variation in late-middle age were associated with a higher risk of dementia. Early monitoring of these individuals is needed to prevent dementia in older individuals.

Effectiveness of eHealth interventions for cancer-related pain, fatigue, and sleep disorders in cancer survivors: A systematic review and meta-analysis of randomized controlled trials.

PURPOSE: To systematically evaluate the effects of Electronic health (eHealth) interventions on fatigue, pain, and sleep disorders in cancer survivors. DESIGN: A systematic review and meta-analysis was conducted. METHODS: Relevant studies were searched from five databases (MEDLINE, Embase, the Cochrane Central Register of Controlled trials, CINAHL, and PsycINFO). The comprehensive literature search was done in December 2020. Only randomized controlled trials (RCTs) that examined the effects of eHealth interventions among cancer survivors were included. FINDINGS: Twenty-five RCTs were included. The meta-analysis showed that eHealth interventions had a positive impact on pain interference (SMD = -0.37, 95% CI: -0.54 to -0.20, p = 0.0001) and sleep disorders (SMD = -0.43, 95% CI: -0.77 to -0.08, p = 0.02) but not on pain severity or fatigue in cancer survivors. The sensitivity and subgroup analyses indicated that the pooled results were robust and reliable. CONCLUSION: eHealth interventions are effective in improving pain interference and sleep disorders in cancer survivors. Additional high-quality RCTs are needed to test the effectiveness of eHealth interventions on fatigue, pain, and sleep disorders in cancer survivors. CLINICAL RELEVANCE: This systematic review and meta-analysis provides evidence to offer effective and sustainable eHealth care for symptom management among cancer survivors.

Clinicopathological and prognostic significance of speckle-type POZ protein in cancers: a systematic review and meta-analysis.

BACKGROUND: Controversial findings have been reported in the impact of speckle-type POZ protein (SPOP) on clinicopathological features and prognosis in diverse cancers. We conducted this meta-analysis to confirm whether SPOP was an effective biomarker to predict clinical stage, cancer differentiation and survival. METHODS: We searched studies published before June 2021 through Medline, Embase, the Cochrane library register of controlled trials and Wanfang databases. The corrections of SPOP expression with expression disparity, tumor differentiation, clinical stage and survival were analyzed. RESULTS: Our meta-analysis found that higher expression of SPOP was significantly associated with earlier clinical stage, well differentiation and better overall survival. Subgroup analysis showed that the SPOP expression of adjacent tissue was significantly higher than that in cancer tissues of prostate and liver. However, renal cancer presented improved expression of SPOP in cancer tissue. CONCLUSIONS: SPOP has the potential function to act as a novel and effective biomarker for cancer diagnosis and prognostic stratification.

RNA quality score evaluation: A preliminary study of RNA integrity number (RIN) and RNA integrity and quality number (RNA IQ).

In the past several years, with the in-depth development of RNA-related research, exploring the application of transcriptome and corresponding RNA biomarkers has become one of the research hotspots in the field of forensic science. High-quality RNA is essential for successful downstream workflows, especially in the steps of screening biomarkers by microarray or RNA sequencing (RNA-seq). Thus, accurately evaluating the quality of RNA samples is a critical step in obtaining meaningful expression data. The RNA integrity number (RIN) generated from the Agilent Bioanalyzer system has been widely used for RNA quality control in the past two decades. Recently, Thermo Fisher Scientific launched a ratiometric fluorescence-based method to quickly check whether an RNA sample has degraded, and the results are presented as RNA integrity and quality number (RNA IQ). Both quality score systems determine RNA quality using a numerical system based on a scale of 1-10, with 1 denoting significantly degraded specimens and 10 representing high-quality, intact RNA samples. In this preliminary study, we evaluated the consistency, reproducibility and linearity of two quality scores in RNA quality determination by analyzing heat- and RNase- artificially degraded samples. Meanwhile, the expression levels of three microRNAs (hsa-let-7 g-5p, hsa-miR-93-5p and hsa-miR-191-5p) in intact and severely degraded RNA samples were estimated by TaqMan-qPCR and droplet digital PCR. Overall, both quality scores showed good repeatability and reproducibility in their respective tests. In the samples subjected to thermal degradation, RIN showed a trend corresponding to heating time, while RNA IQ value showed almost no change on the time gradient. However, in RNase A mediated degradation, RNA IQ value observed better linearity. Furthermore, the expression levels of three microRNAs in the severely degraded samples did not show significant changes compared to the intact RNA samples. RNA degradation is a very complex and highly variable process, which is difficult to comprehensively evaluate through any one index and cannot directly compare these two parameters. Nevertheless, combined with previous research results and the expression levels of three microRNAs in this study, analyzing RNA biomarkers with stable regions or small sizes in challenged samples may be a conservative and reliable approach.

A proof-of-principle study: The potential application of MiniHap biomarkers in ancestry inference based on the QNome nanopore sequencing.

Haplotyped SNPs convey forensic-related information, and microhaplotypes (MHs), as the most representative of this kind of marker, have proved the potential value for human forensics. In recent years, nanopore sequencing technology has developed rapidly, with its outstanding ability to sequence long continuous DNA fragments and obtain phase information, making the detection of longer haplotype marker possible. In this proof-of-principle study, we proposed a new type of forensic marker, MiniHap, based on five or more SNPs within a molecular distance less than 800 bp, and investigated the haplotype data of 56 selected MiniHaps in five Chinese populations using the QNome nanopore sequencing. The sequencing performance, allele (haplotype) frequencies, forensic parameters, effective number of alleles (Ae), and informativeness (In) were subsequently calculated. In addition, we performed principal component analysis (PCA), phylogenetic tree, and structure analysis to investigate the population genetic relationships and ancestry components among the five investigated populations and 26 worldwide populations. MiniHap-04 exhibited remarkable forensic efficacy, with 148 haplotypes reported and the Ae was 66.9268. In addition, the power of discrimination (PD) was 0.9934, the probability of exclusion (PE) was 0.9898, and the In value was 0.7893. Of the 56 loci, 85.71% had PD values above 0.85, 66.07% had PE values above 0.54, 67.86% had Ae values over 7.0%, and 55.36% were with In values above 0.2 across all samples, indicating that most of the MiniHaps are suitable for individual identification, paternity testing, mixture deconvolution, and ancestry inference. Moreover, the results of PCA, phylogenetic tree and structure analysis demonstrated that this MiniHap panel had the competency in continental population ancestry inference, but the differentiation within intracontinental/linguistically restricted subpopulations was not ideal. Such findings suggested that the QNome device for MiniHap detection was feasible and this novel marker has the potential in ancestry inference. Yet, the establishment of a more comprehensive database with sufficient reference population data remains necessary to screen more suitable MiniHaps.

Massively parallel sequencing of 74 microhaplotypes and forensic characteristics in three Chinese Sino-Tibetan populations.

Microhaplotype (MH), as an emerging type of forensic genetic marker in recent years, has the potential to support multiple forensic applications, especially for mixture deconvolution and biogeographic ancestry inference. Herein, we investigated the genotype data of 74 MHs included in a novel MH panel, the Ion AmpliSeq MH-74 Plex Microhaplotype Research Panel, in three Chinese Sino-Tibetan populations (Han, Tibetan, and Yi) using the Ion Torrent semiconductor sequencing. The sequencing performance, allele frequencies, effective number of alleles (Ae), informativeness (In), and forensic parameters were subsequently estimated and calculated. In addition, principal component analysis (PCA) and structure analysis were performed to explore the population relationships among the three populations and the ancestry component distribution. Overall, this novel MH panel is robust and reliable, and has an excellent sequencing performance. The Ae values ranged from 1.0126 to 7.0855 across all samples, and 75.68 % of MHs had Ae values >2.0000. Allele frequencies at some loci varied considerably among the three studied populations, and the mean In value was 0.0195. Moreover, the genetic affinity between Tibetans and Yis was closer than that between Tibetans and Hans. The aforementioned results suggest that the Ion AmpliSeq MH-74 Plex Microhaplotype Research Panel is highly polymorphic in three investigated populations and could be used as an effective tool for human forensics. Although these 74 MHs have demonstrated the competency in continental population stratification, a higher resolution for distinguishing intracontinental subpopulations and a more comprehensive database with sufficient reference population data still remain to be accomplished.

Forensic biogeographical ancestry inference: recent insights and current trends.

BACKGROUND: As a powerful complement to the paradigmatic DNA profiling strategy, biogeographical ancestry inference (BGAI) plays a significant part in human forensic investigation especially when a database hit or eyewitness testimony are not available. It indicates one's biogeographical profile based on known population-specific genetic variations, and thus is crucial for guiding authority investigations to find unknown individuals. Forensic biogeographical ancestry testing exploits much of the recent advances in the understanding of human genomic variation and improving of molecular biology. OBJECTIVE: In this review, recent development of prospective ancestry informative markers (AIMs) and the statistical approaches of inferring biogeographic ancestry from AIMs are elucidated and discussed. METHODS: We highlight the research progress of three potential AIMs (i.e., single nucleotide polymorphisms, microhaplotypes, and Y or mtDNA uniparental markers) and discuss the prospects and challenges of two methods that are commonly used in BGAI. CONCLUSION: While BGAI for forensic purposes has been thriving in recent years, important challenges, such as ethics and responsibilities, data completeness, and ununified standards for evaluation, remain for the use of biogeographical ancestry information in human forensic investigations. To address these issues and fully realize the value of BGAI in forensic investigation, efforts should be made not only by labs/institutions around the world independently, but also by inter-lab/institution collaborations.

Glycolysis-cholesterol metabolic axis in immuno-oncology microenvironment: emerging role in immune cells and immunosuppressive signaling.

Cell proliferation and function require nutrients, energy, and biosynthesis activity to duplicate repertoires for each daughter. It is therefore not surprising that tumor microenvironment (TME) metabolic reprogramming primarily orchestrates the interaction between tumor and immune cells. Tumor metabolic reprogramming affords bioenergetic, signaling intermediates, and biosynthesis requirements for both malignant and immune cells. Different immune cell subsets are recruited into the TME, and these manifestations have distinct effects on tumor progression and therapeutic outcomes, especially the mutual contribution of glycolysis and cholesterol metabolism. In particularly, glycolysis-cholesterol metabolic axis interconnection plays a critical role in the TME modulation, and their changes in tumor metabolism appear to be a double-edged sword in regulating various immune cell responses and immunotherapy efficacy. Hence, we discussed the signature manifestation of the glycolysis-cholesterol metabolic axis and its pivotal role in tumor immune regulation. We also highlight how hypothetical combinations of immunotherapy and glycolysis/cholesterol-related metabolic interventions unleash the potential of anti-tumor immunotherapies, as well as developing more effective personalized treatment strategies.

Frailty trajectory predicts subsequent cognitive decline: A 26-year population-based longitudinal cohort study.

Frailty refers to a decline in the physiological functioning of one or more organ systems. It remained unclear whether variations in the trajectory of frailty over time were associated with subsequent cognitive change. The aim of the current study was to investigate the association between frailty trajectories and subsequent cognitive decline based on the Health and Retirement Study (HRS). A total of 15,454 participants were included. The frailty trajectory was assessed using the Paulson-Lichtenberg Frailty Index, while the cognitive function was evaluated using the Langa-Weir Classification. Results showed that severe frailty was significantly associated with the subsequent decline in cognitive function (ß [95% CI] = -0.21 [-0.40, -0.03], p = 0.03). In the five identified frailty trajectories, participants with mild frailty (inverted U-shaped, ß [95% CI] = -0.22 [-0.43, -0.02], p = 0.04), mild frailty (U-shaped, ß [95% CI] = -0.22 [-0.39, -0.06], p = 0.01), and frailty (ß [95% CI] = -0.34 [-0.62, -0.07], p = 0.01) were all significantly associated with the subsequent cognition decline in the elderly. The current study suggested that monitoring and addressing frailty trajectories in older adults may be a critical approach in preventing or mitigating cognitive decline, which had significant implications for healthcare.

Exploring rare differences in mitochondrial genome between MZ twins using Ion Torrent semiconductor sequencing.

Monozygotic (MZ) twins are considered to be genetically identical in that they have the same genomic DNA sequences in theory, and thus cannot be differentiated using forensic standard STR-based DNA profiling. However, a recent study employed deep sequencing to explore extremely rare mutations in the nuclear genome and reported that the mutation analysis could be applied to differentiate between MZ twins. Compared with the nuclear genome, the mitochondrial DNA (mtDNA) exhibits higher mutation rates due to fewer DNA repair mechanisms in the mitochondrial genome (mtGenome) and the lack of proofreading capability of the mtDNA polymerase. In a previous study, we used Illumina ultra-deep sequencing to describe point heteroplasmy (PHP) and nucleotide variant of the mtGenomes in venous blood samples of MZ twins. In the present study, we characterized minor differences of the mtGenomes in three tissue samples from seven sets of MZ twins using Ion Torrent semiconductor sequencing (Thermo Fisher Ion S5 XL system) and commercialized mtGenome sequencing kit (Precision ID mtDNA Whole Genome Panel). PHP was observed in blood samples from one set of MZ twins and in saliva samples from two sets of twins, but it presented in hair shaft samples from all seven sets of MZ twins. Overall, the coding region of the mtGenome exhibits more PHPs than the control region. The results of this study have further attested the competence of mtGenome sequencing in differentiating between MZ twins, and that among the three kinds of samples tested, hair shaft is more likely to accumulate minor differences in the mtGenomes of MZ twins.

Association of active immunotherapy with outcomes in cancer patients with COVID-19: a systematic review and meta-analysis.

BACKGROUND: During the COVID-19 pandemic, there are growing concerns about the safety of administering immunotherapy in cancer patients with COVID-19. However, current clinical guidelines provided no clear recommendation. METHODS: Studies were searched and retrieved from electronic databases. The meta-analysis was performed by employing the generic inverse-variance method. A random-effects model was used to calculate the unadjusted odds ratios (ORs) and adjusted ORs with the corresponding 95% CIs. RESULTS: This meta-analysis included 20 articles with 6,042 cancer patients diagnosed with COVID-19. According to the univariate analysis, the acceptance of immunotherapy within 30 days before COVID-19 diagnosis did not increase the mortality of cancer patients (OR: 0.92; 95% CI: 0.68-1.25; P=0.61). Moreover, after adjusting for confounders, the adjusted OR for mortality was 0.51, with borderline significance (95% CI: 0.25-1.01; P=0.053). Similarly, the univariate analysis showed that the acceptance of immunotherapy within 30 days before COVID-19 diagnosis did not increase the risk of severe/critical disease in cancer patients (OR: 1.07; 95% CI: 0.78-1.47; P=0.66). No significant between-study heterogeneity was found in these analyses. CONCLUSIONS: Accepting immunotherapy within 30 days before the diagnosis of COVID-19 was not significantly associated with a higher risk of mortality or severe/critical disease of infected cancer patients. Further prospectively designed studies with large sample sizes are required to evaluate the present results.

Cancer-specific survival after diagnosis in men versus women: A pan-cancer analysis.

Comprehensive understanding of cancer-specific survival differences in gender is critical for cancer prevention and treatment. Based on the Surveillance Epidemiology and End Results database, we included data from the most prevalent cancers (lung, esophageal, liver, pancreatic, stomach, colorectal, kidney, and bladder cancer). Cox proportional hazards regression models were constructed to estimate hazard ratios, simultaneously adjusting for demographic, clinical, and treatment factors. Overall, male patients had a worse cancer-specific survival than female patients. After adjustment for cancer prevalence with 1:1 matching, gender remained a significant factor in cancer-specific survival. Among the included cancer types, female patients showed survival benefit in lung, liver, colorectal, pancreatic, stomach, and esophageal cancer, and male patients showed better survival in bladder cancer. Except for kidney cancer, the gender disparity was consistent between cancer patients with nonmetastatic and metastatic disease. Overall, gender appears to be a significant factor influencing cancer-specific survival, and the prognosis of female patients is better than male patients in most cancers. This work might inspire the development of strategies for gender-specific precision cancer prevention and treatment.

Metformin has no Significant Anticancer Effect on Patients with Advanced or Unresectable Cancer: A Systematic Review and Meta-analysis.

BACKGROUND: At present, the antitumor effect of metformin is controversial. Previous meta-analyses included observational studies, of which the results can be influenced by many confounders, affecting the result of meta-analyses and weakening the strength of evidence. Therefore, we conducted a meta-analysis to confirm the effect of metformin use on patients with advanced or unresectable cancers, including randomized clinical trials (RCTs). METHODS: We searched for RCTs in accordance with the inclusion and exclusion criteria. A meta-analysis was conducted to combine hazard ratios (HRs) or risk ratios (RRs) and their 95% confidence intervals (CIs) using a random-effects model. RESULTS: Finally, 7 eligible RCTs were included in the meta-analysis. Overall, the combined results revealed that treatment with metformin did not improve the overall survival (OS) of patients (HR, 1.12; 95% CI, 0.91-1.37, p>0.05), and there was no clear evidence that metformin use was related to improved progression-free survival (PFS) (HR, 1.17; 95% CI, 0.97-1.40; p>0.05). The pooled RR for grade III or IV adverse events was 0.92 (95% CI, 0.52- 1.60; p>0.05), indicating that the use of metformin was not significantly related to increased toxicity. CONCLUSION: Metformin does not significantly improve the survival of patients with advanced or unresectable cancer, regardless of cancer type and region.

Comparison of Second-Line Treatments for Patients with Platinum-Resistant Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: A Systematic Review and Bayesian Network Meta-Analysis.

Several new drugs and combination strategies can be used to treat patients with recurrent or metastatic head and neck squamous cell carcinoma in the second-line treatment. Questions regarding the relative efficacy and safety of any two of the multiple second-line treatment strategies have emerged. This study aims to compare second-line treatments for patients with platinum-resistant recurrent or metastatic head and neck squamous cell carcinoma. Medline, Embase, and the Cochrane Central Register of Controlled Trials were searched to identify relevant articles. Direct and indirect evidence in terms of the objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and treatment-related adverse events grade ≥ 3 (grade ≥ 3 trAE) were analyzed in this Bayesian network meta-analysis. A total of twenty-three trials involving 5039 patients were included. These studies compared 20 different treatments, including the standard of care (SOC: docetaxel, methotrexate, or cetuximab), PD-1 inhibitors (nivolumab or pembrolizumab), durvalumab, tremelimumab, durvalumab + tremelimumab, palbociclib + SOC, tivantinib + SOC, sorafenib + SOC, EMD1201081 + SOC, vandetanib + SOC, PX-866 + SOC, 5-fluorouracil + SOC, cixutumumab + SOC, gefitinib + SOC, cabazitaxel, nolatrexed, duligotuzumab, zalutumumab, gefitinib, and afatinib. Among the currently available treatment options, compared to the standard of care (SOC: docetaxel, methotrexate, or cetuximab), the PD inhibitor significantly improved OS, ORR, and grade ≥ 3 trAE. Afatinib presented a better PFS and ORR than the SOC. Compared with afatinib, the PD-1 inhibitor had a better OS but a worse PFS. In conclusion, compared to the SOC, the PD-1 inhibitor significantly improved the OS, ORR, and grade ≥ 3 trAE. Afatinib presented a better PFS and ORR than the SOC. Compared with afatinib, the PD-1 inhibitor had a better OS but a worse PFS.

Associations of sleep and circadian phenotypes with COVID-19 susceptibility and hospitalization: an observational cohort study based on the UK Biobank and a two-sample Mendelian randomization study.

STUDY OBJECTIVES: Sleep and circadian phenotypes are associated with several diseases. The present study aimed to investigate whether sleep and circadian phenotypes were causally linked with coronavirus disease 2019 (COVID-19)-related outcomes. METHODS: Habitual sleep duration, insomnia, excessive daytime sleepiness, daytime napping, and chronotype were selected as exposures. Key outcomes included positivity and hospitalization for COVID-19. In the observation cohort study, multivariable risk ratios (RRs) and their 95% confidence intervals (CIs) were calculated. Two-sample Mendelian randomization (MR) analyses were conducted to estimate the causal effects of the significant findings in the observation analyses. Odds ratios (ORs) and the corresponding 95% CIs were calculated and compared using the inverse variance weighting, weighted median, and MR-Egger methods. RESULTS: In the UK Biobank cohort study, both often excessive daytime sleepiness and sometimes daytime napping were associated with hospitalized COVID-19 (excessive daytime sleepiness [often vs. never]: RR = 1.24, 95% CI = 1.02-1.5; daytime napping [sometimes vs. never]: RR = 1.12, 95% CI = 1.02-1.22). In addition, sometimes daytime napping was also associated with an increased risk of COVID-19 susceptibility (sometimes vs. never: RR = 1.04, 95% CI = 1.01-1.28). In the MR analyses, excessive daytime sleepiness was found to increase the risk of hospitalized COVID-19 (MR IVW method: OR = 4.53, 95% CI = 1.04-19.82), whereas little evidence supported a causal link between daytime napping and COVID-19 outcomes. CONCLUSIONS: Observational and genetic evidence supports a potential causal link between excessive daytime sleepiness and an increased risk of COVID-19 hospitalization, suggesting that interventions targeting excessive daytime sleepiness symptoms might decrease severe COVID-19 rate.

Local radiotherapy versus nonradiotherapy to distant lesions for metastatic nasopharyngeal carcinoma: Retrospective cohort study.

BACKGROUND: To evaluate the efficiency of local radiotherapy to metastatic lesions in patients with metastatic nasopharyngeal carcinoma (mNPC). METHODS: The overall survival was observed and compared for mNPC patients who received local radiotherapy versus nonradiotherapy to metastatic lesions by using the Kaplan-Meier method and Cox analysis. RESULTS: One hundred and nine patients with NPC were involved in this study, with 61 (56.0%) received radiotherapy to metastatic sites and 48 (44.0%) did not receive radiotherapy to metastatic sites. The 2- and 5-year OS for patients who received local radiotherapy to metastatic lesions were 65.8% and 35.7%, and for patients who did not receive radiotherapy to metastatic lesions were 45.3% and 26.2%. The multivariable adjusted hazard radios for local radiotherapy versus nonradiotherapy to metastatic lesions were 0.482 (95% confidence interval is 0.278-0.834, p = 0.009). CONCLUSIONS: Local radiotherapy to metastatic lesions might be a protective factor for patients with mNPC.