Streptococcus salivarius K12 Alleviates Oral Mucositis in Patients Undergoing Radiotherapy for Malignant Head and Neck Tumors: A Randomized Controlled Trial.

PURPOSE: Oral mucositis (OM) is a common debilitating toxicity associated with radiotherapy (RT) for malignant head and neck tumors. This prospective, randomized, double-blind, placebo-controlled trial aimed to evaluate the efficacy and safety of Streptococcus salivarius K12 (SsK12) in reducing the incidence, duration, and severity of severe OM (SOM). METHODS: A total of 160 patients with malignant head and neck tumors undergoing definitive or postoperative adjuvant RT were randomly assigned (1:1) to receive SsK12 probiotic (n = 80) or placebo (n = 80) at West China Hospital, Sichuan University, Chengdu, China. Patients were instructed to suck SsK12 or placebo lozenges thrice daily from the initiation to the end of RT. OM was evaluated twice a week during RT and once a week thereafter for up to 8 weeks. The primary end point was the incidence of SOM. Adverse events were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0. RESULTS: Baseline patient characteristics were similar in the SsK12 and placebo groups. The incidence of SOM was significantly lower in the SsK12 group as compared with the placebo group (36.6% v 54.2%; P = .0351). The duration (median, 0.0 days v 7.0 days; mean, 8.9 days v 18.3 days; P = .0084) and time to develop SOM (median, not estimable v 42.0 days; hazard ratio, 0.55 [95% CI, 0.34 to 0.89]; log-rank test: P = .0123) were also improved in the case of the SsK12 group. Adverse events were similar between the groups, and mild or moderate gastrointestinal reactions (flatulence or dyspepsia) associated with the lozenges were observed in two patients in the SsK12 group. High-throughput sequencing results indicated that SsK12 inhibited opportunistic pathogens and enriched oral commensals during RT. CONCLUSION: In this prospective, randomized clinical trial, SsK12 probiotic significantly reduced the incidence, onset, and duration of SOM with a good safety profile.

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.

Association between neutrophil-to-albumin ratio and long-term mortality of aneurysmal subarachnoid hemorrhage.

OBJECTIVE: The prognosis of aneurysmal subarachnoid hemorrhage (aSAH) survivors is concerning. The goal of this study was to investigate and demonstrate the relationship between the neutrophil-to-albumin ratio (NAR) and long-term mortality of aSAH survivors. METHODS: A retrospective observational cohort study was conducted at Sichuan University West China Hospital between January 2009 and June 2019. The investigation of relationship between NAR and long-term mortality was conducted using univariable and multivariable Cox regression models. To demonstrate the predictive performance of different biomarkers over time, time-dependent receiver operating characteristic curve (ROC) analysis and decision curve analysis (DCA) were created. RESULTS: In total, 3173 aSAH patients were included in this study. There was a strong and continuous relationship between NAR levels and long-term mortality (HR 3.23 95% CI 2.75-3.79, p < 0.001). After adjustment, the result was still significant (adjusted HR 1.78 95% CI 1.49-2.12). Compared with patients with the lowest quartile (< 0.15) of NAR levels, the risk of long-term mortality in the other groups was higher (0.15-0.20: adjusted HR 1.30 95% CI 0.97-1.73; 0.20-0.28: adjusted HR 1.37 95% CI 1.03-1.82; >0.28: adjusted HR 1.74 95% CI 1.30-2.32). Results in survivors were found to be still robust. Moreover, out of all the inflammatory markers studied, NAR demonstrated the highest correlation with long-term mortality. CONCLUSIONS: A high level of NAR was associated with increased long-term mortality among patients with aSAH. NAR was a promising inflammatory marker for long-term mortality of aSAH.

Association between inflammatory bowel disease and pancreatic cancer: results from the two-sample Mendelian randomization study.

Background: The nuanced relationship between inflammatory bowel disease (IBD) and pancreatic cancer is noticed in recent years. However, the underlying causal effects of these two diseases are still unclear. Methods: The two-sample mendelian randomization (MR) was conducted to explore the causal effect of IBD condition on pancreatic cancer. Methods of Wald ratio, inverse variance weighted (IVW), MR-Egger, weighted median, and weighted mode were used to investigate the causal relationship between IBD and pancreatic cancer. Besides, Cochrane's Q test, MR-Egger, and leave-one-out method were further conducted to detect heterogeneity, stability, and pleiotropy of MR results. Results: In the MR analysis, we found Crohn's disease had a significant causal effect on pancreatic cancer. Specifically, Crohn's disease would increase 11.1% the risk of pancreatic cancer by the IVW method (p= 0.022), 33.8% by MR Egger (p= 0.015), by 35.3% by the Weighted model (p= 0.005). Regarding ulcerative colitis, there was no statistically significant causal effect observed on pancreatic cancer (p>0.05). Additionally, the pleiotropic test and Leave-one-out analysis both proved the validity and reliability of the present two-sample MR analyses. Conclusion: This study indicates that IBD, particularly Crohn's disease, is causality associated with increased risk of pancreatic cancer. Our results may help public health managers to make better follow-up surveillance of IBD patients.

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.

Assessing the role of lipid-lowering therapy on multi-cancer prevention: A mendelian randomization study.

Background: Statin use for cancer prevention has raised wide attention but the conclusions are still controversial. Whether statins use have exact causal effects on cancer prevention remains unclear. Methods: Based on the Genome-Wide Association Studies (GWAS) datasets from the large prospective UK Biobank and other consortium databases, two-sample mendelian randomization (MR) analysis was conducted to explore the causal effects of statins use on varied site-specific cancer risks. Five MR methods were applied to investigate the causality. The stability, heterogeneity, and pleiotropy of MR results were also evaluated. Results: The atorvastatin use could increase the risk of colorectal cancer (odd ratio (OR) = 1.041, p = 0.035 by fixed-effects inverse variance weighted (IVW) method (IVWFE), OR = 1.086, p = 0.005 by weighted median; OR = 1.101, p = 0.048 by weighted mode, respectively). According to the weighted median and weighted mode, atorvastatin could modestly decrease the risk of liver cell cancer (OR = 0.989, p = 0.049, and OR = 0.984, p = 0.004, respectively) and head and neck cancer (OR = 0.972, p = 0.020). Besides, rosuvastatin use could reduce the bile duct cancer risk by 5.2% via IVWEF method (OR = 0.948, p = 0.031). No significant causality was determined in simvastatin use and pan-cancers via the IVWFE or multiplicative random-effects IVW (IVWMRE) method if applicable (p > 0.05). There was no horizontal pleiotropy observed in the MR analysis and the leave-one-out analysis proved the stability of the results. Conclusion: The causalities between statin use and cancer risk were only observed in colorectal cancer and bile duct cancer in the European ancestry population. Future works are warranted to provide more robust evidence for supporting statin repurposing for cancer prevention.

Improving the models for prognosis of aneurysmal subarachnoid hemorrhage with the neutrophil-to-albumin ratio.

Objective: Many peripheral inflammatory markers were reported to be associated with the prognosis of aneurysmal subarachnoid hemorrhage (aSAH). We aimed to identify the most promising inflammatory factor that can improve existing predictive models. Methods: The study was based on data from a 10 year retrospective cohort study at Sichuan University West China Hospital. We selected the well-known SAFIRE and Subarachnoid Hemorrhage International Trialists' (SAHIT) models as the basic models. We compared the performance of the models after including the inflammatory markers and that of the original models. The developed models were internally and temporally validated. Results: A total of 3,173 patients were included in this study, divided into the derivation cohort (n = 2,525) and the validation cohort (n = 648). Most inflammatory markers could improve the SAH model for mortality prediction in patients with aSAH, and the neutrophil-to-albumin ratio (NAR) performed best among all the included inflammatory markers. By incorporating NAR, the modified SAFIRE and SAHIT models improved the area under the receiver operator characteristics curve (SAFIRE+NAR vs. SAFIRE: 0.794 vs. 0.778, p = 0.012; SAHIT+NAR vs. SAHIT: 0.831 vs. 0.819, p = 0.016) and categorical net reclassification improvement (SAFIRE+NAR: 0.0727, p = 0.002; SAHIT+NAR: 0.0810, p < 0.001). Conclusion: This study illustrated that among the inflammatory markers associated with aSAH prognosis, NAR could improve the SAFIRE and SAHIT models for 3 month mortality of aSAH.

Prevalence and Prognostic Significance of Malnutrition in Patients with Brain Metastasis.

BACKGROUND: Malnutrition is a severe but modifiable risk factor for cancers. However, the relationship between malnutrition and the survival of patients with brain metastases has not been fully revealed. We aimed to evaluate the prevalence of malnutrition and assess its prognostic value on patients with brain metastases. METHODS: We retrospectively recruited 2,633 patients with brain metastases between January 2014 and September 2020. Three malnutrition scores were used to evaluate patients' malnutrition status at their first admission, including controlling nutritional status, the nutritional risk index, and the prognostic nutritional index. The association between malnutrition and overall survival (OS) was estimated. RESULTS: The three malnutrition scores were associated with each other and with body mass index (BMI). Malnutrition assessed by any of the three scores was significantly associated with poor OS. All three malnutrition scores were better indicators than BMI, and adding malnutrition scores to the Graded Prognostic Assessment (GPA) scoring system could significantly improve the accuracy of prognosis prediction. CONCLUSIONS: Malnutrition monitoring using any of the three malnutrition scores on patients' first admission could be a better survival indicator for patients with brain metastases compared with BMI alone. IMPACT: Malnutrition is a more significant indicator of survival stratification compared with BMI. Adding malnutrition to the GPA score system achieves better survival prediction.

Association of smoking with the survival of patients with brain metastasis of lung cancer.

Background: Smoking is associated with increased mortality in patients with cancer. However, there are limited data on the impact of smoking on the survival of patients with brain metastases. Therefore, this study aimed to evaluate whether smoking was associated with survival and whether smoking cessation was beneficial to these patients. Methods: This study used lung cancer with a brain metastasis cohort of the West China Hospital of Sichuan University from 2013 to 2021. Patients were stratified according to smoking history; the distribution, clinical characteristics, and survival data of each group were estimated. Kaplan-Meier analysis and risk analysis were performed for the survival endpoint. Results: Of the 2,647 patients included in the analysis, the median age was 57.8 years, and 55.4% were men. Among them, 67.1% had no smoking history, 18.9% still smoked, and 14% reported quitting smoking. Compared with never smokers, current smokers [HR, 1.51 (95% CI, 1.35-1.69), p < 0.01] and former smokers [HR, 1.32 (95% CI, 1.16-1.49), p<0.01] had an increased risk of death. However, quitting smoking was not associated with improved survival [HR, 0.90 (95% CI, 0.77-1.04), p = 0.16]. The overall survival increased with the increase of smoking cessation years. Conclusions: In lung cancer patients with brain metastases, smoking was associated with an increased risk of death, but quitting smoking was not associated with improved survival.

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.

Survival outcomes following treatment delays among patients with early-stage female cancers: a nationwide study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) severely hindered the timely receipt of health care for patients with cancer, especially female patients. Depression and anxiety were more pronounced in female patients than their male counterparts with cancer during treatment wait-time intervals. Herein, investigating the impact of treatment delays on the survival outcomes of female patients with early-stage cancers can enhance the rational and precise clinical decisions of physicians. METHODS: We analyzed five types of cancers in women from the Surveillance, Epidemiology, and End Results (SEER) program between Jan 2010 and Dec 2015. Univariate and multivariate Cox regression analyses were used to determine the impacts of treatment delays on the overall survival (OS) and cancer-specific survival (CSS) of the patients. RESULTS: A total of 241,661 females with early-stage cancer were analyzed (12,617 cases of non-small cell lung cancer (NSCLC), 166,051 cases of infiltrating breast cancer, 31,096 cases of differentiated thyroid cancer, 23,550 cases of colorectal cancer, and 8347 cases of cervical cancer). Worse OS rates were observed in patients with treatment delays ≥ 3 months in stage I NSCLC (adjustedHazard ratio (HR) = 1.11, 95% Confidence Interval (CI): 1.01-1.23, p = 0.044) and stage I infiltrating breast cancer (adjustedHR = 1.23, 95% CI 1.11-1.37, p < 0.001). When the treatment delay intervals were analyzed as continuous variables, similar results were observed in patients with stage I NSCLC (adjustedHR = 1.04, 95% CI 1.01-1.06, p = 0.010) and in those with stage I breast cancer (adjustedHR = 1.03, 95% CI 1.00-1.06, p = 0.029). However, treatment delays did not reduce the OS of patients with differentiated thyroid cancer, cervical cancer, or colorectal cancer in the early-stage. Only intermediate treatment delays impaired the CSS of patients with cervical cancer in stage I (adjustedHR = 1.31, 95% CI 1.02-1.68, p = 0.032). CONCLUSION: After adjusting for confounders, the prolonged time from diagnosis to the initiation of treatment (< 6 months) showed limited negative effects on the survival of most of the patients with early-stage female cancers. Whether our findings serve as evidence supporting the treatment deferral decisions of clinicians for patients with different cancers in resource-limited situations needs further validation.

Standard or extended STUPP? Optimal duration of temozolomide for patients with high-grade gliomas: a retrospective analysis.

PURPOSE: Brain radiotherapy combined with concomitant and six cycles of adjuvant temozolomide (TMZ) is the standard treatment for newly diagnosed high-grade gliomas (HGGs). However, the optimal number of cycles of TMZ is still controversial. We conducted this retrospective cohort study to evaluate whether prolonging adjuvant TMZ beyond six cycles resulted in better survival outcomes. METHODS: Patients with high-grade gliomas treated with standard brain radiotherapy combined with TMZ were retrospectively analysed. The duration of adjuvant TMZ ranged from 6 to 12 cycles. Those with 6 cycles of adjuvant TMZ were defined as the standard STUPP group, and those with 7-12 cycles were called the extended STUPP group. Median progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method. The Cox proportional hazards model was adopted to estimate the Hazard ratio (HR) associated with PFS and OS. RESULTS: From September 2011 to May 2021, 372 patients were eligible (143 in the standard group, 229 in the extended group). Patients who received extended STUPP had better PFS and OS compared with standard STUPP. The median PFS for the standard STUPP group was 12 months and for the extended STUPP group 22 months (log-rank P < 0.001). The median OS for the standard STUPP group and extended STUPP group were 12 months and 36 months, respectively (log-rank P < 0.001). In the subgroup analysis, the two treatments did not differ in IDH-mutated patients, while patients with IDH wild-type had a significantly better response to extended treatment than to standard treatment (PFS: log-rank P = 0.004; OS log-rank P = 0.001). Patients with MGMT promoter methylation treated with extended STUPP obtained longer PFS and OS than those treated with standard STUPP (PFS: log-rank P = 0.015; OS log-rank P = 0.010). Adverse events including leukopenia (P < 0.001), thrombocytopenia (P = 0.090), fatigue (P < 0.001) and nausea/vomiting (P = 0.004) were more frequent in the extended group. CONCLUSION: Extended TMZ treatment was superior to standard 6-cycle TMZ for both PFS and OS. The incidence of toxicities in extended group was higher but tolerable.

Association between Vitamin D Supplementation and Cancer Mortality: A Systematic Review and Meta-Analysis.

BACKGROUND: Vitamin D deficiency is related to increased cancer risk and deaths. However, whether vitamin D supplementation reduces cancer mortality remains unclear, and several randomized controlled trials yield inconsistent results. METHODS: Medline, Embase, and the Cochrane Central Register of Controlled Trials were searched from their inception until 28 June 2022, for randomized controlled trials investigating vitamin D supplementation. Pooled relative risks (RRs) and their 95% confidence intervals (CIs) were estimated. Trials with vitamin D supplementation combined with calcium supplementation versus placebo alone and recruiting participants with cancer at baseline were excluded in the present study. RESULTS: This study included 12 trials with a total of 72,669 participants. Vitamin D supplementation did not reduce overall cancer mortality (RR 0.96, 95% CI 0.80-1.16). However, vitamin D supplementation was associated with a reduction in lung cancer mortality (RR 0.63, 95% CI 0.45-0.90). CONCLUSIONS: Vitamin D supplementation could not reduce cancer mortality in this highly purified meta-analysis. Further RCTs that evaluate the association between vitamin D supplementation and total cancer mortality are still needed.

Association of Vitamin D Supplementation with Cardiovascular Events: A Systematic Review and Meta-Analysis.

BACKGROUND: low vitamin D status has been associated with an increased incidence of cardiovascular events. However, whether vitamin D supplementation would reduce the incidence of cardiovascular events remains unclear. PURPOSE: To perform a systematic review and meta-analysis of the effect of vitamin D supplementation on the mortality and incidence of cardiovascular events. DATA SOURCES: We searched Medline, Embase, and the Cochrane Central Register of Controlled Trials from their inception until 3 May 2022. STUDY SELECTION: Two authors searched for randomized clinical trials that reported vitamin D supplementation's effect on cardiovascular events outcomes. DATA EXTRACTION: Two authors conducted independent data extraction. DATA SYNTHESIS: We identified 41,809 reports; after exclusions, 18 trials with a total of 70,278 participants were eligible for analysis. Vitamin D supplementation was not associated with the mortality of cardiovascular events (RR 0.96, 95% CI 0.88-1.06, I2 = 0%), the incidence of stroke (RR 1.05, 95% CI 0.92-1.20, I2 = 0%), myocardial infarction (RR 0.97, 95% CI 0.87-1.09, I2 = 0%), total cardiovascular events (RR 0.97, 95% CI 0.91-1.04, I2 = 27%), or cerebrovascular events (RR 1.01, 95% CI 0.87-1.18, I2 = 0%). LIMITATION: Cardiovascular events were the secondary outcome in most trials and thus, might be selectively reported. CONCLUSION: In this meta-analysis of randomized clinical trials, vitamin D supplementation was not associated with a lower risk of cardiovascular events than no supplementation. These findings do not support the routine use of vitamin D supplementation in general.

Lactate dehydrogenase as promising marker for prognosis of brain metastasis.

BACKGROUND: Lactate dehydrogenase (LDH) is a biomarker for cancer. However, the relationship between serum LDH levels and the survival of patients with brain metastasis has been fully revealed. We aimed to evaluate the serum LDH levels and assess its prognostic value in patients with BM. METHODS: The serum LDH levels were collected from 2507 patients with BM. Patients were categorized into four groups according to the quartile of serum LDH levels. The association between serum LDH levels and overall survival (OS) was evaluated using Cox regression models and Kaplan-Meier curves. Three predictive models were used to evaluate patients. RESULTS: The Kaplan-Meier curve for survival by the serum LDH group demonstrates clear separation between four groups (P < 0.001). The participants in the lower group had longer OS than those in the higher group. After adjusting in multivariate Cox regression models remained significant for patients in the Q4 compared with patients in the Q1 (Q4:Q1 OR 1.58, 95% CI 1.38-1.80). Furthermore, the GPA-LDH model generates a pooled area under the curve of 0.630 (95% CI 0.600, 0.660). CONCLUSIONS: Serum LDH levels and OS in patients with brain metastasis is an inverse association. Moreover, Serum LDH levels can improve the prognosis of the GPA model.

Association of Underweight and Weight Loss With Poor Prognosis and Poor Therapy Effectiveness in Brain Metastases: A Retrospective Study.

Background: The prognostic role of body mass index (BMI) in patients with brain metastases is controversial. We aim to investigate the impact of BMI on prognosis and anti-cancer therapy effectiveness in brain metastases. Methods: Patients diagnosed with brain metastases between Oct 2010 and July 2019 were followed for mortality through April 2021. The prognostic role of BMI on overall survival was assessed by a restricted cubic spline (RCS) using a flexible model to visualize the relationship between the BMI values and hazard ratios of all-cause mortality, followed by a cox regression model. The disparity of survival outcomes in patients receiving anti-cancer therapies or those did not was evaluated according to the classification of BMI. Results: A total of 2,466 patients were included in the analysis, including 241 in the underweight (BMI < 18.5 kg/m2) group, 1,503 in the normal weight group (BMI 18.5-23.9 kg/m2), and 722 in the overweight (BMI ≥ 24 kg/m2) group. Relative to the normal weight group, underweight patients were associated with poor prognosis (adjusted HR 1.25, 95% CI 1.07-1.46, p = 0.005). However, those in the overweight group showed similar overall survival when compared to the normal-weight group. Patients with weight loss were associated with a higher risk of mortality compared with patients without significant weight loss. In underweight patients, there was an insignificant difference in survival outcomes whether they received anti-cancer therapies or not. Conclusion: Underweight and significant weight loss were associated with poor prognosis in brain metastases. Meanwhile, anti-cancer therapies did not significantly improve overall survival in patients with underweight. These findings suggest that improving nutrition to maintain body weight is critical for patients with brain metastases.

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.