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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.

Supplementary Figure 4 The Sankey plot showing the relationship between different malnutrition categories.

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 metastasesMethods: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.

Supplementary Table 4 The results of multivariate Cox analyses of CONUT (A), PNI (B), and NRI (C) scores with overall survival in patients with brain metastases.

Supplementary Figure 3 The correlation analysis for three malnutrition scores and BMI. Scores and BMI were treated as continuous variables. For CONUT, higher scores are associated with worse malnutrition status. For NRI and PNI, lower scores are associated with worse malnutrition status.

Supplementary Table 3. Patients' malnutrition status stratified by BMI groups.

Supplementary Table 1. The comparison of baseline characteristics of included and excluded patients with brain metastases.

Supplementary Figure 1 The statistical and graphical diagnostics test based on Schoenfeld residuals for proportional hazards assumption.

Supplementary Figure 2 The flow chart of patient selection.

Supplementary Table 5. The Cox proportional analyses of malnutrition scores with overall survival in patients with brain metastases in lung cancer and non-lung cancer patients.

Supplementary Figure 7 Kaplan-Meier curves for overall survival in patients who received target therapy and immune checkpoint blockade.

Supplementary Figure 5. Time-dependent ROC curves of malnutrition scores.

Supplementary Table 2 Baseline Characteristics of included patients stratified by CONUT (A), PNI (B), and NRI (C) categories.

Background: 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 5942 eligible participants were included in the study. Four depression trajectories were identified. Compared with the non-depression trajectory, all other depression trajectories were associated with worse cognitive performance (β [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.

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.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.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.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.

OBJECTIVE: Interleukin 6 (IL-6) is an inflammatory cytokine released into the periphery after stroke, involved in the prognosis of aneurysmal subarachnoid hemorrhage (aSAH). We aimed to explore the relationship between serum IL-6 with long-term mortality after aSAH.METHODS: We retrospectively reviewed the medical records of 18824 SAH patients for collection of serum IL-6 levels during hospitalization from a large, single-center aSAH database of Sichuan University West China Hospital. Patient deaths were determined through a national death record registration system. The primary outcome was long-term mortality. Cox regression models were used to investigate univariate and multivariate relationships between predictors and outcomes. A propensity score-matched analysis was conducted to minimize bias from confounding variables.RESULTS: In total, we included 1131 aSAH patients with 3288 records of IL-6 collections. Initial serum IL-6 values were elevated in all, ranging from 1.50 to 4522.00 pg/ml. After logarithmic transformation, the IL-6 was associated with long-term mortality (HR 1.32, 95% CI 1.21-1.44). The results maintained significant in the multivariate cox regression and propensity score-matched analysis (adjusted HR 1.23, 95% CI 1.11-1.36, p103.00 pg/ml vs IL-6≤103. 00 pg/ml, PSM HR 1.94, 95% CI 1.48-2.55, pCONCLUSIONS: Serum IL-6 is independently associated with long-term mortality of aSAH patients. Our study provided new evidence for the investigation of inflammation after aSAH and the association of inflammatory cytokines with the long-term prognosis of aSAH and might support future management decisions.

Study ObjectivesSleep 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.MethodsHabitual 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.ResultsIn 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.ConclusionsObservational 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.

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.