Introduction Frailty and impaired cognitive functioning often co-occur in older adults and are associated with adverse health outcomes. However, their relationship is unclear. This study sought to examine the association of frailty status with cognitive functioning in older adults. Method The study population consisted of 2,296 older adults aged ≥60 from the National Health and Nutrition Examination Survey 2011–2014. Frailty status was measured based on the Fried Phenotype and the participants were categorized into three groups- robust, pre-frailty, and frailty. Cognitive functioning was measured using the Consortium to Establish a Registry for Alzheimer’s Disease Word Learning subtest (CERAD-WL) immediate and delayed recall tests, the Animal Fluency test (AFT), and the Digit Symbol Substitution Test (DSST). Test-specific and global cognition z-scores were calculated. Multinomial linear regression models were constructed to examine the association between frailty status (reference: robust) and test-specific and global cognition z-scores. Multiple linear regression models were used to examine the relationship between the number of frailty dimensions and test-specific and global cognition z-scores. All models controlled for age, race/ethnicity, education, total cholesterol level, and systolic blood pressure. Results About half of the participants (median age 68 years) were female (49.9%) and non-Hispanic White (48.7%). A quarter (23.3%) of the participants completed some college and above. Multinominal linear regression showed that compared with participants who were robust, those with frailty had worse DSST [β = –0.234, 95% confidence interval (CI): –0.391, –0.078, P = 0.003] and global cognition z scores (β = –0.129, 95% CI –0.233, –0.025, P = 0.02). Multiple linear regression model showed that the number of frailty dimensions was significantly associated with decreased the DSST (β = –0.065, 95% CI –0.103, –0.026, P = 0.001) and global cognition z-scores (β= –0.034, 95% CI –0.06, –0.009, P = 0.009). Conclusion Frailty is associated with worse processing speed, sustained attention, working memory, and global cognition in older adults. Prevention and treatment of frailty in older adults may help protect their cognitive functioning. Further, clinicians should consider assessing cognitive functioning, especially processing speed, sustained attention, and working memory, among frail older patients, which may allow early identification and interventions of cognitive impairment.

/pdf/frailty-is-associated-with-worse-cognitive-functioning-in-1evfx4qv.pdf

Frailty is associated with worse cognitive functioning in older adults

Comparison of efficacy and safety of PD-1/PD-L1 combination therapy in first-line treatment of advanced NSCLC: an updated systematic review and network meta-analysis.

Abstract Introduction Small cell lung cancer (SCLC) is a highly aggressive lung cancer variant known for its elevated risk of brain metastases (BM). While earlier meta‐analyses supported the use of prophylactic cranial irradiation (PCI) to reduce BM incidence and enhance overall survival, modern MRI capabilities raise questions about PCI's universal benefit for limited‐stage SCLC (LS‐SCLC) patients. As a response, we have created a predictive model for BM, aiming to identify low‐risk individuals who may not require PCI. Methods A total of 194 LS‐SCLC patients without PCI treated between 2009 and 2021 were included. We conducted both univariate and multivariate analyses to pinpoint the factors associated with the development of BM. A nomogram for predicting the 2‐ and 3‐year probabilities of BM was then constructed. Results Univariate and multivariate analyses revealed several significant independent risk factors for the development of BM. These factors include TNM stage, the number of chemotherapy (ChT) cycles, Ki‐67 expression level, pretreatment serum lactate dehydrogenase (LDH) levels, and haemoglobin (HGB) levels. These findings underscore their respective roles as independent predictors of BM. Based on the results of the final multivariable analysis, a nomogram model was created. In the training cohort, the nomogram yielded an area under the receiver operating characteristic curve (AUC) of 0.870 at 2 years and 0.828 at 3 years. In the validation cohort, the AUC values were 0.897 at 2 years and 0.789 at 3 years. The calibration curve demonstrated good agreement between the predicted and observed probabilities of BM. Conclusions A novel nomogram has been developed to forecast the likelihood of BM in patients diagnosed with LS‐SCLC. This tool holds the potential to assist healthcare professionals in formulating more informed and tailored treatment plans.

Construction of brain metastasis prediction model in limited stage small cell lung cancer patients without prophylactic cranial irradiation

Abstract Objectives Klotho, consisting of membrane klotho and soluble alpha-klotho, is found to be associated with better cognitive outcomes in small samples of the aged population. We aimed to examine the association of serum soluble alpha-klotho with cognitive functioning among older adults using a nationally representative sample of U.S. older adults. Method A total of 2,173 U.S. older adults aged 60–79 years in the National Health and Nutrition Examination Survey from 2011 to 2014 were included in this cross-sectional analysis. Serum soluble alpha-klotho was measured in the laboratory and analyzed with an ELISA kit. Cognitive function was measured using the Consortium to Establish a Registry for Alzheimer’s Disease Word Learning subtest (CERAD-WL) immediate and delayed memory, the Animal fluency test (AFT), and the Digit Symbol Substitution Test (DSST). Test-specific and global cognition z-scores were calculated based on sample means and standard deviations. Multivariable linear regression models were applied to examine the association of quartiles and continuous value of serum soluble alpha-klotho with test-specific and global cognition z-scores. Subgroup analysis was conducted by sex. The following covariates were included in the analysis- age, sex, race/ethnicity, education, depressive symptoms, smoking status, body mass index (BMI), physical activity, stroke, prevalent coronary heart disease, total cholesterol, and systolic blood pressure. All the information was self-reported or obtained from health exams. Results Serum soluble alpha-klotho level in the lowest quartile was associated with lower z-scores for DSST (beta [β] =-0.13, 95% confidence interval [CI]: -0.25, -0.01). For subgroup analysis, serum soluble alpha-klotho level in the lowest quartile was associated with lower z-scores for DSST (β=-0.16, 95% CI: -0.32, -0.003) and global cognition (β=-0.14, 95% CI: -0.28, -0.01) among female participants. No association was found between continuous serum soluble alpha-klotho and cognitive functioning among the participants. Conclusions Lower serum soluble alpha-klotho quartile was associated with poorer cognitive functioning among older women. Future studies are expected to examine the longitudinal association between klotho levels and cognitive outcomes. 

Serum soluble alpha-klotho klotho and cognitive functioning in older adults aged 60 and 79: an analysis of cross-sectional data of the National Health and Nutrition Examination Survey 2011 to 2014

ABSTRACT Optimal treatment for metastatic non-small cell lung cancer (NSCLC) with mesenchymal epithelial transition gene (MET) exon 14 skipping mutation has not been established yet. MET inhibitors were demonstrated to be effective and tolerated in patients with this condition, while evidence on safety and efficacy of immunotherapy and/or chemotherapy in this population is limited. Here we report the case of an 86-year-old male with metastatic NSCLC harboring MET exon 14 skipping mutation and with high programmed cell death ligand 1 (PD-L1) expression (tumor proportion score ≥50%). The patient received the MET inhibitor tepotinib as first-line treatment, achieving a partial response, with G2 peripheral edema as adverse event that was successfully managed with temporary discontinuation, dose reduction, diuretics and physical therapy. After 31 months, the patient is still receiving tepotinib, with an ongoing response. Tepotinib is a valuable therapeutic option for first-line treatment of older patients with NSCLC harboring MET exon 14 skipping mutation, even in the presence of high PD-L1 expression.

First-line tepotinib for a very elderly patient with metastatic NSCLC harboring MET exon 14 skipping mutation and high PD-L1 expression

Introduction Secondhand smoke (SHS) is common in older adults; however, its cognitive effect is unclear. We aimed to examine the association between serum cotinine level and cognitive functioning among non-smoking older adults. Materials and methods A total of 2,703 older adults aged 60 and above from the National Health and Nutrition Examination (NHANES) Survey 2011–2014 were included. Serum cotinine level was analyzed in the laboratory. A level ≤10 ng/ml and a response of “no” to the question “Do you currently smoke?” were used to select non-smokers. Cognitive functioning was measured using the Consortium to Establish a Registry for Alzheimer’s disease Word Learning subtest (CERAD-WL) immediate and delayed recall tests, the Animal Fluency test (AFT), and the Digit Symbol Substitution test (DSST). Multivariable linear regression models were constructed to examine the association between serum cotinine level quartile and test-specific and global cognition z scores adjusting for age, race/ethnicity, education, depressive symptoms, body mass index, alcohol use, smoking history, prevalent coronary heart disease (CHD), stroke, and systolic blood pressure. Results About half of the participants (mean age 70.5 years) were female (53.6%), non-Hispanic White (48.3%), and completed some college and above (50.2%). Multivariate linear regressions with a reference group being those in the 1st quantile (lowest) showed that participants in the 4th quartile (highest) of serum cotinine level had lower immediate recall [β = −0.16, 95% confidence interval (CI) = −0.29, −0.03], AFT (β = −0.19, 95% CI = −0.33, −0.05), DSST (β = −0.27, 95% CI = −0.39, −0.15), and global cognition (β = −0.26, 95% CI = −0.39, −0.14) z scores. Participants in the 3rd quartile had lower immediate recall (β = −0.16, 95% CI = −0.30, −0.02) and global cognition (β = −0.16, 95% CI = −0.29, −0.02) z scores. Participants in the 2nd quartile had lower delayed recall z scores (β = −0.16, 95% CI = −0.29, −0.02). Conclusion Higher serum cotinine level was associated with worse cognitive functioning in non-smoking older adults. Prevention and reduction of SHS in older adults may help protect their cognitive functioning.

Higher blood cotinine level is associated with worse cognitive functioning in non-smoking older adults

BACKGROUND
Immune checkpoint inhibitors (ICIs) have changed the treatment pattern of advanced and metastatic NSCLC. A series of ICI based therapies have emerged in the first-line treatment field, but the comparative efficacy was unclear.


METHOD
We searched multiple databases and abstracts of major conference proceedings up to Apri1, 2022 for phase III randomised trials of advanced driver-gene wild type NSCLC patients receiving first-line therapy. Outcomes analyzed included progression free survival (PFS), overall survival (OS), and et al.


RESULTS
Thirty-two double-blind RCTs were included, involving 18,656 patients assigned to 22 ICI-based first-line regimens. A series of ICI regiments (including ICI plus chemotherapy), ICI monotherapy, doublet ICIs, doublet ICIs plus chemotherapy) emerged, and showed significant PFS and OS benefit than chemotherapy and chemotherapy + bevacizumab (BEV) for advanced wild-type NSCLC. In comprehensive terms of PFS, chemoimmunotherapy (CIT) were significantly more effective than ICI monotherapy and doublet ICIs. In terms of OS for patients with non-squamous NSCLC, pembrolizumab containing CIT was associated with a median rank of the best regimens, and followed by Atezolizumab+BEV based CIT; while for OS in patients with squamous NSCLC, Cemiplimab and sintilimab based CIT were the most effective regimens. For more than 2 years follow-up, the atezolizumab, pembrolizumab, nivolumab and durvalumab containing ICI therapy all provide a durable long-term OS benefit over chemotherapy and BEV + chemotherapy.


CONCLUSIONS
The findings of the present NMA represent the most comprehensive evidence, which might suggest or provide basis for first-line ICI therapy decision for advanced NSCLC patients without oncogenic driver mutations.

Identifying optimal first-line immune checkpoint inhibitors based regiments for advanced non-small cell lung cancer without oncogenic driver mutations: A systematic review and network meta-analysis.

The aim was to develop and validate a nomogram for the prediction of brain metastases (BM) in small cell lung cancer (SCLC), to explore the risk factors and assist clinical decision‐making.

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/crj.13615

Development and validation of a nomogram for the prediction of brain metastases in small cell lung cancer

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Higher blood cotinine level is associated with worse cognitive functioning in non-smoking older adults

Identifying optimal first-line immune checkpoint inhibitors based regiments for advanced non-small cell lung cancer without oncogenic driver mutations: A systematic review and network meta-analysis.

Development and validation of a nomogram for the prediction of brain metastases in small cell lung cancer