Increased levels of GM-CSF and CXCL10 and low CD8+ memory stem T Cell count are markers of immunosenescence and severe COVID-19 in older people.

BACKGROUND: Ageing leads to altered immune responses, resulting in higher susceptibility to certain infections in the elderly. Immune ageing is a heterogeneous process also associated with inflammaging, a low-grade chronic inflammation. Altered cytotoxic T cell responses and cytokine storm have previously been described in severe COVID-19 cases, however the parameters responsible for such immune response failures are not well known. The aim of our study was to characterize CD8+ T cells and cytokines associated with ageing, in a cohort of patients aged over 70 years stratified by COVID-19 severity. RESULTS: One hundred and four patients were included in the study. We found that, in older people, COVID-19 severity was associated with (i) higher level of GM-CSF, CXCL10 (IP-10), VEGF, IL-1ß, CCL2 (MCP-1) and the neutrophil to lymphocyte ratio (NLR), (ii) increased terminally differentiated CD8+T cells, and (ii) decreased early precursors CD8+ T stem cell-like memory cells (TSCM) and CD27+CD28+. The cytokines mentioned above were found at higher concentrations in the COVID-19+ older cohort compared to a younger cohort in which they were not associated with disease severity. CONCLUSIONS: Our results highlight the particular importance of the myeloid lineage in COVID-19 severity among older people. As GM-CSF and CXCL10 were not associated with COVID-19 severity in younger patients, they may represent disease severity specific markers of ageing and should be considered in older people care.

Prognostic impact of neurocognitive disorders in older patients with cancer: the ELCAPA prospective cohort study.

OBJECTIVE: To assess the prognostic value of neurocognitive disorder (NCD) for 12 month-overall mortality in patients aged 70 or more with a solid cancer. DESIGN: prospective, observational, multicenter cohort. SETTING AND PARTICIPANTS: We analyzed data from the ELCAPA longitudinal multicenter observational cohort of patients aged 70 or over, referred for a geriatric assessment (GA) before a new cancer treatment modality between January 31st, 2007, and December 29th, 2017. We defined the baseline NCD in four classes: no NCD, mild NCD, moderate NCD, and major NCD, based on the Mini-Mental State Examination (MMSE) score, memory complaint, and the Instrumental Activities of Daily Living (IADL) score. STATISTICAL METHODS: We compared the baseline characteristics of patients according to NCD classes, globally and by pairs (with Bonferroni' correction). Prognosis value of NCD classes were analysed by using univariable and then multivariable 12 month survival analysis with age as time-variable and with and without adjustement for the treatment strategy (curative, palliative or exclusive supportive care). RESULTS: 2784 patients with solid-cancer were included, with a median [interquartile range] age of 82 [78;86]. 36% of the patients were free of NCD, 34% had a mild NCD, 17% had a moderate NCD, and 13% had a major NCD. We identified the following independent prognostic factors for 12 month-overall mortality: NCD (adjusted hazard ratio (aHR) [95% confidence interval (CI)] for a major NCD = 1.54 [1.19-1.98] (p < 0.001), type of cancer, metastatic status, inpatient consultation, poor general health (assessed as the level of fatigue and Eastern Cooperative Oncology Group performance status [ECOG-PS]), greater weight loss, palliative treatment, and exclusive supportive care. Additional adjustment for the treatment strategy did not greatly change the strength of the association of a major NCD with 12 month-overall mortality (HR [95%CI] = 1.78 [1.39-2.29] (p < 0.001). CONCLUSION: Our results suggest that the presence of a major NCD has direct prognostic value (independently of other geriatric factors, the type of cancer and the treatment strategy) in older patients with a solid cancer.

Brain Health Registry Study Partner Portal: Novel infrastructure for digital, dyadic data collection.

BACKGROUND: In Alzheimer's disease (AD) research, subjective reports of cognitive and functional decline from participant-study partner dyads is an efficient method of assessing cognitive impairment and clinical progression. METHODS: Demographics and subjective cognitive/functional decline (Everyday Cognition Scale [ECog]) scores from dyads enrolled in the Brain Health Registry (BHR) Study Partner Portal were analyzed. Associations between dyad characteristics and both ECog scores and study engagement were investigated. RESULTS: A total of 10,494 BHR participants (mean age = 66.9 ± 12.16 standard deviations, 67.4% female) have enrolled study partners (mean age = 64.3 ± 14.3 standard deviations, 49.3% female), including 8987 dyads with a participant 55 years of age or older. Older and more educated study partners were more likely to complete tasks and return for follow-up. Twenty-five percent to 27% of older adult participants had self and study partner-report ECog scores indicating a possible cognitive impairment. DISCUSSION: The BHR Study Partner Portal is a unique digital tool for capturing dyadic data, with high impact applications in the clinical neuroscience and AD fields. Highlights The Brain Health Registry (BHR) Study Partner Portal is a novel, digital platform of >10,000 dyads. Collection of dyadic online subjective cognitive and functional data is feasible. The portal has good usability as evidenced by positive study partner feedback. The portal is a potential scalable strategy for cognitive impairment screening in older adults.

Overall Survival and Prognostic Factors among Older Patients with Metastatic Pancreatic Cancer: A Retrospective Analysis Using a Hospital Database.

Pre-therapeutic factors associated with overall survival (OS) among older patients ≥70 years with metastatic pancreatic cancer (mPC) are not known. This was a retrospective single-centre cohort study in Paris including 159 consecutive older patients with mPC between 2000 and 2018. Alongside geriatric parameters, specific comorbidities, cancer-related data and chemotherapy regimens were retrieved. Cox multivariate models were run to assess predictors for OS. The median age was 80 years, 52% were women, 21.5% had diabetes, and 48% had pancreatic head cancer and 72% liver metastases. 62% of the patients (n = 99) received chemotherapy, among which the gemcitabine + nab-paclitaxel (GnP) regimen was the most frequent (72%). Median OS [95%CI] was 7.40 [5.60-10.0] and 1.40 [0.90-2.20] months respectively for patients with and without chemotherapy. The GnP regimen (aHR [95%CI] = 0.47 [0.25-0.89], p = 0.02) and diabetes (aHR = 0.44 [0.24-0.77], p = 0.004) (or anti-diabetic therapy) were multivariate protective factors for death, while ECOG-PS, liver metastases, and the neutrophil cell count were multivariate risk factors for death. In the chemotherapy group, ECOG-PS, number of metastatic sites and the GnP remained significantly associated with OS. Our study confirms the feasibility and efficacy of chemotherapy and the protective effects of diabetes among older patients with mPC.

Serum Leptin Levels, Nutritional Status, and the Risk of Healthcare-Associated Infections in Hospitalized Older Adults.

We aimed to determine whether serum leptin levels are predictive of the occurrence of healthcare-associated infections (HAIs) in hospitalized older patients. In a prospective cohort, 232 patients had available data for leptin and were monitored for HAIs for 3 months. Admission data included comorbidities, invasive procedures, the Mini Nutritional Assessment (MNA), BMI, leptin, albumin and C-reactive protein levels, and CD4 and CD8 T-cell counts. Multivariate logistic regression modelling was used to identify predictors of HAIs. Of the 232 patients (median age: 84.8; females: 72.4%), 89 (38.4%) experienced HAIs. The leptin level was associated with the BMI (p < 0.0001) and MNA (p < 0.0001) categories. Women who experienced HAIs had significantly lower leptin levels than those who did not (5.9 µg/L (2.6-17.7) and 11.8 (4.6-26.3), respectively; p = 0.01; odds ratio (OR) (95% confidence interval): 0.67 (0.49-0.90)); no such association was observed for men. In a multivariate analysis of the women, a lower leptin level was significantly associated with HAIs (OR = 0.70 (0.49-0.97)), independently of comorbidities, invasive medical procedures, and immune status. However, leptin was not significantly associated with HAIs after adjustments for malnutrition (p = 0.26) or albuminemia (p = 0.15)-suggesting that in older women, the association between serum leptin levels and subsequent HAIs is mediated by nutritional status.

[Specificities of supportive care in geriatric oncology]. / Spécificités onco-gériatriques des soins de support.

Supportive care in geriatric oncology is crucial care that should be proposed from the beginning of cancer treatment. More than the quantity of life, the quality of life is a primary goal when treating cancer in the older patients. An initial assessment of the frailty of the older patients should be carried out. The eight domains requiring in-depth assessment are social environment, functional status, walking and balance, cognition, psychological status, co-morbidity and polypharmacy, nutrition and sensory deficiencies. The alteration of these domains has an impact on the patient's outcome, his quality of life and the tolerance of the treatment. One of the major challenges is to maintain the autonomy of the older patient, which involves preserving his functional status, his neuropsychological state and his nutritional state. Corrective actions for each of the domains must be implemented and must be adjusted throughout the course. It is also important to anticipate risks that may compromise or delay the continuation of anti-tumor treatment such as falls, delirium, organ decompensation, iatrogenic risk and social isolation.

Complications and Discharge after Radical Cystectomy for Older Patients with Muscle-Invasive Bladder Cancer: The ELCAPA-27 Cohort Study.

Radical cystectomy is the standard of care for localized bladder cancer but is associated with high morbidity and mortality rates-especially among older patients with comorbidities. The association between geriatric assessment parameters on post-operative complications and discharge has not previously been investigated. The present analysis of the Elderly Cancer Patient (ELCAPA) prospective cohort included all patients aged ≥70 having undergone a geriatric assessment and then radical cystectomy for localized muscle-invasive bladder cancer between 2007 and 2018. The primary endpoint was the proportion of patients with one or more complications in the first 30 days after cystectomy. The secondary endpoints were the length of hospital stay (LOS), the 30-day mortality, and discharge rates. Sixty-two patients (median age: 81; range: 79-83.8) were included. The 30-day complication rate was 73%, and 49% of the patients had experienced a major complication, according to the Clavien-Dindo classification. The 30-day mortality rate was 4%. None of the geriatric, oncological, or laboratory parameters were significantly associated with the occurrence or severity of complications. The median (interquartile range) LOS was 18 days (15-23) overall and was longer in patients with complications (19 days vs. 15 days in those without complications; p = 0.013). Thirty days after cystectomy, 25 patients (53%) had been discharged to home and 22 (47%) were still in a rehabilitation unit. In a univariate analysis, a Geriatric-8 score ≤ 14, a loss of one point on the Activities of Daily Living Scale, anemia, at least one grade ≥ 3 comorbidity on the Cumulative Illness Rating Scale-Geriatric, and an inpatient geriatric assessment were associated with a risk of not being discharged to home. In older patients having undergone a geriatric assessment, radical cystectomy is associated with a high complication rate, a longer LOS, and functional decline at 30 days.