Altered Basal Lipid Metabolism Underlies the Functional Impairment of Naive CD8+ T Cells in Elderly Humans.

Aging is associated with functional deficits in the naive T cell compartment, which compromise the generation of de novo immune responses against previously unencountered Ags. The mechanisms that underlie this phenomenon have nonetheless remained unclear. We found that naive CD8+ T cells in elderly humans were prone to apoptosis and proliferated suboptimally in response to stimulation via the TCR. These abnormalities were associated with dysregulated lipid metabolism under homeostatic conditions and enhanced levels of basal activation. Importantly, reversal of the bioenergetic anomalies with lipid-altering drugs, such as rosiglitazone, almost completely restored the Ag responsiveness of naive CD8+ T cells. Interventions that favor lipid catabolism may therefore find utility as adjunctive therapies in the elderly to promote vaccine-induced immunity against targetable cancers and emerging pathogens, such as seasonal influenza viruses and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

In-hospital mortality of older patients with COVID-19 throughout the epidemic waves in the great Paris area: a multicenter cohort study.

BACKGROUND: Mortality is high in older patients hospitalized with COVID-19. Previous studies observed lower mortality during the Omicron wave, yet no data is available on older patients. The objective was to compare in-hospital mortality between the Omicron and previous waves in older patients hospitalized with COVID-19. METHODS: This retrospective observational multicenter cohort study used the Greater Paris University Hospitals Group's data warehouse (38 hospitals). Patients aged ≥ 75 years with a confirmed COVID-19 diagnosis and hospitalized from March 2020 to January 2022 were included. The study period was divided into five waves. The fifth wave (January 1st to 31st 2022) was considered as the Omicron wave as it was the predominant variant (≥ 50%), and was compared with waves 1 (March-July 2020), 2 (August-December 2020), 3 (January-June 2021) and 4 (July-December 2021). Primary outcome was in-hospital mortality. Secondary outcome was occurrence of ICU admission or in-hospital death. Multivariate logistic regression was performed, with a sensitivity analysis according to variant type. RESULTS: Of the 195,084 patients hospitalized with COVID-19, 19,909 patients aged ≥ 75 years were included (median age 85 [IQR 79-90] years, 53% women). Overall in-hospital mortality was 4,337 (22%), reaching 345 (17%) during wave 5. Waves 1 and 3 were significantly associated with increased in-hospital mortality in comparison with wave 5 (adjusted Odds Ratios aOR 1.42 [95%CI 1.21-1.66] and 1.56 [95%CI 1.33-1.83] respectively). Waves 1 to 3 were associated with an increased risk of occurrence of ICU admission or in-hospital death in comparison with wave 5: aOR 1.29 [95% CI 1.12 to 1.49] for wave 1, aOR 1.25 [95% CI 1.08 to 1.45] for wave 2 and aOR 1.56 [95% CI 1.36 to 1.79] for wave 3. Sensitivity analysis found that Omicron variant was associated with decreased mortality, in comparison with previous variants. CONCLUSIONS: Mortality was lower during the 5th Omicron wave in the older population, but remained high, implying that this variant could be considered as "milder" but not "mild". This persistently high mortality during the 5th Omicron wave highlights the importance of including older patients in clinical trials to confirm the benefit/risk balance of COVID-19 treatments in this fragile population.

Modifiable factors associated with postoperative atrial fibrillation in older patients with hip fracture in an orthogeriatric care pathway: a nested case-control study.

BACKGROUND: Few data are available regarding post-operative atrial fibrillation (POAF) in non-cardiothoracic surgery, particularly orthopedic surgery. Hence, given the frequent incidence of POAF after surgery and its marked impact, we need to identify modifiable factors associated with POAF after hip fracture surgery in older patients. METHODS: We conducted a nested case-control study in the unit for perioperative geriatric care of an academic hospital in Paris from July 1, 2009 to December 31, 2019, enrolling all consecutive patients aged ≥ 70 years with hip fracture surgery and no history of permanent AF before admission (retrospective analysis of prospectively collected data). Patients with and without POAF were matched 1:5 on 5 baseline characteristics (age, hypertension, diabetes, coronary artery disease, cardiac failure). RESULTS: Of the 757 patients included, 384 were matched, and 64 had POAF. The incidence of POAF was 8.5%. The mean age was 86 ± 6 years, 298 (78%) patients were female, and the median Charlson Comorbidity Index was 6 (interquartile range 4-8). The median time from surgery to the occurrence of POAF was 2 days (1-4). On multivariable conditional logistic regression analysis (matched cohort), the modifiable factors present at admission associated with POAF were time to surgery > 48 h (odds ratio [OR] = 1.66, 95% confidence interval [1.01-2.81]) and > 2 units of packed red blood cells (OR = 3.94, [1.50-10.03]). CONCLUSIONS: This study provides new information about POAF in older patients with hip fracture surgery, a surgical emergency whose complexity requires multidisciplinary care.

Prevalence of hyposmia and hypogeusia in 390 COVID-19 hospitalized patients and outpatients: a cross-sectional study.

Anecdotal evidence rapidly accumulated during March 2020 from sites around the world that sudden hyposmia and hypogeusia are significant symptoms associated with the SARS-CoV-2 pandemic. Our objective was to describe the prevalence of hyposmia and hypogeusia and compare it in hospitalized and non-hospitalized COVID-19 patients to evaluate an association of these symptoms with disease severity. We performed a cross-sectional survey during 5 consecutive days in March 2020, within a tertiary referral center, associated outpatient clinic, and two primary care outpatient facilities in Paris. All SARS-CoV-2-positive patients hospitalized during the study period and able to be interviewed (n = 198), hospital outpatients seen during the previous month (n = 129), and all COVID-19-highly suspect patients in two primary health centers (n = 63) were included. Hospitalized patients were significantly more often male (64 vs 40%) and older (66 vs 43 years old in median) and had significantly more comorbidities than outpatients. Hyposmia and hypogeusia were reported by 33% of patients and occurred significantly less frequently in hospitalized patients (12% and 13%, respectively) than in the health centers' outpatients (33% and 43%, respectively) and in the hospital outpatients (65% and 60%, respectively). Hyposmia and hypogeusia appeared more frequently after other COVID-19 symptoms. Patients with hyposmia and/or hypogeusia were significantly younger and had significantly less respiratory severity criteria than patients without these symptoms. Olfactory and gustatory dysfunction occurs frequently in COVID-19, especially in young, non-severe patients. These symptoms might be a useful tool for initial diagnostic work-up in patients with suspected COVID-19.

New Insights into Lymphocyte Differentiation and Aging from Telomere Length and Telomerase Activity Measurements.

αß CD8+, γδ, and NK lymphocytes are fundamental effector cells against viruses and tumors. These cells can be divided into multiple subsets according to their phenotype. Based on progressive telomere attrition from naive to late effector memory cells, human CD8+ T cell subsets have been positioned along a pathway of differentiation, which is also considered as a process of lymphocyte aging or senescence. A similar categorization has not been clearly established for γδ and NK cell populations. Moreover, the distinction between the aging of these populations due to cellular differentiation or due to the chronological age of the donor has not been formally considered. In this study, we performed systematic measurements of telomere length and telomerase activity in human αß CD8+, γδ, and NK lymphocytes based on subset division and across age to address these points and better understand the dichotomy between differentiation and temporal aging. This approach enables us to position phenotypically distinct γδ or NK subsets along a putative pathway of differentiation, such as for CD8+ T cells. Moreover, our data show that both cellular differentiation and donor aging have profound but independent effects on telomere length and telomerase activity of lymphocyte subpopulations, implying distinct mechanisms and consequences on the immune system.

[Geriatric pathways and organisation in response to the needs of EDS]. / Organisation et filières gériatriques en réponse aux besoins des SAU.

The emergency department remains the main method of admission for older people to hospital. The management of old elderly in these departments is a complex subject. It's particularities and the specificities of the evaluation of their health contribute to the difficulties of the care teams. For the elderly, a visit to the emergency room is a significant medical event in the care process that can have repercussions on their functional decline. The promotion of a geriatric culture in emergency departments is essential and can be done in different ways, but collaboration between emergency physicians and geriatricians remains essential for successful care adapted to the specific characteristics of elderly patients.

[A pragmatic approach to iatrogenic risk in the emergency room]. / Approche pragmatique du risque iatrogène aux urgences.

The links between the emergency department (ED) and drug-related harm are close. In practice, it is necessary to ask systematically if an iatrogenic accident is possible and to evaluate a new prescription carefully so as not to create iatrogenia during the visit to the emergency department. Any situation in which a nurse takes charge of an emergency room must be subject to precautions. Simple measures should be put in place during any hospitalisation of an elderly person.

Coordinated expansion of both memory T cells and NK cells in response to CMV infection in humans.

NK cells are key players in the fight against persistent viruses. Human cytomegalovirus (HCMV) infection is associated with the presence of a population of CD16(+) CD56(dim) NKG2C(+) NK cells in both acutely and latently infected individuals. Here, we studied the nature of these terminally differentiated NK cells in different human populations infected with HCMV: healthy donors stratified by age, thymectomized individuals, pregnant women suffering from primary CMV infection, and lung transplant patients. Both CD16(+) CD56(dim) NK- and CD8 T-cell phenotypes as well as functional capacities were determined and stratified according to age and/or CMV event. Similarly to T-cell responsiveness, we observe an accumulation over time of NKG2C(+) NK cells, which preferentially expressed CD57. This accumulation is particularly prominent in elderly and amplified further by CMV infection. Latent HCMV infection (without replication) is sufficient for NKG2C(+) CD57(+) NK cells to persist in healthy individuals but is not necessarily required in old age. Collectively, the present work supports the emerging concept that CMV shapes both innate and adaptive immunity in humans.

Exposure to psychotropics in the French older population living with dementia: a nationwide population-based study.

BACKGROUND: Little is known about the level of psychotropic chronic exposure in all patients living with dementia. The aim of the study was to quantify chronic psychotropic exposure in older adults with dementia compared with the general population of the same age. METHODS: This prospective cohort study was conducted in France between 2009 and 2011. Aged at least 65 years, 10,781,812 individuals (440,215 of them with dementia) either community based or nursing home residents were included. The numbers of single or combined prescriptions, per year for antipsychotics, antidepressants, anxiolytics, or hypnotics were measured. RESULTS: Of patients with dementia, 15.5% are exposed to antipsychotics compared with 2.2% of the age-matched population (relative risk [RR] = 6.44, 95% confidence interval [CI] [6.39-6.48]), 39.5% to antidepressants compared with 12.6% (RR = 4.10, 95% CI [.4.07-4.12]), and 39.6% to anxiolytics or hypnotics compared with 26.9% (RR = 1.74, 95% CI [1.72-1.75]). Among older adults with dementia, 13.8% simultaneously consumed at least three psychotropics. All class age of older patients with dementia is more exposed to all psychotropics except for long-acting benzodiazepines. During the study period, chronic anxiolytic/hypnotic and antipsychotic exposure slightly decreased in population with dementia while chronic exposure to antidepressant drugs tended to increase. CONCLUSION: This nationwide, population-based, drug-used study showed for the first time that older patients with dementia are chronically overexposed not only to antipsychotics but also to psychotropics.

Biomarkers of vascular dysfunction and cognitive decline in patients with Alzheimer's disease: no evidence for association in elderly subjects.

BACKGROUND: Several studies have suggested that vascular dysfunction plays an important role in Alzheimer's disease. AIMS: We hypothesized that significant differences might be observed in the levels of blood endothelial biomarkers across elderly population of subjects with dementia. METHODS: We analyzed, in a prospective monocentric study, three different endothelial biomarkers, endothelial microparticles (EMPs), endothelial progenitor cells (EPCs) and circulating endothelial cells (CECs) in 132 older patients who underwent a full evaluation of a memory complaint. RESULTS: There was no difference in specific EMP, EPC or CEC levels between demented or non-demented patients, nor considering cognitive decline. DISCUSSION: Blood endothelial biomarkers may be too sensitive and it is likely that the multimorbidity observed in our patients may lead to opposite and confounding effects on endothelial biomarkers levels. CONCLUSION: Unlike younger AD patients, our results suggest that endothelial biomarkers are not valuable for the diagnosis of dementia in elderly patients.

Outcomes After Hip Fracture Surgery Compared With Elective Total Hip Replacement.

IMPORTANCE: Patients undergoing surgery for a hip fracture have a higher risk of mortality and major complications compared with patients undergoing an elective total hip replacement (THR) operation. The effect of older age and comorbidities associated with hip fracture on this increased perioperative risk is unknown. OBJECTIVE: To determine if there was a difference in hospital mortality among patients who underwent hip fracture surgery relative to an elective THR, after adjustment for age, sex, and preoperative comorbidities. DESIGN, SETTING, AND PARTICIPANTS: Using the French National Hospital Discharge Database from January 2010 to December 2013, patients older than 45 years undergoing hip surgery at French hospitals were included. The International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10), codes were used to determine patients' comorbidities and complications after surgery. A population matched for age, sex, and preoperative comorbidities of patients who underwent elective THR or hip fracture surgery was created using a multivariable logistic model and a greedy matching algorithm with a 1:1 ratio. EXPOSURE: Hip fracture. MAIN OUTCOMES AND MEASURES: Postoperative in-hospital mortality. RESULTS: A total of 690,995 eligible patients were included from 864 centers in France. Patients undergoing elective THR surgery (n = 371,191) were younger, more commonly men, and had less comorbidity compared with patients undergoing hip fracture surgery. Following hip fracture surgery (n = 319,804), 10,931 patients (3.42%) died before hospital discharge and 669 patients (0.18%) died after elective THR. Multivariable analysis of the matched populations (n = 234,314) demonstrated a higher risk of mortality (1.82% for hip fracture surgery vs 0.31% for elective THR; absolute risk increase, 1.51% [95% CI, 1.46%-1.55%]; relative risk [RR], 5.88 [95% CI, 5.26-6.58]; P < .001) and of major postoperative complications (5.88% for hip fracture surgery vs 2.34% for elective THR; absolute risk increase, 3.54% [95% CI, 3.50%-3.59%]; RR, 2.50 [95% CI, 2.40-2.62]; P < .001) among patients undergoing hip fracture surgery. CONCLUSIONS AND RELEVANCE: In a large cohort of French patients, hip fracture surgery compared with elective THR was associated with a higher risk of in-hospital mortality after adjustment for age, sex, and measured comorbidities. Further studies are needed to define the causes for these differences.

[Cost accounting of a geriatric perioperative unit]. / Compte de résultat analytique d’une unité périopératoire gériatrique.

AIM: Hip fracture management in a dedicated geriatric perioperative unit improves long-term mortality. In this "we report the" health economics evaluation of this geriatric perioperative care unit (UPOG). METHODS: This study was conducted in 2011. Direct expenditures were obtained from the Assistance Publique-Hopitaux de Paris database, indirect expenditures from the hospital cost accounting,and financial incomes from the PMSI Pilot programme. Emergency department incomes and expenditures were estimated together with additional incomes related to orthopaedic surgery. We estimated expenditures related to operating room (OR) activities in the framework of several models, one with an emergency OR open 24h/24, and one with a standard OR. Lastly, we compared incomes/expenditures according to regular paramedical staff or according to the paramedical staff that would appear to be necessary to ensure patient care. RESULTS: 253 patients were admitted to the UPOG during the study J215 (84%) of whom underwent surgery. The income statement was positive for both an emergency OR (+741,000 Euros) and a standard OR ( +490,000 Euros) and remained positive when paramedical staff was increased (+629,000 and +156,000 Euros, respectively). CONCLUSION: The UPOG income statement shows a positive result regardless of the model used, emergency 24h/24 OR or standard OR, and even when paramedical staff is increased

[An essential multi-disciplinary approach in geriatric perioperative units]. / Les unités périopératoires gériatriques, une pluridisciplinarité essentielle.

A hip fracture, often a surgical emergency, is a geriatric as much as an orthopaedic pathology. A multi-disciplinary approach is essential especially in the management of complications. The geriatric perioperative unit of Pitié-Salpétrière-Charles Foix hospital has demonstrated the benefits of such a dedicated care pathway.

[Comparaison du déclin fonctionnel entre des patients atteints de démence à corps de Lewy et de la maladie d'Alzheimer]. / Functional decline in Lewy body dementia compared to Alzheimer disease.

Lewy body dementia (LBD) is the second most frequent neurodegenerative disorder after Alzheimer disease (AD). In this study, we compared functional decline between LBD and AD patients, considering motor dysfunction, over an 18-month follow-up period. We included all patients >70 years of age, with initial MMSE ≥ 20 and a diagnosis of possible or probable LBD or AD, who consulted at the memory centre of the Pitié-Salpêtrière hospital. Statistical analyses were performed using univariate tests and multivariate linear regression. Thirty-seven AD and 36 LBD patients were included, with a median age of 81 and a median MMSE score of 24/30. Global ADL Katz score decreased significantly for LBD people, compared to AD patients: -0.40 ± 0.75 versus 0 ± 0.24; p=0.003. Global IADL score decreased in the two populations but without a significant difference between the two groups: -1.71 ± 2.19 in LBD versus -1.32 (± 1.55); p=0.38. This study shows a significant decrease in autonomy in LBD patients over time that was faster than that in AD patients, related, in particular, to bathing, dressing and personal care.

NSAIDs for Pain Control During the Peri-Operative Period of Hip Fracture Surgery: A Systematic Review.

BACKGROUND: Hip fracture (HF) mostly affects older adults and is responsible for increased morbidity and mortality. Non-steroidal anti-inflammatory drugs (NSAIDs) are part of the peri-operative multimodal analgesic management, but their use could be associated with adverse events in older adults. This systematic review aimed to assess outcomes associated with NSAIDs use in the peri-operative period of HF surgery. METHODS: This systematic review was conducted according to the PRISMA guidelines. Three databases (PubMed/EMBASE/Cochrane Central) were used to search for clinical trials and observational studies assessing efficacy, safety and impact of NSAIDs use on non-specific post-operative outcomes, such as functional status and post-operative complications. RESULTS: Among the 1320 references initially identified, four provided data on efficacy, four on safety and six on non-specific post-operative outcomes (three randomized controlled clinical trials, three observational studies). Mean study population ages ranged from 68 to 87 years. Two studies found that NSAIDs were effective on pain control, but two studies found conflicting results on opioid sparing. No increased risk of acute kidney injury was observed, while results concerning bleeding risk and delirium were conflicting. No study has found any effect of NSAIDs use on walk recovery. Quality of evidence was high for pain control, but low to very low for all the other studied outcomes. CONCLUSIONS: The use of NSAIDs may be effective for pain control in the peri-operative period of HF surgery. However, safety data were conflicting with low levels of certainty. Further studies are needed to assess their benefit-risk balance in this context. The research protocol was previously registered on PROSPERO (registration number: CRD42021237649).

Factors associated with adverse events resulting from medical errors in the emergency department: two work better than one.

BACKGROUND: The Emergency Department (ED) is an environment at risk for medical errors. OBJECTIVE: Our aim was to determine the factors associated with the adverse events resulting from medical errors in the ED among patients who were admitted. METHODS: This was a prospective observational study. For a 1-month period, we included all ED patients who were subsequently admitted to the medical ward. Detection of medical errors was made by the admitting physician and then validated by two experts who reviewed all available data and medical charts pertaining to the patient's hospital stay, including the first review from the ward physician. Related adverse events resulting from medical errors were then classified by type and severity. Adverse events were defined as medical errors that needed an intervention or caused harm to the patient. Univariate analysis examined relationships between characteristics of both patients and physicians and the risk of adverse events. RESULTS: From 197 analyzed patients, 130 errors were detected, of these, 34 were categorized as adverse events among 19 patients (10%). Seventy-six percent of these were categorized as proficiency errors. The only factors associated with a lower risk of adverse events were the transition of care involving a handoff within the ED (0% vs. 19%; p = 0.03) and the involvement of a resident (junior doctor) in addition to the senior physician (37% vs. 67%; p < 0.01). CONCLUSIONS: In our study, the involvement of more than one physician was associated with a lower risk of adverse events.

Expression of immune checkpoint on subset of monocytes in old patients.

BACKGROUND: Immune checkpoints and their ligands are important actors of lymphocytes and monocytes activation's regulation. Their expression level within T cells changes with aging. Despite the major impact of aging on monocytes, there is no data about the expression of ICs on monocytes from old patients. The objective of our study is to describe the expression of ICs and their ligands on monocytes from young individuals compared to old patients. METHODS: We included 18 old control (>75 years old), 10 young control (<55 years old) and 45 old patients with hip fracture (HF). Phenotypical and functional analyses were performed on cryopreserved PBMCs. RESULTS: There is a differential expression of immune checkpoints and their ligands within monocyte subtypes regardless of age at baseline. After stimulation, a differential expression of immune checkpoints in young subjects but not in old subjects was observed which would be in favor of a regulation defect in old subjects. We hypothesize that this lack of regulation could partially explain the excess production of pro-inflammatory cytokines by the stimulated monocytes in old subjects. In HF, we also observe a differential expression of immune checkpoints, especially in old patients with a poor prognosis. CONCLUSION: Our results suggest that the immune regulation which should take place post-acute stress may be affected in old individuals.

Lumbar puncture training with healthcare simulation improves self-confidence and practical skills of French medical residents in geriatrics.

PURPOSE: To assess the skill level and self-confidence of medical residents in geriatrics with regard to conducting the lumbar puncture (LP) procedure and to study the potential benefits of training with simulation and virtual reality. METHODS: First, a questionnaire survey was conducted among all French residents in geriatrics in the Paris area to assess their knowledge and self-confidence regarding the practice of LP in older adults. Second, we set up a simulation LP training session combined with virtual reality (3D video) training for selected respondents of the first survey. Third, we performed post-simulation survey for the attendees of the simulation training. Finally, a follow-up survey was conducted to examine the change in self-confidence and the success rate in clinical practice. RESULTS: Fifty-five residents responded to the survey (response rate = 36.4%). The importance of mastering LP was fully recognized by the residents in geriatrics (95.3%), so most of them (94.5%) advocated for the need for additional practical training. Fourteen residents took part in the training (average rating = 4.7 on a 5-point scale). Simulation was regarded by 83% of the respondents as the most useful tool for their practice. We observed a significant pre/post-training mean improvement in self-estimated success of 20.6% (Wilcoxon matched-pairs signed-rank W = - 36, p = 0.008). The post-training success rate of the residents in real-life clinical practice was good (85.8%). CONCLUSION: Residents were aware of the importance of mastering LP and requested additional training. Simulation may represent a major driver to improve their self-confidence and practical skills.