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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).
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Envejecimiento/inmunología , Linfocitos T CD8-positivos/inmunología , Inmunocompetencia/efectos de los fármacos , Metabolismo de los Lípidos , Adulto , Anciano , Anciano de 80 o más Años , Apoptosis , Linfocitos T CD8-positivos/metabolismo , COVID-19/inmunología , Vacunas contra el Cáncer/inmunología , División Celular , Femenino , Fenofibrato/farmacología , Glucosa/metabolismo , Antígeno HLA-A2/inmunología , Humanos , Hipolipemiantes/farmacología , Hipolipemiantes/uso terapéutico , Gripe Humana/inmunología , Metabolismo de los Lípidos/efectos de los fármacos , Activación de Linfocitos , Antígeno MART-1/química , Antígeno MART-1/inmunología , Masculino , Persona de Mediana Edad , Neoplasias/inmunología , Fragmentos de Péptidos/inmunología , Rosiglitazona/farmacología , Método Simple Ciego , Vacunación , Vacunas Virales/inmunología , Adulto JovenRESUMEN
BACKGROUND: Few data are available on the long-term mortality and functional status of geriatric patients surviving after hospitalization for COVID-19. We compared the mortality and functional status 18 months after hospitalization for geriatric patients who were hospitalized for COVID-19 or another diagnosis. METHODS: This was a multicentric cohort study in Paris from January to June 2021. We included patients aged 75 years and over who were hospitalized with COVID-19 or not during this period and compared their vital and functional status 18 months after hospitalization. RESULTS: We included 254 patients (63 hospitalized for COVID-19). As compared with patients hospitalized for other reasons, those hospitalized for COVID-19 were younger (mean [SD] age 86 [6.47] vs. 88 [6.41] years, p = 0.03), less frail (median Clinical Frailty Scale score 5 [4-6] vs. 6 [4-6], p 0.007) and more independent at baseline (median activities of daily living score 5.5 [4-6] vs. 5 [3.5-6], p 0.03; instrumental activities of daily living score 3 [1-4] vs. 2 [0-3], p 0.04). At 18 months, 50.8% (n = 32/63) of COVID-19 patients had died versus 66% (n = 126/191) of non-COVID-19 patients (p 0.03). On multivariate analysis, COVID-19 positivity was not significantly associated with 18-month mortality (adjusted hazard ratio 0.67, 95% confidence interval 0.40 to 1.13). At 18 months, the two groups did not differ in activities of daily living or frailty scores. CONCLUSIONS: In this multicenter study of long-term mortality in geriatric patients discharged alive after hospitalization, positive COVID-19 status was not associated with excess mortality.
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COVID-19 , Hospitalización , Humanos , COVID-19/mortalidad , COVID-19/terapia , COVID-19/epidemiología , Masculino , Femenino , Anciano de 80 o más Años , Hospitalización/tendencias , Anciano , Estudios de Cohortes , Actividades Cotidianas , Estado Funcional , Evaluación Geriátrica/métodos , Anciano Frágil , SARS-CoV-2 , Paris/epidemiologíaRESUMEN
PURPOSE: The objective was to conduct a systematic review of mortality and factors independently associated with mortality of older patients admitted to an intensive care unit (ICU) for COVID-19. MATERIALS AND METHODS: Data sources were MEDLINE, EMBASE, the Cochrane Library, and references of included studies. Two reviewers independently selected studies evaluating mortality of older patients (≥ 70 years) admitted to an ICU for COVID-19. They extracted general characteristics, mortality rate, and factors independently associated with mortality. The methodological quality of each study was evaluated by using the Critical Appraisal Skills Programme checklist. RESULTS: We selected 36 studies (11,989 patients). Many of the studies were conducted in Europe (42%) and many were retrospective (61%) and multicenter (61%). ICU mortality ranged from 8% to 90%, 1-month mortality from 33% to 90% and 3-month mortality, reported in five studies, from 46% to 60%. Frailty, assessed by the Clinical Frailty Score (CFS), was significantly associated with 1-month and 3-month mortality respectively in two studies (hazard ratio [HR]: 3.2 [2.56-4.13] and HR: 2.83 [95% CI: 1.96-4.08]). CONCLUSION: In this systematic review of older patients admitted to an ICU with COVID-19, we documented high heterogeneity of mortality rates.
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COVID-19 , Fragilidad , Humanos , Anciano , Estudios Retrospectivos , Hospitalización , Unidades de Cuidados Intensivos , Mortalidad Hospitalaria , Estudios Multicéntricos como AsuntoRESUMEN
Rationale: Sepsis is the leading cause of death in adult ICUs. At present, sepsis diagnosis relies on nonspecific clinical features. It could transform clinical care to have immune-cell biomarkers that could predict sepsis diagnosis and guide treatment. For decades, neutrophil phenotypes have been studied in sepsis, but a diagnostic cell subset has yet to be identified. Objectives: To identify an early, specific immune signature of sepsis severity that does not overlap with other inflammatory biomarkers and that distinguishes patients with sepsis from those with noninfectious inflammatory syndrome. Methods: Mass cytometry combined with computational high-dimensional data analysis was used to measure 42 markers on whole-blood immune cells from patients with sepsis and control subjects and to automatically and comprehensively characterize circulating immune cells, which enables identification of novel, disease-specific cellular signatures. Measurements and Main Results: Unsupervised analysis of high-dimensional mass cytometry data characterized previously unappreciated heterogeneity within the CD64+ immature neutrophils and revealed two new subsets distinguished by CD123 and PD-L1 (programmed death ligand 1) expression. These immature neutrophils exhibited diminished activation and phagocytosis functions. The proportion of CD123-expressing neutrophils correlated with clinical severity. Conclusions: This study showed that these two new neutrophil subsets were specific to sepsis and detectable through routine flow cytometry by using seven markers. The demonstration here that a simple blood test distinguishes sepsis from other inflammatory conditions represents a key biological milestone that can be immediately translated into improvements in patient care.
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Antígeno B7-H1/sangre , Subunidad alfa del Receptor de Interleucina-3/sangre , Neutrófilos/metabolismo , Sepsis/diagnóstico , Biomarcadores/sangre , Estudios de Casos y Controles , Reglas de Decisión Clínica , Diagnóstico Diferencial , Citometría de Flujo , Humanos , Modelos Lineales , Estudios Longitudinales , Receptores de IgG/sangre , Sensibilidad y Especificidad , Sepsis/sangre , Sepsis/inmunología , Índice de Severidad de la EnfermedadRESUMEN
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.
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Prueba de COVID-19 , COVID-19 , Humanos , Femenino , Anciano , Anciano de 80 o más Años , Masculino , Mortalidad Hospitalaria , Estudios de Cohortes , Paris/epidemiología , Estudios Retrospectivos , SARS-CoV-2 , Hospitales UniversitariosRESUMEN
OBJECTIVES: To conduct a systematic review of mortality and factors independently associated with mortality in older patients admitted to ICU. DATA SOURCES: MEDLINE via PubMed, EMBASE, the Cochrane Library, and references of included studies. STUDY SELECTION: Two reviewers independently selected studies conducted after 2000 evaluating mortality of older patients (≥ 75 yr old) admitted to ICU. DATA EXTRACTION: General characteristics, mortality rate, and factors independently associated with mortality were extracted independently by two reviewers. Disagreements were solved by discussion within the study team. DATA SYNTHESIS: Because of expected heterogeneity, no meta-analysis was performed. We selected 129 studies (median year of publication, 2015; interquartile range, 2012-2017) including 17 based on a national registry. Most were conducted in Europe and North America. The median number of included patients was 278 (interquartile range, 124-1,068). ICU and in-hospital mortality were most frequently reported with considerable heterogeneity observed across studies that was not explained by study design or location. ICU mortality ranged from 1% to 51%, in-hospital mortality from 10% to 76%, 6-month mortality from 21% to 58%, and 1-year mortality from 33% to 72%. Factors addressed in multivariate analyses were also heterogeneous across studies. Severity score, diagnosis at admission, and use of mechanical ventilation were the independent factors most frequently associated with ICU mortality, whereas age, comorbidities, functional status, and severity score at admission were the independent factors most frequently associated with 3- 6 and 12 months mortality. CONCLUSIONS: In this systematic review of older patients admitted to intensive care, we have documented substantial variation in short- and long-term mortality as well as in prognostic factors evaluated. To better understand this variation, we need consistent, high-quality data on pre-ICU conditions, ICU physiology and treatments, structure and system factors, and post-ICU trajectories. These data could inform geriatric care bundles as well as a core data set of prognostic factors to inform patient-centered decision-making.
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Resultados de Cuidados Críticos , Cuidados Críticos/estadística & datos numéricos , Enfermedad Crítica/mortalidad , Mortalidad Hospitalaria/tendencias , Anciano , Anciano de 80 o más Años , Europa (Continente) , Femenino , Humanos , Unidades de Cuidados Intensivos/organización & administración , Masculino , América del Norte , Evaluación de Resultado en la Atención de Salud , Pronóstico , Factores de RiesgoRESUMEN
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.
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Fracturas de Cadera/terapia , Unidades Hospitalarias , Grupo de Atención al Paciente , Atención Perioperativa , Anciano , Francia , HumanosRESUMEN
OBJECTIVES: To report the safety and efficacy of tocilizumab in patients with severe and refractory non-infectious uveitis. METHODS: Eight consecutive unselected patients with severe and refractory non-infectious uveitis [Birdshot chorioretinopathy (n=1), Behçet's disease (n=1) and idiopathic bilateral panuveitis (n=6)] treated with tocilizumab (8mg/kg every 4 weeks intravenously) were included. The primary outcome was the response to treatment, defined by decrease of inflammatory ocular signs. RESULTS: Four (50%) patients were of female gender and the median (IQR) age was 41 (31-47) years. The median number of previous immunosupressants was of 5.5 (4-6.7). Seven patients had been previously treated with anti-TNF-α [infliximab (n=5) and adalimumab (n=2)]. The immunosupressive drugs used in association with tocilizumab were azathioprine (n=2), mycophenolate mofetil (n=2) and methotrexate (n=2). After a median follow-up of 8 months (6-25), 6/8 (75%) improved under tocilizumab and 2 (25%) were non-responders. The visual acuity improved in five patients. The median dose of prednisolone decreased from 16mg/day (10.6-20.5) to 10 mg/day (10-13.7), at baseline and at the end of follow-up, respectively. Tolerance of tocilizumab was satisfactory and side effects included bronchitis (n=1) and grade 1 leukopenia (n=1) and thrombocytopenia (n=1). CONCLUSIONS: Tocilizumab seems to be a safe and promising therapy in severe and refractory non-infectious uveitis.
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Antiinflamatorios/administración & dosificación , Anticuerpos Monoclonales Humanizados/administración & dosificación , Síndrome de Behçet/tratamiento farmacológico , Uveítis/tratamiento farmacológico , Adulto , Anciano , Antiinflamatorios/efectos adversos , Anticuerpos Monoclonales Humanizados/efectos adversos , Síndrome de Behçet/complicaciones , Resistencia a Medicamentos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Uveítis/etiologíaRESUMEN
Very old critically ill patients pose a growing challenge for intensive care. Critical illness and the burden of treatment in the intensive care unit (ICU) can lead to a long-lasting decline of functional and cognitive abilities, especially in very old patients. Multi-complexity and increased vulnerability to stress in these patients may lead to new and worsening disabilities, requiring careful assessment, prevention and rehabilitation. The potential for rehabilitation, which is crucial for optimal functional outcomes, requires a systematic, multi-disciplinary approach and careful long-term planning during and following ICU care. We describe this process and provide recommendations and checklists for comprehensive and timely assessments in the context of transitioning patients from ICU to post-ICU and acute hospital care, and review the barriers to the provision of good functional outcomes.
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BACKGROUND: Activation of innate immunity is a first line of host defense during acute critical illness (ACI) that aims to contain injury and avoid tissue damages. Aberrant activation of innate immunity may also participate in the occurrence of organ failures during critical illness. This review aims to provide a narrative overview of recent advances in the field of innate immunity in critical illness, and to consider future potential therapeutic strategies. MAIN TEXT: Understanding the underlying biological concepts supporting therapeutic strategies modulating immune response is essential in decision-making. We will develop the multiple facets of innate immune response, especially its cellular aspects, and its interaction with other defense mechanisms. We will first describe the pathophysiological mechanisms of initiation of innate immune response and its implication during ACI. We will then develop the amplification of innate immunity mediated by multiple effectors. Our review will mainly focus on myeloid and lymphoid cellular effectors, the major actors involved in innate immune-mediated organ failure. We will third discuss the interaction and integration of innate immune response in a global view of host defense, thus considering interaction with non-immune cells through immunothrombosis, immunometabolism and long-term reprogramming via trained immunity. The last part of this review will focus on the specificities of the immune response in children and the older population. CONCLUSIONS: Recent understanding of the innate immune response integrates immunity in a highly dynamic global vision of host response. A better knowledge of the implicated mechanisms and their tissue-compartmentalization allows to characterize the individual immune profile, and one day eventually, to develop individualized bench-to-bedside immunomodulation approaches as an adjuvant resuscitation strategy.
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The demographic shift, together with financial constraint, justify a re-evaluation of the trajectory of care of very old critically ill patients (VIP), defined as older than 80 years. We must avoid over- as well as under-utilisation of critical care interventions in this patient group and ensure the inclusion of health care professionals, the patient and their caregivers in the decision process. This new integrative approach mobilises expertise at each step of the process beginning prior to intensive care unit (ICU) admission and extending to long-term follow-up. In this review, several international experts have contributed to provide recommendations that can be universally applied. Our aim is to define a minimum core dataset of information to be shared and discussed prior to ICU admission and to facilitate the shared-decision-making process with the patient and their caregivers, throughout the patient journey. Documentation of uncertainty may contribute to a tailored level of care and ultimately to discussions around possible limitations of life sustaining treatments. The goal of ICU care is not only to avoid death, but more importantly to maintain an acceptable quality of life and functional autonomy after hospital discharge. Societal consideration is important to highlight, together with alternatives to ICU admission. We discuss challenges for the future and potential areas of research. In summary, this review provides a state-of-the-art current overview and aims to outline future directions to address the challenges in the treatment of VIP.
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Enfermedad Crítica , Calidad de Vida , Humanos , Enfermedad Crítica/terapia , Cuidados Críticos , Personal de Salud , HospitalizaciónRESUMEN
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.
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Citocinas , Monocitos , Humanos , Anciano , Ligandos , Citocinas/metabolismo , Envejecimiento , Linfocitos TRESUMEN
In this narrative review, we describe the most important age-related "syndromes" found in the old ICU patients. The syndromes are frailty, comorbidity, cognitive decline, malnutrition, sarcopenia, loss of functional autonomy, immunosenescence and inflam-ageing. The underlying geriatric condition, together with the admission diagnosis and the acute severity contribute to the short-term, but also to the long-term prognosis. Besides mortality, functional status and quality of life are major outcome variables. The geriatric assessment is a key tool for long-term qualitative outcome, while immediate severity accounts for acute mortality. A poor functional baseline reduces the chances of a successful outcome following ICU. This review emphasises the importance of using a geriatric assessment and considering the older patient as a whole, rather than the acute illness in isolation, when making decisions regarding intensive care treatment.
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Following acute stress such as trauma or sepsis, most of critically ill elderly patients become immunosuppressed and susceptible to secondary infections and enhanced mortality. We have developed a virus-based immunotherapy encoding human interleukin-7 (hIL-7) aiming at restoring both innate an adaptative immune homeostasis in these patients. We assessed the impact of this encoded hIL-7 on the ex vivo immune functions of T cells from PBMC of immunosenescent patients with or without hip fracture. T-cell ex vivo phenotyping was characterized in terms of senescence (CD57), IL-7 receptor (CD127) expression, and T cell differentiation profile. Then, post stimulation, activation status, and functionality (STAT5/STAT1 phosphorylation and T cell proliferation assays) were evaluated by flow cytometry. Our data show that T cells from both groups display immunosenescence features, express CD127 and are activated after stimulation by virotherapy-produced hIL-7-Fc. Interestingly, hip fracture patients exhibit a unique functional ability: An important T cell proliferation occurred compared to controls following stimulation with hIL-7-Fc. In addition, stimulation led to an increased naïve T cell as well as a decreased effector memory T cell proportions compared to controls. This preliminary study indicates that the produced hIL-7-Fc is well recognized by T cells and initiates IL-7 signaling through STAT5 and STAT1 phosphorylation. This signaling efficiently leads to T cell proliferation and activation and enables a T cell "rejuvenation." These results are in favor of the clinical development of the hIL-7-Fc expressing virotherapy to restore or induce immune T cell responses in immunosenescent hip fracture patients.
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Inmunosenescencia , Interleucina-7 , Linfocitos T , Anciano , Humanos , Inmunoterapia , Interleucina-7/farmacología , Leucocitos Mononucleares/metabolismo , Factor de Transcripción STAT5/metabolismo , Linfocitos T/metabolismoRESUMEN
BACKGROUND: Little is known about the impact of hospital trajectory on survival and functional decline of older critically ill patients. We evaluate 6-month outcomes after admission to: intensive care units (ICU), intermediate care units (IMCU) or acute medical wards (AMW). METHODS: Data from the randomised prospective multicentre clinical trial ICE-CUB2 was secondarily analysed. Inclusion criteria were: presenting at emergency departments in critical condition; age ≥ 75 years; activity of daily living (ADL) ≥ 4; preserved nutritional status; and no active cancer. A Cox model was fitted to compare survival according to admission destination adjusting for patient characteristics. Sensitivity analysis using multiple imputation for missing data and propensity score matching were performed. RESULTS: Among 3036 patients, 1675 (55%) were women; median age was 85 [81-99] years; simplified acute physiology score (SAPS-3) 62 [55-69]; 1448 (47%) were hospitalised in an ICU, 504 in IMCU (17%), and 1084 (36%) in AMW. Six-month mortality was 629 (44%), 155 (31%) and 489 (45%) after admission in an ICU, IMCU and AMW (p < 0.001), respectively. In multivariate analysis, AMW admission was associated with worse 6-month survival (HR 1.31, 95% CI 1.04-1.63) in comparison with IMCU admission, after adjusting for age, gender, comorbidities, ADL, SAPS-3 and diagnosis. Survival was not significantly different between patients admitted in an ICU and an IMCU (HR 1.17, 95% CI 0.95-1.46). Sensitivity analysis using multiple imputation for missing data and propensity score matching found similar results. Hospital destination was not significantly associated with the composite criterion loss of 1-point ADL or mortality. Physical and mental components of the 12-Item Short-Form Health Survey were significantly lower in the acute medical ward group (34.3 [27.5-41.7], p = 0.037 and 44.3 [38.6-48.6], p = 0.028, respectively) than in the ICU group (34.7 [28.4-45.3] and 45.5 [40.0-50.0], respectively) and IMCU group (35.7 [29.7-43.8] and 44.5 [39.7-48.4], respectively). CONCLUSIONS: Admission in an AMW was associated with worse 6-month survival in older critically ill patients in comparison with IMCU admission, with no difference of survival between ICU and IMCU admission. There were no clinically relevant differences in quality of life in each group. These results should be confirmed in specific studies and raise the question of dedicated geriatric IMCUs.
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BACKGROUND: Few data are available on the prognosis of older patients who received corticosteroids for COVID-19. We aimed to compare the in-hospital mortality of geriatric patients hospitalized for COVID-19 who received corticosteroids or not. METHODS: We conducted a multicentric retrospective cohort study in 15 acute COVID-19 geriatric wards in the Paris area from March to April 2020 and November 2020 to May 2021. We included all consecutive patients aged 70 years and older who were hospitalized with confirmed COVID-19 in these wards. Propensity score and multivariate analyses were used. RESULTS: Of the 1 579 patients included (535 received corticosteroids), the median age was 86 (interquartile range 81-91) years, 56% of patients were female, the median Charlson Comorbidity Index (CCI) was 2.6 (interquartile range 1-4), and 64% of patients were frail (Clinical Frailty Score 5-9). The propensity score analysis paired 984 patients (492 with and without corticosteroids). The in-hospital mortality was 32.3% in the matched cohort. On multivariate analysis, the probability of in-hospital mortality was increased with corticosteroid use (odds ratio [OR] = 2.61 [95% confidence interval (CI) 1.63-4.20]). Other factors associated with in-hospital mortality were age (OR = 1.04 [1.01-1.07], CCI (OR = 1.18 [1.07-1.29], activities of daily living (OR = 0.85 [0.75-0.95], oxygen saturation < 90% on room air (OR = 2.15 [1.45-3.17], C-reactive protein level (OR = 2.06 [1.69-2.51], and lowest lymphocyte count (OR = 0.49 [0.38-0.63]). Among the 535 patients who received corticosteroids, 68.3% had at least one corticosteroid side effect, including delirium (32.9%), secondary infections (32.7%), and decompensated diabetes (14.4%). CONCLUSIONS: In this multicentric matched-cohort study of geriatric patients hospitalized for COVID-19, the use of corticosteroids was significantly associated with in-hospital mortality.
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COVID-19 , Actividades Cotidianas , Corticoesteroides/uso terapéutico , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Mortalidad Hospitalaria , Humanos , Masculino , Estudios Retrospectivos , SARS-CoV-2RESUMEN
Highlights: Innate immune activation during Covid-19 infection is associated with pernicious clinical outcome. Background: Coronavirus disease 2019 (Covid-19) is a worldwide threat that has already caused more than 3 000 000 deaths. It is characterized by different patterns of disease evolution depending on host factors among which old-age and pre-existing comorbidities play a detrimental role. Previous coronavirus epidemics, notably SARS-CoV, were associated with increased serum neopterin levels, which can be interpreted as a sign of acute innate immunity in response to viral infection. Here we hypothesize that neopterin may serve as a biomarker of SARS-CoV-2 viral infection and Covid-19 disease severity. Methods: We measured neopterin blood levels by ELISA. Seric concentration was quantified from 256 healthy donors and 374 Covid-19 patients at hospital admission. Enrolled Covid-19 patients were all symptomatic and displayed a large spectrum of comorbidities. Patients were followed until disease resolution or death. Results: Severe and critically ill SARS-CoV-2 infected patients were characterized by a profound exacerbation of immune activation characterized by elevated neopterin blood levels. Systemic neopterin levels above 19nM stratified healthy individuals from Covid-19 patients with 87% specificity and 100% sensitivity. Moreover, systemic neopterin levels above 53nM differentiated non-survivors from survivors with 64% specificity and 100% sensitivity. Conclusion: We propose that neopterin concentration measured at arrival to hospital is a hallmark of severe Covid-19 and identifies a high-risk population of pernicious clinical outcome with a need for special medical care.
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COVID-19 , Neopterin , Enfermedad Crítica , HumanosRESUMEN
BACKGROUND: There is limited information describing the characteristics and outcomes of hospitalized older patients with confirmed coronavirus disease 2019 (COVID-19). METHOD: We conducted a multicentric retrospective cohort study in 13 acute COVID-19 geriatric wards, from March 13 to April 15, 2020, in Paris area. All consecutive patients aged 70 years and older, with confirmed COVID-19, were enrolled. RESULTS: Of the 821 patients included in the study, the mean (SD) age was 86 (7) years; 58% were female; 85% had ≥2 comorbidities; 29% lived in an institution; and the median [interquartile range] Activities of Daily Living scale (ADL) score was 4 [2-6]. The most common symptoms at COVID-19 onset were asthenia (63%), fever (55%), dyspnea (45%), dry cough (45%), and delirium (25%). The in-hospital mortality was 31% (95% confidence interval [CI] 27-33). On multivariate analysis, at COVID-19 onset, the probability of in-hospital mortality was increased with male gender (odds ratio [OR] 1.85; 95% CI 1.30-2.63), ADL score <4 (OR 1.84; 95% CI 1.25-2.70), asthenia (OR 1.59; 95% CI 1.08-2.32), quick Sequential Organ Failure Assessment score ≥2 (OR 2.63; 95% CI 1.64-4.22), and specific COVID-19 anomalies on chest computerized tomography (OR 2.60; 95% CI 1.07-6.46). CONCLUSIONS: This study provides new information about older patients with COVID-19 who are hospitalized. A quick bedside evaluation at admission of sex, functional status, systolic arterial pressure, consciousness, respiratory rate, and asthenia can identify older patients at risk of unfavorable outcomes.