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1.
J Am Geriatr Soc ; 68(12): 2735-2743, 2020 12.
Article in English | MEDLINE | ID: mdl-33045106

ABSTRACT

BACKGROUND: Clinical presentation and risk factors of death in COVID-19 in oldest adults have not been well characterized. OBJECTIVES: To describe clinical features and outcome of COVID-19 in patients older than 85 years and study risk factors for mortality. DESIGN: Prospective cohort. PARTICIPANTS AND SETTING: Patients aged 85 years and older, admitted in noncritical care units at the University Hospital Lariboisière Fernand-Widal (Paris, France) for confirmed severe acute respiratory syndrome coronavirus 2 infection were included and followed up for 21 days. MEASUREMENTS: Clinical and laboratory findings were collected. Cox survival analysis was performed to explore factors associated with death. RESULTS: From March 14 to April 11, 2020, 76 patients (median age = 90 (86-92) years; women = 55.3%) were admitted for confirmed COVID-19. Of the patients, 64.5% presented with three or more comorbidities. Most common symptoms were asthenia (76.3%), fever (75.0%) and confusion and delirium (71.1%). An initial fall was reported in 25.0% of cases, and digestive symptoms were reported in 22.4% of cases. COVID-19 was severe in 51.3% of cases, moderate in 32.9%, and mild in 15.8%. Complications included acute respiratory syndrome (28.9%), cardiac decompensation (14.5%), and hypotensive shock (9.0%). Fatality at 21 days was 28.9%, after a median course of disease of 13 (8-17) days. Males were overrepresented in nonsurvivors (68.2%). In survivors, median length of stay was 12 (9-19.5) days. Independent predictive factors of death were C-reactive protein level at admission and lymphocyte count at nadir. CONCLUSION: Specific clinical features, multiorgan injury, and high case fatality rate are observed in older adults with COVID-19. However, rapid diagnosis, appropriate care, and monitoring seem to improve prognosis.


Subject(s)
COVID-19 , Hospitalization/statistics & numerical data , SARS-CoV-2/isolation & purification , Aged, 80 and over , C-Reactive Protein/analysis , COVID-19/blood , COVID-19/mortality , COVID-19/physiopathology , COVID-19/therapy , Cohort Studies , Comorbidity , Female , France/epidemiology , Humans , Intensive Care Units/statistics & numerical data , Lymphocyte Count/methods , Male , Mortality , Outcome and Process Assessment, Health Care , Prognosis , Risk Factors , Survival Analysis , Symptom Assessment/methods , Symptom Assessment/statistics & numerical data
2.
J Exp Med ; 214(2): 491-510, 2017 02.
Article in English | MEDLINE | ID: mdl-28057804

ABSTRACT

Natural killer (NK) cells are innate lymphoid cells with antitumor functions. Using an N-ethyl-N-nitrosourea (ENU)-induced mutagenesis screen in mice, we identified a strain with an NK cell deficiency caused by a hypomorphic mutation in the Bcl2 (B cell lymphoma 2) gene. Analysis of these mice and the conditional deletion of Bcl2 in NK cells revealed a nonredundant intrinsic requirement for BCL2 in NK cell survival. In these mice, NK cells in cycle were protected against apoptosis, and NK cell counts were restored in inflammatory conditions, suggesting a redundant role for BCL2 in proliferating NK cells. Consistent with this, cycling NK cells expressed higher MCL1 (myeloid cell leukemia 1) levels in both control and BCL2-null mice. Finally, we showed that deletion of BIM restored survival in BCL2-deficient but not MCL1-deficient NK cells. Overall, these data demonstrate an essential role for the binding of BCL2 to BIM in the survival of noncycling NK cells. They also favor a model in which MCL1 is the dominant survival protein in proliferating NK cells.


Subject(s)
Killer Cells, Natural/physiology , Proto-Oncogene Proteins c-bcl-2/physiology , Animals , Antigens, Ly/physiology , Bcl-2-Like Protein 11/physiology , Bridged Bicyclo Compounds, Heterocyclic/pharmacology , Cell Cycle , Cell Survival , Female , Lymphocyte Activation , Male , Mice , Mice, Inbred C57BL , Natural Cytotoxicity Triggering Receptor 1/physiology , Sulfonamides/pharmacology
3.
Asian Cardiovasc Thorac Ann ; 17(4): 362-7, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19713331

ABSTRACT

Outcomes of off-pump multivessel coronary artery bypass were compared with those of the on-pump procedure. From July 2001 to June 2006, 3,637 patients with multivessel coronary disease underwent off-pump coronary artery bypass, and 3,586 patients had on-pump coronary artery bypass in our center. The rates of operative mortality, permanent stroke, renal failure and perioperative myocardial infarction were significantly lower in the off-pump group, and these patients required fewer blood transfusions, shorter durations of ventilatory support, and shorter hospital stays. However, the patients who underwent on-pump coronary artery bypass were considered more high-risk and tended to have more complex procedures.


Subject(s)
Coronary Artery Bypass, Off-Pump/adverse effects , Coronary Artery Bypass/adverse effects , Coronary Artery Disease/surgery , Outcome and Process Assessment, Health Care , Aged , Aged, 80 and over , Blood Transfusion , Coronary Artery Bypass/mortality , Coronary Artery Bypass, Off-Pump/mortality , Coronary Artery Disease/mortality , Female , Humans , Length of Stay , Male , Myocardial Infarction/etiology , Registries , Renal Insufficiency/etiology , Respiration, Artificial , Risk Assessment , Severity of Illness Index , Stroke/etiology , Time Factors , Treatment Outcome
4.
Diabetes ; 58(7): 1544-9, 2009 Jul.
Article in English | MEDLINE | ID: mdl-19389827

ABSTRACT

OBJECTIVE: Insulin plays an important role in the hypothalamic control of energy balance, especially by reducing food intake. Emerging data point to a pivotal role of reactive oxygen species (ROS) in energy homeostasis regulation, but their involvement in the anorexigenic effect of insulin is unknown. Furthermore, ROS signal derived from NADPH oxidase activation is required for physiological insulin effects in peripheral cells. In this study, we investigated the involvement of hypothalamic ROS and NADPH oxidase in the feeding behavior regulation by insulin. RESEARCH DESIGN AND METHODS: We first measured hypothalamic ROS levels and food intake after acute intracerebroventricular injection of insulin. Second, effect of pretreatment with a ROS scavenger or an NADPH oxidase inhibitor was evaluated. Third, we examined the consequences of two nutritional conditions of central insulin unresponsiveness (fasting or short-term high-fat diet) on the ability of insulin to modify ROS level and food intake. RESULTS: In normal chow-fed mice, insulin inhibited food intake. At the same dose, insulin rapidly and transiently increased hypothalamic ROS levels by 36%. The pharmacological suppression of this insulin-stimulated ROS elevation, either by antioxidant or by an NADPH oxidase inhibitor, abolished the anorexigenic effect of insulin. Finally, in fasted and short-term high-fat diet-fed mice, insulin did not promote elevation of ROS level and food intake inhibition, likely because of an increase in hypothalamic diet-induced antioxidant defense systems. CONCLUSIONS: A hypothalamic ROS increase through NADPH oxidase is required for the anorexigenic effect of insulin.


Subject(s)
Cerebral Ventricles/physiology , Energy Intake/physiology , Hypothalamus/physiology , Insulin/pharmacology , NADPH Oxidases/metabolism , Reactive Oxygen Species/metabolism , Animals , Blood Glucose/metabolism , Cerebral Ventricles/drug effects , Energy Intake/drug effects , Energy Metabolism , Glutathione/metabolism , Homeostasis/drug effects , Homeostasis/physiology , Insulin/administration & dosage , Insulin/blood , Male , Mice , Mice, Inbred C57BL
5.
Clin J Pain ; 24(7): 637-40, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18716503

ABSTRACT

BACKGROUND: Complex regional pain syndrome (CRPS) is a common problem presenting to orthopedic surgeons or pain therapists, most frequently encountered after trauma or surgery to a limb. Because of a lack of a simple objective diagnostic test, diagnosis is reliant on clinical assessment. Prospective studies have repeatedly demonstrated a higher incidence than retrospective studies, an observation that has been challenged owing to the lack of uniformity of diagnostic criteria across specialties and workers researching the condition. METHODS: A series of 262 adult patients presenting to the Bristol Royal Infirmary with a closed unilateral distal radial fracture were assessed at a mean of 9.47 weeks after their injury by a single clinician (J.A.L.). Each assessment made allowed comparison of the modified International Association for the Study of Pain (Bruehl) criteria for the presence of CRPS with the criteria described by Atkins. FINDINGS: The incidence of CRPS was similar using either criteria (Bruehl 20.61% vs. Atkins 22.52%). Using the Bruehl criteria as a gold standard, there was strong diagnostic agreement (kappa=0.79, sensitivity=0.87, specificity=0.94). Disagreements between the 2 criteria methods were found in 19 patients. The majority of these discordances were due to differences in pain and sensory abnormality assessment. INTERPRETATION: These findings show that the Bruehl and Atkins criteria are basically concordant. The differences reflect only minor variations in the assessment of pain. Agreement between researchers in the orthopedic and pain therapy communities will allow improved understanding of CRPS.


Subject(s)
Pain Measurement/methods , Reflex Sympathetic Dystrophy/diagnosis , Adult , Aged , Aged, 80 and over , England , Female , Humans , Male , Middle Aged , Reproducibility of Results , Sensitivity and Specificity
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