Prognostic Value of Routinely Measured Inflammatory Biomarkers in Older Cancer Patients: Pooled Analysis of Three Cohorts

BACKGROUND: The prognostic assessment of older cancer patients is complicated by their heterogeneity. We aimed to assess the prognostic value of routine inflammatory biomarkers. METHODS: A pooled analysis of prospective multicenter cohorts of cancer patients aged >/=70 was performed. We measured CRP and albumin, and calculated Glasgow Prognostic Score (GPS) and CRP/albumin ratio. The GPS has three levels (0 = CRP /= 35 g/L, i.e., normal values; 1 = one abnormal value; 2 = two abnormal values). One-year mortality was assessed using Cox models. Discriminative power was assessed using Harrell's C index (C) and net reclassification improvement (NRI). RESULTS: Overall, 1800 patients were analyzed (mean age: 79 +/- 6; males: 62%; metastases: 38%). The GPS and CRP/albumin ratio were independently associated with mortality in patients not at risk of frailty (hazard ratio [95% confidence interval] = 4.48 [2.03-9.89] for GPS1, 11.64 [4.54-29.81] for GPS2, and 7.15 [3.22-15.90] for CRP/albumin ratio > 0.215) and in patients at risk of frailty (2.45 [1.79-3.34] for GPS1, 3.97 [2.93-5.37] for GPS2, and 2.81 [2.17-3.65] for CRP/albumin ratio > 0.215). The discriminative power of the baseline clinical model (C = 0.82 [0.80-0.83]) was increased by adding GPS (C = 0.84 [0.82-0.85]; NRI events (NRI+) = 10% [2-16]) and CRP/albumin ratio (C = 0.83 [0.82-0.85]; NRI+ = 14% [2-17]). CONCLUSIONS: Routine inflammatory biomarkers add prognostic value to clinical factors in older cancer patients

Strong Ifitm1 Expression In Cd4 T Cells In Hiv Controllers Is Correlated With Immune Activation

International audienceno abstrac

Defining standard and high dosages for β-lactam agents administered by intermittent, prolonged or continuous infusion: a PK/PD simulation study

International audienceBackground: The new definitions of antimicrobial susceptibility categories proposed by EUCAST in 2020 require the definition of standard and high dosages of antibiotic. For injectable β-lactams, standard and high dosages have been proposed for short-infusion regimens only.Objectives: To evaluate dosages for β-lactams administered by prolonged infusion (PI) and continuous infusion (CI).Methods: Monte Carlo simulations were performed for seven injectable β-lactams: aztreonam, cefepime, cefotaxime, cefoxitin, ceftazidime, piperacillin and temocillin. Various dosage regimens based on short infusion, PI or CI were simulated in virtual patients. Pharmacokinetic (PK) profiles and PTAs were obtained based on reference population PK models, as well as PK/pharmacodynamic targets and MIC breakpoints proposed by EUCAST. Alternative dosage regimens associated with PTA values similar to those of recommended dosages up to the breakpoints were considered acceptable.Results: Adequate PTAs were confirmed for most EUCAST short-infusion dosage regimens. A total of 9 standard and 14 high dosages based on PI (3 to 4 h) or CI were identified as alternatives. For cefepime and aztreonam, only PI and CI regimens could achieve acceptable PTAs for infections caused by Pseudomonas spp.: 2 g q8h as PI of 4 h or 6 g/24 h CI for cefepime; 2 g q6h as PI of 3 h or 6 g/24 h CI for aztreonam.Conclusions: These alternative standard and high dosage regimens are expected to provide antibiotic exposure compatible with new EUCAST definitions of susceptibility categories and associated MIC breakpoints. However, further clinical evaluation is necessary

Geriatric impairments were directly and indirectly associated with mortality in older patients with cancer: a structural equation analysis

International audienceOBJECTIVE: We assessed the direct and indirect effects between six geriatric domains and 6- and 12-month mortality in older cancer patients. STUDY DESIGN AND SETTING: We included cancer patients aged ≥70 from the ELCAPA cohort, referred for geriatric assessment between 2007 and 2016. We used structural equation modelling to examine the interrelationships between six geriatric domains (function and mobility, nutrition, cognition, mood, comorbidities and polypharmacy, and social support) and the direct and indirect relationships between these domains, the cancer stage, site, and treatment on one hand and mortality on the other. RESULTS: The analysis included 1434 patients (mean age: 80 ± 5.6; women: 48%; main cancer sites: digestive tract (36.2%), urinary tract and prostate (26.6%), and breast (16.5%); metastatic cancer: 48%). Direct relationships to 6- and 12- month mortality were identified for functional impairment (standardized coefficient (SC): 0.37 (P<0.001) and 0.32 (P<0.001), respectively), poor nutritional status (SC: 0.11 (P=0.005) and 0.14 (P=0.001)), poor social support (SC=0.07 (P=0.08) and 0.09 (P=0.02)), cancer site, stage, and treatment. The effects of comorbidities, cognitive impairment and depression on mortality were mediated by functional and nutritional status. CONCLUSION: In older cancer patients, functional and nutritional impairments were the strongest direct prognostic geriatric factors for mortality

Functional decline in geriatric rehabilitation ward; is it ascribable to hospital acquired infection? A prospective cohort study

International audienceAbstract Background In some European countries, including France, older patients with functional decline in acute units are transferred to geriatric rehabilitation units. Some patients may not benefit from their stay in a geriatric rehabilitation unit and paradoxically worsened their functional status. Previous prognostic models of functional decline are based on only baseline parameters. However, some events can occur during rehabilitation and modify the association between baseline parameters and rehabilitation performance such as heart failure episode, falls or hospital-acquired infection (HAI). The incidence of functional decline in these units and factors associated with this decline have not been clearly identified. Methods We used a prospective cohort of consecutive patients aged ≥75 years admitted to a geriatric rehabilitation unit in a French university hospital. The main endpoint was functional decline defined by at least an one-point decrease in Activities of Daily Living (ADL) score during the stay. Baseline social and geriatric characteristics were recorded and comorbidities were sought by the Cumulative Illness Rating Scale for Geriatrics (CIRS-G). During follow-up, hospital-acquired infection (HAI) was recorded, as was ADL score at discharge. Multivariate logistic regression and mediation analyses were used to identify factors associated with ADL decrease. Results Among the 252 eligible patients, 160 (median age 84 years [interquartile range (IQR) 80–88] had available ADL scores at baseline (median score 7 [IQR 4–10]) and at discharge (median 9 [6–12]). Median CIRS-G score was 11 [8–13], 23 (14%) had a pulmonary HAI; 28 (17.5%) showed functional decline. On multivariable analysis, functional decline was associated with comorbidities (global CIRS-G score, P = 0.02, CIRS-G for respiratory disease [CIRS-G-R] ≥2, P = 0.02, or psychiatric disease, P = 0.02) and albumin level < 35 g/l ( p = 0.03). Significant associations were found between functional decline and CIRS-G-R (OR 3.07 [95%CI 1.27–7.41], p = 0.01), between functional decline and pulmonary HAI (OR 3.12 [1.17–8.32], p = 0.02), and between CIRS-G-R and pulmonary HAI (OR 12.9[4.4–37.7], p = 0.0001). Theses associations and the reduced effect of CIRS-G-R on functional decline after adjusting for pulmonary HAI (OR 2.26 [0.83–6.16], p = 0.11) suggested partial mediation of pulmonary HAI in the relation between CIRS-G-R and functional decline. Conclusion Baseline comorbidities were independently associated with functional decline in patients hospitalized in a geriatric rehabilitation unit. Pulmonary HAI may have mediated this association. We need to better identify patients at risk of functional decline before transfer to a rehabilitation unit and to test the implementation of modern and individual programs of rehabilitation outside the hospital for these patients

HIV infection and COVID-19: risk factors for severe disease

International audienceDominique Salmon a,b , the COVID-19 ID Team We performed an observational prospective monocentric study in patients living with HIV (PLWH) diagnosed with COVID-19. Fifty-four PLWH developed COVID-19 with 14 severe (25.9%) and five critical cases (9.3%), respectively. By multivariate analysis, age, male sex, ethnic origin from sub-Saharan Africa and metabolic disorder were associated with severe or critical forms of COVID-19. Prior CD4 R T cell counts did not differ between groups. No protective effect of a particular antiretroviral class was observed

A Two-Step Frailty Assessment Strategy in Older Patients With Solid Tumors: A Decision Curve Analysis

International audiencePURPOSE: The intended clinical value of frailty screening is to identify unfit patients needing geriatric assessment (GA) and to prevent unnecessary GA in fit patients. These hypotheses rely on the sensitivity and specificity of screening tests, but they have not been verified. METHODS: We performed a cross-sectional analysis of outpatients age >/= 70 years with prostate, breast, colorectal, or lung cancer included in the ELCAPA cohort study (ClinicalTrials.gov identifier: NCT02884375) between February 2007 and December 2019. The diagnostic accuracy of the G8 Geriatric Screening Tool (G8) and modified G8 scores for identifying unfit patients was determined on the basis of GA results. We used decision curve analysis to calculate the benefit of frailty screening for detecting unfit patients and avoiding unnecessary GA in fit patients across different threshold probabilities. RESULTS: We included 1,648 patients (median age, 81 years), and 1,428 (87%) were unfit. The sensitivity and specificity were, respectively, 85% (95% CI, 84 to 87) and 59% (95% CI, 57 to 61) for G8, and 86% (95% CI, 84 to 87) and 60% (95% CI, 58 to 63) for the modified G8 score. For decision curve analysis, the net benefit (NB) for identifying unfit patients were 0.72 for G8, 0.72 for the modified G8, and 0.82 for GA at a threshold probability of 0.25. At a threshold probability of 0.33, the NBs were 0.71, 0.72, and 0.80, respectively. At a threshold probability of 0.5, the NBs were 0.68, 0.69, and 0.73, respectively. No screening tool reduced unnecessary GA in fit patients at predefined threshold probabilities. CONCLUSION: Although frailty screening tests showed good diagnostic accuracy, screening showed no clinical benefits over the GA-for-all strategy. NB approaches, in addition to diagnostic accuracy, are necessary to assess the clinical value of tests