Etienne Audureau

Six Months of Hydroxyurea Reduces Albuminuria in Patients with Sickle Cell Disease

The earliest symptom of glomerular injury in patients with sickle cell disease (SCD) is microalbuminuria. The effect of hydroxyurea (HU) on urine albumin-to-creatinine ratio (ACR) is unclear and should be determined, because increasing numbers of patients with SCD take this drug to improve red blood cell function. In this cohort study of 58 SS-homozygous adults with SCD who initiated HU therapy, we evaluated ACR changes and relationships of these changes with demographic, clinical, and biologic parameters at HU initiation (baseline) and 6 months later (follow-up). Between baseline and follow-up, ACR declined significantly for the entire population (3.0-1.7 mg/mmol; P<0.01), but this was primarily driven by the ACR reduction in the microalbuminuria subgroup (8.1-2.3 mg/mmol; P=0.03; n=23). According to bivariate analyses on 39 patients who did not receive a blood transfusion during the study period, the baseline to follow-up ACR decline was strongly associated with decreases in levels of hemolysis markers, percentage of dense red blood cells, and systolic BP. Bivariate analysis also revealed a close association between the ACR decrease and high baseline levels of hemolysis markers and percentage of dense red blood cells. These results show that urine ACR decreased significantly after 6 months of HU and confirm a close relationship between ACR and hemolysis evolution in patients with SCD.

Accuracy of the G-8 geriatric-oncology screening tool for identifying vulnerable elderly patients with cancer according to tumour site: The ELCAPA-02 study

BACKGROUND/OBJECTIVE G-8 screening tool showed good screening properties for identifying vulnerable elderly patients with cancer who would benefit from a comprehensive geriatric assessment (CGA). We investigated whether tumour site and metastatic status affected its accuracy. MATERIALS AND METHODS DESIGN Cross-sectional analysis of a prospective cohort study. SETTING Geriatric-oncology clinics of two teaching hospitals in the urban area of Paris. PARTICIPANTS Patients aged 70 or over (n = 518) with breast ( n= 113), colorectal (n = 108), urinary-tract (n = 89), upper gastrointestinal/liver (n = 85), prostate (n = 69), or other cancers (n = 54). MEASUREMENTS Reference standard for diagnosing vulnerability was the presence of at least one abnormal test among the Activities of Daily Living (ADLs), Instrumental ADL, Mini-Mental State Examination, Mini Nutritional Assessment, Cumulative Illness Rating Scale-Geriatrics, Timed Get-Up-and-Go, and Mini-Geriatric Depression Scale. Sensitivity, specificity and likelihood ratios of G-8 scores ≤ 14 were compared according to tumour site and patient characteristics. RESULTS Median age was 80; 48.2% had metastases. Prevalence of vulnerability and abnormal G-8 score was 84.2% (95% confidence interval [95% CI], 81-87.3) and 79.5% (95% CI, 76-83). The G-8 was 86.9% sensitive (95% CI, 83.4-89.9) and 59.8% specific (95% CI, 48.3-70.4). G-8 performance varied significantly (all p values < 0.001) across tumour sites (sensitivity, 65.2% in prostate cancer to 95.1% in upper gastrointestinal/liver cancer; and specificity, 23.1% in colorectal cancer to 95.7% in prostate cancer) and metastatic status (sensitivity and specificity, 93.8% and 53.3% in patients with metastases vs. 79.5% and 63.3% in those without, respectively). Differences remained significant after adjustment on age and performance status. CONCLUSION These G-8 accuracy variations across tumour sites should be considered when using G-8 to identify elderly patients with cancer who could benefit from CGA.

Performance of Four Frailty Classifications in Older Patients With Cancer: Prospective Elderly Cancer Patients Cohort Study

Purpose Frailty classifications of older patients with cancer have been developed to assist physicians in selecting cancer treatments and geriatric interventions. They have not been compared, and their performance in predicting outcomes has not been assessed. Our objectives were to assess agreement among four classifications and to compare their predictive performance in a large cohort of in- and outpatients with various cancers. Patients and Methods We prospectively included 1,021 patients age 70 years or older who had solid or hematologic malignancies and underwent a geriatric assessment in one of two French teaching hospitals between 2007 and 2012. Among them, 763 were assessed using four classifications: Balducci, International Society of Geriatric Oncology (SIOG) 1, SIOG2, and a latent class typology. Agreement was assessed using the κ statistic. Outcomes were 1-year mortality and 6-month unscheduled admissions. Results All four classifications had good discrimination for 1-year mortality (C-index ≥ 0.70); discrimination was best with SIOG1. For 6-month unscheduled admissions, discrimination was good with all four classifications (C-index ≥ 0.70). For classification into three (fit, vulnerable, or frail) or two categories (fit v vulnerable or frail and fit or vulnerable v frail), agreement among the four classifications ranged from very poor (κ ≤ 0.20) to good (0.60 < κ ≤ 0.80). Agreement was best between SIOG1 and the latent class typology and between SIOG1 and Balducci. Conclusion These four frailty classifications have good prognostic performance among older in- and outpatients with various cancers. They may prove useful in decision making about cancer treatments and geriatric interventions and/or in stratifying older patients with cancer in clinical trials.

Optimizing the G8 Screening Tool for Older Patients With Cancer: Diagnostic Performance and Validation of a Six-Item Version

BACKGROUND A multidimensional geriatric assessment (GA) is recommended in older cancer patients to inventory health problems and tailor treatment decisions accordingly but requires considerable time and human resources. The G8 is among the most sensitive screening tools for selecting patients warranting a full GA but has limited specificity. We sought to develop and validate an optimized version of the G8. PATIENTS AND METHODS We used a prospective cohort of cancer patients aged ≥ 70 years referred to geriatricians for GA (2007-2012: n = 729 [training set]; 2012-2014: n = 414 [validation set]). Abnormal GA was defined as at least one impaired domain across seven validated tests. Multiple correspondence analysis, multivariate logistic regression, and bootstrapped internal validation were performed sequentially. RESULTS The final model included six independent predictors for abnormal GA: weight loss, cognition/mood, performance status, self-rated health status, polypharmacy (≥ 6 medications per day), and history of heart failure/coronary heart disease. For the original G8, sensitivity was 87.2% (95% confidence interval, 84.3-89.7), specificity 57.7% (47.3-67.7), and area under the receiver-operating characteristic curve (AUROC) 86.5% (83.5-89.6). The modified G8 had corresponding values of 89.2% (86.5-91.5), 79.0% (69.4-86.6), and 91.6% (89.3; 93.9), with higher AUROC values for all tumor sites and stable properties on the validation set. CONCLUSION A modified G8 screening tool exhibited better diagnostic performance with greater uniformity across cancer sites and required only six items. If these features are confirmed in other settings, the modified tool may facilitate selection for a full GA in older patients with cancer. IMPLICATIONS FOR PRACTICE Several screening tools have been developed to identify older patients with cancer likely to benefit from a complete geriatric assessment, but none combines appropriate sensitivity and specificity. Based on a large prospective cohort study, an optimized G8 tool was developed, combining a systematic statistical approach with expert judgment to ensure optimal discriminative power and clinical relevance. The improved screening tool achieves high sensitivity, high specificity, better homogeneity across cancer types, and greater parsimony with only six items needed, facilitating selection for a full geriatric assessment.

Aging-related systemic manifestations in COPD patients and cigarette smokers.

Rationale Chronic obstructive pulmonary disease (COPD) is often associated with age-related systemic abnormalities that adversely affect the prognosis. Whether these manifestations are linked to the lung alterations or are independent complications of smoking remains unclear. Objectives To look for aging-related systemic manifestations and telomere shortening in COPD patients and smokers with minor lung destruction responsible for a decline in the diffusing capacity for carbon monoxide (DLCO) corrected for alveolar volume (KCO). Methods Cross-sectional study in 301 individuals (100 with COPD, 100 smokers without COPD, and 101 nonsmokers without COPD). Measurements and Main Results Compared to control smokers, patients with COPD had higher aortic pulse-wave velocity (PWV), lower bone mineral density (BMD) and appendicular skeletal muscle mass index (ASMMI), and shorter telomere length (TL). Insulin resistance (HOMA-IR) and glomerular filtration rate (GFR) were similar between control smokers and COPD patients. Smokers did not differ from nonsmokers for any of these parameters. However, smokers with normal spirometry but low KCO had lower ASMMI values compared to those with normal KCO. Moreover, female smokers with low KCO, had lower BMD and shorter TL compared to those with normal KCO. Conclusions Aging-related abnormalities in patients with COPD are also found in smokers with minor lung dysfunction manifesting as a KCO decrease. Decreased KCO might be useful, particularly among women, for identifying smokers at high risk for aging-related systemic manifestations and telomere shortening.

Aortic stenosis and transthyretin cardiac amyloidosis: the chicken or the egg?

BACKGROUND Aortic stenosis (AS) and transthyretin cardiac amyloidosis (TTR-CA) are both frequent in elderly. The combination of these two diseases has never been investigated. AIMS To describe patients with concomitant AS and TTR-CA. METHODS Six cardiologic French centres identified retrospectively cases of patients with severe or moderate AS associated with TTR-CA hospitalized during the last 6 years. RESULTS Sixteen patients were included. Mean ± SD age was 79 ± 6 years, 81% were men. Sixty per cent were NYHA III-IV, 31% had carpal tunnel syndrome, and 56% had atrial fibrillation. Median (Q1;Q4) NT-proBNP was 4382 (2425;4730) pg/mL and 91% had elevated cardiac troponin level. Eighty-eight per cent had severe AS (n = 14/16), of whom 86% (n = 12) had low-gradient AS. Mean ± SD interventricular septum thickness was 18 ± 4 mm. Mean left ventricular ejection fraction and global LS were 50 ± 13% and -7 ± 4%, respectively. Diagnosis of TTR-CA was histologically proven in 38%, and was based on strong cardiac uptake of the tracer at biphosphonate scintigraphy in the rest. Eighty-one per cent had wild-type TTR-CA (n = 13), one had mutated Val122I and 19% did not had genetic test (n = 3). Valve replacement was surgical in 63% and via transcatheter in 13%. Median follow-up in survivors was 33 (16;65) months. Mortality was of 44% (n = 7) during the whole follow-up period. CONCLUSIONS Combination of AS and TTR-CA may occur in elderly patients particularly those with a low-flow low-gradient AS pattern and carries bad prognosis. Diagnosis of TTR-CA in AS is relevant to discuss specific treatment and management.

Comprehensive evaluation of embarrassment and pain associated with invasive urodynamics.

To evaluate pain and embarrassment associated with invasive urodynamics and to determine underlying factors.

Update on 2-year outcomes of the TOMS™ transobturator male sling for the treatment of male stress urinary incontinence

To update the 2‐year outcomes of the TOMS™ transobturator male sling for treating post‐prostatectomy urinary incontinence (pRP‐UI) in a group of patients previously evaluated at 1 year.

Evaluation of urinary symptoms in patients with post-prostatectomy urinary incontinence treated with the male sling TOMS.

To evaluate stress urinary incontinence (SUI), overactive bladder (OAB), and obstructive symptoms in patients with post‐radical prostatectomy urinary incontinence (pRP‐UI) treated with the bulbar compressive sling TOMS, and investigate the effect of each urinary symptom on urinary bother.

Interrelations of immunological parameters, nutrition, and healthcare-associated infections: Prospective study in elderly in-patients

BACKGROUND & AIMS Healthcare-associated infections [HAI] are common in elderly individuals and may be related to both nutritional deficiencies and immunosenescence. Here, we assessed whether overall malnutrition and/or specific nutrient deficiencies were associated with HAI via alterations in immune parameters. METHODS Prospective observational cohort study in patients aged ≥ 70 years admitted to the geriatric rehabilitation unit of a teaching hospital in France between July 2006 and November 2008. Clinical and laboratory parameters reflecting nutritional status and immune function were collected at baseline. Flow cytometry was used to assess blood lymphocyte subsets including the naive CD4 T-cell count, naive and memory CD8 T-cell counts, effector CD8 T-cell count, and CD4/CD8 ratio. Patients were monitored for HAI for 3 months or until discharge from the geriatric unit or death. RESULTS Of 252 consecutive in-patients aged ≥ 70 years [mean age, 85 ± 6.2 years], 181 [72%] met French National Authority for Health criteria for malnutrition and 97 [38%] experienced one or more HAI. Patients who subsequently experienced HAI had significantly lower baseline values for energy intake [odds ratio (OR), 0.76; 95% confidence interval (95%CI), 0.59-0.99], serum albumin [OR, 0.43; 95%CI, 0.32-0.58], serum zinc [OR, 0.77; 95%CI, 0.62-0.97], selenium [OR, 0.76; 95%CI, 0.61-0.95], and vitamin C [OR, 0.71; 95%CI, 0.54-0.93]. Associations linking these five variables to HAI were not significantly changed by adjusting for flow cytometry T-cell subset values. CONCLUSION Our results suggest a direct effect of nutritional parameters on HAI rather than an indirect effect mediated by immune parameters.