Influence of 4 preservation solutions on ICU stay, graft and patient survival following liver transplantation.

OBJECTIVE: The goal of this study was to evaluate the prognostic role of four preservation solutions in liver transplantation (LT). PATIENTS AND METHODS: This is a retrospective study originating from 22 French centers performing LT, registered in the prospective databank of the Cristal Biomedicine Agency between 2008 and 2013. The preservation solutions used were Celsior (CS), Institut Georges Lopez (IGL)-1, Solution de Conservation des Organes et des Tissus (SCOT) 15 and University of Wisconsin (UW) solutions. Exclusion criteria were preservation with unknown or inhomogeneous solutions, or Histidine-tryptophan-ketoglutarate (HTK) solution (representing only 3% of LT). Patient survival was the main endpoint. Secondary endpoints were graft survival and duration of stay in intensive care. RESULTS: Of 6347 LT performed, 4928 were included in this study, for which the distribution of preservation solution was CS (30%), IGL-1 (44%), SCOT 15 (10%) and UW (16%). Patient survival was 86%, 80% and 74% at 1, 3 and 5 years after LT, respectively, without any statistically significant difference between the four solutions (P=0.78). Graft survival was 82%, 75% and 69% at 1, 3 and 5 years after LT, respectively, without any statistically significant difference between the four solutions (P=0.80). Duration of intensive care was different according to the solution used in univariate analysis (P<0.001), but this effect disappeared in multivariate analysis when the center performing the transplantation was accounted for. CONCLUSION: The type of preservation solution used (CS, IGL-1, SCOT 15 or UW) did not have any influence on patient or graft survival after LT.

Impact of graft preservation solutions for liver transplantation on early cytokine release and postoperative organ dysfunctions. A pilot study.

INTRODUCTION: During liver transplantation, graft ischemia-reperfusion injury leads to a systemic inflammatory response producing postoperative organ dysfunctions. The aim of this observational and prospective study was to compare the impact of Solution de conservation des organes et tissus (SCOT) 15 and University of Wisconsin (UW) preservation solutions on early cytokine release, postreperfusion syndrome and postoperative organ dysfunctions. METHODS: Thirty-seven liver transplantations were included: 21 in UW Group and 16 in SCOT 15 group. Five cytokines were measured in systemic blood after anesthetic induction, 30minutes after unclamping portal vein and on postoperative day 1. RESULTS: Following unclamping portal vein, cytokines were released in systemic circulation. Systemic cytokine concentrations were higher in UW than in SCOT 15 group: Interleukin-10, Interleukine-6. In SCOT 15 group, significant reduction of postreperfusion syndrome incidence and acute kidney injury were observed. Alanine and aspartate aminotransferase peak concentrations were higher in SCOT 15 group than in UW group. However, from postoperative day 1 to day 10, aminotransferase returned to normal values and did not differ between groups. CONCLUSIONS: Compared to UW, SCOT 15 decreases systemic cytokine release resulting from graft ischemia-reperfusion injury and reduces incidence of postreperfusion syndrome and postoperative renal failure.

Anticonvulsants and suicide attempts in bipolar I disorders.

OBJECTIVE: To identify risk factors for suicide attempts (SA) in individuals commencing treatment for a manic or mixed episode. METHOD: A total of 3390 manic or mixed cases with bipolar disorder (BD) type I recruited from 14 European countries were included in a prospective, 2-year observational study. Poisson regression models were used to identify individual and treatment factors associated with new SA events. Two multivariate models were built, stratified for the presence or absence of prior SA. RESULTS: A total of 302 SA were recorded prospectively; the peak incidence was 0-12 weeks after commencing treatment. In cases with a prior history of SA, risk of SA repetition was associated with younger age of first manic episode (P = 0.03), rapid cycling (P < 0.001), history of alcohol and/or substance use disorder (P < 0.001), number of psychotropic drugs prescribed (P < 0.001) and initiation of an anticonvulsant at study entry (P < 0.001). In cases with no previous SA, the first SA event was associated with rapid cycling (P = 0.02), lifetime history of alcohol use disorder (P = 0.02) and initiation of an anticonvulsant at study entry (P = 0.002). CONCLUSION: The introduction of anticonvulsants for a recent-onset manic or mixed episode may be associated with an increased risk of SA. Further BD studies must determine whether this link is causal.

Effects of haemolysis, icterus and lipaemia on coagulation tests as performed on Stago STA-Compact-Max analyser.

INTRODUCTION: Haemolysis, icterus and lipaemia (HIL) may affect haemostasis test results. This may be influenced by the level of interfering substance and the reagents and end-point detection system used. METHODS: We assessed the influence of HIL on prothrombin time, activated partial thromboplastin time and fibrinogen assay using a viscosity-based detection analyser. RESULTS: Spontaneous haemolysis that occurred during sample collection and processing had no effect on PT with either a rabbit tissue factor extract or recombinant human tissue factor reagents. In contrast, addition of mechanically haemolysed cells impacted on PT for the highest haemoglobin concentration. For APTTs determined with STA®-Cephascreen® reagent, there was no significant difference between results in haemolysed and nonhaemolysed samples. For the other two reagents studied, APTTs were statistically significantly shorter in haemolysed samples compared with nonhaemolysed samples. This bias was clinically significant only for STA®-PTT Automate. For all three APTT reagents, the impact of haemolysis was sufficient to impact patient management decisions, and in some samples, the effects of lipaemia and icterus were not clinically significant. CONCLUSION: Overall, our results confirm that PT and fibrinogen were not clinically significantly affected by HIL. The APTTs of some haemolysed samples were falsely normal. Haemolysed samples for APTT determination should be rejected.

Using admixture analysis to examine birth-cohort effects on age at onset of bipolar disorder.

OBJECTIVE: It is suggested that age at onset (AAO) of bipolar I disorder (BP-I) is decreasing. We tested for a birth-cohort effect on AAO using admixture analysis. METHOD: A clinical sample of 3896 BP-I cases was analysed using two approaches: (i) in a subsample with untruncated AAO × birth year distribution (n = 1865), we compared the best-fitting model for the observed AAO in patients born ≤1960 and >1960, (ii) to control for potential confounders, two separate subsamples born ≤1960 and >1960 were matched for age at interview (n = 250), and a further admixture analysis was undertaken. RESULTS: The two approaches indicated that the proportion of cases in the early AAO category was significantly greater in cases born >1960; manic onsets were also more frequent in the early onset BP-I cases born >1960. CONCLUSION: The decrease in AAO of BP-I in recent birth-cohorts appears to be associated with an increase in the proportion of cases in the early onset subgroup; not with a decrease in the mean AAO in each putative subgroup. This could indicate temporal changes in exposure to risk factors for mania.

Vemurafenib pharmacokinetics and its correlation with efficacy and safety in outpatients with advanced BRAF-mutated melanoma.

Vemurafenib is a BRAF kinase inhibitor approved for first-line treatment of metastatic BRAF (V600) -mutant melanoma. However, data on the pharmacokinetic/pharmacodynamic (PK/PD) relationship are lacking. The aim of this prospective, multicenter study was to explore the PK/PD relationship for vemurafenib in outpatients with advanced BRAF-mutated melanoma. Fifty-nine patients treated with single-agent vemurafenib were prospectively analyzed. Vemurafenib plasma concentration (n = 159) was measured at days 15, 30, 60, and 90 after treatment initiation. Clinical and biological determinants (including plasma vemurafenib concentration) for efficacy and safety were assessed using Cox's model and multivariate stepwise logistic regression. Median progression-free survival (PFS) and overall survival were 5.0 (95 % confidence interval [95 % CI] 2.0-6.0) and 11.0 (95% CI 7.0-16.0) months, respectively. Twenty-nine patients (49 %) experienced any grade ≥3 toxicity and the most frequent grade ≥2 toxicity was skin rash (37 %). Severe toxicities led to definitive discontinuation in seven patients (12 %). Grade ≥2 skin rash was not statistically associated with better objective response at day 60 (p = 0.06) and longer PFS (hazard ratio 0.47; 95 % CI 0.21-1.08; p = 0.075). Grade ≥2 skin rash was statistically increased in patients with ECOG ≥ 1 (odds ratio 4.67; 95 % CI 1.39-15.70; p = 0.012). Vemurafenib concentration below 40.4 mg/L at day 15 was significantly associated with a shorter PFS (1.5 [0.5-5.5] vs. 4.5 [2-undetermined] months, p = 0.029). Finally, vemurafenib concentration was significantly greater in patients developing grade ≥2 rash (61.7 ± 25.0 vs. 36.3 ± 17.9 mg/L, p < 0.0001). These results suggest that early plasma drug monitoring may help identify outpatients at high risk of non-response or grade ≥ 2 skin rash.

Chimerism analysis in peripheral blood using indel quantitative real-time PCR is a useful tool to predict post-transplant relapse in acute leukemia.

Detection of increasing mixed chimerism (IMC) using standard PCR correlates with relapse after allo-SCT for acute leukemias (ALs). Quantitative real-time PCR of insertion/deletion polymorphism (indel qrtPCR) is a much more sensitive method, which can be performed on peripheral blood. We studied the significance of low increases of recipient cells (0.1%) detected by indel qrtPCR in a cohort of 89 transplants. We did not observe relapse among the 32 patients with no IMC. Fifty-seven patients presented a first IMC, which was followed by four different scenarios: a decreasing MC (26 cases, no relapse), a stable MC (1 case, 1 relapse), a second IMC (24 cases, 15 relapse) or no control of chimerism (6 cases, 5 relapses). In multivariate analysis, detection of two successive IMCs was strongly associated with relapse (hazard ratio (HR): 9.4, 95% confidence interval (CI): 3.8-23; P<0.0001). Among the 57 patients who presented at least one IMC, 27 underwent immunomodulation (tapering of immunosuppression or donor lymphocyte injection), leading to a 1-year relapse rate of 15.7% vs 57.6% in the 30 other patients (P=0.0007). Altogether, these results indicate that chimerism analysis using indel qrtPCR in peripheral blood is a useful tool for detection of relapse in patients transplanted for AL.

[Relationship between maintenance dosages of fluindione (Préviscan) and warfarin (Coumadin) for patients 70 years and older]. / Nomogramme d'équivalence entre les posologies de fluindione (Préviscan) et de warfarine (Coumadine) pour des patients de 70 ans et plus.

INTRODUCTION: Switching from fluindione, an indanedione vitamin K antagonist derivative, to warfarin, a coumarin one, or vice versa, requires to know the relationships between dosages of these two molecules. METHODS: We conducted a prospective study in 288 consecutive patients aged 70 years and over, converted from fluindione to warfarin. Patients who were retained for the analysis were those for whom maintenance dosages were obtained for both vitamin K antagonists. RESULTS: Eighty-two patients, mean aged 83 ± 6 years, were analysed. The average daily maintenance dosages were 13.8 ± 6.7 mg (range 5-35) and 3.7 ± 1.7 mg (range 1-8) for fluindione and warfarin, respectively. Using a linear regression model, we built a transition algorithm for the maintenance dosages of warfarin and fluindione. CONCLUSION: This is the first study to propose a conversion algorithm to help prescribers to estimate the maintenance dosage when it is necessary for a patient to switch from fluindione to warfarin or conversely.

[Evaluation of the impact of a training program on vitamin K antagonists (VKA) implemented by pharmacy students aiming at improving the knowledge of patients receiving vitamin K antagonists during their hospital clinical training course]. / Évaluation de l'impact d'un programme de formation aux antagonistes de la vitamine K (AVK) pour les étudiants en pharmacie sur l'amélioration des connaissances des patients traités par AVK pris en charge au cours de leur stage clinique hospitalier.

INTRODUCTION: We developed a training program for pharmacy students aiming at supporting patients receiving vitamin K antagonists (VKAs). The objective was to estimate how the program impacts VKA-treated patient knowledge acquisition and/or improvement on their anticoagulant treatment. METHOD: Using dedicated tools, pharmacy students received education on VKA treatment. Once appointed to clinical wards of Assistance publique-Hôpitaux de Paris, they were in charge of evaluating patient's knowledge on VKA treatment before and after training. Evaluation was conducted using a face-to-face standardized interview (14-item questionnaire). A global score was calculated for each patient. An univariate and multivariate analysis was performed to identify potential variables influencing score result. RESULTS: One hundred and seventy VKA-treated patients were recruited in seven hospitals for evaluation of their knowledge on VKA treatment and on clinical at risk situations. Before intervention, patients obtained an average score of 12.3±3.2 (maximum: 18). Factors significantly associated with the score were possession of a VKA information booklet, VKA treatment duration, treatment initiation and age. Fifty-two patients with a low score were further trained by the pharmacy student. After intervention, their initial score was improved significantly, from 9.9±3.3 to 13.5±2.3 (P<0.0001). DISCUSSION AND CONCLUSION: Increasing patient knowledge is a way to decrease the rate of adverse effects. This study demonstrates that patients with primary poor knowledge improved it significantly thanks to pharmacy students' intervention. This may contribute to lower the VKA-associated risk of adverse events and consequently to the improvement of patients quality of life and healthcare expenditures.

[Freezing effects on the in vitro development of mice preantral follicles]. / Influence du type de congélation sur les courbes de croissance in vitro de follicules ovariens murins.

OBJECTIVES: Comparison of in vitro development, survival and oocyte maturation rates of mice preantral follicles frozen by various methods. MATERIALS AND METHODS: Cryopreservation of the germinal cells using the slow freezing method for entire ovary (Ova Cong) or isolated preantral follicles (Iso Cong) and vitrification in a closed system of isolated preantral follicles (Iso Vitr). Non-freezing follicles were considered as the control group. The four groups were simultaneous cultured for 12 days in a microdrop system. At each day of the culture, mean diameter was measured and at the end of the culture, follicular survival and mature oocyte rates were compared. RESULTS: Iso Cong and Ova Cong follicles achieved a smaller diameter (423.0 ± 47.1 µm et 450.3 ± 15.7 µm, respectively) than control group (680.7 ± 12.3 µm) at the 12th day of culture. At the end of the culture 6.21 % of Iso Cong follicles, 53.41 % of Ova Cong follicles and 83,77 % of Control follicles were alive. Mature oocyte rates were similar for the cryopreserved groups, 44.4 % for Iso Cong group and 44.7 % for Ova Cong group, but smaller than the Control group with 90 % of mature oocytes. Only 1/171 of the Iso Vitr follicles survived to the culture. DISCUSSION AND CONCLUSIONS: This study shows that mice's ovarian follicles can grow in vitro after cryopreservation but their diameter, survival and oocytes maturation rates are smaller than in the control group.

Focal dependent pleural thickening at MDCT: pleural lesion or functional abnormality?

PURPOSE: To describe the characteristics of reversible focal pleural thickenings (PTs) mimicking real plaques, that firstly suggest asbestos exposure or pleural metastasis; to propose an imaging strategy and propose an explanation for their mechanism of formation. PATIENTS AND METHODS: Retrospective review of data from 19 patients with PTs fitting the description of pleural plaques at chest computed tomography (CT) and presenting modifications (clearance or appearance) of at least one PT at an additional chest examination in prone position. RESULTS: A total of 152 PTs were recorded on the first chest CT examinations with a range of two to 19 pleural opacities per patient. All PTs had a posterior distribution in the lower lobes. On the additional acquisitions, 144 PTs disappeared. Seventeen patients presented complete regression of PTs and two patients presented persistence of eight PTs. CONCLUSION: Additional low dose acquisition in prone position should be performed in all patients presenting with focal PT in a dependent and basal location. This may allow to exclude a pleural plaque in case of asbestos exposure but also a pleural metastasis in oncologic patients. These reversible dependent PTs could be related to physiological focal accumulation of lymphatic fluid in subpleural area.

[An evaluation of fatigue in patients with glioblastoma relapse treated with the combination of irinotecan-bevacizumab]. / Évaluation de la fatigue dans les glioblastomes en récidive traités par l'association irinotécan-bévacizumab.

OBJECTIVE: The combination of irinotecan-bevacizumab is effective in patients with glioblastoma relapse but fatigue is a commonly reported side effect. The objective of this study was to evaluate the level and evolution of fatigue in a series of patients treated with therapeutic combination. PATIENTS AND METHODS: We used two self-evaluation tools to quantify the physical and emotional aspects of this fatigue. The Norris Visual Analog Scale (VAS Norris) and the Multidimensional Fatigue Inventory-20 (MFI) tools were undertaken by 39 patients with glioblastoma relapse treated with irinotecan-bevacizumab, initially before the first cycle and thereafter with each cycle up until tumor progression. RESULTS: Analysis of the results of the VAS Norris scale did not demonstrate an increase in emotional fatigue but did show an increase in physical fatigue that did not reach statistical significance. With regards to the MFI 20 tool, analysis of the results demonstrated a significant increase in general (P=0.0260) as well as physical (P=0.0141) fatigue but there was no difference in the other indices. CONCLUSION: This study demonstrated a progressive increase in physical fatigue in patients with glioblastoma relapse treated with irinotecan-bevacizumab. We suspect that this is as a direct consequence of the treatment. There are however other confounding factors: insidious tumour progression not detected on follow-up imaging or delayed side effects of the initial radiotherapy-chemotherapy.

Randomised active programs on healthcare workers' flu vaccination in geriatric health care settings in France: the VESTA study.

BACKGROUND: Because of a lack of efficacy of influenza vaccination in elderly population, there are still numerous outbreaks in geriatric health care settings. The health care workers (HCW) flu vaccination is known to get herd immunity and decrease the impact of influenza in elderly population living in geriatric health care settings. However, the rates of vaccinated HCWs are still low in France. The French Geriatric Infection Risk Institute (ORIG) performed the VESTA study, a three-phase multicentre to identify factors limiting vaccination in HCWs, and to develop and implement active programs promoting HCWs influenza vaccination. OBJECTIVES: To implement multicenter programs to enhance HCW influenza vaccination. DESIGN: It was a cluster randomised interventional studies. SETTING: 43 geriatric health care settings (GHCSs), long term care and rehabilitation care settings in France. PARTICIPANTS: 1814 Health care workers from 20 GHCSs in the interventional group and 2,435 health care workers in 23 GHCSs in the control group. INTERVENTION: After the failure of a first educational program giving scientific information and. tested during the 2005-06 flu season in 43 HCSs, a second program was designed with the help of marketing experts, one year after Program 1. The objectives were to involve HCWs in the creation of "safety zones", and to give personal satisfaction. Program 2 was tested during the 2006-07 season. 20 of the 24 HCSs from the Program 1 cluster were included in the Program 2 cluster (1,814 HCWs), and 16 of the 19 HCSs from the Control 1 cluster, plus 7 new HCSs with interest in participating, were included in the Control 2 cluster (23 HCSs; 2,435 HCWs). MEASUREMENTS: The efficacy of each program was assessed by calculating and comparing the percentage of vaccinated HCWs, from all HCSs taken together, in the program and control clusters. RESULTS: Program 1 failed to increase the HCW vaccination coverage rate (VCR) (Program 1: 34%; Control 1: 32%; p > 0.05),). Program 2 increased the VCR in HCWs (Program 2: 44%; Control 2: 27%; Chi2 test, p < 0.001) regardless their occupational group but only in the non previous vaccinated subgroup. CONCLUSIONS: In geriatric health care centres in France, an active multicenter program giving personal satisfaction and taking into account the profile of non-vaccinated HCWs was more effective in promoting flu vaccination than a scientifically factual information program. HCW involvement is required in program implementation in order to avoid rejection of top-down information.

Predicting the warfarin maintenance dose in elderly inpatients at treatment initiation: accuracy of dosing algorithms incorporating or not VKORC1/CYP2C9 genotypes.

BACKGROUND: Initiating warfarin is challenging in frail elderly patients because of low-dose requirements and interindividual variability. OBJECTIVES: We investigated whether incorporating VKORC1 and CYP2C9 genotype information in different models helped to predict the warfarin maintenance dose when added to clinical data and INR values at baseline (Day 0), and during warfarin induction. PATIENTS: We prospectively enrolled 187 elderly inpatients (mean age, 85.6 years), all starting on warfarin using the same 'geriatric dosing-algorithm' based on the INR value measured on the day after three 4-mg warfarin doses (INR(3)) and on INR(6 ± 1). RESULTS: On Day 0, the clinical model failed to accurately predict the maintenance dose (R(2) < 0.10). Adding the VKORC1 and CYP2C9 genotypes to the model increased R(2) to 0.31. On Day 3, the INR(3) value was the strongest predictor, completely embedding the VKORC1 genotype, whereas the CYP2C9 genotype remained a significant predictor (model- R(2) 0.55). On Day 6 ± 1, none of the genotypes predicted the maintenance dose. Finally, the simple 'geriatric dosing-algorithm' was the most accurate algorithm on Day 3 (R(2) 0.77) and Day 6 (R(2) 0.81), under-estimating (≥ 1 mg) and over-estimating the dose (≥ 1 mg) in fewer than 10% and 2% of patients, respectively. Clinical models and the 'geriatric dosing-algorithm' were validated on an independent sample. CONCLUSIONS: Before starting warfarin therapy, the VKORC1 genotype is the best predictor of the maintenance dose. Once treatment is started using induction doses tailored for elderly patients, the contribution of VKORC1 and CYP2C9 genotypes in dose refinement is negligible compared with two INR values measured during the first week of treatment.

Genetic factors (VKORC1, CYP2C9, EPHX1, and CYP4F2) are predictor variables for warfarin response in very elderly, frail inpatients.

Determining the optimal dose of warfarin for frail elderly patients is a challenging task because of the low dose requirements in such patients, the wide interindividual variability of response, and the associated risk of bleeding. The objective of this study was to address the influence of 13 common variations in eight genes on the maintenance dose of warfarin in a cohort of frail elderly inpatients. For our study, we enrolled 300 Caucasian subjects who were hospital inpatients, with a mean age of 86.7 +/- 6 years. In addition to age, genetic variants of VKORC1, CYP2C9, CYP4F2, and EPHX1 were found to be significant predictor variables for the maintenance dose of warfarin, explaining 26.6% of dose variability. Among 132 patients in whom warfarin therapy was initiated with the same low-dose regimen, we studied the relative influences of genetic and nongenetic factors. The time to first international normalized ratio (INR) > or =2 was influenced by VKORC1 and CYP2C9 genotypes (P = 0.0003 and P = 0.0016, respectively); individuals with multiple variant alleles were at highest risk for overanticoagulation (INR >4) (odds ratio, 12.8; 95% confidence interval, 2.73-60.0). In this special population of frail elderly patients with multiple comorbidities and polypharmacy, we demonstrated the main impact of genetic factors on warfarin response.

Segmental progression of early untreated Parkinson's disease: a novel approach to clinical rating.

OBJECTIVE: To assess the ability of potentially neuroprotective compounds to slow the progression of Parkinson's disease (PD), sensitive rating scales are needed to detect clinically meaningful effects. The topographical progression of motor signs in early untreated PD was evaluated to complement current clinical ratings and enhance the sensitivity to detect disease progression. METHODS: 12 patients referred for diagnostic evaluation of untreated de novo PD underwent detailed clinical assessment of motor parkinsonian signs at baseline and after 6 and 12 months of follow-up using the Unified Parkinson's Disease Rating Scale, motor part (UPDRS-III), and a newly developed approach of detailed segmental rating taking into account the localisation of motor signs in all of the major joints and muscle groups in the body. The progression of PD, as measured with the UPDRS-III, was compared with the segmental ratings. RESULTS: UPDRS-III scores and segmental ratings for rigidity and rest and postural tremor, but not bradykinesia, progressed significantly during the observation period. Progression of normalised segmental ratings for rigidity and tremor was significantly larger than the UPDRS-III ratings over 1 year. The segmental ratings for rigidity and tremor as well as their combination with the UPDRS-III bradykinesia rating were more sensitive a measure for progression of PD than the UPDRS-III. CONCLUSIONS: Taking into account the segmental evolution of parkinsonian signs may be a useful adjunct to UPDRS-III evaluations to measure clinical disease progression of PD. If validated in subsequent larger cohorts, this may be useful in trials of neuroprotective agents.

[Evaluation of a computer aided detection system for lung nodules with ground glass opacity component on multidetector-row CT]. / Evaluation d'un système de détection assisté par ordinateur des nodules parenchymateux pulmonaires avec verre dépoli au scanner multidétecteur.

PURPOSE: To determine the performance of a CAD system for lung nodules with ground glass opacity component on multidetector-row CT. Materials and methods. The CT examinations of 17 patients with at least one persistent subsolid nodule were reviewed. A first non-blinded consensus review by two expert radiologists resulted in the detection of 104 subsolid nodules larger than 3 mm (74 nodules of ground glass attenuation and 30 mixed nodules with solid and ground glass components). The results from this review were used as a gold standard to determine the performances of the CAD system and 3 independent clinical radiologists involved with the primary interpretations. RESULTS: The sensitivity of the CAD system for the detection of ground glass opacities and mixed nodules was 53% and 73% respectively. These values were not statistically different from the values for the 3 independent observers (42-66% for ground glass opacities and 63-80% for mixed nodules). The sensitivity of each observer significantly increased when the nodules detected by the CAD system were added to those detected by each observer (p<0.0001). CONCLUSION: A CAD system has a potential impact on the detection rate of subsolid nodules by radiologists.

Leptin a new biological marker for evaluating malnutrition in elderly patients.

BACKGROUND: There is no single universally accepted biochemical marker of nutritional status in the elderly. Many markers are affected by non-nutritional factors. OBJECTIVE: The purpose of this study was to determine the biological parameters best related to anthropometric markers of malnutrition in an elderly polypathological population, and determine cutoff values for these potential parameters to diagnose malnutrition. DESIGN: This prospective study enrolled 116 elderly hospitalized patients and 76 elderly outpatients. Nutritional status (albumin, transthyretin, body mass index (BMI), skinfold thickness) and biological parameters (leptin, insulin-like growth factor-1 (IGF-1), IGF binding protein-1 (IGFBP-1), IGFBP-3, C-reactive protein (CRP), orosomucoid) were assessed. We defined malnutrition according to the lowest quartile of BMI and skinfold thickness measured in a large healthy elderly French sample population. RESULTS: In this sample of elderly patients (age: 85+/-7 years old), leptin concentration was the only biological parameter significantly related to nutrition status. Independent correlations were found between leptin concentration and BMI, skinfold thickness and sex. The relationship between nutritional status and leptin concentration is significantly different in each sex: the more the patients are undernourished, the lower the leptin concentration in both sexes. The optimal leptin cutoff value for the diagnosis of malnutrition in this population was 4 microg/l in men (sensitivity 0.89, specificity 0.82) and 6.48 microg/l in women (sensitivity 0.90, specificity 0.83). CONCLUSION: Leptin concentration is highly correlated with anthropometric data whereas albumin or transthyretin are known to be also influenced by morbidity and inflammatory conditions. Serum leptin concentration could be used for nutritional assessment in elderly patients with acute diseases.