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Purpose: To determine whether 2D or 3D Choi and modified Choi (mChoi) criteria could assess the efficacy of everolimus against metastatic renal cell carcinoma (mRCC).Methods: RECIST-1.1, Choi, and mChoi criteria were applied retrospectively to analyse baseline and 2-month contrast-enhanced computed tomography (CECT) images in 48 patients with mRCC enrolled in the everolimus arm of the French randomized double-blind multicentre phase III trial comparing everolimus versus placebo (RECORD-1). The primary endpoint was centrally reviewed progression-free survival (PFS) calculated from the initial RECORD-1 analysis. Mean attenuation was determined for 2D target lesion regions of interest drawn on CECT sections whose largest diameters had been measured, and for the 3D whole target lesion.Results: The median PFS was 5.5 months. The median PFS for everolimus responders defined using 3D mChoi criteria was significantly longer than for non-responders (7.6 versus 5.4 months, respectively), corresponding to a hazard ratio for progression of 0.45 (95 % CI: 0.22-0.92), with respective 1-year survival rates of 31 % and 9 %. No other 2D or 3D imaging criteria at 2 months identified patients who would benefit from everolimus.Conclusions: At 2 months, only 3D mChoi criteria were able to identify mRCC patients with a PFS benefit from everolimus.Key Points: Choi criteria could not identify everolimus-treated patients with significantly prolonged PFS. mCHOI enabled identification of everolimus-treated mRCC patients with a PFS benefit. 3D attenuation measurement criteria appeared to perform better than single-slice measurement. [ABSTRACT FROM AUTHOR]

Introduction: This article is a summary of the French intergroup guidelines regarding the management of non-metastatic colon cancer (CC), revised in November 2022., Methods: These guidelines represent collaborative work of all French medical and surgical societies involved in the management of CC. Recommendations were graded in three categories (A, B, and C) according to the level of evidence found in the literature published up to November 2022., Results: Initial evaluation of CC is based on clinical examination, colonoscopy, chest-abdomen-pelvis computed tomography (CT) scan, and carcinoembryonic antigen (CEA) assay. CC is usually managed by surgery and adjuvant treatment depending on the pathological findings. The use of adjuvant therapy remains a challenging question in stage II disease. For high-risk stage II CC, adjuvant chemotherapy must be discussed and fluoropyrimidine monotherapy or oxaliplatin-based chemotherapy proposed according to the type and number of poor prognostic features. Oxaliplatin-based chemotherapy (FOLFOX or CAPOX) is the current standard for adjuvant therapy of patients with stage III CC. However, these regimens are associated with significant oxaliplatin-induced neurotoxicity. The results of the recent IDEA study provide evidence that 3 months of treatment with CAPOX is as effective as 6 months of oxaliplatin-based therapy in patients with low-risk stage III CC (T1-3 and N1). A 6-month oxaliplatin-based therapy remains the standard of care for high-risk stage III CC (T4 and/or N2). For patients unfit for oxaliplatin, fluoropyrimidine monotherapy is recommended., Conclusion: French guidelines for non-metastatic CC management help to offer the best personalized therapeutic strategy in daily clinical practice. Each individual case must be discussed within a multidisciplinary tumor board and then the treatment option decided with the patient., Competing Interests: Conflict of interest T. Lecomte: Amgen, Merck Serono, Pierre Fabre, and Servier. D. Tougeron: Amgen, Merck Serono, Pierre Fabre, Servier, MSD, BMS, Astra Zeneca, Sanofi, and Roche. F. Bibeau: Astellas, Astra-Zeneca, BMS, Incyte, MSD, Pierre Fabre, and Sanofi. R. Cohen: MSD Oncology, Pierre Fabre, Bristol-Myers Squibb, Mylan Medical, Servier, Exeliom Biosciences, and Enterome Bioscience. T. Aparicio: MSD, Pierre Fabre, BMS, Servier, and Amgen. O. Bouché: Amgen, Apmomia Therapeutics Bayer, Grunenthal, Merck KGaA, MSD, Pierre Fabre, and Servier. The other authors have reported no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Excess visceral fat (VF) or high body mass index (BMI) is risk factors for severe COVID-19. The receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is expressed at higher levels in the VF than in the subcutaneous fat (SCF) of obese patients., Aim: To show that visceral fat accumulation better predicts severity of COVID-19 outcome compared to either SCF amounts or BMI., Methods: We selected patients with symptomatic COVID-19 and a computed tomography (CT) scan. Severe COVID-19 was defined as requirement for mechanical ventilation or death. Fat depots were quantified on abdominal CT scan slices and the measurements were correlated with the clinical outcomes. ACE 2 mRNA levels were quantified in fat depots of a separate group of non-COVID-19 subjects using RT-qPCR., Results: Among 165 patients with a mean BMI of 26.1 ± 5.4 kg/m 2 , VF was associated with severe COVID-19 (p = 0.022) and SCF was not (p = 0.640). Subcutaneous fat was not different in patients with mild or severe COVID-19 and the SCF/VF ratio was lower in patients with severe COVID-19 (p = 0.010). The best predictive value for severe COVID-19 was found for a VF area ≥128.5 cm 2 (ROC curve), which was independently associated with COVID-19 severity (p < 0.001). In an exploratory analysis, ACE 2 mRNA positively correlated with BMI in VF but not in SCF of non-COVID-19 patients (r 2  = 0.27 vs 0.0008)., Conclusion: Severe forms of COVID-19 are associated with high visceral adiposity in European adults. On the basis of an exploratory analysis ACE 2 in the visceral fat may be a trigger for the cytokine storm, and this needs to be clarified by future studies., Competing Interests: Declaration of competing interest None for any of the authors., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To evaluate the diagnostic performance of the initial chest CT to diagnose COVID-19 related pneumonia in a French population of patients with respiratory symptoms according to the time from the onset of country-wide confinement to better understand what could be the role of the chest CT in the different phases of the epidemic., Material and Method: Initial chest CT of 1064 patients with respiratory symptoms suspect of COVID-19 referred between March 18th, and May 12th 2020, were read according to a standardized procedure. The results of chest CTs were compared to the results of the RT-PCR., Results: 546 (51%) patients were found to be positive for SARS-CoV2 at RT-PCR. The highest rate of positive RT-PCR was during the second week of confinement reaching 71.9%. After six weeks of confinement, the positive RT-PCR rate dropped significantly to 10.5% (p<0.001) and even 2.2% during the two last weeks. Overall, CT revealed patterns suggestive of COVID-19 in 603 patients (57%), whereas an alternative diagnosis was found in 246 patients (23%). CT was considered normal in 215 patients (20%) and inconclusive in 1 patient. The overall sensitivity of CT was 88%, specificity 76%, PPV 79%, and NPV 85%. At week-2, the same figures were 89%, 69%, 88% and 71% respectively and 60%, 84%, 30% and 95% respectively at week-6. At the end of confinement when the rate of positive PCR became extremely low the sensitivity, specificity, PPV and NPV of CT were 50%, 82%, 6% and 99% respectively., Conclusion: At the peak of the epidemic, chest CT had sufficiently high sensitivity and PPV to serve as a first-line positive diagnostic tool but at the end of the epidemic wave CT is more useful to exclude COVID-19 pneumonia., Competing Interests: The authors have declared that no competing interests exist.

Background: Since 1920, a decrease in serum cholesterol has been identified as a marker of severe pneumonia. We have assessed the performance of serum apolipoprotein-A1, the main transporter of HDL-cholesterol, to identify the early spread of coronavirus disease 2019 (Covid-19) in the general population and its diagnostic performance for the Covid-19., Methods: We compared the daily mean serum apolipoprotein-A1 during the first 34 weeks of 2020 in a population that is routinely followed for a risk of liver fibrosis risk in the USA (212,297 serum) and in France (20,652 serum) in relation to a local increase in confirmed cases, and in comparison to the same period in 2019 (266,976 and 28,452 serum, respectively). We prospectively assessed the sensitivity of this marker in an observational study of 136 consecutive hospitalized cases and retrospectively evaluated its specificity in 7,481 controls representing the general population., Results: The mean serum apolipoprotein-A1 levels in the survey populations began decreasing in January 2020, compared to the same period in 2019. This decrease was highly correlated with the daily increase in confirmed Covid-19 cases in the following 34 weeks, both in France and USA, including the June and mid-July recovery periods in France. Apolipoprotein-A1 at the 1.25 g/L cutoff had a sensitivity of 90.6% (95%CI84.2-95.1) and a specificity of 96.1% (95.7-96.6%) for the diagnosis of Covid-19. The area under the characteristics curve was 0.978 (0.957-0.988), and outperformed haptoglobin and liver function tests. The adjusted risk ratio of apolipoprotein-A1 for survival without transfer to intensive care unit was 5.61 (95%CI 1.02-31.0; P = 0.04)., Conclusion: Apolipoprotein-A1 could be a sentinel of the pandemic in existing routine surveillance of the general population. NCT01927133, CER-2020-14., Competing Interests: TP has several USPTO patents related to the performance of Apoa1 in patients with liver disease, including #10,198,552 Method of diagnosis of fibrotic diseases, #7,860,656 Diagnosis method of hepatic steatosis using biochemical markers, 7,856,319, Diagnosis method of alcoholic steato-hepatitis using biochemical markers, #7,225,080 Diagnosis method of inflammatory, fibrotic or cancerous disease using biochemical markers, and # 6,631,330 Diagnosis method of inflammatory, fibrotic or cancerous disease using biochemical markers, and applications pending: #20200011879 Method of diagnosis of drug induced liver injury, 20190265241 Method of diagnosis of non-alcoholic fatty liver diseases, #3 20140329260 Method of diagnosis of fibrotic diseases, and #20090111132 Diagnosis method of hepatic steatosis using biochemical markers. The data underlying the findings described in the manuscript are fully detailed including the confounding factors, without restriction, in the numerous supplementary files. The commercial affiliation does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Although the FibroTest has been validated as a biomarker to determine the stage of fibrosis in non-alcoholic fatty liver disease (NAFLD) with results similar to those in chronic hepatitis C (CHC), B (CHB), and alcoholic liver disease (ALD), it has not yet been confirmed for the prediction of liver-related death., Aim: To validate the 10-year prognostic value of FibroTest in NAFLD for the prediction of liver-related death., Method: Patients in the prospective FibroFrance cohort who underwent a FibroTest between 1997 and 2012 were pre-included. Mortality status was obtained from physicians, hospitals or the national register. Survival analyses were based on univariate (Kaplan-Meier, log rank, AUROC) and multivariate Cox risk ratio taking into account age, sex and response to anti-viral treatment as covariates. The comparator was the performance of the FibroTest in CHC, the most validated population., Results: 7082 patients were included; 1079, 3449, 2051, and 503 with NAFLD, CHC, CHB, and ALD, respectively. Median (range) follow-up was 6.0 years (0.1-19.3). Ten year survival (95% CI) without liver-related death in patients with NAFLD was 0.956 (0.940-0.971; 38 events) and 0.832 (0.818-0.847; 226 events; P = 0.004) in CHC. The prognostic value (AUROC / Cox risk ratio) of FibroTest in patients with NAFLD was 0.941 (0.905-0.978)/1638 (342-7839) and even higher than in patients with CHC 0.875 (0.849-0.901; P = 0.01)/2657 (993-6586)., Conclusions: The FibroTest has a high prognostic value in NAFLD for the prediction of liver-related death. (ClinicalTrials.gov number, NCT01927133)., (© 2018 The Authors. Alimentary Pharmacology & Therapeutics Published by John Wiley & Sons Ltd.)

Objectives: Dynamic contrast-enhanced ultrasound (DCE-US) has been used in single-center studies to evaluate tumor response to antiangiogenic treatments: the change of area under the perfusion curve (AUC), a criterion linked to blood volume, was consistently correlated with the Response Evaluation Criteria in Solid Tumors response. The main objective here was to do a multicentric validation of the use of DCE-US to evaluate tumor response in different solid tumor types treated by several antiangiogenic agents. A secondary objective was to evaluate the costs of the procedure., Materials and Methods: This prospective study included patients from 2007 to 2010 in 19 centers (8 teaching hospitals and 11 comprehensive cancer centers). All patients treated with antiangiogenic therapy were eligible. Dynamic contrast-enhanced ultrasound examinations were performed at baseline as well as on days 7, 15, 30, and 60. For each examination, a perfusion curve was recorded during 3 minutes after injection of a contrast agent. Change from baseline at each time point was estimated for each of 7 fitted criteria. The main end point was freedom from progression (FFP). Criterion/time-point combinations with the strongest correlation with FFP were analyzed further to estimate an optimal cutoff point., Results: A total of 1968 DCE-US examinations in 539 patients were analyzed. The median follow-up was 1.65 years. Variations from baseline were significant at day 30 for several criteria, with AUC having the most significant association with FFP (P = 0.00002). Patients with a greater than 40% decrease in AUC at day 30 had better FFP (P = 0.005) and overall survival (P = 0.05). The mean cost of each DCE-US was 180&OV0556;, which corresponds to $250 using the current exchange rate., Conclusions: Dynamic contrast-enhanced ultrasound is a new functional imaging technique that provides a validated criterion, namely, the change of AUC from baseline to day 30, which is predictive of tumor progression in a large multicenter cohort. Because of its low cost, it should be considered in the routine evaluation of solid tumors treated with antiangiogenic therapy.

Objectives: To assess the cost-effectiveness of three colorectal-cancer (CRC) screening strategies in France: fecal-occult-blood tests (FOBT), computed-tomography-colonography (CTC) and optical-colonoscopy (OC)., Methods: Ten-year simulation modeling was used to assess a virtual asymptomatic, average-risk population 50-74 years old. Negative OC was repeated 10 years later, and OC positive for advanced or non-advanced adenoma 3 or 5 years later, respectively. FOBT was repeated biennially. Negative CTC was repeated 5 years later. Positive CTC and FOBT led to triennial OC. Total cost and CRC rate after 10 years for each screening strategy and 0-100% adherence rates with 10% increments were computed. Transition probabilities were programmed using distribution ranges to account for uncertainty parameters. Direct medical costs were estimated using the French national health insurance prices. Probabilistic sensitivity analyses used 5000 Monte Carlo simulations generating model outcomes and standard deviations., Results: For a given adherence rate, CTC screening was always the most effective but not the most cost-effective. FOBT was the least effective but most cost-effective strategy. OC was of intermediate efficacy and the least cost-effective strategy. Without screening, treatment of 123 CRC per 10,000 individuals would cost €3,444,000. For 60% adherence, the respective costs of preventing and treating, respectively 49 and 74 FOBT-detected, 73 and 50 CTC-detected and 63 and 60 OC-detected CRC would be €2,810,000, €6,450,000 and €9,340,000., Conclusion: Simulation modeling helped to identify what would be the most effective (CTC) and cost-effective screening (FOBT) strategy in the setting of mass CRC screening in France., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Introduction: Smoking is highly addictive, and nicotine abstinence is associated with withdrawal syndrome in hospitalized patients. In this study, we aimed to evaluate the impact of sudden nicotine abstinence on the development of agitation and delirium, and on morbidities and outcomes in critically ill patients who required respiratory support, either noninvasive ventilation or intubation, and mechanical ventilation., Methods: We conducted a prospective, observational study in two intensive care units (ICUs). The 144 consecutive patients admitted to ICUs and requiring mechanical ventilation for >48 hours were included. Smoking status was assessed at ICU admission by using the Fagerström Test of Nicotine Dependence (FTND). Agitation, with the Sedation-Agitation Scale (SAS), and delirium, with the Intensive Care Delirium Screening Checklist (ICDSC), were tested twice daily during the ICU stay. Agitation and delirium were defined by SAS >4 and ICDSC >4, respectively. Nosocomial complications and outcomes were evaluated., Results: Smokers (n = 44) were younger and more frequently male and were more likely to have a history of alcoholism and to have septic shock as the reason for ICU admission than were nonsmokers. The incidence of agitation, but not delirium, increased significantly in the smoker group (64% versus 32%; P = 0.0005). Nicotine abstinence was associated with higher incidences of self-removal of tubes and catheters, and with more interventions, including the need for supplemental sedatives, analgesics, neuroleptics, and physical restraints. Sedation-free days, ventilator-free days, length of stay, and mortality in ICUs did not differ between groups. Multivariate analysis identified active smoking (OR, 3.13; 95% CI, 1.45-6.74; P = 0.003) as an independent risk factor for agitation. Based on a subgroup of 56 patients, analysis of 28 pairs of patients (smokers and nonsmokers in a 1:1 ratio) matched for age, gender, and alcoholism status found similar results regarding the role of nicotine withdrawal in increasing the risk of agitation during an ICU stay., Conclusions: Nicotine withdrawal was associated with agitation and higher morbidities in critically ill patients. These results suggest the need to look specifically at those patients with tobacco dependency by using the FTND in ICU settings. Identifying patients at risk of behavioral disorders may lead to earlier interventions in routine clinical practice.

The recent introduction of high-end ultrasound equipment combined with recent contrast agents provides marked improvements in the characterization of focal liver lesions as previously reported by monocentric studies. The aim of the present study was to evaluate the diagnostic performance of Contrast-Enhanced Ultrasonography (CEUS) using SonoVue as well as its medico-economic value for characterization of focal liver lesions. These nodules were not characterized on previous CT or conventional sonography. This prospective multicentric study conducted in 15 French centres found diagnostic performances similar to those reported for CT and MRI, with a concordance rate of 84.5%, sensitivity greater than 80% and specificity greater than 90% for all types of lesions. Higher acceptance was found for CEUS compared to other imaging modalities. Economical assessment based on examination reimbursment and contrast agent cost showed a lower cost for contrast ultrasound versus CT and MRI. This French multicentric study confirmed the high diagnostic value of CEUS for focal liver lesion characterization and demonstrated a lower economical impact compared to other imaging modalities such as CT and MRI.