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Objective: In acute lung injury (ALI) activated protein C (APC) may reopen occluded lung vessels and minimize lung inflammation. We aimed at assessing the effect of APC on regional lung perfusion, aerated lung volume, cytokine production and oxygenation in experimental ALI.Design and Setting: Prospective, controlled study in an imaging facility.Participants: Pigs tracheotomized and mechanically ventilated.Intervention: Pigs were randomly given intravenously APC (n = 8) or saline (n = 8). Thirty minutes later, ALI was induced by injecting oleic acid.Measurements and Results: Lung perfusion and aerated lung volume measured with positron emission tomography, plasma cytokines and arterial blood gas were determined just before ALI and 110 and 290 min thereafter. Lung cytokines were measured at the end of the experiment. PaO2 under F I O2 1 was significantly lower in the APC group before lung injury (473+/-129 vs. 578+/-54 mmHg) and 110 min (342+/-138 vs. 446+/-103 mmHg) and 290 min (303+/-171 vs. 547+/-54 mmHg) thereafter (p < 0.05). Lung perfusion nonsignificantly tended to redistribute towards dorsal lung regions with APC. Total aerated lung volume was not different between APC and control before ALI (10.0+/-1.5 vs. 11.0+/-2.5 ml/kg) (p > 0.05) or thereafter. Plasma IL-6 and IL-8 at 110 min were greater with APC (p < 0.05).Conclusions: In contrast to studies using other models, pretreatment with APC was associated with worsening oxygenation in the present investigation. This might be due to ventilation-perfusion mismatch, with more perfusion to dependent nonaerated areas. [ABSTRACT FROM AUTHOR]

Purpose: Common variable immunodeficiency (CVID) is known to cause infectious, inflammatory, and autoimmune manifestations. Pulmonary hypertension (PH) is an unusual complication of CVID with largely unknown characteristics and mechanisms., Methods: We report the clinical, functional, hemodynamics, radiologic and histologic characteristics, and outcomes of CVID-associated PH patients from the French PH Network., Results: Ten patients were identified. The median (range) age at CVID diagnosis was 36.5 (4-49) years and the median delay between CVID and PH diagnosis was 12 (0-30) years. CVID-associated PH affected predominantly women (female-to-male ratio 9:1). Most patients were New York Heart Association functional class III with a severe hemodynamic profile and frequent portal hypertension (n = 6). Pulmonary function tests were almost normal in 70% of patients and showed a mild restrictive syndrome in 30% of patients while the diffusing capacity for carbon monoxide was decreased in all but one patient. High-resolution computed tomography found enlarged mediastinal nodes, mild interstitial infiltration with reticulations and nodules. Two patients had a CIVD-interstitial lung disease, and one presented with bronchiectasis. Pathologic assessment of lymph nodes performed in 5 patients revealed the presence of granulomas (n = 5) and follicular lymphoid hyperplasia (n = 3). At last follow-up (median 24.5 months), 9 patients were alive, and one patient died of Hodgkin disease., Conclusion: PH is a possible complication of CVID whose pathophysiological mechanisms, while still unclear, would be due to the inflammatory nature of CVID. CVID-associated PH presents as precapillary PH with multiple possible causes, acting in concert in some patients: a portal hypertension, a pulmonary vascular remodeling, sometimes a pulmonary parenchymal involvement and occasionally an extrinsic compression by mediastinal lymphadenopathies, which would be consistent with its classification in group 5 of the current PH classification., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To assess the role of biomarkers of Alzheimer disease (AD), neurodegeneration, and small vessel disease (SVD) as mediators in the association between diabetes mellitus and cognition., Methods: The study sample was derived from MEMENTO, a cohort of French adults recruited in memory clinics and screened for either isolated subjective cognitive complaints or mild cognitive impairment. Diabetes was defined based on blood glucose assessment, use of antidiabetic agent, or self-report. We used structural equation modeling to assess whether latent variables of AD pathology (PET mean amyloid uptake, Aβ 42 /Aβ 40 ratio, and CSF phosphorylated tau), SVD (white matter hyperintensities volume and visual grading), and neurodegeneration (mean cortical thickness, brain parenchymal fraction, hippocampal volume, and mean fluorodeoxyglucose uptake) mediate the association between diabetes and a latent variable of cognition (5 neuropsychological tests), adjusting for potential confounders., Results: There were 254 (11.1%) participants with diabetes among 2,288 participants (median age 71.6 years; 61.8% women). The association between diabetes and lower cognition was significantly mediated by higher neurodegeneration (standardized indirect effect: -0.061, 95% confidence interval: -0.089, -0.032), but not mediated by SVD and AD markers. Results were similar when considering latent variables of memory or executive functioning., Conclusion: In a large clinical cohort in the elderly, diabetes is associated with lower cognition through neurodegeneration, independently of SVD and AD biomarkers., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Background: Superficial oesophageal adenocarcinoma can be resected endoscopically, but data to define a curative endoscopic resection are scarce., Objective: Our study aimed to assess the risk of lymph node metastasis depending on the depth of invasion and histological features of oesophageal adenocarcinoma., Methods: We retrospectively included all patients undergoing an endoscopic resection for T1 oesophageal adenocarcinoma among seven expert centres in France in 2004-2016. Mural invasion was defined as either intramucosal or submucosal tumours; the latter were further divided into superficial submucosal (<1000 mm) and deep submucosal (>1000 mm). Absence or presence of lymphovascular invasion and/or poorly differentiated cancer (G3) defined a low-risk or a high-risk tumour, respectively. For submucosal tumours, invasion depth and histological features were systematically confirmed after a second dedicated histological assessment (new 2-mm thick slices) performed by a second pathologist. Occurrence of lymph node metastasis was recorded during the follow-up from histological or PET CT reports when an invasive procedure was not possible., Results: In total, 188 superficial oesophageal adenocarcinomas were included with a median follow-up of 34 months. No lymph node metastases occurred for intramucosal oesophageal adenocarcinomas (n = 135) even with high-risk histological features. Among submucosal oesophageal adenocarcinomas, only tumours with lymphovascular invasion or poorly differentiated cancer or with a depth of invasion >1000 μm developed lymph node metastasis tumours (n = 10/53%; 18.9%; hazard ratio 12.04). No metastatic evolution occurred under a 1000-mm threshold for all low-risk tumours (0/25), nor under 1200 mm (0/1) and three over this threshold (3/13%, 23.1%)., Conclusion: Intramucosal and low-risk tumours with shallow submucosal invasion up to 1200 mm were not associated with lymph node metastasis during follow-up. In case of high-risk features and/or deep submucosal invasion, endoscopic resections are not sufficient to eliminate the risk of lymph node metastasis, and surgical oesophagectomy should be carried out. These results must be confirmed by larger prospective series., (© 2020 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC. on behalf of United European Gastroenterology.)

Since october 2015, PET/MR has been used extensively for clinical routine in the nuclear medicine department of the Pitié-Salpêtrière Hospital (Paris, France) with a throughput of 11 to 15 patients each day. While many studies have been conducted to investigate dose reduction strategies to patients with hybrid PET/MR devices, no study has focused on staff radiation safety. Knowing that patient positioning within the scanner takes longer in PET/MR than in PET/CT because of the placement of several local MR receive coils, a retrospective study was carried out to measure the radiation doses to nuclear medicine technologists from the patient. The analysis was conducted during one year on 1332 clinical PET/MR studies performed with the Signa PET/MR system (General Electric Healthcare) in our department. The whole-body exposure of the technologist staff was on average for all PET/MR exams10.3 ± 4 nSv per injected MBq of 18 F. When performing brain PET/MR exams only, the whole-body exposure was on average 8.7 ± 2 nSv per injected MBq of 18 F. Brain PET/MR provides lower radiation dose than whole-body examinations for cancer screening due to a lower injected activity (2 vs. 3 MBq kg -1 ) and shorter patient positioning (5 vs. 15 min). When starting PET/MR in a nuclear medicine department, an important step is to optimise patient positionning within the scanner to minimise radiation dose received by the technical staff from patients.

Coxiella burnetii cardiovascular prosthetic infections are associated with high morbidity and mortality and represent a major health problem due to the lack of standardized management. We were confronted with a C. burnetii infection on Bentall-De Bono prosthesis characterized by a history of vascular infection with relapse that prompted us to screen for cases of C. burnetii on Bentall-De Bono vascular prosthesis monitored in our center. We screened patients between 1991 and 2019, from the French national reference center for Q fever. A microbiological criterion in addition to a lesional criterion was necessary to diagnose C. burnetii persistent vascular infection. Two thousand five hundred and eighty two patient were diagnosed with Coxiella burnetii infection and 160 patients with persistent C. burnetii vascular infection prosthesis, 95 of whom had a vascular prosthesis, including 12 with Bentall-De Bono prosthesis. Among patients with persistent C. burnetii prosthetic vascular infection, patients with Bentall-De Bono prostheses were significantly more prone to develop complications such as aneurysm, fistula, and abscess (62 versus 32%, two-sided Chi-square test, p = 0.04). All but one patient were treated with doxycycline and hydroxychloroquine for a mean (± standard deviation) period of 29.4 ± 13.6 months. Among the 12 patients, 5 had cardio-vascular complications, and 5 had prolonged antibiotherapy with doxycycline and hydroxychloroquine. Patients with C. burnetii vascular infection on Bentall-De Bono tend to be at high risk of developing complications (fistula, aneurysm, abscess, death). Surgery is rarely performed. Clinical, serological, and PET scanner imaging follow-up is recommended.

We propose a method for recruiting asymptomatic Amyloid positive individuals in clinical trials, using a two-step process. We first select during a pre-screening phase a subset of individuals which are more likely to be amyloid positive based on the automatic analysis of data acquired during routine clinical practice, before doing a confirmatory PET-scan to these selected individuals only. This method leads to an increased number of recruitments and to a reduced number of PET-scans, resulting in a decrease in overall recruitment costs. We validate our method on three different cohorts, and consider five different classification algorithms for the pre-screening phase. We show that the best results are obtained using solely cognitive, genetic and socio-demographic features, as the slight increased performance when using MRI or longitudinal data is balanced by the cost increase they induce. We show that the proposed method generalizes well when tested on an independent cohort, and that the characteristics of the selected set of individuals are identical to the characteristics of a population selected in a standard way. The proposed approach shows how Machine Learning can be used effectively in practice to optimize recruitment costs in clinical trials.

Lower-respiratory-tract (LRT) amyloidosis has rarely been investigated. Our study presents characteristics, outcomes and survival of LRT amyloidosis. This multicenter retrospective study, from 1995 to 2017, included 73 patients with amyloidosis and LRT involvement. Respiratory patterns were: tracheobronchial (n = 17), nodular (n = 10), interstitial (n = 14) or composite (several respiratory involvements, n = 32). Interstitial and composite patterns were associated with multi-organ amyloidosis (n = 37, 80%) while tracheobronchial and nodular patterns were associated with organ-limited amyloidosis (n = 21, 78%). Amyloid light chain (AL) amyloidosis was diagnosed in 43 patients (59%), mainly of lambda type (n = 33, 77%). Smokers' proportion was higher in tracheobronchial (71%) and nodular (90%) patterns than in interstitial (14%) and composite (34%) patterns. The B-cell neoplasms involved 15 patients (21%), solid neoplasms 8 (11%), connective tissue diseases 8 (11%) and multiple myeloma 6 (8%). The B-cell and solid neoplasms were most prevalent in nodular pattern. Median follow-up was 4.4 years (2.2-8.9). Twenty-four patients died, mostly from respiratory infection. Survival at 1, 5, 10 years was respectively 88%, 70% and 54% for multi-organ amyloidosis, 96%, 89% and 69% for organ-limited amyloidosis (P = .125). Tracheobronchial and nodular patterns survival was better than in other respiratory patterns (P = .039). Death risk factors (multivariate analysis) were: cardiac localization (hazard-ratio [HR] 4.3 [95% confidence interval 1.6-11.5]; P = .004), age (HR 2.1 [1.2-3.7]; P = .008) and dyspnea at diagnosis (HR 4.0 [1.3-12.3]; P = .014). Various LRT amyloidosis patterns depend on smoking habits, organ-limited or multi-organ extension and comorbidities. They are associated with a different survival, which is also predicted by age, cardiac localization and dyspnea at presentation., (© 2019 Wiley Periodicals, Inc.)

Background: The aim of this study was to evaluate tocilizumab (TCZ) as an add-on therapy to glucocorticoids (GC) during the first 3 months of treatment of giant cell arteritis (GCA)., Methods: GCA patients, as defined by ≥3/5 ACR criteria and positive temporal artery biopsy (TAB) or angio-CT-scan or PET-scan-proven aortitis, were included in this prospective open-label study. Prednisone was started at 0.7 mg/kg/day and then tapered according to a standardized protocol. All patients received four infusions of TCZ (8 mg/kg/4 weeks) after inclusion. The primary endpoint was the percentage of patients in remission with ≤0.1 mg/kg/day of prednisone at week 26 (W26). Patients were followed for 52 weeks and data prospectively recorded., Results: Twenty patients with a median (IQR) age of 72 (69-78) years were included. TAB were positive in 17/19 (90%) patients and 7/16 (44%) had aortitis. Remission was obtained in all cases. At W26, 15 (75%) patients met the primary endpoint. Ten patients experienced relapse during follow-up, mainly patients with aortitis (P = 0.048), or CRP >70 mg/L (P = 0.036) or hemoglobin ≤10 g/dL (P = 0.015) at diagnosis. Among 64 adverse events (AE) reported in 18 patients, three were severe and 30, mostly non-severe infections (n = 15) and hypercholesterolemia (n = 8), were imputable to the study., Conclusion: This study shows that an alternative strategy using a short-term treatment with TCZ can be proposed to spare GC for the treatment of GCA. However, 50% of patients experienced relapse during the 9 months following TCZ discontinuation, especially patients with aortitis, or CRP > 70 mg/L or Hb ≤ 10 g/dL at diagnosis., Trial Registration: ClinicalTrials.gov (NCT01910038)., (Copyright © 2018 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Purpose: To assess the localizing value of 18 F-FDG PET in patients operated on for drug-resistant epilepsy due to focal cortical dysplasia type 2 (FCD 2 )., Methods: We analysed 18 F-FDG PET scans from 103 consecutive patients (52 males, 7-65 years old) with histologically proven FCD 2 . PET and MRI data were first reviewed by visual analysis blinded to clinical information and FCD 2 location. The additional value of electroclinical data and PET/MRI coregistration was assessed by comparison with pathological results and surgical outcomes., Results: Visual analysis of PET scans showed focal or regional hypometabolism corresponding to the FCD 2 in 45 patients (44%), but the findings were doubtful or misleading in 37 patients and negative in 21. When considering electroclinical data, positive localization was obtained in 73 patients, and this increased to 85 (83%) after coregistration of PET and MRI data. Under the same conditions, MRI was positive in 61 patients (59%), doubtful in 15 and negative in 27. The additional value of PET was predominant in patients negative or doubtful on MRI, localizing the FCD 2 in 35 patients (83%). Interobserver agreement correlated with the grade of hypometabolism: it was good in patients with mild to severe hypometabolism (82-95%), but moderate in those with subtle/doubtful hypometabolism (45%). The main factors influencing positive PET localization were the grade of hypometabolism and the size of the FCD 2 (P < 0.0001). Misleading location (nine patients) was associated with a small FCD 2 in the mesial frontal and central regions. Following limited cortical resection mainly located in extratemporal areas (mean follow-up 5.6 years), a seizure-free outcome was achieved in 94% of patients, including Engel's class IA in 72%., Conclusion: In this series, 18 F-FDG PET contributed to the localization of FCD 2 in 83% of patients. This high localizing value was obtained by integration of electroclinical data and PET/MRI coregistration. This approach may help improve the surgical outcome in extratemporal epilepsy, even in patients negative on MRI.

Introduction: Although some studies have previously addressed the clinical impact of amyloid positron emission tomography (PET), none has specifically addressed its selective and hierarchical implementation in relation to cerebrospinal fluid analysis in a naturalistic setting., Methods: This multicenter study was performed at French tertiary memory clinics in patients presenting with most complex clinical situations (i.e., early-onset, atypical clinical profiles, suspected mixed etiological conditions, unexpected rate of progression), for whom cerebrospinal fluid analysis was indicated but either not feasible or considered as noncontributory (ClinicalTrials.gov: NCT02681172)., Results: Two hundred five patients were enrolled with evaluable florbetaben PET scans; 64.4% of scans were amyloid positive. PET results led to changed diagnosis and improved confidence in 66.8% and 81.5% of patients, respectively, and altered management in 80.0% of cases., Discussion: High-level improvement of diagnostic certainty and management is provided by selective and hierarchical implementation of florbetaben PET into current standard practices for the most complex dementia cases., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Mastocytosis is a clonal haematological disease characterized by uncontrolled proliferation and the activation of mast cells. The value of FDG-PET/CT (FDG-PET) in mastocytosis has yet to be determined., Methods: We retrospectively identified patients with an established diagnosis of systemic mastocytosis (SM), according to the WHO criteria, who underwent PET using the French Reference Centre for Mastocytosis database. Semi-quantitative and visual analysis of FDG-PET was performed and compared to the clinico-biological data., Results: Our cohort included 19 adult patients, median age 65 years [range 58-74], including three with smouldering SM (SSM), three with aggressive SM (ASM), 10 with an associated clonal haematological non-mast-cell lineage disease (SM-AHNMD), and three with mast cell sarcoma (MCS). FDG-PET was performed at the time of the SM diagnosis (15/19), to evaluate lymph node (LN) activity (3/19) or the efficacy of therapy (1/19). FDG uptake was observed in the bone marrow (BM) (9/19, 47%), LN (6/19, 32%), spleen (12/19, 63%), or liver (1/19, 5%). No significant FDG uptake was observed in the SSM and ASM patients. A pathological FDG uptake was observed in the BM of 6/10 patients with SM-AHNMD, appearing as diffuse and homogeneous, and in the LN of 5/10 patients. All 3 MCS patients showed intense and multifocal BM pathological uptake, mimicking metastasis. No correlation was found between the FDG-PET findings and serum tryptase levels, BM mast cell infiltration percentage, and CD30 and CD2 expression by mast cells., Conclusions: FDG uptake does not appear to be a sensitive marker of mast cell activation or proliferation because no significant FDG uptake was observed in most common forms of mastocytosis (notably purely aggressive SM). However, pathological FDG uptake was observed in the SM-AHNMD and in MCS cases, suggesting a role of FDG-PET in their early identification and as a tool of therapeutic assessment in this subgroup of patients.

Background: Aggressive histopathologic subtypes of differentiated thyroid cancer (DTC) are fluorodeoxyglucose (FDG)-avid tumors and are at high risk for persistent/recurrent disease. In these patients, fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) is performed in cases of suspicion of recurrence based on thyroglobulin (Tg) levels or thyroglobulin antibodies (TgAb). The goals of this study were to evaluate the sensitivity of systematic postoperative FDG-PET/CT and to identify risk factors for abnormal FDG-PET/CT., Methods: Single-center retrospective study of 38 consecutive patients (16 males, 22 females; mean age, 57 years) with aggressive histology DTC, without known persistent disease at the time of postoperative radioactive iodine (RAI) ablation. The most frequent aggressive histologic subtypes were tall cell papillary carcinoma (45%) and poorly differentiated carcinoma (42%)., Results: A total of 86 lesions were found in 20 (53%) patients, distributed in 33 organs. FDG-PET/CT and the postablation whole-body scan (RAI WBS) showed persistent disease in 15 and 12 patients, respectively. FDG-PET/CT was more sensitive than WBS for the detection of individual lesions (69% vs. 59%). Both imaging techniques were complementary with 41% of the lesions detected only by FDG-PET/CT and 31% only by RAI WBS. The only risk factor of abnormal FDG-PET/CT was a stimulated Tg level (Tg/TSH) measured at ablation >10 ng/mL with persistent disease showing FDG uptake in 72% of the patients with a Tg/TSH >10 ng/mL and in 10% of the patients with Tg/TSH ≤10 ng/mL., Conclusion: Postoperative FDG-PET/CT should be performed routinely in patients with aggressive histology DTC.

This pilot study was designed to assess the efficacy of low-frequency repetitive transcranial magnetic stimulation (rTMS) over the right orbitofrontal cortex (OFC) by means of a double-cone coil in patients suffering from obsessive-compulsive disorder. We hypothesized that low-frequency stimulation of the OFC would lead to a reduction in clinical symptoms, as measured on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). A randomized, double-blind, crossover design was implemented with two 1-week treatment periods (active stimulation versus sham stimulation) separated by a 1-month washout period. Concomitantly, a subgroup of patients underwent a positron emission tomography (PET) scan after each stimulation sequence. Statistical analyses compared the Y-BOCS scores at the end of each period. At day 7, we observed a significant decrease from baseline in the Y-BOCS scores, after both active (P<0.01) and sham stimulation (P=0.02). This decrease tended to be larger after active stimulation than after sham stimulation: -6 (-29, 0) points versus -2 (-20, 4) points (P=0.07). Active versus sham PET scan contrasts showed that stimulation was related to a bilateral decrease in the metabolism of the OFC. The OFC should definitely be regarded as a key neuroanatomical target for rTMS, as it is easier to reach than either the striatum or the subthalamic nucleus, structures favored in neurosurgical approaches.

Osteoarticular infection is an uncommon presentation of Q fever. Positron emission tomography (PET) scanning is a valuable tool for the diagnosis of Coxiella burnetii graft prosthesis infection and endocarditis. Our objective was to test a series of culture-negative osteoarticular samples using molecular assays for Coxiella burnetii. We tested for C. burnetii by molecular assays targeting the IS1111 and the IS30A spacer regions, using culture-negative osteoarticular samples obtained in our laboratory between January 2011 and December 2012. We examine a total of 1,410 osteoarticular samples, and we observed two cases of arthritis and subacromial bursitis caused by C. burnetii. The infections were localized using PET scanning, and the diagnosis was confirmed through serology. For one, a C. burnetii strain with a multispacer sequence type 8 genotype was isolated from synovial fluid culture. Q fever articular infections could be undiagnosed because of the long evolution of articular attack, and patients with high antibody titers against C. burnetii should be tested using PET scanning to localize the site of infection.

Objective: To evaluate the potential of (18)F-fluoro-deoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) for early therapeutic intervention in patients with probable or confirmed tuberculosis (TB)., Methods: Twenty-one consecutive human immunodeficiency virus negative patients were prospectively included. All patients underwent (18)F-FDG PET/CT before and after 1 month of anti-tuberculosis treatment. The maximum standardised uptake value (SUV(max)) of the most (18)F-FDG avid lesions was recorded., Results: The median age of patients was 36 years (range 18-84); 33.3% were male, 80.9% were born in endemic countries, and 23.8% had a past history of TB. TB was confirmed on culture in 8, on histology in 9 and on the basis of clinical symptoms in 4 patients. (18)F-FDG PET/CT detected active pulmonary TB (n = 1), extra-pulmonary (n = 10) or both (n = 10). The second (18)F-FDG PET/CT showed reduced radiotracer uptake intensity in 19 of 21 patients, with a median percentage decrease of SUV(max) of 31% (range 2-84). Two patients showed no improvement. TB was ruled out in one patient during follow-up; the final diagnosis was a non-Hodgkin's lymphoma. The other patient was smear-positive for 3 months., Conclusion: (18)F-FDG PET/CT allows an easy evaluation of early therapeutic response in patients with TB, particularly extra-pulmonary TB.

There is evidence for the interest of (18)F-fluoro-deoxyglucose positron emission tomography with computed tomography ((18)F-FDG-PET/CT) in fever of unknown origin (FUO) clinical investigation. However, little and conflicting data exist about its place in the investigation procedure. The aim of this work was to evaluate the clinical value of (18)F-FDG-PET/CT in patients with FUO and identify patients who need early (18)F-FDG-PET/CT rather than a last-resort procedure. We performed a 2-year retrospective cohort study at the Nîmes University Hospital, France. A total of 79 patients (36 men, 43 women, mean age 54.0 ± 16.2 years) with FUO underwent (18)F-FDG-PET/CT. A final diagnosis was established in 61 (77.2 %) cases. Aetiologies of FUO were determined using (18)F-FDG-PET/CT findings in 45 (73.8 % of patients with diagnosis) cases. The sensibility and specificity value were 98 % and 87 %, respectively. The presence of adenopathy, low haemoglobin and increased C-reactive protein (CRP) were predictors of high-yield (18)F-FDG-PET/CT. (18)F-FDG-PET/CT may help to detect most causes of FUO. The predictors of high-yield (18)F-FDG-PET/CT found in this study can help identify patients likely to benefit from specific and early imaging techniques.

Objectives: To determine the quantitative parameters of DCE-US for predicting early functional response of patients with metastatic gastrointestinal stromal tumors (GIST)., Materials and Methods: Phase II multicentre clinical trial in patients with metastatic GIST treated with masatinib mesylate (7.5 mg/kg daily by oral route) Patients followed using three different imaging techniques: 1) DCE-US before treatment and on days 1, 7, 15 and after 1, 2, 4, 6 months and every 3 months. 2) CT assessments, using RECIST criteria, before treatment, after 2, 4, 6 months and then every 3 months. 3) FDG PET before treatment and after 1 month., Results: Twenty patients included and followed-up for up to 36 months, with 269 DCE-US examinations performed. No significant changes in the 7 selected DCE-US variables on day 1 and 7 vs baseline. On day 15, significant reductions in all the variables related to blood volume recorded: area under the curve (AUC) (p = 0. 004), area under the wash-in (AUWI) (p = 0.002), area under the wash-out (AUWO) (p = 0.002) and Peak Intensity (p = 0.005). Also slope of wash-in changed significantly (p = 0.003). An important reduction in Standard Uptake Values (SUV) recorded in 7/11 patients (PFS >18 months). Decrease in DCE-US AUC, AUWI and AUWO values on day 7 were predictive of PET-CT results., Conclusions: AUC AUWI, AUWO are the DCE-US parameters related to blood volume that at D 15 can predict the response of GISTs to treatment with masatinib. Additional studies are ongoing.

Skin-brain signalling in itch reactions has been demonstrated with neuroimaging techniques showing specific brain activation. With positron emission tomography (PET), the itch model used must be adapted to technical and practical constraints. The technique of itch induction by histamine iontophoresis enables modulation of the sensation via the electrical charge applied. This itch model was validated on normal forearm skin of 56 subjects, with itch visual analogue scores peaking to approximately 1.0 cm after 3-4 min, falling to 0.2 cm at 15 min, with no influence of sex, zone, or order. Subsequently, the model was used in a PET study on 14 male volunteers, comparing histamine with physiological saline (control). The results show that the brain is able to discriminate these two conditions, with activated areas similar to those described previously, with, in addition, the anterior cingulate cortex and the insula being positively correlated with the intensity of the sensation.

Takayasu arteritis (TA) is an uncommon large-vessel arteritis. We report our French single-center experience in the management of patients with TA (Pitié-Salpêtrière Hospital, Paris). TA is diagnosed in patients presenting with a large-vessel arteriopathy, in whom several inflammatory and non-inflammatory differential diagnoses are ruled out by appropriate investigations. Treatment of active disease is primarily based on corticosteroids but other immunosuppressive drugs are frequently needed. Anti-platelets agents, statins and antihypertensive drugs are frequently considered. There is no validated disease activity criterion in TA; thus, we generally consider the disease as being active in the presence of the following criteria: firstly, the presence of constitutional or ischemic symptoms; secondly, the increased acute phase reactants; thirdly, the mural contrast enhancement in CT-scan or fourthly, the mural contrast enhancement or signal abnormalities in MRI; fifthly, the abnormal vascular uptake in PET-scan. When TA is active, our follow-up recommendation is to perform an ultrasonography of the supra-aortic vessels and an aortic MRI or CT-scan twice a year. When TA appears to be inactive, we recommend to perform these investigations once a year. Surgical treatment of TA is limited to a few indications. The overall prognosis of TA is good but the quality of life is altered. Management of TA patients is difficult because of the lack of reliable diagnostic criteria, consensual therapeutic strategies and validated disease activity criteria. Further studies should focus on the pathogenesis of the disease and help define better disease activity criteria., (2009 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.)

Human alveolar echinococcosis is a parasitic zoonosis with intermediate (rodents and small lagomorphs) and final (carnivores) hosts. The latter can transmit the parasite to humans, by their feces, which are contaminated by the oncospheres of Echinococcus multilocularis, the larvae of which develop in the liver like a slow cancer. Political, socioeconomic, and ecological factors can affect the intermediate and final hosts and thus influence the long-term emergence and stability of endemic areas. The past 20 years have been marked by: Epidemiologic changes: discovery of an endemic area in China, the largest in the world; extension of the European endemic range to the east and north; extension of the French endemic range to the west and south; and the settlement of contaminated foxes in urban centers, which will modify the populations at risk over time. Progress in diagnosis: initial use of liver ultrasound to screen for asymptomatic disease; value of magnetic resonance imaging to confirm diagnosis and assess extension of disease before beginning treatment; mastery of immunological and genetic diagnosis; and the introduction of positron emission tomography combined with computed tomography to assess the functional activity of the lesions and monitor treatment. Consensus has defined the main directions of a multidisciplinary treatment approach: radical liver resection when possible; avoidance of palliative surgical procedures; use of interventional radiology or endoscopy to treat biliary and vascular complications, whenever possible; consideration of liver transplantation only when all other treatment possibilities have been exhausted; and treatment of all patients, without exception, by albendazole for at least two years after radical surgery and long term (at least several years) in other cases. In France, survival and quality of life have improved very substantially, due to earlier diagnosis, clinical classification of cases, and rigorous follow-up as part of the FrancEchino network. Better understanding of the immunological and immunogenetic mechanisms that underlie the course of disease may open up the possibility of immunomodulation that could replace or round out the current treatments. These are far from satisfactory, in view of the constraints of prolonged, most often life-long treatment by benzimidazoles and their side effects., (Copyright 2009. Published by Elsevier Masson SAS.)

Purpose: The aim of this study was to evaluate the prognostic factors and morbidities of patients undergoing completion surgery for locally advanced-stage cervical cancer after initial chemoradiation therapy (CRT)., Patients and Methods: Patients fulfilling the following inclusion criteria were studied: stage IB2-IVA cervical carcinoma, tumor initially confined to the pelvic cavity on conventional imaging, pelvic external radiation therapy with delivery of 45 Gy to the pelvic cavity and concomitant chemotherapy (cisplatin, 40 mg/m(2) per week) followed by uterovaginal brachytherapy, and completion surgery after the end of radiation therapy including at least a hysterectomy., Results: One-hundred fifty patients treated in 1998-2007 fulfilled the inclusion criteria. Prognostic factors for overall survival in the multivariate analysis were the presence and level of nodal spread (positive pelvic nodes alone: hazard ratio [HR], 2.03; positive para-aortic nodes: HR, 5.46; p < .001) and the presence and size of residual disease (RD) in the cervix (p = .02). Thirty-seven (25%) patients had 55 postoperative complications. The risk for complications was higher with a radical hysterectomy (p = .04) and the presence of cervical RD (p = .01)., Conclusion: In this series, the presence and size of RD and histologic nodal involvement were the strongest prognostic factors. Such results suggest that the survival of patients treated using CRT for locally advanced cervical cancer could potentially be enhanced by improving the rate of complete response in the irradiated area (cervix or pelvic nodes) and by initially detecting patients with para-aortic spread so that treatment could be adapted in such patients. The morbidity of completion surgery is high in this context.

Background: Previous studies showed that at the individual level, positron emission tomography (PET) has some benefits for patients and physicians in terms of cancer management and staging. We aimed to describe the benefits of (PET) in the management of solitary pulmonary nodules (SPNs) in a population level, in terms of the number of diagnostic and invasive tests performed, time to diagnosis and factors determining PET utilization., Methods: In an observational study, we examined reports of computed tomography (CT) performed and mentioning "spherical lesion", "nodule" or synonymous terms. We found 11,515 reports in a before-PET period, 2002-2003, and 20,075 in an after-PET period, 2004-2005. Patients were followed through their physician, who was responsible for diagnostic management., Results: We had complete data for 112 patients (73.7%) with new cases of SPN in the before-PET period and 250 (81.4%) in the after-PET period. Patients did not differ in mean age (64.9 vs. 64.8 years). The before-PET patients underwent a mean of 4 tests as compared with 3 tests for the after-PET patients (p = 0.08). Patients in the before-PET period had to wait 41.4 days, on average, before receiving a diagnosis as compared with 24.0 days, on average, for patients in the after-PET period who did not undergo PET (p < 0.001). In the after-PET period, 11% of patients underwent PET during the diagnostic process. A spiculated nodule was more likely to determine prescription for PET (p < 0.001). Multivariate analysis revealed that patients in both periods underwent fewer tests when PET was prescribed by general practitioners (p < 0.001) and if the nodule was not spiculated (p < 0.001). The proportion of unnecessary invasive approaches prescribed (47% vs. 49%) did not differ between the groups., Conclusion: In our study, 1 year after the availability of PET, the technology was not the first choice for diagnostic management of SPN. Even though we observed a tendency for reduced number of tests and mean time to diagnosis with PET, these phenomena did not fully relate to PET availability in health communities. In addition, the availability of PET in the management of SPN diagnosis did not reduce the overall rate of unnecessary invasive approaches.

Purpose: This study was aimed at establishing a list of radionuclides of interest for nuclear medicine that can be produced in a high-intensity and high-energy cyclotron., Methods: We have considered both therapeutic and positron emission tomography radionuclides that can be produced using a high-energy and a high-intensity cyclotron such as ARRONAX, which will be operating in Nantes (France) by the end of 2008. Novel radionuclides or radionuclides of current limited availability have been selected according to the following criteria: emission of positrons, low-energy beta or alpha particles, stable or short half-life daughters, half-life between 3 h and 10 days or generator-produced, favourable dosimetry, production from stable isotopes with reasonable cross sections., Results: Three radionuclides appear well suited to targeted radionuclide therapy using beta ((67)Cu, (47)Sc) or alpha ((211)At) particles. Positron emitters allowing dosimetry studies prior to radionuclide therapy ((64)Cu, (124)I, (44)Sc), or that can be generator-produced ((82)Rb, (68)Ga) or providing the opportunity of a new imaging modality ((44)Sc) are considered to have a great interest at short term whereas (86)Y, (52)Fe, (55)Co, (76)Br or (89)Zr are considered to have a potential interest at middle term., Conclusions: Several radionuclides not currently used in routine nuclear medicine or not available in sufficient amount for clinical research have been selected for future production. High-energy, high-intensity cyclotrons are necessary to produce some of the selected radionuclides and make possible future clinical developments in nuclear medicine. Associated with appropriate carriers, these radionuclides will respond to a maximum of unmet clinical needs.