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Purpose: To evaluate the efficacy and safety of dabrafenib-trametinib-131I for the treatment of radioactive iodine refractory metastatic differentiated thyroid cancer (DTC) with a BRAF p.V600E mutation. Patients and Methods: A prospective phase II trial including patients with RECIST progression within 18 months and no lesion > 3 cm. Following a baseline recombinant human (rh)TSH-stimulated diagnostic whole-body scan (dc1-WBS), dabrafenib and trametinib were given for 42 days. A second rhTSH-stimulated dc WBS (dc2-WBS) was done at day 28 and 131I (5.5 GBq–150 mCi after rhTSH) was administered at day 35. Primary endpoint was the 6-month RECIST objective response rate. In case of partial response (PR) at 6 or 12 months, a second treatment course could be given. Among 24 enrolled patients, 21 were evaluable at 6 months. Results: Abnormal 131I uptake was present on 5%, 65%, and 95% of the dc1-WBS, dc2-WBS, and post-therapy scans, respectively. At 6 months, PR was achieved in 38%, stable disease in 52%, and progressive disease (PD) in 10%. Ten patients received a second treatment course: one complete response and 6 PRs were observed at 6 months. The median progression-free survival (PFS) was not reached. The 12- and 24-month PFS were 82% and 68%, respectively. One death due to PD occurred at 24 months. Adverse events (AE) occurred in 96% of the patients, with 10 grade 3–4 AEs in 7 patients. Conclusions: Dabrafenib-trametinib is effective in BRAF p.V600E-mutated DTC patients for restoring 131I uptake with PR observed 6 months after 131I administration in 38% of the patients.

Waterfall plot of the RECIST response

Quality of Life scores

Purpose:To evaluate the efficacy and safety of dabrafenib-trametinib-131I for the treatment of radioactive iodine refractory metastatic differentiated thyroid cancer (DTC) with a BRAF p.V600E mutation.Patients and Methods:A prospective phase II trial including patients with RECIST progression within 18 months and no lesion > 3 cm. Following a baseline recombinant human (rh)TSH-stimulated diagnostic whole-body scan (dc1-WBS), dabrafenib and trametinib were given for 42 days. A second rhTSH-stimulated dc WBS (dc2-WBS) was done at day 28 and 131I (5.5 GBq–150 mCi after rhTSH) was administered at day 35. Primary endpoint was the 6-month RECIST objective response rate. In case of partial response (PR) at 6 or 12 months, a second treatment course could be given. Among 24 enrolled patients, 21 were evaluable at 6 months.Results:Abnormal 131I uptake was present on 5%, 65%, and 95% of the dc1-WBS, dc2-WBS, and post-therapy scans, respectively. At 6 months, PR was achieved in 38%, stable disease in 52%, and progressive disease (PD) in 10%. Ten patients received a second treatment course: one complete response and 6 PRs were observed at 6 months. The median progression-free survival (PFS) was not reached. The 12- and 24-month PFS were 82% and 68%, respectively. One death due to PD occurred at 24 months. Adverse events (AE) occurred in 96% of the patients, with 10 grade 3–4 AEs in 7 patients.Conclusions:Dabrafenib-trametinib is effective in BRAF p.V600E-mutated DTC patients for restoring 131I uptake with PR observed 6 months after 131I administration in 38% of the patients.

Male hypogonadism is poorly characterized in young-to-middle-aged people with HIV (PWH). We used a reliable free testosterone assay to assess the prevalence and predictive factors for male hypogonadism in PWH on effective combined antiretroviral therapy (cART).A French cross-sectional study from January 2013 to June 2016.We included HIV-1-infected men aged between 18 and 50years with HIV loads of 50 RNA copies/ml or less, on effective cART for at least 6 months. Hypogonadism was defined, according to guidelines, as a mean calculated serum free testosterone concentration less than 70pg/ml (Vermeulen equation). Sociodemographic, anthropo-metric, bone-densitometry, hormonal, immunovirological, metabolic, and therapeutic parameters were collected. The IIEF-5, HAM-D, and AMS scales, respectively, assessed erectile function, depression, and quality of life.Overall, 240 patients were enrolled, 231 were analyzed. Low free testosterone concentrations (70pg/ml) were recorded in 20 patients (8.7%), and were exclusively of secondary origin. In multivariable analysis, the risk factors predictive of male hypogonadism were age more than 43 years [adjusted odds ratio (aOR) 3.17, 95% confidence interval (95% CI) 1.02-9.86; P = 0.04], total fat percentage more than 19% (aOR3.5, 95% CI 1.18-10.37; P = 0.02), and treatment including efavirenz (aOR3.77, 95% CI 1.29-10.98; P = 0.02). A nadir CD4+ T-cell count more than 200 cells / μl (aOR 0.22, 95% CI 0.07-0.65;P 0.01) were protective.Male hypogonadism remains common in young-to-middle-aged PWH with stably suppressed viral replication. Treatment including efavirenz, being over 43 years old, and having a total body fat percentage greater than 19% could be used as criteria for identifying PWH at risk. Early screening for male hypogonadism might improve care by identifying patients requiring testosterone replacement.

Background: Lymph node dissection (LND) in primary treatment of differentiated thyroid carcinoma is controversial. The aim of our retrospective study was to analyse the risk factors of post-thyroidectomy complications and to assess the morbidity of lymph node dissection, especially in the central neck compartment, since prophylactic central lymph node dissection has not been proven to bring an overall survival benefit. Methods: We performed a retrospective analysis of postoperative complications from 1547 consecutive patients with differentiated thyroid carcinoma in an academic department of endocrine surgery over a period of 10 years. Results: A total of 535 patients underwent lymph node dissection, whereas the other 1012 did not. The rate of postoperative hypoparathyroidism was higher in patients with LND (17.6% vs. 11.4%, p = 0.001). No significant difference in the rate of permanent hypoparathyroidism (2.4% vs. 1.3%, p = 0.096) was observed between these two groups. A multivariate analysis was performed. Female gender, ipsilateral and bilateral central LND (CLND), parathyroid autotransplantation, and the presence of the parathyroid gland on the resected thyroid were associated with transient hypoparathyroidism. Bilateral CLND and the presence of the parathyroid gland on specimen were associated with permanent hypoparathyroidism. The rate of transient recurrent laryngeal nerve (RLN) injury (15.3% vs. 5.4%, p < 0.001) and permanent RLN injury (6.5% vs. 0.9%, p < 0.001) were higher in the LND group. In multivariate analysis, ipsilateral and bilateral lateral LND (LLND) were the main predictive factors of transient and permanent RLN injury. Bilateral RLN injury (2.6% vs. 0.4%, p < 0.001), chyle leakage (2.4% vs. 0%, p < 0.001), other nerve injuries (2.2% vs. 0%, p < 0.001), and abscess (2.4% vs. 0.5%, p = 0.001) were higher in the patients with LND. Conclusions: The surgical technique and the extent of lymph node dissection during surgery for thyroid carcinoma increase postoperative morbidity. A wider knowledge of lymph-node-dissection-related complications associated with thyroid surgery could help surgeons to carefully evaluate the surgical and medical therapeutic options.

Background The aim of this study was to evaluate the role of dual isotope 123Iodine/99mTc-MIBI thyroid scintigraphy (IMS) in discriminating between malignant and benign lesions in indeterminate nodules using quantitative analysis methods. Methods Thirty-five consecutive patients with thyroid nodules of indeterminate or non-diagnostic cytology and cold on 123Iodine scintigraphy (10 Bethesda I, 24 Bethesda III-IV, 1 in which cytology was impossible) underwent IMS between 2017 and 2019 with uptake quantification at two time points ahead of thyroidectomy: early and late. Images were analyzed by two blinded physicians. Results Twelve nodules were malignant and 23 benign on histopathology. Mean uptake values were lower in benign than in malignant nodules at both time points: early, 8.7 ± 4.1 versus 12.9 ± 3.5 (P = 0.005); and late, 5.3 ± 2.7 versus 7.7 ± 1.1 (P = 0.008). Interobserver reproducibility was excellent. The intraclass correlation coefficient was 0.86 in benign and 0.92 in malignant lesions for early uptake result (ER) and 0.94 and 0.85 respectively for late uptake result (LR). The optimal LR cut-off to exclude a diagnosis of malignancy was set at 5.9 . The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of this cut-off were, respectively, 100%, 65.2%, 60%, 100% and 77.1%. Conclusion Despite some study limitations, quantitative analysis of 99mTc-MIBI thyroid scintigraphy had a good reproducibility, which could help to rule out malignancy in non-diagnostic or indeterminate thyroid nodules and thereby reducing the number of patients undergoing unnecessary surgery when LR is below 5.9.

Radioactive iodine (131I) therapy may be used to treat thyroid cancer in end-stage renal disease patients who undergo hemodialysis. Because iodine uses predominantly renal clearance, treatment management in hemodialysis patients may be problematic, and no formal recommendations on hemodialysis currently exist. This work details our experience with treating thyroid cancer with iodine in chronic renal failure patients who require hemodialysis and details the dosimetry results obtained during treatment to ensure that the dose to the bone marrow (BM) was acceptable. Methods: We treated 6 patients in the metabolic radiotherapy unit after thyroid stimulation. Two hemodialysis sessions in the metabolic radiotherapy unit were performed at 42 and 90 h after radiopharmaceutical administration. BM toxicity was estimated with activity measurements from blood samples and with whole-body measurements that were regularly repeated during hospitalization and measured with a γ-counter. The patients underwent thyroid and hematologic monitoring to assess treatment efficacy and therapeutic toxicity in the short, medium, and long term. Results: Whole-body activity was reduced on average by 66.7% (range, 60.1%–71.5%) after the first dialysis session and by 53.3% (range, 30.4%–67.8%) after the second. The mean estimated total absorbed dose to the BM was 0.992 Gy for all patients (range, 0.431–2.323 Gy). We did not observe any significant hematologic toxicity, and the clinical, biologic, and ultrasound test results confirmed the success of ablative treatment for most patients. Conclusion: In hemodialysis patients with thyroid cancer, an 131I activity approximately 30% lower than the nominal dose appears to strike an appropriate balance between absence of BM toxicity and therapeutic efficacy. To avoid overirradiation, we recommend pretherapeutic dosimetry studies for metastatic patients to calculate the amount of activity to be administered. We also recommend dosimetry monitoring during the hemodialysis sessions performed after therapeutic dose administration and under the same conditions.

Context Dercum’s disease (DD) and Roch-Leri mesosomatic lipomatosis (LMS) are rare and poorly characteri -zed diseases. The clinical presentation combines multiple lipomas, painful in DD in contrast with LMS, without lipoatrophy. ObjectiveTo identify any specific metabolic and immune phenotype of DD and LMS with the aim to improve their treatment.Design & PatientsThis monocentric retrospective study included 38 patients: 9 DD, 11 LMS and 18 healthy controls. Metabolic and immunohematological characteristics of each group were compared.Results The median age of the patients was similar in the 3 groups (31 years). The number of women, and of basophils, and CD3+, CD4+ and CD8 + T lymphocytes was significantly higher in the DD versus the LMS group, without any difference of the metabolic parameters. Weight, BMI, blood pressure, gamma-GT, leptin, fasting insulin and C-peptide levels, fat mass percentage, and intra/total abdominal fat ratio were significantly higher in each lipomatosis group compared with the control group. Compared with the control group, the DD group had significantly higher fasting blood glucose, LDL-cholesterol, platelets, leukocytes, basophils, and a lower NK cell count, whereas the LMS group had a significantly lower rate of CD3, CD4, and CD8 lymphocytes.ConclusionDD and LMS show a common background of obesity and metabolic phenotype, but a distinct immunohematological profile characterized by a higher number of platelets, leukocytes and basophils in DD patients, an inflammatory profile that could contribute to pain. T lymphocyte depletion was present in LMS. These findings could offer specific therapeutic opportunities, especially for painful DD.NCT0178428

The aim of this study was to evaluate the role of dual isotopeThirty-five consecutive patients with thyroid nodules of indeterminate or non-diagnostic cytology and cold onTwelve nodules were malignant and 23 benign on histopathology. Mean uptake values were lower in benign than in malignant nodules at both time points: early, 8.7±4.1 versus 12.9±3.5 (P=0.005); and late, 5.3±2.7 versus 7.7±1.1 (P=0.008). Interobserver reproducibility was excellent. The intraclass correlation coefficient was 0.86 in benign and 0.92 in malignant lesions for early uptake result (ER) and 0.94 and 0.85 respectively for late uptake result (LR). The optimal LR cut-off to exclude a diagnosis of malignancy was set at 5.9 . The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of this cut-off were, respectively, 100%, 65.2%, 60%, 100% and 77.1%.Despite some study limitations, quantitative analysis of

In order to explore pituitary adenoma (PA), magnetic resonance imaging (MRI) remains the cornerstone. However, there are some limitations and MRI can be non-conclusive. The development of additional imaging modalities like nuclear medicine explorations may help to confirm PA diagnosis, guide management and follow up. Nuclear medicine uses radiopharmaceuticals for imaging with single photon emission computed tomography (SPECT), or positron emission tomography (PET), coupled to CT scan. Radiopharmaceuticals products target specific cellular elements which allow to explore several biological pathways. Nuclear medicine may also be used for therapeutic purposes and recent developments of approach based on Peptide Receptor Radionuclide Therapy (PRRT) for treatment of aggressive PA and pituitary carcinoma will be reviewed. Several radiotracers have been studied in the context of PA, and the aim of this paper is to discuss their respective performances and clinical interest.

Background: Lipomatosis is a condition in which multiple lipomas are present on the body. Different entities which are accompanied by multiple lipomas include Proteus syndrome, Cowden syndrome and related disorders due to PTEN gene mutations, MEN1, benign symmetric lipomatosis (Madelung or Launois-Bensaude disease), Dercum’s Disease, familial lipodystrophy, hibernomas, epidural lipomatosis, familial angiolipomatosis, and meso-somatous lipomatosis (LMS) still called Roch-Leri lipomatosis. LMS is characterized by the presence of many discrete, encapsulated lipomas of 2 to 5 cm, painless, at the level of the trunk and forearms. The aim of the present study was to determine the clinico-biological phenotype of LMS, as compared to controls. Patients and methods: In this single-center study (NCT01784289), 18 healthy controls (C) and 11 LMS were included after examining the cohort of 76 patients referred for suspected lipodystrophic syndrome between 2009 and 2019 in the Endocrinology Department of a University Hospital. Clinical (sex, age, weight, BMI, blood pressure (BP), alcohol consumption), metabolic (fasting blood glucose (FBG) and insulin levels, lipid balance, ASAT, ALAT, GammaGT, leptin), immuno-inflammatory (CBC, lymphocyte immunophenotyping), and anthropometric (% of body fat in DEXA, steatosis and intra-abdominal / total abdominal fat ratio (IAF / TAF) in MRI) were evaluated. Results: The following parameters, expressed as % or median, differed significantly between LMS vs. C groups, respectively: weight 100 vs. 69kg (p 5 in 82% of LMS patients and lipomas were localized first to the forearms (82%), then the thighs (73%) and the abdomen (55%). At diagnosis, the age of LMS patients was 20 years old; 55% of the LMS patients had a BMI above 30 and 45% above 25. No patient had excessive alcohol consumption. Five had a history of auto-immuneor inflammatory disease: 1 hyperthyroidism, 1 hypothyroidism, 1 multiple sclerosis, 1 vitiligo, 1 Raynaud syndrome. Conclusion: LMS mainly affects overweight men and is associated with hypertension, hyperinsulinism, increased gammaGT and a decrease in CD3, CD4 and CD8 lymphocytes, suggesting an immune dysregulation, all the more so that 45% had an associated auto-immune/inflammatory disease.

Background: The aim of this study was to determine the frequency and characteristics of bone and joint complications, specifically bone fragility, joint replacement surgery, and arthropathy, in hereditary hemochromatosis (HH) and related factors. Methods: This study was a cross-sectional observational study of 93 patients with HH. Radiographs of the hands, wrists, knees, and ankles were scored for joint space narrowing, erosions and cysts, osteophytes, and chondrocalcinosis. Prevalent (vertebral and non-vertebral) fragility fractures were recorded and bone mineral density (BMD) was systematically evaluated by dual energy X-ray absorptiometry. Bone fragility was defined as (i) a T-score ⩽ −2.5 at any site with or without a prevalent fragility fracture, or (ii) a T-score between −1.0 and −2.5 at any site and a prevalent fragility fracture. Results: The mean age of the patients was 60.0 (11.2) years, and 58.0% of them were men. The frequency of radiographic MCP2–3 arthropathy was 37.6% (95% CI 0.28–0.48). Radiographic MCP2–3 arthropathy was independently associated with older age [OR 1.17 (1.09–1.26) per year, p Discussion: Radiographic MCP2–3 arthropathy was found to occur in 37.6% of patients with HH. The association observed between this form of arthropathy and C282Y homozygosity, male sex, and older age suggests that demographic characteristics and genetic background are likely to be major determinants of this joint disorder and play a more important role than severity of iron overload. Bone fragility was observed in a fifth of the patients with HH, independently of genetic background and severity of iron overload, and was strongly associated with hepatic cirrhosis. Conclusion: Future investigations should focus on pathogenesis and early identification of patients at risk of developing bone and joint complications secondary to HH.

CONTEXT Recombinant human thyrotropin (rhTSH) has been shown to be an effective stimulation method for radioactive iodine (RAI) therapy in differentiated thyroid cancer, including in those with nodal metastases (N1 DTC). OBJECTIVES To demonstrate the noninferiority of rhTSH vs thyroid hormone withdrawal (THW) in preparation to RAI regarding disease status at the first evaluation in the real-life setting in patients with N1 DTC. DESIGN This was a French multicenter retrospective study. Groups were matched according to age ( 5 lymph nodes), and stage (pT1-T2/pT3). RESULTS The cohort consisted of 404 patients pT1-T3/N1/M0 DTC treated with rhTSH (n = 205) or THW (n = 199). Pathological characteristics and initially administrated RAI activities (3.27 ± 1.00 GBq) were similar between the two groups. At first evaluation (6 to 18 months post-RAI), disease-free status was defined by thyroglobulin levels below threshold and a normal ultrasound. Disease-free rate was not inferior in the rhTSH group (75.1%) compared with the THW group (71.9%). The observed difference between the success rates was 3.3% (-6.6 to 13.0); rhTSH was therefore considered noninferior to THW because the upper limit of this interval was

Objectif Decrire le phenotype osseux de patientes FPLD2, un modele d’insulinoresistance hypoleptinemique, contrastant avec l’obesite, modele d’insulinoresistance hyperleptinemique. Patients et methodes Les parametres cliniques (âge, poids, taille, IMC), biologiques (metaboliques, osseux, leptine) et de composition corporelle (masse grasse, maigre, et T-score en DEXA ; graisse intra-abdominale (GIA) et abdominale totale (GT) en IRM) ont ete compares entre 3 groupes de femmes : 20 FPLD2 (mutation LMNA R482) ; 20 obeses dont 8 diabetiques et 11 temoins de poids normal. Resultats Poids, IMC, pourcentage de sujets diabetiques, glycemie et C-peptide a jeun, HbA1c, masses grasses et maigre absolues ou rapportees a la taille au carre, GIA, GT, rapport GIA/GT, leptine, phosphatemie, 25-OH vitamine et osteocalcine differaient significativement entre les 3 groupes. L’âge, la taille, la calcemie, le T-score, la PTH et le crosslaps ne differaient pas. Il existait une correlation negative significative entre osteocalcine et glycemie, C-peptide a jeun, HbA1c, masse maigre, masse maigre/taille2, T-score, GIA, GIA/GT et une correlation positive entre osteocalcine et cross laps. Il n’existait pas de correlation entre osteocalcine et poids, IMC, masse grasse et leptine. Discussion Les FPLD2 differaient des sujets obeses ou temoins par la phosphatemie, l’osteocalcine et le crosslaps plus bas dans les FPLD2, en lien avec un degre d’insulinoresistance et d’adiposite viscerale plus eleves, peut-etre par l’intermediaire du FGF23. L’osteocalcine est donc un marqueur d’insulinoresistance, correle negativement au T-score mais aussi a la masse maigre, soulignant les relations entre os, muscle et insulinoresistance.

La maladie de Dercum et la lipomatose mesosomatique de Roch-Leri, de physiopathologie inconnue, associent des lipomes sans lipoatrophie, douloureux dans le Dercum. Objectif Identifier le phenotype metabolique et immunitaire de ces lipomatoses rares. Materiels et methodes Etude transversale comparant les caracteristiques metaboliques et immunohematologiques de 46 patients: 9 Dercum, 11 Roch-Leri, 18 temoins minces et 8 temoins obeses (NCT0178428). Resultats L’âge median des 4 groupes etait similaire (31 ans). Le nombre de femmes, de lymphocytes basophiles et T (LT) CD3+, CD4+ et CD8+ etait significativement plus eleve chez les « Dercum » compares aux « Roch-Leri », sans difference metabolique. Le poids, l’IMC, la pression arterielle, les medianes de gamma-GT, leptine, insuline a jeun, le pourcentage de graisse et le rapport de graisse intra-abdominale/abdominale totale etaient significativement plus eleves dans les groupes lipomatoses compares aux temoins minces. Les « Dercum » presentaient une glycemie, un cholesterol-LDL, des plaquettes, leucocytes et basophiles significativement plus eleves et un nombre de cellules NK plus faible, que les temoins minces, tandis que les « Roch-Leri » presentaient un taux de LT plus faible. Les basophiles restaient plus eleves chez les Dercum, et les LT plus bas chez les Roch-Leri, que chez les temoins obeses. Discussion Ces lipomatoses partagent un phenotype metabolique commun avec l’obesite mais s’en distinguent au plan immuno-hematologique. L’activation des basophiles, forme mature des mastocytes susceptibles de liberer de la serotonine, pourrait ouvrir de nouvelles perspectives therapeutiques tout particulierement dans le Dercum (Yabut Nat Commun 2020).

Contexte L’insulinome, tumeur neuroendocrine pancreatique rare, parfois multiple, en particulier dans le cadre de la neoplasie endocrinienne multiple de type 1, est a l’origine d’une secretion inappropriee d’insuline, responsable d’hypoglycemies severes. Le traitement curatif est chirurgical. L’exerese de la lesion doit etre ciblee afin d’eviter le risque de diabete secondaire. Sa localisation preoperatoire est donc indispensable. Les examens actuellement realises lors du bilan morphologique preoperatoire ont une sensibilite variable mais ne sont pas specifiques. Objectif Evaluer l’apport de l’imagerie fonctionnelle aux analogues du GLP-1 sur la prise en charge chirurgicale de l’insulinome. Methode De 2000 a 2018, 54 patients ont ete explores chirurgicalement pour suspicion d’insulinome. Le bilan preoperatoire comprenait scanner, echo-endoscopie, IRM, OctreoscanO, echographie, TEP F-DOPA, imagerie aux analogues du GLP-1, TEP 18FDG, SACS et arteriographie. Resultats 54 insulinomes ont ete resequees chez 51 patients, 1 lesion a ete laissee en place devant un rapport benefice/risque defavorable, 1 lesion n’a pas ete retrouvee, 1 patiente presentait une nesidioblastose. La confrontation des examens radiologiques aux resultats anatomopathologique retrouvait des sensibilites bonnes pour le scanner, l’IRM et l’echo-endoscopie (78,6, 84,8 et 89,2 %) mais des specificites moyennes a faible (74,1, 50 et 22,2 %). Seule l’imagerie au GLP-1 avait une bonne sensibilite (88,9 %) et une bonne specificite (100 %). Conclusion Le developpement de nouvelles techniques d’imagerie fonctionnelle comme l’imagerie aux analogues du GLP-1, tres sensible et specifique de l’insulinome, ameliore la chirurgie ciblee de l’insulinome, en particulier en cas de lesions multiples. Sa plus grande disponibilite lui permettrait de devenir l’examen de reference.

Introduction Les metastases osseuses (MO) sont frequentes dans les cancers thyroidiens differencies (CTD). Elles alterent la qualite de vie et representent la principale cause de morbi-mortalite chez ces patients. Les objectifs de cette etude etaient de determiner la survie globale (SG), les facteurs predictifs de survie et de reponse a l’iode chez des patients atteintes de CTD avec MO. Methode 178 patients consecutifs suivis au CHU de Lille et a Gustave Roussy de 1989 a 2015 pour un CTD avec MO ont ete inclus dans cette etude retrospective. Resultats La SG mediane depuis le diagnostic des MO etait de 57 mois (24–93 mois), avec un taux de survie a 5 et 10 ans de 56,5 % et 15,3 % respectivement chez les patients fixant l’iode au niveau des MO, de 28,6 % et 4,8 % chez ceux sans fixation. En analyse multivariee, la SG etait significativement diminuee en cas de fixation des MO en TEP-TDM-FDG (HR : 3,8 ; IC95 %[1,2-11,7], p = 0,0204). Parmi les 145 non refractaires a l’iode au moment du diagnostic des MO, 46 ont presente une reponse complete dont 32 cas avec iode seul, 14 cas avec iode et traitements locoregionaux. La fixation des MO en TEP-TDM-FDG reduit la possibilite d’obtenir une reponse complete a l’iode seul (OR : 5,5 ; IC95 % [0,04-0,8], p = 0,024). Discussion Parmi les patients suivis pour un CTD associe a des MO, la fixation en TEP-TDM-FDG des MO est un facteur pronostique pejoratif pour une reponse complete osseuse a l’iode et pour la SG. Cet examen est indispensable des le diagnostic de MO.

Radioactive iodine (

CYP24A1 gene mutations induce infantile hypercalcemia, with high 1,25(OH)2D contrasting with low PTH levels. The adult phenotype is not well known. Two unrelated adult patients were referred for nephrolithiasis, hypertension, hypercalcemia, hypercalciuria, normal 25-OHD levels, and inappropriate PTH levels (22 to 92pg/mL;N: 15-68) suggesting primary hyperparathyroidism, leading to surgery. Hypercalciuria improved despite persistent hypercalcemia, treated with cinacalcet. The ratio 25-OHD3/24-25-(OH)2D3>100 (N

Thyroglobulin (Tg) is a high molecular weight glycoprotein located mainly in thyroid follicles, where thyroid hormones are synthesized and stored. In patients with differentiated thyroid cancer of follicular origin, serum Tg levels become undetectable following total thyroidectomy and iodine-131 remnant ablation. It is a key biomarker to follow-up patients with differentiated thyroid cancer, in combination with neck ultrasound monitoring. The measurement of Tg in the wash-out of the needle used for fine needle aspiration biopsy is a valuable aid to the diagnosis of lymph node metastasis. The presence of anti-thyroglobulin antibodies affects reliability of Tg results measured in serum or plasma. Systematic investigation of such antibodies is required to validate any Tg assay. Elevated or rising levels of anti-thyroglobulin antibodies can in turn be used as a surrogate tumor marker of thyroid cancer. The development of second-generation Tg assay (automated, highly sensitive) has enabled significant advances in the management of differentiated thyroid cancer: early detection of persistent or recurrent disease and follow-up care simplified in low-risk patients. Testing of serum Tg can also be useful in evaluating other clinical situations such as congenital hypothyroidism, endemic goiter and thyrotoxicosis factitia.

Male hypogonadism is poorly defined in people living with HIV. Using a reliable free-testosterone assay, we examined the prevalence and risk factors of male hypogonadism among people living with HIV on effective antiretroviral therapy. Male hypogonadism was found in 12.4% of patients, twice the rate reported in the general population of the same age. Two risk thresholds, namely 5 years of antiretroviral therapy and 19% total body fat, may help to identify patients at risk.

Introduction Reports of elevated bone mass (EBM) on routine DXA scanning are not infrequent. However, epidemiological studies of EBM are few in number and definition thresholds variable. The purpose of this study was to assess the prevalence and causes of EBM in the general population referred to a single university hospital - catering for a population of 4 million inhabitants - for DXA scanning. Material and methods DXA databases were initially searched for individuals with a bone mineral density (BMD) Z-score ≥+4 at any site in the lumbar spine or hip from April 1st, 2008 to April 30st, 2018. Two Hologic scanners were available at the Lille University Hospital (France). Prevalence of EBM was evaluated, as were causes associated with EBM. Results At the lumbar spine, 18,229 bone density tests were performed in women and 10,209 in men. At the hip, 17,390 tests were performed in women and 9857 in men. The total number of patients who had at least one bone density test was 14,745, of which 64.2% were female. Of these 14,745 patients, 211 had a Z-score ≥+4 at any site, i.e. a prevalence of 1.43% [1.25%-1.64%]. The DXA scans and medical records of 92 men and 119 women with elevated BMD were reviewed to assess causes. An artefactual cause was found in 164 patients (75%) with EBM (mostly degenerative disease of the spine), and an acquired cause of focal EBM was found in only 2 patients, both of whom had sclerotic bone metastases from prostate cancer. An acquired cause of generalized EBM was found in 32 patients (15%), the vast majority of whom had renal osteodystrophy (n = 11), followed by hematological disorders (n = 9; e.g. myeloproliferative syndromes and mastocytosis) and diffuse bone metastases from solid cancer (n = 5). Of the remaining causes, rare hereditary diseases (e.g. osteopetrosis…) and unexplained EBM were found in 10 and 6 cases respectively. Conclusion The prevalence of EBM (Z-score ≥+4 at any site) was 1.43% [1.25%-1.64%]. In nearly all instances (97.1%) the explanation for EBM could be found in the medical record and through conventional investigations. This study suggests that the main cause of EBM is degenerative disease of the spine. Further studies are needed to differentiate artefactual EBM from hereditary or acquired EBM, and to investigate unexplained EBM. Genetic testing may prove useful in elucidating rare unknown causes.

Introduction Les lipomatoses de Dercum et de Roch Leri sont definies par la presence d’au moins 2 lipomes, douloureux dans le Dercum. Objectif Determiner le phenotype de ces lipomatoses en comparaison a des temoins. Patients et methodes Etude cas-temoins retrospective monocentrique (2009-2019) des caracteristiques metaboliques et immuno-hematologiques de 38 patients : 9 Dercum, 11 Roch-Leri et 18 temoins sains de poids normal (PHRC Clin.gov2009-AO-1169-48). Resultats Les groupes de Dercum/Roch-Leri avaient un poids (88/100 vs 69 kgs ; p Conclusion Ces lipomatoses rares sont toutes 2 associees a une obesite et un syndrome metabolique mais leur profil immuno-hematologique differe : activation basophile chez les Dercum, depletion lymphocytaire chez les Roch-Leri suggerant de nouvelles pistes physiopathologiques (Yabut Nat Commun. 2020).

OBJECTIVE Reduced bone mineral density (BMD) is a frequent comorbidity observed in people living with HIV (PLHIV). We aimed to determine the prevalence of reduced BMD and its associated factors among young PLHIV men, virologically controlled by combination antiretroviral therapy (cART). DESIGN A bicentric cross-sectional study. METHODS We selected men, aged less than 50 years, treated by cART, with HIV-RNA less than 50 copies/ml. BMDs of lumbar spine and hip were measured by dual-energy X-ray absorptiometry (DXA). A Z-score at either site between -1.0 and -2.0 or -2 or less defined osteopenia or osteoporosis, respectively. Linear and polytomous logistic regression analyses were performed. RESULTS Among 230 men with a median age of 43 [interquartile range (IQR), 36-47] years, BMI of 23.5 (21.3-25.3) kg/m(2) and median duration of cART of 4.2 (1.7-8.5) years, reduced BMD was diagnosed in 48.3%. In multivariate analyses, BMI decrease was associated with a risk of osteopenia [odds ratio (OR) = 1.17, P

Aim The adipo-myokine irisin regulates energy expenditure and fat metabolism. LMNA-associated familial partial lipodystrophy (FPLD2) comprises insulin resistance, muscle hypertrophy and lipoatrophy. The aim of this study was to investigate whether irisin could be a biomarker of FPLD2. Patients and methods This case control study included 19 FPLD2 subjects, 13 obese non-diabetic (OND) patients and 19 healthy controls (HC) of normal weight (median BMI: 26, 39 and 22 kg/m2, respectively). Serum irisin and leptin levels, body composition (DXA/MRI) and metabolic/inflammatory parameters were compared in these three groups. Results BMI and MRI intra-abdominal fat significantly differed among these three groups, whereas DXA total fat mass and leptin levels were higher in the OND group, but did not differ between HC and FPLD2. Lipodystrophy patients had higher intra-abdominal/total abdominal fat ratios than the other two groups. Irisin levels were higher in FPLD2 and OND patients than in HC (medians: 944, 934 and 804 ng/mL, respectively). However, irisin/leptin ratios and lean body mass percentages were strikingly higher, and lean mass indices lower, in FPLD2 and HC than in the OND (median irisin/leptin ratios: 137, 166 and 21, respectively). In the entire study group, irisin levels positively correlated with BMI, lean body mass and index, intra-abdominal/total abdominal fat ratio, triglyceride, cholesterol, insulin, glucose and HbA1c levels. Also, intra-abdominal/total abdominal fat ratio and lean body mass better differentiated the three groups only in female patients. Conclusion Circulating irisin is similarly increased in FPLD2 and OND patients, who are characterized by higher lean body mass regardless of their clearly different fat mass. However, irisin/leptin ratios, strikingly higher in FPLD2 than in OND patients, could help to make the diagnosis and prompt genetic testing in clinically atypical cases.

Rationale Peptide receptor radionuclide therapy (PRRT) with radiolabeled somatostatin analogs is a targeted internal radiotherapy method used to treat tumors expressing somatostatin receptors. Concomitant amino acids perfusion is systematically performed in order to inhibit the proximal tubular uptake of the radionuclide and thus prevent nephrotoxicity. PATIENT CONCERNS:: a 67-year-old woman with an intestinal neuroendocrine tumor with multiple lymphadenopathies and liver metastases. The patient displayed a carcinoid syndrome with flushes including facial erythrosis and paresthesia. During the treatment, the patient exhibited emesis and severe cramps. Diagnosis We describe incomplete proximal tubulopathy induced by an amino acid therapy with [177Lu]-DOTA0-Tyr3-octreotate, which was reversible after treatment discontinuation. This diagnosis relies on metabolic acidosis, hypophosphatemia due to renal loss, tubular proteinuria and generalized aminoaciduria. Serum creatinine remained stable during and after the procedure. Interventions PRRT with radiolabeled somatostatin analog ([177Lu]-DOTA0-Tyr3-octreotate). In order to prevent PRRT induced nephrotoxicity, we used a solution of 20 amino acids including 22 g/L Lysine and 16.8 g/L Arginine. Metoclopramide was successfully used to control vomiting. During the treatment and at the time of cramps, the blood sample showed hypophosphatemia at 0.3 mmol/L justifying intravenous phosphate supplementation. The cramps disappeared after this infusion. Outcomes Hypophosphatemia with low TmPO4/GFR was observed as well as an increase in β2-microglobulinuria, urinary polyclonal light chains, and amino aciduria involving all amino acids. All these disturbances disappeared the day after the treatment and there was no acute kidney injury after 5 PRRT sessions. Six months after PRRT discontinuation, the patient had neither renal failure nor proximal tubulopathy. Aminoacid induced tubulopathy involves the main ligands of the megalin receptor. It has recently been demonstrated that cilastatin is a megalin inhibitor in the proximal tubule and therefore could represent an attractive alternative to amino acids for this purpose. Lessons This case report is a description of a nephroprotective strategy in which partial, and transient tubulopathy is induced, in order to decrease proximal absorption of a tubulotoxic molecule. This little known strategy could be used to prevent proximal tubular injury caused by others megalin-mediated nephrotoxicity medication.

Aims To investigate the performance of two proposed methods for assessing the prognosis of poorly differentiated thyroid carcinomas (PDTC): the Turin proposal and Hiltzik's histological grade (HHG). This was done using a series of 82 thyroid carcinomas of follicular origin. Results The two methods were able to classify patients accurately into two different prognosis groups. Although the Turin proposal and HHG displayed discrepant cases, they provided similar prognostic information. The Turin proposal gave accurate numbers and thresholds of PTDC criteria (loss of follicular architecture and mitoses, necrosis or convoluted nuclei). One Turin criterion, convoluted nuclei, failed to provide any prognostic value. Hiltzik's histological grade was also a simple and reliable method, allowing detection of tumours with high-grade features (mitosis and/or tumour necrosis), notably some papillary carcinomas that displayed an intermediate prognosis. We show that Ki67 labelling (≥ 4%) was an independent factor and predictor of cause-specific survival. Conclusion With similar performances in predicting prognosis, the Turin proposal and HHG provided complementary results in identifying a larger group of ‘intermediate prognosis’ thyroid carcinomas, which require adequate treatment and follow-up.

Introduction L’etat d’hyperhormonemie thyroidienne est parfois difficilement accessible aux antithyroidiens de synthese (ATS). Ces molecules peuvent conduire d’une part, a des effets hematologiques, certes rares mais graves, et d’autre part, a des urticaires generalisees invalidantes, voire des œdemes de Quincke, ce qui pousse a proposer rapidement un traitement radical, par iratherapie par exemple. On connait l’impact des sels de lithium sur la fonction thyroidienne depuis 1973 : ils entrainent une desiodation de la T4, une diminution du relargage hypothalamique de TRH mais aussi une modulation du relargage de l’iode au niveau thyroidien. Materiel Nous rapportons ici notre etude portant sur 17 patients (16 atteints d’une maladie de Basedow et un d’un goitre multiheteronodulaire toxique) traites par lithium avant et pendant l’iratherapie. L’objectif etait de documenter notre pratique et d’evaluer la rapidite de la remission biologique et clinique de l’hyperthyroidie apres traitement. Resultats Nous avons releve les profils des patients au moment du diagnostic (29 % en euthyroidie, 6 recidives, âge median de 61 ans) ainsi que les indications a l’iratherapie (intolerance grave aux ATS [62,5 %], chirurgie contre-indiquee [11,7 %], inefficacite des traitements [17,6 %], autres [8,2 %]). Certains patients etaient traites de facon concomitante par cholestyramine (58,8 %) et/ou par corticotherapie (29 %). Les effets indesirables ont ete repertories. Nous avons ensuite etudie leur bilan thyroidien a 1, 3 et 6 mois. Le delai moyen d’obtention de l’euthyroidie etait de 6 semaines. Discussion Nos resultats etaient comparables aux donnees de la litterature. Le lithium est une des cles de l’optimisation du traitement des hyperthyroidies compliquees.

Introduction Le SBS est un syndrome lipodystrophique partiel considere comme acquis caracterise par une lipoatrophie cephalothoracique progressive, d’origine mal connue immunologique (complement) ou genetique (LMNB2…). Cette etude avait pour but de preciser le phenotype metabolique du SBS en comparaison a des temoins sains et des syndromes lipodytrophiques partiels familiaux de type 2 (FPLD2) lies a une laminopathie. Patients et methodes Cette etude retrospective monocentrique a compare les parametres metaboliques et anthropometriques (DEXA, IRM) de 6 SBS, 16 femmes FPLD2 et 9 femmes temoins sains appariees pour l’âge. Resultats Cinq femmes et un homme le seul avec C3Nef et nephropathie, tous d’origine caucasienne presentaient un SBS dont quatre, familial. Trois patients avaient un diabete, deux une intolerance, quatre une hypertriglyceridemie, trois une steatose hepatique (10–28 % ; IRM), deux une degenerescence graisseuse musculaire. Les cinq femmes SBS, dont une mutee LMNA , avaient un(e) IMC (29(26–33) vs. 22(20–22)kg/m 2 ; p = 0,0035), glycemie a jeun (0,93(0,91–1,80) vs. 0,83(0,79–0,84)g/L ; p = 0,006), HbA1c (8,7(5,4–12,0) vs. 5(4,9–5,1) % ; p = 0,0098), leptinemie (31(30–32) vs. 10(4–13)ng/mL ; p = 0,002), graisse intra-abdominale (GIA : 122(110–139) vs. 21(19–35)cm 3 ; p = 0,0098), rapport graisse intra-abdominale/abdominale totale (GIA/GAT : 0,39(0,29–0,53) vs. 0,11(0,10–0,18) ; p = 0,0112) et CRP (3(3–4) vs. 0(0)mg/L ; p = 0,0005) augmente(e) compares aux temoins. Lipides, insulinemie et pourcentage de masse grasse (%DEXA) ne differaient pas entre SBS et temoins. Leptinemie (FPLD2 : 6,9(4,4–11,2) ; p = 0,0004) et %DEXA (FPLD2 : 20,7(16,9–27,5) ; p p = 0,0643). Conclusion Le SBS semble plus rare que le FPLD2 et plus souvent familial qu’anterieurement admis. Leptinemie et CRP accrues etaient les meilleurs biomarqueurs des SBS compares aux temoins et FPLD2.

International audience; Forensic medical personnel are at risk of exposure to blood-borne viruses including hepatitis C virus (HCV). The aim of this study was to determine prevalence of HCV markers among a cadaver population at the medicolegal institute in Lille. Seventy-seven consecutive cadavers were screened for antibodies to HCV and for HCV RNA. Positive results were confirmed by an immunoblot assay. Fifty-three cadavers had a histopathologic study. Anti-HCV was detected in 13 (16.9%) and accompanied by HCV RNA in 7 (9%) cases. The rate of HCV RNA detection among seropositive cases was 53.8%. Five cases had histopathologic lesions suggestive of hepatitis. This is the first HCV RNA screening in forensic cadavers. The results highlight the high prevalence rate of HCV cases in medicolegal practice in Lille. All forensic specimens should be treated as potentially infectious and universal precautions should be taken.

Introduction. The diagnosis of non-HIV lipodystrophies is challenging, especially since borderline forms with type 2 diabetes have been described (Strickland Diabetes Care 2013). Aim: to identify the most specific anthropometric and biological parameters enabling to differentiate lipodystrophic from obese and control subjects. Methods. This prospective study (clin.gov 2009-AO-1169-48) included 94 patients divided in 3 groups adjusted for age and gender: 52 lipodystrophic patients (among whom 16 LMNA –mutated lipodystrophies (LDM), 16 non- LMNA mutated partial lipodystrophies (LDNM), and 20 other types of lipodystrophies), 28 obese (O; 12 diabetic (OD) and 16 non-diabetic (OND)) and 14 normal-weighed healthy subjects (C). The anthropometric (DEXA, MRI) characteristics and leptin levels of the patients were recorded. Three ratios were calculated to assess the respective part of fat and lean mass (FM/LM), intra- and whole abdominal fat (IAF/WAF) and adipose tissue function (leptin/WAF). Results. The three groups differed by the FM, LM, IAF, WAF, leptinemia, trunk FM/LM ( P

Background: A diminished or totally blocked IFN-α production in cells from HIV-1-infected patients has been reported. Objective: To investigate the relationship between the decreased in vitro production of IFN-α and the plasma level of HIV-1 RNA. Study design: Whole blood samples of 39 healthy subjects and 44 HIV-1-infected patients were incubated in the presence of Sendai virus for 24 h. IFN-α contained in supernatants was assayed by using an immunochemical method (DELFIA) and by using an antiviral assay. Plasma HIV-1 RNA was measured by the Amplicor HIV-1 monitor test. Results: The levels of IFN-α obtained were significantly lower in cultures from HIV-1 infected patients than in control subjects (P

We investigated the biological properties of interferon (IFN)-alpha produced by Sendai virus (SV)-activated whole blood cultures in 20 patients infected with human immunodeficiency virus (HIV)-1 and 24 healthy controls. Supernatants of cultures were assayed for IFN-alpha by using an immunological method (DELFIA), biological methods and an in-vitro MxA induction assay. The levels of intracellular MxA protein were detected by an immunochemiluminescence assay. The levels of IFN-alpha in patients measured by DELFIA were significantly lower than those in healthy controls (P < 0.0001), but the antiviral activity of IFN-alpha in patients infected with HIV-1 was lower than predicted from DELFIA. The IFN-alpha produced by cells of patients infected with HIV-1 was able to induce MxA protein in human amnions WISH cells but was unable to protect these cells against Vesicular Stomatitis Virus (VSV)-induced cytopathic effects. A relative increased capability to induce the production of MxA protein in vitro was observed with the IFN-alpha contained in culture supernatant of virus-activated whole blood of HIV-1-infected patients with increased levels of MxA in their peripheral blood. These data suggest that biological properties of IFN-alpha produced in the course of HIV-1 infection are different from those observed with IFN-alpha of healthy subjects.

The value of soluble receptor for tumor necrosis factor type II (sTNFRII) as a strong and early predictor of HIV disease progression was suggested. Recently it has been reported that sTNFRII may provide an indication of the HIV load. In this work we focused on the relationship between sTNFRII and HIV burden in 95 HIV-1+ patients without AIDS grouped according to the 1993 classification of the CDC as group A, n = 55, and group B, n = 40. Compared with healthy controls, higher values of sTNFRII were obtained in all groups of HIV-1 infected patients (P0.001), but we found no inverse correlation between sTNFRII and CD4+ lymphocyte counts in CDC group A and B of the disease, and no correlation with log RNA copy number in patients with CD4 T-cell counts499/microl. A correlation was obtained between sTNFRII and the viral load in patients with CD4 T-cell counts ranging from 200 to 499/microl, but only in CDC group B patients (P0.01, n = 26). There was no correlation between the variations of sTNFRII and HIV-1 RNA levels in 19 CDC group A and 15 CDC group B clinically stable patients in the course of a short follow up. The plasma level of sTNFRII do not appear as a valuable surrogate marker of the plasma level of HIV-1 RNA in patients. Further investigations are needed to define the mechanism of the raised level of sTNFRII in HIV-1 infected patients.

Introduction L'irisine, myokine dont la concentration est correlee a la masse maigre (MM), s'eleve a l'effort chez le sujet sain, malgre une association a certains marqueurs d'insulinoresistance (Mantzoros 2014). Une augmentation du volume musculaire est decrite dans les FPLD parallelement a la lipoatrophie sous-cutanee distale (Ji JCEM 214). L'objectif de ce travail est de determiner si l'irisine est un marqueur des FPLD. Materiels et methodes L'irisine a ete dosee chez 20 patients FPLD laminopa-thiques, 19 temoins normoponderaux (T) et 13 obeses non diabetiques (OND), puis correlee aux parametres de composition corporelle evalues par DEXA/IRM, aux parametres metaboliques (glycemie/insuline a jeun, HbA1c, cholesterol total, transaminases, leptine) et inflammatoires (leucocytes CD4, CD8, CRP). Resultats La mediane d'irisine differe entre les trois groupes ( p = 0,007), plus elevee chez les OND ( p =0,001) et les FPLD ( p =0,047) compares aux T, sans difference entre FPLD et OND. L'irisinemie, comparable entre les deux sexes, est correlee positivement a la MM/taille2 ( r =0,51 ; p r =0,45 ; p =0.0008), les triglycerides ( r =0,49 ; p =0,0002), l'insuline ( r =0,42 ; p =0,0026), et plus faiblement au poids ( r =0,38 ; p =0,005), a la MM(g) ( r =0,33 ; p =0,01), la graisse intra-abdominale (GIA) ( r =0,34 ; p =0,01), le GIA/graisse abdominale totale ( r =0,39 ; p =0,0069), la glycemie ( r =0,33 ; p =0,01), l'HbA1c ( r =0,34 ; p =0,01), le cholesterol ( r =0,39 ; p =0,0039), les transaminases ( r =0,33 ; p =0,01). La MM/taille2 differe entre les trois groupes ( p p p =0,037) compares aux T, sans difference entre FPLD et OND. L'irisine n'est correlee ni a la leptine ni aux parametres inflammatoires. Conclusion L'irisine est elevee en cas d'augmentation de la mm, independamment de la MG. Couplee a la leptine, elle pourrait etre un marqueur des FPLD. Sa correlation avec la mm mais aussi la graisse viscerale suggere un role de senseur de l'equilibre entre les compartiments musculaires/adipocytaires (Weber JCEM 2014). Declaration d’interet Les auteurs declarent ne pas avoir d'interet direct ou indirect (financier ou en nature) avec un organisme prive, industriel ou commercial en relation avec le sujet presente.

The changes in type 1 (IL12, IFN gamma, IL2) and type 2(IL4, IL10) cytokine profiles may be associated with virological parameters of progression of the disease in HIV-1-infected patients. The production of cytokines was studied in LPS + PHA-activated whole-blood culture in HIV-1-infected individuals at different stages of the disease. The association was investigated between IL12p40 and IL12p70 profiles and other cytokines (IFN gamma, IL4, IL10), as well as the isolation of cytopathogenic HIV-1 strains. The phenotype of HIV strains was studied by a micromethod based on P4 cell line, allowing detection of cytopathic effects of HIV-1 isolates (syncytium-induction and cell-killing without syncytium induction). The individual variations in IL12p40 and IL12p70 production were limited in the healthy controls. Low values were observed in HIV-1-infected patients. The production of IL12 (p40 and p70) and the IL12p70/IL4 ratio and the IFN gamma/IL4 ratio were significantly lower in patients with cytopathic isolates compared with patients with noncytopathic isolates, and a correlation was obtained between the values of IL12 (IL12p40 and IL12p70) and those of IFN gamma/IL4 ratio. There was no increase in the secretion of IL4 and IL10 in patients with cytopathic strains compared with other patients. The results indicate a decreased production of type 1 cytokines (IL12, IFN gamma) in the presence of a relatively preserved production of type 2 cytokines (IL4, IL10) in HIV-1-infected patients. In conclusion, the defect of production of IL12 by whole blood is associated with virological correlates of progression of HIV-1 disease.

Interferon alpha (IFNalpha), a type I interferon, can be considered as a viral infection marker because this cytokine is induced during many viral infections. However, it is quite difficult to detect IFNalpha in sera. Investigations are interested in various intra-cellular IFNalpha-induced proteins as viral infection markers. However the activity of these enzymes increased not only in response to type I IFNs but also to type II IFN. MxA protein can be detected in the cytoplasm of IFNalpha/beta-treated cells, whereas other cytokines, including IFNgamma, are poor inducers. Using an immunochemiluminescent assay, we studied MxA protein in whole blood of 34 patients with various viral infections. The whole blood was drawn into sterile vacuum tubes containing heparin or EDTA. MxA values were relatively similar in heparin-treated samples and EDTA-treated samples, with differences not exceeding 1 ng/ml. The levels of MxA protein were compared in whole blood obtained by using two different lysis procedures. A correlation was found between the MxA levels obtained by using procedure I and procedure II, but higher amounts of MxA protein were found with procedure II. The second procedure is rapid and more convenient than the other and it is carried out in one step which reduce technical problems. High levels of MxA protein were found in peripheral blood cells of patients with acute viral infections (Rotavirus, Adenovirus, RSV, CMV), but MxA protein was not elevated in bacterial infections. The MxA levels were also studied in peripheral blood of 32 HCV positive patients. MxA protein was not found in most of IFNalpha-untreated patients, even those with high viral load. In contrast, high levels of MxA protein were found in IFNalpha-treated patients. MxA quantitation can be considered as a specific marker of acute viral infections, and could be useful in the management of treatment with IFNalpha.

Le sirolimus, inhibiteur de mTOR utilise en greffe d’ilots, peut avoir des effets deleteres sur la fonction gonadotrope, conduisant a une certaine prudence dans les indications de greffe chez les sujets jeunes. Le but de ce travail etait d’evaluer le profil gonadique d’hommes diabetiques de type 1 greffes d’ilots sous sirolimus-tacrolimus entre 2003 et 2014. Patients et methodes Dix-huit hommes (6 deja greffes d’un rein) d’IMC Resultats A T0, 78 % des hommes (mediane (IQR) : âge 43 (37–53), duree de diabete 27 (18–30), duree de suivi post-greffe 5 (3–10) ans ; dysfonction erectile (28 %) etaient peres. Entre T0 et T5, testosteronemie (T0 vs.T5 : 5,5 [3,1–6,3] vs. 4,8 [3,3–6,4] ng/mL), SBP (48 [41–53] vs. 45 [25–62] nmol/L), rapport testosterone/SBP (39 [21–56] vs. 35 [30–51]), LH (5,6 [4,2–8,8] vs. 4,8 [3,8–6,2] UI/L), FSH (7,6 [4,7–15,8] vs. 5,0 [3,9–7,4] UI/L), volume testiculaire (droit 13 [10–18]vs. 14 [10–17] ; gauche 12 [8–17]vs. 12 [11–14]), T-scores vertebraux (0,1 [-1,2–1,5] vs. 0,1 [-0,5–1,3]) demeuraient stables et normaux. Il existait une osteopenie femorale, stable (-0,9 [-1,9–0,7] vs. -1,9 [-2,5–-0,6]). Trois patients presentaient une ascension transitoire des gonadotrophines post-greffe dont un azoospermique a 1 an. Les sept patients ayant arrete ou modifie leur immunosuppression n’ont pas eu de variation hormonale mais l’un qui avait perdu son greffon s’est plaint de dysfonction erectile. Conclusion L’association tacrolimus-sirolimus n’a pas eu d’impact deletere sur la fonction gonadotrope ou le T-score de ces hommes supplementes en vitamine D, 5 ans apres greffe d’ilots.