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The influence of psychosocial stressors on psychosis risk has usually been studied in isolation and after the onset of the disorder, potentially ignoring important confounding relationships or the fact that some stressors that may be the consequence of the disorder rather than preexisting. The study of subclinical psychosis could help to address some of these issues. In this study, we investigated whether there was (i) an association between dimensions of subclinical psychosis and several psychosocial stressors including: childhood trauma, self-reported discrimination experiences, low social capital, and stressful life experiences, and (ii) any evidence of environment-environment (ExE) interactions between these factors. Data were drawn from the EUGEI study, in which healthy controls (N = 1497) and siblings of subjects with a psychotic disorder (N = 265) were included in six countries. The association between psychosocial stressors and subclinical psychosis dimensions (positive, negative and depressive dimension as measured by the Community Assessment of Psychic Experiences (CAPE) scale) and possible ExE interactions were assessed using linear regression models. After adjusting for sex, age, ethnicity, country, and control/sibling status, childhood trauma (beta for positive dimension: 0.13, negative: 0.49, depressive: 0.26) and stressful life events (positive: 0.08, negative: 0.16, depressive: 0.17) were associated with the three dimensions. Lower social capital was associated with the negative and depression dimensions (negative: 0.26, depressive: 0.13), and self-reported discrimination experiences with the positive dimension (0.06). Our findings are in favor of independent, cumulative and non-specific influences of social adversities in subclinical psychosis in non-clinical populations, without arguments for E * E interactions. © The Author(s) 2021. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Funder: FP7 Ideas: European Research Council; doi: http://dx.doi.org/10.13039/100011199; Grant(s): HEALTH-F2-2010-241909, Purpose: The EUropean Network of National Schizophrenia Networks Studying Gene–Environment Interactions (EU-GEI) study contains an unparalleled wealth of comprehensive data that allows for testing hypotheses about (1) variations in incidence within and between countries, including by urbanicity and minority ethnic groups; and (2) the role of multiple environmental and genetic risk factors, and their interactions, in the development of psychotic disorders. Methods: Between 2010 and 2015, we identified 2774 incident cases of psychotic disorders during 12.9 million person-years at risk, across 17 sites in 6 countries (UK, The Netherlands, France, Spain, Italy, and Brazil). Of the 2774 incident cases, 1130 cases were assessed in detail and form the case sample for case–control analyses. Across all sites, 1497 controls were recruited and assessed. We collected data on an extensive range of exposures and outcomes, including demographic, clinical (e.g. premorbid adjustment), social (e.g. childhood and adult adversity, cannabis use, migration, discrimination), cognitive (e.g. IQ, facial affect processing, attributional biases), and biological (DNA via blood sample/cheek swab). We describe the methodology of the study and some descriptive results, including representativeness of the cohort. Conclusions: This resource constitutes the largest and most extensive incidence and case–control study of psychosis ever conducted.

Systemic light-chain (AL) amyloidosis is a plasma cell disorder characterized by extracellular deposition of monoclonal immunoglobulin light chains leading to organ dysfunction. Cardiac involvement...

The work was supported by Guarantors of Brain post-doctoral clinical fellowship to DQ; Clinician Scientist Medical Research Council fellowship (project reference MR/M008436/1) to MDF; Heisenberg professorship from the German Research Founda- tion (grant no. 389624707) to UR; the National Institute for Health Research (NIHR) Maudsley Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. The EU-GEI Project is funded by the European Community’s Seventh Framework Programme under grant agreement No. HEALTH-F2-2010-241909 (Project EU-GEI). The Brazilian study was funded by the São Paulo Research Foundation under grant number 2012/0417-0., Quattrone D., Reininghaus U., Richards A.L., Tripoli G., Ferraro L., Quattrone A., Marino P., Rodriguez V., Spinazzola E., Gayer-Anderson C., Jongsma H.E., Jones P.B., La Cascia C., La Barbera D., Tarricone I., Bonora E., Tosato S., Lasalvia A., Szöke A., Arango C., Bernardo M., Bobes J., Del Ben C.M., Menezes P.R., Llorca P.-M., Santos J.L., Sanjuán J., Arrojo M., Tortelli A., Velthorst E., Berendsen S., de Haan L., Rutten B.P.F., Lynskey M.T., Freeman T.P., Kirkbride J.B., Sham P.C., O’Donovan M.C., Cardno A.G., Vassos E., van Os J., Morgan C., Murray R.M., Lewis C.M., Di Forti M., Hubbard K., Beards S., Stilo S.A., Parellada M., Fraguas D., Castro M.R., Andreu-Bernabeu Á., López G., Matteis M., González E., Durán-Cutilla M., Díaz-Caneja C.M., Cuadrado P., Rodríguez Solano J.J., Carracedo A., Costas J., Sánchez E., Amoretti S., Lorente-Rovira E., Garcia-Portilla P., Jiménez-López E., Franke N., van Dam D., Termorshuizen F., van der Ven E., Messchaart E., Leboyer M., Schürhoff F., Jamain S., Baudin G., Ferchiou A., Pignon B., Richard J.-R., Charpeaud T., Tronche A.-M., Frijda F., Marrazzo G., Sideli L., Sartorio C., Seminerio F., Loureiro C.M., Shuhama R., Ruggeri M., Bonetto C., Cristofalo D., Berardi D., Seri M., D’Andrea G.

Probe-based confocal laser endomicroscopy (pCLE) is a noninvasive and real-time imaging technique allowing acquisition of in situ images of the tissue microarchitecture during oral surgery. We aimed to assess the diagnostic performance of pCLE combined with patent blue V (PB) in improving the management of early oral cavity, oro/hypopharyngeal, and laryngeal cancer by imaging squamous cell carcinoma in vivo. The prospective study enrolled 44 patients with early head and neck lesions. All patients underwent white-light inspection or panendoscopy depending on the lesion’s location, followed by pCLE imaging of the tumor core and its margins after topical application of PB. Each zone imaged by pCLE was interpreted at distance of the exam by three pathologists blinded to final histology. Most imaged zones could be presented to pathologists; the final sensitivity and specificity of pCLE imaging in head and neck cancers was 73.2–75% and 30–57.4%, respectively. During imaging, head and neck surgeons encountered some challenges that required resolving, such as accessing lesions with the flexible optical probe, achieving sufficiently precise imaging on the targeted tissues, and heterogeneous tissue staining by fluorescent dye. Final sensitivity scores were reasonable but final specificity scores were low. pCLE zones used to calculate specificity were acquired in areas of tumor margins, and the poor quality of the images acquired in these areas explains the final low specificity scores. Practical adjustments and technical training are needed to analyze head and neck lesions in various anatomical sites in real-time by pCLE.

Psychotic patients with a lifetime history of cannabis use generally show better cognitive functioning than other psychotic patients. Some authors suggest that cannabis-using patients may have been less cognitively impaired and less socially withdrawn in their premorbid life. Using a dataset comprising 948 patients with first-episode psychosis (FEP) and 1313 population controls across 6 countries, we examined the extent to which IQ and both early academic (Academic Factor [AF]) and social adjustment (Social Factor [SF]) are related to the lifetime frequency of cannabis use in both patients and controls. We expected a higher IQ and a better premorbid social adjustment in psychotic patients who had ever used cannabis compared to patients without any history of use. We did not expect such differences in controls. In both patients and controls, IQ was 3 points higher among occasional-users than in never-users (mean difference [Mdiff] = 2.9, 95% CI = [1.2, 4.7]). Both cases and control daily-users had lower AF compared to occasional (Mdiff = −0.3, 95% CI = [−0.5; −0.2]) and never-users (Mdiff = −0.4, 95% CI = [−0.6; −0.2]). Finally, patient occasional (Mdiff = 0.3, 95% CI = [0.1; 0.5]) and daily-users (Mdiff = 0.4, 95% CI = [0.2; 0.6]) had better SF than their never-using counterparts. This difference was not present in controls (Fgroup*frequency(2, 2205) = 4.995, P = .007). Our findings suggest that the better premorbid social functioning of FEP with a history of cannabis use may have contributed to their likelihood to begin using cannabis, exposing them to its reported risk-increasing effects for Psychotic Disorders.

Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background Neutrophil extracellular traps have been associated with tissue damage. Whether these are involved in the pathogenesis of human acute respiratory distress syndrome (ARDS) and could be a potential therapeutic target is unknown. The authors quantified bronchoalveolar and blood neutrophil extracellular traps in patients with pneumonia-related ARDS and assessed their relationship with ventilator-free days. Methods Immunocompetent patients with pneumonia and moderate or severe ARDS (n = 35) and controls (n = 4) were included in a prospective monocentric study. Neutrophil extracellular trap concentrations were quantified (as DNA–myeloperoxidase complexes) in bronchoalveolar lavage fluid and serum by enzyme-linked immunosorbent assay. The relationship between bronchoalveolar lavage neutrophil extracellular trap concentrations and the primary clinical endpoint (i.e., the number of live ventilator-free days at day 28) was assessed using linear regression analyses. Results There was no significant relationship between bronchoalveolar lavage neutrophil extracellular trap concentrations and ventilator-free days by multiple regression analysis (β coefficient = 2.40; 95% CI, −2.13 to 6.92; P = 0.288). Neutrophil extracellular trap concentrations were significantly higher in bronchoalveolar lavage than in blood of ARDS patients (median [first to third quartiles]:154 [74 to 1,000] vs. 26 [4 to 68] arbitrary units, difference: −94; 95% CI, −341 to −57; P < 0.0001). Bronchoalveolar concentrations of patients were higher than those of controls (154 [74 to 1,000] vs. 4 [4 to 4] arbitrary units, difference: −150; 95% CI, −996 to −64; P < 0.001) and associated with bronchoalveolar interleukin-8 (Spearman’s ρ = 0.42; P = 0.012) and neutrophil concentrations (ρ = 0.57; P < 0.0001). Intensive care unit mortality (12%, n = 2 of 17 vs. 17%, n = 3 of 18; P > 0.99) and the number of ventilator-free days at day 28 (22 [14 to 25] vs. 14 [0 to 21] days; difference: −5; 95% CI, −15 to 0; P = 0.066) did not significantly differ between patients with higher (n = 17) versus lower (n = 18) bronchoalveolar neutrophil extracellular trap concentrations. Conclusions Bronchoalveolar neutrophil extracellular trap concentration was not significantly associated with mechanical ventilation duration in pneumonia-related ARDS.

Angioimmunoblastic T-cell lymphoma (AITL) is a frequent T-cell lymphoma in the elderly population that has a poor prognosis when treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) therapy. Lenalidomide, which has been safely combined with CHOP to treat B-cell lymphoma, has shown efficacy as a single agent in AITL treatment. We performed a multicentric phase 2 trial combining 25 mg lenalidomide daily for 14 days per cycle with 8 cycles of CHOP21 in previously untreated AITL patients aged 60 to 80 years. The primary objective was the complete metabolic response (CMR) rate at the end of treatment. Seventy-eight of the 80 patients enrolled were included in the efficacy and safety analysis. CMR was achieved in 32 (41%; 95% confidence interval [CI], 30%-52.7%) patients, which was below the prespecified CMR rate of 55% defined as success in the study. The 2-year progression-free survival (PFS) was 42.1% (95% CI, 30.9%-52.8%), and the 2-year overall survival was 59.2% (95% CI, 47.3%-69.3%). The most common toxicities were hematologic and led to treatment discontinuation in 15% of patients. This large prospective and uniform series of AITL treatment data was used to perform an integrative analysis of clinical, pathologic, biologic, and molecular data. TET2, RHOA, DNMT3A, and IDH2 mutations were present in 78%, 54%, 32%, and 22% of patients, respectively. IDH2 mutations were associated with distinct pathologic and clinical features and DNMT3A was associated with shorter PFS. In conclusion, the combination of lenalidomide and CHOP did not improve the CMR in AITL patients. This trial clarified the clinical impact of recurrent mutations in AITL. This trial was registered at www.clincialtrials.gov as #NCT01553786.

Background Biomarkers of disease severity might help individualizing the management of patients with the acute respiratory distress syndrome (ARDS). Whether the alveolar compartmentalization of biomarkers has a clinical significance in patients with pneumonia-related ARDS is unknown. This study aimed at assessing the interrelation of ARDS/sepsis biomarkers in the alveolar and blood compartments and explored their association with clinical outcomes. Methods Immunocompetent patients with pneumonia-related ARDS admitted between 2014 and 2018 were included in a prospective monocentric study. Bronchoalveolar lavage (BAL) fluid and blood samples were obtained within 48 h of admission. Twenty-two biomarkers were quantified in BAL fluid and serum. HLA-DR+ monocytes and CD8+ PD-1+ lymphocytes were quantified using flow cytometry. The primary clinical endpoint of the study was hospital mortality. Patients undergoing a bronchoscopy as part of routine care were included as controls. Results Seventy ARDS patients were included. Hospital mortality was 21.4%. The BAL fluid-to-serum ratio of IL-8 was 20 times higher in ARDS patients than in controls (p p = 0.026), IL-6 (p = 0.002), IP-10/CXCL10 (p = 0.024) and IL-10 (p = 0.023) than others. The BAL fluid-to-serum ratio of IL-1Ra was more elevated in hospital survivors than decedents (p = 0.006), even after adjusting for SOFA and driving pressure (p = 0.036). There was no significant association between alveolar or alveolar/blood monocytic HLA-DR or CD8+ lymphocytes PD-1 expression and hospital mortality. Conclusions IL-8 was the most compartmentalized cytokine and lower BAL fluid-to-serum concentration ratios of IL-1Ra were associated with hospital mortality in patients with pneumonia-associated ARDS.

Objective To explore the sociodemographic characteristics that might explain the increased incidence of psychosis among immigrants and their descendants in France. Methods Data were collected for all subjects with first contact for psychosis aged between 18 and 64 years, in two catchment areas in the Paris region. Incidence rates (IR) and incidence rate ratios (IRR) were adjusted for gender and age. Results During 805,396 persons‐year at risk, we identified 321 cases of first‐episode psychosis, of which 129 were immigrants and 78 descendants of immigrants. We found that the geographic origin was associated with the risk of psychosis although generation has little impact. Sub‐Saharan African immigrants and their descendants showed the highest risk (IRR = 3.1 and IRR = 2.9, respectively). We observed that living in deprived areas increased the incidence of psychosis (IRR = 1.3, 95CI%: 1.0–1.6), particularly among immigrants (IRR = 1.6; 95% CI: 1.1–2.5). Finally, our study showed that subjects having unstable housing (a proxy for “hard to count population”) could inflate the incidence rates among immigrants. Conclusion The current study shows that the increased risk of psychosis in groups with an immigration background in France is associated with their origin and highlights the importance of socioeconomic factors in modulating this risk., The aim of the present study is to explore the characteristics that might explain this increase: geographic origin, generation (immigrants or their descendants), social environment, and living conditions. We observed that living in deprived areas increased the incidence of psychosis, particularly among immigrants. Geographic origin was associated with the risk of psychosis although generation has little impact and Sub‐Saharan African immigrants and their descendants showed the highest risk.

Background Progressive multifocal leukoencephalopathy (PML) is a severe complication of natalizumab (NTZ) treatment in multiple sclerosis (MS) patients. Based on the analysis of cryopreserved cells, several reports have showed that CD62L+ CD4+ T-cells percentage drops before PML onset. Objective To analyze CD62L and CD45RA expression on fresh-blood CD4+ and CD8+ T-cells from NTZ-treated patients, according to their estimated PML risk. Methods We prospectively enrolled 74 MS patients, including 62 NTZ-treated, and stratified them into low, intermediate and high PML risk groups. Circulating naive and memory T-cell subsets were analyzed by flow cytometry. Results We found no correlation between the percentage of CD62L+ CD4+ T-cells and PML risk. In contrast, the repartition of CD8+ T-cells subpopulations was altered in the high risk group: both the percentage and absolute count of CD8+ CD62L- CD45RA- effector memory T- cells (TEM) was significantly higher compared to patients at lower risk despite similar CD3+ and CD8+ T-cell counts. One high-risk patient with elevated CD8+ TEM and CD62L+ CD4+ T-cell levels developed PML six months after sampling. Conclusion Our results suggest that CD8+ TEM cells should be evaluated in larger studies as a potential surrogate marker of PML risk in NTZ-treated patients.

International audience; BACKGROUND: Obinutuzumab monotherapy has shown promising efficacy in mantle cell lymphoma. We aimed to investigate the activity of obinutuzumab plus DHAP (dexamethasone, high-dose cytarabine, and cisplatin), measured by minimal residual disease quantitative (q)PCR status in the bone marrow after four cycles. METHODS: LyMa-101 was a prospective, open-label, single-arm, phase 2 trial. Participants were enrolled from 28 hospitals in France. Newly diagnosed patients with mantle cell lymphoma (aged 18 to

Complete molecular response (CMR) after first-line immunochemotherapy reflects treatment efficacy and may predict prognosis in patients with follicular lymphoma (FL). RELEVANCE is the first phase 3 trial comparing the chemotherapy-free regimen lenalidomide/rituximab (R2) vs rituximab/chemotherapy (R-Chemo) in previously untreated FL patients (ClinicalTrials.gov identifier: NCT01650701). The objective of the minimal residual disease (MRD) analysis was to determine the ability of a chemotherapy-free regimen to induce CMR. Of 440 French patients participating in the Lymphoma Study Association (LYSA) RELEVANCE MRD study, all 222 patients with a BIOMED-2–detectable BCL2-JH translocation at diagnosis were analyzed. MRD was quantified by droplet digital polymerase chain reaction with a sensitivity ≤10−4. At week 24 (end of induction treatment), 98% and 78% of patients achieved CMR in peripheral blood (PB) and bone marrow (BM), respectively. Achievement of CMR (in PB and/or BM) had a significant impact on progression-free survival (PFS), with 3-year PFS of 84% and 55% for patients with CMR and detectable MRD, respectively (P = .015). CMR at week 24 was reached more frequently in the R2 arm (105/117; 90%) than in the R-Chemo arm (70/90; 77%) (P = .022). The poor prognostic value in terms of PFS for the persistence of molecular disease was observed irrespective of treatment arm (interaction test, P = .31). In agreement with the clinical results of the RELEVANCE trial, our results show that R2 immunomodulatory treatment in first-line FL can achieve high rates of CMR.

The oncogenic events involved in breast implant-associated anaplastic large cell lymphoma (BI-ALCL) remain elusive. To clarify this point, we have characterized the genomic landscape of 34 BI-ALCLs (15 tumor and 19 in situ subtypes) collected from 54 BI-ALCL patients diagnosed through the French Lymphopath network. Whole-exome sequencing (n = 22, with paired tumor/germline DNA) and/or targeted deep sequencing (n = 24) showed recurrent mutations of epigenetic modifiers in 74% of cases, involving notably KMT2C (26%), KMT2D (9%), CHD2 (15%), and CREBBP (15%). KMT2D and KMT2C mutations correlated with a loss of H3K4 mono- and trimethylation by immunohistochemistry. Twenty cases (59%) showed mutations in ≥1 member of the JAK/STAT pathway, including STAT3 (38%), JAK1 (18%), and STAT5B (3%), and in negative regulators, including SOCS3 (6%), SOCS1 (3%), and PTPN1 (3%). These mutations were more frequent in tumor-type samples than in situ samples (P = .038). All BI-ALCLs expressed pSTAT3, regardless of the mutational status of genes in the JAK/STAT pathway. Mutations in the EOMES gene (12%) involved in lymphocyte development, PI3K-AKT/mTOR (6%), and loss-of-function mutations in TP53 (12%) were also identified. Copy-number aberration (CNA) analysis identified recurrent alterations, including gains on chromosomes 2, 9p, 12p, and 21 and losses on 4q, 8p, 15, 16, and 20. Regions of CNA encompassed genes involved in the JAK/STAT pathway and epigenetic regulators. Our results show that the BI-ALCL genomic landscape is characterized by not only JAK/STAT activating mutations but also loss-of-function alterations of epigenetic modifiers.

International audience; Chemotherapy plus rituximab has been the mainstay of treatment for follicular lymphoma (FL) for two decades but is associated with immunosuppression and relapse. In phase 2 studies, lenalidomide combined with rituximab (R 2 ) has shown clinical synergy in front-line and relapsed/refractory FL. Here, we show that lenalidomide reactivated dysfunctional T and Natural Killer (NK) cells ex vivo from FL patients by enhancing proliferative capacity and T-helper cell type 1 (Th1) cytokine release. In combination with rituximab, lenalidomide improved antibody-dependent cellular cytotoxicity in sensitive and chemo-resistant FL cells, via a cereblon-dependent mechanism. While single-agent lenalidomide and rituximab increased formation of lytic NK cell immunological synapses with primary FL tumour cells, the combination was superior and correlated with enhanced cytotoxicity. Immunophenotyping of FL patient samples from a phase 3 trial revealed that R 2 treatment increased circulating T- and NK-cell counts, while R-chemotherapy was associated with reduced cell numbers. Finally, using an in vitro model of myeloid differentiation, we demonstrated that lenalidomide caused a reversible arrest in neutrophil maturation that was distinct from a cytotoxic chemotherapeutic agent, which may help explain the lower rates of neutropenia observed with R 2 versus R-chemotherapy. Taken together, we believe these data support a paradigm shift in the treatment of FL – moving from combination immunochemotherapy to chemotherapy-free immunotherapy. © 2019 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley and Sons Ltd.

Objectives Incidence-prevalence-mortality (IPM) models have been developped to estimate incidence or prevalence when one of these two measures is unavailable. We aimed to test the consistency of an IPM model of psychotic disorders on a recent incidence-prevalence couple dataset and to identify potential causes of inconsistency by applying the model to (a) the whole population, (b) female and male subgroups, (c) migrant subgroups, and (d) psychotic disorders with age at onset (AAO) between 18 and 24 (18-24 AAO). Methods We modelled prevalence (MP) using incidence data and the expected mortality and remission values. We then compared the MP to the observed prevalence (OP). Results In the whole population, the model significantly underestimated the prevalence (MP = 3.30, 95% CI [2.97, 3.66]; OP = 4.98, 95% CI [4.58, 5.41]). The results were similar for the two genders. In the migrants group, results were in the opposite direction, the model significantly overestimating the prevalence. Finally, in the 18-24 AAO subgroup, the model performed well, with OP and MP not significantly different. Conclusion These results suggest that standard IPM models do not perform well for psychotic disorders and more complex models taking into account the heterogeneity of the sample (in terms of remission, mortality, population movements, etc.) need to be developed.

International audience; Outcomes for follicular lymphoma (FL) have greatly improved, but most patients will ultimately relapse. High total metabolic tumor volume (TMTV), computed from baseline 18F-fluorodeoxyglucose-positron emission tomography (PET), is associated with shorter progression-free survival (PFS), but circulating tumor cells (CTCs) and cell-free DNA (cfDNA) may also reflect tumor burden and be of prognostic value. The aim of our study was to correlate CTCs and cfDNA with TMTV in FL at diagnosis and to determine their prognostic values. We retrospectively analyzed 133 patients (with previously untreated FL and a baseline PET) from 2 cohorts with either a baseline plasma sample (n = 61) or a bcl2-JH-informative peripheral blood (PB) sample (n = 68). Quantification of circulating bcl2-JH+ cells and cfDNA was performed by droplet digital polymerase chain reaction. A significant correlation was found between TMTV and both CTCs (P < .0001) and cfDNA (P < .0001). With a median 48-month follow-up, 4-year PFS was lower in patients with TMTV > 510 cm3 (P = .0004), CTCs >0.0018 PB cells (P = .03), or cfDNA >2550 equivalent-genome/mL (P = .04). In comparison with TMTV alone, no additional prognostic information was obtained by measuring CTCs. In contrast, Cox multivariate analysis, including cfDNA and TMTV, showed that both cfDNA and TMTV remained predictive of outcome. In conclusion, CTCs and cfDNA correlate with TMTV in FL, and all 3 influence patient outcome. PFS was shorter for patients with high cfDNA and TMTV, suggesting that these parameters provide relevant information for tumor-tailored therapy.

Antenatal renal vein thrombosis is a rarely described diagnostic finding, with variable consequences on kidney function. We present the case of an affected fetus, born at 35-week gestation, with intrauterine oligohydramnios and two small kidneys. A renal ultrasound carried out after birth confirmed the presence of prenatal abnormalities. Renal vein thrombosis was not diagnosed at the time. The baby died 20 days later of kidney failure, metabolic acidosis, and polypnea with severe hypotrophy. Autopsy revealed atrophied kidneys and adrenal glands. The vena cava had thrombosis occupying most of its length. The right renal vein was normal, while the left renal vein was threadlike and not permeable. Histologically, there was necrosis of the left adrenal gland with asymmetrical bilateral renal impairment and signs of ischemic and hemorrhagic lesions. A review of thrombophilia was carried out and a heterozygous mutation in Factor V was found in both the mother and the child.

International audience; This study evaluates the long-term outcomes of a retrospective cohort of breast cancer (BC) patients who had received curatively intended premastectomy radiation therapy (RT). We analysed locoregional control, disease-free survival (DFS) and overall survival (OS), pathological complete remission (pCR), predictors thereof, and immediate safety. The series consisted of 187 patients with a median age of 49 years [43-60] and T2-T4 or N2 tumours. Between 1970 and 1984, they had received slightly hypofractionated RT to the whole breast, ipsilateral supraclavicular fossa and axilla ± the internal mammary chain (45-55 Gy/18 fractions of 2.5 Gy/34 days) systematically followed by a modified radical mastectomy with an axillary dissection. No other preoperative treatment was given. Among the 166 centrally reviewed tumour biopsy specimens, 22% had a triple-negative (TN) phenotype, 17% were HER2 3 + or amplified and 61% were ER+. The median follow-up was 32 years [23-35]. The 25-year locoregional control rate was 89% [93%-82%] and the 25-year DFS and OS rates were identical, 30% [24%-37%]. A pCR in the tumour and lymph nodes had been achieved in 18 among all patients (10%), but in 26% with TN disease. In the multivariate analysis, the TN status was the only predictive factor of pCR (OR = 5.49, 95% confidence interval [CI] 1.87-16.1, p = 0.002). Also, the pN status (HR = 1.69, [1.28-2.22], p = 0.0002) and TN subtype (HR = 1.80, [1.00-3.26], p = 0.05) exerted a significant prognostic impact on OS. The postoperative complication rate (grade >2) was 19% with 4.3% of localized skin necrosis. Preoperative RT followed by radical surgery is feasible and associated with good long-term locoregional control.

Introduction: Diffuse large B-cell lymphoma (DLBCL) is an aggressive and heterogeneous disease characterized by recurrent genetic alterations. Several adverse prognostic factors are well known as International Prognostic Index (IPI) parameters or MYC and BCL2 and/or BCL6 gene rearrangements (High-Grade B-cell Lymphoma double/triple hit, HGBL-DH/TH, according to the 2016 WHO classification). Other factors are controversial as previous history of indolent lymphoma, cell of origin (COO), co-expression of MYC and BCL2 proteins (double expressor (DE) status), MYC partner gene if rearranged. The aim of this study is to describe a « real life » cohort of patients treated in our institution for aggressive (non-Burkitt) B-cell lymphoma and to evaluate the prognostic impact of phenotypic and genetic alterations. Methods: We collected clinical and histological characteristics of patients uniformly treated between January 2009 and June 2017 with rituximab R-CHOP/CHOP-like chemotherapy. Treatment was reinforced with high dose methotrexate in case of central nervous system (CNS) localization or HGBL subtype. All tumor samples were analysed for MYC and BCL2 protein expression by immunohistochemistry. BCL2, BCL6 and MYC break were analysed by Interphase Fluorescence In Situ Hybridization (FISH) with breakapart probes. When MYC was rearranged MYC partner gene was analysed with double fusion probes (MYC/IgH, MYC/IgL, MYC/IgK). Positron Emission Tomography (PET scanner) was performed with maximal Standardized Uptake Value (SUV max) at baseline in all patients except 7. Results: 242 patients were studied. Baseline characteristics were: median age: 61 y (18-88), IPI 3-5: 49.6%, CNS localization: 6.6%. With a median follow-up of 4.4 years, 5y-overall survival (OS) and 5y-progression free survival (PFS) were 72% (66.0-78.5) and 65% (58.5-71.3), respectively. SUV max at baseline was 17,1 (minimum value 2,4 - maximal value 39,3).Histological diagnoses were DLBCL-not otherwise specified (NOS): 57%, transformed DLBCL: 26%, HGBL: 7.9%, primary mediastinal B-cell lymphoma (PMBL): 4.1% and others: 5%. Using Hans algorithm, 48.8% were classified as germinal center (GC), 47.9% as non-GC, 3.3% could not be evaluated and 38% were DE. MYC rearrangement was detected in 36 cases (14.9%) with an immunoglobulin partner gene (IgH, IgL or IgK) in 24 (77.4%) of 31 evaluable cases. BCL2 and BCL6 rearrangement were observed in 45 cases (18.6%) and 62 (25.6%) cases respectively. Fifteen cases were HGBL DH/TH including 7 DH MYC/BCL2, 5 DH MYC/BCL6 and 3 TH MYC/BCL2/BCL6. Four cases were HGBL-NOS. IPI score 3-5 (p Conclusions: This monocentric study in a large cohort of aggressive B-cell lymphoma patients treated in real life conditions confirms previous reports on the negative prognostic impact of DE status, MYC and BCL2 translocations and HGBL subtype. These genetic and immuno-histological characteristics should have implications in the design and interpretation of future clinical trials. Disclosures Le Bras: Takeda: Research Funding; Pfizer: Other: Travel grant; Jansen: Other: Travel grant. Belhadj:Celgene: Other: personal fees from Celgene, personal fees from Amgen, personal fees from Takeda, personal fees from Janssen, outside the submitted work. Haioun:servier: Honoraria; amgen: Honoraria; janssen cilag: Consultancy; takeda: Consultancy; gilead: Consultancy; novartis: Honoraria; celgene: Honoraria; roche: Consultancy; celgene: Consultancy.

Background: Population-based mammography screening has resulted in the increased detection of suspicious, non-palpable lesions that require histopathological assessment. When a “pre-malignant” lesion, such as lobular carcinoma in situ (LCIS), atypical ductal or lobular hyperplasia (ADH and ALH) or flat epithelial atypia (FEA), is discovered on the primary biopsy, a surgical excision is recommended due to the risk of underestimation of the lesion. DCIS or invasive carcinoma is finally retrieved in 10–30% of the patients, meaning a large part receive unnecessary surgery. The aim of this study was to define a nomogram integrating clinical, imaging and histological data to predict for the risk of underestimation of the lesion. Intentionally, we decided to include all the premalignant lesions which implied the same management, whereas most of the previous models of the literature are focused in only one or another type of atypia. Patients and Methods: We collected complete clinical, radiological and double-reading histological data on all patients with a diagnosis of pure atypical lesion (CLIS, ADH, ALH, FEA) on image-guided biopsy performed at the One-Stop Unjt of our breast care center from 2004 to 2011. Univariate and multivariate logistic regression analyses were used to develop a model predicting for the presence of DCIS or invasive carcinoma on the final surgical sample, and build a nomogram. This nomogram was evaluated on a training set of 205 patients treated at IGR. Results: 205 patients were eligible for the study. Of these 205 patients, 50 cancers (24.4%) were diagnosed at definitive surgery (21 DCIS, 20 ductal and 9 lobular invasive carcinoma). Univariate analysis retrieved age (p = 0.03), number of biopsy cores (p = 0.02) and type of radiological anomalies (p = 0.02) as factors associated with cancer at surgery. The presence of microcalcifications on biopsies of limit significance was included in the multivariate analysis (p = 0.09). The final most informative nomogram included information on patient age (p = 0.03), type of radiological anomalies (p = 0.02) and number of biopsy cores (p = 0.04). The predictive accuracy of the nomogram was 0.71 and 0.68 in the training set before and after bootstrapping, respectively. The calibration of the nomogram was good. The sensitivity, specificity, positive predictive value, and negative predictive values were 68%, 73%, 45%, and 88%, respectively. Conclusion: This nomogram could help identify a subset of patients with premalignant disease for whom surgery could be spared and who would be eligible for exclusive clinical follow-up. A validation study is currently undergoing in an external dataset. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-12-01.

// Asma Beldi-Ferchiou 1, 2, 11 , Marion Lambert 1, 2 , Stephanie Dogniaux 3 , Frederic Vely 4, 5 , Eric Vivier 4, 5 , Daniel Olive 6 , Stephanie Dupuy 1 , Frank Levasseur 1 , David Zucman 7 , Celeste Lebbe 8 , Damien Sene 1, 2, 9 , Claire Hivroz 4 , Sophie Caillat-Zucman 1, 2, 10 1 Institut National de Recherche Medicale (INSERM) UMR1149, Centre de Recherche Sur l’Inflammation, Equipe Immunite Innee Chez l’enfant, Hopital Robert Debre, Paris, France 2 Universite Paris Diderot, Sorbonne Paris Cite, Paris, France 3 Institut Curie, Centre de Recherche, PSL Research University, INSERM U932 Immunite et Cancer, Paris, France 4 Centre d’Immunologie de Marseille-Luminy, Aix-Marseille Universite UM2, INSERM U1104, CNRS UMR7280, Marseille, France 5 Immunologie, Hopital de la Conception, Assistance Publique- Hopitaux de Marseille, Marseille, France 6 Centre de Cancerologie de Marseille, INSERM U1068, Equipe Immunite et Cancer, Institut Paoli-Calmettes, Aix-Marseille Universite, CNRS, UMR7258, Marseille, France 7 Hopital Foch, Service de Medecine Interne, Suresnes, France 8 Assistance Publique-Hopitaux de Paris (AP-HP), Hopital Saint-Louis, Departement de Dermatologie, INSERM U976, Universite Paris Diderot, Paris, France 9 Assistance Publique-Hopitaux de Paris (AP-HP), Hopital Lariboisiere, Departement de Medecine Interne, Paris, France 10 Assistance Publique-Hopitaux de Paris (AP-HP), Hopital Saint-Louis, Laboratoire d’Immunologie, Paris, France 11 Present address: Assistance Publique-Hopitaux de Paris (AP-HP), Hopital Henri Mondor, Laboratoire d’Immunologie, Creteil, France Correspondence to: Sophie Caillat-Zucman, email: sophie.caillat@inserm.fr Keywords: NK cells, Kaposi sarcoma, PD-1, immune checkpoint, tumor escape Received: March 31, 2016 Accepted: September 13, 2016 Published: September 20, 2016 ABSTRACT Programmed Death-1 (PD-1), an inhibitory receptor expressed by activated lymphocytes, is involved in regulating T- and B-cell responses. PD-1 and its ligands are exploited by a variety of cancers to facilitate tumor escape through PD-1-mediated functional exhaustion of effector T cells. Here, we report that PD-1 is upregulated on Natural Killer (NK) cells from patients with Kaposi sarcoma (KS). PD-1 was expressed in a sub-population of activated, mature CD56 dim CD16 pos NK cells with otherwise normal expression of NK surface receptors. PD-1 pos NK cells from KS patients were hyporesponsive ex vivo following direct triggering of NKp30, NKp46 or CD16 activating receptors, or short stimulation with NK cell targets. PD-1 pos NK cells failed to degranulate and release IFNγ, but exogenous IL-2 or IL-15 restored this defect. That PD-1 contributed to NK cell functional impairment and was not simply a marker of dysfunctional NK cells was confirmed in PD-1-transduced NKL cells. In vitro , PD-1 was induced at the surface of healthy control NK cells upon prolonged contact with cells expressing activating ligands, i.e. a condition mimicking persistent stimulation by tumor cells. Thus, PD-1 appears to plays a critical role in mediating NK cell exhaustion. The existence of this negative checkpoint fine-tuning NK activation highlights the possibility that manipulation of the PD-1 pathway may be a strategy for circumventing tumor escape not only from the T cell-, but also the NK-cell mediated immune surveillance.

After the publication of our article titled “Extensive Thrombosis of the Inferior Vena Cava and Left Renal Vein in a Neonate” [1], a reader noted that in the Discussion (treatment paragraph) we have not taken into consideration some references when we discussed surgical treatment of renal vein thrombosis, especially when we talked about thrombectomy.

Auto-reactive cytotoxic T lymphocytes play a key role in the progressive loss or destruction of melanocytes in vitiligo but the mechanism underlying the loss of self-tolerance is unknown. A deregulation of regulatory T-cell biology has recently been suggested. The analysis of the suppressive effects of peripheral T regulatory cells in vitiligo patients revealed a functional defect in seven of 15 cases. This defect was strongly correlated with disease activity. The evaluation of the percentage of peripheral regulatory T lymphocytes did not reveal any intrinsic quantitative defect. Yet, a decrease in the percentage of such cells was noted in patients with progressive forms, suggesting a recruitment of regulatory T cells from the peripheral blood to the site of injury. This was further corroborated by the significant increase of Forkhead box P3 expression in the vitiliginous skin of patients. Our data support the involvement of a functional defect of peripheral regulatory T cells in the pathogenesis of vitiligo and open new possibilities to advance therapeutic approaches.

The inflammatory myofibroblastic tumour has clinical, biological or histological features sometimes misleading with a septic condition. Presenting symptoms are variable and arising circumstances remain obscure. We report three cases occurring in a postpartum context. The first patient, a 28-year-old female, had left psoitis with a sepsis the first day postpartum in relation with an inflammatory myofibroblastic tumour of the meso-ovary. The second patient, a 40-year-old woman, had a hepatic inflammatory myofibroblastic tumour revealed by a ruptured sub-capsular haematoma of the liver in the forth day postpartum. The third patient, a 32-year-old woman, had a pulmonary inflammatory myofibroblastic tumour, diagnosed 5 months after a delivery and which recurred 10 years after surgical treatment. These cases illustrate the difficulty to diagnose inflammatory myofibroblastic tumour, particularly in postpartum.

SOURCE MONITORING FRAMEWORK: Source monitoring refers to the ability to remember the origin of information. Three source monitoring processes can be distinguished: external source monitoring, internal or self-monitoring and reality monitoring (i.e. discrimination between internal and external sources of information). Source monitoring decisions are based on memory characteristics recorded such as perceptions, contextual information or emotional reactions and heuristic or more controlled judgement processes. BRAIN STRUCTURES: Several studies suggested that specific structures in the prefrontal and the mediotemporal lobes are the main areas implicated in source monitoring. ASSESSMENT: A typical source monitoring paradigm includes an items generation stage and a second stage of recognition of items (old versus new) and identification of their sources: external (usually the examiner) or internal (the subject). Several indices can be calculated based on the raw data such as the number of false alarms, attribution biases or discrimination indexes. To date, there is no standardized source monitoring task and differences in the type of items used (words, pictures), in the cognitive or emotional effort involved or in the delay between the two test stages, contribute to the heterogeneity of results. FACTORS INFLUENCING SOURCE MONITORING: Factors such as age (either very young or very old) and emotions influence source monitoring performances. Influence of gender was not properly explored, whereas the role of IQ and selective attention is still debated. SOURCE MONITORING DEFICITS IN NEUROLOGICAL DISORDERS: Source monitoring deficits are observed mainly in disorders affecting frontotemporal areas, such as frontal trauma, Alzheimer's disease or frontotemporal dementia. SOURCE MONITORING AND SCHIZOPHRENIA: Source monitoring errors (e.g. external misattribution of self-generated information) are observed in schizophrenia and seem to correlate with positive symptomatology, in particular auditory hallucinations, thought intrusion and alien control symptoms. These results are of particular interest in clinical research because source monitoring is one of the rare cognitive tests showing a correlation with the positive dimension. Source monitoring deficits have been proposed as a potential explanation for the positive symptoms and some, but not all studies lent support to this hypothesis. Heterogeneity of studied samples, in particular different criteria to define hallucinating subjects (e.g. currently versus anytime during their lives), could explain the discordant results. SOURCE MONITORING IN PSYCHIATRIC DISORDERS WITHIN THE SCHIZOPHRENIC SPECTRUM: Source monitoring impairments were observed in pharmacological models of psychosis, in first degree relatives of schizophrenic patients, and also in the general population associated with schizotypal dimensions. These results support a relationship between source monitoring deficits and some of the symptomatic dimensions of the schizophrenic spectrum but still await replication. SOURCE MONITORING AND OTHER PSYCHIATRIC DISORDERS: Some studies found source monitoring deficits in other psychiatric conditions such as mania or obsessive-compulsive disorder. Thus, those studies suggest that source monitoring deficits may be not specific to schizophrenia. CONCLUSION: Source monitoring competencies are critical for good (i.e. adapted) everyday functioning. Source monitoring deficits have been suggested as a potential explanation for some (or all) positive psychotic symptoms. However, to date, methodological inconsistencies (especially with regard to test design and choice of subjects' samples) have precluded firm, definite conclusions.

Background Primary upper aerodigestive tract malignancy remains a cancer having a poor prognosis, despite current progress in treatment, due to a generally late diagnosis. Objectives: We conducted a preliminary assessment of five dyes approved for human use for the imaging of head and neck tissues at the cellular level, which could be considered for clinical examination. Methods We investigated fluorescence endomicroscopic images on fresh samples obtained from head and neck surgeries after staining with hypericin, methylene blue, toluidine blue, patent blue or indocyanine green to provide a preliminary consideration as to whether these images contain enough information for identification of non-pathologic and pathologic tissues. The distribution pattern of dye has been examined using probe-based confocal laser endomicroscopy (pCLE) in ex vivo specimens and compared with corresponding histology. Results In most samples, the image quality provided by pCLE with both dyes allowed pathologists to recognize histological characteristics to identify the tissues. Conclusion The combination of pCLE imaging with these dyes provides interpretable images close to conventional histology; a promising clinical tool to assist physicians in examination of upper aerodigestive tract, as long as depth imaging issues can be overcome.

Resume Objectif. – Evaluer l’apport de l’hysteroscopie dans le traitement des synechies uterines notamment en ce qui concerne les troubles de la fertilite. Patientes et methodes. – Nous avons analyse retrospectivement une serie de 120 patientes porteuses de synechies uterines traitees exclusivement par hysteroscopie. L’âge moyen etait de 34 ans (extremes : 21–45 ans). Cent neuf patientes (90,8 %) presentaient des troubles de la fertilite, 110 (91,7 %) des troubles des regles et 2 etaient asymptomatiques (0,2 %). Cent cinquante-cinq hysteroscopies operatoires etaient realisees dont 124 electrosections (80 %) et 31 effondrements (20 %). Quatre-vingt-seize patientes ont ete traitees en une seule seance endoscopique, 17 en 2 seances, 3 en 3 seances et 4 en 4 seances. Le recul moyen d’observation est de 26,8 mois (extremes : 6–52 mois). Resultats. – Cent seize patientes (96,7 %) avaient un bon resultat anatomique apres 1, 2 ou 3 gestes iteratifs. Un bon resultat sur les troubles des regles etait note dans 58,2 % des cas. Quarante-neuf grossesses etaient obtenues (44,9 %), reparties en : 35 naissances vivantes, 13 avortements et une grossesse molaire. Discussion et conclusion. – L’hysteroscopie, geste simple, reproductible, de faible morbidite doit etre indiquee de premiere intention dans tous les cas de synechies avec infertilite. Le pronostic de fertilite est etroitement lie a la gravite de la synechie et a sa localisation.

Background The genetic heterogeneity of HER2 gene amplification (GA) in breast cancer has previously been described, but the clinical significance of this phenomenon remains unknown. We studied the genetic categories of a series of consecutive 2+ IHC cases over 5 years, with a focus on cases with HER2 GA detected in minor clone(s). We compared the HER2 status in primary tumors and positive axillary lymph nodes (ALN) when available to test the hypothesis that HER2 amplified cells are more aggressive and metastase quicker than non amplified cells. Material and methods: From January 1st. 2006 to May 30. 2011, 4491 invasive breast carcinomas had HER2 immunohistochemical (IHC) and/or HER2 gene status evaluation on their tumor sample in Institut Gustave Roussy. The distribution according to their IHC was as follows: 0 in 2915 cases (65%), 1+ in 569 cases (12.6%), 2+ in 536 cases (11.8%) and 3+ in 471 cases (10.6%). All 2+ samples were checked by Fluorescence in situ hybridization (FISH). For each case we analysed 100 invasive cells in 10 microscopic fields. Heterogeneous amplification was defined as presence of 5–50% of amplified cells (ratio>2,2) within the tumors otherwise classified as not amplified or borderline (ratio for 100 cells: Results: FISH with HER2/cen17 probes can classify IHC 2+ tumors into 5 genetic categories: normal gene status (two chromosomes (chr) 17 and two HER2 genes): 90 cases; chr 17 “ polysomy “/17q gain: 145 cases; HER2 gain: 122 cases; HER2 amplification (major clone): 135 cases and chr 17 monosomy: 44 cases. We focused our interest to IHC 2+ cases where the major clone showed no HER2 amplification, but minority clone (cut off 5%) showed the HER2 amplification (ratio >2,2 or >6 HER2 copies per cell). We found 48 such cases (10% of 2+ cases). These cases had been reported as not amplified (42/48) or borderline (6/48). To find out if the amplified cells are those which metastase, we checked 10 involved ALN: they all showed the similar genetic heterogeneity as a primary tumor with a global ratio < 2,2. Other cases with involved ALN are in ongoing study by FISH. Conclusions: The genetic heterogeneity of IHC 2+ tumors is a common event and five different genetic categories can be detected. A part of the HER2 negative cases contained one or several HER2 amplified clones. Preliminary results show a similar genetic heterogeneity of metastatic population. Our results on the small series of cases do not confirm the hypothesis that the only amplified clones metastase, but all clones (amplified and not amplified) has a metastatic capacity. A multi-center collaboration is needed to collect the high number of cases with heterogeneous amplification to: 1) Find out a proportion of such patients in HER2 IHC 2+ group (10% in our study). 2) Study a status of the gene in relapse cases. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-05-07.

Histological assessment is an essential tool in the diagnosis and guidance of the treatment of various diseases, in particular cancer, of the head and neck. Recent major advances in optical imaging techniques have made it possible to acquire high-resolution in vivo images at the cellular scale. Confocal endomicroscopy is a non-invasive technique, which can be highly useful whenever meaningful in situ histological information is required. The technical aspects of confocal endomicroscopy are introduced, followed by an overview of major clinical studies in the field of head and neck cancer. Ongoing technical developments, contributing to improvements in imaging of the upper aero-digestive tract, are also discussed. Finally, the potential complementarities of functional and molecular imaging, as compared to morphological endomicroscopy, are highlighted.

BRCA2 mutation carriers typically develop luminal B breast cancers. Data on the effectiveness of neoadjuvant chemotherapy in these patients are limited because of small patient numbers and lack of prospective studies. We used our 15-year genetic clinic database to compare retrospectively the pathological complete response rates (pCR) and rates of post-chemotherapy nodal involvement among BRCA2 carriers and BRCA1/2-negative (WT) patients with luminal B tumours, all treated with neoadjuvant anthracyclines ± taxanes-based chemotherapy. Twenty-nine BRCA2 carriers and 67 WT patients fulfilled the inclusion criteria and were analysed. Patients and treatment characteristics were represented. A pCR occurred in 3 (10 %) BRCA2 patients and 13 (19 %) WT patients (p = 0.43). Twenty (69 %) BRCA2 carriers and 34 (51 %) WT patients remained node-positive at surgery (p = 0.17). BRCA2 germline mutations are associated with a low probability of pCR and a high risk of axillary invasion. Alternative treatments are highly expected, and clinical trials are needed to set the best treatment regimen in this population.

Cannabis consumption can cause abuse and dependence and increase risk of developing psychiatric and somatic disorders. Several literature reviews explored the link between cannabis consumption and schizophrenia but none summarized the rich literature on cannabis and psychometric schizotypy. The aim of our review is to synthesize data from studies that explored the association between cannabis consumption and schizoptypal dimensions. A systematic review of the literature and, when needed, contact with the authors, allowed us to gather data from 29 cross-sectional studies. We compared schizotypy scores between subjects that never used cannabis and subjects that used it at least once ("never vs. ever") and between current users and subjects that do not use cannabis currently ("current vs. other"). We conducted separate analyses for total schizotypy score and each of the three classical schizotypal dimensions (positive, negative, disorganized). For all eight comparisons, the cannabis group ("ever" or "current") had higher schizotypy scores. Differences were in the small or medium range and, with the exception of the negative score in the current vs. other comparison, statistically significant. Cannabis consumption is associated with increased schizotypal traits. More research, using different approaches (e.g. longitudinal studies) is needed to explore the cause of this association.

High risk Human Papilloma virus (HR-HPV) associated oropharyngeal cancers are on the increase. Although, the scientific community is aware of the importance of Human Papilloma Virus (HPV) testing, there is no consensus on the assays that are required to reliably identify HR-HPV related tumors. A wide range of methods have been developed. The most widely used techniques include viral DNA detection, with polymerase chain reaction (PCR) or In Situ Hybridization, and p16 detected by immunohistochemistry. However, these tests provide different information and have their own specific limitations. In this review, we summarize these different techniques, in light of the recent literature. p16 Overexpression, which is an indirect marker of HPV infection, is considered by many head and neck oncologists to be the most important marker for patient stratification. We describe the frequent lack of concordance of this marker with other assays and the possible reasons for this. The latest developments in HPV testing are also reported, such as the RNAscope™ HPV test, and how they fit into the existing framework of techniques. HPV testing must not be considered in isolation, as there are important interactions with other parameters, such as tobacco exposure. This is an important and rapidly evolving field and is likely to become pivotal to staging and choice of treatment of oropharyngeal carcinoma in the future.

When any atypical feature is identified on a percutaneous biopsy specimen of a suspicious breast lesion, surgical excision is mandatory, leading to unnecessary surgeries in 70-90% of the cases. The purpose of this study was to develop a model to predict the presence of cancer at surgery that would be applicable to all atypical lesions.We collected complete clinical, radiological, and double-reading histological data concerning all patients with a diagnosis of a pure atypical lesion on image-guided biopsy performed at the One-Stop Breast Care Unit between 2004 and 2011.Among the 204 eligible patients, 49 cancers (24%) had been diagnosed at definitive surgery (20 ductal carcinoma in situ, 20 invasive ductal, and 9 invasive lobular carcinoma). The univariate analysis retrieved age (p=0.03), the focus size in mm (p=0.02), the number of biopsy cores (p=0.02), the disappearance of radiological anomalies after biopsy (p=0.05), the mean number of atypical foci (p=0.05) and the percentage of atypical lobules and ducts for lobular neoplasia (p=0.04) as factors associated with cancer at surgery, whereas neither Ki67 nor ALDH1 expression was significantly correlated. The final most informative nomogram comprised information on patient age, the disappearance of radiological anomalies after biopsy and a focus size15 mm. For the optimal threshold (risk of cancer=21%), sensitivity, specificity, positive predictive value, and negative predictive value were 78, 66, 36, and 90%, respectively.After validation, this model could help to identify a subset of patients with premalignant disease who could be spared surgery.

International audience; BACKGROUND: The mechanisms underlying the loss of self-tolerance in systemic lupus erythematosus (SLE) are incompletely deciphered. TGF-β plays a key role in self-tolerance demonstrated by the onset of a fatal autoimmune syndrome associated with lupus autoantibodies in mice lacking a functional TGF-β receptor. The present work aims to define whether resistance to TGF-β might contribute to the pathogenesis of SLE. METHODS: Twenty-two patients with active SLE, 16 with other connective tissue diseases, and 10 healthy controls were prospectively included in this study. The effects of exogenous TGF-β1 on IL-2-dependent T-cell proliferation, IFN-γ secretion, and target gene transcription were analyzed on peripheral blood mononuclear cells. RESULTS: Our results showed that 75% of patients with SLE or other connective tissue diseases were totally or partially resistant to the effects of TGF-β1. The responses to the anti-proliferative and transcriptional effects of TGF-β were, however, discordant in a high proportion of our patients. Hence, we distinguish three distinct profiles of resistance to TGF-β1 and suggest that patients may exhibit different defects affecting distinct points of TGF-β1 signaling pathways. CONCLUSION: Our data demonstrate the presence of an impaired response of peripheral cells to TGF-β1 in patients with active SLE that may participate to the pathogenesis of the disease. Further studies will be necessary to delineate the mechanisms underlying the lymphocyte resistance to TGF-β1 in SLE.

This is a non-final version of an article published in final form in Journal of Nervous & Mental Disease; International audience; Impairments in selective attention have been proposed as an explanation for the source monitoring deficits in schizophrenia. We tested this hypothesis by examining correlations between source monitoring variables and a measure of selective attention (from the Stroop Test) in 54 individuals with schizophrenia subjects and 42 normal controls. We did not find significant correlations between source monitoring measures and selective attention. Selective attention impairments do not explain source monitoring deficits observed in schizophrenia. Source monitoring deficits deserve continued efforts to elucidate their causes and consequences.

ObjectiveTo test if specific correlations exist between cognitive measures and psychotic dimensions in schizophrenic subjects and if similar correlations, between cognition and schizotypal dimensions, are present in non-psychotic subjects.MethodsWe administered the same battery of cognitive tests (Source Monitoring, Verbal Fluency [VF] and Stroop tests) to schizophrenic subjects (N = 54), their first-degree relatives (N = 37) and controls (N = 41). Scores of negative, positive and disorganisation dimensions were derived from the Signs and Symptoms of Psychotic Illness scale in schizophrenic subjects, and from the Schizotypal Personality Questionnaire in relatives and controls.ResultsIn schizophrenic subjects, as hypothesised, the negative dimension correlated with performance on VF and disorganisation with performance in the Stroop test. The positive dimension did not correlate with any cognitive measure.With only one exception, the significant correlations observed in non-psychotic subjects did not match correlations seen in schizophrenic subjects. In non-psychotic subjects greater disorganisation was associated with more clustered words in VF suggesting that excessive automatic spreading of activation in semantic networks could underlie this dimension.ConclusionAs a whole, data lent partial support to our hypothesis of specific cognitive–clinical correlations in schizophrenic subjects but did not support the existence of similar correlations in non-psychotic subjects.

La malade decrite, une tunisienne de 10 ans, presentait une camptodactylie, une arthropathie et de multiples dysplasies epiphysaires interessant les hanches et les genoux dans lesquelles la coxa vara etait un epiphenomene. La malade ne presentait pas de nanisme. L'arthropathie associee a la camptodactylie peut etre un element du syndrome du rhumatisme chondrodysplasique decrit par Kahn et Coll.