Diagnostic Value of FDG PET-CT Quantitative Parameters and Deauville-Like 5 Point-Scale in Predicting Malignancy of Focal Thyroid Incidentaloma

Objective: To evaluate the diagnostic value of FDG PET-CT metabolic parameters and Deauville-like 5 point-scale to predict malignancy in a population of patients presenting focal thyroid incidentaloma (fTI).Design: This retrospective study included 41 fTI, classified according to cytological and histological data as benign (BL) or malignant lesion (ML). FDG PET-CT semi-quantitative parameters (SUVmax, SUVmean, SUVpeak, MTV, TLG), tumor to liver SUVmean ratio (TLRmax and TLRmean), tumor to blood-pool SUVmean ratio (TBRmax and TBRmean) were calculated. Each fTI was also classified on a Deauville-like 5-point scale (DS) currently used in lymphoma. Comparison between BL and ML was performed for each parameter and a ROC analysis was conducted.Results: All quantitative PET metabolic parameters (SUV parameters, volume based parameters and SUV ratio) were higher in ML compared with BL, yet no significant difference was reported. fTI (uptake) malignancy rate according to DS grades 2, 3, 4, and 5 was, respectively, 25% (1 of 4), 28.6% (2 of 7), 8.3% (1 of 12), and 33.3% (6 of 18) with no significant difference between ML and BL groups. Results of ROC analysis showed that mean TBR had the highest AUC in our cohort (0.66 95%CI [0.41; 0.91]) with a cut-off value of 2.2. Specificity of MTV and TLG was 100% (cut-off values: MTV 9.6 ml, TLG 22.9 g) and their sensitivity was 30 and 40%, respectively.Conclusion: Our study did not highlight any FDG PET/CT parameter predictor of fTI malignancy

Leukemic plasmacytoid dendritic cells share phenotypic and functional features with their normal counterparts.

This work aims to further characterize the newly described leukemic plasmacytoid dendritic cells (LPDC), for which we had previously demonstrated their normal, PDC-like ability to produce IFN-alpha. In addition, LPDC also express the specific antigens BDCA-2 and BDCA-4. Importantly, they become fully competent antigen-presenting cells (APC) after a short maturation induced by IL-3 + CD40L or virus, exhibiting a characteristic APC phenotype (high expression of CD83 and of the costimulatory molecules CD40, CD80, CD86). Whereas IL-3 + CD40L-activated LPDC prime naive CD4(+) T cells towards a Th2 pathway (IL-4-secreting T cells), virus-activated LPDC drive a Th1 profile (IFN-gamma-secreting T cells). Moreover, we show in one case that LPDC are able to capture, process and present exogenous antigens, leading to the activation of both CD4(+) and CD8(+) T cell clones in an antigen-specific manner. This study further characterizes the phenotype and immunological functions of LPDC

Malignancy rate of focal thyroid incidentaloma detected by FDG PET–CT: results of a prospective cohort study

International audienc

Evaluation of diffusive gradients in thin films (DGT) technique for speciation of trace metals in estuarine waters - A multimethodological approach

International audienc

Diagnostic Value of FDG PET-CT Quantitative Parameters and Deauville-Like 5 Point-Scale in Predicting Malignancy of Focal Thyroid Incidentaloma

International audienc

Flow cytometry minimal residual disease after allogeneic transplant for chronic lymphocytic leukemia

International audienc

Removal of GP160 induced bio-hazards for a safe AIDS vaccine candidate

In the first AIDS vaccine trial, immunizing preparations were based on HIV-1 Env protein (gp160). Immunogenic properties of gp160 which trigger both a humoral and cellular immune response have since justified its use in various vaccine programs, both past and present. Many reports however have underlined deleterious effects on the immune system - anti-HIV-1 enhanced antibodies, anti-CD4 autoantibodies, and inhibition of T cell activation by HIV-1 - particularly associated with the Env protein. The present study shows that gp160 presented in a biologically inactivated but immunogenic form, as used in our trial, could avoid these complications. Bio-hazards associated with gp0000 which indeed could be removed by appropriate treatment of the native protein, should be taken into consideration in AIDS vaccine programs. anti-AIDS vaccine / HIV-1 Env gp160 protein enhancing antibodies / anti-CD4 autoantibodies. © 1992.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Linking the KIR phenotype with STAT3 and TET2 mutations to identify chronic lymphoproliferative disorders of NK cells

International audienceDistinguishing chronic lymphoproliferative disorders of NK cells (CLPD-NK) from reactive NK-cell expansion is challenging. We assessed the value of killer immunoglobulin-like receptor(KIR) phenotyping and targeted high-throughput sequencing in a cohort of 114 consecutive patients with NK cell proliferation, retrospectively assigned to a CLPD-NK group (n = 46) and a reactive NK group (n = 68). We then developed an NK-cell clonality score combining flow cytometry and molecular profiling with a positive predictive value of 93%. STAT3 and TET2 mutations were respectively identified in 27% and 34% of the patients with CLPD-NK, constituting a new diagnostic hallmark for this disease. TET2-mutated CLPD-NK preferentially exhibited a CD16low phenotype, more frequently displayed a lower platelet count, and was associated with other hematologic malignancies such as myelodysplasia. To explore the mutational clonal hierarchy of CLPD-NK, we performed whole-exome sequencing of sorted, myeloid, T, and NK cells and found that TET2 mutations were shared by myeloid and NK cells in 3 of 4 cases. Thus, we hypothesized that TET2 alterations occur in early hematopoietic progenitors which could explain a potential link between CLPD-NK and myeloid malignancies. Finally, we analyzed the transcriptome by RNA sequencing of 7 CLPD-NK and evidenced 2 groups of patients. The first group displayed STAT3 mutations or SOCS3 methylation and overexpressed STAT3 target genes. The second group, including 2 TET2-mutated cases, significantly underexpressed genes known to be downregulated in angioimmunoblastic T-cell lymphoma. Our results provide new insights into the pathogenesis of NK-cell proliferative disorders and, potentially, new therapeutic opportunities

Image 1_v1_Population-based input function (PBIF) applied to dynamic whole-body 68Ga-DOTATOC-PET/CT acquisition.tif

RationalTo validate a population-based input function (PBIF) model that alleviates the need for scanning since injection time in dynamic whole-body (WBdyn) PET.MethodsThirty-seven patients with suspected/known well-differentiated neuroendocrine tumors were included (GAPETNET trial NTC03576040). All WBdyn 68Ga-DOTATOC-PET/CT acquisitions were performed on a digital PET system (one heart-centered 6 min-step followed by nine WB-passes). The PBIF model was built from 20 image-derived input functions (IDIFs) obtained from a respective number of patients’ WBdyn exams using an automated left-ventricle segmentation tool. All IDIF peaks were aligned to the median time-to-peak, normalized to patient weight and administrated activity, and then fitted to an exponential model function. PBIF was then applied to 17 independent patient studies by scaling it to match the respective IDIF section at 20–55 min post-injection time windows corresponding to WB-passes 3–7. The ratio of area under the curves (AUCs) of IDIFs and PBIF3–7 were compared using a Bland–Altman analysis (mean bias ± SD). The Patlak-estimated mean Ki for physiological uptake (Ki-liver and Ki-spleen) and tumor lesions (Ki-tumor) using either IDIF or PBIF were also compared.ResultsThe mean AUC ratio (PBIF/IDIF) was 0.98 ± 0.06. The mean Ki bias between PBIF3–7 and IDIF was −2.6 ± 6.2% (confidence interval, CI: −5.8; 0.6). For Ki-spleen and Ki-tumor, low relative bias with low SD were found [4.65 ± 7.59% (CI: 0.26; 9.03) and 3.70 ± 8.29% (CI: −1.09; 8.49) respectively]. For Ki-liver analysis, relative bias and SD were slightly higher [7.43 ± 13.13% (CI: −0.15; 15.01)].ConclusionOur study showed that the PBIF approach allows for reduction in WBdyn DOTATOC-PET/CT acquisition times with a minimum gain of 20 min.</p

Image 2_v1_Population-based input function (PBIF) applied to dynamic whole-body 68Ga-DOTATOC-PET/CT acquisition.tif

RationalTo validate a population-based input function (PBIF) model that alleviates the need for scanning since injection time in dynamic whole-body (WBdyn) PET.MethodsThirty-seven patients with suspected/known well-differentiated neuroendocrine tumors were included (GAPETNET trial NTC03576040). All WBdyn 68Ga-DOTATOC-PET/CT acquisitions were performed on a digital PET system (one heart-centered 6 min-step followed by nine WB-passes). The PBIF model was built from 20 image-derived input functions (IDIFs) obtained from a respective number of patients’ WBdyn exams using an automated left-ventricle segmentation tool. All IDIF peaks were aligned to the median time-to-peak, normalized to patient weight and administrated activity, and then fitted to an exponential model function. PBIF was then applied to 17 independent patient studies by scaling it to match the respective IDIF section at 20–55 min post-injection time windows corresponding to WB-passes 3–7. The ratio of area under the curves (AUCs) of IDIFs and PBIF3–7 were compared using a Bland–Altman analysis (mean bias ± SD). The Patlak-estimated mean Ki for physiological uptake (Ki-liver and Ki-spleen) and tumor lesions (Ki-tumor) using either IDIF or PBIF were also compared.ResultsThe mean AUC ratio (PBIF/IDIF) was 0.98 ± 0.06. The mean Ki bias between PBIF3–7 and IDIF was −2.6 ± 6.2% (confidence interval, CI: −5.8; 0.6). For Ki-spleen and Ki-tumor, low relative bias with low SD were found [4.65 ± 7.59% (CI: 0.26; 9.03) and 3.70 ± 8.29% (CI: −1.09; 8.49) respectively]. For Ki-liver analysis, relative bias and SD were slightly higher [7.43 ± 13.13% (CI: −0.15; 15.01)].ConclusionOur study showed that the PBIF approach allows for reduction in WBdyn DOTATOC-PET/CT acquisition times with a minimum gain of 20 min.</p