Differential diagnosis of focal nodular hyperplasia with quantitative parametric analysis in contrast-enhanced sonography

OBJECTIVES: We investigated the potential of quantitative parametric analysis in the differential diagnosis of focal nodular hyperplasia (FNH) from other hypervascularized liver focal lesions. MATERIALS AND METHODS: Eighty-five focal liver lesions (in 83 patients) were explored using contrast-enhanced ultrasound (SonoVue and Cadence Contrast Pulse Sequencing) consisting of typical FNH (n=52), hepatocellular carcinoma (n=11), hemangioma with high flow (n=8), hypervascular metastases (n=10), and hepatocellular adenoma (n=4). QontraXt software (AMID, Italy) was used here to estimate the following parameters: maximum peak value, Tr (time corresponding to time for obtaining 63% of the plateau), beta parameter corresponding to the exponential factor, and slope corresponding to the tangent value of the first phase of enhancement. These parameters were obtained from the time-intensity curves derived from the enhancement observed in 2 regions of interest corresponding, respectively, to the whole lesion and the central region only. RESULTS: A significant statistical difference (P<0.05) was found in the values of Tr, beta, and slope between FNH and other hypervascularized lesions on both the whole lesion and central region. Among these parameters, slope appeared as the most valuable whatever the region of interest, ie, central or whole lesion (P<0.01). Central region was more accurate in the differentiation of FNH and concordant with visual characterization. CONCLUSION: Quantitative parametric curve analysis of the different hypervascularized lesions confirms the depiction of the central artery in FNH and thus could help in differentiating this specific focal liver lesion from the others.     

A rapid and inexpensive method for anticipating severe toxicity to fluorouracil and fluorouracil-based chemotherapy

Dihydropyrimidine dehydrogenase (DPD) deficiency leads to dramatic overexposure to fluorouracil (5-FU), resulting in a potentially lethal outcome in patients treated with standard doses. The aim of this study was to validate, in a routine clinical setting, a simple and rapid method to determine the DPD status in a subset of cancer patients, all presenting with life-threatening toxicities following 5-FU or capecitabine intake. In this study, 80 out of 615 patients (13%) suffered severe toxicities, including 5 lethal ones (0.8%), during or after chemotherapy with a fluoropyrimidine drug. Patients with severe toxicities were treated with 5-FU (76 patients) or capecitabine-containing protocols (4 patients). Simplified uracil to di-hydrouracil (U/UH2) ratio determination in plasma was retrospectively performed in these 80 patients, as a surrogate marker of DPD activity. When possible, 5-FU Css determination was performed, and screenings for the canonical IVS14+1G>A mutation were systematically carried out. Comparison of the U/UH2 ratios with a reference, non-toxic population, showed abnormal values suggesting impaired DPD activity in 57 out of the 80 toxic patients (71%) included in this study, and in 4 out of 5 patients (80%) with a fatal outcome. Similarly, drug exposures up to 15 times higher than the range observed in the non-toxic population were also observed. Importantly, no IVS14+1G>A mutation was found in these patients, including those displaying the most severe or lethal toxicities. These data warrant systematic detection of DPD-deficient patients prior to fluoropyrimidine administration, including when oral capecitabine (Xeloda) is scheduled. Finally, the simplified methodology presented here proved to be a low cost and rapid way to identify routinely patients at risk of toxicity with 5-FU or capecitabine.     

Simplified evaluation of CONsciousness disorders (SECONDs) in individuals with severe brain injury: A validation study

BackgroundThe Coma Recovery Scale-Revised (CRS-R) is the gold standard to assess severely brain-injured patients with prolonged disorders of consciousness (DoC). However, the amount of time needed to complete this examination may limit its use in clinical settings. Objective. We aimed to validate a new faster tool to assess consciousness in individuals with DoC.MethodsThis prospective validation study introduces the Simplified Evaluation of CONsciousness Disorders (SECONDs), a tool composed of 8 items: arousal, localization to pain, visual fixation, visual pursuit, oriented behaviors, command-following, and communication (both intentional and functional). A total of 57 individuals with DoC were assessed on 2 consecutive days by 3 blinded examiners: one CRS-R and one SECONDs were performed on 1 day, whereas 2 SECONDs were performed on the other day. A Mann-Whitney U test was used to compare the duration of administration of the SECONDs versus the CRS-R, and weighted Fleiss’ kappa coefficients were used to assess inter-/intra-rater reliability as well as concurrent validity.ResultsIn the 57 participants, the SECONDs was about 2.5 times faster to administer than the CRS-R. The comparison of the CRS-R versus the SECONDs on the same day or the best of the 3 SECONDs led to “substantial” or “almost perfect” agreement (kappa coefficients ranging from 0.78 to 0.85). Intra-/inter-rater reliability also showed almost perfect agreement (kappa coefficients from 0.85 to 0.91 and 0.82 to 0.85, respectively).ConclusionsThe SECONDs appears to be a fast, reliable and easy-to-use scale to diagnose DoC and may be a good alternative to other scales in clinical settings where time constraints preclude a more thorough assessment.     

Lenalidomide maintenance fails to overcome the unfavourable prognosis of low NK-cell counts in rituximab–chemotherapy responsive elderly DLBCL patients: A LYSA group study

Low baseline NK-cell counts (NKCCs) in patients with diffuse large B-cell lymphoma (DLBCL) are associated with a poor prognosis. The REMARC phase III trial (NCT01122472) showed that lenalidomide maintenance prolonged PFS in rituximab–chemotherapy responders. We conducted a REMARC ancillary study analysing the impact of lenalidomide maintenance on the prognostic value of low NKCCs. Blood samples from 335 elderly French patients enrolled in the REMARC trial were analysed by flow cytometry to obtain NKCCs at diagnosis (n = 220), at randomization (n = 186) and/or six months after randomization (n = 184). Baseline NKCCs < 100 cells/μl were associated with shorter PFS and OS (HRs = [2.2 (1.4, 3.3), p < 0.001] and [2.8 (1.7, 4.5), p < 0.001], respectively), independently of aaIPI. In a competing risk analysis, low NKCCs at baseline were associated with a higher risk of relapse/progression (p = 0.0025), but not of death without progression (p = 0.33). Lenalidomide did not affect the prognosis value of low baseline NKCCs (p  = 0.6349). Similar results were obtained for low NKCCs at randomization. Our results demonstrate that low NKCCs at baseline and post rituximab–chemotherapy are robust prognostic factors in DLBCL and reveal that lenalidomide has no impact on this parameter. Other therapeutic strategies aiming at improving NK-cell function could improve outcomes in DLBCL.     

Differential adhesion-inhibitory patterns of antibodies raised against two major variants of the NTS-DBL2X region of VAR2CSA

Background

VAR2CSA is a large polymorphic Plasmodium falciparum protein expressed on infected erythrocytes (IE) that allows their binding in the placenta, thus precipitating placental malaria (PM). The N-terminal part of VAR2CSA that contains the binding site to placental chondroitin sulfate A (CSA) is currently recognized as the most attractive region for vaccine development. An ultimate challenge is to define epitopes in this region that induce a broad cross-reactive adhesion inhibitory antibody response.

Methods

Based on phylogenetic data that identified a dimorphic sequence motif in the VAR2CSA DBL2X, we raised antibodies against the NTS-DBL2X constructs containing one sequence or the other (3D7 and FCR3) and tested their functional properties on P. falciparum isolates from pregnant women and on laboratory-adapted strains.

Results

The CSA binding inhibitory capacity of the antibodies induced varied from one parasite isolate to another (range, 10%–100%), but the combined analysis of individual activity highlighted a broader functionality that increased the total number of isolates inhibited. Interestingly, the differential inhibitory effect of the antibodies observed on field isolates resulted in significant inhibition of all field isolates tested, suggesting that optimal inhibitory spectrum on field isolates from pregnant women might be achieved with antibodies targeting limited variants of the N-terminal VAR2CSA.

Conclusions

Our findings indicate that the NTS-DBL2X region of VAR2CSA can elicit strain-transcending anti-adhesion antibodies and suggest that the combination of the two major variants used here could represent the basis for an effective bivalent VAR2CSA-based vaccine.     

Effectiveness of latex agglutination slide test in the diagnosis of imported invasive amoebiasis in the emergency department

We compared a latex agglutination test (LAT) with enzyme-linked immunosorbent assay and indirect hemagglutination assay in the diagnosis of invasive amoebiasis. A retrospective biological records review has included 639 patients for whom these three serological tests were performed. The sensitivity of the LAT was 97.8% and the specificity was 97%.