Diffusion-weighted MR imaging of native and transplanted kidneys

Applications of diffusion-weighted (DW) magnetic resonance (MR) imaging outside the brain have gained increasing importance in recent years. Owing to technical improvements in MR imaging units and faster sequences, the need for noninvasive imaging without contrast medium administration, mainly in patients with renal insufficiency, can be met successfully by applying this technique. DW MR imaging is quantified by the apparent diffusion coefficient (ADC), which provides information on diffusion and perfusion simultaneously. By using a biexponential fitting process of the DW MR imaging data, these two entities can be separated, because this type of fitting process can serve as an estimate of both the perfusion fraction and the true diffusion coefficient. DW MR imaging can be applied for functional evaluation of the kidneys in patients with acute or chronic renal failure. Impairment of renal function is accompanied by a decreased ADC. Acute ureteral obstruction leads to perfusion and diffusion changes in the affected kidney, and renal artery stenosis results in a decreased ADC. In patients with pyelonephritis, diffuse or focal changes in signal intensity are seen on the high-b-value images, with increased signal intensity corresponding to low signal intensity on the ADC map. The feasibility and reproducibility of DW MR imaging in patients with transplanted kidneys have already been demonstrated, and initial results seem to be promising for the assessment of allograft deterioration. Overall, performance of renal DW MR imaging, presuming that measurements are of high quality, will further boost this modality, particularly for early detection of diffuse renal conditions, as well as more accurate characterization of focal renal lesions.

Metastases in normal-sized pelvic lymph nodes: detection with diffusion-weighted MR imaging

PURPOSE To prospectively assess the diagnostic performance of diffusion-weighted (DW) magnetic resonance (MR) imaging in the detection of pelvic lymph node metastases in patients with prostate and/or bladder cancer staged as N0 with preoperative cross-sectional imaging. MATERIALS AND METHODS This study was approved by an independent ethics committee. Written informed consent was obtained from all patients. Patients with no enlarged lymph nodes on preoperative cross-sectional images who were scheduled for radical resection of the primary tumor and extended pelvic lymph node dissection were enrolled. All patients were examined with a 3-T MR unit, and examinations included conventional and DW MR imaging of the entire pelvis. Image analysis was performed by three independent readers blinded to any clinical information. Metastases were diagnosed on the basis of high signal intensity on high b value DW MR images and morphologic features (shape, border). Histopathologic examination served as the standard of reference. Sensitivity and specificity were calculated, and bias-corrected 95% confidence intervals (CIs) were obtained with the bootstrap method. The Fleiss and Cohen κ and median test were applied for statistical analyses. RESULTS A total of 4846 lymph nodes were resected in 120 patients. Eighty-eight lymph node metastases were found in 33 of 120 patients (27.5%). Short-axis diameter of these metastases was less than or equal to 3 mm in 68, more than 3 mm to 5 mm in 13, more than 5 mm to 8 mm in five; and more than 8 mm in two. On a per-patient level, the three readers correctly detected metastases in 26 (79%; 95% CI: 64%, 91%), 21 (64%; 95% CI: 45%, 79%), and 25 (76%; 95% CI: 60%, 90%) of the 33 patients with metastases, with respective specificities of 85% (95% CI: 78%, 92%), 79% (95% CI: 70%, 88%), and 84% (95% CI: 76%, 92%). Analyzed according to hemipelvis, lymph node metastases were detected with histopathologic examination in 44 of 240 pelvic sides (18%); the three readers correctly detected these on DW MR images in 26 (59%; 95% CI: 45%, 73%), 19 (43%; 95% CI: 27%, 57%), and 28 (64%; 95% CI: 47%, 78%) of the 44 cases. CONCLUSION DW MR imaging enables noninvasive detection of small lymph node metastases in normal-sized nodes in a substantial percentage of patients with prostate and bladder cancer diagnosed as N0 with conventional cross-sectional imaging techniques.

Systematic analysis of the intravoxel incoherent motion threshold separating perfusion and diffusion effects: Proposal of a standardized algorithm

PURPOSE To systematically evaluate the dependence of intravoxel-incoherent-motion (IVIM) parameters on the b-value threshold separating the perfusion and diffusion compartment, and to implement and test an algorithm for the standardized computation of this threshold. METHODS Diffusion weighted images of the upper abdomen were acquired at 3 Tesla in eleven healthy male volunteers with 10 different b-values and in two healthy male volunteers with 16 different b-values. Region-of-interest IVIM analysis was applied to the abdominal organs and skeletal muscle with a systematic increase of the b-value threshold for computing pseudodiffusion D*, perfusion fraction Fp , diffusion coefficient D, and the sum of squared residuals to the bi-exponential IVIM-fit. RESULTS IVIM parameters strongly depended on the choice of the b-value threshold. The proposed algorithm successfully provided optimal b-value thresholds with the smallest residuals for all evaluated organs [s/mm2]: e.g., right liver lobe 20, spleen 20, right renal cortex 150, skeletal muscle 150. Mean D* [10(-3) mm(2) /s], Fp [%], and D [10(-3) mm(2) /s] values (±standard deviation) were: right liver lobe, 88.7 ± 42.5, 22.6 ± 7.4, 0.73 ± 0.12; right renal cortex: 11.5 ± 1.8, 18.3 ± 2.9, 1.68 ± 0.05; spleen: 41.9 ± 57.9, 8.2 ± 3.4, 0.69 ± 0.07; skeletal muscle: 21.7 ± 19.0; 7.4 ± 3.0; 1.36 ± 0.04. CONCLUSION IVIM parameters strongly depend upon the choice of the b-value threshold used for computation. The proposed algorithm may be used as a robust approach for IVIM analysis without organ-specific adaptation. Magn Reson Med, 2014. © 2014 Wiley Periodicals, Inc.

Accelerated magnetic resonance diffusion tensor imaging of the median nerve using simultaneous multi-slice echo planar imaging with blipped CAIPIRINHA.

PURPOSE To investigate the feasibility of MR diffusion tensor imaging (DTI) of the median nerve using simultaneous multi-slice echo planar imaging (EPI) with blipped CAIPIRINHA. MATERIALS AND METHODS After federal ethics board approval, MR imaging of the median nerves of eight healthy volunteers (mean age, 29.4 years; range, 25-32) was performed at 3 T using a 16-channel hand/wrist coil. An EPI sequence (b-value, 1,000 s/mm(2); 20 gradient directions) was acquired without acceleration as well as with twofold and threefold slice acceleration. Fractional anisotropy (FA), mean diffusivity (MD) and quality of nerve tractography (number of tracks, average track length, track homogeneity, anatomical accuracy) were compared between the acquisitions using multivariate ANOVA and the Kruskal-Wallis test. RESULTS Acquisition time was 6:08 min for standard DTI, 3:38 min for twofold and 2:31 min for threefold acceleration. No differences were found regarding FA (standard DTI: 0.620 ± 0.058; twofold acceleration: 0.642 ± 0.058; threefold acceleration: 0.644 ± 0.061; p ≥ 0.217) and MD (standard DTI: 1.076 ± 0.080 mm(2)/s; twofold acceleration: 1.016 ± 0.123 mm(2)/s; threefold acceleration: 0.979 ± 0.153 mm(2)/s; p ≥ 0.074). Twofold acceleration yielded similar tractography quality compared to standard DTI (p > 0.05). With threefold acceleration, however, average track length and track homogeneity decreased (p = 0.004-0.021). CONCLUSION Accelerated DTI of the median nerve is feasible. Twofold acceleration yields similar results to standard DTI. KEY POINTS • Standard DTI of the median nerve is limited by its long acquisition time. • Simultaneous multi-slice acquisition is a new technique for accelerated DTI. • Accelerated DTI of the median nerve yields similar results to standard DTI.

Consolidation properties and strength characteristics of ODP Site 204-1244 sediments

Eight whole-core samples from Ocean Drilling Program Site 1244, Hydrate Ridge, Cascadia continental margin, were provided to Massachusetts Institute of Technology (Cambridge, Massachusetts, USA) for geotechnical characterization. The samples were collected from depths ranging from 5 to 136 meters below seafloor (mbsf). Seven of the eight whole-core samples were located within the gas hydrate stability zone, whereas the eighth sample was located in the free gas zone. Atterberg limits testing showed that the average liquid limit of the soil is 81% and the average plastic limit is 38%, giving an average plasticity index of 43%. The liquid limit is sensitive to oven drying, shown by a drop in liquid limit to 64% when tests were performed on an oven-dried sample. Loss on ignition averages 5.45 wt%. Constant rate of strain consolidation (CRSC) tests were performed to obtain the compression characteristics of the soil, as well as to determine the stress history of the site. CRSC tests also provided hydraulic conductivity and coefficient of consolidation characteristics for these sediments. The compression ratio (Cc) ranges from 0.340 to 0.704 (average = 0.568). Cc is fairly constant to a depth of 79 mbsf, after which Cc decreases downhole. The recompression ratio (Cr) ranges from 0.035 to 0.064 (average = 0.052). Cr is constant throughout the depth range. In situ hydraulic conductivity varies between 1.5 x 10**-7 and 3 x 10**-8 cm/s and shows no trend with depth. Ko-consolidated undrained compression/extension (CKoUC/E) tests were also performed to determine the peak undrained shear strength, stress-strain curve, and friction angle. The normalized undrained strength ranges from 0.29 to 0.35. The friction angle ranges from 27 to 37. Because of the limited amount of soil, CRSC and CKoUC/E tests were also conducted on resedimented specimens.

Influence of glycerin and lecithin inclusion in the diet on liver characteristics and lipid fraction in the serum of brownegg laying hens at 55 week of age

The effects of the inclusion of raw glycerin (GLYC) and raw lecithin, in the diet (23 to 55 wk) on liver characteristics and various serum lipid fractions were studied in brown egg-laying hens at 55 wk of age. The control diets were based on corn, soybean meal, and 4% supplemental fat and contained 2,750 kcal AMEn/kg, 16.5% CP, and 0.73% digestible Lys. The diets were arranged as a 2 × 3 factorial with 2 levels of GLYC (0 and 7%) and 3 animal fat to lecithin ratios (4:0, 2:2, and 0:4%). Each treatment was replicated 8 times and the experimental unit was a cage with 10 hens. At 55 wk of age, 2 hens per cage replicate were randomly selected, weighed individually, and slaughtered by CO2 inhalation. Liver was immediately removed and weighed and the color recorded by spectrophotometry. In addition, blood samples from one bird per replicate were collected from the wing vein and the concentration of total cholesterol, low and high density lipoprotein cholesterol, and triglycerides were determined. The data were analyzed as a completely randomized design and the main effects of GLYC and lecithin content of the diet and the interactions were determined. No interactions between GLYC and lecithin content of the diets were detected for any of the variables studied. Liver characteristics and serum lipid traits were not affected by the inclusion of GLYC in the diet. The substitution of animal fat by lecithin, however, reduced the redness (a* 14.9 to 13.8) and yellowness (b* 8.60 to 7.20) values of the liver (P < 0.05) but did not affect the content of serum lipid fractions. It is concluded that the inclusion of GLYC and lecithin in the diet did not affect liver size or serum lipid fraction. However, the inclusion of lecithin reduced the a* and b* value of the liver

Do stressful times call for team-based working? A study of psychiatric nurses in UK mental healthcase

Background: Team-based working is now an inherent part of effective health care delivery. Previous research has identified that team working is associated with positive mental health and well-being outcomes for individuals operating in an effective team environment. This is a particularly important topic in the health services context, although little empirical attention has been paid to mental-health services. Psychiatric nurses work on a day-to-day basis with a particularly stressful and demanding client group in an environment which is characterised by high demands, uncertainty, and limited resources. This paper specifically focuses on psychiatric nurses working in National Health Service (NHS) and casts some light on the ways in which effective team-based working can help to alleviate a number of occupational stressors and strains. Method: A questionnaire method (2005 NHS Staff Survey) was employed to collect data from 6655 psychiatric nurses from 64 different NHS Trusts. The hypotheses were concerned with four overall measures from the survey; effective team working, occupational stress, work pressure and social support. Hypothesis 1 stated that effective team working will have a significant negative relationship with occupational stress and work pressure. Further, Hypothesis 2 stated that social support from supervisors and co-workers will moderate this relationship. Findings: Data was treated with a series of regression analyses. For Hypothesis 1, working in a real team did have main effects on work pressure and accounted for 1.6 per cent of the variance. Using the Nagelkerke R square value, working in a real team also had main effects on occupational stress an accounted for approximately 2.8 per cent of the variance. Further, the Exp (B) value of 0.662 suggests that the odds of suffering from occupational stress are cut by 33.8 per cent when a psychiatric nurse works in a real team. Results failed to provide support for Hypothesis 2. The analysis then went on to adopt a unique approach for assessing the extent of real team-based working, distinguishing between real teams, and a number of pseudo team typologies, as well as the absence of teamwork all together. As was hypothesised, results demonstrated that psychiatric nurses working in real teams (ones with clear objectives, where-by team members work closely with one another to achieve team objectives and meet regularly to discuss team effectiveness and how it can be improved) experienced the lowest levels of stress and work pressure of the sample. However, contrary to prediction, results indicated that psychiatric nurses working in any type of pseudo team actually experienced significantly higher levels of stress and work pressure than those who did not report as working in a team at all. Discussion: These findings have serious implications for NHS Mental Health Trusts, which may not be implementing, structuring and managing their nursing teams adequately. Indeed, results suggest that poorly-structured team work may actually facilitate stress and pressure in the workplace. Conversely, well-structured real teams serve to reduce stress and work pressure, which in turn not only enhances the working lives and well-being of psychiatric nurses, but also greatly improves the service that the NHS provides to its users.

Stressful times call for team-based measures:psychiatric nursing in the UK National Health Service

Background: Team-based working is now an inherent part of effective health care delivery. Previous research has identified that team working is associated with positive mental health and well-being outcomes for individuals operating in an effective team environment. This is a particularly important topic in the health services context, although little empirical attention has been paid to mental-health services. Psychiatric nurses work on a day-to-day basis with a particularly stressful and demanding client group in an environment which is characterised by high demands, uncertainty, and limited resources. This paper specifically focuses on psychiatric nurses working in National Health Service (NHS) and casts some light on the ways in which effective team-based working can help to alleviate a number of occupational stressors and strains. Method: A questionnaire method (2005 NHS Staff Survey) was employed to collect data from 6655 psychiatric nurses from 64 different NHS Trusts. The hypotheses were concerned with four overall measures from the survey; effective team working, occupational stress, work pressure and social support. Hypothesis 1 stated that effective team working will have a significant negative relationship with occupational stress and work pressure. Further, Hypothesis 2 stated that social support from supervisors and co-workers will moderate this relationship. Findings: Data was treated with a series of regression analyses. For Hypothesis 1, working in a real team did have main effects on work pressure and accounted for 1.6 per cent of the variance. Using the Nagelkerke R square value, working in a real team also had main effects on occupational stress an accounted for approximately 2.8 per cent of the variance. Further, the Exp (B) value of 0.662 suggests that the odds of suffering from occupational stress are cut by 33.8 per cent when a psychiatric nurse works in a real team. Results failed to provide support for Hypothesis 2. The analysis then went on to adopt a unique approach for assessing the extent of real team-based working, distinguishing between real teams, and a number of pseudo team typologies, as well as the absence of teamwork all together. As was hypothesised, results demonstrated that psychiatric nurses working in real teams (ones with clear objectives, where-by team members work closely with one another to achieve team objectives and meet regularly to discuss team effectiveness and how it can be improved) experienced the lowest levels of stress and work pressure of the sample. However, contrary to prediction, results indicated that psychiatric nurses working in any type of pseudo team actually experienced significantly higher levels of stress and work pressure than those who did not report as working in a team at all. Discussion: These findings have serious implications for NHS Mental Health Trusts, which may not be implementing, structuring and managing their nursing teams adequately. Indeed, results suggest that poorly-structured team work may actually facilitate stress and pressure in the workplace. Conversely, well-structured real teams serve to reduce stress and work pressure, which in turn not only enhances the working lives and well-being of psychiatric nurses, but also greatly improves the service that the NHS provides to its users.

Length-weight relationship of benthic bivalves of the Andoni Flats, Niger Delta, Nigeria

The length weight relationship of three benthic bivalves namely, Senilia (= Anadara) senilis (bloody cockle), Tagelus adansonii (knife clam), Tellina nymphalis (soft shell clam) from the Andoni Flats were determined. The bivalves which are of ecological importance were obtained from the intertidal areas of the Andoni Flats. Shell lengths of the bivalves were measured and corresponding dry weight measurements were also taken. The data obtained were then subjected to regression analysis using the FAO-ICLARM Fish Stock Assessment Tools (FiSAT). The length weight relationships obtained from the FiSAT analysis indicated isometric growth for Senilia (= Anadara) senilis, with slope (b) value of 2.942; positive allometric growth for Tagelus adansonii, with a ‘b’ value of 3.395 and negative allometric growth for Tellina nymphalis with ‘b’ value of 2.633. KEYWORDS: bivalves, length-weight, isometric growth, allometric growth, cockle, clam.

Length-weight relationships of six syngnathid species from Ria Formosa, SW Iberian coast

In this study, the length-weight (LWR) parameters were estimated for six syngnathid species, including 2 seahorses and 4 pipefishes, from Ria Formosa, a temperate lagoon from the south coast of Portugal. A total of 5070 fishes were used to determine the LWR. The estimated b value ranged from 2.95 (Nerophis ophidion) to 3.36 (Syngnathus abaster). To the authors' best knowledge, LWR parameters were estimated for the first time for Nerophis ophidion and Syngnathus typhle for the Atlantic waters. Data here present are essential for management and conservation of these flagship species.

Voriconazole-Induced Inhibition of the Fungicidal Activity of Amphotericin B in Candida Strains with Reduced Susceptibility to Voriconazole: an Effect Not Predicted by the MIC Value Alone.

An antagonistic effect of voriconazole on the fungicidal activity of sequential doses of amphotericin B has previously been demonstrated in Candida albicans strains susceptible to voriconazole. Because treatment failure and the need to switch to other antifungals are expected to occur more often in infections that are caused by resistant strains, it was of interest to study whether the antagonistic effect was still seen in Candida strains with reduced susceptibility to voriconazole. With the hypothesis that antagonism will not occur in voriconazole-resistant strains, C. albicans strains with characterized mechanisms of resistance against voriconazole, as well as Candida glabrata and Candida krusei strains with differences in their degrees of susceptibility to voriconazole were exposed to voriconazole or amphotericin B alone, to both drugs simultaneously, or to voriconazole followed by amphotericin B in an in vitro kinetic model. Amphotericin B administered alone or simultaneously with voriconazole resulted in fungicidal activity. When amphotericin B was administered after voriconazole, its activity was reduced (median reduction, 61%; range, 9 to 94%). Levels of voriconazole-dependent inhibition of amphotericin B activity differed significantly among the strains but were not correlated with the MIC values (correlation coefficient, -0.19; P = 0.65). Inhibition was found in C. albicans strains with increases in CDR1 and CDR2 expression but not in the strain with an increase in MDR1 expression. In summary, decreased susceptibility to voriconazole does not abolish voriconazole-dependent inhibition of the fungicidal activity of amphotericin B in voriconazole-resistant Candida strains. The degree of interaction could not be predicted by the MIC value alone.

Value of PET/CT versus contrast-enhanced CT in identifying chest wall invasion (T3) by NSCLC [B-671]

Purpose: To determine the diagnostic value of 18F-FDG PET/CT versus contrastenhanced CT in identifying chest wall invasion by NSCLC. Methods and Materials: The primary selection criterion was a peripheral tumor of any size with contact to the chest wall. A total of 25 patients with pathologically proven NSCLC satisfied these criteria. Chest wall invasion was interpreted upon PET/CT when a frank costal or intercostal 18F-FDG uptake was identified with or without concomitant morphologic alterations. On the other hand, the existence of periosteal rib reaction/erosion, chest wall thickening or obliteration of the pleural fat layer either separately or combined were considered essential diagnostic criteria for disease extension into the chest wall upon contrast-enhanced CT. The results were correlated with the final histological analysis. Results: Among the studied cohort, 13/25 (52%) patients had chest wall invasion consistent with T3 disease. Both PET/CT and contrast-enhanced CT successfully identified 12/13 (92%) of these patients. The single false-negative result was due to parietal pleural invasion. On the other hand, one false-positive result was encountered by PET/CT in a dyspneic patient; whereas, CT analysis revealed false-positive results in six patients. In these patients, periosteal rib reaction (n = 2) or asymmetric enlargement of adjacent chest wall muscles (n = 1) were identified along with an obliterated pleural fat layer (n = 6). The sensitivity, specificity, and accuracy of PET/CT and contrast-enhanced CT were 92, 91 and 92% versus 92, 50 and 72%. Conclusion: 18F-FDG PET/CT is an accurate diagnostic modality in identifying.

The predictive value of preoperative B-type natriuretic peptide in children undergooing heart surgery.

Introduction: Low cardiac output syndrome is frequent in childrenafter heart surgery for congenital heart disease and may result in pooroutcome and increased morbidity. In the adult population, preoperativebrain natriuretic peptide (BNP) was shown to be predictive of postoperative complications. In children, the value of preoperative BNP onpostoperative outcome is not so clear. The aim of this study was todetermine the predictive value of preoperative BNP on postoperativeoutcome and low cardiac output syndrome in children after heartsurgery for congenital heart disease.Methods: We examined, retrospectively, the postoperative course of97 pediatric patients (mean age 3.7 years, range 0-14 years old) whounderwent heart surgery in a tertiary care pediatric intensive caresetting. NTproBNP was measured preoperatively in all patients(median 412 pg/ml, range 12-35'000 pg/ml). Patients were divided intothree groups according to their NTproBNP levels (group 1: 0-300 pg/ml, group 2: 300-600 pg/ml, group 3: >600 pg/ml) and then,correlations with postoperative outcomes were examined.Results: We found that patients with a high preoperative BNP requiredmore frequently prolonged (>2 days) mechanical ventilation (33%vs 40% vs 61%, p = 0.045) and stayed more frequently longer than6 days in the intensive care unit (42% vs 50% vs 71%, p = 0.03).However, high preoperative BNP was not correlated with occurrenceof low cardiac output syndrome.Conclusion: Preoperative BNP cannot be used, in children, as areliable and sole predictor of postoperative low cardiac outputsyndrome. However it may help identify, before surgery, those patientsat risk of having a difficult postoperative course.

Integrated Analysis of High-Resolution Gene Expression and Copy Number Profiling Identified Biallelic Deletion of CDKN2A/2B Tumor Suppressor Locus As the Most Frequent and Unique Genomic Abnormality in Diffuse Large B-Cell Lymphoma (DLBCL) with Strong Prognostic Value in Both GCB and ABC Subtypes and Not Overcome by a Dose-Intensive Immunochemotherapy Regimen Plus Rituximab. Results of a Prospective GELA Clinical Trial Program

Background and aim of the study: Genomic gains and losses play a crucial role in the development and progression of DLBCL and are closely related to gene expression profiles (GEP), including the germinal center B-cell like (GCB) and activated B-cell like (ABC) cell of origin (COO) molecular signatures. To identify new oncogenes or tumor suppressor genes (TSG) involved in DLBCL pathogenesis and to determine their prognostic values, an integrated analysis of high-resolution gene expression and copy number profiling was performed. Patients and methods: Two hundred and eight adult patients with de novo CD20+ DLBCL enrolled in the prospective multicentric randomized LNH-03 GELA trials (LNH03-1B, -2B, -3B, 39B, -5B, -6B, -7B) with available frozen tumour samples, centralized reviewing and adequate DNA/RNA quality were selected. 116 patients were treated by Rituximab(R)-CHOP/R-miniCHOP and 92 patients were treated by the high dose (R)-ACVBP regimen dedicated to patients younger than 60 years (y) in frontline. Tumour samples were simultaneously analysed by high resolution comparative genomic hybridization (CGH, Agilent, 144K) and gene expression arrays (Affymetrix, U133+2). Minimal common regions (MCR), as defined by segments that affect the same chromosomal region in different cases, were delineated. Gene expression and MCR data sets were merged using Gene expression and dosage integrator algorithm (GEDI, Lenz et al. PNAS 2008) to identify new potential driver genes. Results: A total of 1363 recurrent (defined by a penetrance > 5%) MCRs within the DLBCL data set, ranging in size from 386 bp, affecting a single gene, to more than 24 Mb were identified by CGH. Of these MCRs, 756 (55%) showed a significant association with gene expression: 396 (59%) gains, 354 (52%) single-copy deletions, and 6 (67%) homozygous deletions. By this integrated approach, in addition to previously reported genes (CDKN2A/2B, PTEN, DLEU2, TNFAIP3, B2M, CD58, TNFRSF14, FOXP1, REL...), several genes targeted by gene copy abnormalities with a dosage effect and potential physiopathological impact were identified, including genes with TSG activity involved in cell cycle (HACE1, CDKN2C) immune response (CD68, CD177, CD70, TNFSF9, IRAK2), DNA integrity (XRCC2, BRCA1, NCOR1, NF1, FHIT) or oncogenic functions (CD79b, PTPRT, MALT1, AUTS2, MCL1, PTTG1...) with distinct distribution according to COO signature. The CDKN2A/2B tumor suppressor locus (9p21) was deleted homozygously in 27% of cases and hemizygously in 9% of cases. Biallelic loss was observed in 49% of ABC DLBCL and in 10% of GCB DLBCL. This deletion was strongly correlated to age and associated to a limited number of additional genetic abnormalities including trisomy 3, 18 and short gains/losses of Chr. 1, 2, 19 regions (FDR < 0.01), allowing to identify genes that may have synergistic effects with CDKN2A/2B inactivation. With a median follow-up of 42.9 months, only CDKN2A/2B biallelic deletion strongly correlates (FDR p.value < 0.01) to a poor outcome in the entire cohort (4y PFS = 44% [32-61] respectively vs. 74% [66-82] for patients in germline configuration; 4y OS = 53% [39-72] vs 83% [76-90]). In a Cox proportional hazard prediction of the PFS, CDKN2A/2B deletion remains predictive (HR = 1.9 [1.1-3.2], p = 0.02) when combined with IPI (HR = 2.4 [1.4-4.1], p = 0.001) and GCB status (HR = 1.3 [0.8-2.3], p = 0.31). This difference remains predictive in the subgroup of patients treated by R-CHOP (4y PFS = 43% [29-63] vs. 66% [55-78], p=0.02), in patients treated by R-ACVBP (4y PFS = 49% [28-84] vs. 83% [74-92], p=0.003), and in GCB (4y PFS = 50% [27-93] vs. 81% [73-90], p=0.02), or ABC/unclassified (5y PFS = 42% [28-61] vs. 67% [55-82] p = 0.009) molecular subtypes (Figure 1). Conclusion: We report for the first time an integrated genetic analysis of a large cohort of DLBCL patients included in a prospective multicentric clinical trial program allowing identifying new potential driver genes with pathogenic impact. However CDKN2A/2B deletion constitutes the strongest and unique prognostic factor of chemoresistance to R-CHOP, regardless the COO signature, which is not overcome by a more intensified immunochemotherapy. Patients displaying this frequent genomic abnormality warrant new and dedicated therapeutic approaches.

The predictive value of preoperative B-type natriuretic peptide in children undergoing cardiac surgery

Introduction: B-type natriuretic peptide (BNP) is a biomarker of myocardial stress. In children, the value of preoperative BNP on postoperative outcome is unclear. The aim of this study was to determine the predictive value of preoperative NT-proBNP on postoperative outcome in children after congenital heart surgery. Results: Ninety-seven patients were included in the study with a median age of 3.3 years [0.7-5.2]. Preoperative median NT-proBNP was 412 pg/ml [164-1309]. NT-proBNP was above the P95 reference value for age in 56 patients (58%). Preoperative NT-proBNP was significantly higher in patients who had mechanical ventilation duration of more than 2 days (1156 pg/ml [281-1951] vs. 267 pg/ml [136-790], p=0.003) and who stayed more than 6 days in the pediatric intensive care unit (727 pg/ml [203-1951] vs. 256 pg/ml [136-790], p=0.007). However, preoperative NT-proBNP was not significantly higher in patients with an increased inotropic score, a prolonged cardiopulmonary bypass time or an increased surgical risk category. Conclusions: An elevated preoperative NT-proBNP reflects hemodynamic status and cardiac dysfunction, and therefore is a valuable adjunct in predicting a complicated postoperative course. ___________________________________ Introduction: Le peptide natriurétique type B (BNP) est un marqueur reflétant le stress myocardique. Dans la population pédiatrique, la signification des valeurs préopératoire de BNP, en particulier sur l'évolution postopératoire, n'est pas clairement établie. Le but de l'étude est de déterminer la valeur prédictive de la partie NT sérique du BNP (NT-proBNP) sur l'évolution post opératoire d'enfants porteur d'une cardiopathie congénitale et ayant eu une chirurgie cardiaque. Résultats: Nonante-sept enfants ont été inclus dans l'étude, avec un âge médian de 3.3 ans [0.7-5.2]. La valeur médiane du NT-proBNP préopératoire était de 412 pg/ml [164-1309]. Le NT-proBNP préopératoire était supérieur au P95 des valeurs de référence pour l'âge chez 56 patients (58%). Le NT-proBNP préopératoire était significativement plus élevé chez les patients ayant eu plus de deux jours de ventilation mécanique dans la période postopératoire (1156 pg/ml [281-1951] vs. 267 pg/ml [136-790], p=0.003) et ayant été hospitalisés plus de 6 jours dans l'unité de soins intensifs pédiatrique (727 pg/ml [203-1951] vs. 256 pg/ml [136-790], p=0.007). Par contre, le NT-proBNP préopératoire n'était pas significativement plus élevé chez les patients ayant eu un score d'inotrope élevé pendant leur hospitalisation aux soins intensifs, un temps de circulation extracorporelle prolongé ou ayant subi une chirurgie avec un risque chirurgical élevé. Conclusions: Un NT-proBNP sérique élevé en préopératoire reflète l'importance du stress myocardique induit par l'hémodynamique et la dysfonction myocardique, il est un marqueur qui permet d'améliorer l'identification des patients à risque d'avoir une évolution post opératoire compliquée.