Five-year outcomes of rapid-deployment aortic valve replacement with the Edwards Intuity valve.

BACKGROUND: This report presents 5-year outcomes of the rapid-deployment Edwards Intuity valve in a prospective, single-center study. METHODS: All patients who underwent an aortic valve replacement (AVR) with an Edwards Intuity bioprosthesis at La Timone Hospital, Marseille, France, from July 2012 to June 2015 were assessed over a 5-year follow-up period. The primary outcome was overall mortality at 5 years. Secondary outcomes were reoperation, overall mortality and stroke, cardiovascular mortality, composite endpoints defined by the updated Valve Academic Research Consortium-2 (VARC-2), periprosthetic regurgitation, prosthesis-patient mismatch, and the need for new pacemaker implantation. RESULTS: In total, 170 consecutive patients were assessed, of which 67.1% were males. The mean age was 76 years, mean EuroSCORE II was 3.5% and 5-year overall mortality was 12.4%. At 5 years, reoperation was 2.9%, overall mortality and stroke was 4.1% per patient-year, and cardiovascular mortality was 4.7%. VARC clinical efficacy and VARC time-related valve safety were achieved in 46.0% and 59.9% of patients, respectively. At one month VARC device success was 71.2% and VARC early safety was 87.1%. At one year, mild and moderate periprosthetic regurgitation were 2.4% and 0.6%, respectively, and moderate and severe prosthesis-patient mismatch were 18.8% and 4.8%, respectively. Conduction disturbances needing new PPI occurred in 3.5% patients. CONCLUSION: The 5-year outcomes of AVR with the Edwards Intuity valve system demonstrate satisfactory midterm safety and excellent haemodynamic performance.

[COVID-19 inside dialysis units]. / La dialyse chronique face à la COVID-19.

COVID-19 has been the center of global attention and concern for the last months. Patients undergoing dialysis and especially those treated at the hospital are likely to be infected, due to their mandatory presence at the hospital several times a week and due to their intrinsic fragility in regard of chronic kidney disease, often an older age, and the presence of many associated comorbidities. Thereby, patients with chonic kidney disease treated by haemodialysis have higher odds of a more severe COVID-19 infection with a high mortality rate. Prevention is thus a high priority for these patients.

Au cours des derniers mois, la COVID-19 a été au centre des préoccupations et de l'attention de chacun. Les patients dialysés, et surtout ceux hémodialysés en centre, représentent une population particulièrement à risque de contamination vu la nécessité de se rendre à l'hôpital plusieurs fois par semaine et compte tenu de leur fragilité intrinsèque liée au statut de malade rénal chronique, un âge souvent plus avancé, et de nombreuses comorbidités. Ils ont donc un risque de développer une infection grave et potentiellement mortelle. Dès lors, la stratégie de prévention est d'une importance capitale pour ces patients.

Survival in dialysis patients is different between patients with diabetes as primary renal disease and patients with diabetes as a co-morbid condition.

AIMS/HYPOTHESIS: A previous study in Dutch dialysis patients showed no survival difference between patients with diabetes as primary renal disease and those with diabetes as a co-morbid condition. As this was not in line with our hypothesis, we aimed to verify these results in a larger international cohort of dialysis patients. METHODS: For the present prospective study, we used data from the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry. Incident dialysis patients with data on co-morbidities (n = 15,419) were monitored until kidney transplantation, death or end of the study period (5 years). Cox regression was performed to compare survival for patients with diabetes as primary renal disease, patients with diabetes as a co-morbid condition and non-diabetic patients. RESULTS: Of the study population, 3,624 patients (24%) had diabetes as primary renal disease and 1,193 (11%) had diabetes as a co-morbid condition whereas the majority had no diabetes (n = 10,602). During follow-up, 7,584 (49%) patients died. In both groups of diabetic patients mortality was higher compared with the non-diabetic patients. Mortality was higher in patients with diabetes as primary renal disease than in patients with diabetes as a co-morbid condition, adjusted for age, sex, country and malignancy (HR 1.20, 95% CI 1.10, 1.30). An analysis stratified by dialysis modality yielded similar results. CONCLUSIONS/INTERPRETATION: Overall mortality was significantly higher in patients with diabetes as primary renal disease compared with those with diabetes as a co-morbid condition. This suggests that survival in diabetic dialysis patients is affected by the extent to which diabetes has induced organ damage.

Dispersal capacities of pollen, seeds and spores: insights from comparative analyses of spatial genetic structures in bryophytes and spermatophytes.

Introduction: The dramatic fluctuations of climate conditions since the late Tertiary era have resulted in major species range shifts. These movements were conditioned by geographic barriers and species dispersal capacities. In land plants, gene flow occurs through the movement of male gametes (sperm cells, pollen grains), which carry nDNA, and diaspores (spores, seeds), which carry both cpDNA and nDNA, making them an ideal model to compare the imprints of past climate change on the spatial genetic structures of different genomic compartments. Based on a meta-analysis of cpDNA and nDNA sequence data in western Europe, we test the hypotheses that nDNA genetic structures are similar in bryophytes and spermatophytes due to the similar size of spores and pollen grains, whereas genetic structures derived from the analysis of cpDNA are significantly stronger in spermatophytes than in bryophytes due to the substantially larger size of seeds as compared to spores. Methods: Sequence data at 1-4 loci were retrieved for 11 bryophyte and 17 spermatophyte species across their entire European range. Genetic structures between and within southern and northern populations were analyzed through F and N statistics and Mantel tests. Results and discussion: Gst and Nst between southern and northern Europe derived from cpDNA were significantly higher, and the proportion of significant tests was higher in spermatophytes than in bryophytes. This suggests that in the latter, migrations across mountain ranges were sufficient to maintain a homogenous allelic structure across Europe, evidencing the minor role played by mountain ranges in bryophyte migrations. With nDNA, patterns of genetic structure did not significantly differ between bryophytes and spermatophytes, in line with the hypothesis that spores and pollen grains exhibit similar dispersal capacities due to their size similarity. Stronger levels of genetic differentiation between southern and northern Europe, and within southern Europe, in spermatophytes than in bryophytes, caused by higher long-distance dispersal capacities of spores as compared to seeds, may account for the strikingly higher levels of endemism in spermatophytes than in bryophytes in the Mediterranean biodiversity hotspot.

Disentangling the roles of chance, abiotic factors and biotic interactions among epiphytic bryophyte communities in a tropical rainforest (Yunnan, China).

Epiphytes offer an appealing framework to disentangle the contributions of chance, biotic and abiotic drivers of species distributions. In the context of the stress-gradient theory, we test the hypotheses that (i) deterministic (i.e., non-random) factors play an increasing role in communities from young to old trees, (ii) negative biotic interactions increase on older trees and towards the tree base, and (iii) positive interactions show the reverse pattern. Bryophyte species distributions and abiotic conditions were recorded on a 1.1 ha tropical rainforest canopy crane site. We analysed co-occurrence patterns in a niche modelling framework to disentangle the roles of chance, abiotic factors and putative biotic interactions among species pairs. 76% of species pairs resulted from chance. Abiotic factors explained 78% of non-randomly associated species pairs, and co-occurrences prevailed over non-coincidences in the remaining species pairs. Positive and negative interactions mostly involved species pairs from the same versus different communities (mosses versus liverworts) and life forms, respectively. There was an increase in randomly associated pairs from large to small trees. No increase in negative interactions from young to old trees or from the canopy to the base was observed. Our results suggest that epiphytic bryophyte community composition is primarily driven by environmental filtering, whose importance increases with niche complexity and diversity. Biotic interactions play a secondary role, with a very marginal contribution of competitive exclusion. Biotic interactions vary among communities (mosses versus liverworts) and life forms, facilitation prevailing among species from the same community and life form, and competition among species from different communities and life forms.

[The follow-up of chronic renal failure]. / Le suivi de l'insuffisance rénale chronique.

The follow-up of chronic kidney failure is a long and complex process. The diagnosis of the kidney disease and the level of renal failure have first to be established. A strategy for slowing the evolution of chronic kidney disease has to be build. The blockade of the renin angiotensin system and the control of the cardiovascular risk factors are the main components of this strategy. The evaluation and the treatment of the classical complications of chronic kidney disease should also take place. Correction of anemia, and of phosphocalcic complications need specific therapies. Preparation for dialysis and transplantation have to be taken into account. Such a follow-up deserves a close collaboration between general practitioners and nephrologists.

Bryophytes are predicted to lag behind future climate change despite their high dispersal capacities.

The extent to which species can balance out the loss of suitable habitats due to climate warming by shifting their ranges is an area of controversy. Here, we assess whether highly efficient wind-dispersed organisms like bryophytes can keep-up with projected shifts in their areas of suitable climate. Using a hybrid statistical-mechanistic approach accounting for spatial and temporal variations in both climatic and wind conditions, we simulate future migrations across Europe for 40 bryophyte species until 2050. The median ratios between predicted range loss vs expansion by 2050 across species and climate change scenarios range from 1.6 to 3.3 when only shifts in climatic suitability were considered, but increase to 34.7-96.8 when species dispersal abilities are added to our models. This highlights the importance of accounting for dispersal restrictions when projecting future distribution ranges and suggests that even highly dispersive organisms like bryophytes are not equipped to fully track the rates of ongoing climate change in the course of the next decades.

Cardiac magnetic resonance assessment of left ventricular dilatation in chronic severe left-sided regurgitations: comparison with standard echocardiography.

PURPOSE: The purpose of this study was to investigate the potential additional value of cardiac magnetic resonance (CMR) in the assessment of left ventricular (LV) dilatation and dysfunction by comparison to standard echocardiography in patients with chronic left-sided valvular regurgitation. MATERIALS AND METHODS: We prospectively enrolled patients with chronic severe mitral regurgitation (MR) or aortic regurgitation (AR). They underwent standard echocardiography and CMR using aortic flow and LV-function sequences. LV dilatation or dysfunction was assessed with each technique, based on thresholds used for surgery indication. Reference regurgitation severity was defined following previously reported CMR-based regurgitant volume thresholds. RESULTS: A total of 71 patients with chronic severe MR (n=44) or severe AR (n=27) were prospectively included. There were 60 men and 11 women with a mean age of 61±14 (SD) years (range: 18-83 years). CMR-based regurgitation severity was significantly greater in the LV dysfunction group when assessed with CMR (MR, P=0.011; AR, P=0.006) whereas it was not different when LV dysfunction was assessed using standard echocardiography. Among standard echocardiography and CMR volumetric indices, CMR-derived end-diastolic volume showed the best ability to predict regurgitation severity (area under the curve [AUC]=0.78 for MR; AUC=0.91 for AR). Diagnostic thresholds identified on receiver operating characteristics-curve analysis were lower than those of current European recommendations and closer to North-American guidelines. CONCLUSION: CMR assessment of LV end-diastolic volume in chronic severe left-sided regurgitations is more reliably associated with CMR-based regurgitant volume by comparison with standard echocardiography diameter. CMR may provide useful evaluation before surgery decision for severe asymptomatic regurgitations.

X-ray crystal structure of GarR-tartronate semialdehyde reductase from Salmonella typhimurium.

Tartronate semialdehyde reductases (TSRs), also known as 2-hydroxy-3-oxopropionate reductases, catalyze the reduction of tartronate semialdehyde using NAD as cofactor in the final stage of D-glycerate biosynthesis. These enzymes belong to family of structurally and mechanically related beta-hydroxyacid dehydrogenases which differ in substrate specificity and catalyze reactions in specific metabolic pathways. Here, we present the crystal structure of GarR a TSR from Salmonella typhimurium determined by the single-wavelength anomalous diffraction method and refined to 1.65 A resolution. The active site of the enzyme contains L-tartrate which most likely mimics a position of a glycerate which is a product of the enzyme reaction. The analysis of the TSR structure shows also a putative NADPH binding site in the enzyme.

[Heavy-hearted: chronic constrictive pericarditis]. / "Un coeur serré": péricardite chronique constrictive.

The purpose of this report is to describe a case involving a 62-year-old Moroccan woman hospitalized for generalized edema that lead to diagnosis of chronic constrictive pericarditis. Diagnosis was confirmed on the basis of pericardial calcification and typical hemodynamic findings. New imaging techniques such as cardiac MRI allow accurate anatomical and physiological assessment in difficult cases. While tuberculosis is rarely involved in industrialized countries, it is a frequent factor in developing countries. The usual treatment consists of pericardectomy in association with standard antituberculosis drugs if association with tuberculosis is established or highly likely.

[Surgical management of cardiac wounds: cardiac or general surgical service?]. / Plaies du coeur, prise en charge de chirurgie cardiaque ou générale?

OBJECTIVE: To define modalities of cardiac wound management with a special emphasis on the initial direction of the patient toward a surgical service, rapid diagnosis, and surgical treatment. METHOD: Sixteen patients with thoracic injury to the region of the heart treated between 1996 and 2006 were evaluated retrospectively. Pre-operative clinical data, echography, and CT results were collected; time elapsed between injury and treatment, type of surgical treatment, use of cardio-pulmonary bypass, morbidity and mortality were evaluated. RESULTS: There were 16 patients (12 men); age ranged from 18 to 80 with an average of 45.7 years. Nine patients had penetrating cardiac wounds, two had blunt trauma, and five suffered iatrogenic trauma. Cardio-pulmonary bypass was used in two cases. The mean time elapsed between trauma and surgical evaluation was 63 minutes (p=0.18). In all cases, surgery consisted of a myorraphy without coronary or valvular repair. Post-operative complications occurred in 4 patients (25%) and resulted in 2 deaths (12.5%). Complication and death were associated with a prolonged interval between injury and surgical management. CONCLUSION: Patients with cardiac wounds should be transported to the nearest surgical hospital. There are no benefits to cardio-pulmonary bypass in cardiac trauma.

[World kidney Day 2008: the impact of epidemiology of kidney diseases in Belgium]. / Journée Mondiale du Rein 2008 : impact de l'epidémiologie des maladies rénales en Belgique.

The World Kidney Day offers a crucial opportunity to the Belgian associations of nephrologists to inform public and medical communities about the global problem of chronic kidney disease (CKD). According to epidemiological data from GNFB/ NBVN registries in our country, cardiovascular diseases and diabetes 2 are responsible for an increasing amount of CKD cases with pejorative evolution to end-stage renal disease requiring cost-effective renal replacement therapies (haemodialysis, peritoneal dialysis or renal transplantation). In these patients, the high level of comorbidities and the late referral to the nephrologists are recognized as enhanced morbidity and mortality factors. These facts underline the need for the nephrologists to stimulate collaboration with general practitioners and specialists from other disciplines in order to set up systematic screening procedures and early follow-up of patients at risk of developing CKD. These procedures should contribute to reduce the progression rate of renal function impairment.

Amplification of the IMP dehydrogenase gene in Chinese hamster cells resistant to mycophenolic acid.

The regulation of IMP dehydrogenase (IMPDH) was analyzed in Chinese hamster V79 cell variants that exhibit different degrees of resistance to the cytotoxic effect of mycophenolic acid, a specific inhibitor of IMPDH. Western blot (immunoblot) analysis with an IMPDH antiserum revealed a 14- to 27-fold increase in the amount of enzyme in the mycophenolic acid-resistant cells. The antiserum was also used to screen for a phage containing the IMPDH cDNA sequence from a lambda gt11 expression library. Northern blot (RNA blot) analyses of total cellular and poly(A)+ RNA showed that an IMPDH cDNA probe hybridized to a 2.2-kilobase transcript, the amount of which was associated with increased resistance. Southern blotting with the probe indicated an amplification of the IMPDH gene in the mycophenolic acid-resistant cells. Our findings suggest that the acquired mycophenolic acid resistance of the V79 cell variants is associated with increases in the amount and activity of IMPDH and the number of IMPDH gene copies.

Regulation of IMP dehydrogenase gene expression by its end products, guanine nucleotides.

To study the regulation of IMP dehydrogenase (IMPDH), the rate-limiting enzyme of guanine nucleotide biosynthesis, we examined the effects of nucleosides, nucleotides, nucleotide analogs, or the IMPDH inhibitor mycophenolic acid (MPA) on the steady-state levels of IMPDH mRNA. The results indicated that IMPDH gene expression is regulated inversely by the intracellular level of guanine ribonucleotides. We have shown that treatment with guanosine increased the level of cellular guanine ribonucleotides and subsequently reduced IMPDH steady-state mRNA levels in a time- and dose-dependent manner. Conversely, MPA treatment diminished the level of guanine ribonucleotides and increased IMPDH mRNA levels. Both of these effects on the steady-state level of IMPDH mRNA could be negated by cotreatment with guanosine and MPA. The down regulation of IMPDH gene expression by guanosine or its up regulation by MPA was not due to major changes in transcriptional initiation and elongation or mRNA stability in the cytoplasm but rather was due to alterations in the levels of the IMPDH mRNA in the nucleus. These results suggest that IMPDH gene expression is regulated by a posttranscriptional, nuclear event in response to fluctuations in the intracellular level of guanine ribonucleotides.

Crystal structures of delta1-pyrroline-5-carboxylate reductase from human pathogens Neisseria meningitides and Streptococcus pyogenes.

L-proline is an amino acid that plays an important role in proteins uniquely contributing to protein folding, structure, and stability, and this amino acid serves as a sequence-recognition motif. Proline biosynthesis can occur via two pathways, one from glutamate and the other from arginine. In both pathways, the last step of biosynthesis, the conversion of delta1-pyrroline-5-carboxylate (P5C) to L-proline, is catalyzed by delta1-pyrroline-5-carboxylate reductase (P5CR) using NAD(P)H as a cofactor. We have determined the first crystal structure of P5CR from two human pathogens, Neisseria meningitides and Streptococcus pyogenes, at 2.0 angstroms and 2.15 angstroms resolution, respectively. The catalytic unit of P5CR is a dimer composed of two domains, but the biological unit seems to be species-specific. The N-terminal domain of P5CR is an alpha/beta/alpha sandwich, a Rossmann fold. The C-terminal dimerization domain is rich in alpha-helices and shows domain swapping. Comparison of the native structure of P5CR to structures complexed with L-proline and NADP+ in two quite different primary sequence backgrounds provides unique information about key functional features: the active site and the catalytic mechanism. The inhibitory L-proline has been observed in the crystal structure.

Increased inosine-5'-phosphate dehydrogenase gene expression in solid tumor tissues and tumor cell lines.

Inosine-5'-phosphate (IMP) dehydrogenase, a regulatory enzyme of guanine nucleotide biosynthesis, may play a role in cell proliferation and malignancy. To assess this role we examined IMP dehydrogenase expression in a series of human solid tumor tissues and tumor cell lines in comparison with their normal counterparts. Increased IMP dehydrogenase gene expression was observed in brain tumors relative to normal brain tissue and in sarcoma cells relative to normal fibroblasts. Similarly, in several B- and T-lymphoid leukemia cell lines, elevated levels of IMP dehydrogenase mRNA and cellular enzyme were observed in comparison with the levels in peripheral blood lymphocytes. These results are consistent with an association between increased IMP dehydrogenase expression and either enhanced cell proliferation or malignant transformation.

Value of CMR in quantification of paravalvular aortic regurgitation after TAVI.

AIMS: To assess the value of cardiac magnetic resonance (CMR) using phase-contrast velocity mapping for paravalvular aortic regurgitation (PAR) quantification. METHODS AND RESULTS: All patients undergoing transcatheter aortic valve implantation (TAVI) in our centre between November 2012 and August 2013, without CMR-contraindication were included. PAR severity was assessed 5 days after TAVI using: transthoracic echocardiography (TTE) and CMR [regurgitant volume (RV), regurgitant fraction (RF)]. Aortic regurgitation (AR) index was obtained during TAVI. Thirty of 51 patients who underwent TAVI were included (COREVALVE, n = 10; or EDWARDS SAPIEN XT, n = 20). At TTE, PAR was mild in 22, moderate in 3, and severe in 5 patients. Reliable phase-contrast images were acquired at the sino-tubular junction for SAPIEN and at the tubular portion of the ascending aorta for COREVALVE. The reproducibility of CMR was high (coefficient of correlation = 0.99 for intra- and inter-operator variability). At CMR, RV, and RF were significantly (P < 0.0005) correlated with AR severity at TTE, with mean RF values at 9.2 ± 7.6% in mild, 20.3 ± 4.2% in moderate, and 46.8 ± 10.8% in severe PAR. A cut-off value of RF < 14% at CMR accurately discriminated mild from moderate/severe (sensitivity: 100%, specificity: 82%). The mean AR index was 29.4 ± 6 for mild and 13.8 ± 5 for moderate/severe PAR. Three patients had a RF > 14% and a low AR index <25 despite a mild PAR at TTE, suggesting an underestimation at TTE. CONCLUSION: CMR is a reproducible, accurate, and reliable method to assess PAR severity. CMR may allow correcting an underestimation at TTE when AR index is doubtful.

Induction of differentiation in human promyelocytic HL-60 leukemia cells activates p21, WAF1/CIP1, expression in the absence of p53.

The melanoma differentiation associated gene, mda-6, which is identical to the P53-inducible gene WAF1/CIP1, encodes an M(r) 21,000 protein (p21) that can directly inhibit cell growth by repressing cyclin dependent kinases. mda-6 was identified using subtraction hybridization by virtue of its enhanced expression in human melanoma cells induced to terminally differentiate by treatment with human fibroblast interferon and the anti-leukemic compound mezerein (Jiang and Fisher, 1993). In the present study, we demonstrate that mda-6 (WAF1/CIP1) is an immediate early response gene induced during differentiation of the promyelocytic HL-60 leukemia cell line along the granulocytic or macrophage/monocyte pathway. mda-6 gene expression in HL-60 cells is induced within 1 to 3 h during differentiation along the macrophage/monocyte pathway evoked by 12-0-tetradecanoyl phorbol-13-acetate (TPA) or 1,25-dihydroxyvitamin D3 (Vit D3) or the granulocytic pathway produced by retinoic acid (RA) or dimethylsulfoxide (DMSO). Immunoprecipitation analyses using an anti-p21 antibody indicate a temporal induction of p21 protein following treatment with TPA, DMSO or RA. A relationship between rapid induction of mda-6 gene expression and differentiation is indicated by a delay in this expression in an HL-60 cell variant resistant to TPA-induced growth arrest and differentiation. A similar delay in mda-6 gene expression is not observed in Vit D3 treated TPA-resistant variant cells that are also sensitive to induction of monocytic differentiation. Since HL-60 cells have a null-p53 phenotype, these results demonstrate that p21 induction occurs during initiation of terminal differentiation in a p53-independent manner. In this context, p21 may play a more global role in growth control and differentiation than originally envisioned.

p210 bcr-abl confers overexpression of inosine monophosphate dehydrogenase: an intrinsic pathway to drug resistance mediated by oncogene.

The p210 bcr-abl fusion protein tyrosine kinase oncogene has been implicated in the pathogenesis of chronic granulocytic leukemia (CGL). Specific intracellular functions performed by p210 bcr-abl have recently been delineated. We considered the possibility that p210 bcr-abl may also regulate the abundance of inosine 5'-monophosphate dehydrogenase (IMPDH) which is a rate-limiting enzyme for de novo guanylate synthesis. We performed studies of the inhibition of IMPDH by tiazofurin, which acts as a competitive inhibitor through its active species that mimics nicotinamide adenine dinucleotide (NAD), i.e. thiazole-4-carboxamide adenine dinucleotide (TAD). The mean inhibitory concentration (IC50) of tiazofurin for cellular proliferation inhibition was 2.3-2.8-fold greater in cells expressing p210 bcr-abl than in their corresponding parent cells proliferating under the influence of growth factors or in growth factor-independent derivative cells not expressing detectable p210 bcr-abl. IMPDH activity was 1.5-2.3-fold greater within cells expressing p210 bcr-abl than in their parent cells. This increase in enzyme activity was a result of 2-fold increased IMPDH protein as determined by immunoblotting. In addition, an increase in the Km value for NAD utilization by IMPDH was observed in p210 bcr-abl transformed cells, but this increase was within the range of resident NAD concentrations observed in the cells. Increased IMPDH protein in p210 bcr-abl transformed cells was traced to an increased level of IMP dehydrogenase II messenger RNA. Thus, regulation of IMPDH gene expression is mediated at least in part by the bcr-abl gene product and may therefore be indicative of a specific mechanism of intrinsic resistance to tiazofurin.

Renal hematoma in a patient undergoing hemodialysis. Complication of acquired renal cystic disease.

A spontaneous renal hematoma developed in a patient treated by long-term intermittent maintenance hemodialysis. This scanty complication of hemodialysis was related to the recently described acquired cystic disease of the kidneys. Diagnosis was ascertained before nephrectomy by computed tomography and selective renal angiography.