Beneficial hemodynamic effects of inhibiting ANP catabolism in congestive heart failure

Pepper, Beverly (escultora)Primer pla de l'obra. També conegut com a "Cel caigut, Espiral arbrada", realitzat amb ceràmica

Impact of timing administration of mesenchymal stromal cells on serum creatinine following renal ischemia/ reperfusion in rats

peer reviewedExperimental models of renal ischemia/reperfusion (I/R) have suggested protective effects of mesenchymal stromal cells (MSC) therapy. Still, param- eters of MSC injection, including volume, route and timing of cell administration, remain largely debated. Particularly, MSC infusion in mouse has been shown to be beneficial “a priori” but deleterious “a posteriori” of renal I/R injury. In order to further investigate the influence of the timing of MSC administration, we used 10-week-old Lewis rats categorized in 4 groups. Groups 1 (MSC D-7, n = 10) and 2 (MSC D + 1, n = 7) received caudal i.v. injection of MSC (1.5 9 106 in 1 ml of saline) 7 days before or 1 day after renal I/R, respectively. Control groups 3 (saline D-7, n = 6) and 4 (saline D + 1, n = 6) received equal volume of saline at similar time points. Left renal ischemia (by clamping of the renal pedicle) lasted 45 min. Right nephrectomy was simultaneously performed. Blood sample was collected from inferior vena cava at 48 h post reperfusion. MSC phenotype was confirmed by FACS analysis. In groups 1 and 3, serum creatinine (SCr) reached 1.4 ` 0.7 versus 2.4 ` 0.8 mg/dl, respectively (p < 0.05). In groups 2 and 4, SCr was 4.9 ` 0.7 versus 3.3 ` 0.9 mg/dl, respectively (p < 0.001). Furthermore, SCr levels were statistically worse when MSC were administered after renal I/R in comparison to a priori infusion (p < 0.0001). In conclusion, MSC administration 7 days prior to renal I/R attenuates kidney injury in comparison to (i) saline infusion or (ii) MSC infusion 1 day after renal I/R. Conversely, on the basis of SCr levels, MSC therapy performed after renal I/R worsens kidney injury in rats

Mesenchymal Stromal Cell Therapy in Ischemia/Reperfusion Injury.

Ischemia/reperfusion injury (IRI) represents a worldwide public health issue of increasing incidence. IRI may virtually affect all organs and tissues and is associated with significant morbidity and mortality. Particularly, the duration of blood supply deprivation has been recognized as a critical factor in stroke, hemorrhagic shock, or myocardial infarction, as well as in solid organ transplantation (SOT). Pathophysiologically, IRI causes multiple cellular and tissular metabolic and architectural changes. Furthermore, the reperfusion of ischemic tissues induces both local and systemic inflammation. In the particular field of SOT, IRI is an unavoidable event, which conditions both short- and long-term outcomes of graft function and survival. Clinically, the treatment of patients with IRI mostly relies on supportive maneuvers since no specific target-oriented therapy has been validated thus far. In the present review, we summarize the current literature on mesenchymal stromal cells (MSC) and their potential use as cell therapy in IRI. MSC have demonstrated immunomodulatory, anti-inflammatory, and tissue repair properties in rodent studies and in preliminary clinical trials, which may open novel avenues in the management of IRI and SOT

Felodipine-metoprolol combination tablet: A valuable option to initiate antihypertensive therapy?

The aim of the present study was to assess the efficacy and tolerability of a calcium antagonist/β-blocker fixed combination tablet used as first-line antihypertesnive therapy in comparison with an angiotensin converting enzyme inhibitor and placebo. Patients with uncomplicated essential hypertension (diastolic blood pressure between 95 and 110 mm Hg at the end of a 4-week run-in period) were randomly allocated to a double-blind, 12-week treatment with either a combination tablet of felodipine and metoprolol (Logimax), 5/50 mg daily (n = 321), enalapril, 10 mg daily (n = 321), or placebo (n = 304), with the possibility of doubling the dose after 4 or 8 weeks of treatment if needed (diastolic blood pressure remaining >90 mm Hg). The combined felodipine-metoprolol treatment controlled blood pressure (diastolic ≤90 mm Hg 24 h after dose) in 72% of patients after 12 weeks, as compared with 49% for enalapril and 30% for placebo. A dose adjustment was required in 38% of patients receiving the combination, in 63% of patients allocated to placebo, and 61% of enalapril-treated patients. The overall incidence of adverse events was 54.5% during felodipine-metoprolol treatment; the corresponding values for enalapril and placebo were 51.7% and 47.4%, respectively. Withdrawal of treatment due to adverse events occurred in 18 patients treated with the combination, in 10 patients on enalapril, and 12 patients on placebo. No significant change in patients' well-being was observed in either of the three study groups. These results show that a fixed combination tablet of felodipine and metoprolol allows to normalize blood pressure in a substantially larger fraction of patients than enalapril given alone. This improved efficacy is obtained without impairing the tolerability. The fixed-dose combination of felodipine and metoprolol, therefore, may become a valuable option to initiate antihypertensive treatment. Am J Hypertens 1999;12:915-920 © 1999 American Journal of Hypertension, Lt

Genetic diversity of Echinococcus multilocularis specimens isolated from Belgian patients with alveolar echinococcosis using EmsB microsatellites analysis.

The genetic diversity of Echinococcus multilocularis (E. multilocularis) specimens isolated from patients with alveolar echinococcosis (AE), is a major field of investigation to correlate with sources of infection, clinical manifestations and prognosis of the disease. Molecular markers able to distinguish samples are commonly used worldwide, including the EmsB microsatellite. Here, we report the use of the EmsB microsatellite polymorphism data mining for the retrospective typing of Belgian specimens of E. multilocularis infecting humans. A total of 18 samples from 16 AE patients treated between 2006 and 2021 were analyzed through the EmsB polymorphism. Classification of specimens was performed through a dendrogram construction in order to compare the similarity among Belgian samples, some human referenced specimens on the EWET database (EmsB Website for the Echinococcus Typing) and previously published EmsB profiles from red foxes circulating in/near Belgium. According to a comparison with human European specimens previously genotyped in profiles, the 18 Belgian ones were classified into three EmsB profiles. Four specimens could not be assigned to an already known profile but some are near to EWET referenced samples. This study also highlights that some specimens share the same EmsB profile with profiles characterized in red foxes from north Belgium, the Netherlands, Luxembourg and French department near to the Belgian border. Furthermore, Belgian specimens present a genetic diversity and include one profile that don't share similarities with the ones referenced in the EWET database. However, at this geographical scale, there is no clear correlation between EmsB profiles and geographical location. Further studies including additional clinical samples and isolates from foxes and rodents of south Belgium are necessary to better understand the spatial and temporal circumstances of human infections but also a potential correlation between EmsB profiles and parasite virulence

Evaluation of a commercial IgG monotest assay: a new automated chemiluminescent immunoassay for the serodiagnosis of cystic echinococcosis

Background: Cystic echinococcosis (CE) is a zoonotic disease caused by the tapeworm Echinococcus granulosus complex. The geographical distribution is worldwide with variable incidences. In Belgium, only few imported cases are reported each year. Serodiagnosis of CE is performed by using a combination of immunoassays which are mainly based on crude hydatid antigens. The Belgian National Reference Laboratory, has evaluated the CE-IVD Hydatidosis VirClia® IgG chemiluminescent immunoassay and compared it with two other immunoassays. Methods: A total of 79 sera were retrospectively included from 15 patients with CE, 29 with alveolar echinococcosis, 16 with toxocariasis and 19 negative controls. Three immunoassays were compared: the Hydatidosis VirClia® IgG monotest assay which was run on the Virclia® Lotus (Vircell, Spain); the Ridascreen® Echinococcus IgG assay (R-Biopharm, Germany) and the Bordier® Echinococcus granulosus IgG ELISA (Bordier, Switzerland), which were tested on the ETI-Max 3000 immunoassay analyzer (DiaSorin, Italy). The McNemar test is used for statistical analysis. Results: All three methods showed 100% sensitivity. Regarding specificity, the Ridascreen® (78.1%) and VirClia® (76.6%) assays showed comparable performance (p-value: 1), while the Bordier® assay had poor results (54,7%) (p-value: 0,0007). The Bordier® assay showed 76% cross-reactions with E. multilocularis (22/29) and 31% with Toxocara sp. (5/16), while the VirClia® assay showed 51,7% (15/29) and no cross-reaction with Toxocara antigens. For Ridascreen® assay, 34% and 19% cross-reactions were observed for E. multilocularis (10/29) and Toxocara sp. (3/16), respectively. Non-specific reactions in negative controls were only observed with the Ridascreen® (1/19) and Bordier® assays (2/19). The shortest turnaround time was observed with Virclia® Lotus: 1 hour versus 3 hours for two other assays. Conclusions: All assays showed very high sensitivity. However, regarding specificity, the VirClia® performs better than the Bordier® and similarly to the Ridascreen® assay. Besides, the ready-to-use monotest format offers many advantages such as a quicker methodology and a reduced workflow. Therefore, the VirClia® assay is an efficient screening method for the detection of CE but should always be combined with an immunoblot assay to assess the specificity

Molecular typing of Belgian Echinococcus multilocularis specimens from alveolar echinococcosis human lesions using EmsB microsatellites analysis

peer reviewedBackground. The genetic diversity of Echinococcus multilocularis (Em) is a major field of investigations to correlate with sources of infection or variable clinical manifestations of the alveolar echinococcosis (AE). Molecular markers able to distinguish strains are already used such as EmsB microsatellites. This marker is present in about 40 copies in the Em genome. Here, we report the use of EmsB microsatellite polymorphism for the typing of Belgian specimens isolated from patients with AE between 2019 and 2020. Material and methods. Total genomic DNA was isolated from liver, pleural fluid and bile samples using a DNA extraction kit for tissue (Qiagen). The PCR was performed according to Knapp et al, 2020. The EmsB A primer was 5’-labeled with FAM-fluorochrome. Fragment size analysis was performed on an ABI3500 automatic sequencer (ThermoFisher). The fluorescence signal was detected by colorimetric reading. Correspondences were established to assess the size of the amplified fragments using Gene mapper (ThermoFisher). “R studio” was used to generate a distance matrix, calculate the Euclidian distance and obtain a UPGMA method dendrogram in order to assess the similarity among samples. The profiles obtained were compared with those included in the EWET data collection. Results Seven specimens have been successfully analyzed. According to a comparison with European samples previously characterized (Knapp et al., 2020), 3 Belgian specimens shared the same P5 genomic profile while one strain had a P8 profile. These P5 and P8 strains were included into European profiles with strains from France, Switzerland and Germany. The three other isolates could not be classified into existing profiles but were placed between P6 and P7 profiles. Five strains originated from patients living in Wallonia, the Southern part of Belgium (Namur, Hainaut and Luxembourg) while the two others originated from neighboring provinces (Walloon Brabant and Bruxelles). Conclusions The EmsB microsatellites analysis allowed to genotypically characterize Em clinical specimens isolated in Belgium for the first time. This study highlights that some samples share the same genotypic profile but that heterogenetic diversity exist in Belgium. Some profiles are unique and differ from other European profiles. Further studies including more clinical samples are ongoing

Impact of donor age over 70 years in donation after circulatory death liver transplantation: a 15 years of experience

peer reviewedBackground: Advanced donor age has been identified as a risk factor in donation after circulatory death (DCD 3) liver transplantation (LT), associated with poor graft function and development of ischemic cholangiopathy. In this study, we evaluated the results after DCD 3 LT using grafts from donors over 70 years compared to younger grafts (<70 years). Methods: We retrospectively analysed outcome after DCD 3 LT (n=228), comparing donors 70 years (n=53) and <70 years (n=175) from our center between 2003 and 2020. The two age groups were compared in terms of graft and patient survivals at 1, 3 and 5 years, in terms of donor and recipient demographics, transplant conditions and labora- tory values. Results: The overall graft survivals at 1, 3 and 5 years were 88, 75, 70 per cent respectively. Graft survival rates were not significantly diffe- rent at 5 years between the two groups (P = 0,536). No difference was noted in incidence of acute rejection, biliary strictures, hepatic artery thrombosis or retransplantation rates between the two groups. The time of cold ischemia was significatively lower in the older group (mean 235 min; SD 72) than in younger donor (mean 258 min; SD 72) (p=0.012). The posttransplant AST peak was significatively higher in the advanced age donor group than the second group with 2201±2703 U/L vs 1561U/L (SD 2151±2151 U/L), respectively (p= 0.04).Conclusions: Results for DCD LT from 70-yr-old grafts were similar to those from younger donors. Advanced donors should not be discarded for liver donation if other donor risk factors (such as cold ischemia time and graft quality) are limited

Early liver transplantation for severe alcohol-related hepatitis not responding to medical treatment: a prospective controlled study

peer reviewedBackground: Early liver transplantation for severe alcohol-related hepatitis is an emerging treatment option. We aimed to assess the risk of alcohol relapse 2 years after early liver transplantation for alcohol-related hepatitis compared with liver transplantation for alcohol-related cirrhosis after at least 6 months of abstinence. Methods: We conducted a multicentre, non-randomised, non-inferiority, controlled study in 19 French and Belgian hospitals. All participants were aged 18 years or older. There were three groups of patients recruited prospectively: patients with severe alcohol-related hepatitis who did not respond to medical treatment and were eligible for early liver transplantation according to a new selection scoring system based on social and addiction items that can be quantified in points (early transplantation group); patients with alcohol-related cirrhosis listed for liver transplantation after at least 6 months of abstinence (standard transplantation group); patients with severe alcohol-related hepatitis not responding to medical treatment not eligible for early liver transplantation according to the selection score (not eligible for early transplantation group), this group did not enter any further liver transplantation processes. We also defined a historical control group of patients with severe alcohol-related hepatitis unresponsive to medical therapy and non-transplanted. The primary outcome was the non-inferiority of 2-year rate of alcohol relapse after transplantation in the early transplantation group compared with the standard transplantation group using the alcohol timeline follow back (TLFB) method and a prespecified non-inferiority margin of 10%. Secondary outcomes were the pattern of alcohol relapse, 2-year survival rate post-transplant in the early transplantation group compared with the standard transplantation group, and 2-year overall survival in the early transplantation group compared with patients in the not eligible for early transplantation group and historical controls. This trial is registered with ClinicalTrials.gov, NCT01756794. Findings: Between Dec 5, 2012, and June 30, 2016, we included 149 patients with severe alcohol-related hepatitis: 102 in the early transplantation group and 47 in the not eligible for early transplantation group. 129 patients were included in the standard transplantation group. 68 patients in the early transplantation group and 93 patients in the standard transplantation group received a liver transplant. 23 (34%) patients relapsed in the early transplantation group, and 23 (25%) patients relapsed in the standard transplantation group; therefore, the non-inferiority of early transplantation versus standard transplantation was not demonstrated (absolute difference 9·1% [95% CI –∞ to 21·1]; p=0·45). The 2-year rate of high alcohol intake was greater in the early transplantation group than the standard transplantation group (absolute difference 16·7% [95% CI 5·8–27·6]) The time spent drinking alcohol was not different between the two groups (standardised difference 0·24 [95% CI −0·07 to 0·55]), but the time spent drinking a large quantity of alcohol was higher in the early transplantation group than the standard transplantation group (standardised difference 0·50 [95% CI 0·17–0·82]). 2-year post-transplant survival was similar between the early transplantation group and the standard transplantation group (hazard ratio [HR] 0·87 [95% CI 0·33–2·26]); 2-year overall survival was higher in the early transplantation group than the not eligible for early transplantation group and historical controls (HR 0·27 [95% CI 0·16–0·47] and 0·21 [0·13–0·32]). Interpretation: We cannot conclude non-inferiority in terms of rate of alcohol relapse post-transplant between early liver transplantation and standard transplantation. High alcohol intake is more frequent after early liver transplantation. This prospective controlled study confirms the important survival benefit related to early liver transplantation for severe alcohol-related hepatitis; and this study provides objective data on survival and alcohol relapse to tailor the management of patients with severe alcohol-related hepatitis. Funding: The present study has been granted by the French Ministry of Health—Programme Hospitalier de Recherche Clinique 2010