Thromboelastometry used for evaluation of blood coagulability in dogs with kidney diseases

Kidney diseases as protein-losing nephropathies are predisposing conditions for thrombosis/thromboembolism in dogs due to increased blood coagulability. The aim of this study was to use thromboelastometry for investigation of changes in haemostasis in dogs affected by renal proteinuria alone or concomitant with azotemia. The study was done at 55 client-owned, healthy (n = 34), proteinuric (n = 14), and proteinuric/azotemic (n = 7) dogs. Blood coagulation was assessed by means of standard coagulation profile and thromboelastometry (in-TEM, ex-TEM, and fib-TEM). In proteinuric dogs only the maximum clot firmness and maximum clot elasticity significantly increased (P P < 0.05) of the variables clotting time, clot formation time, α angle, maximum clot firmness and maximum clot elasticity. After correction for group affiliation, the linear regression analysis showed a non significant association between changes in proteinuria and thromboelastometric profiles. In conclusion, thromboelastometric changes indicating hypercoagulabilty were more consistently found in the dogs with proteinuria/azotemia, than in those with proteinuria alone, suggesting that the former dogs can be considered at higher thrombotic risk. This is the first study where thromboelastometry has been applied to the investigation of haemostatic changes in dogs with kidney diseases

High-Dose Melphalan Plus Thiotepa as Conditioning Regimen before Second Autologous Stem Cell Transplantation for “De Novo” Multiple Myeloma Patients: A Phase II Study

AbstractHigh-dose melphalan (MEL) is the standard therapy for autologous stem cell transplantation (ASCT) in multiple myeloma (MM), although the optimal conditioning regimen remains yet to be identified. Thiotepa (THIO) appears to be a potentially effective option, with broad-spectrum antitumor efficacy that can be added to myeloablative multiagent regimens for ASCT in hematopoietic tumors. We conducted a phase II trial, adding THIO (275 mg/m2) to high-dose MEL (140 mg/m2) before a second ASCT, in a tandem ASCT strategy, in 64 patients with “de novo” MM. Overall, there was no transplant-related mortality. The incidence of neutropenic fever and mucositis (grades 3 to 4) was 39% and 9%, respectively. Median number of days to neutrophil and platelet engraftment were 11 and 12, respectively. After the second transplantation, the complete response improved to 43.8%. Overall response rate was 86%. After a median follow-up of 18.1 months, 13 patients had progressed and 3 died from MM. Median progression-free survival was not reached, and actuarial 2-year rates of progression-free and overall survival were 71% and 88.9%, respectively. Our results suggest that THIO/MEL is a feasible and safe conditioning regimen for ASCT in MM and should be explored for efficacy in a phase III study

Anti-PD1 Consolidation in Patients with Hodgkin Lymphoma at High Risk of Relapse after Autologous Stem Cell Transplantation: A Multicenter Real-Life Study

(1) Background: Consolidation therapy is an emerging strategy for patients with relapsed/refractory (RR) Hodgkin Lymphoma (HL) at high risk of failing salvage autologous stem cell transplantation (ASCT). (2) Objectives: To assess the safety and effectiveness of PD1-blockade consolidation for these high-risk patients. (3) Design: Multi-center retrospective analysis. (4) Methods: We identified 26 patients given anti-PD1 consolidation, from June 2016 to May 2020. (5) Results: Patients displayed the following risk factors: refractory disease (69%), relapse 3, occurred in 12 patients (46.15%) and mainly included skin rashes (41.7%), transaminitis (33.3%), and thyroid hypofunction (25%). Patients completed a median of 13 courses (range 6–30). At a median follow-up of 25.8 months post-ASCT, the median progression-free (PFS) was 42.6 months, with a 2-year PFS and overall survival rates of 79% and 87%, respectively. (6) Conclusions: Post-ASCT consolidation with anti-PD1 is feasible and effective. Further studies are warranted to define the optimal treatment length and patients’ subsets more likely to benefit from this approach

Oral ondansetron versus domperidone for acute gastroenteritis in pediatric emergency departments: Multicenter double blind randomized controlled trial

The use of antiemetics for vomiting in acute gastroenteritis in children is still a matter of debate. We conducted a double-blind randomized trial to evaluate whether a single oral dose of ondansetron vs domperidone or placebo improves outcomes in children with gastroenteritis. After failure of initial oral rehydration administration, children aged 1-6 years admitted for gastroenteritis to the pediatric emergency departments of 15 hospitals in Italy were randomized to receive one oral dose of ondansetron (0.15 mg/kg) or domperidone (0.5 mg/kg) or placebo. The primary outcome was the percentage of children receiving nasogastric or intravenous rehydration. A p value of 0.014 was used to indicate statistical significance (and 98.6% CI were calculated) as a result of having carried out two interim analyses. 1,313 children were eligible for the first attempt with oral rehydration solution, which was successful for 832 (63.4%); 356 underwent randomization (the parents of 125 children did not give consent): 118 to placebo, 119 to domperidone, and 119 to ondansetron. Fourteen (11.8%) needed intravenous rehydration in the ondansetron group vs 30 (25.2%) and 34 (28.8%) in the domperidone and placebo groups, respectively. Ondansetron reduced the risk of intravenous rehydration by over 50%, both vs placebo (RR 0.41, 98.6% CI 0.20-0.83) and domperidone (RR 0.47, 98.6% CI 0.23-0.97). No differences for adverse events were seen among groups. In a context of emergency care, 6 out of 10 children aged 1-6 years with vomiting due to gastroenteritis and without severe dehydration can be managed effectively with administration of oral rehydration solution alone. In children who fail oral rehydration, a single oral dose of ondansetron reduces the need for intravenous rehydration and the percentage of children who continue to vomit, thereby facilitating the success of oral rehydration. Domperidone was not effective for the symptomatic treatment of vomiting during acute gastroenteritis

Microtensile bond strength of a resin cement to feldpathic ceramic after different etching and silanization regimens in dry and aged conditions

Objectives. This study evaluated the durability of bond strength between resin cement and a feldspathic ceramic submitted to different etching regimens with and without silane coupling agent application.Methods. Thirty-two blocks (6.4 mm x 6.4 mm x 4.8 mm) were fabricated using a microparticulate feldspathic ceramic (Vita VM7), ultrasonically cleaned with water for 5 min and randomly divided into four groups, according to the type of etching agent and silanization method: method 1, etching with 10% hydrofluoric (HF) acid gel for I min + silanization; method 2, HF only; method 3, etching with 1.23% acidulated phosphate fluoride (APF) for 5 min + silanization; method 4, APF only. Conditioned blocks were positioned in their individual silicone molds and resin cement (Panavia F) was applied on the treated surfaces. Specimens were stored in distilled water (37 degrees C) for 24 h prior to sectioning. After sectioning the ceramic-cement blocks in x- and Y-axis with a bonded area of approximately 0.6 mm(2), the microsticks of each block were randomly divided into two storage conditions: Dry, immediate testing; TC, thermal cycling (12,000 times) + water storage for 150 d, yielding to eight experimental groups. Microtensile bond strength tests were performed in universal testing machine (cross-head speed: 1 mm/min) and failure types were noted. Data obtained (MPa) were analyzed with three-way ANOVA and Tukey's test (alpha = 0.05).Results. Significant influence of the use of silane (p < 0.0001), storage conditions (p = 0.0013) and surface treatment were observed (p = 0.0014). The highest bond strengths were achieved in both dry and thermocycled conditions when the ceramics were etched with HF acid gel and silanized (17.4 +/- 5.8 and 17.4 +/- 4.8 MPa, respectively). Silanization after HF acid gel and APT treatment increased the results dramatically (14.5 +/- 4.2-17.4 +/- 4.8 MPa) compared to non-silanized groups (2.6 +/- 0.8-8.9 +/- 3.1 MPa) where the failure type was exclusively (100%) adhesive between the cement and the ceramic.Significance. Silanization of the feldspathic ceramic surface after APF or HF acid etching increased the microtensile bond strength results significantly, with the latter providing higher results. Long-term thermocycling and water storage did not decrease the results in silanized groups. (C) 2006 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved

SEM analysis of the in situ early bacterial colonization on two novel feldspathic ceramics submitted to different types of glazing

Aim: The aim of this study was to evaluate in situ, the early bacterial colonization on feldspar-ceramics submitted to different glazing. Methods and Materials: Fourteen standardized disc specimens (diameter: 5 mm, thickness: 1.5 mm) of each of two micro-particulate feldspathic ceramics (VM7 and VM13, Vita) were produced according to manufacturers' specifications for a total of 28 specimens (24 for the analysis of biofilm and 4 for topographic analysis analyzing the ceramic surfaces). Specimens from each type of ceramic were submitted to two different glazing methods composing four groups: VM7 glazed using glazing liquid Vita Akzent® 25 (G1) and glaze firing (G2), VM13 glazed using glazing liquid (G3) and glaze firing (G4). Six individuals (n=6) wore oral appliances with four ceramic specimens, fixed on the buccal face of the appliances. After 8 hours, each sample was evaluated for the presence (1) or absence (0) of bacterial colonization under a scanning electron microscope (SEM) on five randomly selected fields. The value for each sample was cumulative of the results observed in the fields. One sample from each group was evaluated under a SEM to verify the topographic pattern. Results: There was no difference with regard to bacterial colonization between the feldspar-ceramics and between the glazing types (Kruskal-Wallis non-parametric test). Conclusion: Feldspar-ceramics submitted to firing or glaze firing with Vita Akzent® 25 present a similar condition for in situ bacterial colonization. The similar topographic pattern of the ceramic surfaces seems to have influenced the bacterial colonization

Effect of Exercise on Circulating Endothelial Progenitor Cells in Microvascular Angina

Background:\u2002Circulating endothelial progenitor cells (EPCs) might limit endothelial dysfunction in patients with microvascular angina (MVA). Endothelial colony-forming cells (ECFCs; displaying the CD34+/KDR+/CD45- phenotype) are currently regarded as true EPCs. The aim of this study was to evaluate exercise-induced ECFC mobilization and platelet reactivity in patients with MVA or with obstructive coronary artery disease (CAD). Methods and Results:\u2002Exercise stress test (EST) was performed in 20 MVA patients, 20 CAD patients and 20 controls. Platelet reactivity was assessed before and after EST as formation of monocyte-platelet aggregates (MPAs) and CD41 platelet expression, without and with adenosine diphosphate (ADP) stimulation. ECFC number was measured before and 24h after EST. At rest, MPAs and CD41 platelet expression increased more with ADP in MVA patients (+71\ub111.0% and +37\ub17.5%, respectively), than in CAD patients (+37\ub18.6% and +19\ub14.5%, respectively) and controls (+29\ub13.5% and +21\ub13.1%, respectively; P<0.001 for both). At rest, ECFCs tended to be lower in CAD patients, compared to MVA patients and controls (4.1\ub15.0%, 7.2\ub16.0% and 7.3\ub17.0% cells/10(5), respectively; P=0.056). After EST, ECFCs increased less in MVA patients (+2.8\ub111) compared to CAD patients (+3.3\ub115; P<0.05) and controls (+7.4\ub124; P<0.01). Conclusions:\u2002In MVA patients, EST is able to blunt the peculiar increase of platelet reactivity to ADP present at rest; in contrast, no potential protective response of ECFCs to exercise was seen in these patients

Upper arm intermittent ischaemia reduces exercise-related increase of platelet reactivity in patients with obstructive coronary artery disease

Objective: To assess whether upper arm ischaemia influences exercise-induced myocardial ischaemia and platelet activation in patients with coronary artery disease (CAD). Design: Crossover study. Setting: University hospital. Patients: Twenty patients (17 men) of mean±SD age 64±8 years with stable CAD. Interventions: Patients underwent two exercise stress tests (ESTs) on two separate days in a randomised manner: (1) a maximal EST only (EST-1); (2) a maximal EST after intermittent upper arm ischaemia (cycles of alternating 5-min inflation and 5-min deflation of a standard blood pressure cuff) (EST-2). Blood samples were obtained to evaluate platelet reactivity. Main outcome measures: Platelet reactivity was assessed by flow cytometry at rest and after EST, with and without ADP stimulation, by measuring the percentage of monocyte-platelet aggregates (MPAs) and CD41 platelet expression measured as mean fluorescence intensity. Results: Remote ischaemia had no significant effect on EST-induced myocardial ischaemia. At rest there were no differences before EST-1 and EST-2 in basal MPA (20.7±2.3 vs 20.8±2.4, p=0.56) and CD41 (21.5±2.3 vs 21.3±2.3, p=0.39), and ADP stimulation induced a similar increase in both MPA (+15.2±8.2% vs +14.9±8.4%, p=0.71) and CD41 (+15.7±5.7% vs 13.37±6.9%, p=0.59). While no differences in the increase in MPA and CD41 expression were observed after EST-1 and EST-2, ADP stimulation after EST-2 induced a lower increase in MPA (+18.3±8.1% vs +27.9±9.7%, p<0.001) and CD41 (+18.3±9.2% vs +27.2±12.4%, p<0.001) than after EST-1. Conclusion: These results show that, in patients with stable CAD, remote ischaemia induces protection against an exercise-related increase in platelet reactivity