Dacarbazine (DTIC) versus vaccination with autologous peptide-pulsed dendritic cells (DC) in first-line treatment of patients with metastatic melanoma: a randomized phase III trial of the DC study group of the DeCOG

Background: This randomized phase III trial was designed to demonstrate the superiority of autologous peptide-loaded dendritic cell (DC) vaccination over standard dacarbazine (DTIC) chemotherapy in stage IV melanoma patients. Patients and methods: DTIC 850 mg/m2 intravenously was applied in 4-week intervals. DC vaccines loaded with MHC class I and II-restricted peptides were applied subcutaneously at 2-week intervals for the first five vaccinations and every 4 weeks thereafter. The primary study end point was objective response (OR); secondary end points were toxicity, overall (OS) and progression-free survival (PFS). Results: At the time of the first interim analysis 55 patients had been enrolled into the DTIC and 53 into the DC-arm (ITT). OR was low (DTIC: 5.5%, DC: 3.8%), but not significantly different in the two arms. The Data Safety & Monitoring Board recommended closure of the study. Unscheduled subset analyses revealed that patients with normal serum LDH and/or stage M1a/b survived longer in both arms than those with elevated serum LDH and/or stage M1c. Only in the DC-arm did those patients with (i) an initial unimpaired general health status (Karnofsky = 100) or (ii) an HLA-A2+/HLA-B44− haplotype survive significantly longer than patients with a Karnofsky index <100 (P = 0.007 versus P = 0.057 in the DTIC-arm) or other HLA haplotypes (P = 0.04 versus P = 0.57 in DTIC-treated patients). Conclusions: DC vaccination could not be demonstrated to be more effective than DTIC chemotherapy in stage IV melanoma patients. The observed association of overall performance status and HLA haplotype with overall survival for patients treated by DC vaccination should be tested in future trials employing DC vaccine

Имплантируемые устройства: мост к трансплантации сердца

Terminal stage heart failure represents a substantial worldwide problem for the healthcare system. Despite significant improvements (medical heart failure treatment, implantable cardioverters, cardiac resynchronization devices), long-term survival and quality of life of these patients remain poor. Heart transplantation has been an effective therapy for terminal heart failure, but it remains limited by an increasing shortage of available donor organs along with strict criteria defining acceptable recipients.Терминальная стадия сердечной недостаточности представляет существенную проблему для системы здравоохранения во всем мире. Несмотря на значительные усовершенствования (медикаментозное лечение сердечной недостаточности, имплантируемые кардиовертеры, устройства ресинхронизации), длительная выживаемость и качество жизни таких больных остаются неудовлетворительными. Трансплантация сердца является эффективным методом лечения терминальной сердечной недостаточности, однако ее применение ограничено увеличивающимся дефицитом доступных донорских органов одновременно с жесткими критериями отбора реципиентов

The influence of left ventricular assist device inflow cannula position on thrombosis risk

\ua9 2020 The Authors. Artificial Organs published by International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.The use of left ventricular assist devices (LVADs) as a treatment method for heart failure patients has been steadily increasing; however, pathological studies showed presence of thrombi around the HeartWare ventricular assist device inflow cannula (IC) in more than 95% of patients after device explantation. Flow fields around the IC might trigger thrombus formation and require further investigation. In this study flow dynamics parameters were evaluated for different patient geometries using computational fluid dynamics (CFD) simulations. Left ventricular (LV) models of two LVAD patients were obtained from CT scans. The LV volumes of Patient 1 (P1) and Patient 2 (P2) were 264 and 114 cm3 with an IC angle of 20\ub0 and 9\ub0 from the mitral-IC tip axis at the coronal plane. The IC insertion site at the apex was central for P1, whereas it was lateral for P2. Transient CFD simulations were performed over 9 cardiac cycles. The wedge area was defined from the cannula tip to the wall of the LV apex. Mean velocity magnitude and blood stagnation region (volume with mean velocity &lt;5 mm/s) as well as the wall shear stress (WSS) at the IC surface were calculated. Cardiac support resulted in a flow mainly crossing the ventricle from the mitral valve to the LVAD cannula for P2, while the main inflow jet deviated toward the septal wall in P1. Lower WSS at the IC surface and consequently larger stagnation volumes were observed for P2 (P1: 0.17, P2: 0.77 cm3). Flow fields around an LVAD cannula can be influenced by many parameters such as LV size, IC angle, and implantation site. Careful consideration of influencing parameters is essential to get reliable evaluations of the apical flow field and its connection to apical thrombus formation. Higher blood washout and lower stagnation were observed for a central implantation of the IC at the apex

Left atrial appendage occlusion in ventricular assist device patients to decrease thromboembolic events: A computer simulation study

Copyright \ua9 2022 Ghodrati-Misek, Schl\uf6glhofer, Gross, Maurer, Zimpfer, Beitzke, Zonta, Moscato, Schima and Aigner. Atrial fibrillation (AF) is a common comorbidity in left ventricular assist device (LVAD) patients and has been identified as a risk factor for thromboembolic stroke. Blood stagnation within the left atrial appendage (LAA) is considered a possible major source of thrombosis and clinical studies have shown reduced thromboembolic risk after LAA occlusion (LAAO). Therefore, this study aims to investigate the effect of LAAO on thrombosis-related parameters using patient-specific simulations. Left ventricular and left atrial geometries of an LVAD patient were obtained from computed tomography and combined with hemodynamic data with either sinus rhythm (SR) or AF generated by a lumped parameter model. In four simulations applying contractile walls, stagnation volume and blood residence times were evaluated with or without AF and with or without LAAO. Reduced atrial contraction in AF resulted in unfavorable flow dynamics within the left atrium. The average atrial velocity was lower for the AF simulation when compared to SR, resulting in a 55% increase in the atrial stagnation volume (from 4.2 to 6.5 cm3). Moreover, blood remained in the LAA for more than 8 cardiac cycles. After LAAO the atrial stagnation decreased from 4.2 to 1.4 cm3 for SR and from 6.5 to 2.3 cm3 for the AF simulation. A significant stagnation volume was found in the LAA for both SR and AF, with larger values occurring with AF. These regions are known as potential sources for thrombus formation and can be diminished by LAAO. This significantly improved the thrombus-related flow parameters and may also lower the risk of thromboembolic events from the appendage

Effects of the atrium on intraventricular flow patterns during mechanical circulatory support

\ua9 The Author(s) 2021. Simulations of the ventricular flow patterns during left ventricular assist device (LVAD) support are mainly performed with idealized cylindrical inflow, neglecting the influence of the atrial vortex. In this study, the influence of the left atrium (LA) on the intra-ventricular flow was investigated via Computational Fluid Dynamics (CFD) simulations. Ventricular flow was simulated by a combined Eulerian (carrier flow)/Lagrangian (particles) approach taking into account either the LA or a cylindrical inflow section to mimic a fully support condition. The flow deviation at the mitral valve, the blood low-velocity volume as well as the residence time and shear stress history of the particles were calculated. Inclusion of the LA deflects the flow at the mitral valve by 25\ub0, resulting in an asymmetric flow jet entering the left ventricle. This reduced the ventricular low-velocity volume by 40% (from 6.4 to 3.9 cm3), increased (40%) the shear stress experienced by particles and correspondingly increased (27%) their residence time. Under the studied conditions, the atrial geometry plays a major role in the development of intraventricular flow patterns. A reliable prediction of blood flow dynamics and consequently thrombosis risk analysis within the ventricle requires the consideration of the LA in computational simulations

Use of intraventricular ribbon gauze to reduce particulate emboli during aortic valve replacement

BACKGROUND: The incidence of cerebrovascular accidents following aortic valve surgery remains a devastating complication. The aim of this study was to determine the number of potential embolic material arising during aortic valve replacement and to examine the efficacy of using ribbon gauze in the left ventricle during removal of the native valve and decalcification of the aortic annulus. METHODS: Ribbon gauze was inserted into the left ventricular cavity prior to aortic valve excision in an unselected, prospectively studied series of 30 patients undergoing aortic valve replacement. A further 30 lengths of ribbon gauze were soaked in the pericardiotomy blood of the same patients and all were subjected to histological analysis. RESULTS: The median number of tissue fragments from the aortic valve replacement group was significantly higher than in the control group 5 (0–18) versus 0 (0–1) (p = 3.6 × 10(-5)). The size of tissue fragments varied between 0.1 and 9.0 mm with a mean of 0.61 ± 1.12 mm and a median of 0.2 mm. There was a significantly higher number of tissue fragments associated with patients having surgery for aortic stenosis when compared with patients who had aortic regurgitation with median of 5 (0–18) versus 0 (0–3) (p = 0.8 × 10(-3)). CONCLUSION: Significant capture of particulate debris by the intraventricular ribbon gauze suggests that the technique of left ventricular ribbon gauze insertion during aortic valve excision has merit

Assessment of the fabric's wear by sound measurements on soldier's uniforms

This study focuses on the evaluation of fabrics friction sound using two different approaches (instrumental and sensory) to analyze the influence of fabric wear on friction sounds. For this purpose, four fabrics were selected and have undergone multiple washes (up to 50). A specific device reproducing the human arm motion is used to produce and record the fabric friction sounds. From these recordings, some acoustic parameters like the total noise level can be determined. Meanwhile, a sensory panel dedicated to hearing assessed the friction sounds by several attributes. This paper identifies the significant correlations between acoustic, mechanical and sensory properties