Gene therapy of Maligant Gliomas

Ondanks ontwikkelingen in de neurochirurgie, radiotherapie en chemotherapie is het niet mogelijk om patiënten met maligne gliomen (o.a. glioblastomen) te genezen. Ieder jaar overlijden hieraan 450 patiënten in Nederland (25.000 sterfgevallen per jaar in Europa en Noord-Amerika). Ondanks initiële behandeling krijgen alle patiënten uiteindelijk een recidief. Bij 80% van hen ligt dit binnen een marge van 2-3 cm van de oorspronkelijke tumor op CT/MRI. Zelden is er sprake van een uitzaaiing buiten de schedel. Vanwege het infiltratieve groeipatroon is radicale chirurgische resectie, met oncologische marges, niet mogelijk. De locoregionale aard van maligne gliomen en de slechte prognose maken deze tumoren tot geschikte kandidaten voor adjuvante behandelingstechnieken zoals gentherapie. In de afgelopen jaren zijn er diverse klinische gentherapie trials, o.a. in Rotterdam, bij maligne gliomen uitgevoerd met adenovirussen die een gen tot expressie kunnen brengen maar die niet kunnen repliceren. In dit proefschrift wordt onderzoek gedaan met als doel het effect van gentherapie te verbeteren. Ten eerste is gekeken naar adenovirussen die kunnen vermenigvuldigen in cellen die voldoen aan een bepaalde voorwaarde (conditioneel replicerende adenovirus). In dit proefschrift wordt de ontwikkeling van een conditioneel replicerend adenovirus onder de controle van een glial fibrillary acidic protein (GFAP) promoter beschreven. Vervolgens is gezocht naar manieren om de adenovirale verspreiding te optimaliseren, waaruit blijkt dat een virus beter verspreid wordt door multiple injecties dan door een enkele injectie of een injectie met een enkele uren durende continue infusie van adenovirus (convection enhanced delivery). Tenslotte wordt ingegaan op nieuwe ontwikkelingen in ! de nucleaire beeldvorming (imaging) van adenovirale vectoren in hersentumoren

A case report of an interrupted inferior vena cava and azygos continuation:Implications for preoperative screening in minimally invasive cardiac surgery

Background: Femoral cannulation is commonly used in minimally invasive cardiac surgery to establish extracorporeal circulation. We present a case with a finding that should be evaluated when screening candidates for minimally invasive cardiac surgery. Case summary: A 57-year-old male patient was scheduled for minimally invasive repair of the mitral and tricuspid valve and a MAZE procedure. During surgery there was difficulty advancing the venous cannula inserted in the right femoral vein. On transoesophageal echocardiography a guidewire advanced from the femoral vein was observed entering the right atrium from the superior vena cava. Despite inserting a second venous cannula in the jugular vein, venous drainage was insufficient for minimal invasive surgery. The approach was converted to a median sternotomy with bicaval cannulation. Re-examination of the preoperative computed tomography (CT) scan showed an interrupted inferior vena cava (IVC) with azygos continuation. Discussion: In patients with major venous malformations such as the interrupted IVC with azygos continuation a full sternotomy is the preferred approach. The venous system should be evaluated when screening candidates for minimally invasive mitral valve surgery with preoperative CT. Additional cues to suspect interruption of the IVC are polysplenia and a broad superior mediastinal projection on the chest radiograph, mimicking a right paratracheal mass.</p

Cost-effectiveness of hepatitis C virus screening, and subsequent monitoring or treatment among pregnant women in the Netherlands

Background The prevalence of diagnosed chronic hepatitis C virus (HCV) infection among pregnant women in the Netherlands is 0.26%, yet many cases remain undiagnosed. HCV screening and treatment of pregnant HCV carriers could reduce the burden of disease and limit vertical transmission from mother to child. We assessed the impact of HCV screening and subsequent treatment with new direct-acting antivirals (DAAs) among pregnant women in the Netherlands. Methods An HCV natural history Markov transition state model was developed, to evaluate the public-health and economic impact of HCV screening and treatment. Besides all 179,000 pregnant women in the Netherlands (cohort 1), we modelled 3 further cohorts: all 79,000 first-time pregnant women (cohort 2), 33,000 pregnant migrant women (cohort 3) and 16,000 first-time pregnant migrant women (cohort 4). Each cohort was analyzed in various scenarios:i no intervention, i.e., the current practice,ii screen-and-treat, i.e., the most extensive approach involving treatment of all individuals found HCV-positive, andiii screen-and-treat/monitor, i.e., a strategy involving treatment of symptomatic (F1-F4) patients and follow-up of asymptomatic (F0) HCV carriers with subsequent treatment only at progression. Results For all cohorts, comparison betweenscenarios(ii) and (i) resulted in ICERs between euro9,306 and euro10,173 per QALY gained and 5 year budget impacts varying between euro6,283,830 and euro19,220,405. For all cohorts, comparison betweenscenarios(iii) and (i) resulted in ICERs between euro1,739 and euro2,749 per QALY gained and budget impacts varying between euro1,468,670 and euro5,607,556. For all cohorts, the ICERs (scenario iiiversusii) involved in delayed treatment of asymptomatic (F0) HCV carriers varied between euro56,607 and euro56,892, well above the willingness-to-pay (WTP) threshold of euro20,000 per QALY gained and even above a threshold of euro50,000 per QALY gained. Conclusion Universal screening for HCV among all pregnant women in the Netherlands is cost-effective. However, it would be reasonable to consider smaller risk groups in view of the budget impact of the intervention

Mitochondrial Oxygenation During Cardiopulmonary Bypass: A Pilot Study

ObjectiveAdequate oxygenation is essential for the preservation of organ function during cardiac surgery and cardiopulmonary bypass (CPB). Both hypoxia and hyperoxia result in undesired outcomes, and a narrow window for optimal oxygenation exists. Current perioperative monitoring techniques are not always sufficient to monitor adequate oxygenation. The non-invasive COMET® monitor could be a tool to monitor oxygenation by measuring the cutaneous mitochondrial oxygen tension (mitoPO2). This pilot study examines the feasibility of cutaneous mitoPO2 measurements during cardiothoracic procedures. Cutaneous mitoPO2 will be compared to tissue oxygenation (StO2) as measured by near-infrared spectroscopy.Design and MethodThis single-center observational study examined 41 cardiac surgery patients requiring CPB. Preoperatively, patients received a 5-aminolevulinic acid plaster on the upper arm to enable mitoPO2 measurements. After induction of anesthesia, both cutaneous mitoPO2 and StO2 were measured throughout the procedure. The patients were observed until discharge for the development of acute kidney insufficiency (AKI).ResultsCutaneous mitoPO2 was successfully measured in all patients and was 63.5 [40.0–74.8] mmHg at the surgery start and decreased significantly (p &lt; 0.01) to 36.4 [18.4–56.0] mmHg by the end of the CPB run. StO2 at the surgery start was 80.5 [76.8–84.3]% and did not change significantly. Cross-clamping of the aorta and the switch to non-pulsatile flow resulted in a median cutaneous mitoPO2 decrease of 7 mmHg (p &lt; 0.01). The cessation of the aortic cross-clamping period resulted in an increase of 4 mmHg (p &lt; 0.01). Totally, four patients developed AKI and had a lower preoperative eGFR of 52 vs. 81 ml/min in the non-AKI group. The AKI group spent 32% of the operation time with a cutaneous mitoPO2 value under 20 mmHg as compared to 8% in the non-AKI group.ConclusionThis pilot study illustrated the feasibility of measuring cutaneous mitoPO2 using the COMET® monitor during cardiothoracic procedures. Moreover, in contrast to StO2, mitoPO2 decreased significantly with the increasing CPB run time. Cutaneous mitoPO2 also significantly decreased during the aortic cross-clamping period and increased upon the release of the clamp, but StO2 did not. This emphasized the sensitivity of cutaneous mitoPO2 to detect circulatory and microvascular changes

Категоріальна ситуація перфектності як засіб вираження відношень різночасності дій у рамках абзацу

Мета - довести, що категоріальна ситуація перфектності є основним із засобів вираження різночасності дій у тексті

Increasing cardio-thoracic productivity at Erasmus MC

The Thoraxcenter of Erasmus MC started an improvement project in 2015 in order to increase the number of open-heart surgeries by 150 for three consecutive years (450 in total, +46%), and to decrease the access time from 12–14 to 2–3 weeks by the end of 2016. This was required to attain economy of scale in a highly competitive market. In this paper we describe the first year of the project, focusing on its structure and interventions taken, resulting in 165 additional open-heart surgeries carried out in 2016 and a significantly shorter access time of 2–3 weeks

Preoperative anaemia and outcome after elective cardiac surgery:a Dutch national registry analysis

Background: Previous studies have shown that preoperative anaemia in patients undergoing cardiac surgery is associated with adverse outcomes. However, most of these studies were retrospective, had a relatively small sample size, and were from a single centre. The aim of this study was to analyse the relationship between the severity of preoperative anaemia and short- and long-term mortality and morbidity in a large multicentre national cohort of patients undergoing cardiac surgery. Methods: A nationwide, prospective, multicentre registry (Netherlands Heart Registration) of patients undergoing elective cardiac surgery between January 2013 and January 2019 was used for this observational study. Anaemia was defined according to the WHO criteria, and the main study endpoint was 120-day mortality. The association was investigated using multivariable logistic regression analysis. Results: In total, 35 484 patients were studied, of whom 6802 (19.2%) were anaemic. Preoperative anaemia was associated with an increased risk of 120-day mortality (adjusted odds ratio [aOR] 1.7; 95% confidence interval [CI]: 1.4–1.9; P<0.001). The risk of 120-day mortality increased with anaemia severity (mild anaemia aOR 1.6; 95% CI: 1.3–1.9; P<0.001; and moderate-to-severe anaemia aOR 1.8; 95% CI: 1.4–2.4; P<0.001). Preoperative anaemia was associated with red blood cell transfusion and postoperative morbidity, the causes of which included renal failure, pneumonia, and myocardial infarction. Conclusions: Preoperative anaemia was associated with mortality and morbidity after cardiac surgery. The risk of adverse outcomes increased with anaemia severity. Preoperative anaemia is a potential target for treatment to improve postoperative outcomes

Psychological well-being in Europe after the outbreak of war in Ukraine

The Russian invasion of Ukraine on February 24, 2022, has had devastating effects on the Ukrainian population and the global economy, environment, and political order. However, little is known about the psychological states surrounding the outbreak of war, particularly the mental well-being of individuals outside Ukraine. Here, we present a longitudinal experience-sampling study of a convenience sample from 17 European countries (total participants = 1,341, total assessments = 44,894, countries with >100 participants = 5) that allows us to track well-being levels across countries during the weeks surrounding the outbreak of war. Our data show a significant decline in well-being on the day of the Russian invasion. Recovery over the following weeks was associated with an individual’s personality but was not statistically significantly associated with their age, gender, subjective social status, and political orientation. In general, well-being was lower on days when the war was more salient on social media. Our results demonstrate the need to consider the psychological implications of the Russo-Ukrainian war next to its humanitarian, economic, and ecological consequences

A global experience-sampling method study of well-being during times of crisis : The CoCo project

We present a global experience-sampling method (ESM) study aimed at describing, predicting, and understanding individual differences in well-being during times of crisis such as the COVID-19 pandemic. This international ESM study is a collaborative effort of over 60 interdisciplinary researchers from around the world in the “Coping with Corona” (CoCo) project. The study comprises trait-, state-, and daily-level data of 7490 participants from over 20 countries (total ESM measurements = 207,263; total daily measurements = 73,295) collected between October 2021 and August 2022. We provide a brief overview of the theoretical background and aims of the study, present the applied methods (including a description of the study design, data collection procedures, data cleaning, and final sample), and discuss exemplary research questions to which these data can be applied. We end by inviting collaborations on the CoCo dataset