Results from a nationwide prospective registry on open surgical or endovascular repair of juxtarenal abdominal aortic aneurysms

Background: Juxtarenal abdominal aortic aneurysms (JRAAAs) can be treated either with open surgical repair (OSR) including suprarenal clamping or by complex endovascular aneurysm repair (cEVAR). In this study, we present the comparison between the short-term mortality and complications of the elective JRAAA treatment modalities from a national database reflecting daily practice in the Netherlands. Methods: All patients undergoing elective JRAAA open repair or cEVAR (fenestrated EVAR or chimney EVAR) between January 2016 and December 2018 registered in the Dutch Surgical Aneurysm Audit (DSAA) were eligible for inclusion. Descriptive perioperative variables and outcomes were compared between patients treated with open surgery or endovascularly. Adjusted odds ratios for short-term outcomes were calculated by logistic regression analysis. Results: In all, 455 primary treated patients with JRAAAs could be included (258 OSR, 197 cEVAR). Younger patients and female patients were treated more often with OSR vs cEVAR (72 ± 6.1 vs 76 ± 6.0; P < .001 and 22% vs 15%; P = .047, respectively). Patients treated with OSR had significantly more major and minor complications as well as a higher chance of early mortality (OSR vs cEVAR, 45% vs 21%; P < .001; 34% vs 23%; P = .011; and 6.6% vs 2.5%; P = .046, respectively). After logistic regression with adjustment for confounders, patients who were treated with OSR showed an odds ratio of 3.64 (95% confidence interval [CI], 2.25-5.89; P < .001) for major complications compared with patients treated with cEVAR, and for minor complications, the odds ratios were 2.17 (95% CI, 1.34-3.53; P = .002) higher. For early mortality, the odds ratios were 3.79 (95% CI, 1.26-11.34; P = .017) higher after OSR compared with cEVAR. Conclusions: In this study, after primary elective OSR for JRAAA, the odds for major complications, minor complications, and short-term mortality were significantly higher compared with cEVAR

Expression of a retinoic acid signature in circulating CD34 cells from coronary artery disease patients

<p>Abstract</p> <p>Background</p> <p>Circulating CD34+ progenitor cells have the potential to differentiate into a variety of cells, including endothelial cells. Knowledge is still scarce about the transcriptional programs used by CD34+ cells from peripheral blood, and how these are affected in coronary artery disease (CAD) patients.</p> <p>Results</p> <p>We performed a whole genome transcriptome analysis of CD34+ cells, CD4+ T cells, CD14+ monocytes, and macrophages from 12 patients with CAD and 11 matched controls. CD34+ cells, compared to other mononuclear cells from the same individuals, showed high levels of KRAB box transcription factors, known to be involved in gene silencing. This correlated with high expression levels in CD34+ cells for the progenitor markers HOXA5 and HOXA9, which are known to control expression of KRAB factor genes. The comparison of expression profiles of CD34+ cells from CAD patients and controls revealed a less naïve phenotype in patients' CD34+ cells, with increased expression of genes from the Mitogen Activated Kinase network and a lowered expression of a panel of histone genes, reaching levels comparable to that in more differentiated circulating cells. Furthermore, we observed a reduced expression of several genes involved in CXCR4-signaling and migration to SDF1/CXCL12.</p> <p>Conclusions</p> <p>The altered gene expression profile of CD34+ cells in CAD patients was related to activation/differentiation by a retinoic acid-induced differentiation program. These results suggest that circulating CD34+ cells in CAD patients are programmed by retinoic acid, leading to a reduced capacity to migrate to ischemic tissues.</p

Lipid-mediated Wnt protein stabilization enables serum-free culture of human organ stem cells

Wnt signalling proteins are essential for culture of human organ stem cells in organoids, but most Wnt protein formulations are poorly active in serum-free media. Here we show that purified Wnt3a protein is ineffective because it rapidly loses activity in culture media due to its hydrophobic nature, and its solubilization requires a detergent, CHAPS (3-[(3-cholamidopropyl) dimethylammonio]-1-propanesulfonate), that interferes with stem cell self-renewal. By stabilizing the Wnt3a protein using phospholipids and cholesterol as carriers, we address both problems: Wnt activity remains stable in serum-free media, while non-toxic carriers allow the use of high Wnt concentrations. Stabilized Wnt3a supports strongly increased self-renewal of organ and embryonic stem cells and the serum-free establishment of human organoids from healthy and diseased intestine and liver. Moreover, the lipophilicity of Wnt3a protein greatly facilitates its purification. Our findings remove a major obstacle impeding clinical applications of adult stem cells and offer advantages for all cell culture uses of Wnt3a protein

GATE : a simulation toolkit for PET and SPECT

Monte Carlo simulation is an essential tool in emission tomography that can assist in the design of new medical imaging devices, the optimization of acquisition protocols, and the development or assessment of image reconstruction algorithms and correction techniques. GATE, the Geant4 Application for Tomographic Emission, encapsulates the Geant4 libraries to achieve a modular, versatile, scripted simulation toolkit adapted to the field of nuclear medicine. In particular, GATE allows the description of time-dependent phenomena such as source or detector movement, and source decay kinetics. This feature makes it possible to simulate time curves under realistic acquisition conditions and to test dynamic reconstruction algorithms. A public release of GATE licensed under the GNU Lesser General Public License can be downloaded at the address http://www-lphe.epfl.ch/GATE/

Protocol for the STRONG trial: stereotactic body radiation therapy following chemotherapy for unresectable perihilar cholangiocarcinoma, a phase I feasibility study

INTRODUCTION: For patients with perihilar cholangiocarcinoma (CCA), surgery is the only treatment modality that can result in cure. Unfortunately, in the majority of these patients, the tumours are found to be unresectable at presentation due to either local invasive tumour growth or the presence of distant metastases. For patients with unresectable CCA, palliative chemotherapy is the standard treatment yielding an estimated median overall survival (OS) of 12-15.2 months. There is no evidence from randomised trials to support the use of stereotactic body radiation therapy (SBRT) for CCA. However, small and most often retrospective studies combining chemotherapy with SBRT have shown promising results with OS reaching up to 33-35 months.METHODS AND ANALYSIS: This study has been designed as a single-centre phase I feasibility trial and will investigate the addition of SBRT after standard chemotherapy in patients with unresectable perihilar CCA (T1-4 N0-1 M0). A total of six patients will be included. SBRT will be delivered in 15 fractions of 3-4.5 Gy (risk adapted). The primary objective of this study is to determine feasibility and toxicity. Secondary outcomes include local tumour control, progression-free survival (PFS), OS and quality of life. Length of follow-up will be 2 years. As an ancillary study, the personalised effects of radiotherapy will be measured in vitro, in patient-derived tumour and bile duct organoid cultures.ETHICS AND DISSEMINATION: Ethics approval for the STRONG trial has been granted by the Medical Ethics Committee of Erasmus MC Rotterdam, the Netherlands. It is estimated that all patients will be included between October 2017 and October 2018. The results of this study will be published in a peer-reviewed journal, and presented at national and international conferences.TRIAL REGISTRATION NUMBER: NCT03307538; Pre-results

Multimodal prehabilitation to reduce the incidence of delirium and other adverse events in elderly patients undergoing elective major abdominal surgery: An uncontrolled before-and-after study

Background Delirium is a common and serious complication in elderly patients undergoing major abdominal surgery, with significant adverse outcomes. Successful strategies or therapies to reduce the incidence of delirium are scarce. The objective of this study was to assess the role of prehabilitation in reducing the incidence of delirium in elderly patients. Methods A single-center uncontrolled before-and-after study was conducted, including patients aged 70 years or older who underwent elective abdominal surgery for colorectal carcinoma or an abdominal aortic aneurysm between January 2013 and

Malnutrition in patients treated for oral or oropharyngeal cancer—prevalence and relationship with oral symptoms: an explorative study

This study aimed to assess prevalence of malnutrition after treatment for oral/oropharyngeal cancer and to explore how oral symptoms relate to malnutrition after treatment. In this cross-sectional study, malnutrition (weight loss a parts per thousand yenaEuro parts per thousand 10% in 6 months or a parts per thousand yen5% in 1 month), oral symptoms (EORTC QLQ-H&N35 questionnaire and additional questions to assess chewing problems), dental status, trismus and dietary intake were assessed in 116 adult patients treated for oral/oropharyngeal cancer. Prevalence of malnutrition was 16% (95%CI: 10% to 23%). Prevalence of malnutrition in the period 0-3 months after treatment was significantly higher (25%) than in the periods > 3-12 months (13%) and > 12-36 months after treatment (3%, p = 0.008). Logistic multivariate regression analysis revealed that swallowing problems (p = 0.021) and insufficient protein intake were significantly related to malnutrition (p = 0.016). In conclusion, malnutrition is a considerable problem in patients treated for oral/oropharyngeal cancer, shortly after treatment. Of all oral symptoms, only swallowing problems were significantly related to malnutrition in the period after treatment for oral/oropharyngeal cancer

A multicomponent prehabilitation pathway to reduce the incidence of delirium in elderly patients in need of major abdominal surgery

__Background:__ Due to the increase in elderly patients who undergo major abdominal surgery there is a subsequent increase in postoperative complications, prolonged hospital stays, health-care costs and mortality rates. Delirium is

STAT1 Hyperphosphorylation and Defective IL12R/IL23R Signaling Underlie Defective Immunity in Autosomal Dominant Chronic Mucocutaneous Candidiasis

We recently reported the genetic cause of autosomal dominant chronic mucocutaneous candidiasis (AD-CMC) as a mutation in the STAT1 gene. In the present study we show that STAT1 Arg274Trp mutations in the coiled-coil (CC) domain is the genetic cause of AD-CMC in three families of patients. Cloning and transfection experiments demonstrate that mutated STAT1 inhibits IL12R/IL-23R signaling, with hyperphosphorylation of STAT1 as the likely underlying molecular mechanism. Inhibition of signaling through the receptors for IL-12 and IL-23 leads to strongly diminished Th1/Th17 responses and hence to increased susceptibility to fungal infections. The challenge for the future is to translate this knowledge into novel strategies for the treatment of this severe immunodeficiency