Mesenchymal tumor organoid models recapitulate rhabdomyosarcoma subtypes

Rhabdomyosarcomas (RMS) are mesenchyme-derived tumors and the most common childhood soft tissue sarcomas. Treatment is intense, with a nevertheless poor prognosis for high-risk patients. Discovery of new therapies would benefit from additional preclinical models. Here, we describe the generation of a collection of 19 pediatric RMS tumor organoid (tumoroid) models (success rate of 41%) comprising all major subtypes. For aggressive tumors, tumoroid models can often be established within 4–8 weeks, indicating the feasibility of personalized drug screening. Molecular, genetic, and histological characterization show that the models closely resemble the original tumors, with genetic stability over extended culture periods of up to 6 months. Importantly, drug screening reflects established sensitivities and the models can be modified by CRISPR/Cas9 with TP53 knockout in an embryonal RMS model resulting in replicative stress drug sensitivity. Tumors of mesenchymal origin can therefore be used to generate organoid models, relevant for a variety of preclinical and clinical research questions

Hollow microneedle-mediated micro-injections of a liposomal HPV E7(43-63) synthetic long peptide vaccine for efficient induction of cytotoxic and T-helper responses

Drug Delivery Technolog

The unique characteristics of intussusception after renal tumor surgery in children

Introduction: To further optimize survival rates as well as quality of cure for pediatric kidney tumors, attention for treatment related morbidity and mortality has become increasingly important. Intussusception is a rare but important complication after tumornephrectomy in children, causing morbidity, mortality and prolonged hospitalization. In this study, we describe two recent cases in our institute and provide a comprehensive review of the literature. Methods: For our narrative review, we searched for all reported cases of post tumor nephrectomy intussusception published until November 2016, using Pubmed and Embase libraries. Results: A total of 52 pediatric renal tumor cases who developed intussusception after tumor nephrectomy were identified. Median age was 23 months (range 3–84). Median time of onset was postoperative day 6 (range 1–18). Of 41 patients described in detail, only 4/41 were ileocolic, the others suffered from a small bowel intussusception. Most frequent presenting symptom was bilious vomiting. Preceding treatment approach was documented in 47 cases; i.e. preoperative chemotherapy had been administered to 10/47 patients. In 29 of 30 well documented cases, successful manually reduction during re-laparotomy was described and only 1 patient needed resection. All patients survived without recurrence of intussusception. Conclusion: In pediatric renal tumor patients, small bowel obstruction seems to reflect mostly post nephrectomy intussusception cases in contrast to the ileocolic idiopathic intussusceptions that are observed in healthy children. Symptoms of intussusception mimic chemotherapy related toxicity and general post-surgical symptoms, thereby initiating a significant delay in diagnosis. Awareness of intussusception after renal tumor surgery is warranted

Mifepristone followed by misoprostol compared with placebo followed by misoprostol as medical treatment for early pregnancy loss (the Triple M trial): A double-blind placebo-controlled randomised trial

Contains fulltext : 232470.pdf (Publisher’s version ) (Open Access)BACKGROUND: Worldwide, millions of women seek treatment for early pregnancy loss (EPL) annually. Medical management with misoprostol is widely used, but only effective 60% of the time. Pre-treatment with mifepristone prior to misoprostol might improve the success rate of medical management. METHODS: This was a multi-centre, double-blind, placebo-controlled randomised trial in 17 Dutch hospitals. Women with a non-viable pregnancy between 6 and 14 weeks of gestation were eligible for inclusion after at least one week of expectant management. Participants were randomised (1:1) between oral mifepristone 600 mg or an oral placebo tablet. Participants took 400 μg misoprostol orally, repeated after four hours on day two and, if necessary, day three. Primary outcome was expulsion of gestational sac and endometrial thickness <15 mm after 6-8 weeks. Analyses were done according to intention-to-treat principles. This trial is registered with ClinicalTrials.gov, NCT03212352. FINDINGS: Between June 28th 2018 and January 8th 2020, 175 women were randomised to mifepristone and 176 to placebo, including 344 in the intention-to-treat analysis. In the mifepristone group 136 (79•1%) of 172 participants reached complete evacuation compared to 101 (58•7%) of 172 participants in the placebo group (p<0•0001, RR 1•35, 95% CI 1•16-1•56). Incidence of serious adverse events was significantly lower in the mifepristone group with 24 (14%) patients affected versus 55 (32%) in the placebo group (p = 0•0005) (Table 3). INTERPRETATION: Pre-treatment with mifepristone prior to misoprostol was more effective than misoprostol alone in managing EPL. FUNDING: Healthcare Insurers Innovation Foundation, Radboud University Medical Centre, Canisius Wilhelmina Hospital

Climate knowledge agenda : Knowledge agenda on climate research for a climate neutral and resilient Europe by Wageningen University and Research KB 34

This climate knowledge agenda is initiated and funded by the KB programme Circular and Climate neutral. In 2020, this programme started as one of the five One Wageningen research programmes. Establishing a One Wageningen Climate Research programme was one of the advices from the One Wageningen Climate strategy to stimulate internal cooperation and to improve the visibility of ourclimate research. The climate knowledge agenda also contributes to the goals of the One Wageningen Climate strategy. The results of this project will be used to draft the future of the KB programme

Multi-dimensional computed cardiac visualization

During the past decade, coronary radiology has undergone rapid development. This second edition of the only available monograph on the subject places special emphasis on the role of non-invasive techniques, which can supply information on the condition of the coronary arteries within one simple and short examination. The modalities considered in detail include CT angiography with multidetector and dual-source tomography, 2D and 3D visualization techniques, and MR coronary angiography. Invasive procedures are not neglected, however, and a separate section includes chapters on conventional catheterization, quantitative angiography, and intravascular and quantitative ultrasound. In addition, a section devoted to coronary calcification clearly explains its development and the use of modern techniques in its visualization and quantification. The informative text is supported by a large number of high-quality color images of the coronary and cardiac anatomy