This study describes the advantages and disadvantages of using the rabbit as an animal model for surgical training in the Nissen laparoscopic fundoplication technique. Six New Zealand rabbits ...weighing between 2.5 and 3.5 kg were used. Nissen fundoplication was performed successfully in five out of six animals. Average procedure time was 47 minutes, with a maximum of 80 minutes for the first surgery and a minimum of 30 minutes for the last. Main advantages of the rabbit model are ease of animal restrain and low cost. The rabbit allows for the recreation of the human surgical environment, albeit showing a lower degree of difficulty. We thus consider this surgical model to be valuable only for skill development on basic stages of the laparoscopic Nissen fundoplication technique. For advanced stages of this surgical procedure, use of other animal models with further anatomical similarities to humans, such as the swine model, are recommended.
Abstract
Excess sarcoma risks after childhood cancer are well established, but risks among young adulthood cancer survivors are poorly understood. Using US population-based cancer registry data, we ...compared bone and soft-tissue sarcoma risk vs the general population among 186 351 individuals who were diagnosed with nonsarcoma first primary malignancies at ages 20–39 years from 1975 to 2014 (follow-up through 2015) and survived at least 1 year. Bone sarcomas were rare (n = 50), but risk was statistically significantly elevated overall (2.9-fold) and greater than fivefold after Hodgkin lymphoma, non-Hodgkin lymphoma, and central nervous system tumors. Soft-tissue sarcomas were more common (n = 284) and risks were statistically significantly elevated approximately twofold overall and after melanoma and carcinomas of the breast, thyroid, and testis, and greater than fourfold after Hodgkin lymphoma and central nervous system tumors. Risks varied markedly by subtype, with the highest risks (greater than fourfold) for osteosarcoma and the soft-tissue subtypes of rhabdomyosarcoma and blood vessel and nerve sheath sarcomas. These data demonstrate elevated risk for sarcoma after a range of young adulthood cancers.
Active valvular endocarditis could be considered a contraindication to heart transplantation. Nevertheless, there have been some reports of success with this form of treatment, despite the ...characteristics of the infection and its aggressive nature. Here, we describe the case of a patient with acute bicuspid aortic valvular endocarditis caused by Staphylococcus aureus and with a periannular abscess. Cryopreserved aortic homograft replacement of the aortic root was initially carried out, in addition to debridement and reconstruction of the interventricular septum with a pericardial patch. Early recurrence occurred, however, with extensive tissue destruction, a periaortic abscess and involvement of multiple valves, associated with severe sepsis. In view of the failure of 'conventional' surgery, an emergency heart transplantation was decided on after discussing the case with the Spanish National Transplant Organization (ONT), because of the theoretical contraindication of transplantation in this case. Transplantation was finally carried out after a waiting period of 3 days, in emergency code conditions, and the postoperative course proved uneventful, with no reinfection during the follow-up period. The present case suggests that heart transplantation may be an alternative option in patients suffering aggressive endocarditis with extensive involvement of the heart structures.
Gastroesophageal reflux can be a catastrophic illness in small animals during anesthesia since its complications can cause serious pathologies, such as esophagitis, esophageal stenosis and aspiration ...pneumonia. With an incidence from 12 to 78.5% in anesthetized dogs, gastroesophageal reflux is normally silent during anesthesia and will be notices only if regurgitation occurs and stomach acid is present in the nasal or oral cavities. In humans, gastroesophageal reflux disease (GERD) is a well-defined pathology where the lower esophageal sphincter has a sustained weakness. However, in dogs, gastroesophageal reflux disease as such is not well established, if at all; it has only been described as gastroesophagic reflux, occurring principally in anesthetized animals. This paper aims to discuss a series of conditions that could predispose dogs to gastroesophageal reflux during anesthesia and to assist in the prevention and diagnosis of this condition.
Homologous recombination deficiency (HRD) is a phenotype that is characterized by the inability of a cell to effectively repair DNA double-strand breaks using the homologous recombination repair ...(HRR) pathway. Loss-of-function genes involved in this pathway can sensitize tumors to poly(adenosine diphosphate ADP-ribose) polymerase (PARP) inhibitors and platinum-based chemotherapy, which target the destruction of cancer cells by working in concert with HRD through synthetic lethality. However, to identify patients with these tumors, it is vital to understand how to best measure homologous repair (HR) status and to characterize the level of alignment in these measurements across different diagnostic platforms. A key current challenge is that there is no standardized method to define, measure, and report HR status using diagnostics in the clinical setting.
Friends of Cancer Research convened a consortium of project partners from key healthcare sectors to address concerns about the lack of consistency in the way HRD is defined and methods for measuring HR status.
This publication provides findings from the group's discussions that identified opportunities to align the definition of HRD and the parameters that contribute to the determination of HR status. The consortium proposed recommendations and best practices to benefit the broader cancer community.
Overall, this publication provides additional perspectives for scientist, physician, laboratory, and patient communities to contextualize the definition of HRD and various platforms that are used to measure HRD in tumors.
On 11 March 2020, coronavirus disease 2019 (COVID-19) was declared a pandemic by the World Health Organization (WHO). This study focuses on a narrative review about the illness during the first year ...of the pandemic in relation to obesity. Databases were used to search studies published up to 8 December 2020. In total, 4430 articles and other scientific literature were found, and 24 articles were included in this one-year narrative review. The mean BMI value of severe COVID-19 patients ranged from 24.5 to 33.4 kg/m
, versus <18.5 to 24.3 kg/m
for non-severe patients. Articles using the terms obesity or overweight without indicating the BMI value in these patients were common, but this is not useful, as the anthropometric parameters, when not defined by this index, are confusing due to the classification being different in the West compared to among Asian and Korean criteria-based adults. We proposed a new term, called COVID obesity, to define the importance of this anthropometric parameter, among others, in relation with this pandemic.
Summary Background Identification of robust biomarkers of malignancy and methods to establish disease progression is a major goal in paediatric neuro-oncology. We investigated whether methylation of ...the TERT promoter can be a biomarker for malignancy and patient outcome in paediatric brain tumours. Methods For the discovery cohort, we used samples obtained from patients with paediatric brain tumours and individuals with normal brain tissues stored at the German Cancer Research Center (Heidelberg, Germany). We used methylation arrays for genome-wide assessment of DNA. For the validation cohort, we used samples obtained from several tissues for which full clinical and follow-up data were available from two hospitals in Toronto (ON, Canada). We did methylation analysis using quantitative Sequenom and pyrosequencing of an identified region of the TERT promoter. We assessed TERT expression by real-time PCR. To establish whether the biomarker could be used to assess and predict progression, we analysed methylation in paired samples of tumours that transformed from low to high grade and from localised to metastatic, and in choroid plexus tumours of different grades. Finally, we investigated overall survival in patients with posterior fossa ependymomas in which the identified region was hypermethylated or not. All individuals responsible for assays were masked to the outcome of the patients. Findings Analysis of 280 samples in the discovery cohort identified one CpG site (cg11625005) in which 78 (99%) of 79 samples from normal brain tissues and low-grade tumours were not hypermethylated, but 145 (72%) of 201 samples from malignant tumours were hypermethylated (>15% methylated; p<0·0001). Analysis of 68 samples in the validation cohort identified a subset of five CpG sites (henceforth, upstream of the transcription start site UTSS) that was hypermethylated in all malignant paediatric brain tumours that expressed TERT but not in normal tissues that did not express TERT (p<0·0001). UTSS had a positive predictive value of 1·00 (95% CI 0·95–1·00) and a negative predictive value of 0·95 (0·87–0·99). In two paired samples of paediatric gliomas, UTSS methylation increased during transformation from low to high grade; it also increased in two paired samples that progressed from localised to metastatic disease. Two of eight atypical papillomas that had high UTSS methylation progressed to carcinomas, while the other six assessed did not progress or require additional treatment. 5-year overall survival was 51% (95% CI 31–71) for 25 patients with hypermethylated UTSS posterior fossa ependymomas and 95% (86–100) for 20 with non-hypermethylated tumours (p=0·0008). 5-year progression-free survival was 86% (68–100) for the 25 patients with non-hypermethylated UTSS tumours and 30% (10–50) for those with hypermethylated tumours (p=0·0008). Interpretation Hypermethylation of the UTSS region in the TERT promoter is associated with TERT expression in cancers. In paediatric brain tumours, UTSS hypermethylation is associated with tumour progression and poor prognosis. This region is easy to amplify, and the assay to establish hypermethylation can be done on most tissues in most clinical laboratories. Therefore the UTSS region is a potentially accessible biomarker for various cancers. Funding The Canadian Institute of Health Research and the Terry Fox Foundation.
Ensembl (https://www.ensembl.org) has produced high-quality genomic resources for vertebrates and model organisms for more than twenty years. During that time, our resources, services and tools have ...continually evolved in line with both the publicly available genome data and the downstream research and applications that utilise the Ensembl platform. In recent years we have witnessed a dramatic shift in the genomic landscape. There has been a large increase in the number of high-quality reference genomes through global biodiversity initiatives. In parallel, there have been major advances towards pangenome representations of higher species, where many alternative genome assemblies representing different breeds, cultivars, strains and haplotypes are now available. In order to support these efforts and accelerate downstream research, it is our goal at Ensembl to create high-quality annotations, tools and services for species across the tree of life. Here, we report our resources for popular reference genomes, the dramatic growth of our annotations (including haplotypes from the first human pangenome graphs), updates to the Ensembl Variant Effect Predictor (VEP), interactive protein structure predictions from AlphaFold DB, and the beta release of our new website.
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