Aortic valve stenosis (AS) is the most common valvular pathology and has traditionally been managed using surgical aortic valve replacement (SAVR). A large proportion of affected patient demographics, however, are unfit to undergo major surgery given underlying comorbidities. Since its introduction in 2002, transcatheter aortic valve implantation (TAVI) has gained popularity and transformed the care available to different-risk group patients with severe symptomatic AS. Specific qualifying criteria and refinement of TAVI techniques are fundamental in determining successful outcomes for intervention. Given the successful applicability in high-risk patients, TAVI has been further developed and trialed in intermediate and low-risk patients. Within intermediate-risk patient groups, TAVI was shown to be noninferior to SAVR evaluating 30-d mortality and secondary endpoints such as the risk of bleeding, development of acute kidney injury, and length of admission. The feasibility of expanding TAVI procedures into low-risk patients is still a controversial topic in the literature. A number of trials have recently been published which demonstrate TAVI as noninferior and even superior over SAVR for primary study endpoints. K E Y W O R D S aortic valve, surgery, TAVI, valve replacement 1 | INTRODUCTION Aortic valve stenosis (AS) is the most common valvular pathology, with between 2% and 4% of patients over the age of 75 years bring affected. 1 For decades, surgical aortic valve replacement (SAVR) has been considered the class I recommendation in the management of AS. 2 However, given that advanced age, frailty, and significant comorbidities are increasingly prevalent in affected patients; more than one-third of high-risk and severe symptomatic AS patients were not considered physiologically fit enough for major surgical intervention. 2,3 This merited the development of TAVI, an intervention suitable for high-risk patients and those deemed unfit for surgery. With a shift in clinical paradigm toward minimally invasive procedures, the development of TAVI has revolutionized clinical outcomes in AS, particularly in those once considered inoperable. 4 The decision to use TAVI vs SAVR for aortic valve replacement (AVR) is determined by clinical, anatomical, and technical considerations. Since its introduction in 2002, 5 TAVI has increasingly replaced SAVR, the once considered gold standard treatment, in aortic valve diseases. 6-10 More recently, trials such as the Placement of Aortic Trans-Catheter Valve II (PARTNER II) and Surgical Replacement and Transcatheter Aortic Valve Implantation (SURTAVI) 11,12 have further established the use of TAVI in intermediate-risk patients as well. Given this validation of TAVI within high-and intermediate-risk patients, a need has now developed to evaluate the clinical efficacy of TAVI within low-risk surgical candidates. 13Selective candidate criteria, as well as advances in operative techniques within TAVI, are mainstay contributors to successful outcomes. Fundamentally, there exist both retrogr...
BackgroundRectal cancers show a highly varied response to neoadjuvant radiotherapy/chemoradiation (RT/CRT) and the impact of the tumor immune microenvironment on this response is poorly understood. Current clinical tumor regression grading systems attempt to measure radiotherapy response but are subject to interobserver variation. An unbiased and unique histopathological quantification method (change in tumor cell density (ΔTCD)) may improve classification of RT/CRT response. Furthermore, immune gene expression profiling (GEP) may identify differences in expression levels of genes relevant to different radiotherapy responses: (1) at baseline between poor and good responders, and (2) longitudinally from preradiotherapy to postradiotherapy samples. Overall, this may inform novel therapeutic RT/CRT combination strategies in rectal cancer.MethodsWe generated GEPs for 53 patients from biopsies taken prior to preoperative radiotherapy. TCD was used to assess rectal tumor response to neoadjuvant RT/CRT and ΔTCD was subjected to k-means clustering to classify patients into different response categories. Differential gene expression analysis was performed using statistical analysis of microarrays, pathway enrichment analysis and immune cell type analysis using single sample gene set enrichment analysis. Immunohistochemistry was performed to validate specific results. The results were validated using 220 pretreatment samples from publicly available datasets at metalevel of pathway and survival analyses.ResultsΔTCD scores ranged from 12.4% to −47.7% and stratified patients into three response categories. At baseline, 40 genes were significantly upregulated in poor (n=12) versus good responders (n=21), including myeloid and stromal cell genes. Of several pathways showing significant enrichment at baseline in poor responders, epithelial to mesenchymal transition, coagulation, complement activation and apical junction pathways were validated in external cohorts. Unlike poor responders, good responders showed longitudinal (preradiotherapy vs postradiotherapy samples) upregulation of 198 immune genes, reflecting an increased T-cell-inflamed GEP, type-I interferon and macrophage populations. Longitudinal pathway analysis suggested viral-like pathogen responses occurred in post-treatment resected samples compared with pretreatment biopsies in good responders.ConclusionThis study suggests potentially druggable immune targets in poor responders at baseline and indicates that tumors with a good RT/CRT response reprogrammed from immune “cold” towards an immunologically “hot” phenotype on treatment with radiotherapy.
Objective To understand the current evidence and guidelines behind the appropriate management of cardiac tumours. Methods A comprehensive electronic literature search has been performed in major databases - PubMed, Embase, Scopus, Ovid, and Google Scholar. All articles that discussed all different forms of cardiac tumours, their clinical presentation, diagnosis, and management methods have been critically appraised in this narrative review. Results All relevant studies have been summarized in appropriate sections within our review. Cardiac tumours are rare but can be catastrophic and life-threatening if not identified and managed on timely manner. Utilization of all the available imaging methods can be of equivocal importance, relevant to each cardiac tumour. Surgical excision is the ultimate treatment method, however histopathological results can guide the adjunct treatment. Conclusion Early detection of cardiac tumours has significant effect on planning the method of intervention. Technological advancements and increased availability of imaging modalities have enabled earlier and more accurate detection of these tumours. Novel medical therapies, recommendations for screening, and operative techniques have all contributed to overall improving knowledge of these tumours and ultimately patient outcomes.
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