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Incidence, etiology, and outcomes of pre- and post-operative atrial fibrillation in mitral valve procedures: a review
No full textAlthough pre-procedural and post-procedural atrial fibrillation occur commonly in mitral valve (MV) patients, the impact on patient outcomes and resource utilization has not been well documented. A comprehensive PubMed review was performed using a combination of MeSH terms related to atrial fibrillation, MV disease, MV and atrial fibrillation procedures, and medical management. Additional publications were selected from the reference lists of studies identified in the literature search. This review found that several studies conflict with the short-term outcomes associated with pre- and post-operative atrial fibrillation in MV patients. In general, both pre- and post-operative atrial fibrillation have clear negative long-term impacts on MV patients’ mortality and risk of stroke, major bleeding and other thromboembolic events. Surgical ablation for pre-operative atrial fibrillation and transcatheter ablation for medically resistant post-operative atrial fibrillation appears to be safe and effective procedure; these percutaneous and surgical interventions have been documented to mitigate MV-related thromboembolic risk. For MV patients, evidence suggests that the first step should be to optimize the current medical therapy; for persistent symptoms not addressed medically, ablation procedures should be considered. To optimize MV patients’ quality of care, however, additional research appears warranted to prevent long-term adverse outcomes
A literature review: pre-/post-operative atrial fibrillation for thoracic aortic aneurysm procedures
No full textAtrial fibrillation (AF) is among the most frequent cardiac surgical arrhythmias documented. The global AF prevalence is estimated at over 33 million cases, with estimates ranging up to 6.1 million cases in the United States. Among cardiac surgical patients, the risk factors for new-onset post-operative AF (POAF) include Caucasian race with increased prevalence documented in older men. Due to trends of earlier thoracic aortic aneurysm (TAA) detection and treatment, it is timely to review the AF association with adverse TAA clinical outcomes. Towards this goal, a comprehensive PubMed literature review was performed. For this initial Medline literature search, the MeSH search strategy included “thoracic aortic aneurysm” and “atrial fibrillation”. Based on the pertinent articles identified, the limited literature available for preoperative TAA AF and the predictors of POAF following TAA procedures were reviewed. Given only a handful of publications addressing these pre-/post-operative AF topics were identified using this very broad initial search approach, a knowledge chasm exists–as very little is known about TAA patients with pre-operative or new-onset post-operative AF. Given the paucity of evidence-based information available, clinically relevant TAA-specific research questions have been raised to guide future TAA AF-related investigations
Cost-effectiveness of colonoscopy and related procedures: population screening perspectives
No full textColorectal cancer (CRC) screening can reduce the incidence and mortality of CRC, and many countries with moderate-to-high incidences of CRC have implemented population screening programs. Colonoscopy plays a pivotal role in the context of CRC screening as the primary screening modality, the diagnostic exam after a positive noninvasive test, the therapeutic procedure for resecting detected neoplasms, and the surveillance exam after the removal of neoplastic lesions. Although colonoscopy outperforms other noninvasive tests in detecting colorectal neoplasms, it is associated with higher cost, manpower, and invasiveness. Owing to the heterogeneity of healthcare systems in terms of the scale of health revenue, population demographics, and the payment systems in each country, the optimal or most cost-effective screening strategy may vary. Accordingly, economic appraisal of different approaches is essential, especially in organized screening programs within which the resources and the clinical capacity are constrained, and each step of the screening flow needs careful monitoring. The therapeutic procedures applied to manage screening-detected lesions and subsequent surveillance procedures also contribute to substantial additional costs. The level of willingness to pay is affected by various factors, including demographics, income, educational level, and health consciousness, and largely affects the optimal strategies. Herein, we systematically review and summarize the current evidence regarding the cost-effectiveness of colonoscopic screening, related therapeutic procedures, and subsequent surveillance and provide a balanced view from the perspective of population screening programs. It was revealed that 10-year colonoscopy is the most effective strategy compared to other strategies under the higher willingness-to-pay threshold or low colonoscopy cost. There are, however, discrepancies in the results among studies from different countries, which could be associated with the different cost parameters and assumptions used in the models. As for various therapeutic procedures for colorectal neoplasms such as polypectomy, endoscopic mucosal resection, or endoscopic submucosal dissection, strategies based on the risk of advanced histology or deep submucosal invasion based on image-enhanced endoscopy are the least expensive and avoid more recurrences. Furthermore, subsequent surveillance strategies that are based on the risk of CRC are more cost-effective. This article provides a comprehensive review of the literatures and a balanced view from the perspective of population screening programs
New insights for drug resistance in metastatic castration-resistant prostate cancer
No full textProstate cancer is the most common cancer and is the second leading cause of cancer-related deaths among men in the United States. Androgen deprivation therapy (ADT) is the standard treatment for advanced-stage prostate cancer; however, this treatment eventually fails, leading to an incurable disease subtype known as metastatic castration-resistant prostate cancer (mCRPC). There are several molecular mechanisms that facilitate the development of mCRPC engaging androgen receptor (AR) growth axis, including AR amplification, gain of function AR mutations, and AR splice variants that are constitutively active and are a foremost factor for mCRPC development. AR-independent mechanisms with exceptionally low or absent AR expression found in cancer cells suppress ADT effectiveness and contribute to aggressive variants, including neuroendocrine differentiation. Several other AR regulatory factors such as epigenetic modification(s), and DNA damage response have been reported during post-ADT exposure and play a crucial role in mCRPC development. Therefore, targeting prostate cancer cells before their progression to mCRPC would improve patient outcomes. This special issue in “Cancer Drug Resistance” focuses on understanding the mechanism(s) and development of mCRPC resistance. This special issue also highlights the therapeutic strategies to combat against resistant subtype. This issue comprehensively reviews the mCRPC and delivers the update in the forum of mCRPC resistance development
Mechanisms of neratinib resistance in HER2-mutant metastatic breast cancer
No full textHuman epidermal growth factor receptor 2 (HER2) is a major drug target and clinical biomarker in breast cancer treatment. Targeting HER2 gene amplification is one of the greatest successes in oncology, resulting in the use of a wide array of HER2-directed agents in the clinic. The discovery of HER2-activating mutations as novel therapeutic targets in breast and other cancers marked a significant advance in the field, which led to the metastatic breast and other solid tumor trials MutHER (NCT01670877), SUMMIT (NCT01953926), and one arm of plasmaMATCH (NCT03182634). These trials reported initial clinical benefit followed by eventual relapse ascribed to either primary or acquired resistance. These resistance mechanisms are mediated by additional secondary genomic alterations within HER2 itself and via hyperactivation of oncogenic signaling within the downstream signaling axis
Drug resistance and minimal residual disease in multiple myeloma
No full textGreat progress has been made in improving survival in multiple myeloma (MM) patients over the last 30 years. New drugs have been introduced and complete responses are frequently seen. However, the majority of MM patients do experience a relapse at a variable time after treatment, and ultimately the disease becomes drug-resistant following therapies. Recently, minimal residual disease (MRD) detection has been introduced in clinical trials utilizing novel therapeutic agents to measure the depth of response. MRD can be considered as a surrogate for both progression-free and overall survival. In this perspective, the persistence of a residual therapy-resistant myeloma plasma cell clone can be associated with inferior survivals. The present review gives an overview of drug resistance in MM, i.e., mutation of β5 subunit of the proteasome; upregulation of pumps of efflux; heat shock protein induction for proteasome inhibitors; downregulation of CRBN expression; deregulation of IRF4 expression; mutation of CRBN, IKZF1, and IKZF3 for immunomodulatory drugs and decreased target expression; complement protein increase; sBCMA increase; and BCMA down expression for monoclonal antibodies. Multicolor flow cytometry, or next-generation flow, and next-generation sequencing are currently the techniques available to measure MRD with sensitivity at 10-5. Sustained MRD negativity is related to prolonged survival, and it is evaluated in all recent clinical trials as a surrogate of drug efficacy
DNA damage and metabolic mechanisms of cancer drug resistance
No full textCancer drug resistance is one of the main barriers to overcome to ensure durable treatment responses. While many pivotal advances have been made in first combination therapies, then targeted therapies, and now broadening out to immunomodulatory drugs or metabolic targeting compounds, drug resistance is still ultimately universally fatal. In this brief review, we will discuss different strategies that have been used to fight drug resistance from synthetic lethality to tumor microenvironment modulation, focusing on the DNA damage response and tumor metabolism both within tumor cells and their surrounding microenvironment. In this way, with a better understanding of both targetable mutations in combination with the metabolism, smarter drugs may be designed to combat cancer drug resistance
Ovarian cancer recurrence: is the definition of platinum resistance modified by PARPi and other intervening treatments? The evolving landscape in the management of platinum-resistant ovarian cancer
No full textDefinitions of platinum resistance have been questioned and changed over the last five years, even though no predictive biomarker of resistance exists. These have sculpted how we approach platinum retreatment and, consequently, how we devise new treatment strategies for those patients with tumour progression on platinum therapy. Platinum-non-eligible ovarian cancer is treated with single-agent non-platinum drugs. When bevacizumab can be added to chemotherapy, progression-free survival improves significantly. For patients with a BRCA mutation, PARP inhibitor monotherapy is an option compared to chemotherapy. There is currently no clearly identified role for immune-checkpoint inhibition in this patient population. This review describes some of the challenges in treating patients with platinum resistance and suggests refinements in the selection of patients most likely to benefit from targeting a DNA damage response, angiogenesis or immune modulation. It also describes novel agents of interest and possible mechanisms of the synergy of therapeutic combinations
The potential of artificial intelligence as an equalizer of gender disparity in surgical training and education
No full textThe aim of this work is to offer a panoramic view on how artificial intelligence (AI) can help to break down gender disparity in enrollment and training of women in surgery. Nowadays, many visible and concealed obstacles still exist for women who pursue a surgical career. Impediments due to gender disparity prevent women from choosing surgical specialties. Furthermore, female surgical trainees have to face many difficulties during their training, such as inequity during the residency selection process, sexual harassment, discrimination in pregnancy experience and parental leave, and work-life balance problems. AI has been successfully employed for several applications in surgery to improve patient management, implement the decision-making process, and support training. AI could represent an effective way to overcome barriers related to gender disparity and overcome the obstacles women face during surgical education and training. Virtual and augmented reality, remote mentoring, and simulators could help female surgeons deal with disparities during their training and could positively impact the choice of women when pursuing a surgical career
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