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Percutaneous catheter-based repeat revascularization in patients with previous PCI or CABG: a comprehensive review of the evidence
No full textRepeat revascularization after percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) is one of the most common long-term complications which warrants continuous clinical follow up. Re-interventions negatively impact long-term survival in patients with coronary artery disease. The repeat revascularization after PCI can be either a target lesion revascularization (stent thrombosis/in-stent restenosis) or a revascularization of native coronary artery after PCI (target vessel revascularization/non-target vessel revascularization). The EVENT registry reports that repeat revascularization rates in patients undergoing PCI is 12% in the first year of follow up. Repeat revascularization with additional stent deployment increases the rate of stent thrombosis and restenosis, thereby leading to recurrent ischemic events. Repeat revascularization after CABG can be either in the early postoperative period or later due to native disease progression or late graft stenosis. The need for re-intervention after surgical or percutaneous revascularization is inevitable and is dependent on modifiable and non-modifiable risk factors
Colonoscopy quality and endoscopist factors: what are the required endoscopist conditions for high-quality colonoscopy to reduce colorectal cancer incidence and mortality?
No full textTo maximize the effectiveness of colonoscopy in decreasing the incidence and mortality of colorectal cancer (CRC), high-quality colonoscopy procedures are essential. Considering that the colonoscopy quality varies among endoscopists, it is important to understand the endoscopist factors that influence the colonoscopy quality. In this paper, we reviewed the endoscopist factors related to colonoscopy quality. There are several quality indicators of colonoscopy, among which the adenoma detection rate is the most established indicator with evidence of its correlation with post-colonoscopy CRC. With respect to lesion detectability during colonoscopy, there are other measurements such as the sessile serrated lesion detection rate; however, further evidence on their relationships with post-colonoscopy CRC is needed. Previous studies that have examined the endoscopist characteristics influencing colonoscopy quality have suggested that several factors, including experience, the volume of colonoscopy procedures, and endoscopist specialty, are related to lesion detectability. However, discrepancies exist regarding the studies’ results; in particular, the influence of endoscopist specialty on coloscopy quality is controversial. Some recent studies have demonstrated that endoscopist specialty is not related to lesion detectability when considering confounding factors. Furthermore, it has been reported that nurse endoscopists can provide high-quality colonoscopy after training. It may be possible for endoscopists to improve their colonoscopy quality, regardless of specialty. Training, monitoring, and feedback of colonoscopy quality measurements are useful interventions for endoscopists to ensure high-quality procedures. Owing to the continuous development of endoscopic technologies, it is believed that training is useful for both inexperienced and experienced endoscopists
Referring hospital involvement in early discharge post transcatheter aortic valve implantation: the TAVI (R-) EXPRES program
No full textAim: Over the past decade, transcatheter aortic valve implantation (TAVI) has matured into a valid treatment strategy for elderly patients with severe aortic stenosis. TAVI programs will grow with its adoption in low-risk patients. The aim of this study was to evaluate safety and feasibility of early discharge protocols, either home or back to a referring hospital.Methods: Consecutive patients undergoing TAVI between July 2017 and July 2019 were stratified into three discharge pathways from TAVI center: (1) early home (EXPRES); (2) early transfer to referring hospital (R-EXPRES); and (3) routine discharge (standard). Baseline, procedural, and 30-day outcomes were prospectively collected and compared per discharge pathway.Results: In total, 22 (5%) patients were enrolled in the EXPRES cohort [median age 78 (IQR: 73-81); mean Society of Thoracic Surgeons (STS) 2.4% ± 1.5%], 121 (29%) in the R-EXPRES cohort [median age 81 (IQR: 77-84); mean STS 4.3% ± 2.8%], and 269 (65%) in the routine discharge cohort [median age 80 (IQR: 75-85); mean STS 4.4% ± 3.1%]. EXPRES patients trended to be younger (P = 0.13) and had lower STS (P = 0.02). Early clinical outcome was similar through the different pathways including re-hospitalization rate. Median length of stay was one day longer for R-EXPRES vs. routine discharge patients [5 (IQR: 4-7) vs. 4 (IQR: 3-6); P < 0.01]. Median length of stay (LOS) was two days (IQR: 1-3 days) for EXPRES patients.Conclusion: Early discharge pathways home and to referral hospitals are safe and help streamline TAVI programs. LOS in referring hospitals may be further reduced
Prevention of bariatric complications: best practices
No full textThe prevalence of obesity in both the United States and worldwide has grown significantly over the last several decades. With this growing pandemic, more patients are seeking surgical alternatives to achieve weight loss goals. Bariatric surgery has multiple proven health benefits, including weight loss and resolution of several co-morbidities, including diabetes. Advances in surgical techniques, including laparoscopy, have allowed bariatric surgery to increase in popularity among obese patients. However, bariatric surgery is not without complications. Key to successful weight loss surgery includes appropriate pre-operative laboratory workup, a multidisciplinary approach with other health care providers, proper peri-operative techniques as well as close post-operative follow up. This article will highlight several important criteria bariatric surgeons should bear in mind when evaluating patients in pre-operative, peri-operative and post-operative states to help prevent common complications seen in weight loss surgery
Emerging mechanisms of immunotherapy resistance in sarcomas
No full textSarcomas are a heterogeneous group of over 150 mesenchymal neoplasms of bone and soft tissue. Clinical prognosis remains poor in the metastatic and refractory setting, despite treatment with traditional chemotherapies. A subset of sarcoma patients can exhibit remarkable responses to novel immune therapies; however, most patients will not respond. Emerging data from genetic and transcriptomic datasets suggests that patients who are resistant to checkpoint inhibitor monotherapy may have low expression of immune-related genes, suggesting that the sarcoma was not sufficiently immunogenic to trigger or maintain an immune response to generate tumor-specific immune effector cells. In this review, we discuss the emerging data surrounding potential mechanisms of resistance, including various biomarkers explored in clinical trials of immune therapy for sarcomas. We also review future directions in clinical trials that are focused on boosting tumor immunogenicity to improve the activity of checkpoint inhibitors, as well as adoptive cellular therapy approaches to bypass deficiencies in neoantigens or antigen presentation
Combating CHK1 resistance in triple negative breast cancer: EGFR inhibition as potential combinational therapy
No full textTriple negative breast cancer (TNBC) is marked by a lack of expression of the Estrogen Receptor, Progesterone Receptor, and human epidermal growth factor receptor 2. Therefore, targeted therapies are being investigated based on the expression profiles of tumors. Due to the potential for acquired and intrinsic resistance, there is a need for combination therapy to overcome resistance. In the article by Lee et al., the authors identify that, while prexasertib (a CHK1 inhibitor) lacks efficacy alone, combination with an EGFR inhibitor provides synergistic anti-tumor effects. Advances in targeted therapy for TNBC will benefit the clinical landscape for this disease, with this study initiating a new avenue of investigation
The complex relationship between multiple drug resistance and the tumor pH gradient: a review
No full textMultiple drug resistance (MDR) is the tumor’s way of escaping the cytotoxic effects of various unrelated chemotherapeutic drugs. It can be either innate or acquired. MDR represents the end of the therapeutic pathway, and it practically leaves no treatment alternatives. Reversing MDR is an unfulfilled goal, despite the important recent advances in cancer research. MDR, the main cause of death in cancer patients, is a multi-factorial development, and most of its known causes have been thoroughly discussed in the literature. However, there is one aspect that has not received adequate consideration - intracellular alkalosis - which is part of wider pH deregulation where the pH gradient is inverted, meaning that extracellular pH is decreased and intracellular pH increased. This situation interacts with MDR and with the proteins involved, such as P-gp, breast cancer resistance protein, and multidrug associated resistance protein 1. However, there are also situations in which these proteins play no role at all, and where pH takes the lead. This is the case in ion trapping. Reversing the pH gradient to normal can be an important contribution to managing MDR. The drugs to manipulate pH exist, and most of them are FDA approved and in clinical use for other purposes. Furthermore, they have low or no toxicity and are inexpensive compared with any chemotherapeutic treatment. Repurposing these drugs and combining them in a reasonable fashion is one of the points proposed in this paper, which discusses the relationship between cancer’s peculiar pH and MDR
Multi-level storage based auditing scheme for 5G and beyond defined edge computing
No full textAim: Edge computing has become one of the most essential approaches for processing user-side data in the future, thanks to the portability of storage and computing devices. 5G and beyond defined edge computing has become one of the most urgently required technologies. However, there are still several issues that must be resolved. Edge computing's present storage structure is incapable of adapting to new and flexible application scenarios. Simultaneously, data stored on edge devices are more vulnerable to attacks, and the integrity of the data needs to be protected.Method: For 5G and beyond defined edge computing, a novel auditing scheme based on multi-level storage is proposed in this paper. To reduce the response time of data queries, we first present a storage system with neighborhood servers. Then, a scheme for third-party-assisted auditing is described. Users can audit their data using self-defined file names.Results: The scheme is secure and efficient, according to the security analysis and performance simulation. Our scheme cost less computation overhead than the compared related work.Conclusion: The result shows that the novel proposal is efficient for the application in 5G and beyond defined edge computing
Different E-box binding transcription factors, similar neuro-developmental defects: ZEB2 (Mowat-Wilson syndrome) and TCF4 (Pitt-Hopkins syndrome)
No full textZEB2 and TCF4 are transcription factors (TFs) whose locations in embryos overlap in many sites and developmental phases, including in the forebrain and its cortical neurons. De novo mutations cause the phenotypically overlapping, haploinsufficient Mowat-Wilson (MOWS, in the ZEB2 gene) and Pitt-Hopkins (PTHS, in TCF4) syndromes, which currently cannot be cured. Mutant alleles have been mapped and defects documented (also in brain function) in MOWS and PTHS patients. Appropriately designed mouse models and cells derived from these, as well as cellular models including cultured pluripotent cells, enable investigating the genetic and molecular mechanisms underlying the developmental deficiencies that manifest after birth in the nervous systems and their multiple cell types, as well as those of organs other than the brain, in MOWS and PTHS. Biochemical analyses of cell type-specific transcriptomic changes in these perturbation models as compared to control cells, the identification of the intact-factor dependent and direct target genes, and of partner proteins including chromatin modulators, are revealing complex and multiple modes of action that eventually will explain target gene selectivity for these TFs. Both TFs have also been found to operate in acute and chronic diseases and cell-based repair processes after tissue or organ injury. In addition, the defective function also arises from their aberrant gene expression, which will require a deeper investigation of how the transcription of these TF genes is regulated. Furthermore, these two factors genetically and biochemically interact. This review combines the essentials and recent progress for both TFs for the first time, with a focus on MOWS and PTHS
An intriguing canting dipole configuration and its evolution under an electric field in La-doped Pb(Zr,Sn,Ti)O3 perovskites
No full textDespite the fact that electric dipole ordering plays a key role in the unique physical properties of dielectric materials, electric dipole configurations mostly appear simply as either parallel or antiparallel. Here, we report a canting electric dipole configuration in La-doped Pb(Zr,Sn,Ti)O3 perovskites based on advanced neutron, synchrotron X-ray and three-dimensional electron diffraction techniques. It is revealed that, arising from the coupling between the atomic displacement and oxygen octahedral tilting, this unique electric dipole configuration displays a canting arrangement aligned in the (110)p plane that possesses an antiparallel component along the [110]P direction and a parallel component along the [001]P direction. Remarkably, under an in-situ electric field, the electric dipoles continuously rotate with a gradually reduced canting angle, as confirmed by phase-field simulations, and ultimately evolve into a ferroelectric ordering. Such an evolution gives rises to a small hysteresis and an equivalent lattice strain to the macroscopic strain. These findings enrich the current understanding of the types of electric dipole configurations in dielectric materials and are expected to aid the design of new dielectric materials with emergent properties
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