Strategies for the Long-Term Preservation of Site for Future Implantation of Cardiac Implantable Electronic Devices (CIEDs): Two Decades of Experience.

Introduction Implantation of cardiac implantable electronic devices (CIEDs) is an art of science. As the volume of implantation has increased worldwide, so has the rate of complications. Infection, fibrosis, lead and device erosion, lead displacement, right ventricle perforation, lead fracture, and insulation break are the common complications in the implantation process. This exposes the patient for reopening and threatens the implantation for further complication due to infection, fibrosis of veins, failure to retrieve the implanted wire, and failure to re-implant the device on the same site. We slightly changed our implantation technique to preserve the implantation site for future implantation and reduce the rate of complication in the index implantation. Methods This randomized control trial was conducted from January 2016 to September 2019 at Hayatabad Medical Complex Peshawar, Pakistan. A consecutive sampling technique was used to obtain a sample size of 602 patients keeping a 95% confidence interval and a 5% margin error. We adopted a strategy to take prick, for implantation of devices, inside the pocket, which reduces the number of sutures, hastens the procedure, prevents erosion, and minimizes the chance of subclavian crush syndrome and insulation break. We also selected the minimum possible length of leads. This will possibly decrease the chances of cumbersome fibrosis around the lead and device and will make future implantation convenient. Results There was a total of 602 procedures in the study period. About 253 (42%) procedures were done in the newly adopted strategy and 349 (58%) were performed in the conventional way. Our complication rate grossly reduces in the novel way of implantation in which we took our prick inside the pocket. Conclusion A slight modification in the implantation of CIEDs not only prevents the rate of complication in the index implantation but will also possibly preserve the site for future implantation.

Innovation in Permanent Pacemaker's Implantation Technique: Trans-Axillary Approach.

INTRODUCTION: Permanent pacemakers' (PPM) implantation is an integral part of electrophysiology and general cardiology. The implantation technique has evolved a lot since the first implantation. Several innovations have been undertaken to improve the effectiveness, life of the transplant, and patient outcomes. In this study, we introduced a new implantation technique to improve the procedure and possibly reduce the rate of complication. METHODS: This study was conducted from January 2016 to February 2017 in Hayatabad Medical Complex, Peshawar. Patients destined for implantation of PPM based on a clinical treatment plan, after proper explanation of the procedure, were brought to the catheterization laboratory. Venogram of the upper limb performed. Patients were scrubbed and draped. The axillary vein was approached via the Seldinger technique. About 2 to 3 cm superolateral to the puncture site, a skin incision was made and subcutaneous pocket constructed, and a guidewire external end was pulled in from inside the pocket keeping the venous end at the place. Subsequently, in a routine way, lead was placed, secured and the wound was closed in layers. RESULTS: A total of 690 PPM were implanted under the study. About 290 devices were implanted in the conventional way and 380 devices via the trans-axillary approach. The mean implantation time was less than 30 minutes via the trans-axillary approach. Immediate and delayed complications of the procedure were minimal. CONCLUSION: Trans-axillary approach holds some significant advantages over the conventional technique. The subcutaneous pocket and venous puncture successfully reduce the burden of foreign material, minimize the tension on the wound, shorten implantation time and reduce the chances of erosion of the device.

Restoring TRAIL mediated signaling in ovarian cancer cells.

Ovarian cancer has emerged as a multifaceted and genomically complex disease. Genetic/epigenetic mutations, suppression of tumor suppressors, overexpression of oncogenes, rewiring of intracellular signaling cascades and loss of apoptosis are some of the deeply studied mechanisms. In vitro and in vivo studies have highlighted different molecular mechanisms that regulate tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) mediated apoptosis in ovarian cancer. In this review, we bring to limelight, expansion in understanding systematical characterization of ovarian cancer cells has led to the rapid development of new drugs and treatments to target negative regulators of TRAIL mediated signaling pathway. Wide ranging synthetic and natural agents have been shown to stimulate mRNA and protein expression of death receptors. This review is compartmentalized into programmed cell death protein 4, platelet-derived growth factor signaling and miRNA control of TRAIL mediated signaling to ovarian cancer. Mapatumumab and PRO95780 have been tested for efficacy against ovarian cancer. Use of high-throughput screening assays will aid in dissecting the heterogeneity of this disease and increasing a long-term survival which might be achieved by translating rapidly accumulating information obtained from molecular and cellular studies to clinic researches.

Ovarian cancer: interplay of vitamin D signaling and miRNA action.

Increasing attention is being devoted to the mechanisms by which cells receive signals and then translate these into decisions for growth, death, or migration. Recent findings have presented significant breakthroughs in developing a deeper understanding of the activation or repression of target genes and proteins in response to various stimuli and of how they are assembled during signal transduction in cancer cells. Detailed mechanistic insights have unveiled new maps of linear and integrated signal transduction cascades, but the multifaceted nature of the pathways remains unclear. Although new layers of information are being added regarding mechanisms underlying ovarian cancer and how polymorphisms in VDR gene influence its development, the findings of this research must be sequentially collected and re-interpreted. We divide this multi-component review into different segments: how vitamin D modulates molecular network in ovarian cancer cells, how ovarian cancer is controlled by tumor suppressors and oncogenic miRNAs and finally how vitamin D signaling regulates miRNA expression. Intra/inter-population variability is insufficiently studied and a better understanding of genetics of population will be helpful in getting a step closer to personalized medicine.

Nip the HPV encoded evil in the cancer bud: HPV reshapes TRAILs and signaling landscapes.

HPV encoded proteins can elicit ectopic protein-protein interactions that re-wire signaling pathways, in a mode that promotes malignancy. Moreover, accumulating data related to HPV is now providing compelling substantiation of a central role played by HPV in escaping immunosurveillance and impairment of apoptotic response. What emerges is an intricate network of Wnt, TGF, Notch signaling cascades that forms higher-order ligand-receptor complexes routing downstream signaling in HPV infected cells. These HPV infected cells are regulated both extracellularly by ligand receptor axis and intracellularly by HPV encoded proteins and impair TRAIL mediated apoptosis. We divide this review into different sections addressing how linear signaling pathways integrate to facilitate carcinogenesis and compounds that directly or indirectly reverse these aberrant interactions offer new possibilities for therapy in cancer. Although HPV encoded proteins mediated misrepresentation of pathways is difficult to target, improved drug-discovery platforms and new technologies have facilitated the discovery of agents that can target dysregulated pathways in HPV infected cervical cancer cells, thus setting the stage for preclinical models and clinical trials.