A Large Case-Control Study Performed in Spanish Population Suggests That RECQL5 Is the Only RECQ Helicase Involved in Breast Cancer Susceptibility.

Around 50% of the familial breast cancer (BC) cases are estimated to be caused by germline variants in known low-, moderate-, and high-risk susceptibility genes, while the other half is of unknown genetic origin. In the present study, we wanted to evaluate the role of the RECQ helicases, some of which have been studied in the past as candidates, with unclear results about their role in the disease. Using next-generation sequencing (NGS) technology, we analyzed the whole coding sequence of BLM, RECQL1, RECQL4, RECQL5, and WRN in almost 2000 index cases from BC Spanish families that had previously tested negative for the known BC susceptibility genes (BRCAX) and compared the results with the controls extracted from gnomAD. Our results suggest that BLM, RECQL1, RECQL4, and WRN do not play a major role in BC susceptibility. However, in the combined analysis, joining the present results with those previously reported in a series of 1334 BC Spanish patients and controls, we found a statistically significant association between Loss of Function (LoF) variants in RECQL5 and BC risk, with an OR of 2.56 (p = 0.009; 95% CI, 1.18-4.98). Our findings support our previous work and places the RECQL5 gene as a new moderate-risk BC gene.A.O. is partially funded by FIS PI19/00640 supported by FEDER funds and the Spanish Network on Rare Diseases (CIBERER). M.d.l.H. is partially funded by FIS PI20/00110 supported by FEDER funds.S

Is the failure of SYMPLICITY HTN-3 trial to meet its efficacy endpoint the "end of the road" for renal denervation?

Resistant hypertension is a common medical problem that is increasing with the advent of an increasingly older and heavier population. The etiology of resistant hypertension is almost always multifactorial, but the results of numerous studies indicate that renal sympathetic activation is a particularly common cause of resistance to antihypertensive treatment. Consistent with the belief in a pivotal role of renal sympathetic stimulation, there has been a growing interest in renal denervation (RDN) treatment strategies. The long-awaited results of SYMPLICITY HTN-3 study disclosed that the reduction in blood pressure by the SYMPLICITY device did not differ from that in the sham-procedure arm of the study. In the present article, we identify several factors that explain why the study failed to demonstrate any benefit from the intervention. The reasons are multifactorial and include inadequate screening at entry and frequent medication changes during the study. Additional problems include the lack of experience of many operators with the SYMPLICITY device and procedure variability, as attested to by a diminished number of ablation "quadrants." Also a factor was the inability of the first generation Medtronic device to allow four ablations to be performed simultaneously. We recommend that future RDN studies adhere to more rigorous screening procedures, and utilize newer multi-site denervation systems that facilitate four ablations simultaneously. Drug optimization should be achieved by monitoring adherence throughout the study. Nevertheless, we are optimistic about a future role of RDN. To optimize chances of success, increased efforts are necessary to identify the appropriate patients for RDN and investigators must use second and third generation denervation devices and techniques

Renal Denervation Therapy : Available Evidence, Catheters, and Techniques

Arterial hypertension is a leading cause of cardiovascular morbidity and mortality. Although antihypertensive drugs have been shown to reduce cardiovascular events and are widely available, in many patients, blood pressure is not reduced to guideline‐recommended values despite multi‐drug therapy. Because the sympathetic nervous system plays a substantial role in hypertension, device‐based therapies have been introduced to lower blood pressure by modulating nervous system activity. This chapter will review the data behind and technical aspects of one of those technologies: renal denervation (RND)

Myocardial Protection During Acute Myocardial Infarction and Angioplasty

This chapter contains sections titled: The timing and mechanism of reperfusion Making myocytes more resistant to ischemic injury Reducing oxygen requirements Reducing reperfusion injury Summar

Two Hearts

This 64-year-old man with ischemic cardiomyopathy underwent cardiac transplantation. The recipient's native heart (N) was left in place. The heterotopic donor heart (D) functions as a biologic left ventricular assist device. A 64-year-old man presented with progressive shortness of breath and exercise intolerance due to end-stage ischemic cardiomyopathy. Since he remained severely symptomatic despite maximal medical therapy, he underwent a heterotopic cardiac transplantation. Because of the presence of severe pulmonary hypertension, the recipient's native heart (N) was left in place and the allograft was implanted in the right chest. The native heart maintains right circulation in spite of chronic pulmonary hypertension, while the heterotopic donor heart (D) functions as a biologic left ventricular assist device. The post-transplantation electrocardiogram shows two QRS complexes with different axes (Panel A). The allograft can be . .