Post-transcatheter aortic valve implantation isolated PR prolongation: incidence and clinical significance.

AIMS: Conduction abnormalities post-transcatheter aortic valve implantation (TAVI) are common. Post-TAVI PR prolongation was mainly studied as an adjunct to new-onset bundle branch block. The net effect of isolated PR prolongation (IPRP) without post-TAVI QRS changes is not well known. The aim of this study was to define the incidence and clinical significance of post-TAVI IPRP. METHODS AND RESULTS: A total of 1108 consecutive TAVI patients were reviewed. Patients with IPRP were compared with patients without post-TAVI electrocardiogram (ECG) changes. Clinical outcomes included permanent pacemaker implantation (PPI) and overall mortality. A total of 146 patients with IPRP were compared with 290 patients without post-TAVI ECG changes. At 1 year follow-up, 4 (2.7%) and 7 (2.4%) patients underwent PPI (P = 0.838) and 10 (6.8%) and 25 (8.6%) died (P = 0.521), from the study and control groups, respectively. No patient with IPRP and narrow QRS underwent PPI during 1 year post-TAVI, and all death events were non-cardiac except one unknown cause. Permanent pacemaker implantation rates among patients with IPRP and wide QRS were higher (n = 4, 12.1%), compared with patients with wide QRS without post-TAVI ECG change (n = 3, 4%) however not reaching statistical significance (P = 0.126). Multivariate Cox proportional hazards model demonstrated that in patients with narrow QRS, neither PR prolongation nor baseline or maximal PR intervals was associated with the combined endpoint of PPI and mortality. However, in patients with wide QRS, baseline PR intervals and QRS width, but not PR prolongation were associated with the combined outcome. CONCLUSION: Post-TAVI IPRP in patients with narrow QRS is not associated with adverse outcome. This finding may translate clinically into a more permissive approach to these patients.

[THE LIQUID BIOPSY REVOLUTION IN BREAST CANCER - APPLICATIONS AND POSSIBILITIES].

INTRODUCTION: Over the past two decades there have been significant developments in the fields of laboratory technology, genetics and bioinformatics. These developments have raised the attractiveness of liquid biopsy - a test aimed to detect tumor markers in body fluids. One of the liquid biopsy methods is based on identification of circulating tumor DNA - fragments of DNA originating from the tumor which are evident in the bloodstream - revealing the various tumor characteristics via simple blood tests. This novel approach has several advantages over the traditional biopsy: it is noninvasive and thus more convenient and safer for the patient; it reflects the characteristics of the entire tumor tissue present in the patient's body in a single test; it is performed quickly and safely by a phlebotomist and does not rely on the subjective interpretation of the pathologist. The liquid biopsy is a highly valuable tool for the diagnosis and monitoring of cancer, which can be recruited for the clinical management of breast cancer - the most common malignancy in females which is estimated to affect one in every eight women. In this review we will present the existing and the potential applications of the liquid biopsy in breast cancer patients, regarding the various settings of patient care - diagnosis, treatment and follow-up.

Potential Refinement of Recurrence Score by pSTAT3 Status.

The likelihood of recurrence in breast cancer patients with hormone receptor-positive (HR-positive) tumors is influenced by clinical, histopathological, and molecular features. Recent studies suggested that activated STAT3 (pSTAT3) might serve as a biomarker of outcome in breast cancer patients. In the present work, we have analyzed the added value of pSTAT3 to OncotypeDx Recurrence Score (RS) in patient prognostication. We have found that patients with low RS (<26) and low pSTAT3 might represent a population at a higher risk for cancer recurrence. Furthermore, we have observed that a positive pSTAT3 score alone can be a favorable marker for patients with HR-positive breast cancer under the age of 50. In an era of personalized medicine, these findings warrant further appraisal of chemotherapy benefit in this population.

"High-Risk Breast Cancer Screening in BRCA1/2 Carriers Leads to Early Detection and Improved Survival After a Breast Cancer Diagnosis".

BACKGROUND: Germline BRCA1/2 pathogenic variant (PV) carriers have high lifetime risk of developing breast cancer and therefore subjected to intense lifetime screening. However, solid data on the effectiveness of high-risk screening of the BRCA1/2 carrier population is limited. PATIENTS AND METHODS: Retrospectively, we analyzed 346 women diagnosed with breast tumors. Patients were divided according to the timing of BRCA1/2 PVrecognition, before (BRCA-preDx awareness, N = 62) or after (BRCA-postDx awareness group, N = 284) cancer diagnosis. RESULTS: Median follow-up times were 131.42 and 93.77 months in the BRCA-preDx awareness and BRCA-postDx awareness groups, respectively. In the BRCA-preDx awareness group, 78.7% of the patients had invasive tumors and 21.3% were diagnosed with pure ductal carcinoma in situ. In contrast, in the BRCA-postDx awareness group over 93% of women were diagnosed with invasive cancer and only 6.4% had in situ disease. The mode of tumor detection differed significantly between the groups: 71.9% in the BRCA-postDx awareness group and 26.2% in the BRCA-preDx awareness group were diagnosed after personally palpating a lump. Tumor size and nodal involvement were significantly more favorable in the BRCA-preDx awareness group. T stage was significantly lower in the BRCA-preDx awareness group: 54.84% at T1 and 20.96% at Tis. In the BRCA-postDx awareness group, only 37.54% were at T1 and 6.49% at Tis. The N stage was also significantly lower in the BRCA-preDx awareness group: 71% had no lymph node metastases, compared with 56.1% in the BRCA-postDx awareness group. Additionally, therapeutic procedures varied between the groups: BRCA-preDx awareness group patients underwent more breast conserving surgeries. Axillary lymph node dissection was done in 38% of women in the BRCA-postDx awareness group and in only 8.7% of the BRCA-preDx awareness group patients. Interestingly, improved survival was found among patients who underwent high-risk screening (hazard ratio=0.34). CONCLUSIONS: High-risk screening might facilitate downstaging of detected breast tumor among BRCA1/2 carrier population.

Taxation of sugar sweetened beverages and unhealthy foods: a qualitative study of key opinion leaders' views.

BACKGROUND: Fiscal policies to fight obesity such as taxation of unhealthy foods or sugar-sweetened beverages (SSBs) have gained considerable attention in recent years. Many studies modelling the impact of various magnitudes of taxes on SSB purchasing and their potential effects on various health outcomes have been published; however, legislation and implementation of such taxes have encountered many obstacles in the countries that have implemented them to date. We investigated the perceptions and views of key opinion leaders, policy makers and various other Israeli stakeholders on taxation of SSBs and unhealthy snacks. We also evaluated the challenges and barriers that may be expected for initiating such a policy. METHODS: A qualitative study based on 39 in-depth interviews with Israeli stakeholders in the fields of health, nutrition, economics, public advocacy and policymaking. RESULTS: All stakeholders viewed obesity as a combined societal and personal issue that should be under government responsibility. Only stakeholders from economic sectors thought that taxation of SSBs and unhealthy snacks would reduce their consumption, while the prevailing notion among non-economists was that such a tax would not be acceptable because the higher price would not decrease consumption. Concerns were raised that the tax would mostly affect individuals from low socioeconomic backgrounds. Some of the stakeholders indicated that they would support such a tax only if its revenue would be directed to specific causes such as health-promoting plans. Potential barriers to taxation include: opposition of various sectors, technical and bureaucratic obstacles impeding tax implementation, difficulties in defining which products to tax, and opposition of the treasury to earmark tax revenue for health education. CONCLUSIONS: Taxation should be a part of a multipronged strategy rather than a sole measure for fighting obesity. Dedicating tax revenues to specific predefined causes should be considered, particularly towards health promotion activities, obesity treatment and prevention, education, and subsidies of healthy food.

Effect of metformin and lipid emulsion on the circadian gene expression in muscle cells.

The circadian clock influences nearly all aspects of metabolism. However, little is known regarding the effect of the energy status on circadian rhythms. Our aim was to test the effect of two opposing energy situations, metformin and lipid emulsion (LE), on clock and metabolic circadian expression in differentiated C2C12 myotubes. Metformin treatment led to depleted ATP levels accompanied by elevated NADH levels, whereas LE treatment led to increased ATP and NAD(+) levels. Nevertheless, both LE and metformin treatments activated the AMP-activated protein kinase (AMPK) pathway. In contrast, the effect on circadian rhythms was completely different. LE led to disrupted clock and metabolic gene expression, whereas metformin led to mainly high-amplitude shifted rhythms. Combination of metformin and LE led to an antagonistic effect on circadian gene expression. Although metformin and LE have an opposing effect on circadian gene expression and on the cellular energy status, they both lead to AMPK activation.