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More than 300,000 patients worldwide have undergone transcatheter aortic valve replacement (TAVR) for severe aortic stenosis (AS). The rise in TAVR as a treatment option is driven in large part by evidence showing its benefits compared with medical treatment in patients with symptomatic severe AS who were too ill to undergo surgical aortic valve replacement. Cardiac rehabilitation (CR) is recommended after valvular cardiac surgery for improving exercise capacity, with data also now showing its utility to improve quality of life, moderate frailty, and increase survival. This review describes the state of the art of CR for TAVR., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: A reciprocal link between inflammation, oxidative/nitrosative stress, and endothelial dysfunction has been postulated in chronic heart failure (CHF). The endothelial repair mechanisms involved remain to be determined. Our aim was to investigate whether there are detectable signs of ongoing angiogenesis in serum of CHF patients and to evaluate the correlation with indexes of haemodynamic and functional impairment., Methods and Results: Enzyme-linked immunosorbent assay tests were used to quantify angiogenin, angiopoietin-1, angiopoietin-2, vascular endothelial growth factor, Tie-2, and brain natriuretic peptide in serum of 87 patients with CHF of increasing severity according to New York Heart Association (NYHA; class I, n = 8; II, n = 45; and III, n = 34) and in 14 healthy subjects matched for age and sex. Angiogenin, angiopoietin-2, and Tie-2 were significantly increased in CHF of increasing severity (Kruskal-Wallis: p = 0.0004, p < 0.0001, and p = 0.017, respectively). Angiopoietin-2 was inversely correlated with the 6-min walking test (r = -0.65, p < 0.0001), peak oxygen consumption (VO(2max); r = -0.57, p = 0.0002), and deceleration time (r = -0.61, p < 0.0001). Multiple regression analysis showed that angiopoietin-2 was mainly associated with VO(2max) (p = 0.018). The angiopoietin-2 area under the receiver operating characteristic curve for CHF diagnosis was 0.94 (95% CI 0.88-0.99; p < 0.001)., Conclusions: These data demonstrate that angiopoietin-2 and selected serum markers of angiogenesis progressively increase with haemodynamic and functional decline in CHF.

We evaluated the effectiveness and the cost of axillary staging in breast cancer patients by ultrasound-guided fine-needle aspiration cytology (US-FNAC), sentinel node biopsy (SNB), and frozen sections of the sentinel node to achieve the target of the highest number of immediate axillary dissections. From January 2003 through October 2005, a total of 404 consecutive eligible breast cancer patients underwent US-FNAC of suspicious axillary lymph nodes. If tumor cells were found, immediate axillary dissection was proposed (33% of node-positive cases). If US or cytology was negative, SNB was performed. Frozen sections of the sentinel node allowed immediate axillary dissection in 31% of node-positive cases. The remaining 36% underwent delayed axillary dissection. We compared our policy with clinical evaluation of the axilla, showing better specificity of US-FNAC, the cost balanced by a 12% reduction of SNBs, and a marked reduction of unnecessary axillary dissections resulting from false-positive clinical staging. Moreover, the comparison between our policy and permanent histology of the sentinel node showed an 8% cost saving, mainly associated with the immediate axillary dissections. US-FNAC of axillary lymph nodes in breast cancer patients reliably predicts the presence of metastases and therefore refers a significant number of patients to the appropriate surgical treatment, avoiding an SNB. As cost saving to the health care system in our study is mainly related to one-step axillary surgery, US-FNAC of axillary lymph nodes and frozen section of the sentinel node generate significant cost saving for patients who have metastatic nodes.

The first GROCTA trial compared 5-year tamoxifen treatment to ten chemotherapy cycles in a group of 504 pre-/post-menopausal, node-positive, ER-positive breast cancer patients. This study also included an arm combining tamoxifen with chemotherapy. Fifteen-year results showed no difference between tamoxifen and tamoxifen plus chemotherapy, while both treatments were significantly superior to chemotherapy alone. A confirmatory study (GROCTA 02) was performed in 244 pre-/perimenopausal patients by comparing 5 years of tamoxifen treatment (plus 2 years of goserelin) to six CMF cycles. No difference has emerged so far between the tamoxifen and CMF arms at a median follow-up time of 62 months. Post-menopausal women were scheduled to receive 3 years of tamoxifen treatment and then to be randomly allocated to further 2 years of tamoxifen or to 2 years of low-dose aminoglutethimide (GROCTA 04B). So far 662 patients have been entered, 375 of whom have been randomized to tamoxifen (n = 188) or aminoglutethimide (n = 187). Preliminary results (median follow-up time 32 months) show no major difference in patients' outcome. A new trial (ITA trial) with a similar design but employing anastrozole in place of aminoglutethimide has been activated in 1998. The GROCTA 03 study investigated the potential superiority of alternating adjuvant chemotherapy over standard CMF. This study, which included 107 node-positive ER-negative pre-menopausal women, was prematurely closed because more patients allocated to the triple alternated chemotherapy appeared to have relapsed and died at the first interim analysis. The use of high-dose chemotherapy (HDC) was explored by the GROCTA 06 trial which included 53 patients with ten or more involved nodes and a maximum age of 55 years. These patients were scheduled to receive three standard CEF cycles followed by one cycle of HDC (cyclophosphamide 5 g/m2; etoposide 1.5 g/m2; cisplatin 150 mg/m2) without any form of bone marrow rescue. This HDC program proved to be feasible but was not superior to CMF-based chemotherapy we had previously employed in a comparable group of patients in previous GROCTA trials. These findings prompted us to explore new HDC programmes with the use of peripheral stem cell support and in addition the possible value of new drugs such as Taxol and vinorelbine. New-generation trials will also explore the value of new prognostic indicators such as tumor proliferative activity, which are prospectively used to allocate patients to different treatment options.