Management of Anticoagulation Around Cardiac Implantable Electronic Device Surgery

The number of patients requiring cardiovascular implantable electronic device (CIED, e.g., pacemaker and defibrillator) surgery is increasing rapidly and at least a quarter of them are using chronic oral anticoagulation (OAC). Recently, the traditional approach of withholding anticoagulation and using heparin bridging has been challenged by studies showing safety of performing CIED surgery under anticoagulation with vitamin K antagonists. Bridging with heparin is associated with incremental healthcare costs, prolonged hospital admission, and also with an augmented relative risk of pocket hematoma. The risk of embolic events seems to be low and similar with the use of two strategies (heparin bridging and continuous warfarin). Experience with novel oral anticoagulants is limited. Few studies suggest that withholding 48–72 hours before surgery and performing the procedure under anticoagulation are safe alternatives. However, larger randomized clinical trials are needed before definitive conclusions. In this chapter, we review the management of anticoagulation around cardiac implantable electronic device surgery under new conditions

Direct Experimental Evidence for Differing Reactivity Alterations of Minerals following Irradiation: The Case of Calcite and Quartz

Concrete, a mixture formed by mixing cement, water, and fine and coarse mineral aggregates is used in the construction of nuclear power plants (NPPs), e.g., to construct the reactor cavity concrete that encases the reactor pressure vessel, etc. In such environments, concrete may be exposed to radiation (e.g., neutrons) emanating from the reactor core. Until recently, concrete has been assumed relatively immune to radiation exposure. Direct evidence acquired on Ar$^+$-ion irradiated calcite and quartz indicates, on the contrary, that, such minerals, which constitute aggregates in concrete, may be significantly altered by irradiation. Specifically, while quartz undergoes disordering of its atomic structure resulting in a near complete lack of periodicity, i.e., similar to glassy silica, calcite only experiences random rotations, and distortions of its carbonate groups. As a result, irradiated quartz shows a reduction in density of around 15%, and an increase in chemical reactivity, described by its dissolution rate, similar to a glassy silica; i.e., an increase of around 3 orders of magnitude. Calcite however, shows little change in dissolution rates - although its density noted to reduce by around 9%. These differences are correlated with the nature of bonds in these minerals, i.e., being dominantly ionic or covalent, and the rigidity of the mineral's atomic network that is characterized by the number of topological constraints (n$_c$) that are imposed on the atoms in the network. The outcomes are discussed within the context of the durability of concrete structural elements formed with calcitic/quartzitic aggregates in nuclear power plants

Neoadjuvant therapy for breast cancer

Objective: To evaluate the frequency of neoadjuvant therapy (NT) in women with stage I–III breast cancer in Italy and whether it is influenced by biological characteristics, screening history, and geographic area. Methods: Data from the High Resolution Study conducted in 7 Italian cancer registries were used; they are a representative sample of incident cancers in the study period (2009–2013). Included were 3546 women aged <85 years (groups <50, 50–69, 70–64, and 75+) with stage I–III breast cancer at diagnosis who underwent surgery. Women were classified as receiving NT if they received chemotherapy, target therapy, and/or hormone therapy before the first surgical treatment. Logistic models were built to test the association with biological and contextual variables. Results: Only 8.2% of women (290 cases) underwent NT; the treatment decreases with increasing age (14.5% in age <50 and 2.2% in age 75+), is more frequent in women with negative receptors (14.8%), HER2-positive (15.7%), and triple-negative (15.6%). The multivariable analysis showed the probability of receiving NT is higher in stage III (odds ratio [OR] 3.83; 95% confidence interval [CI] 2.83–5.18), luminal B (OR 1.87; 95% CI 1.27–2.76), triple-negatives (OR 1.88; 95% CI 1.15–3.08), and in symptomatic cancers (OR 1.98; 95% CI 1.13–3.48). Use of NT varied among geographic areas: Reggio Emilia had the highest rates (OR 2.29; 95% CI 1.37–3.82) while Palermo had the lowest (OR 0.41; 95% CI 0.24–0.68). Conclusions: The use of NT in Italy is limited and variable. There are no signs of greater use in hospitals with more advanced care

The application of MCP techniques and CFD modelling for wind resource assessment in a mediterranean island context

Paper presented at the 9th International Conference on Heat Transfer, Fluid Mechanics and Thermodynamics, Malta, 16-18 July, 2012.This paper presents salient results from an ongoing investigation into wind behaviour and resources characterisation on the central Mediterranean Maltese archipelago. The ultimate aim is to enable a more accurate determination of the potential for electrical wind power generation in the onshore and inshore marine environments. One area of this research is seeking to generate longer-term wind characteristics at selected locations. The strategy used involves a combination of field measurements at a number of onshore points and the use of Measure-Correlate-Predict (MCP) techniques in conjunction with Computational Fluid Dynamics (CFD) software. This current study will present selected results from the validation process underway to establish the performance of MCP and CFD in a sub-tropical island context.dc201

Medical ovariectomy in menopausal breast cancer patients with high testosterone levels : a further step toward tailored therapy

Five years of adjuvant therapy with anti-estrogens reduce the incidence of disease progression by about 50% in estrogen receptor-positive breast cancer patients, but late relapse can still occur after anti-estrogens have been discontinued. In these patients, excessive androgen production may account for renewed excessive estrogen formation and increased risks of late relapse. In the 50% of patients who do not benefit with anti-estrogens, the effect of therapy is limited by de novo or acquired resistance to treatment. Androgen receptor and epidermal growth factor receptor overexpression are recognized mechanisms of endocrine resistance suggesting the involvement of androgens as activators of the androgen receptor pathway and as stimulators of epidermal growth factor synthesis and function. Data from a series of prospective studies on operable breast cancer patients, showing high serum testosterone levels are associated to increased risk of recurrence, provide further support to a role for androgens in breast cancer progression. According to the above reported evidence, we proposed to counteract excessive androgen production in the adjuvant setting of estrogen receptor-positive patients and suggested selecting postmenopausal patients with elevated levels of serum testosterone, marker of ovarian hyperandrogenemia, for adjuvant treatment with a gonadotropins-releasing hormone analogue (medical oophorectomy) in addition to standard therapy with anti-estrogens. The proposed approach provides an attempt of personalized medicine that needs to be further investigated in clinical trials

First-line imatinib vs second- and third-generation TKIs for chronic-phase CML: a systematic review and meta-analysis

Imatinib, the first tyrosine kinase inhibitor (TKI) for the treatment of chronic myeloid leukemia (CML), improves overall survival (OS), but the introduction of newer TKIs requires the definition of the optimal first-line TKI for newly diagnosed Philadelphia chromosome-positive (Ph+) chronic-phase (CP) CML. This systematic review of randomized controlled trials (RCTs) compares the efficacy and safety of imatinib vs second-generation (dasatinib, nilotinib, bosutinib) and third-generation TKIs (ponatinib) in adults with newly diagnosed Ph+ CP CML, concentrating on OS, progression-free survival (PFS), and hematological and nonhematological adverse events. The quality of the evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) method. Seven RCTs published between 1990 and 2019 (involving 3262 participants) satisfied the eligibility criteria. Two RCTs (imatinib vs nilotinib and imatinib vs dasatinib) found no difference in 5-year OS or PFS. Second- and third-generation TKIs improved 3-month major molecular responses (relative risk [RR], 4.28; 95% confidence interval [CI], 2.20-8.32) and other efficacy outcomes, decreased accelerated/blastic-phase transformations (RR, 0.44; 95% CI, 0.26-0.74), but were associated with more cases of thrombocytopenia (RR, 1.57; 95% CI, 1.20-2.05), cardiovascular events (RR, 2.54; 95% CI, 1.49-4.33), and pancreatic (RR, 2.29; 95% CI, 1.32-3.96) and hepatic effects (RR, 3.51; 95% CI 1.55-7.92). GRADE showed that the certainty of the evidence ranged from high to moderate. This study shows that, in comparison with imatinib, second- and third-generation TKIs improve clinical responses, but the safer toxicity profile of imatinib may make it a better option for patients with comorbidities

Substantial variation in therapy for colorectal cancer across Europe: EUROCARE analysis of cancer registry data for 1987

To provide a quantitative description of the treatments applied to malignant colorectal cancer across Europe, we analysed all cases (11 333) of colorectal cancer registered in 1987 by 15 Cancer Registries in eight European countries. In a third of cancer registries, therapy was known for all cases, in the others 1-15% of registrations lacked treatment information. Eighty per cent of all patients received surgical resection, ranging from 58% (Estonia) to 92% (Tarn). The proportion of resections decreased with advancing age (85-73% for colon cancer; 85-70% for rectal cancer for 74 years, respectively). Only 4% of colon cancer patients received adjuvant or palliative chemotherapy, range 1-12%. Sixteen per cent of rectal cancer patients received radiotherapy with great inter-registry variability (1-43%). Since the proportion of surgically resected patients correlated positively with the 5-year relative survival probability reported by the recently published EUROCARE study, this may be part of the explanation for the major differences in survival for these cancers among different European populations. The most likely determinant of this correlation is stage at diagnosis, but, quality of, and access to surgery, as well as access to endoscopy, may differ among countries and registry areas, and these may also contribute to inter-country survival differences. Copyrigh

Global citizenship education in Latin America

This Handbook is a much needed international reference work, written by leading writers in the field of global citizenship and education