Left atrial appendage closure: A new technique for clinical practice

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Emerging treatment strategies in recurrent platinum-sensitive ovarian cancer: focus on trabectedin.

Ovarian cancer (OC) is the leading cause of death from gynecological malignancies. In spite of high response rates to the standard front-line treatment for advanced disease with cytoreductive surgical debulking, followed by platinum/taxane-based chemotherapy, most patients eventually relapse developing drug-resistant disease. Owing to the molecular heterogeneity, genetic instability and mutagenicity of OC, increases in survival might be achieved by translating recent insights at the morpho-molecular levels to individual therapeutic strategies. Several emerging treatments have been shown to be active in platinum-sensitive (PS) recurrent OC (ROC), but an optimal strategy still has not been established. Based on the recent results, it is likely that the introduction of novel non-platinum based chemotherapies and molecular targeted therapies will have a major impact on the management of ROC. Some current strategies are focused on the extension of platinum-free interval (PFI) in patients with PS, particularly in those with partially PS disease. Apparently, the PFI extension by an effective non-platinum intervention, such as trabectedin plus pegylated liposomal doxorubicin (PLD), may reduce cumulative platinum-induced toxicities leading to longer survival after the reintroduction of subsequent platinum. The introduction of novel therapies, such as the antiangiogenic monoclonal antibody bevacizumab, opens a new field of targeted therapies in this indication. In this review, we aim to outline the therapeutic potential of new emerging approaches, particularly the role of non-platinum therapy with trabectedin in combination with PLD in patients with PS ROC. © 2013 The Authors

Analysis of the human Y-chromosome haplogroup Q characterizes ancient population movements in Eurasia and the Americas

Background: Recent genome studies of modern and ancient samples have proposed that Native Americans derive from a subset of the Eurasian gene pool carried to America by an ancestral Beringian population, from which two well-differentiated components originated and subsequently mixed in different proportion during their spread in the Americas. To assess the timing, places of origin and extent of admixture between these components, we performed an analysis of the Y-chromosome haplogroup Q, which is the only Pan-American haplogroup and accounts for virtually all Native American Y chromosomes in Mesoamerica and South America. Results: Our analyses of 1.5 Mb of 152 Y chromosomes, 34 re-sequenced in this work, support a "coastal and inland routes scenario" for the first entrance of modern humans in North America. We show a major phase of male population growth in the Americas after 15 thousand years ago (kya), followed by a period of constant population size from 8 to 3 kya, after which a secondary sign of growth was registered. The estimated dates of the first expansion in Mesoamerica and the Isthmo-Colombian Area, mainly revealed by haplogroup Q-Z780, suggest an entrance in South America prior to 15 kya. During the global constant population size phase, local South American hints of growth were registered by different Q-M848 sub-clades. These expansion events, which started during the Holocene with the improvement of climatic conditions, can be ascribed to multiple cultural changes rather than a steady population growth and a single cohesive culture diffusion as it occurred in Europe. Conclusions: We established and dated a detailed haplogroup Q phylogeny that provides new insights into the geographic distribution of its Eurasian and American branches in modern and ancient samples

ESMO management and treatment adapted recommendations in the COVID-19 era: gynaecological malignancies

The rapid spread of severe acute respiratory syndrome coronavirus 2 infection and its related disease (COVID-19) has required an immediate and coordinate healthcare response to face the worldwide emergency and define strategies to maintain the continuum of care for the non-COVID-19 diseases while protecting patients and healthcare providers. The dimension of the COVID-19 pandemic poses an unprecedented risk especially for the more vulnerable populations. To manage patients with cancer adequately, maintaining the highest quality of care, a definition of value-based priorities is necessary to define which interventions can be safely postponed without affecting patients’ outcome. The European Society for Medical Oncology (ESMO) has endorsed a tiered approach across three different levels of priority (high, medium, low) incorporating information on the value-based prioritisation and clinical cogency of the interventions that can be applied for different disease sites. Patients with gynaecological cancer are at particular risk of COVID-19 complications because of their age and prevalence of comorbidities. The definition of priority level should be based on tumour stage and histology, cancer-related symptoms or complications, aim (curative vs palliative) and magnitude of benefit of the oncological intervention, patients’ general condition and preferences. The decision-making process always needs to consider the disease-specific national and international guidelines and the local healthcare system and social resources, and a changing situation in relation to COVID-19 infection. These recommendations aim to provide guidance for the definition of deferrable and undeferrable interventions during the COVID-19 pandemic for ovarian, endometrial and cervical cancers within the context of the ESMO Clinical Practice Guidelines

Metodología para evaluar efectos del deslumbramiento en amétropes corregidos

Light originated at a glare source and entering the eye, produces a veiling luminance that causes contrast decrease in retinal images and this effect could differ if the subject wears lenses or not. In this work the glare effects in subjects wearing lenses is studied inducing ammetropies in emmetropes. Contrast thresholds of sinusoidal patterns of 2 cpd and 0.5 cd/m2 are evaluated without and with glare, the glare source being steady, at 12o and producing 60 lx at the cornea. To exemplify the use of this methodology, 2 emmetropes under 8 different conditions are considered: naked eye; 3 control conditions (wearing neutral lenses) and 4 ammetropic conditions, inducing low (2 D) and medium (5 D) myopia and hyperopia with positive and negative contact lenses and correcting them with adequate ophthalmic lenses. The contrast threshold differences between the naked eye and the other 7 conditions are statistically not significant without glare and significant (up to more than 100%) with glare, independently of lens power and probably due to ectopic scattering and multiple reflections. The method proposed enables the determination of the glare effects if lenses are worn though a greater population is required to attain conclusive data.La luz originada en una fuente deslumbrante que entra al ojo, produce una luminancia de velo que causa una disminución de contraste en las imágenes retinianas y este efecto podría diferir si el sujeto usa lentes o no. En este trabajo se estudian los efectos del deslumbramiento en sujetos que usan lentes induciendo ametropías en emétropes. Se evalúan contrastes umbrales de patrones sinusoidales de 2 cpd y 0.5 cd/m2 sin y con deslumbramiento, la fuente deslumbrante siendo estable, a 12º y produciendo 60 lx en la córnea. Para ejemplificar el uso de esta metodología, se consideran 2 emétropes en 8 condiciones diferentes: ojo desnudo; 3 condiciones de control (lentes neutras) y 4 condiciones ametrópicas, induciendo miopía e hipermetropía baja (±2 D) y media (±5 D) con lentes de contacto positivas y negativas y corrigiéndolas con adecuadas lentes oftálmicas. Las diferencias de contraste entre el ojo desnudo y las otras 7 condiciones son estadísticamente no significativas sin deslumbramiento y significativas (hasta más de 100%) con deslumbramiento, independientemente de la potencia de la lente y probablemente debido a scattering ectópico y reflexiones múltiples. El método propuesto permite determinar los efectos de deslumbramiento al usar lentes aunque, para tener datos contundentes, se requiere una mayor poblaciónFil: de Paul Camacho, Anibal Gabriel. Universidad Nacional de Tucuman. Facultad de Cs.exactas y Tecnologia. Departamento de Luminotecnia, Luz y Vision; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucuman. Instituto de Investigacion En Luz, Ambiente y Vision; ArgentinaFil: Colombo, Elisa Margarita. Universidad Nacional de Tucuman. Facultad de Cs.exactas y Tecnologia. Departamento de Luminotecnia, Luz y Vision; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucuman. Instituto de Investigacion En Luz, Ambiente y Vision; ArgentinaFil: Comastri, Silvia Ana Elva. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ingenieria. Departamento de Fisica; ArgentinaFil: Aparicio, Juan A.. Universidad de Valladolid. Facultad de Ciencias; EspañaFil: Menéndez, José Antonio. Universidad de Valladolid. Facultad de Ciencias; EspañaFil: Issolio, Luis Alberto. Universidad Nacional de Tucuman. Facultad de Cs.exactas y Tecnologia. Departamento de Luminotecnia, Luz y Vision; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucuman. Instituto de Investigacion En Luz, Ambiente y Vision; Argentin

Long Stent Implantation on the Left Anterior Descending Coronary Artery at a Follow-Up of More Than Five Years

Background: Stent implantation represents the standard of care in coronary intervention. While a short stent implanted on a focal lesion located on the left anterior descending artery (LAD) seems a reasonable alternative to an internal mammary implant, the same for long stents is still debated. Methods: We reported the long-term data of 531 consecutive patients who underwent Percutaneous Coronary Intervention (PCI) with long stents in two highly specialized centres. The main inclusion criteria were the implantation of stents longer than 30 mm on the LAD and a minimum follow-up (FU) of five years. The primary endpoint was mortality, and the secondary endpoints were any myocardial infarction (MI), target vessel and lesion revascularization (TVR and TLR, respectively), and stent thrombosis (ST) observed as definite, probable, or possible. Results: In this selected population with characteristics of complex PCI (99.1%), the long-term follow-up (mean 92.18 ± 35.5 months) estimates of all-cause death, cardiovascular death, and any myocardial infarction were 18.3%, 10.5%, and 9.3%, respectively. Both all-cause and cardiovascular deaths are significantly associated with three-vessel disease (HR 6.8; confidence of interval (CI) 95% 3.844–11.934; p &lt; 0.001, and HR 4.7; CI 95% 2.265–9.835; p &lt; 0.001, respectively). Target lesion (TLR) and target vessel revascularization (TVR) are associated with the presence of three-lesion disease on the LAD (HR 3.4; CI 95% 1.984–5.781; p &lt; 0.001; HR 3.9 CI 95% 2.323–6.442; p &lt; 0.001, respectively). Re-PCI for any cause occurred in 31.5% of patients and shows an increased risk for three-lesion stenting (HR 4.3; CI 95% 2.873–6.376; p &lt; 0.001) and the treatment of bifurcation with two stents (HR 1.6; 95% CI 1.051–2.414; p = 0.028). Stent thrombosis rate at the 5-year FU was 4.4% (1.3% definite; 0.9% probable; 2.1% possible), including a 1.7% rate of very-late thrombosis. The stent length superior to 40 mm was not associated with poor outcomes (all-cause death p = 0.349; cardiovascular death p = 0.855; MI p = 0.691; re-PCI p = 0.234; TLR p = 0.805; TVR p = 0.087; ST p = 0.189). Conclusion: At an FU of longer than five years, patients treated with stents longer than 30 mm in their LAD showed acceptable procedural results but poor outcomes.</p

Long Stent Implantation on the Left Anterior Descending Coronary Artery at a Follow-Up of More Than Five Years

Background: Stent implantation represents the standard of care in coronary intervention. While a short stent implanted on a focal lesion located on the left anterior descending artery (LAD) seems a reasonable alternative to an internal mammary implant, the same for long stents is still debated. Methods: We reported the long-term data of 531 consecutive patients who underwent Percutaneous Coronary Intervention (PCI) with long stents in two highly specialized centres. The main inclusion criteria were the implantation of stents longer than 30 mm on the LAD and a minimum follow-up (FU) of five years. The primary endpoint was mortality, and the secondary endpoints were any myocardial infarction (MI), target vessel and lesion revascularization (TVR and TLR, respectively), and stent thrombosis (ST) observed as definite, probable, or possible. Results: In this selected population with characteristics of complex PCI (99.1%), the long-term follow-up (mean 92.18 ± 35.5 months) estimates of all-cause death, cardiovascular death, and any myocardial infarction were 18.3%, 10.5%, and 9.3%, respectively. Both all-cause and cardiovascular deaths are significantly associated with three-vessel disease (HR 6.8; confidence of interval (CI) 95% 3.844–11.934; p &lt; 0.001, and HR 4.7; CI 95% 2.265–9.835; p &lt; 0.001, respectively). Target lesion (TLR) and target vessel revascularization (TVR) are associated with the presence of three-lesion disease on the LAD (HR 3.4; CI 95% 1.984–5.781; p &lt; 0.001; HR 3.9 CI 95% 2.323–6.442; p &lt; 0.001, respectively). Re-PCI for any cause occurred in 31.5% of patients and shows an increased risk for three-lesion stenting (HR 4.3; CI 95% 2.873–6.376; p &lt; 0.001) and the treatment of bifurcation with two stents (HR 1.6; 95% CI 1.051–2.414; p = 0.028). Stent thrombosis rate at the 5-year FU was 4.4% (1.3% definite; 0.9% probable; 2.1% possible), including a 1.7% rate of very-late thrombosis. The stent length superior to 40 mm was not associated with poor outcomes (all-cause death p = 0.349; cardiovascular death p = 0.855; MI p = 0.691; re-PCI p = 0.234; TLR p = 0.805; TVR p = 0.087; ST p = 0.189). Conclusion: At an FU of longer than five years, patients treated with stents longer than 30 mm in their LAD showed acceptable procedural results but poor outcomes.</p

Risk Profile and 3-Year Outcomes From the SYNTAX Percutaneous Coronary Intervention and Coronary Artery Bypass Grafting Nested Registries

ObjectivesThe aim of this study was to evaluate the use of percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) in “real-world” patients unsuitable for the alternative treatment.BackgroundNo data are available on the risk profile and outcomes of patients that can only undergo PCI or CABG.MethodsIn the SYNTAX (Synergy between PCI with TAXUS and Cardiac Surgery) trial, a multidisciplinary Heart Team reached a consensus on whether PCI and CABG could result in clinical equipoise; if so, the patient was randomized. If not, the patient was enrolled in a CABG-ineligible PCI registry or PCI-ineligible CABG registry. A proportion (60%) of patients in the CABG registry was randomly assigned to be followed up for 5 years. No statistical comparisons were performed between randomized and registry patients. Major adverse cardiac or cerebrovascular event (MACCE) rates are presented as observational only.ResultsA total of 3,075 patients were treated in the SYNTAX trial; 198 (6.4%) and 1,077 (35.0%) patients were included in PCI and CABG registries, respectively. The main reason for inclusion in the CABG registry was too complex coronary anatomy (70.9%), and the main reason for inclusion in the PCI registry was too high-risk for surgery (70.7%). Three-year MACCE was 38.0% after PCI and 16.4% after CABG. Stratification by SYNTAX score terciles demonstrated a step-wise increase of MACCE rates in both PCI and CABG registries.ConclusionsThe SYNTAX Heart Team concluded that PCI and CABG remained the only treatment options for 6.4% and 35.0% of patients, respectively. Inoperable patients with major comorbidities that underwent PCI had high MACCE rates. In patients not suitable for PCI, surgical results were excellent. (SYNTAX Study: TAXUS Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries, NCT00114972

Impact of Side Branch Predilation on Percutaneous Coronary Intervention in Complex Coronary Bifurcation Lesions

ABSTRACTBackgroundThe treatment of coronary bifurcation lesions with single stenting in the main vessel and provisional side branch stenting may be limited by the degree of anatomical/morphological complexity. Side branch predilation, a procedural step that is typically avoided, may be required to maintain side branch patency. The impact of side branch predilation on the immediate results of percutaneous coronary intervention in complex coronary bifurcation lesions was investigated.MethodsBetween May, 2008 and August, 2009, 59 patients with single coronary bifurcation lesions and significant involvement of the main and side branches were included in the study. The main exclusion criteria were the involvement of the left main coronary artery, ST-elevation acute myocardial infarction (< 72 hours) and in-stent restenosis.ResultsThe mean age of patients was 61.2±11 years, 25.4% were female, and 30.1% had diabetes mellitus. Lesions were most prevalent in the left anterior descending artery/diagonal branch (86.4%). During the procedure, 8.5% (5/59) of lesions had unsuccessful side branch predilation, and four of these bifurcations were treated with two stents. In the multivariate model, side branch stenosis at baseline was the only significant predictor of unsuccessful side branch predilation (odds ratio 1.15, 95%CI: 1.01–1.30; P=0.04), and side branch stenosis > 87.6% was identified as the most accurate cut-off value to predict failure in the receiver operating characteristic (ROC) curve.ConclusionsSide branch predilation was associated with immediate side branch failure in < 10% of cases, and the only significant predictor in the multivariate model was side branch stenosis severity (> 85%) at baseline