Experience with Sunitinib in metastatic renal cell carcinoma (mRCC) patients: pooled analysis from 3 Spanish observational prospective studies

[Abstract] Background: A pivotal, randomized, phase III trial demonstrated a statistically significant superiority of sunitinib over interferon-α in metastatic renal cell carcinoma (mRCC) patients. Objective: To evaluate the effectiveness and safety of sunitinib in patients with advanced or mRCC in routine clinical practice. Methods: Retrospective pooled analysis of clinical data from three observational and prospective studies carried out between 2007 and 2011 in 33 Spanish hospitals. Tumor response, Progression-free survival (PFS) and overall survival (OS), and main sunitinib-related toxicities were registered. Results: 224 patients were analyzed. Median PFS 10.6 months (95% CI: 9.02–12.25), median OS 21.9 months (95% CI: 17.2–26.6). Objective response rate (ORR) 43.8% (95% CI: 36.8–50.7). Median time to PR was 3.8 months (95% CI: 3.86–5.99) and to CR 8.2 months (95% CI: 4.75–9.77). The most common ≥ grade-3 AEs were asthenia/fatigue (18.7%), hand-foot syndrome (6.2%), hypertension (5.8%) and neutropenia (4.8%). Hand-foot syndrome, diarrhea and mucositis were confirmed as independent predictors for PFS and/or OS in a multivariate analysis (p < 0.05) Conclusions: Outcomes with sunitinib in daily clinical practice resemble those obtained in clinical trials. Long-term benefit with sunitinib is possible in advanced RCC patients but the appropriate management of toxicities is mandatory to enable patients to remain on treatment

Synergistic effect of antimetabolic and chemotherapy drugs in triple-negative breast cancer

The triple-negative breast cancer (TNBC) subtype comprises approximately 15% of all breast cancers and is associated with poor long-term outcomes. Classical chemotherapy remains the standard of treatment, with toxicity and resistance being major limitations. TNBC is a high metabolic group, and antimetabolic drugs are effective in inhibiting TNBC cell growth. We analyzed the combined effect of chemotherapy and antimetabolic drug combinations in MDA-MB-231, MDA-MB-468 and HCC1143 human TNBC cell lines. Cells were treated with each drug or with drug combinations at a range of concentrations to establish the half-maximal inhibitory concentrations (IC50). The dose-effects of each drug or drug combination were calculated, and the synergistic or antagonistic effects of drug combinations were defined. Chemotherapy and antimetabolic drugs exhibited growth inhibitory effects on TNBC cell lines. Antimetabolic drugs targeting the glycolysis pathway had a synergistic effect with chemotherapy drugs, and antiglycolysis drug combinations also had a synergistic effect. The use of these drug combinations could lead to new therapeutic strategies that reduce chemotherapy drug doses, decreasing their toxic effect, or that maintain the doses but enhance their efficacy by their synergistic effect with other drugsMaría I. Lumbreras-Herrera and Andrea Zapater-Moros are supported by Consejería de Educación e Investigación de la Comunidad de Madrid (IND2018/BMD-9262). Elena López-Camacho is supported by the Spanish Economy and Competitiveness Ministry (PTQ2018–009760). This work is supported by an unrestricted grant from Roch

Patients' preferences for subcutaneous trastuzumab versus conventional intravenous infusion for the adjuvant treatment of HER2-positive early breast cancer: final analysis of 488 patients in the international, randomized, two-cohort PrefHer study

PrefHer revealed compelling and consistent patient preference for subcutaneous (s.c.) trastuzumab, regardless of delivery by single-use injection device or hand-held syringe. s.c. trastuzumab was well-tolerated and safety data, including immunogenicity, were consistent with previous reports. No new safety signals were identified compared with the known intravenous trastuzumab profile in early breast cance

Best Practice Guide for Positive Parenting. A resource for practitioners working with families

[spa] El modo en que se concibe el ejercicio de la parentalidad ha cambiado sustancialmente en nuestra sociedad. Ello no sólo se debe a la gran variedad de formas familiares y diversidad de culturas que conviven actualmente en su seno, sino también a un cambio conceptual que afecta al núcleo básico de la tarea parental. Nos referimos a la necesidad de sustituir el concepto de autoridad parental, centrado únicamente en la necesidad de lograr metas de obediencia y disciplina en los hijos e hijas, por otro más complejo y demandante como es el concepto de responsabilidad parental. Según este concepto, la cuestión clave no es si las figuras parentales deben ejercer la autoridad para que sus hijos/as les obedezcan, sino cómo ejercerla de modo responsable para que se preserven los derechos de los mismos, sin menoscabar los de padres y madres, y se fomenten sus capacidades críticas y de participación en el proceso de socialización, al mismo tiempo que se promueve progresivamente su autonomía y contribución a la vida comunitaria. Ante este cambio cualitativo en la manera de entender las responsabilidades parentales, se alzan muchas voces de desánimo entre los propios padres y madres, quienes en ocasiones se ven impotentes en su tarea al no saber cómo actuar para lograr metas educativas tan complejas y sentir, al mismo tiempo, que están perdiendo capacidades de control sobre sus hijos e hijas. En otras ocasiones, el desánimo y el estrés ante la tarea parental no surge por no saber llevarla a cabo sino por no poder hacerlo adecuadamente debido a la situación de la persona que educa en solitario o en pareja sin contar con redes de apoyo apropiadas. Esto crea situaciones límite que repercuten negativamente en todos y cada uno de los miembros de la familia, especialmente en los más vulnerables.[eng] Our conception of what parenting should look like has changed considerably in our society. This is due not only to the large variety of family structures and the diversity of cultures that currently co-exist in our society, but also to a shift in mindset that touches the very heart of the parenting task. This can be expressed as the need to replace the concept of parental authority, which focuses solely on meeting aims related to the child’s obedience and discipline, with the much more complex and demanding concept of parental responsibility. Here, the key question is not whether the parent figure should exert the necessary authority to ensure a child’s obedience. Rather, it is about how this authority can be exerted responsibly in a way that protects the child’s rights - without of course neglecting the mother’s and father’s rights - and that fosters the child’s skills in critical thinking and participation in the socialisation process, while at the same time progressively fostering the child’s autonomy and contribution to community life. There has been much concern expressed in response to this qualitative shift in how a parent’s responsibilities are viewed, including amongst mothers and fathers themselves. Parents often feel powerless to act, as they do not know how to achieve such complex parenting goals, and feel like they are losing control over their children. Other times, feelings of discouragement and stress arise not because parents do not how to go about the task of parenting, but rather because they find themselves unable to do so, as may be the case for single parents or couples raising children without the necessary support networks. This can lead to extreme situations which can have a negative impact on the entire family, and especially its most vulnerable members

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Spatiotemporal Characteristics of the Largest HIV-1 CRF02_AG Outbreak in Spain: Evidence for Onward Transmissions

Background and Aim: The circulating recombinant form 02_AG (CRF02_AG) is the predominant clade among the human immunodeficiency virus type-1 (HIV-1) non-Bs with a prevalence of 5.97% (95% Confidence Interval-CI: 5.41–6.57%) across Spain. Our aim was to estimate the levels of regional clustering for CRF02_AG and the spatiotemporal characteristics of the largest CRF02_AG subepidemic in Spain.Methods: We studied 396 CRF02_AG sequences obtained from HIV-1 diagnosed patients during 2000–2014 from 10 autonomous communities of Spain. Phylogenetic analysis was performed on the 391 CRF02_AG sequences along with all globally sampled CRF02_AG sequences (N = 3,302) as references. Phylodynamic and phylogeographic analysis was performed to the largest CRF02_AG monophyletic cluster by a Bayesian method in BEAST v1.8.0 and by reconstructing ancestral states using the criterion of parsimony in Mesquite v3.4, respectively.Results: The HIV-1 CRF02_AG prevalence differed across Spanish autonomous communities we sampled from (p &lt; 0.001). Phylogenetic analysis revealed that 52.7% of the CRF02_AG sequences formed 56 monophyletic clusters, with a range of 2–79 sequences. The CRF02_AG regional dispersal differed across Spain (p = 0.003), as suggested by monophyletic clustering. For the largest monophyletic cluster (subepidemic) (N = 79), 49.4% of the clustered sequences originated from Madrid, while most sequences (51.9%) had been obtained from men having sex with men (MSM). Molecular clock analysis suggested that the origin (tMRCA) of the CRF02_AG subepidemic was in 2002 (median estimate; 95% Highest Posterior Density-HPD interval: 1999–2004). Additionally, we found significant clustering within the CRF02_AG subepidemic according to the ethnic origin.Conclusion: CRF02_AG has been introduced as a result of multiple introductions in Spain, following regional dispersal in several cases. We showed that CRF02_AG transmissions were mostly due to regional dispersal in Spain. The hot-spot for the largest CRF02_AG regional subepidemic in Spain was in Madrid associated with MSM transmission risk group. The existence of subepidemics suggest that several spillovers occurred from Madrid to other areas. CRF02_AG sequences from Hispanics were clustered in a separate subclade suggesting no linkage between the local and Hispanic subepidemics

Factores pronosticos en el carcioma de pulmon no microcitico

Centro de Informacion y Documentacion Cientifica (CINDOC). C/Joaquin Costa, 22. 28002 Madrid. SPAIN / CINDOC - Centro de Informaciòn y Documentaciòn CientìficaSIGLEESSpai

Factores pronósticos en el carcioma de pulmón no microcítico

Tesis doctoral inédita. Universidad Autónoma de Madrid. Facultad de Medicina, Departamento de Medicina, 199