Un martes en la consulta de Medicina Interna

We describe the case of a pluripathological and dependent elderly man who attends to Internal Medicine office. He complained about dizziness, sweating, digestive discomfort and anorexia, which led him to consult in Primary Care and Emergency Department. He denied therapeutic changes and referenced good adherence to the prescribed treatment. Through an exhaustive reconciliation of the medication, adherence failures, improperly prescribed drugs and possible medication side effects are detected, allowing the deprescription of some medications.Describimos el caso de un hombre anciano pluripatológico y dependiente que acude a revisión en consulta de Medicina Interna. Presenta malestar general, mareo, sudoración, molestias digestivas y anorexia, que le llevaron a consultar en Atención Primaria y Urgencias. Niega cambios terapéuticos y refiere buena adherencia al tratamiento prescrito. Mediante una exhaustiva conciliación de la medicación, se detectan fallos de adherencia, fármacos inadecuadamente prescritos y posibles efectos secundarios medicamentosos, lo que permite realizar la desprescripción de varios medicamentos

Localized leishmaniasis of the oral mucosa. A report of three cases

El término leishmaniasis comprende un grupo de enfermedades causadas por diferentes especies de un protozoo llamado Leishmania. La leishmaniasis se produce en todo el mundo, considerándose endémica en 88 países. Existen tres formas clínicas principales de leishmaniasis: leishmaniasis visceral, leishmaniasis cutánea y leishmaniasis mucocutánea. La afectación de la mucosa, de manera exclusiva, por la Leishmania es muy rara. Presentamos una serie de tres casos de leishmaniasis mucosa localizados en la cavidad oral. El hecho de que todos los casos se produjeran en España, área endémica de L infantum, nos hace presuponer que éste fue el agente causal. La única manifestación de enfermedad de leishmaniasis en los casos descritos, fue la aparición de una lesión oral. Se administró tratamiento con antimoniato de meglumina en dos de ellos, respondiendo favorablemente. Uno de los pacientes abandonó el hospital tras el diagnóstico sin recibir tratamiento y se desconoce la evolución. Realizamos también una revisión de la literatura

Preparation and characterization of 33-S samples for 33-S(n,alpha)30-Si cross-section measurements at the n_TOF facility at CERN

Thin 33S samples for the study of the 33S(n,a)30Si cross-section at the n_TOF facility at CERN were made by thermal evaporation of 33S powder onto a dedicated substrate made of kapton covered with thin layers of copper, chromium and titanium. This method has provided for the first time bare sulfur samples a few centimeters in diameter. The samples have shown an excellent adherence with no mass loss after few years and no sublimation in vacuum at room temperature. The determination of the mass thickness of 33S has been performed by means of Rutherford backscattering spectrometry. The samples have been successfully tested under neutron irradiation.Ministerio de Economía y Competitividad de España-FPA2013-47327- C2-1-R, FPA2014-53290-C2-2-P, FPA2016-77689-C2-1-RJunta de Andalucía-P11-FQM-8229Ministerio de Economía y Empresa de España (Fondos FEDER)-FIS2015-69941-C2-1-PAECC (Asociación Española Contra el Cáncer)-PS16163811POR

Neoadjuvant eribulin in HER2-negative early-stage breast cancer (SOLTI-1007-NeoEribulin): a multicenter, two-cohort, non-randomized phase II trial

Breast cancer; Predictive markers; Translational researchCáncer de mama; Maradores predictivos; Investigación traslacionalCàncer de mama; Marcadors predictius; Recerca translacionalEribulin prolongs overall survival in patients with pre-treated advanced breast cancer. However, no biomarker exists to prospectively select patients who will benefit the most from this drug. SOLTI-1007-NeoEribulin is a phase II, open-label, two-cohort, exploratory pharmacogenomic study in patients with clinical stage I–II HER2-negative breast cancer receiving neoadjuvant eribulin monotherapy treatment. Primary objective was to explore the association of baseline tumor gene expression with pathological complete response in the breast (pCRB) at surgery. Key secondary objectives were pCRB rates in all patients and according to HR status, gene expression changes during treatment and safety. One-hundred one hormonal receptor-positive (HR + ) and seventy-three triple-negative breast cancer (TNBC) patients were recruited. The pCRB rates were 6.4% in all patients, 4.9% in HR + disease and 8.2% in TNBC. The TNBC cohort was interrupted due to a progression disease rate of 30.1%. The pCRB rates differed according to intrinsic subtypes: 28.6% in HER2-enriched, 11.1% in Normal-like, 7.9% in Luminal B, 5.9% in Basal-like and 0% in Luminal A (HER2-enriched vs. others odds ratio = 7.05, 95% CI 1.80–42.14; p-value = 0.032). Intrinsic subtype changes at surgery occurred in 33.3% of cases, mostly (49.0%) Luminal B converting to Luminal A or Basal-like converting to Normal-like. Baseline tumor-infiltrating lymphocytes (TILs) were significantly associated with pCR. Eribulin showed a good safety profile with a low response and pCRB rates. Patients with HER2-negative disease with a HER2-enriched profile may benefit the most from eribulin. In addition, significant biological activity of eribulin is observed in Luminal B and Basal-like subtypes

Procedimiento, cuidado y manejo del catéter central de inserción periférica (PICC) en adultos. FEMORA

O programa FEMORA recompila procedementos estandarizados, con evidencia científica, para os profesionais do Sergas. A protocolización dos coidados confórmase como instrumento indispensable de soporte para a práctica clínica. Entre as súas numerosas vantaxes cabe destacar a redución na diversidade inapropiada da práctica clínica, o que propicia unha atención máis xusta e equitativa aos pacientes. Este procedemento unifica, así mesmo, criterios de actuación que serven de punto de partida para unha avaliación de calidade do proceso asistencial.El programa FEMORA recopila procedimientos estandarizados, con evidencia científica, para los profesionales del Sergas. La protocolización de los cuidados se conforma como instrumento indispensable de soporte para la práctica clínica. Entre sus numerosas ventajas cabe destacar la reducción en la diversidad inapropiada de la práctica clínica, lo que propicia una atención más justa y equitativa a los pacientes. Este procedimiento unifica asimismo, criterios de actuación que sirven de punto de partida para una evaluación de calidad del proceso asistencial

Procedimiento de inserción del catéter central de inserción periférica (PICC) en adultos FEMORA. Procedimientos de enfermería: canalización y cuidados de vías vasculares

O programa FEMORA recompila procedementos estandarizados, con evidencia científica, para os profesionais do Sergas. A protocolización dos coidados confórmase como instrumento indispensable de soporte para a práctica clínica. Entre as súas numerosas vantaxes cabe destacar a redución na diversidade inapropiada da práctica clínica, o que propicia unha atención máis xusta e equitativa aos pacientes. Este procedemento unifica, así mesmo, criterios de actuación que serven de punto de partida para unha avaliación de calidade do proceso asistencial.El programa FEMORA recopila procedimientos estandarizados, con evidencia científica, para los profesionales del Sergas. La protocolización de los cuidados se conforma como instrumento indispensable de soporte para la práctica clínica. Entre sus numerosas ventajas cabe destacar la reducción en la diversidad inapropiada de la práctica clínica, lo que les propicia una atención más justa y equitativa a los pacientes. Este procedimiento unifica, asimismo, criterios de actuación que sirven de punto de partida para una evaluación de calidad del proceso asistencial

Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers Withdrawal Is Associated with Higher Mortality in Hospitalized Patients with COVID-19

Our main aim was to describe the effect on the severity of ACEI (angiotensin-converting enzyme inhibitor) and ARB (angiotensin II receptor blocker) during COVID-19 hospitalization. A retrospective, observational, multicenter study evaluating hospitalized patients with COVID-19 treated with ACEI/ARB. The primary endpoint was the incidence of the composite outcome of prognosis (IMV (invasive mechanical ventilation), NIMV (non-invasive mechanical ventilation), ICU admission (intensive care unit), and/or all-cause mortality). We evaluated both outcomes in patients whose treatment with ACEI/ARB was continued or withdrawn. Between February and June 2020, 11,205 patients were included, mean age 67 years (SD = 16.3) and 43.1% female; 2162 patients received ACEI/ARB treatment. ACEI/ARB treatment showed lower all-cause mortality (p < 0.0001). Hypertensive patients in the ACEI/ARB group had better results in IMV, ICU admission, and the composite outcome of prognosis (p < 0.0001 for all). No differences were found in the incidence of major adverse cardiovascular events. Patients previously treated with ACEI/ARB continuing treatment during hospitalization had a lower incidence of the composite outcome of prognosis than those whose treatment was withdrawn (RR 0.67, 95%CI 0.63-0.76). ARB was associated with better survival than ACEI (HR 0.77, 95%CI 0.62-0.96). ACEI/ARB treatment during COVID-19 hospitalization was associated with protection on mortality. The benefits were greater in hypertensive, those who continue

Metformin induces a fasting- and antifolate-mimicking modification of systemic host metabolism in breast cancer patients

Certain dietary interventions might improve the therapeutic index of cancer treatments. An alternative to the "drug plus diet" approach is the pharmacological reproduction of the metabolic traits of such diets. Here we explored the impact of adding metformin to an established therapeutic regimen on the systemic host metabolism of cancer patients. A panel of 11 serum metabolites including markers of mitochondria! function and intermediates/products of folate-dependent one-carbon metabolism were measured in paired baseline and post-treatment sera obtained from HER2-positive breast cancer patients randomized to receive either metformin combined with neoadjuvant chemotherapy and trastuzumab or an equivalent regimen without metformin. Metabolite profiles revealed a significant increase of the ketone body beta-hydroxybutyrate and of the TCA intermediate alpha-ketoglutarate in the metformin-containing arm. A significant relationship was found between the follow-up levels of homocysteine and the ability of treatment arms to achieve a pathological complete response (pCR). In the metformin-containing arm, patients with significant elevations of homocysteine tended to have a higher probability of pCR. The addition of metformin to an established anticancer therapeutic regimen causes a fasting-mimicking modification of systemic host metabolism. Circulating homocysteine could be explored as a clinical pharmacodynamic biomarker linking the antifolate-like activity of metformin and biological tumor response

SPARC mediates metastatic cooperation between CSC and non-CSC prostate cancer cell subpopulations

Background Tumor cell subpopulations can either compete with each other for nutrients and physical space within the tumor niche, or co-operate for enhanced survival, or replicative or metastatic capacities. Recently, we have described co-operative interactions between two clonal subpopulations derived from the PC-3 prostate cancer cell line, in which the invasiveness of a cancer stem cell (CSC)-enriched subpopulation (PC-3M, or M) is enhanced by a non-CSC subpopulation (PC-3S, or S), resulting in their accelerated metastatic dissemination. Methods M and S secretomes were compared by SILAC (Stable Isotope Labeling by Aminoacids in Cell Culture). Invasive potential in vitro of M cells was analyzed by Transwell-Matrigel assays. M cells were co-injected with S cells in the dorsal prostate of immunodeficient mice and monitored by bioluminescence for tumor growth and metastatic dissemination. SPARC levels were determined by immunohistochemistry and real-time RT-PCR in tumors and by ELISA in plasma from patients with metastatic or non-metastatic prostate cancer. Results Comparative secretome analysis yielded 213 proteins differentially secreted between M and S cells. Of these, the protein most abundantly secreted in S relative to M cells was SPARC. Immunodepletion of SPARC inhibited the enhanced invasiveness of M induced by S conditioned medium. Knock down of SPARC in S cells abrogated the capacity of its conditioned medium to enhance the in vitro invasiveness of M cells and compromised their potential to boost the metastatic behavior of M cells in vivo. In most primary human prostate cancer samples, SPARC was expressed in the epithelial tumoral compartment of metastatic cases. Conclusions The matricellular protein SPARC, secreted by a prostate cancer clonal tumor cell subpopulation displaying non-CSC properties, is a critical mediator of paracrine effects exerted on a distinct tumor cell subpopulation enriched in CSC. This paracrine interaction results in an enhanced metastatic behavior of the CSC-enriched tumor subpopulation. SPARC is expressed in the neoplastic cells of primary prostate cancer samples from metastatic cases, and could thus constitute a tumor progression biomarker and a therapeutic target in advanced prostate cancer

The C Allele of ATM rs11212617 Associates With Higher Pathological Complete Remission Rate in Breast Cancer Patients Treated With Neoadjuvant Metformin

Background: The minor allele (C) of the single-nucleotide polymorphism (SNP) rs11212617, located near the ataxia telangiectasia mutated (ATM) gene, has been associated with an increased likelihood of treatment success with metformin in type 2 diabetes. We herein investigated whether the same SNP would predict clinical response to neoadjuvant metformin in women with early breast cancer (BC). Methods: DNA was collected from 79 patients included in the intention-to-treat population of the METTEN study, a phase 2 clinical trial of HER2-positive BC patients randomized to receive either metformin combined with anthracycline/taxane-based chemotherapy and trastuzumab or equivalent regimen without metformin, before surgery. SNP rs11212617 genotyping was assessed using allelic discrimination by quantitative polymerase chain reaction. Results: Logistic regression analyses revealed a significant relationship between the rs11212617 genotype and the ability of treatment arms to achieve a pathological complete response (pCR) in patients (odds ratio [OR](genotypexarm) = 10.33, 95% confidence interval [CI]: 1.29-82.89, p = 0.028). In the metformin-containing arm, patients bearing the rs11212617 C allele had a significantly higher probability of pCR (ORA/C,C/C = 7.94, 95% CI: 1.60-39.42, p = 0.011). Conversely, no association was found between rs11212617 and clinical response in the reference arm (ORA/C,C/C = 0.77, 95% CI: 0.20-2.92, p = 0.700). After controlling for tumor size and hormone receptor status, the rs11212617 C allele remained a significant predictor of pCR solely in the metformin-containing arm. Conclusions: If reproducible, the rs11212617 C allele might warrant consideration as a predictive clinical biomarker to inform the personalized use of metformin in BC patients