Expression and prognostic significance of apolipoprotein D in breast cancer.

En esta publicación se evaluó la expresión y la significación pronostica de la apolipoproteína D (apo D) en 163 carcinomas mamarios. La apo D es una glicoproteína involucrada en el sistema de transporte de lípidos del plasma humano y presente en grandes cantidades en el líquido de los quistes de mujeres con enfermedad macroquistica mamaria. Además, se ha propuesto como marcador de la acción esteroidea en células de cáncer de mama. La técnica empleada para evaluar la expresión de Apo D en carcinomas de mama fue la tinción con inmunoperoxidasa. Del total, 103 tumores se tiñeron para la apo D con una amplia variabilidad en la intensidad y el porcentaje de positividad. Para la cuantificación de la tinción se utilizó el sistema HSCORE que considera tanto la intensidad de la tinción como el porcentaje de células teñidas. Los resultados de este estudio mostraron una asociación significativa entre la apo D y el estado menopáusico de pacientes y el grado de diferenciación de los tumores. Los valores de apo D fueron más bajos en tumores de mujeres premenopáusicas o en carcinomas pobremente diferenciados, sugiriendo el valor potencial de esta glicoproteína como factor pronóstico en cáncer de mama. Además, el análisis preliminar de supervivencia libre de enfermedad y supervivencia global en un subgrupo de 152 mujeres con un seguimiento medio de 42 meses confirmó que los valores bajos de apo D se asociaban significativamente con una supervivencia libre de enfermedad más corta y una supervivencia global más pobre. No encontramos ninguna correlación significativa entre la apo D y el tamaño del tumor, la afectación de los ganglios linfáticos o parámetros bioquímicos como los receptores de estrógenos, la catepsina D o la proteína pS2. Los resultados de este estudio fueron muy trascendentes ya que nos permitieron proponer que la apo D, en combinación con otros factores pronósticos bien establecidos, podría contribuir a identificar con mayor precisión a subgrupos de pacientes con cáncer de mama con bajo o alto riesgo de recaída y muerte. La importancia de esta publicación se ha visto refrendada en publicaciones recientes donde se ha corroborado que esta lipoproteína está relacionada con la gravedad del cáncer de mama

A multicenter, open-label, randomized, proof-of-concept phase II clinical trial to assess the efficacy and safety of icatibant in patients infected with SARS-CoV-2 (COVID-19) and admitted to hospital units without invasive mechanical ventilation: study protocol (ICAT-COVID)

Background: COVID-19 has quickly become a global pandemic with a substantial number of deaths and is a considerable burden for healthcare systems worldwide. Although most cases are paucisymptomatic and limited to the viral infection-related symptoms, some patients evolve to a second phase, with an impaired inflammatory response (cytokine storm) that may lead to acute respiratory distress syndrome and death. This is thought to be caused by increased bradykinin synthesis. Methods: ICAT-COVID is a multicenter, randomized, open-label, proof-of-concept phase II clinical trial assessing the clinical efficacy and safety of adding icatibant to the standard of care in patients hospitalized with COVID-19 without invasive mechanical ventilation. Patients hospitalized with a confirmed COVID-19 pneumonia diagnosis (RTPCR or antigen test <= 10 days prior to randomization, and radiographic evidence of pulmonary infiltrates), rated 4 or 5' on the WHO's clinical status scale, are eligible. Patients will be randomized on a 1:1 ratio to either standard of care-plus-icatibant (experimental group) or to standard of care alone (control group). The experimental group will receive 30 mg of icatibant subcutaneously 3 times a day for 3 days (for a total of 9 doses). The expected sample size is 120 patients (60 per group) from 2 sites in Spain. Primary outcomes are the efficacy and safety of Icatibant. The main efficacy outcome is the number of patients reaching grades 2 or 1 on the WHO scale within 10 days of starting treatment. Secondary outcomes include long-term efficacy: number of patients discharged who do not present COVID-19-related relapse or comorbidity up until 28 days after discharge, and mortality. Discussion: Icatibant, a bradykinin type 2 receptor antagonist with proven effectiveness and safety against hereditary angioedema attacks, may be beneficial for COVID-19 patients by inhibiting bradykinin's action on endothelial cells and by inhibiting the SARS-CoV-2 M protease. Our working hypothesis is that treatment with standard of care-plus-icatibant is effective and safe to treat patients infected with SARS-CoV-2 admitted to hospital for pneumonia without invasive mechanical ventilation

Prospective individual patient data meta-analysis of two randomized trials on convalescent plasma for COVID-19 outpatients

Data on convalescent plasma (CP) treatment in COVID-19 outpatients are scarce. We aimed to assess whether CP administered during the first week of symptoms reduced the disease progression or risk of hospitalization of outpatients. Two multicenter, double-blind randomized trials (NCT04621123, NCT04589949) were merged with data pooling starting when = 50 years and symptomatic for <= 7days were included. The intervention consisted of 200-300mL of CP with a predefined minimum level of antibodies. Primary endpoints were a 5-point disease severity scale and a composite of hospitalization or death by 28 days. Amongst the 797 patients included, 390 received CP and 392 placebo; they had a median age of 58 years, 1 comorbidity, 5 days symptoms and 93% had negative IgG antibody-test. Seventy-four patients were hospitalized, 6 required mechanical ventilation and 3 died. The odds ratio (OR) of CP for improved disease severity scale was 0.936 (credible interval (CI) 0.667-1.311); OR for hospitalization or death was 0.919 (CI 0.592-1.416). CP effect on hospital admission or death was largest in patients with <= 5 days of symptoms (OR 0.658, 95%CI 0.394-1.085). CP did not decrease the time to full symptom resolution

High-titre methylene blue-treated convalescent plasma as an early treatment for outpatients with COVID-19: a randomised, placebo-controlled trial.

BACKGROUND: Convalescent plasma has been proposed as an early treatment to interrupt the progression of early COVID-19 to severe disease, but there is little definitive evidence. We aimed to assess whether early treatment with convalescent plasma reduces the risk of hospitalisation and reduces SARS-CoV-2 viral load among outpatients with COVID-19. METHODS: We did a multicentre, double-blind, randomised, placebo-controlled trial in four health-care centres in Catalonia, Spain. Adult outpatients aged 50 years or older with the onset of mild COVID-19 symptoms 7 days or less before randomisation were eligible for enrolment. Participants were randomly assigned (1:1) to receive one intravenous infusion of either 250-300 mL of ABO-compatible high anti-SARS-CoV-2 IgG titres (EUROIMMUN ratio ≥6) methylene blue-treated convalescent plasma (experimental group) or 250 mL of sterile 0·9% saline solution (control). Randomisation was done with the use of a central web-based system with concealment of the trial group assignment and no stratification. To preserve masking, we used opaque tubular bags that covered the investigational product and the infusion catheter. The coprimary endpoints were the incidence of hospitalisation within 28 days from baseline and the mean change in viral load (in log10 copies per mL) in nasopharyngeal swabs from baseline to day 7. The trial was stopped early following a data safety monitoring board recommendation because more than 85% of the target population had received a COVID-19 vaccine. Primary efficacy analyses were done in the intention-to-treat population, safety was assessed in all patients who received the investigational product. This study is registered with ClinicalTrials.gov, NCT04621123. FINDINGS: Between Nov 10, 2020, and July 28, 2021, we assessed 909 patients with confirmed COVID-19 for inclusion in the trial, 376 of whom were eligible and were randomly assigned to treatment (convalescent plasma n=188 [serum antibody-negative n=160]; placebo n=188 [serum antibody-negative n=166]). Median age was 56 years (IQR 52-62) and the mean symptom duration was 4·4 days (SD 1·4) before random assignment. In the intention-to-treat population, hospitalisation within 28 days from baseline occurred in 22 (12%) participants who received convalescent plasma versus 21 (11%) who received placebo (relative risk 1·05 [95% CI 0·78 to 1·41]). The mean change in viral load from baseline to day 7 was -2·41 log10 copies per mL (SD 1·32) with convalescent plasma and -2·32 log10 copies per mL (1·43) with placebo (crude difference -0·10 log10 copies per mL [95% CI -0·35 to 0·15]). One participant with mild COVID-19 developed a thromboembolic event 7 days after convalescent plasma infusion, which was reported as a serious adverse event possibly related to COVID-19 or to the experimental intervention. INTERPRETATION: Methylene blue-treated convalescent plasma did not prevent progression from mild to severe illness and did not reduce viral load in outpatients with COVID-19. Therefore, formal recommendations to support the use of convalescent plasma in outpatients with COVID-19 cannot be concluded. FUNDING: Grifols, Crowdfunding campaign YoMeCorono

No Pasaron: Arqueología de la Batalla de Madrid (8-23 de Noviembre de 1936)

Editors: Amalia Pérez-Juez Gil and Jorge Morín de Pablos.Este proyecto se financia fundamentalmente a través de una escuela de trabajo del Institute for Field Research y de vol-untarios británicos. Agradecemos a los estudiantes y voluntarios tanto su aportación económica como su entusiasmo por el proyecto. Otras fuentes de financiación han sido aportadas por la Universidad de Nottingham (gracias a las gestiones de Gareth Stokey), la Universidad del País Vasco (GPAC) y el proyecto NEARCH: New Scenarios for a Community Oriented Archaeology, de la Unión Europea