Effectiveness and safety of anti-CGRP monoclonal antibodies in patients over 65 years: a real-life multicentre analysis of 162 patients

Background Anti-CGRP monoclonal antibodies have shown notable effectiveness and tolerability in migraine patients; however, data on their use in elderly patients is still lacking, as clinical trials have implicit age restrictions and real-world evidence is scarce. In this study, we aimed to describe the safety and effectiveness of erenumab, galcanezumab and fremanezumab in migraine patients over 65 years old in real-life. Methods In this observational real-life study, a retrospective analysis of prospectively collected data from 18 different headache units in Spain was performed. Migraine patients who started treatment with any anti-CGRP monoclonal antibody after the age of 65 years were included. Primary endpoints were reduction in monthly migraine days after 6 months of treatment and the presence of adverse effects. Secondary endpoints were reductions in headache and medication intake frequencies by months 3 and 6, response rates, changes in patient-reported outcomes and reasons for discontinuation. As a subanalysis, reduction in monthly migraine days and proportion of adverse effects were also compared among the three monoclonal antibodies. Results A total of 162 patients were included, median age 68 years (range 65-87), 74.1% women. 42% had dyslipidaemia, 40.3% hypertension, 8% diabetes, and 6.2% previous cardiovascular ischaemic disease. The reduction in monthly migraine days at month 6 was 10.17.3 days. A total of 25.3% of patients presented adverse effects, all of them mild, with only two cases of blood pressure increase. Headache and medication intake frequencies were significantly reduced, and patient-reported outcomes were improved. The proportions of responders were 68%, 57%, 33% and 9% for reductions in monthly migraine days >= 30%,>= 50%,>= 75% and 100%, respectively. A total of 72.8% of patients continued with the treatment after 6 months. The reduction in migraine days was similar for the different anti-CGRP treatments, but fewer adverse effects were detected with fremanezumab (7.7%). Conclusions Anti-CGRP mAbs are safe and effective treatments in migraine patients over 65 years old in real-life clinical practice

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

Infección por HIV, quimioquinas y otros receptores

Fil: Bracco, María Marta. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; ArgentinaFil: Ruibal, Beatriz Haydee. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Apoptosis and HIV infection

La activación generalizada del sistema inmune luego de la infección por HIV conduce a la exacerbación de los mecanismos de apoptosis, no sólo en los linfocitos T CD4, sino también en linfocitos T CD8 y linfocitos B. Los macrófagos desempeñan un importante papel en la remoción de las células apoptóticas, impiden su acumulación en los cultivos in vitro y pueden contribuir a la eliminación selectiva de linfocitos CD4+ in vivo, a través de mecanismos indirectos. Se discute la utilidad de un procedimiento de cultivo de células mononucleares obtenidas a partir de sangre periférica de pacientes HIV+, para evaluar las interacciones celulares, la apoptosis y la multiplicación viral in vitro. El método no involucra el agregado exógeno de estímulos ni el co-cultivo con células alogeneicas, pero permite la replicación viral, especialmente en células de estirpe macrofágica. Se propone que la remoción de las células apoptóticas por los M/M durante el cultivo otorga el estímulo necesario para su diferenciación y para albergar la replicación viral in vitro.Generalized activation of the immune system after HIV infection leads to an exacerbation of all apoptotic mechanisms. CD4+, CD8+ T lymphocytes and B lymphocytes are sensitized to apoptotic stimuli. Macrophages are important in the removal of apoptotic cells, they prevent apoptotic cell accumulation during in vitro culture and they may lead to enhanced CD4+ T lymphocyte cell death through indirect mechanisms. A simple procedure for prolonged culture of peripheral blood mononuclear cells from HIV+ patients is discussed, in relation to its convenience to evaluate apoptosis, cell to cell interaction and HIV replication in the absence of exogenously added stimuli or co-culture of allogeneic cells. In this system, HIV replication takes place primarily in cells of macrophage lineage that may be activated into differentiation through removal of apoptotic debris during the culture.Fil: Ruibal, Beatriz Haydee. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Belmonte de Zalar, Liliana Elizabeth. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Baré, Patricia. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: de Elizalde, Maria Marta. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Inhibición de la replicación del virus de inmunodeficiencia humana por extractos de taninos de Pinus caribaea Morelet

Diferentes concentraciones de 6 extractos de corteza de Pinus caribaea Morelet var. caribaea se enfrentaron a 2 dosis de virus en un ensayo in vitro, sobre células MT4; la actividad antiviral se midió por ensayo inmunoenzimático de captura de proteína 24 del virus. Todas las fracciones mostraron actividad citotóxica moderada y solo una fue altamente tóxica. La fracción 02 mostró un alto porcentaje de inhibición de la replicación viral, en relación con la dosis viral y la concentración del producto, con un índice de selectividad de 100, pero son necesarios estudios adicionales sobre la identificación de la estructura química para definir el mecanismo de acción del producto.<br>Six different fractions from the bark of Pinus caribae Moralet var. caribae were faced in five different concentrations against two viral doses (MOI 0,1 y 0,01) in a vitro assay on MT4 cell lines; the antiviral activity was measured by p24 Ag capture ELISA assay (DAVIH Agp24). All the fractions showed a mild cytotoxicity activity and only one fraction showed the highest cytotoxicity activity. The fraction 02 had the highest percentage of viral replication inhibition, correlated with the viral dose and the product concentration, having a selectivity rate of 100; however, more research about the chemical structure of active compounds, and possible mechanisms of action are needed

Macrophage HIV-1 infection in duodenal tissue of patients on long term HAART

Mucosal surfaces play a major role in human immunodeficiency virus type 1 (HIV-1) transmission and pathogenesis. Since the role of intestinal macrophages as viral reservoirs during chronic HIV-1 infection has not been elucidated, we investigated the effects of successful therapy on intestinal HIV-1 persistence. Intestinal macrophage infection was demonstrated by the expression of p24 antigen by flow cytometry and by the presence of proviral DNA, assessed by PCR. Proviral DNA was detected in duodenal mucosa of HIV-infected patients under treatment with undetectable plasma viral load. These findings confirm that intestinal macrophages can act as viral reservoirs and permit HIV-1 production even after viral suppression following antiretroviral therapy. © 2010 Elsevier B.V.Fil: Zalar, Alberto. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Juan A. Fernández"; ArgentinaFil: Figueroa, Maria Ines. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Juan A. Fernández"; ArgentinaFil: Ruibal Ares, Beatriz. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Baré, Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Cahn, Pedro. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Juan A. Fernández"; ArgentinaFil: de Bracco, Maria Marta de E.. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Belmonte de Zalar, Liliana Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; Argentin

Increased lymphocyte viability after non-stimulated peripheral blood mononuclear cell (PBMC) culture in patients with X-linked lymphoproliferative disease (XLP)

Survival of lymphocytes after prolonged culture was studied in two asymptomatic XLP patients. Viability of XLP PBMC after 30 days of non-stimulated culture was higher than that of normal controls (N), mainly due to the persistence of CD8 memory lymphocytes. IFNγ high CD8 T lymphocytes remained higher in XLP than in N after 30 days. The number of perforin+ CD8 lymphocytes was markedly reduced after 30 days in XLP and in N. Increased viability was not related to CD127, PD-1, CD27, or CD62L expression. Concerning B lymphocytes, memory CD27+ CD19+ cells prevailed over CD27- cells after 30 days in both XLP and N, with far more surviving cells in XLP. In N, few CD19+ B lymphocytes were viable after prolonged culture. In XLP, these cells were also IgD+, IgM+ and EBNA2+. These results demonstrate that IFNγ-positive memory CD8 T cells persist in XLP after prolonged culture in association with a subset of viable memory CD27+ B cells expressing latent EBV antigens. The survival advantage of XLP cells might be related to increased frequency of extranodal lymphoma in XLP patients. © 2009 Elsevier Inc. All rights reserved.Fil: Belmonte de Zalar, Liliana Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Parodi Ramoneda, Cecilia María. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Bastón, Mariela Constanza. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Coraglia, Ana Carina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Felippo, Marta Elena. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Baré, Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Malbrán, Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Hospital Británico de Buenos Aires; ArgentinaFil: Ruibal- res, Beatriz. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: González Bracco, María de las Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; Argentin