Effectiveness of treatment with nebulized colistin in patients with COPD

To analyze whether the introduction of nebulized colistin in patients with chronic obstructive pulmonary disease (COPD) and infection with Pseudomonas aeruginosa (PA) is associated with a decrease of the number and duration of severe exacerbations. Thirty six patients with COPD and infection with PA treated with nebulized colistin attending a day hospital during a 5-year (January 2010-December 2014) period were prospectively included. Repeated-measures t -tests were used to assess whether the introduction of colistin was associated with changes in the number of exacerbations or the length of the hospitalizations, comparing for each patient the year prior to the introduction of colistin with the year after. After the introduction of colistin, the number of admissions decreased from 2.0 to 0.9 per individual year (P =0.0007), and hospitalizations were shorter (23.3 vs 10.9 days, P =0.00005). These results persisted when patients with and without bronchiectasis or with and without persistence of Pseudomonas were separately analyzed. No pre-post differences were detected in the number of exacerbations not requiring admission. Nebulized colistin seems associated with a strong decrease in the number and duration of hospitalizations due to exacerbation in patients with COPD and infection with PA. Clinical trials with a larger number of patients are needed in order to confirm these results

Evaluation of a support system for health professionals confined by COVID-19

OBJETIVOS: Evaluar la implementación de un circuito telefónico de apoyo a profesionales sanitarios confinados por COVID-19 en una dirección de Atención Primaria de Barcelona, en España.  MÉTODOS: Estudio observacional, descriptivo y transversal, realizado con profesionales confinados en domicilio entre el 11 de marzo y el 31 de mayo de 2020. Se envió por correo electrónico un cuestionario con 18 preguntas cerradas y una abierta. Se realizó un análisis descriptivo de las respuestas cerradas y un análisis del contenido temático de la pregunta abierta. RESULTADOS: 398 profesionales puntuaron globalmente el circuito con 6,54 en una escala de 1 a 10. El formato de las llamadas realizadas en el circuito de apoyo se estimó con las puntuaciones máximas, la unidad de apoyo psicológico y la coordinación por diferentes colectivos se evaluaron con las puntuaciones más bajas. El análisis del contenido de la pregunta abierta ofrece argumentos explicativos de los resultados cuantitativos.  CONCLUSIONES: El estudio permitió evaluar de manera válida y fiable la implementación de un circuito de apoyo a profesionales confinados, además de reconocer áreas de mejora. OBJECTIVE: To evaluate the implementation of a telephone system in a department of Primary Care in Barcelona, Spain, supporting health professionals confined by COVID-19.  METHODS: We conducted an observational, descriptive, cross-sectional study with confined professionals, between March 11 and May 31, 2020. We emailed a questionnaire with 18 closed-ended questions and one open-ended question and performed a descriptive analysis of the closed-ended answers and an analysis of the thematic content of the open-ended question.  RESULTS: Thirty-nine hundred and ninety-eight professionals evaluated the system overall with a score of 6.54 on a scale of 1 to 10. The evaluation of the format of calls made in the support system had higher scores, while the psychological support unit and the coordination of the different groups had lower scores. The content analysis of the open-ended question provides explanatory arguments for the quantitative results.  CONCLUSIONS: The study allowed a valid and reliable evaluation of the implementation of a support system for confined professionals, in addition to recognizing areas for improvement.

Cell-cycle inhibition and immune microenvironment in breast cancer treated with ribociclib and letrozole or chemotherapy

In this study, we performed genomic analyses of cell cycle and tumor microenvironment changes during and after ribociclib and letrozole or chemotherapy in the CORALLEEN trial. 106 women with untreated PAM50-defined Luminal B early breast cancers were randomly assigned to receive neoadjuvant ribociclib and letrozole or standard-of-care chemotherapy. Ki67 immunohistochemistry, tumor-infiltrating lymphocytes quantification, and RNA sequencing were obtained from tissue biopsies pre-treatment, on day 14 of treatment, and tumor specimens from surgical resection. Results showed that at surgery, Ki67 and the PAM50 proliferation scores were lower after ribociclib compared to chemotherapy. However, consistent reactivation of tumor cell proliferation from day 14 to surgery was only observed in the ribociclib arm. In tumors with complete cell cycle arrest (CCCA) at surgery, PAM50 proliferation scores were lower in the ribociclib arm compared to chemotherapy (p < 0.001), whereas the opposite was observed with tumor cellularity (p = 0.002). Gene expression signatures (GES) associated with antigen-presenting cells (APCs) and innate immune system activity showed increased expression post-chemotherapy but decreased expression post-ribociclib. Interferon-associated GES had decreased expression with CCCA and increased expression with non-CCCA. Our findings suggest that while both treatment strategies decreased proliferation, the depth and the patterns over time differed by treatment arm. Immunologically, ribociclib was associated with downregulated GES associated with APCs and the innate immune system in Luminal B tumors, contrary to existing preclinical data. Further studies are needed to understand the effect of CDK4/6 inhibition on the tumor cells and microenvironment, an effect which may vary according to tumor subtypes

Q-SAPS?: què saben sobre salut pública a l’atenció primària?

Malalties; Declaració obligatòria; Brots epidèmicsEnfermedades; Declaración obligatoria; Brotes epidémicosDiseases; Mandatory declaration; Epidemic outbreaksEl treball d’aquesta comunitat de pràctica (CoP) pretén ajudar a detectar mancances de coneixement sobre la salut pública entre els professionals de l’atenció primària i elaborar un document de propostes per millorar el coneixement referit en aquest àmbit. Amb les següents propostes de valor: 1-Conèixer les funcions de cada actor en les malalties de declaració obligatòria (MDO), emergents i brots epidèmics. 2-Detectar mancances de coneixement i dificultats per a declarar. 3-Saber la utilitat de declarar MDO i brots epidèmics, ja que no és només un simple registre sinó que hi ha una actuació al darrere. 4-Conèixer les actuacions comunitàries que cal fer en cada malaltia per controlar-la, i brots epidèmics.El trabajo de esta comunidad de práctica (CoP) pretende ayudar a detectar carencias de conocimiento sobre la salud pública entre los profesionales de la atención primaria y elaborar un documento de propuestas para mejorar el conocimiento referido en este ámbito. Con las siguientes propuestas de valor: 1-Conocer las funciones de cada actor en las enfermedades de declaración obligatoria (MDO), emergentes y brotes epidémicos. 2-Detectar carencias de conocimiento y dificultades para declarar. 3-Saber la utilidad de declarar EDO y brotes epidémicos, ya que no es sólo un simple registro sino que hay una actuación detrás. 4-Conocer las actuaciones comunitarias a realizar en cada enfermedad para controlarla, y brotes epidémicos.The work of this community of practice (CoP) aims to help detect gaps in knowledge about public health among primary care professionals and prepare a document of proposals to improve the knowledge referred to in this area. With the following value propositions: 1-Know the functions of each actor in notifiable diseases, emerging diseases and epidemic outbreaks. 2-Detect knowledge gaps and difficulties in declaring. 3-Know the usefulness of declaring notifiable diseases and epidemic outbreaks, since it is not just a simple record but there is an action behind it. 4-Know the community actions to be carried out in each disease to control it, and epidemic outbreaks

The EMT signaling pathways in endometrial carcinoma

Endometrial cancer (EC) is the most common gynecologic malignancy of the female genital tract and the fourth most common neoplasia in women. In EC, myometrial invasion is considered one of the most important prognostic factors. For this process to occur, epithelial tumor cells need to undergo an epithelial to mesenchymal transition (EMT), either transiently or stably, and to differing degrees. This process has been extensively described in other types of cancer but has been poorly studied in EC. In this review, several features of EMT and the main molecular pathways responsible for triggering this process are investigated in relation to EC. The most common hallmarks of EMT have been found in EC, either at the level of E-cadherin loss or at the induction of its repressors, as well as other molecular alterations consistent with the mesenchymal phenotype-like L1CAM and BMI-1 up-regulation. Pathways including progesterone receptor, TGFβ, ETV5 and microRNAs are deeply related to the EMT process in EC

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

Anti-Spike antibodies 3 months after SARS-CoV-2 mRNA vaccine booster dose in patients on hemodialysis: the prospective SENCOVAC study

Background: Patients on hemodialysis are at high-risk for complications derived from coronavirus disease 2019 (COVID-19). The present analysis evaluated the impact of a booster vaccine dose and breakthrough severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections on humoral immunity 3 months after the booster dose. Methods: This is a multicentric and prospective study assessing immunoglobulin G anti-Spike antibodies 6 and 9 months after initial SARS-CoV-2 vaccination in patients on hemodialysis that had also received a booster dose before the 6-month assessment (early booster) or between the 6- and 9-month assessments (late booster). The impact of breakthrough infections, type of vaccine, time from the booster and clinical variables were assessed. Results: A total of 711 patients [67% male, median age (range) 67 (20-89) years] were included. Of these, 545 (77%) received an early booster and the rest a late booster. At 6 months, 64 (9%) patients had negative anti-Spike antibody titers (3% of early booster and 29% of late booster patients, P =. 001). At 9 months, 91% of patients with 6-month negative response had seroconverted and there were no differences in residual prevalence of negative humoral response between early and late booster patients (0.9% vs 0.6%, P =. 693). During follow-up, 35 patients (5%) developed breakthrough SARS-CoV-2 infection. Antibody titers at 9 months were independently associated with mRNA-1273 booster (P =. 001), lower time from booster (P =. 043) and past breakthrough SARS-CoV-2 infection (P <. 001). Conclusions: In hemodialysis patients, higher titers of anti-Spike antibodies at 9 months were associated with mRNA-1273 booster, lower time from booster and past breakthrough SARS-CoV-2 infectionThe present project has been supported by Fresenius Medical Care, Diaverum, Vifor Pharma, Vircell, Fundación Renal Iñigo Álvarez de Toledo and ISCIII FEDER funds RICORS2040 (RD21/0005

Effectiveness of treatment with nebulized colistin in patients with COPD

To analyze whether the introduction of nebulized colistin in patients with chronic obstructive pulmonary disease (COPD) and infection with Pseudomonas aeruginosa (PA) is associated with a decrease of the number and duration of severe exacerbations. Thirty six patients with COPD and infection with PA treated with nebulized colistin attending a day hospital during a 5-year (January 2010-December 2014) period were prospectively included. Repeated-measures t -tests were used to assess whether the introduction of colistin was associated with changes in the number of exacerbations or the length of the hospitalizations, comparing for each patient the year prior to the introduction of colistin with the year after. After the introduction of colistin, the number of admissions decreased from 2.0 to 0.9 per individual year (P =0.0007), and hospitalizations were shorter (23.3 vs 10.9 days, P =0.00005). These results persisted when patients with and without bronchiectasis or with and without persistence of Pseudomonas were separately analyzed. No pre-post differences were detected in the number of exacerbations not requiring admission. Nebulized colistin seems associated with a strong decrease in the number and duration of hospitalizations due to exacerbation in patients with COPD and infection with PA. Clinical trials with a larger number of patients are needed in order to confirm these results

Cell-cycle inhibition and immune microenvironment in breast cancer treated with ribociclib and letrozole or chemotherapy

Abstract In this study, we performed genomic analyses of cell cycle and tumor microenvironment changes during and after ribociclib and letrozole or chemotherapy in the CORALLEEN trial. 106 women with untreated PAM50-defined Luminal B early breast cancers were randomly assigned to receive neoadjuvant ribociclib and letrozole or standard-of-care chemotherapy. Ki67 immunohistochemistry, tumor-infiltrating lymphocytes quantification, and RNA sequencing were obtained from tissue biopsies pre-treatment, on day 14 of treatment, and tumor specimens from surgical resection. Results showed that at surgery, Ki67 and the PAM50 proliferation scores were lower after ribociclib compared to chemotherapy. However, consistent reactivation of tumor cell proliferation from day 14 to surgery was only observed in the ribociclib arm. In tumors with complete cell cycle arrest (CCCA) at surgery, PAM50 proliferation scores were lower in the ribociclib arm compared to chemotherapy (p < 0.001), whereas the opposite was observed with tumor cellularity (p = 0.002). Gene expression signatures (GES) associated with antigen-presenting cells (APCs) and innate immune system activity showed increased expression post-chemotherapy but decreased expression post-ribociclib. Interferon-associated GES had decreased expression with CCCA and increased expression with non-CCCA. Our findings suggest that while both treatment strategies decreased proliferation, the depth and the patterns over time differed by treatment arm. Immunologically, ribociclib was associated with downregulated GES associated with APCs and the innate immune system in Luminal B tumors, contrary to existing preclinical data. Further studies are needed to understand the effect of CDK4/6 inhibition on the tumor cells and microenvironment, an effect which may vary according to tumor subtypes

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

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. 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. 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 10.1 ± 7.3 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%). Anti-CGRP mAbs are safe and effective treatments in migraine patients over 65 years old in real-life clinical practice. The online version contains supplementary material available at 10.1186/s10194-023-01585-2