Cyclosporine A in hospitalized COVID-19 pneumonia patients to prevent the development of interstitial lung disease: a pilot randomized clinical trial.

Post-COVID-19 interstitial lung disease (ILD) is a new entity that frequently causes pulmonary fibrosis and can become chronic. We performed a single-center parallel-group open-label pilot randomized clinical trial to investigate the efficacy and safety of cyclosporine A (CsA) in the development of ILD in the medium term among patients hospitalized with COVID-19 pneumonia. Patients were randomized 1:1 to receive CsA plus standard of care or standard of care alone. The primary composite outcome was the percentage of patients without ILD 3 months after diagnosis of pneumonia and not requiring invasive mechanical ventilation (IMV) (response without requiring IMV). The key secondary composite outcomes were the percentage of patients who achieve a response requiring IMV or irrespective of the need for IMV, and adverse events. A total of 33 patients received at least one dose of CsA plus standard of care (n = 17) or standard of care alone (n = 16). No differences were found between the groups in the percentage of patients who achieved a response without requiring IMV or a response requiring IMV. A higher percentage of patients achieved a response irrespective of the need for IMV in the CsA plus standard of care group although the RR was almost significant 2.833 (95% CI, 0.908-8.840; p = 0.057). No differences were found between the groups for adverse events. In hospitalized patients with COVID-19 pneumonia, we were unable to demonstrate that CsA achieved a significant effect in preventing the development of ILD. (EU Clinical Trials Register; EudraCT Number: 2020-002123-11; registration date: 08/05/2020).

Autofluorescent Cancer Stem Cells: Potential Biomarker to Predict Recurrence in Resected Colorectal Tumors.

Cancer stem cells (CSC) in colorectal cancer drive intratumoral heterogeneity and distant metastases. Previous research from our group showed that CSCs can be easily detected by autofluorescence (AF). The aim of the present study was to evaluate the potential role of AF CSCs as a prognostic biomarker for colorectal cancer relapse. Seventy-five freshly resected tumors were analyzed by flow cytometry. AF was categorized as high (H-AF) or low, and the results were correlated with histologic features [grade of differentiation, presence of metastases in lymph nodes (LN), perivascular and lymphovascular invasion] and clinical variables (time to relapse and overall survival). Nineteen of the 75 (25.3%) patients experienced relapse (local or distant); of these 19 patients, 13 showed positive LNs and 6 had H-AF. Of note, four of them died before 5 years. Although patients with H-AF CSC percentages in the global population experienced 1.5 times increased relapse [HR, 1.47; 95% confidence interval (0.60-3.63)], patients with H-AF CSC percentages and LN metastases had the highest risk of relapse [HR, 7.92; P < 0.004; 95% confidence interval (1.97-31.82)]. These data support AF as an accurate and feasible marker to identify CSCs in resected colorectal cancer. A strong statistical association between H-AF CSCs and the risk of relapse was observed, particularly in patients with positive LNs, suggesting that H-AF patients might benefit from adjuvant chemotherapy regimens and intensive surveillance due to their high propensity to experience disease recurrence. Significance: AF has been proven to be an accurate biomarker for CSC identification; however, to date, their role as a prognostic factor after resection of colorectal cancer tumors has not been investigated. Our results show that determining the presence of AF CSCs after tumor resection has prognostic value and represents a potentially important tool for the management of patients with colorectal cancer.

Effectiveness of glucocorticoids in patients hospitalized for severe SARS-CoV-2 pneumonia.

BACKGROUND: Several studies have reported the beneficial effect of glucocorticoids in the treatment of cytokine storm that occurs in patients with severe COVID-19. Various glucocorticoids regimens have been proposed. METHODS: Retrospective observational study that includes patients with severe SARS-CoV-2 pneumonia and compares admission to an Intensive Care Unit (ICU) or death during hospitalization in three groups of patients: no glucocorticoids treatment, use of glucocorticoids doses equivalent to less than 250 mg of prednisone daily and use of equivalent doses greater than or equal to 250 mg of prednisone daily. Multivariate analysis was performed using logistic regression, using the propensity index as a covariant. RESULTS: Of the 259 patients enrolled in the study, 67 (25.9%) had an unfavorable evolution, dying or requiring ICU admission. Comparative analyzes between different glucocorticoids treatments and the association with ICU admission or death were: glucocorticoids treatment (any dose) versus no glucocorticoids treatment (OR: 0.71 [0.30-1.66]), treatment with glucocorticoids (≥250 mg prednisone daily) versus no glucocorticoids treatment (OR: 0.35 [0.11-1.08]) and glucocorticoids treatment (≥250 mg prednisone daily) versus patients with glucocorticoids doses <250 mg prednisone daily or without glucocorticoids treatment (OR: 0.30 [0.10-0.88]). CONCLUSION: The results of this study show that patients with severe SARS-CoV-2 pneumonia treated with glucocorticoids pulses with equivalent doses of prednisone greater than or equal to 250 mg have a more favorable evolution (less mortality and less admission to ICU).

INTRODUCCIÓN: Se han comunicado varios trabajos donde se ha demostrado un efecto beneficioso de los glucocorticoides como tratamiento de la tormenta de citocinas que se asocia a los cuadros graves por SARS-CoV-2, plateándose diferentes pautas de glucocorticoides. MÉTODOS: Estudio observacional retrospectivo que incluye pacientes con neumonía grave por SARS-CoV-2 y compara el ingreso en una unidad de cuidados intensivos (UCI) o fallecimiento durante la hospitalización en 3 grupos de pacientes: sin tratamiento con glucocorticoides, uso de dosis diarias de glucocorticoides equivalentes menores a 250 mg de prednisona y dosis diarias equivalentes mayores o iguales a 250 mg de prednisona. Se realizó un análisis multivariante mediante regresión logística, utilizando el índice de propensión como covariante. RESULTADOS: De los 259 pacientes incorporados al estudio 67 (25,9%) tuvieron una evolución desfavorable, falleciendo o precisando ingreso en UCI. Los análisis comparativos entre diferentes tratamientos con glucocorticoides, y la asociación con ingreso en UCI o fallecimiento fueron: tratamiento con glucocorticoides (cualquier dosis) versus sin tratamiento con glucocorticoides (OR: 0,71 [0,30­1,66]), tratamiento con glucocorticoides (≥250 mg de prednisona al día) versus sin tratamiento con glucocorticoides (OR: 0,35 [0,11­1,08]) y tratamiento con glucocorticoides (≥250 mg de prednisona al día) versus pacientes con dosis de glucocorticoides < 250 mg de prednisona o sin tratamiento con glucocorticoides (OR: 0,30 [0,10­0,88]). CONCLUSIÓN: Los resultados de este estudio muestran que los paciente con neumonía grave por SARS-CoV-2 tratados con pulsos con glucocorticoides con dosis equivalentes de prednisona mayor o igual de 250 mg tienen una evolución más favorable (menos mortalidad e ingreso en UCI).

[Effectiveness of glucocorticoids in patients hospitalized for severe SARS-CoV-2 pneumonia]. / Efectividad de los glucocorticoides en pacientes hospitalizados por neumonía grave por SARS-CoV-2.

INTRODUCTION: Several studies have reported the beneficial effect of glucocorticoids in the treatment of cytokine storm that occurs in patients with severe COVID-19. Various glucocorticoids regimens have been proposed. METHODS: Retrospective observational study that includes patients with severe SARS-CoV-2 pneumonia and compares admission to an Intensive Care Unit (ICU) or death during hospitalization in three groups of patients: no glucocorticoids treatment, use of glucocorticoids doses equivalent to less than 250mg of prednisone daily and use of equivalent doses greater than or equal to 250mg of prednisone daily. Multivariate analysis was performed using logistic regression, using the propensity index as a covariant. RESULTS: Of the 259 patients enrolled in the study, 67 (25.9%) had an unfavorable evolution, dying or requiring ICU admission. Comparative analyzes between different glucocorticoids treatments and the association with ICU admission or death were: glucocorticoids treatment (any dose) versus no glucocorticoids treatment (OR: 0.71 [0.30-1.66]), treatment with glucocorticoids (≥250mg prednisone daily) versus no glucocorticoids treatment (OR: 0.35 [0.11-1.08]) and glucocorticoids treatment (≥250mg prednisone daily) versus patients with glucocorticoids doses <250mg prednisone daily or without glucocorticoids treatment (OR: 0.30 [0.10-0.88]). CONCLUSION: The results of this study show that patients with severe SARS-CoV-2 pneumonia treated with glucocorticoids pulses with equivalent doses of prednisone greater than or equal to 250mg have a more favorable evolution (less mortality and less admission to ICU).