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Importance: Convalescent plasma (CP) has been generally unsuccessful in preventing worsening of respiratory failure or death in hospitalized patients with COVID-19 pneumonia. Objective: To evaluate the efficacy of CP plus standard therapy (ST) vs ST alone in preventing worsening respiratory failure or death in patients with COVID-19 pneumonia. Design, setting, and participants: This prospective, open-label, randomized clinical trial enrolled (1:1 ratio) hospitalized patients with COVID-19 pneumonia to receive CP plus ST or ST alone between July 15 and December 8, 2020, at 27 clinical sites in Italy. Hospitalized adults with COVID-19 pneumonia and a partial pressure of oxygen-to-fraction of inspired oxygen (Pao2/Fio2) ratio between 350 and 200 mm Hg were eligible. Interventions: Patients in the experimental group received intravenous high-titer CP (≥1:160, by microneutralization test) plus ST. The volume of infused CP was 200 mL given from 1 to a maximum of 3 infusions. Patients in the control group received ST, represented by remdesivir, glucocorticoids, and low-molecular weight heparin, according to the Agenzia Italiana del Farmaco recommendations. Main outcomes and measures: The primary outcome was a composite of worsening respiratory failure (Pao2/Fio2 ratio <150 mm Hg) or death within 30 days from randomization. Results: Of the 487 randomized patients (241 to CP plus ST; 246 to ST alone), 312 (64.1%) were men; the median (IQR) age was 64 (54.0-74.0) years. The modified intention-to-treat population included 473 patients. The primary end point occurred in 59 of 231 patients (25.5%) treated with CP and ST and in 67 of 239 patients (28.0%) who received ST (odds ratio, 0.88; 95% CI, 0.59-1.33; P = .54). Adverse events occurred more frequently in the CP group (12 of 241 [5.0%]) compared with the control group (4 of 246 [1.6%]; P = .04). Conclusions and relevance: In patients with moderate to severe COVID-19 pneumonia, high-titer anti-SARS-CoV-2 CP did not reduce t

Summary Eminent writers, like Dante Alighieri, John R. R. Tolkien, Antoine de Saint-Exupéry, León Tolstoi and many others, as well as artists, presidents, scientists, entrepeneurs and pioneers, have lost their parents in early stages. They achieved universal acknowledgement for their creativity and transcended their time. This preliminar and exploratory paper will be focused in the relation between literary genius and parental loss,applied to an eminent writer, that transcended his age and had public recognition for decades, due to his talent and repercussion: John Ronald Reuel Tolkien. His books were translated internationally and editors have published his work in different formats and translations. Attachment figures, support of masters, colleagues and intimate friends will be highlighted, as well as his wife role. Resilience during his life span will be emphasized, in addition to his genius and creativity, Resumen Reconocidos escritores, como Dante Alighieri, John R. R. Tolkien, Antoine de Saint-Exupéry, León Tolstoi y muchos otros, han perdido a sus progenitores en etapas tempranas de la vida, así como artistas, presidentes, científicos, emprendedores e innovadores que alcanzaron reconocimiento universal por su creatividad y trascendieron su propia época. Este trabajo preliminar y exploratorio se centrará en la relación entre genialidad literaria y orfandad, focalizándose en un escritor eminente, que trascendió su época y contó con un público que lo ha reconocido por décadas, debido a su gran resonancia y talento: John Ronald Reuel Tolkien. Sus obras fueron traducidas a nivel mundial y las editoriales se han ocupado de publicarlas ininterrumpidamente, en los más diversos formatos y traducciones. Se destacará el rol que tuvieron en la vida de Tolkien sus figuras de apego, el apoyo que recibió de maestros, colegas y grandes amigos, así como el de su esposa. Asimismo, se enfatizará el desarrollo de la resiliencia en el transcurso de su vida, sumado a su genialidad y creatividad. Palabras clave: genialidad, creatividad, orfandad, apoyo social, resiliencia

Giada Amodeo,1 Dario Bugada,2–4 Silvia Franchi,1 Giorgia Moschetti,1 Stefania Grimaldi,5 Alberto Panerai,1 Massimo Allegri,2 Paola Sacerdote1 1Department of Pharmacological and Biomolecular Sciences, University of Milano, Milano, Italy; 2Study In Multidisciplinary Pain Research Group, 3Department of Anesthesia and ICU, ASST Papa Giovanni XXIII, Bergamo, Italy; 4Department of Anesthesia and ICU, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; 5Department of Anesthesia, IRCCS Humanitas Research Center, Rozzano, Italy Introduction: Impaired immune function during the perioperative period may be associated with worse short- and long-term outcomes. Morphine is considered a major contributor to immune modulation. Patients and methods: We performed a pilot study to investigate postoperative immune function by analyzing peripheral blood mononuclear cells’ functionality and cytokine production in 16 patients undergoing major abdominal surgery. All patients were treated with intravenous (i.v.) patient-controlled analgesia with morphine and continuous wound infusion with ropivacaine+methylprednisolone for 24 hours. After 24 hours, patients were randomized into two groups, one continuing intrawound infusion and the other receiving only i.v. analgesia. We evaluated lymphoproliferation and cytokine production by peripheral blood mononuclear cells at the end of surgery and at 24 and 48 hours postoperatively. Results: A significant reduction in TNF-α, IL-2, IFN-γ and lymphoproliferation was observed immediately after surgery, indicating impaired cell-mediated immunity. TNF-α and IFN-γ remained suppressed up to 48 hours after surgery, while a trend to normalization was observed for IL-2 and lymphoproliferation, irrespective of the treatment group. A significant inverse correlation was present between age and morphine and between age and lymphoproliferation. No negative correlation