A Pad of Unpaid Prescriptions of a Chancellor of the University of Valladolid in the Sixteenth Century

El trabajo que presentamos tiene como objeto fundamental la edición y estudio de las recetas halladas en un pleito litigado en el tribunal de la Chancillería de Valladolid, al que llegaron porque Félix de Manzanedo, rector de la Universidad y Oidor del citado tribunal, no se las pagó al boticario Francisco de Madrid ni a su viuda, María de Ayala, que es quien reclama la deuda y demandó al catedrático. A través del análisis de las recetas se pueden conocer los nombres de dos de los médicos más importantes de Valladolid en el siglo XVI, Juan de Peñaranda y Pedro Enríquez, así como el conocimiento que tienen, tanto ellos como el boticario que las expende, de las sustancias medicinales y el modo en que se preparan y combinan en los años medios del siglo.The present paper aims to offer an edition and study of some prescriptions included in a sixteenth-century lawsuit litigated in the Real Chancillería of Valladolid. María of Ayala, the widow of the apothecary Francisco of Madrid, sued Félix Manzanedo, chancellor of the University of Valladolid and magistrate in the aforesaid court, because he had failed to pay his long-standing debt to the apothecary, and she substantiated her claim with the prescriptions his deceased husband kept. By studying these prescriptions it becomes possible to ascertain the names of two of Valladolid’s most prestigious doctors in the mid-sixteenth century: Juan of Peñaranda and Pedro Enríquez. They give us also an insight into the knowledge that both the doctors and the apothecary had of the active ingredient of medications and into their ability to prepare and combine those ingredients in their efforts to create effective treatments

A blood microRNA classifier for the prediction of ICU mortality in COVID-19 patients: a multicenter validation study

Background: The identification of critically ill COVID-19 patients at risk of fatal outcomes remains a challenge. Here, we first validated candidate microRNAs (miRNAs) as biomarkers for clinical decision-making in critically ill patients. Second, we constructed a blood miRNA classifier for the early prediction of adverse outcomes in the ICU. Methods: This was a multicenter, observational and retrospective/prospective study including 503 critically ill patients admitted to the ICU from 19 hospitals. qPCR assays were performed in plasma samples collected within the first 48 h upon admission. A 16-miRNA panel was designed based on recently published data from our group. Results: Nine miRNAs were validated as biomarkers of all-cause in-ICU mortality in the independent cohort of critically ill patients (FDR < 0.05). Cox regression analysis revealed that low expression levels of eight miRNAs were associated with a higher risk of death (HR from 1.56 to 2.61). LASSO regression for variable selection was used to construct a miRNA classifier. A 4-blood miRNA signature composed of miR-16-5p, miR-192-5p, miR-323a-3p and miR-451a predicts the risk of all-cause in-ICU mortality (HR 2.5). Kaplan‒Meier analysis confirmed these findings. The miRNA signature provides a significant increase in the prognostic capacity of conventional scores, APACHE-II (C-index 0.71, DeLong test p-value 0.055) and SOFA (C-index 0.67, DeLong test p-value 0.001), and a risk model based on clinical predictors (C-index 0.74, DeLong test-p-value 0.035). For 28-day and 90-day mortality, the classifier also improved the prognostic value of APACHE-II, SOFA and the clinical model. The association between the classifier and mortality persisted even after multivariable adjustment. The functional analysis reported biological pathways involved in SARS-CoV infection and inflammatory, fibrotic and transcriptional pathways. Conclusions: A blood miRNA classifier improves the early prediction of fatal outcomes in critically ill COVID-19 patients.11 página

Prognostic implications of comorbidity patterns in critically ill COVID-19 patients: A multicenter, observational study

Background The clinical heterogeneity of COVID-19 suggests the existence of different phenotypes with prognostic implications. We aimed to analyze comorbidity patterns in critically ill COVID-19 patients and assess their impact on in-hospital outcomes, response to treatment and sequelae. Methods Multicenter prospective/retrospective observational study in intensive care units of 55 Spanish hospitals. 5866 PCR-confirmed COVID-19 patients had comorbidities recorded at hospital admission; clinical and biological parameters, in-hospital procedures and complications throughout the stay; and, clinical complications, persistent symptoms and sequelae at 3 and 6 months. Findings Latent class analysis identified 3 phenotypes using training and test subcohorts: low-morbidity (n=3385; 58%), younger and with few comorbidities; high-morbidity (n=2074; 35%), with high comorbid burden; and renal-morbidity (n=407; 7%), with chronic kidney disease (CKD), high comorbidity burden and the worst oxygenation profile. Renal-morbidity and high-morbidity had more in-hospital complications and higher mortality risk than low-morbidity (adjusted HR (95% CI): 1.57 (1.34-1.84) and 1.16 (1.05-1.28), respectively). Corticosteroids, but not tocilizumab, were associated with lower mortality risk (HR (95% CI) 0.76 (0.63-0.93)), especially in renal-morbidity and high-morbidity. Renal-morbidity and high-morbidity showed the worst lung function throughout the follow-up, with renal-morbidity having the highest risk of infectious complications (6%), emergency visits (29%) or hospital readmissions (14%) at 6 months (p<0.01). Interpretation Comorbidity-based phenotypes were identified and associated with different expression of in-hospital complications, mortality, treatment response, and sequelae, with CKD playing a major role. This could help clinicians in day-to-day decision making including the management of post-discharge COVID-19 sequelae. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd

The evolution of the ventilatory ratio is a prognostic factor in mechanically ventilated COVID-19 ARDS patients

Background: Mortality due to COVID-19 is high, especially in patients requiring mechanical ventilation. The purpose of the study is to investigate associations between mortality and variables measured during the first three days of mechanical ventilation in patients with COVID-19 intubated at ICU admission. Methods: Multicenter, observational, cohort study includes consecutive patients with COVID-19 admitted to 44 Spanish ICUs between February 25 and July 31, 2020, who required intubation at ICU admission and mechanical ventilation for more than three days. We collected demographic and clinical data prior to admission; information about clinical evolution at days 1 and 3 of mechanical ventilation; and outcomes. Results: Of the 2,095 patients with COVID-19 admitted to the ICU, 1,118 (53.3%) were intubated at day 1 and remained under mechanical ventilation at day three. From days 1 to 3, PaO2/FiO2 increased from 115.6 [80.0-171.2] to 180.0 [135.4-227.9] mmHg and the ventilatory ratio from 1.73 [1.33-2.25] to 1.96 [1.61-2.40]. In-hospital mortality was 38.7%. A higher increase between ICU admission and day 3 in the ventilatory ratio (OR 1.04 [CI 1.01-1.07], p = 0.030) and creatinine levels (OR 1.05 [CI 1.01-1.09], p = 0.005) and a lower increase in platelet counts (OR 0.96 [CI 0.93-1.00], p = 0.037) were independently associated with a higher risk of death. No association between mortality and the PaO2/FiO2 variation was observed (OR 0.99 [CI 0.95 to 1.02], p = 0.47). Conclusions: Higher ventilatory ratio and its increase at day 3 is associated with mortality in patients with COVID-19 receiving mechanical ventilation at ICU admission. No association was found in the PaO2/FiO2 variation

Carbon Monoxide inhibits hypoxic pulmonary vasoconstriction in rats by a cGMP-independent mechanism

Producción CientíficaHypoxia activates erythropoietin-producing cells, chemoreceptor cells of the carotid body and pul- monary artery smooth muscle cells (PSMC) with a com- Key words Hypoxia · Pulmonary artery · Carbon monoxide&bdy: parable arterial PO2 threshold of some 70 mmHg. The inhibition by CO of the hypoxic responses in the two for- mer cell types has led to the proposal that a haemopro- tein is involved in the detection of the PO2 levels. Here, we report the effect of CO on the hypoxic pulmonary va- soconstriction (HPV). Pulmonary arterial pressure (PAP) was measured in an in situ, blood-perfused lung prepara- tion. PAP in normoxia (20% O2, 5% CO2)

El manejo de la información en las estaciones radiales y la aparición de conflictos sociales en el cantón Ambato

This research purpose isthe enablement of a content department in order to diffuse informative products which do not create reaction spaces as a reply of verbal messages that defame people due to the word-of-mouth misuse. In order to achieve this objective, are considered the aspects where Jürgen Habermas propose communication as intercession in the socio-cultural evolution process where social evolution trial is not understood as rationalization-reification of the awareness but as communicative rationalization of the life’s symbolic structures. The message will be mainly focused in the “myself” ethos as the peacekeeping encourager. These aspects impel the encouragement of a culture which guides the senses in order to improve interpersonal relationships quality to decrease the troubles that can affect connivance and Ecuadorians quality of life.El propósito de este trabajo de investigación es la implementación de un departamento de contenidos para la difusión de productos informativos que no generen espacios de reacción en respuesta a mensajes verbales donde se deslegitiman a las personas, por el inadecuado uso de la palabra. Para lograr este objetivo se consideran aspectos en los que Jürgen Habermas plantea a la acción comunicativa como mediación en el proceso de evolución socio- cultural, donde no se entiende al proceso de evolución social como racionalización-cosificación de la conciencia sino como una racionalización comunicativa de las estructuras simbólicas del mundo de la vida. Los mensajes tendrán una fuerza vigorizante con principios “del yo” como generador de mediación. Aspectos que influyen para fomentar una cultura que oriente los sentidos para mejorar la calidad de las relaciones interpersonales y así disminuir los potenciales eventos adversos que pueden afectar una convivencia y, por tanto, la calidad de vida en los ecuatorianos

Absceso prostático como causa poco frecuente de shock séptico

El absceso prostático es una enfermedad poco frecuente, asociada generalmente a prostatitis, y cuyo diagnóstico puede retrasarse por lo inespecífico de la clínica. Es aún más raro que aparezcan complicaciones graves sistémicas. Será preciso un alto nivel de sospecha y la realización de técnicas de imagen para llegar a un diagnóstico de certeza. Presentamos el caso de un paciente en situación de shock séptico secundario a un absceso de próstata. Tras revisar la bibliografía comprobamos que son escasos los casos documentados de complicaciones sistémicas graves de este tipo de pacientes

Effects of intubation timing in patients with COVID-19 throughout the four waves of the pandemic: a matched analysis

Background: The primary aim of our study was to investigate the association between intubation timing and hospital mortality in critically ill patients with coronavirus disease 2019 (COVID-19)-associated respiratory failure. We also analysed both the impact of such timing throughout the first four pandemic waves and the influence of prior noninvasive respiratory support on outcomes. Methods: This is a secondary analysis of a multicentre, observational and prospective cohort study that included all consecutive patients undergoing invasive mechanical ventilation due to COVID-19 from across 58 Spanish intensive care units (ICUs) participating in the CIBERESUCICOVID project. The study period was between 29 February 2020 and 31 August 2021. Early intubation was defined as that occurring within the first 24 h of ICU admission. Propensity score matching was used to achieve a balance across baseline variables between the early intubation cohort and those patients who were intubated after the first 24 h of ICU admission. Differences in outcomes between early and delayed intubation were also assessed. We performed sensitivity analyses to consider a different time-point (48 h from ICU admission) for early and delayed intubation. Results: Of the 2725 patients who received invasive mechanical ventilation, a total of 614 matched patients were included in the analysis (307 for each group). In the unmatched population, there were no differences in mortality between the early and delayed groups. After propensity score matching, patients with delayed intubation presented higher hospital mortality (27.3% versus 37.1%; p=0.01), ICU mortality (25.7% versus 36.1%; p=0.007) and 90-day mortality (30.9% versus 40.2%; p=0.02) compared with the early intubation group. Very similar findings were observed when we used a 48-h time-point for early or delayed intubation. The use of early intubation decreased after the first wave of the pandemic (72%, 49%, 46% and 45% in the first, second, third and fourth waves, respectively; first versus second, third and fourth waves p<0.001). In both the main and sensitivity analyses, hospital mortality was lower in patients receiving high-flow nasal cannula (HFNC) (n=294) who were intubated earlier. The subgroup of patients undergoing noninvasive ventilation (n=214) before intubation showed higher mortality when delayed intubation was set as that occurring after 48 h from ICU admission, but not when after 24 h. Conclusions: In patients with COVID-19 requiring invasive mechanical ventilation, delayed intubation was associated with a higher risk of hospital mortality. The use of early intubation significantly decreased throughout the course of the pandemic. Benefits of such an approach occurred more notably in patients who had received HFNC