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SARS-CoV-2 is a new coronavirus characterized by a high infection and transmission capacity. A significant number of patients develop inadequate immune responses that produce massive releases of cytokines that compromise their survival. Soluble factors are clinically and pathologically relevant in COVID-19 survival but remain only partially characterized. The objective of this work was to simultaneously study 62 circulating soluble factors, including innate and adaptive cytokines and their soluble receptors, chemokines and growth and wound-healing/repair factors, in severe COVID-19 patients who survived compared to those with fatal outcomes. Serum samples were obtained from 286 COVID-19 patients and 40 healthy controls. The 62 circulating soluble factors were quantified using a Luminex Milliplex assay. Results. The patients who survived had decreased levels of the following 30 soluble factors of the 62 studied compared to those with fatal outcomes, therefore, these decreases were observed for cytokines and receptors predominantly produced by the innate immune system—IL-1α, IL-1α, IL-18, IL-15, IL-12p40, IL-6, IL-27, IL-1Ra, IL-1RI, IL-1RII, TNFα, TGFα, IL-10, sRAGE, sTNF-RI and sTNF-RII—for the chemokines IL-8, IP-10, MCP-1, MCP-3, MIG and fractalkine; for the growth factors M-CSF and the soluble receptor sIL2Ra; for the cytokines involved in the adaptive immune system IFNγ, IL-17 and sIL-4R; and for the wound-repair factor FGF2. On the other hand, the patients who survived had elevated levels of the soluble factors TNFβ, sCD40L, MDC, RANTES, G-CSF, GM-CSF, EGF, PDGFAA and PDGFABBB compared to those who died. Conclusions. Increases in the circulating levels of the sCD40L cytokine; MDC and RANTES chemokines; the G-CSF and GM-CSF growth factors, EGF, PDGFAA and PDGFABBB; and tissue-repair factors are strongly associated with survival. By contrast, large increases in IL-15, IL-6, IL-18, IL-27 and IL-10; the sIL-1RI, sIL1RII and sTNF-RII receptors; the MCP3, IL-8, MIG and IP-10 chemokines; the M-CSF and sIL-2Ra growth factors; and the wound-healing factor FGF2 favor fatal outcomes of the disease, This research was coordinated by ProA Capital and Startlite Foundation, Programa de Actividades de I+D de la Comunidad de Madrid en Biomedicina (B2020/MITICAD-CM), Halekulani S.L., MJR; and Universidad de Alcala COVID-19 UAH 2019/00003/016/001/026 and COVID-19 2021-2020/00003/016/001/027

Introducción. La evaluación y manejo de la presión arterial (PA) es importante en la fase aguda del ictus. La monitorización ambulatoria de la PA (MAPA) se utiliza en el estudio y evaluación de la hipertensión arterial (HTA), pero apenas se ha estudiado en la fase aguda del ictus. Este estudio pretende investigar la PA obtenida por Monitorización de la PA durante 24 horas (MPA24h) el primer día del ictus, utilizando los equipos de la MAPA, analizando sus posibles diferencias según el tipo de ictus y su valor pronóstico precoz. Material y Métodos. Estudio observacional, longitudinal, de cohortes prospectivo sobre ictus de menos de 24 horas de evolución ingresados en el Hospital General La Mancha Centro de Alcázar de San Juan durante 4 años a los que se realizó MPA24h el primer día de ingreso y se determinó la escala de Rankin modificada (mRS) al séptimo día. Se ha realizado regresión lineal y logística binaria multivariante utilizando como variable de control del sesgo de confusión el índice de propensión (IP) obtenido como las probabilidades de respuesta positiva en un modelo de regresión multinominal con la variable dependiente politómica tipo de ictus y la variables independientes predictoras, sexo, HTA, diabetes mellitus (DM), dislipemia, insuficiencia cardiaca (IC), puntuación National Institute of Health Stroke Scale (NIHSS) al ingreso, enfermedad intercurrente, edad, ictus previo y tratamiento antiagregante. Resultados. Se han reclutado 499 ictus, con una mediana de edad de 74 años (amplitud intercuartil –AIC– de 67 a 79 años), 282 (56,5%) son varones, 297 (59,5%) hipertensos y 183 (36,7%) diabéticos. El 20,0% (100 pacientes) habían tenido un ictus previo, 25 (5%) un IAM previo y 68 (13,6%) tenían fibrilación auricular (FA). La mediana de puntuación de la NIHSS al ingreso es de 6 (AIC 3 a 13) puntos. La distribución por tipos de ictus es de 197 (37,5%) ictus lacunares, 99 (19,8%) cardioembólicos, 155 (31,1%) aterotrombóticos y 58 (11,6%) hemorrágicos. Se han encontrado 392 (78,9%) casos de buen pronóstico a los 7 días con mRS 0-3 y 105 (21,1%) casos de mal pronóstico con mRS 4-7. Las medianas de PA sistólica (PAS) son 134 (AIC 119 a 147) mmHg para ictus lacunar, 138 (AIC 124 a 156) mmHg para cardioembólico, 145 (AIC 127 a 160) mmHg para aterotrombótico y 144 (AIC 129 a 161) mmHg para ictus hemorrágico. Las medianas de PA diastólica (PAD) son 71 (AIC 64 a 78,5) mmHg en ictus lacunar, 70 (AIC 62 a 78) mmHg en cardioembólico, 74 (AIC 67 a 84) mmHg en aterotrombótico y 80 (AIC 70 a 93) en hemorrágico. En el análisis multivariante ajustado por el IP, no se observan diferencias significativas en los valores de PAS (p>0,200). Las diferencias significativas se observan en los valores de PAD (p=0,006), con diferencias significativas en las comparaciones múltiples de PAD entre hemorrágico-lacunar (diferencia de medias –DMed– 4,5 mmHg; intervalo de confianza –IC– 95% 0,5 a 8,4 mmHg; p=0,028), hemorrágico-cardioembólico (DMed 7,5 mmHg; IC 95% 3,3 a 11,6 mmHg; p0,200) ni de PAD (p>0,200) ni en los patrones circadianos de PAS (p>0,200), siendo diferentes los patrones circadianos de PAD (p=0,001). Las medianas de PAS y de PAD en el grupo de mal pronóstico son 148 (AIC 132 a 168) mmHg y 74 (AIC 65 a 83,5) mmHg, respectivamente, y en el grupo de buen pronóstico son 136 (AIC 21 a 150) mmHg y 73 (AIC 65 a 81) mmHg, respectivamente. En el análisis con regresión logística binaria multivariante ajustado por el IP, no se asocian a mal pronóstico los valores de PAS (razón de odds –RO– 1,01; IC 95% 1,00 a 1,02; p=0,111) ni de PAD (RO 1,00; IC 95% 0,98 a 1,02; p>0,200) del día 1. Se encuentra relación con el pronóstico en los cocientes nocturno/diurno de PAS (multiplicado por 100: RO 1,05; IC 95% 1,01 a 1,09; p=0,022) y de PAD (multiplicado por 100: RO 1,04; IC 95% 1,00 a 1,07; p=0,045). También tiene relación con el pronóstico la caída el día 7 respecto al día 1 tanto de la PAS (RO 0,97; IC 95% 0,95 a 0,99; p=0,002) como de la PAD (RO 0,93; IC 95% 0,90 a 0,97; p

SUCCOR study: an international European cohort observational study comparing minimally invasive surgery versus open abdominal radical hysterectomy in patients with stage IB1 cervical cancer FREE http://orcid.org/0000-0002-1908-3251Luis Chiva1, Vanna Zanagnolo2, Denis Querleu3, Nerea Martin- Calvo4, Juan Arévalo-Serrano5, Mihai Emil Căpîlna6, Anna Fagotti7, Ali Kucukmetin8, Constantijne Mom9, Galina Chakalova10, Shamistan Aliyev11, Mario Malzoni12, http://orcid.org/0000- 0001-5809-3535Fabrice Narducci13, Octavio Arencibia14, Francesco Raspagliesi15, Tayfun Toptas16, David Cibula17, Dilyara Kaidarova18, http://orcid.org/0000-0001-6763-9720Mehmet Mutlu Meydanli19, Mariana Tavares20, Dmytro Golub21, http://orcid.org/0000-0003-3140-4772Anna Myriam Perrone22, Robert Poka23, Dimitrios Tsolakidis24, Goran Vujić25, http://orcid.org/0000-0001-8935- 0311Marcin A Jedryka26, Petra L M Zusterzeel27, Jogchum Jan Beltman28, Frederic Goffin29, Dimitrios Haidopoulos30, Herman Haller31, Robert Jach32, Iryna Yezhova33, Igor Berlev34, Margarida Bernardino35, Rasiah Bharathan36, Maximilian Lanner37, Minna M Maenpaa38, http://orcid.org/0000-0002-4403-3707Vladyslav Sukhin39, Jean-Guillaume Feron40, Robert Fruscio41, 42, Kersti Kukk43, Jordi Ponce44, Jose Angel Minguez45, http://orcid.org/0000-0002-9618- 5606Daniel Vázquez-Vicente45, Teresa Castellanos45, Enrique Chacon46 and http://orcid.org/0000-0002-9700-0853Juan Luis Alcazar47 On behalf of the SUCCOR study Group Author affiliations Abstract Background Minimally invasive surgery in cervical cancer has demonstrated in recent publications worse outcomes than open surgery. The primary objective of the SUCCOR study, a European, multicenter, retrospective, observational cohort study was to evaluate disease-free survival in patients with stage IB1 (FIGO 2009) cervical cancer undergoing open vs minimally invasive radical hysterectomy. As a secondary objective, we aimed to investigate the association between protective surgical maneuvers and the risk of relapse. Methods We obtained data from 1272 patients that underwent a radical hysterectomy by open or minimally invasive surgery for stage IB1 cervical cancer (FIGO 2009) from January 2013 to December 2014. After applying all the inclusion-exclusion criteria, we used an inverse probability weighting to construct a weighted cohort of 693 patients to compare outcomes (minimally invasive surgery vs open). The first endpoint compared disease-free survival at 4.5 years in both groups. Secondary endpoints compared overall survival among groups and the impact of the use of a uterine manipulator and protective closure of the colpotomy over the tumor in the minimally invasive surgery group. Results Mean age was 48.3 years (range ; 23–83) while the mean BMI was 25.7 kg/m2 (range ; 15–49). The risk of recurrence for patients who underwent minimally invasive surgery was twice as high as that in the open surgery group (HR, 2.07 ; 95% CI, 1.35 to 3.15 ; P=0.001). Similarly, the risk of death was 2.42-times higher than in the open surgery group (HR, 2.45 ; 95% CI, 1.30 to 4.60, P=0.005). Patients that underwent minimally invasive surgery using a uterine manipulator had a 2.76-times higher hazard of relapse (HR, 2.76 ; 95% CI, 1.75 to 4.33 ; P

Objective: To estimate the prevalence of potentially Inadequate drug prescriptions In elderly patients who attend the Emergency Department. Design: A multicentre randomized clinical trial. Patients over 65 years of age attending the Emergency Department are randomized to the control arm or the intervention arm. In the intervention arm, the pharmacist will review the chronic medication of patients and identify any potentially inadequate prescriptions, according to the STOPP-START criteria. The cases are discussed with the Emergency Specialist and, if considered adequate, a recommendation to modify the treatment is sent to the Primary Care Physician. The control arm will receive the standard of care, not including a systematic review of the adequacy to the STOPP-START criteria. This article presents preliminary outcomes regarding the prevalence of potentially inadequate prescriptions. Outcomes: Four hospitals participated in the study, and 665 patients were included (342 in the control arm and 305 in the intervention arm). The mean age in the control arm was 78.2 years vs. 78.99 in the intervention arm. The total number of medications received by patients at the time of inclusion was 3 275. Of these, 9.3% (CI 95%: 8.3-10.4) were considered potentially inadequate prescriptions according to the STOPP criteria. On the other hand, 81.1% (CI 95%: 76.8-85.4) of the patients evaluated presented potentially inadequate prescriptions. Conclusion: This study has detected a high prevalence of potentially inadequate prescriptions in elderly patients attending the Emergency Department. Objetivo: Estimar la prevalencia de prescripciones potencialmente inapropiadas en pacientes mayores que acuden a urgencias Diseño: Ensayo clínico multicéntrico aleatorizado. Los pacientes mayores de 65 años que acuden a urgencias son asignados al grupo control o al de intervención. En el grupo de intervención, el farmacéutico revisa la medicación crónica de los pacientes e identifica aquellas prescripciones potencialmente inapropiadas de acuerdo a los criterios STOPP START. Los casos se discuten con el médico de urgencias y, cuando se considera indicado, se envía una recomendación al médico de atención primaria para que modifique el tratamiento. El grupo control recibe los cuidados habituales, que no incluyen una evaluación sistemática de la adecuación a los criterios STOPP START. En este artículo se presentan resultados preliminares respecto a la prevalencia de prescripciones potencialmente inapropiadas. Resultados: En el estudio han participado cuatro centros y se han incluido 665 pacientes (342 en el grupo control y 305 en el de intervención). La edad media en el grupo control ha sido de 78,2 años frente a 78,99 en el grupo de intervención. El número total de medicamentos que recibían los pacientes en el momento de la inclusión fue de 3.243. De estos, el 9,3% (IC 95%: 8,3-10,4) fueron considerados prescripciones potencialmente inapropiadas de tipo STOPP Por otro lado, el 81,1%. (IC 95%: 76,8-85,4) de los pacientes evaluados presentaron prescripciones potencialmente inapropiadas. Conclusiones: En el estudio se ha detectado una alta prevalencia de prescripciones potencialmente inapropiadas en pacientes mayores que acuden a urgencias.

Objective: To describe the capacity of a broad spectrum of cytokines and growth factors to predict ICU admission and/or death in patients with severe COVID-19. Design: An observational, analytical, retrospective cohort study with longitudinal follow-up. Setting: Hospital Universitario Príncipe de Asturias (HUPA). Participants: 287 patients diagnosed with COVID-19 admitted to our hospital from 24 March to 8 May 2020, followed until 31 August 2020. Main outcome measures: Profiles of immune response (IR) mediators were determined using the Luminex Multiplex technique in hospitalized patients within six days of admission by examining serum levels of 62 soluble molecules classified into the three groups: adaptive IR-related cytokines (n = 19), innate inflammatory IR-related cytokines (n = 27), and growth factors (n = 16). Results: A statistically robust link with ICU admission and/or death was detected for increased serum levels of interleukin (IL)-6, IL-15, soluble (s) RAGE, IP10, MCP3, sIL1RII, IL-8, GCSF and MCSF and IL-10. The greatest prognostic value was observed for the marker combination IL-10, IL-6 and GCSF. Conclusions: When severe COVID-19 progresses to ICU admission and/or death there is a marked increase in serum levels of several cytokines and chemokines, mainly related to the patient’s inflammatory IR. Serum levels of IL-10, IL-6 and GCSF were most prognostic of the outcome measure., This research was coordinated by ProA Capital and Startlite Foundation, Programa de Actividades de I+D de la Comunidad de Madrid en Biomedicina (B2020/MITICAD-CM).