[Impact of days elapsed from the onset of symptoms to hospitalization in COVID-19 in-hospital mortality: Time matters]. / Impacto de los días transcurridos desde el inicio de los síntomas hasta la hospitalización en la mortalidad hospitalaria por COVID-19: el tiempo importa.

Background: COVID-19 shows different clinical and pathophysiological stages over time. Theeffect of days elapsed from the onset of symptoms (DEOS) to hospitalization on COVID-19prognostic factors remains uncertain. We analyzed the impact on mortality of DEOS to hospital-ization and how other independent prognostic factors perform when taking this time elapsedinto account. Methods: This retrospective, nationwide cohort study, included patients with confirmed COVID-19 from February 20th and May 6th, 2020. The data was collected in a standardized online datacapture registry. Univariate and multivariate COX-regression were performed in the generalcohort and the final multivariate model was subjected to a sensitivity analysis in an earlypresenting (EP; < 5 DEOS) and late presenting (LP; ≥5 DEOS) group. Results: 7915 COVID-19 patients were included in the analysis, 2324 in the EP and 5591 in theLP group. DEOS to hospitalization was an independent prognostic factor of in-hospital mortalityin the multivariate Cox regression model along with other 9 variables. Each DEOS incrementaccounted for a 4.3% mortality risk reduction (HR 0.957; 95% CI 0.93---0.98). Regarding variationsin other mortality predictors in the sensitivity analysis, the Charlson Comorbidity Index onlyremained significant in the EP group while D-dimer only remained significant in the LP group. Conclusion: When caring for COVID-19 patients, DEOS to hospitalization should be consideredas their need for early hospitalization confers a higher risk of mortality. Different prognosticfactors vary over time and should be studied within a fixed timeframe of the disease.

Impacto de los días transcurridos desde el inicio de los síntomas hasta la hospitalización en la mortalidad hospitalaria por COVID-19: el tiempo importa / Impact of days elapsed from the onset of symptoms to hospitalization in COVID-19 in-hospital mortality: Time matters

Antecedentes La COVID-19 muestra diferentes fases clínicas y fisiopatológicas a lo largo del tiempo. El efecto de los días transcurridos desde el comienzo de los síntomas (DTCS) hasta la hospitalización sobre los factores pronósticos de la COVID-19 sigue siendo incierto. Analizamos el impacto en la mortalidad de los DTCS hasta la hospitalización y cómo se comportan otros factores pronósticos independientes al tener en cuenta dicho tiempo transcurrido. Métodos En este estudio de cohortes nacional retrospectivo se incluyó a pacientes con COVID-19 confirmada entre el 20 de febrero y el 6 de mayo de 2020. Los datos se recopilaron en un registro normalizado de captura de datos en línea. Se realizó una regresión de Cox uni y multifactorial en la cohorte general y el modelo multifactorial final se sometió a un análisis de sensibilidad en un grupo de presentación precoz (PP) < 5 DTCS y otro de presentación tardía (PT) ≥ 5 DTCS). Resultados En el análisis se incluyó a 7.915 pacientes con COVID-19, 2.324 en el grupo de PP y 5.591 en el de PT. Los DTCS hasta la hospitalización fueron un factor pronóstico independiente de mortalidad intrahospitalaria en el modelo de regresión de Cox multifactorial junto con otras nueve variables. Cada incremento en un DTCS supuso una reducción del riesgo de mortalidad del 4,3% (RRI = 0,957; IC 95%, 0,93-0,98). En cuanto a las variaciones de otros factores predictivos de la mortalidad en el análisis de sensibilidad, únicamente el índice de comorbilidad de Charlson siguió siendo significativo en el grupo de PP, mientras que únicamente el dímero D lo siguió siendo en el grupo de PT. Conclusiones Al atender a pacientes con COVID-19 hay que tener en cuenta los DTCS hasta la hospitalización porque la necesidad de hospitalización precoz confiere un mayor riesgo de mortalidad. Los diferentes factores pronósticos varían con el tiempo y deberían estudiarse dentro de un marco temporal fijo de la enfermedad (AU)

Background COVID-19 shows different clinical and pathophysiological stages over time. Theeffect of days elapsed from the onset of symptoms (DEOS) to hospitalization on COVID-19prognostic factors remains uncertain. We analyzed the impact on mortality of DEOS to hospital-ization and how other independent prognostic factors perform when taking this time elapsedinto account. Methods This retrospective, nationwide cohort study, included patients with confirmed COVID-19 from February 20th and May 6th, 2020. The data was collected in a standardized online datacapture registry. Univariate and multivariate COX-regression were performed in the generalcohort and the final multivariate model was subjected to a sensitivity analysis in an earlypresenting (EP; <5 DEOS) and late presenting (LP; ≥5 DEOS) group. Results 7915 COVID-19 patients were included in the analysis, 2324 in the EP and 5591 in theLP group. DEOS to hospitalization was an independent prognostic factor of in-hospital mortalityin the multivariate Cox regression model along with other 9 variables. Each DEOS incrementaccounted for a 4.3% mortality risk reduction (HR 0.957; 95% CI 0.93---0.98). Regarding variationsin other mortality predictors in the sensitivity analysis, the Charlson Comorbidity Index onlyremained significant in the EP group while D-dimer only remained significant in the LP group. Conclusion When caring for COVID-19 patients, DEOS to hospitalization should be consideredas their need for early hospitalization confers a higher risk of mortality. Different prognosticfactors vary over time and should be studied within a fixed timeframe of the disease (AU)

Impact of days elapsed from the onset of symptoms to hospitalization in COVID-19 in-hospital mortality: time matters.

BACKGROUND: COVID-19 shows different clinical and pathophysiological stages over time. The effect of days elapsed from the onset of symptoms (DEOS) to hospitalization on COVID-19 prognostic factors remains uncertain. We analyzed the impact on mortality of DEOS to hospitalization and how other independent prognostic factors perform when taking this time elapsed into account. METHODS: This retrospective, nationwide cohort study, included patients with confirmed COVID-19 from February 20th and May 6th, 2020. The data was collected in a standardized online data capture registry. Univariate and multivariate COX-regression were performed in the general cohort and the final multivariate model was subjected to a sensitivity analysis in an early presenting (EP; <5 DEOS) and late presenting (LP; ≥5 DEOS) group. RESULTS: 7915 COVID-19 patients were included in the analysis, 2324 in the EP and 5591 in the LP group. DEOS to hospitalization was an independent prognostic factor of in-hospital mortality in the multivariate Cox regression model along with other 9 variables. Each DEOS increment accounted for a 4.3% mortality risk reduction (HR 0.957; 95% CI 0.93-0.98). Regarding variations in other mortality predictors in the sensitivity analysis, the Charlson Comorbidity Index only remained significant in the EP group while D-dimer only remained significant in the LP group. CONCLUSION: When caring for COVID-19 patients, DEOS to hospitalization should be considered as their need for early hospitalization confers a higher risk of mortality. Different prognostic factors vary over time and should be studied within a fixed timeframe of the disease.

Evaluación del valor pronóstico de los parámetros volumétricos metabólicos calculados con la 18F-FDG PET/TC y su valor añadido a las características moleculares en pacientes con linfoma B difuso de células grandes / Evaluation of the prognostic value of the metabolic volumetric parameters calculated with 18F-FDG PET/CT and its value added to the molecular characteristics in patients with diffuse large b-cell lymphoma

Introducción y objetivos: El volumen metabólico tumoral (VMT) y la glicólisis total de la lesión (TLG) son predictores pronósticos en los pacientes con linfoma B difuso de células grandes (LBDCG). El objetivo del presente estudio es evaluar el impacto pronóstico de los parámetros volumétricos basales calculados con la tomografía por emisión de positrones/tomografía computarizada con 18F-fluorodesoxiglucosa (18F-FDG PET/TC) y su valor agregado a las características moleculares en pacientes con LBDCG tipo no especificado (NOS). Metodología: Se trata de un estudio retrospectivo observacional, en el que se incluyeron 35 pacientes sometidos a un 18F-FDG PET/TC basal previo al tratamiento. Se realizó un análisis univariable de los parámetros volumétricos (VMT y TLG), estudio inmunohistoquímico y traslocaciones cromosómicas. El método para el cálculo de los parámetros volumétricos fue el umbral SUV 2,5. La comparación entre los modelos predictivos se seleccionó en función del valor de criterio de información de Akaike (AIC), bayesiano (BIC) y C de Harrell, después de realizar un modelo de regresión de riesgos proporcionales de Cox. Además, se realizó un análisis univariable de los parámetros volumétricos, según los datos del estudio inmunohistoquímico utilizando la prueba de Wilcoxon-Mann-Whitney. Resultados: Al realizar un análisis univariable se evidenció que el VMT y la TLG son predictores de la supervivencia libre de progresión (SLP) y de la supervivencia global (SG), con una alta capacidad de discriminación. El añadir el VMT y la TLG al estudio inmunohistoquímico y a la traslocación cromosómica proporcionó un mejor valor pronóstico a la SLP y SG en los pacientes diagnosticados con LBDCG tipo NOS. Así mismo, se evidenció que los valores de los parámetros volumétricos eran menores en los pacientes que presentaron un fenotipo células B centro germinal (GCB) frente a los pacientes con fenotipo células B activadas (ABC) que presentaron valores mayores (AU)

Introduction and objectives: Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) are prognostic predictors in patients with diffuse large B-cell lymphoma (DLBCL). The objective of this study is to evaluate the prognostic impact of the baseline volumetric parameters calculated with positron emission tomography/computed tomography with 18F-fluorodeoxyglucose (18F-FDG PET/CT) and its added value to the molecular characteristics in patients with DLBCL not otherwise specified (NOS). Methodology: This is a retrospective observational study, which included 35 patients who underwent a baseline 18F-FDG PET/CT prior to treatment. A univariate analysis of the volumetric parameters (MTV and TLG), immunohistochemical study and chromosomal translocations were performed. The method for calculating the volumetric parameters was the SUV 2.5 threshold. The comparison between the predictive models was selected based on the information criterion value of Akaike (AIC), bayesian (BIC) and Harrell's C, after performing a Cox proportional hazards regression model. In addition, a univariate analysis of the volumetric parameters was performed according to the data of the immunohistochemical study using the Wilcoxon-Mann-Whitney test. Results: A univariate analysis revealed that VMT and TLG are predictors of progression-free survival (PFS) and overall survival (OS), with a high discrimination capacity. Adding VMT and TLG to the immunohistochemical study and chromosomal translocation provided a better prognostic value for PFS and OS in patients diagnosed with DLBCL-NOS. Likewise, it was evidenced that the values of the volumetric parameters were lower in patients who presented a germinal center B cell phenotype (GCB) compared to patients with an activated B cell phenotype (ABC) who presented higher values. Conclusion: MTV and TLG added to the immunohistochemical study and chromosomal translocation provided a better prognostic value for PFS and OS (AU)

Evaluation of the prognostic value of the metabolic volumetric parameters calculated with 18F-FDG PET/CT and its value added to the molecular characteristics in patients with diffuse large B-cell lymphoma.

INTRODUCTION AND OBJECTIVES: Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) are prognostic predictors in patients with diffuse large B-cell lymphoma (DLBCL). The objective of this study is to evaluate the prognostic impact of the baseline volumetric parameters calculated with positron emission tomography/computed tomography with 18F-fluorodeoxyglucose (18F-FDG PET/CT) and its added value to the molecular characteristics in patients with DLBCL not otherwise specified (NOS). METHODOLOGY: This is a retrospective observational study, which included 35 patients who underwent a baseline 18F-FDG PET/CT prior to treatment. A univariate analysis of the volumetric parameters (MTV and TLG), immunohistochemical study and chromosomal translocations were performed. The method for calculating the volumetric parameters was the SUV 2.5 threshold. The comparison between the predictive models was selected based on the information criterion value of Akaike (AIC), bayesian (BIC) and Harrell's C, after performing a Cox proportional hazards regression model. In addition, a univariate analysis of the volumetric parameters was performed according to the data of the immunohistochemical study using the Wilcoxon-Mann-Whitney test. RESULTS: A univariate analysis revealed that VMT and TLG are predictors of progression-free survival (PFS) and overall survival (OS), with a high discrimination capacity. Adding VMT and TLG to the immunohistochemical study and chromosomal translocation provided a better prognostic value for PFS and OS in patients diagnosed with DLBCL-NOS. Likewise, it was evidenced that the values of the volumetric parameters were lower in patients who presented a germinal center B cell phenotype (GCB) compared to patients with an activated B cell phenotype (ABC) who presented higher values. CONCLUSION: MTV and TLG added to the immunohistochemical study and chromosomal translocation provided a better prognostic value for PFS and OS in patients diagnosed with DLBCL-NOS.

Clinical characteristics of patients hospitalized with COVID-19 in Spain: Results from the SEMI-COVID-19 Registry. / Características clínicas de los pacientes hospitalizados con COVID-19 en España: resultados del Registro SEMI-COVID-19.

BACKGROUND: Spain has been one of the countries most affected by the COVID-19 pandemic. OBJECTIVE: To create a registry of patients with COVID-19 hospitalized in Spain, in order to improve our knowledge of the clinical, diagnostic, therapeutic, and prognostic aspects of this disease. METHODS: A multicentre retrospective cohort study, including consecutive patients hospitalized with confirmed COVID-19 throughout Spain. Epidemiological and clinical data, additional tests at admission and at seven days, treatments administered, and progress at 30 days of hospitalization were collected from electronic medical records. RESULTS: Up to June 30th 2020, 15,111 patients from 150 hospitals were included. Their median age was 69.4 years (range: 18-102 years) and 57.2% were male. Prevalences of hypertension, dyslipidemia, and diabetes mellitus were 50.9%, 39.7%, and 19.4%, respectively. The most frequent symptoms were fever (84.2%) and cough (73.5%). High values of ferritin (73.5%), lactate dehydrogenase (73.9%), and D-dimer (63.8%), as well as lymphopenia (52.8%), were frequent. The most used antiviral drugs were hydroxychloroquine (85.6%) and lopinavir/ritonavir (61.4%); 33.1% developed respiratory distress. Overall mortality rate was 21.0%, with a marked increase with age (50-59 years: 4.7%, 60-69 years: 10.5%, 70-79 years: 26.9%, ≥80 years: 46.0%). CONCLUSIONS: The SEMI-COVID-19 Network provides data on the clinical characteristics of patients with COVID-19 hospitalized in Spain. Patients with COVID-19 hospitalized in Spain are mostly severe cases, as one in three patients developed respiratory distress and one in five patients died. These findings confirm a close relationship between advanced age and mortality.

Evaluation of the prognostic value of different methods of calculating the tumour metabolic volume with 18F-FDG PET/CT, in patients with diffuse large cell B-cell lymphoma. / Evaluación del valor pronóstico de los diferentes métodos de cálculo del volumen metabólico tumoral con 18F-FDG PET/TC, en pacientes con linfoma B difuso de células grandes.

INTRODUCTION AND OBJECTIVES: Metabolic tumor volume (MTV) is a promising indicator of prognosis in diffuse large B-cell lymphoma (DLBCL). The aim of the present study is to evaluate the different methods for the calculation of the basal metabolic tumor volume with 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in the patients with DLBCL, relating each one of the volumes measured with progression-free survival (PFS) and overall survival (OS). METHODOLOGY: This is a retrospective analytical cohort study, in which 34 patients underwent to 18F-FDG PET/CT baseline prior to treatment. We compared three SUV thresholds 2.5, SUV 40% of the maximum SUV and SUV mean hepatic uptake (PERCIST) for the calculation of MTV and total lesion glycolysis (TLG) biomarkers, relating them to the PFS and OS. The best predictive model was selected based on the Akaike's information criterion (AIC) after performing a Cox proportional hazards regression. RESULTS: In relation to the PFS, they show statistically significant differences: MTV 2.5, TLG 2.5, MTV 40, TLG 40, MTV and TLG calculated with the PERCIST threshold. Among these, the one that has a lower AIC is MTV 2.5, so it is considered the best parameter to predict the PFS. With respect to OS, it shows statistically significant differences: MTV 2.5, VMT and TLG calculated with the PERCIST threshold. Among these three, the one with the lowest AIC is MTV 2.5, which is why it is considered the best parameter to predict OS. In addition, a higher value of MTV and total tumor glycolysis (TLG), is associated with worse PFS and OS CONCLUSION: The MTV calculated with the threshold SUV 2.5 seems to be the best parameter to predict PFS and OS in patients diagnosed with DLBCL with 18F-FDG PET/CT.

[Clinical characteristics of patients hospitalized with COVID-19 in Spain: Results from the SEMI-COVID-19 Registry]. / Características clínicas de los pacientes hospitalizados con COVID-19 en España: resultados del Registro SEMI-COVID-19.

BACKGROUND: Spain has been one of the countries most affected by the COVID-19 pandemic. OBJECTIVE: To create a registry of patients with COVID-19 hospitalized in Spain, in order to improve our knowledge of the clinical, diagnostic, therapeutic, and prognostic aspects of this disease. METHODS: A multicentre retrospective cohort study, including consecutive patients hospitalized with confirmed COVID-19 throughout Spain. Epidemiological and clinical data, additional tests at admission and at seven days, treatments administered, and progress at 30 days of hospitalization were collected from electronic medical records. RESULTS: Up to June 30th 2020, 15,111 patients from 150 hospitals were included. Their median age was 69.4 years (range: 18-102 years) and 57.2% were male. Prevalences of hypertension, dyslipidemia, and diabetes mellitus were 50.9%, 39.7%, and 19.4%, respectively. The most frequent symptoms were fever (84.2%) and cough (73.5%). High values of ferritin (73.5%), lactate dehydrogenase (73.9%), and D-dimer (63.8%), as well as lymphopenia (52.8%), were frequent. The most used antiviral drugs were hydroxychloroquine (85.6%) and lopinavir/ritonavir (61.4%); 33.1% developed respiratory distress. Overall mortality rate was 21.0%, with a marked increase with age (50-59 years: 4.7%, 60-69 years: 10.5%, 70-79 years: 26.9%, ≥ 80 years: 46.0%). CONCLUSIONS: The SEMI-COVID-19 Network provides data on the clinical characteristics of patients with COVID-19 hospitalized in Spain. Patients with COVID-19 hospitalized in Spain are mostly severe cases, as one in three patients developed respiratory distress and one in five patients died. These findings confirm a close relationship between advanced age and mortality.

Predicted change in the number of permanent medical teachers from 2017 to 2026. The training of future physicians in critical condition. / Evolución previsible en el número de profesores permanentes de Medicina del 2017 al 2026. La formación de los futuros médicos en situación crítica.

The significant and progressive reduction in the number of permanent teachers in medical schools (professor, associate professor and assistant professor) is a reason for concern for the National Conference of Deans. This reduction will intensify in the coming decade (2017-2026). Forty-three percent of the permanent faculty will retire, as will 55% of the faculty linked to clinical areas, 34% of the faculty not linked to clinical areas and 32% of the faculty of basic areas. This deficit is significant now, and, in a few years, the situation will be unsustainable, especially in the clinical areas. This report reveals the pressing need to adopt urgent measures to alleviate the present situation and prevent a greater problem. The training of future physicians, immediately responsible for the health of our society, depends largely on the theoretical and practical training taught in medical schools, with the essential collaboration of healthcare institutions. Paradoxically, while the number of teachers decreases substantially, there is an exponential increase in the number of medical schools and students who are admitted every year without academic or healthcare justification.

Biclonal gammopathies: Retrospective study of 47 patients. / Gammapatías biclonales: estudio retrospectivo de 47 pacientes.

OBJECTIVES: Biclonal gammopathies are characterized by the clonal proliferation of plasma cells or their B-lymphoid progenitors and are associated with the production of abnormal immunoglobulins (M proteins or paraproteins). There are no known studies that have analyzed this disease in Spain. We studied the underlying diseases, characteristics of paraproteins and the evolution of a series of patients with biclonal gammopathy. MATERIAL AND METHODS: We reviewed clonal gammopathies at the Department of Immunology of Hospital Puerta de Hierro in Madrid, between 1970 and 2011, selecting those patients with biclonal gammopathy in one reading. We collected data on the patient's epidemiology, underlying disease, associated diseases, therapies and paraprotein and immunoglobulin levels. RESULTS: Of the 1626 cases of clonal gammapathies, 47 were biclonal gammopathy (2.89%). The median follow-up was 2 years. The main associated condition was biclonal gammopathies of undetermined significance (BGUS). The most common paraprotein combination was IgG-IgG. Upon conducting a second paraprotein reading, 81% of the patients had lost at least 1 monoclonal component. A third of the patients had not undergone treatment. CONCLUSIONS: Biclonal gammopathy are fundamentally associated with biclonal gammopathies of undetermined significance. No biclonal gammopathies of undetermined significance evolved to a malignant disease. In a high percentage of patients, at least 1 of the 2 clonal components disappeared, sometimes spontaneously.

Current status of General Pathology training in Spain.

BACKGROUND AND OBJECTIVES: One of the core subjects in university training of the physicians has been General Pathology. Responsibility for this has historically fallen on Internal Medicine specialists. However, we are unaware if this situation is currently maintained. METHODS: A questionnaire was sent to the coordinators of the subject of the 39 Spanish medical schools to know, among other things, the current denomination of the subjects (traditionally known as «General Pathology¼), number of credits, teaching activities included in the subject and number and specialty of the professors responsible for it. Some data from the medical schools that did not respond were obtained from their web pages. RESULTS: A total of 28 of the 39 (72%) medical schools existing in Spain answered the survey. The current denomination of the subject «General Pathology¼ varied greatly. The mean number of credits (one credit=20-25 h) was 11.2 (range 3 to 29). In 22 of 34 schools (65%), the subject was taught in the third year of the studies, but in 21% of the schools, it was partially and in 15% of the schools, totally, taught in the second year. More than half of the professors (54%) who taught the subject were Internal Medicine specialists, although this responsibility was shared with other specialists in a large proportion. CONCLUSIONS: Teaching of General Pathology shows a marked heterogeneity that does not seem to be due to teaching or pedagogic criteria among the different schools of Spain. These facts may be due to less presence in the university setting of Internal Medicine compared to other specialties.

[Lymphocytic variant of the hypereosinophilic syndrome]. / Variante linfoide del síndrome hipereosinófilo.

OBJECTIVES: Hypereosinophilic syndromes (HSS) are a rare group of heterogeneous disorders characterized by prominent and persistent eosinophilia and organ dysfunction. Secondary causes of eosinophilia must be excluded. Recent advances in molecular biology and cytogenetics have permitted the characterization of different subsets of hypereosinophilic syndrome. We describe a patient with the lymphocytic variant. PATIENT: A 46-year old male Philippine patient presented skin lesions, fever, red eyes, enlarged lymph nodes and marked eosinophilia. RESULTS: Lymphocytic phenotyping by flow cytometry analysis was performed on peripheral blood and an aberrant population of T lymphocytes CD3-CD4+ producing interleukin 5 was found. TCR gene rearrangement using PCR amplification confirmed T cell clonality. CONCLUSIONS: The lymphocytic variant of the hypereosinophilic syndrome is a primitive lymphocytic disorder characterized by a non-malignant T cell population expansion producing eosinophilopoietic cytokines, with an indolent clinical course but that can transform into a peripheral T lymphoma. We report the first case of such a variant published in our country and review the characteristics of this variety.