[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.

[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.

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.

[Adaptation of the new medical degree to the European Space for Higher Education. What has been the contribution of Bologna?]. / Adaptación del nuevo Grado en Medicina al Espacio Europeo de Educación Superior. ¿Cuál ha sido la aportación de Bolonia?

In the last three years, the development of a profound reorganization of university teachings has made it possible to comply with the commitments of the Declaration of Bologna and to adapt all teaching to the new structure of the degree program that will be introduced in October 2010. Along these lines (Order ECI/332/2008), the requirements that must be fulfilled by the university degrees to be able to practice the medical profession have been established. In the new study plans, acquisition of skills by the students is given priority and emphasis is placed on the learning methods of these skills, and on the procedures to evaluate their acquisition. The European Credit Transfer System (ACTS), (between 25 and 30h), is the measurement unit that reflects the learning results. Furthermore, acquisition of clinical skills is promoted through the obligatory performance of pre-professional practices, in form of a period of independent clinical rotation and with a final evaluation of the skills, in health care centers, hospitals, and other care centers. In the upcoming years, it will be verified if this curriculum modernization of the study plans improves the professional practice of the new physicians.

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.

[Sclerosing cholangitis, papillary stenosis and B-cell lymphoma in a patient with acquired immunodeficiency syndrome]. / Colangitis esclerosante, estenosis de papila y linfoma-B en un paciente con síndrome de inmunodeficiencia adquirida.

The case of a 31 year old man who had been intravenous drug abuser for years is reported. He was studied because of abdominal pain, jaundice, a weight loss of 10 kg, and the presence of a subclavicular mass. Biopsy of the mass demonstrated a high-grade B-cell non-Hodgkin's lymphoma, and the patient was classified in group IV-D of the human immunodeficiency virus infection because he had HIV serum antibodies and a reduced CD4/CD8 lymphocyte ratio. Although lymphoma had a good response to chemotherapy, persistent cholestasis led to liver and biliary evaluation. Sclerosing cholangitis and papillary stenosis were found. He has been followed for two years, without evidence of any secondary infectious disease associated to the acquired immunodeficiency syndrome.

[Self-limited idiopathic fever. A study of twenty cases (author's transl)]. / Fiebre idiopática autolimitada. Estudio de 20 casos.

Out of 23 cases with a final diagnosis of idiopathic fever, 20 had self-limited fever with complete resolution. Comparing the cases of self-limited fever with other groups of patients with fever of unknown origin, the following differences were apparent: compared with tumoral and collagen diseases, self-limited fever occurred more frequently below age 40, the difference being significant (p less than 0.01). Chills occurred more frequently in self-limited fever than in tumoral and collagen diseases, while the incidence was similar in infectious diseases. Infectious, tumoral and collagen diseases presented with significantly greater weight loss (p less than 0.01) than self-limited fever. A greater incidence of hepatosplenomegaly was noted in self-limited fever than in infectious diseases. Hemoglobin and erythrocyte sedimentation rate (ESR) were significantly higher in self-limited fever than in the other illnesses. The NBT test was positive, with a reduction superior to 30% in the six cases in whom it was performed. In nine cases various invasive procedures were utilized: radiology, biopsy, laparoscopy (two cases), and laparotomy (one case). The data on the present series of self-limited idiopathic fever support an infectious origin of the disease because of the following: absence of an age difference with the group with a demonstrated infectious cause; fever of less than two months duration in most cases; presence of chills and less incidence of weight loss, anemia, and elevated ESR in relation to the other groups of fever of unknown origin; a positive NBT test; and spontaneous evolution to complete resolution of the disease.

[Hormonal multiplicity of an apudoma of the lung and pancreas. Characterization of the different peptides in the tumoral extracts (author's transl)]. / Multiplicidad hormonal en apudoma de pulmón y páncreas. Caracterización de los diferentes péptidos en los extractos tumorales.

The capacity which the cells of some tumors have of synthesizing, storing, and releasing hormonal polypetides constitutes the basic characteristic of the neoplasms of the APUD system. On many occasions these polypeptides are released as hormonal precursors of high molecular weight, with a minimal biological action in comparison with the real hormone (big ACTH, big gastrin, etc.), and they have no clinical expressivity. On other occasions they reproduce, however, the clinical syndrome of the hormone released in excess. The production of multiple hormones by a single tumor is not a common event. Here we present the case of a patient with an oat-cell carcinoma of the lung and a carcinoma of the pancreas, both histopathologically primitive. In this patient a syndrome of inadequate secretion of antidiuretic hormone was detected. By means of radioimmunoassay techniques, the existence of antidiuretic hormone, ACTH with a predominance of the components of high molecular weight (big ACTH and beta-LPH) and MSH was demonstrated in the tumoral extracts from the lung, pancreas, and from a mediastinal metastatic lymph node. While the concentrations of ACTH were much greater in the lung than in the pancreas, the opposite occurred for the antidiuretic hormone. The synthesis of MSH by the hypophyseal gland or by tumors is not at present recognized, but rather is considered as a degradation product during the process of extraction. The APUD system makes up the morphologic substrate of the syndromes of familiar multiple endocrine adenomatosis. The present case could represent a variant of sporadic multiple endocrine neoplasms which would have the same anatomical basis.

[Platelet function in systemic lupus erythematosus (author's transl)]. / Estudio de la función plaquetaria en el lupus eritematoso sistémico (LES).

The platelet function was studied in 23 patients with systemic lupus erythematosus, all of whom met the diagnostic creteria established by the American Rheumatism Association. They were not under any treatment, especially with any drug that might interfere with platelet function. The same study was performed on a control group composed of volunteers donors at a blood bank. The platelet count was definitely lower in the patients with lupus than in the control subjects (p less than 0.0005), although a clear thrombopenia was observed in only two indivduals (8.7 percent). Anti-platelet antibodies were found in only six cases (26 percent). There was a linear correlation between thrombopenia and the presence of hemorrhagic diathesis and low levels of C4 and CH50 components. Plateler adhesiveness was clearly lower in the lupus group than in the control group (p less than 0.0005). The presence of kidney disease determined a greater impairment of the platelet adhesiveness (p less than 0.0025). A notable defect on platelet aggregation was induced by ADP, adrenaline and collagen. This was more apparent in the group of patients exhibiting a higher degree of clinical activity and in those who showed a serum complement decrease. The mechanism responsible for this thrombopathy appears to be an interference in the platelet function due to the presence of circulating immunocomplexes. They adhere to the platelet membrane blocking its function and inhibiting the release of the necessary thrombocytic components for the second phase of the aggregation. This platelet alteration is not usually manifested clinically; for this reason no relationship was found between this platelet defect and the presence of hemorrhagic symptoms in our patients. The condition is reversible and may disappear after therapy with steroids and/or immunosuppresive agents.

[Fever of unknown origin. A study of 100 cases (author's transl)]. / Fiebre de origen desconocido. Análisis de 100 casos.

This report concerns the analysis of 100 cases of fever of unknown origin, defined according to the criteria of Petersdorf and Beeson. An etiological diagnosis could be reached in 77 cases, distributed as follows: infections, 32 cases; tumors, 14 cases; collagen diseases, 13 cases; various etiologies, 18 cases; and idiopathic, 23 cases of whom 20 had selflimited fever. There were 51 male and 49 female. The incidence of infectious diseases was significantly higher below age 40 when compared with the group of collagen diseases. Recurrent fever was common (43 cases) while continuous fever was unusual (3 cases). Recurrent fever was most frequent in neoplastic diseases, the difference in relation to the other groups being statistically significant (p less than 0.05). Chills, diffuse perspiration and myalgia were more frequent in infectious diseases (p less than 0.01) than in the other groups. Collagen diseases had significantly higher (p less than 0.05) white blood cell counts than neoplastic diseases, while the latter had significantly higher (p less than 0.01) serum lactic-dehydrogenase and alpha 2 globulin levels than infectious and collagen diseases. Hepatosplenomegaly was present more frequently in neoplastic than in infectious diseases. When evaluating diagnostic procedures it was noted that invasive techniques (arteriography, biopsy, laparoscopy, laparotomy) were essential to arrive to the final diagnosis in 47 cases, while noninvasive procedures (serological and immunological tests, bacteriology, conventional radiology, clinical course, and response to therapy) were sufficient in 22 cases. In eight cases the etiology of the fever could only be determined by post-mortem examination.

[Hormonal changes in fertile women with quiescent systemic lupus erythematosus]. / Alteraciones hormonales en mujeres fértiles con lupus eritematoso sistémico quiescente.

The hypophyseal-adrenal-ovarian axis was studied in 29 women of childbearing age with systemic lupus erythematosus, as well as in a control group of 14 healthy women. Hormonal levels were measured on days 7th and 21st of menstrual cycle. Women with systemic lupus erythematosus had not significatively lower testosterone levels, but progesterone and 17-alfa-hydroxiprogesterone levels were markedly lower when compared to controls. These facts suggest a decrease in progesterone levels, which could act as a predisposing factor for lupic disease.

[Coeliac disease in the adult]. / Enfermedad celiaca del adulto.

Coeliac disease can by defined as a chronic disease characterized by a typical mucosal lesion of the small intestine and an impaired nutrient absorption which improves on withdrawal of gluten from the diet. The prevalence rate has increased over the last decades and just 1/3 of cases are diagnosed in childhood. There is a striking association with class II histocompatibility antigens, HLA-DR3 and HLA-DQ2. Cellular immune response mediated by intraepithelial and lamina propria lymphocytes is the primary event in the small intestine damage. Up to 50% of adult coeliac patients don't present intestinal symptoms being more frequent subclinic forms. The immunological markers of coeliac disease are antigliadin, antireticulin and antiendomysial antibodies, being the last one the most specific. Mortality of coeliac patient is increased mainly for malignancies, being the most frequent the intestinal T lymphoma.

[The polyangiitis overlap-Schönlein-Henoch purpura-PAN syndrome: a case of more than a rare association]. / Síndrome poliangeítico de solapamiento púrpura de Schönlein Henoch-PAN: un caso más de una rara asociación.

A fifty-four-years old male with palpable purpura, polyarthritis and nephritic syndrome is presented. The renal biopsy disclosed mesangial proliferation with IgA deposits. During hospitalization abdominal pain and upper digestive bleeding also presented. Digital angiography showed splenic artery microaneurysms. Then it's a new case of polyangiitis overlap with mixed features of Schönlein-Henoch purpura and polyarteritis nodosa. Differential diagnosis between several vasculitic associations in a patient is discussed.

[Pattern of blood levels of erythropoietin and proinflammatory cytokines in patients with anemia of chronic disorders secondary to infection]. / Perfil de los niveles séricos de eritropoyetina y citocinas proinflamatorias en pacientes con anemia de trastornos crónicos secundaria a infección.

OBJECTIVE: To evaluate the pattern of erythropoietin (EPO) and some proinflammatory cytokines in the anemia of chronic disorders (ACD) secondary to infection. METHODS: Sequential determination in serum of interleukin-1 beta (IL-1 beta), necrosis tumoral factor alpha (TNF-alpha), gamma interferon (IFN-gamma), interleukin-6 (IL-6), and erythropoietin (EPO) in 25 patients with chronic bacterial infectious diseases and ACD criteria. We evaluated the relationship of these mediators with the anemia and the iron metabolism. RESULTS: Serum EPO levels significatively decreased compared with initial values, and the last control was in normal rank (18.04 +/- 19.10 vs. 8.56 +/- 4.72 UI/mL; p < 0.001; normal rank: 4-15 mUI/mL). In the first control, there was a negative and non significative correlation between the EPO levels and the hemoglobin concentration (r = -0.115, NS), reaching significance in the last control (r = -0.446; p < 0.05). There was negative correlation between the hematocrit and TNF-alpha levels (r = 0.467; p < 0.05) and between the haemoglobin values and the log of serum TNF-alpha (r = 0.424; p < 0.001). An inverse correlation between the IL-6 levels and both, the hemoglobin concentration and the serum iron was found, and there was a direct correlation between this cytokine values and the EPO levels. CONCLUSIONS: Blunted response of erythropoietin and the action of TNF may contribute to the pathogenesis of ACD secondary to infection. Positive correlation between IL-6 and EPO suggest a proerythropoietic action of IL-6 in response to the anemia.

[Necrotizing vasculitis of the panarteritis nodosa type in a long-course primary Sjögren's syndrome]. / Vasculitis necrotizante tipo panarteritis nodosa en un síndrome de Sjögren primario de larga evolución.

Vasculitis is a complication happening in a third of patients with primary Sjögren's Syndrome. It can be of 2 types: neutrophilic or mononuclear and sometimes mixed. Very occasionally, a necrotizing vasculitis polyarteritis nodosa type during the evolution of Sjögren's Syndrome has appeared. A case of a female patient with a Sjögren's Syndrome of large evolution, who suddenly showed a poly-systemic affliction (nervous system, kidneys, muscles and digestive system) secondary to a necrotizing vasculitis type polyarteritis nodosa with a good response to immunosuppressors, is presented.

[Suicidal attempt with colchicine]. / Intento autolítico con colchicina.

Colchicine is an alkaloid that has been successfully used for a long time in the treatment of acute gout episodes. It's efficacy lies in its inhibition of inflammation cell migration and in the action of specific cytokines, as well as of the production of lactic acid and deposition of uric acid in affected tissues. Colchicine toxicity is rare but may entail highly negative consequences for health unless a rapid gastric decontamination with stomach lavage and active carbon is carried out, and adequate support measures are taken as wellas appropriate hydration and electrolyte replacement. We present the case of a patient who was admitted to hospital after ingesting colchicine with suicidal intention. Colchicine inhibits cell division, which explains its distinct toxicity stages. The lack of proportion existing between ingested dose and clinical impact may result from concomitant treatment with other drugs or from peculiarities in its metabolism.