Resistencia a la proteína C activada en los accidentes cerebrovasculares

Tesis de la Universidad Complutense de Madrid, Facultad de Medicina, Departamento de Medicina, leída el 17-01-1997Introducción: la resistencia a la proteína c activada (rpca), es un defecto de carácter congénito que se ha revelado como la mayor causa de trombofilia idiopatica. El defecto consiste en una falta de respuesta a la proteína c activada (pca), potente anticoagulante natural, y se detecta mediante un sencillo test de ttpa (tiempo de cefalina). Objetivos: estandarizar el método de medida de la rpca y determinar su incidencia, en comparación con otras alteraciones hemostáticas, en los pacientes con acv. Material y método: se estudian un total de 433 controles para determinar las diferencias en la rpca según sexo, edad y congelación de las muestras, y para calcular el rango de referencia. Por otro lado, un grupo de 160 pacientes con acv en los que se determinan la rpca y otros parámetros hemostáticos. Rpca se mide por método coagulometrico (test ttpa). Resultados y conclusiones: nuestros resultados coinciden con los de otros autores, perfilándose la rpca como el factor de riesgo para acv mas potente de los estudiados. En la población general, la prevalencia de rpca es similar independientemente de sexo y edad. En cambio, la congelación de las muestras si muestra diferencias, siendo mayores los valores de rpca cuando se determinan en plasma fresco. En cualquier caso, siempre es fundamental estandarizar el método de medida, debiéndose determinar de antemano reactivos y rango de referencia a utilizar por cada laboratorio.Fac. de MedicinaTRUEpu

Macrodystrophia lipomatosa in a healthy newborn

A 15-day-old boy presented with an isolated enlargement of his second left toe. Physical examination showed no oedema, no bruit, no marks of amniotic constriction bands, or changes in the skin or the toenail. Afterwards, the toe exhibited a disproportionate growth with a progressive lateral deviation and dorsal flexion. Radiography showed an increase in size that involved the bone and the soft tissues

Primary Cilia as a Tumor Marker in Pituitary Neuroendocrine Tumors

Pituitary neuroendocrine tumors (PitNETs) account for approximately 15% of all intracranial neoplasms. Although they usually appear to be benign, some tumors display worse behavior, displaying rapid growth, invasion, refractoriness to treatment, and recurrence. Increasing evidence supports the role of primary cilia (PC) in regulating cancer development. Here, we showed that PC are significantly increased in PitNETs and are associated with increased tumor invasion and recurrence. Serial electron micrographs of PITNETs demonstrated different ciliation phenotypes (dot-like versus normal-like cilia) that represented PC at different stages of ciliogenesis. Molecular findings demonstrated that 123 ciliary-associated genes (eg, doublecortin domain containing protein 2, Sintaxin-3, and centriolar coiled-coil protein 110) were dysregulated in PitNETs, representing the upregulation of markers at different stages of intracellular ciliogenesis. Our results demonstrate, for the first time, that ciliogenesis is increased in PitNETs, suggesting that this process might be used as a potential target for therapy in the futureThis work was supported by the following grants: Proyectos de Investigación en Salud PI19/00584, PI22/01404 and PMP22/00021 (funded by Instituto de Salud Carlos III), iTIRONETdP2022/BMD7379 (funded by Comunidad de Madrid), Research project IPI/2022/N5 (funded by Sociedad de Endocrinología, Nutrici on y Diabetes de la Comunidad de Madrid-SENDIMAD), and co-financed by FEDER funds to MM and RMH, as well as by Contratos Predoctorales de Formaci on en Investigaci on en Salud (FI20/00035 to PSG and FI23/00052 to NSB). The funders played no role in the study design, data collection, data analysis, interpretation, or writing of the repor

Gender-Based Differences by Age Range in Patients Hospitalized with COVID-19: A Spanish Observational Cohort Study

There is some evidence that male gender could have a negative impact on the prognosis and severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The aim of the present study was to compare the characteristics of coronavirus disease 2019 (COVID-19) between hospitalized men and women with confirmed SARS-CoV-2 infection. This multicenter, retrospective, observational study is based on the SEMI-COVID-19 Registry. We analyzed the differences between men and women for a wide variety of demographic, clinical, and treatment variables, and the sex distribution of the reported COVID-19 deaths, as well as intensive care unit (ICU) admission by age subgroups. This work analyzed 12,063 patients (56.8% men). The women in our study were older than the men, on average (67.9 vs. 65.7 years; p < 001). Bilateral condensation was more frequent among men than women (31.8% vs. 29.9%; p = 0.007). The men needed non-invasive and invasive mechanical ventilation more frequently (5.6% vs. 3.6%, p < 0.001, and 7.9% vs. 4.8%, p < 0.001, respectively). The most prevalent complication was acute respiratory distress syndrome, with severe cases in 19.9% of men (p < 0.001). In men, intensive care unit admission was more frequent (10% vs. 6.1%; p < 0.001) and the mortality rate was higher (23.1% vs. 18.9%; p < 0.001). Regarding mortality, the differences by gender were statistically significant in the age groups from 55 years to 89 years of age. A multivariate analysis showed that female sex was significantly and independently associated with a lower risk of mortality in our study. Male sex appears to be related to worse progress in COVID-19 patients and is an independent prognostic factor for mortality. In order to fully understand its prognostic impact, other factors associated with sex must be considered

Risk categories in COVID-19 based on degrees of inflammation: data on more than 17,000 patients from the Spanish SEMI-COVID-19 registry

Background: the inflammation or cytokine storm that accompanies COVID-19 marks the prognosis. This study aimed to identify three risk categories based on inflammatory parameters on admission. Methods: retrospective cohort study of patients diagnosed with COVID-19, collected and followed-up from 1 March to 31 July 2020, from the nationwide Spanish SEMI-COVID-19 Registry. The three categories of low, intermediate, and high risk were determined by taking into consideration the terciles of the total lymphocyte count and the values of C-reactive protein, lactate dehydrogenase, ferritin, and D-dimer taken at the time of admission. Results: a total of 17,122 patients were included in the study. The high-risk group was older (57.9 vs. 64.2 vs. 70.4 years; p < 0.001) and predominantly male (37.5% vs. 46.9% vs. 60.1%; p < 0.001). They had a higher degree of dependence in daily tasks prior to admission (moderate-severe dependency in 10.8% vs. 14.1% vs. 17%; p < 0.001), arterial hypertension (36.9% vs. 45.2% vs. 52.8%; p < 0.001), dyslipidemia (28.4% vs. 37% vs. 40.6%; p < 0.001), diabetes mellitus (11.9% vs. 17.1% vs. 20.5%; p < 0.001), ischemic heart disease (3.7% vs. 6.5% vs. 8.4%; p < 0.001), heart failure (3.4% vs. 5.2% vs. 7.6%; p < 0.001), liver disease (1.1% vs. 3% vs. 3.9%; p = 0.002), chronic renal failure (2.3% vs. 3.6% vs. 6.7%; p < 0.001), cancer (6.5% vs. 7.2% vs. 11.1%; p < 0.001), and chronic obstructive pulmonary disease (5.7% vs. 5.4% vs. 7.1%; p < 0.001). They presented more frequently with fever, dyspnea, and vomiting. These patients more frequently required high flow nasal cannula (3.1% vs. 4.4% vs. 9.7%; p < 0.001), non-invasive mechanical ventilation (0.9% vs. 3% vs. 6.3%; p < 0.001), invasive mechanical ventilation (0.6% vs. 2.7% vs. 8.7%; p < 0.001), and ICU admission (0.9% vs. 3.6% vs. 10.6%; p < 0.001), and had a higher percentage of in-hospital mortality (2.3% vs. 6.2% vs. 23.9%; p < 0.001). The three risk categories proved to be an independent risk factor in multivariate analyses. Conclusion: the present study identifies three risk categories for the requirement of high flow nasal cannula, mechanical ventilation, ICU admission, and in-hospital mortality based on lymphopenia and inflammatory parameters

Ethnicity and Clinical Outcomes in Patients Hospitalized for COVID-19 in Spain: Results from the Multicenter SEMI-COVID-19 Registry

Background: This work aims to analyze clinical outcomes according to ethnic groups in patients hospitalized for COVID-19 in Spain. (2) Methods: This nationwide, retrospective, multicenter, observational study analyzed hospitalized patients with confirmed COVID-19 in 150 Spanish hospitals (SEMI-COVID-19 Registry) from 1 March 2020 to 31 December 2021. Clinical outcomes were assessed according to ethnicity (Latin Americans, Sub-Saharan Africans, Asians, North Africans, Europeans). The outcomes were in-hospital mortality (IHM), intensive care unit (ICU) admission, and the use of invasive mechanical ventilation (IMV). Associations between ethnic groups and clinical outcomes adjusted for patient characteristics and baseline Charlson Comorbidity Index values and wave were evaluated using logistic regression. (3) Results: Of 23,953 patients (median age 69.5 years, 42.9% women), 7.0% were Latin American, 1.2% were North African, 0.5% were Asian, 0.5% were Sub-Saharan African, and 89.7% were European. Ethnic minority patients were significantly younger than European patients (median (IQR) age 49.1 (40.5-58.9) to 57.1 (44.1-67.1) vs. 71.5 (59.5-81.4) years, p < 0.001). The unadjusted IHM was higher in European (21.6%) versus North African (11.4%), Asian (10.9%), Latin American (7.1%), and Sub-Saharan African (3.2%) patients. After further adjustment, the IHM was lower in Sub-Saharan African (OR 0.28 (0.10-0.79), p = 0.017) versus European patients, while ICU admission rates were higher in Latin American and North African versus European patients (OR (95%CI) 1.37 (1.17-1.60), p < 0.001) and (OR (95%CI) 1.74 (1.26-2.41), p < 0.001). Moreover, Latin American patients were 39% more likely than European patients to use IMV (OR (95%CI) 1.43 (1.21-1.71), p < 0.001). (4) Conclusion: The adjusted IHM was similar in all groups except for Sub-Saharan Africans, who had lower IHM. Latin American patients were admitted to the ICU and required IMV more often

Anti-Spike antibodies 3 months after SARS-CoV-2 mRNA vaccine booster dose in patients on hemodialysis: the prospective SENCOVAC study

Background: Patients on hemodialysis are at high-risk for complications derived from coronavirus disease 2019 (COVID-19). The present analysis evaluated the impact of a booster vaccine dose and breakthrough severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections on humoral immunity 3 months after the booster dose. Methods: This is a multicentric and prospective study assessing immunoglobulin G anti-Spike antibodies 6 and 9 months after initial SARS-CoV-2 vaccination in patients on hemodialysis that had also received a booster dose before the 6-month assessment (early booster) or between the 6- and 9-month assessments (late booster). The impact of breakthrough infections, type of vaccine, time from the booster and clinical variables were assessed. Results: A total of 711 patients [67% male, median age (range) 67 (20-89) years] were included. Of these, 545 (77%) received an early booster and the rest a late booster. At 6 months, 64 (9%) patients had negative anti-Spike antibody titers (3% of early booster and 29% of late booster patients, P =. 001). At 9 months, 91% of patients with 6-month negative response had seroconverted and there were no differences in residual prevalence of negative humoral response between early and late booster patients (0.9% vs 0.6%, P =. 693). During follow-up, 35 patients (5%) developed breakthrough SARS-CoV-2 infection. Antibody titers at 9 months were independently associated with mRNA-1273 booster (P =. 001), lower time from booster (P =. 043) and past breakthrough SARS-CoV-2 infection (P <. 001). Conclusions: In hemodialysis patients, higher titers of anti-Spike antibodies at 9 months were associated with mRNA-1273 booster, lower time from booster and past breakthrough SARS-CoV-2 infectionThe present project has been supported by Fresenius Medical Care, Diaverum, Vifor Pharma, Vircell, Fundación Renal Iñigo Álvarez de Toledo and ISCIII FEDER funds RICORS2040 (RD21/0005

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Resistencia a la proteína C activada en los accidentes cerebrovasculares

Introducción: la resistencia a la proteína c activada (rpca), es un defecto de carácter congénito que se ha revelado como la mayor causa de trombofilia idiopatica. El defecto consiste en una falta de respuesta a la proteína c activada (pca), potente anticoagulante natural, y se detecta mediante un sencillo test de ttpa (tiempo de cefalina). Objetivos: estandarizar el método de medida de la rpca y determinar su incidencia, en comparación con otras alteraciones hemostáticas, en los pacientes con acv. Material y método: se estudian un total de 433 controles para determinar las diferencias en la rpca según sexo, edad y congelación de las muestras, y para calcular el rango de referencia. Por otro lado, un grupo de 160 pacientes con acv en los que se determinan la rpca y otros parámetros hemostáticos. Rpca se mide por método coagulometrico (test ttpa). Resultados y conclusiones: nuestros resultados coinciden con los de otros autores, perfilándose la rpca como el factor de riesgo para acv mas potente de los estudiados. En la población general, la prevalencia de rpca es similar independientemente de sexo y edad. En cambio, la congelación de las muestras si muestra diferencias, siendo mayores los valores de rpca cuando se determinan en plasma fresco. En cualquier caso, siempre es fundamental estandarizar el método de medida, debiéndose determinar de antemano reactivos y rango de referencia a utilizar por cada laboratorio