Baricitinib reduces 30-day mortality in older adults with moderate-to-severe COVID-19 pneumonia.

BACKGROUND: Older adults are at the highest risk of severe disease and death due to COVID-19. Randomized data have shown that baricitinib improves outcomes in these patients, but focused stratified analyses of geriatric cohorts are lacking. Our objective was to analyze the efficacy of baricitinib in older adults with COVID-19 moderate-to-severe pneumonia. METHODS: This is a propensity score [PS]-matched retrospective cohort study. Patients from the COVID-AGE and Alba-Score cohorts, hospitalized for moderate-to-severe COVID-19 pneumonia, were categorized in two age brackets of age <70 years old (86 with baricitinib and 86 PS-matched controls) or ≥70 years old (78 on baricitinib and 78 PS-matched controls). Thirty-day mortality rates were analyzed with Kaplan-Meier and Cox proportional hazard models. RESULTS: Mean age was 79.1 for those ≥70 years and 58.9 for those <70. Exactly 29.6% were female. Treatment with baricitinib resulted in a significant reduction in death from any cause by 48% in patients aged 70 or older, an 18.5% reduction in 30-day absolute mortality risk (n/N: 16/78 [20.5%] baricitinib, 30/78 [38.5%] in PS-matched controls, p < 0.001) and a lower 30-day adjusted fatality rate (HR 0.21; 95% CI 0.09-0.47; p < 0.001). Beneficial effects on mortality were also observed in the age group <70 (8.1% reduction in 30-day absolute mortality risk; HR 0.14; 95% CI 0.03-0.64; p = 0.011). CONCLUSIONS: Baricitinib is associated with an absolute mortality risk reduction of 18.5% in adults older than 70 years hospitalized with COVID-19 pneumonia.

JAK inhibition reduces SARS-CoV-2 liver infectivity and modulates inflammatory responses to reduce morbidity and mortality.

Using AI, we identified baricitinib as having antiviral and anticytokine efficacy. We now show a 71% (95% CI 0.15 to 0.58) mortality benefit in 83 patients with moderate-severe SARS-CoV-2 pneumonia with few drug-induced adverse events, including a large elderly cohort (median age, 81 years). An additional 48 cases with mild-moderate pneumonia recovered uneventfully. Using organotypic 3D cultures of primary human liver cells, we demonstrate that interferon-α2 increases ACE2 expression and SARS-CoV-2 infectivity in parenchymal cells by greater than fivefold. RNA-seq reveals gene response signatures associated with platelet activation, fully inhibited by baricitinib. Using viral load quantifications and superresolution microscopy, we found that baricitinib exerts activity rapidly through the inhibition of host proteins (numb-associated kinases), uniquely among antivirals. This reveals mechanistic actions of a Janus kinase-1/2 inhibitor targeting viral entry, replication, and the cytokine storm and is associated with beneficial outcomes including in severely ill elderly patients, data that incentivize further randomized controlled trials.

Valoración del colesterol no HDL como predictor de episodios cardiovasculares no mortales en una cohorte prospectiva de origen poblacional / Evaluation of non-HDL cholesterol as a predictor of non-fatal cardiovascular events in a prospective population cohort

Introducción: El colesterol no transportado por las lipoproteínas de alta densidad (c-no-HDL) está adquiriendo relevancia en su participación en la valoración del riesgo cardiovascular y como diana terapéutica. El objetivo del presente estudio ha sido valorar la capacidad predictiva independiente, tanto del c-no-HDL como del colesterol de las lipoproteínas de baja densidad (cLDL), principal prioridad en las dislipidemias para reducir el riesgo cardiovascular (RCV), en la morbilidad de causa cardiovascular, en una muestra de origen poblacional. Métodos: El diseño del estudio corresponde a una cohorte prospectiva en la que han participado 1.186 individuos en el grupo c-no-HDL y 1.177 en el grupo cLDL, seguidos durante 10,7años (DE=2,2), los cuales no habían padecido ningún episodio cardiovascular (CV) previo. Las variables predictoras incluidas en el ajuste han sido: género, edad, hipertensión arterial, diabetes mellitus, estado de fumador y c-no-HDL en un grupo. En el otro grupo, formado por pacientes que presentaban niveles de triglicéridos ≤400mg/dl, se sustituyó el c-no-HDL por el cLDL. Se calcularon curvas de supervivencia (Kaplan-Meier) y se aplicaron dos modelos de regresión de Cox, uno por cada grupo.Resultados: El grupo c-no-HDL presentó un 6,2% de episodios CV no mortales durante el seguimiento, y el grupo cLDL, un 6,0%. Después del ajuste, por cada aumento de 30mg/dl de c-no-HDL, la incidencia de nuevos episodios CV no mortales aumentó un 31% (HR=1,31; IC95%: 1,06-1,61; p=0,018) y en el grupo del cLDL un 27% (HR=1,27; IC95%: 0,97-1,61; p=0,068). Conclusiones: Tras un seguimiento de 10,7años, el c-no-HDL se ha mostrado en nuestra población como un factor pronóstico de enfermedad CV no mortal, pero no el cLDL, aunque su HR se encuentra próxima a la significación estadística (AU)

Introduction: Non-HDL cholesterol (non-HDL-C) is becoming relevant both in its participation in cardiovascular risk assessment and as a therapeutic target. The objective of the present study was to assess the independent predictive capacity of both non-HDL-C and LDL-C (the main priority in dyslipidemias to reduce cardiovascular risk), in cardiovascular morbidity in a population-based sample. Methods: A prospective cohort study involving 1186 individuals in the non-HDL-C group and 1177 in the LDL-C group, followed for 10.7years (SD=2.2), who had not had any previous cardiovascular event. The predictor variables included in the adjustment were: gender, age, arterial hypertension, diabetes mellitus, smoker status and non-HDL-C in one group. In the other group, consisting of patients presenting TG levels of 400mg/dL, non-HDL-C was replaced by LDL-C. Survival curves (Kaplan-Meier) were calculated and two Cox regression models were applied, one for each group. Results: Non-HDL-C group presented 6.2% of non-fatal cardiovascular episodes during follow-up and the LDL-C group 6.0%. After adjustment, for each 30mg/dL increase in non-HDL-C, the incidence of new non-fatal cardiovascular events increased by 31% (HR=1.31, 95%CI: 1.06-1.61; P=.018) and in the LDL-C group by 27% (HR=1.27, 95%CI: 0.97-1.61, P=.068). Conclusions: After a follow-up of 10.7years, non-HDL-C has been shown in our population as a prognostic factor of non-fatal cardiovascular disease, but not LDL-C, although its HR is close to statistical significance (AU)

Evaluation of non-HDL cholesterol as a predictor of non-fatal cardiovascular events in a prospective population cohort. / Valoración del colesterol no HDL como predictor de episodios cardiovasculares no mortales en una cohorte prospectiva de origen poblacional.

INTRODUCTION: Non-HDL cholesterol (non-HDL-C) is becoming relevant both in its participation in cardiovascular risk assessment and as a therapeutic target. The objective of the present study was to assess the independent predictive capacity of both non-HDL-C and LDL-C (the main priority in dyslipidemias to reduce cardiovascular risk), in cardiovascular morbidity in a population-based sample. METHODS: A prospective cohort study involving 1186 individuals in the non-HDL-C group and 1177 in the LDL-C group, followed for 10.7years (SD=2.2), who had not had any previous cardiovascular event. The predictor variables included in the adjustment were: gender, age, arterial hypertension, diabetes mellitus, smoker status and non-HDL-C in one group. In the other group, consisting of patients presenting TG levels of 400mg/dL, non-HDL-C was replaced by LDL-C. Survival curves (Kaplan-Meier) were calculated and two Cox regression models were applied, one for each group. RESULTS: Non-HDL-C group presented 6.2% of non-fatal cardiovascular episodes during follow-up and the LDL-C group 6.0%. After adjustment, for each 30mg/dL increase in non-HDL-C, the incidence of new non-fatal cardiovascular events increased by 31% (HR=1.31, 95%CI: 1.06-1.61; P=.018) and in the LDL-C group by 27% (HR=1.27, 95%CI: 0.97-1.61, P=.068). CONCLUSIONS: After a follow-up of 10.7years, non-HDL-C has been shown in our population as a prognostic factor of non-fatal cardiovascular disease, but not LDL-C, although its HR is close to statistical significance.

Osteomielitis secundaria a espondilodiscitis cervical / Osteomyelitis secondary to cervical spondylodiscitis

La espondilodiscitis es un proceso inflamatorio-infeccioso del disco intervertebral que ocasionalmente puede extenderse a los cuerpos vertebrales adyacentes produciendo una osteomielitis. Esta situación es potencialmente grave, aunque poco frecuente. Los hallazgos clínicos y radiológicos en muchas ocasiones resultan larvados e inespecíficos, al menos inicialmente. Después de dos semanas es posible encontrar ciertos hallazgos radiológicos que ayudan al diagnóstico, como destrucción de las superficies articulares de cuerpos vertebrales, con erosiones e irregularidades, así como pinzamiento o pérdida del espacio discal. A veces es posible identificar en la radiografía una masa de partes blandas prevertebral. La tomografía computerizada puede ayudar al diagnóstico. El 'patrón oro' para su valoración radiológica, se establecerá por resonancia magnética, que permite valorar los hallazgos en fases más precoces, detectando edema en los discos y en los platillos vertebrales, así como la afectación de partes blandas adyacentes (AU)

Spondylodiscitis is an infectious inflammatory process of the intervertebral disc that may occasionally spread to the adjacent vertebral bodies, producing osteomyelitis. This situation is potentially serious, but rare. Clinical and radiological findings are often nonspecific and latent, at least initially. After two weeks certain radiological findings that help diagnosis may be encountered, such as destruction of the articular surfaces of vertebral bodies, with erosions and irregularities, and pinching or loss of disc space. Sometimes it is possible to identify a prevertebral soft tissue mass in an x-ray. Computed tomography may help the diagnosis. The 'gold standard' for radiological assessment shall be established by MRI, which evaluates the findings in earlier stages, detecting edema on discs and endplates, and the involvement of adjacent soft tissues (AU)

[Relationship between inflammation marker and all-cause and cardiovascular mortality in a prospective cohort study]. / Relación entre el proceso inflamatorio y la mortalidad de origen cardiovascular y por todas las causas en un estudio de cohortes prospectivo de base poblacional.

INTRODUCTION: Inflammation is present in every stage of the atherosclerosis process, therefore, inflammation hallmarks such as the fibrinogen can be related to the complications in which it intervenes, mortality is one of them. The objective of this study is to assess the association of the fibrinogen with all-cause mortality in men from general population sample obtained by random sampling in the Spanish region of Albacete. METHODS: A total of 506men without cardiovascular events with 10.6years (SD=2.3) of follow-up, volunteered to participate in a prospective cohort study. The assessment of the fibrinogen as a predictor variable has been calculated after adjusting it by age, hypertension, diabetes mellitus, obesity, total cholesterol, HDL-cholesterol/triglycerides ratio, and smoking habit applying a Cox regression model. The adjustment has been made by adding the fibrinogen to the model, as a qualitative variable (<400 and ≥400mg/dl). RESULTS: The average age of the participants was 46.6years old (DE=16.8). After the adjustment, the hyperfibrinogenemia (≥400mg/dl) showed a hazard ratio (HR) for all-cause mortality of 1.85 (95%CI: 1.05-3.26) and for cardiovascular mortality HR=2.69 (95%CI: 1.09-6.63). CONCLUSIONS: In men without cardiovascular events of our study, fibrinogen was showed as an independent predictor of all-cause mortality and cardiovascular mortality.

Índice tobillo-brazo e incidencia de la mortalidad por todas las causas y morbilidad cardiovascular en una cohorte prospectiva de origen poblacional / Ankle-brachial index and the incidence of all-cause mortality and cardiovascular morbidity in a prospective cohort study of a general population

Introducción El objetivo del estudio ha sido valorar la capacidad predictiva del índice tobillo-brazo (ITB) en la mortalidad por todas las causas y en el criterio compuesto de valoración morbilidad de causa cardiovascular (CV) y mortalidad total en una muestra de origen poblacional. Métodos Estudio de cohortes prospectivo en el que han participado 1.143 individuos seguidos durante 10,8 años (DE=2,2) libres de eventos CV. El ITB se estratificó en 2 niveles: menos de 0,9 y entre 0,9 y 1,4. Las variables predictoras incluidas en el ajuste fueron: sexo, edad (corte en 50 años), hipertensión arterial, diabetes mellitus, obesidad, hipercolesterolemia (corte en 200mg/dl), cociente cHDL/triglicéridos, fumador e hiperfibrinogenemia. Se calcularon curvas de supervivencia (Kaplan-Meier) y se aplicó un modelo de regresión de Cox.ResultadosLa edad media de los participantes (56,8% mujeres) fue de 47,1 años (DE=17,4), rango 18-91 años. Un 6,9% de la muestra presentó un ITB menor de 0,9. Tras el ajuste, un ITB menor de 0,9 presentó para la mortalidad por todas las causas una hazard ratio (HR) de 1,90, intervalo de confianza (IC) del 95%: 1,10-3,26, y para el combinado morbilidad CV y mortalidad por todas las causas una HR de 1,69 (IC del 95%: 1,07-2,67). Conclusiones Un ITB<0,9 ha demostrado ser un factor de riesgo independiente de mortalidad por todas las causas y del combinado morbilidad CV y mortalidad global tras un seguimiento de 10,8 años en la muestra procedente de nuestra población (AU)

Introduction: The aim of this study was to investigate the predictive value of the ankle-brachialindex (ABI) in all-cause mortality and composite end-point all-cause mortality and cardiovascularmorbidity in a sample of a general population. Methods: We performed a prospective cohort study of 1143 individuals free of cardiovascularevents followed up for 10.8 years (SD = 2.2). The ABI was stratified in two levels: less than 0.9and between 0.9 and 1.4. The predictive variables included in the adjustment were sex, age(cut-off: 50 years), hypertension, diabetes, obesity, hypercholesterolemia (cut-off: 200 mg/dl),high-density lipoprotein-cholesterol (HDLc)/triglyceride ratio, smoking and hyperfibrinogenemia. Kaplan-Meier survival curves and multivariate Cox proportional hazards analysis wereused. Results: The mean age of the participants (56.8% female) was 47.1 years (SD = 17.4), range 18-91years. An ABI value < 0.9 was found in 6.9% of the sample. After adjustment, an ABI of < 0.9 hada hazard ratio (HR) of 1.90 [95% confidence interval (CI) 1.10-3.26] for all-cause mortality, andan HR of 1.69 (95% CI 1.07-2.67) for composite all-cause mortality and cardiovascular morbidity.Conclusions: In our population, an ABI < 0.9 was a risk factor independent of all-cause mortalityand of composite all-cause mortality and cardiovascular morbidity after a follow-up of 10.8years (AU)

Crisis Hipertensivas / Hypertensive crises

Las crisis hipertensivas constituyen un motivo frecuente de consulta en los servicios de urgencias.Aproximadamente un 1-2% de los pacientes hipertensos desarrollarán una crisis hipertensiva en algúnmomento de su vida. El presente trabajo pretende revisar las guías clínicas de referencia más actualesen el manejo de esta patología, con el fi n de poder plantear unas recomendaciones clínicas. El temade estudio suele estar incluido en los documentos de consenso que sobre el manejo de la hipertensiónarterial se han publicado, los cuales son muy similares en cuanto a contenidos y recomendaciones.Las guías clínicas evaluadas son muy similares en cuanto a contenidos y recomendaciones, incluyendocasi todas un apartado de introducción, clasifi cación, defi niciones, y manejo general, diferenciandoentre urgencias y emergencias hipertensivas dependiendo de la ausencia o presencia de lesión aguda de órganos diana de la hipertensión arterial.Son escasos los ensayos clínicos aleatorizados publicados que han comparado diferentes fármacoso estrategias de manejo de las crisis hipertensivas.Se han encontrado guías sobre el manejo de la HTA que sustentan sus recomendaciones en niveles de evidencia, pero no se han encontrado guías similares para las crisis hipertensivas, con excepción del manejo de la pre-eclampsia/eclampsia

Hypertensive crises are a frequent motive for consultation in the emergency services. Approximately1-2% of hypertensive patients develop a hypertensive crisis at some time of their lives. The presentwork aims to review the most recent clinical manuals for management of this condition, in order topropose some clinical recommendations. The subject of this study is usually treated in the consensusdocuments published on the management of arterial hypertension.The clinical manuals evaluated have very similar contents and recommendations, almost all of themincluding an introduction section, classifi cation, defi nitions and general management. Differencesappear, however, in hypertensive urgencies and emergencies depending on the absence or presenceof acute lesion of target organs of the arterial hypertension.There are few published randomised clinical trials that have compared different drugs or managementstrategies for hypertensive crises.Manuals have been found on the management of AHT that base their recommendations on evidence,but similar manuals for hypertensive crises do not exist, except for the management of preeclampsia/eclampsia