Krebs von den Lungen-6 glycoprotein circulating levels are not useful as prognostic marker in COVID-19 pneumonia: A large prospective cohort study.

Coronavirus disease 2019 (COVID-19) has rapidly expanded worldwide. Currently, there are no biomarkers to predict respiratory worsening in patients with mild to moderate COVID-19 pneumonia. Small studies explored the use of Krebs von de Lungen-6 circulating serum levels (sKL-6) as a prognostic biomarker of the worsening of COVID-19 pneumonia. We aimed at a large study to determine the prognostic value of sKL-6 in predicting evolving trends in COVID-19. We prospectively analyzed the characteristics of 836 patients with COVID-19 with mild lung disease on admission. sKL-6 was obtained in all patients at least at baseline and compared among patients with or without respiratory worsening. The receiver operating characteristic curve was used to find the optimal cutoff level. A total of 159 (19%) patients developed respiratory worsening during hospitalization. Baseline sKL-6 levels were not higher in patients who had respiratory worsening (median {IQR} 315.5 {209-469} vs. 306 {214-423} U/ml p = 0.38). The last sKL-6 and the change between baseline and last sKL-6 were higher in the respiratory worsening group (p = 0.02 and p < 0.0001, respectively). The best sKL-6 cutoff point for respiratory worsening was 497 U/ml (area under the curve 0.52; 23% sensitivity and 85% specificity). sKL-6 was not found to be an independent predictor of respiratory worsening. A conditional inference tree (CTREE) was not useful to discriminate patients at risk of worsening. We found that sKL-6 had a low sensibility to predict respiratory worsening in patients with mild-moderate COVID-19 pneumonia and may not be of use to assess the risk of present respiratory worsening in inpatients with COVID-19 pneumonia.

Sarilumab (IL-6R antagonist) in critically ill patients with cytokine release syndrome by SARS-CoV2.

ABSTRACT: Blocking IL-6 pathways with sarilumab, a fully human anti-IL-6R antagonist may potentially curb the inflammatory storm of SARS-CoV2. In the present emergency scenario, we used "off-label" sarilumab in 5 elderly patients in life-threatening condition not candidates to further active measures. We suggest that sarilumab can modulate severe COVID-19-associated Cytokine Release Syndrome.

Drug related problems in clinical practice: a cross-sectional study on their prevalence, risk factors and associated pharmaceutical interventions.

Drug-related problems (DRP) cause preventable negative health outcomes, especially during hospital admissions. The aim of our study was to examine the prevalence and characteristics of DRP in regular clinical pharmacy, as well as to determine those factors associated with a higher risk of DRP in the hospital setting. We analyzed data from a standardized registry database of regular pharmacy practice (2015- 2016). DRP were classified according to the Pharmaceutical Care Network Europe v6.2 classification. Cross-sectional data were obtained from 1602 adults admitted to medical wards. Crude and adjusted binary logistic regressions were performed to identify associations between potential risk factors and DRP. Overall DRP prevalence was high across medical specialties (45,1%), in a population characterized by advanced age, polypharmacy and multimorbidity. Problems leading to DRP were mainly classified into two domains (effectiveness and adverse reactions), being drug and dose selection the most frequent causes. Interventions were accepted and DRP were totally or partially solved in 74.1% and 4.81% of cases, respectively. In the adjusted model polypharmacy, allergies, BMI > 25 kg/m2 and clearance < 30 mL/min were associated with a higher risk of DRP. The participation of clinical pharmacists into multidisciplinary teams promotes the detection and solution of DRP. Polypharmacy, obesity, renal impairment and allergy are associated with a higher risk of DRP during admission.

Effectiveness and safety of intravenous tocilizumab to treat COVID-19-associated hyperinflammatory syndrome: Covizumab-6 observational cohort.

Although the starting event in COVID-19 is a viral infection some patients present with an over-exuberant inflammatory response, leading to acute lung injury (ALI) and adult respiratory distress syndrome (ARDS). Since IL-6 plays a critical role in the inflammatory response, we assessed the efficacy and safety of tocilizumab (TCZ) in this single-centre, observational study in all Covid-19 in-patient with a proven SARS-CoV-2 rapidly progressing infection to prevent ALI and ARDS. 104 patients with COVID-19 treated with TCZ had a lower mortality rate (5·8%) compared with the regional mortality rate (11%), hospitalized patient's mortality (10%), and slightly lower than hospitalized patients treated with our standard of care alone (6%). We found that TCZ rapidly decreased acute phase reactants, ferritin and liver release of proteins. D-Dimer decreased slowly. We did not observe specific safety concerns. Early administration of IL6-R antagonists in COVID-19 patients with impending hyperinflammatory response, may be safe and effective treatment to prevent, ICU admission and further complications.

Mediastinitis aguda como complicación atípica de una mononucleosis infecciosa / Acute mediastinitis as a rare complication of an infectious mononucleosis

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Causas de no consecución del objetivo terapéutico del colesterol de las lipoproteínas de baja densidad en pacientes de alto y muy alto riesgo vascular controlados en Unidades de Lípidos y Riesgo Vascular. Estudio EROMOT / Causes of failure to achieve the low density lipoprotein cholesterol therapeutic target in patients with high and very high vascular risk controlled in Lipid and Vascular Risk Units. EROMOT study

Objetivos: Determinar el grado de consecución del objetivo terapéutico del colesterol de las lipoproteínas de baja densidad (cLDL) en pacientes de alto y muy alto riesgo vascular atendidos en las unidades de lípidos, así como las causas de no consecución. Pacientes y método: Estudio observacional retrospectivo multicéntrico. Se incluyó a los pacientes mayores de 18 años con alto o muy alto riesgo vascular, según los criterios de la Guía europea de prevención cardiovascular de 2012, remitidos de forma consecutiva a las unidades de lípidos entre enero y junio del 2012 y con seguimiento a los 2 años de la primera visita. Resultados: Se incluyó a 243 pacientes procedentes de 16 unidades de lípidos. La edad media fue de 52,2 años (DE 13,7) con un 62,6% de varones. Un 40,3% eran de muy alto riesgo. En la primera visita seguían tratamiento hipolipidemiante el 86,8% (en combinación 25,1%) y en la segunda visita el 95,0% (en combinación 47,3%) (p<0,001). El 28% (IC del 95%: 22,4-34,1) alcanzó el objetivo terapéutico. Sobre las causas de no consecución, el 24,6% de ellas estaban relacionadas con el medicamento (10,3% máxima dosis tolerada y 10,9% por aparición de efectos adversos), el 43,4% con el médico (19,4% por inercia, 13,7% por considerar que ya ha llegado al objetivo) y con el paciente el 46,9%, destacando el incumplimiento terapéutico (31,4%). Conclusiones: Se consiguieron los objetivos de cLDL en cerca de un tercio de los pacientes. La baja adherencia del paciente, seguida de la inercia médica, son las causas más frecuentes que pueden explicar estos resultados (AU)

Objectives: Determination of the level of achievement of the low density lipoprotein cholesterol (LDL-C) therapeutic target in patients with high and very high vascular risk treated in Lipid Units, as well as the causes of non-achievement. Patients and method: Multicentre retrospective observational study that included patients over 18 years with high and very high vascular risk, according to the criteria of the 2012 European Guidelines on Cardiovascular Disease Prevention, referred consecutively to Lipid Units between January and June 2012 and with follow-up two years after the first visit. Results: The study included a total of 243 patients from 16 lipid units. The mean age was 52.2 years (SD 13.7), of whom 62.6% were males, and 40.3% of them were very high risk. At the first visit, 86.8% (25.1% in combination) and 95.0% (47.3% in combination) in the second visit (P<.001) were treated with lipid-lowering treatment. The therapeutic target was achieved by 28% (95 CI: 22.4-34.1). As regards the causes of non-achievement, 24.6% were related to the medication (10.3% maximum tolerated dose and 10.9% due to the appearance of adverse effects), 43.4% due to the physician (19.4% by inertia, 13.7% considering that target already reached), and 46.9% due to the patient, highlighting the therapeutic non-compliance (31,4%). Conclusions: LDL-C targets were achieved in about one-third of patients. The low adherence of the patient, followed by medical inertia are the most frequent causes that can explain these results (AU)

Causes of failure to achieve the low density lipoprotein cholesterol therapeutic target in patients with high and very high vascular risk controlled in Lipid and Vascular Risk Units. EROMOT study. / Causas de no consecución del objetivo terapéutico del colesterol de las lipoproteínas de baja densidad en pacientes de alto y muy alto riesgo vascular controlados en Unidades de Lípidos y Riesgo Vascular. Estudio EROMOT.

OBJECTIVES: Determination of the level of achievement of the low density lipoprotein cholesterol (LDL-C) therapeutic target in patients with high and very high vascular risk treated in Lipid Units, as well as the causes of non-achievement. PATIENTS AND METHOD: Multicentre retrospective observational study that included patients over 18 years with high and very high vascular risk, according to the criteria of the 2012 European Guidelines on Cardiovascular Disease Prevention, referred consecutively to Lipid Units between January and June 2012 and with follow-up two years after the first visit. RESULTS: The study included a total of 243 patients from 16 lipid units. The mean age was 52.2 years (SD 13.7), of whom 62.6% were males, and 40.3% of them were very high risk. At the first visit, 86.8% (25.1% in combination) and 95.0% (47.3% in combination) in the second visit (P<.001) were treated with lipid-lowering treatment. The therapeutic target was achieved by 28% (95 CI: 22.4-34.1). As regards the causes of non-achievement, 24.6% were related to the medication (10.3% maximum tolerated dose and 10.9% due to the appearance of adverse effects), 43.4% due to the physician (19.4% by inertia, 13.7% considering that target already reached), and 46.9% due to the patient, highlighting the therapeutic non-compliance (31,4%). CONCLUSIONS: LDL-C targets were achieved in about one-third of patients. The low adherence of the patient, followed by medical inertia are the most frequent causes that can explain these results.

Hipertensión arterial resistente sin lesión de órgano diana: un nuevo caso de síndrome de Munchausen / Resistant hypertension and no organ damage: a new case of Munchausen syndrome

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Diferencias en la reducción de la presión arterial en función de la toma de la medicación en horario diurno o nocturno / Differences in the reduction of blood pressure according to drug administration at activity hours or rest hours

Fundamento y objetivo: Se analizaron 123 registros de presión arterial (PA) efectuados mediante monitorización ambulatoria de PA realizados durante el año 2011 en un hospital universitario español de tercer nivel, con el objetivo de determinar si existían diferencias según la hora de la administración de la medicación en las medias de PA en los 3 períodos (24 h, actividad y descanso) en aquellos pacientes que tomaban 2, 3 o 4 fármacos antihipertensivos. Pacientes y método: Se compararon aquellos sujetos que tomaban toda la medicación durante el día (grupo 1, n = 70) con aquellos que tomaban al menos uno de los antihipertensivos por la noche (grupo 2, n = 53). Resultados: Se observaron diferencias significativas, con medias inferiores de PA diastólica en el grupo 2 durante el período de 24 h, actividad y noche; medias inferiores de PA sistólica casual; y medias inferiores de PA media en los 3 períodos, con una tendencia (no significativa) a medias inferiores para PA sistólica a favor del grupo 2. En el cociente de variación noche/día no se alcanzaron diferencias significativas. Sí se encontraron entre ambos grupos en cuanto al número de fármacos utilizado (medias superiores en el grupo 2) y en el tipo de fármaco empleado (betabloqueantes y antagonistas del calcio). Se realizó un análisis multivariante ajustando a estas variables, en el que se mantuvo la significación estadística. Conclusión: La administración de parte de la medicación antihipertensiva por la noche podría contribuir a unas menores cifras de PA, lo que plantea la conveniencia de considerar esta estrategia en pacientes con hipertensión arterial no controlada (AU)

Background and objective: In this study, 123 recordings of blood pressure (BP) obtained by ambulatory BP monitoring were analyzed. These recordings were measured in 2011 in patients from a Spanish tertiary university hospital. All participating patients were treated with 2, 3 or 4 anti-hypertensive drugs. The main aim of this study was to determine differences in BP control, if any, depending on the medication schedule. Thus, BP levels were studied at 3 periods of the day: activity hours, rest hours and 24 h. Patients and method: We compared subjects taking all anti-hypertensive agents during the day (n = 70, group 1) with those taking at least one at night (n = 53, group 2). Results: Significant differences were found on diastolic BP, where group 2 patients had lower levels at activity, 24 h periods and sleep-time. Even if it was not statistically significant, lower levels of systolic BP from group 2 were also observed at activity and 24 h periods as well as lower levels of systolic, diastolic and mean BP at rest hours periods. There were also significant group differences in relation to the number of prescribed agents (with the mean being higher for group 2) and the type of agent (beta-blockers and calcium antagonists were more prevalent in group 2). Nevertheless, the multivariate regression analysis done taking into account these variables did not change the observed statistical significance. Conclusion: The administration of anti-hypertensive drugs at night could be associated with lower BP levels (AU)

[Differences in the reduction of blood pressure according to drug administration at activity hours or rest hours]. / Diferencias en la reducción de la presión arterial en función de la toma de la medicación en horario diurno o nocturno.

BACKGROUND AND OBJECTIVE: In this study, 123 recordings of blood pressure (BP) obtained by ambulatory BP monitoring were analyzed. These recordings were measured in 2011 in patients from a Spanish tertiary university hospital. All participating patients were treated with 2, 3 or 4 anti-hypertensive drugs. The main aim of this study was to determine differences in BP control, if any, depending on the medication schedule. Thus, BP levels were studied at 3 periods of the day: activity hours, rest hours and 24h. PATIENTS AND METHOD: We compared subjects taking all anti-hypertensive agents during the day (n=70, group 1) with those taking at least one at night (n=53, group 2). RESULTS: Significant differences were found on diastolic BP, where group 2 patients had lower levels at activity, 24h periods and sleep-time. Even if it was not statistically significant, lower levels of systolic BP from group 2 were also observed at activity and 24h periods as well as lower levels of systolic, diastolic and mean BP at rest hours periods. There were also significant group differences in relation to the number of prescribed agents (with the mean being higher for group 2) and the type of agent (beta-blockers and calcium antagonists were more prevalent in group 2). Nevertheless, the multivariate regression analysis done taking into account these variables did not change the observed statistical significance. CONCLUSION: The administration of anti-hypertensive drugs at night could be associated with lower BP levels.

[Atherosclerosis and anti-oxidized low density lipoprotein antibodies in an elderly population]. / Aterosclerosis y anticuerpos anti-OxLDL en una población geriátrica.

BACKGROUND: Antibodies to oxidized LDL (anti-OxLDL) have been found to be associated with atherosclerosis. The aim of the study was to evaluate the relationship between anti-OxLDL antibodies and atherosclerosis in the elderly. PATIENTS AND METHOD: We studied several risk factors and different clinical manifestations of atherosclerosis in 100 people older than 65 years and in 48 healthy blood donor controls (age range: 20 to 55 years). Anti-OxLDL antibodies were measured by ELISA. RESULTS: Thirty-one percent of the patients tested positive for anti-OxLDL. This percentage increased in the group of subjects without any risk factor or clinical manifestation (66.6%) as it was the case of the mean optical density (O.D.) value (O.D. = 0.671 vs. 0.357 in our general geriatric population). Most of those with a proven atherosclerotic event tested negative for anti-OxLDL antibodies and a statistically significant difference was shown for those with a calcified aortic arch (P = 0.041, 95% CI 0.15-0.97). Mean value of risk factors and clinical manifestations was 3.50 among anti-OxLDL-negative patients, whereas it was 2.51 in the anti-OxLDL-positive group (P = 0.035, 95% CI 0.07-1.91). Actually, when more adverse effects were present, patients' trend to test negative for anti-OxLDL antibodies was higher. An inverse correlation was observed between anti-OxLDL titers and the relative risk of coronary heart disease (P = 0.020). CONCLUSIONS: The cause of the decrease of free anti-OxLDL antibodies in situations that lead to an oxidative stress is unknown but it may be explained by the formation of immunocomplexes in an effort to ease the clearance of oxidized substrates.