Putative Secondary Structure at 5'UTR as a Potential Antiviral Target against SARS-CoV-2.

SARS-CoV-2 is an enveloped positive-sense single-stranded RNA coronavirus that causes COVID-19, of which the current outbreak has resulted in a high number of cases and fatalities throughout the world, even vaccine doses are being administered. The aim of this work was to scan the SARS-CoV-2 genome in search for therapeutic targets. We found a sequence in the 5'UTR (NC\_045512:74-130), consisting of a typical heptamer next to a structured region that may cause ribosomal frameshifting. The potential biological value of this region is relevant through its low similarity with other viruses, including coronaviruses related to SARS-CoV, and its high sequence conservation within multiple SARS-CoV-2 isolates. We have predicted the secondary structure of the region by means of different bioinformatic tools. We have suggested a most probable secondary structure to proceed with a 3D reconstruction of the structured segment. Finally, we carried out virtual docking on the 3D structure to look for a binding site and then for drug ligands from a database of lead compounds. Several molecules that could be probably administered as oral drugs show promising binding affinity within the structured region, and so it could be possible interfere its potential regulatory role.

Efecto de la variabilidad glucémica intrahospitalaria en la mortalidad de los pacientes con diabetes / Effect of in-hospital glycemic variability on mortality in patients with diabetes

Introducción El objectivo fue evaluar la importancia de glucemia media (GM) y variabilidad glucémica (VG) durante la hospitalización sobre la mortalidad tras el alta.Material y métodosEstudio de cohortes retrospectivo longitudinal analítico. Se incluyeron pacientes dados de alta del Servicio de Medicina Interna con algún diagnóstico relacionado con la diabetes. El pronóstico evaluado fue la mortalidad. Se recogieron durante el ingreso variables clínicas, analíticas y relacionadas con el control glucémico hospitalario (GM, VG e hipoglucemias). La VG se midió con el coeficiente de variación (CV).Se calcularon las tasas de mortalidad por cada 1000 pacientes-año y se compararon con curvas de Kaplan-Meier. La determinación de los factores predictivos de mortalidad se realizó mediante regresión de Cox.ResultadosSe incluyeron 276 pacientes con edad media 77,6 (DE 10,2) años. La duración mediana del seguimiento extrahospitalario fue de 2,7 años.En análisis multivariante, una GM > 140 (HR=1,72; IC 95% 1,14-2,61; p=0,01) y un CV > 0,29 (HR=1,52; IC 95% 1,12-2,06; p=0,006), no así la presencia de hipoglucemias, se asociaron a incremento del riesgo de mortalidad de forma aditiva e independiente. Tener una GM > 140 simultáneamente con un CV > 0,29 incrementó las tasas de mortalidad (123 vs. 317 por 1.000 pacientes-año; p <0,001) y el riesgo ajustado de mortalidad (HR=2,70; IC 95% 1,71-4,27; p<0,001) respecto a tener una GM ≤ 140mg/dl.ConclusiónLa presencia simultánea de GM y VG elevadas constituye una potente herramienta de estratificación del riesgo de mortalidad tras el alta hospitalaria. (AU)

Introduction The aim of this study was to evaluate the impact of mean blood glucose (MBG) and glycaemic variability (GV) during hospitalisation on mortality after discharge.Material and methodsWe conducted a retrospective longitudinal analytical cohort study that included patients discharged form a department of internal medicine with a diabetes-related diagnosis The evaluated prognosis was mortality. During hospitalisation, the patients’ clinical, laboratory and glycaemic control-related variables were recorded (MBG, GV and hypoglycaemia). The GV was measured with the coefficient of variation (CV).We calculated the mortality rates for every 1000 patient-years and compared them with Kaplan-Meier curves. We determined the predictors of mortality by performing a Cox regression.ResultsThe study included 276 patients with a mean age of 77.6 (SD, 10.2) years. The median outpatient follow-up duration was 2.7 years.In the multivariate analysis, an MBG >140mg/dl (HR, 1.72; 95% CI 1.14–2.61; p=.01) and a CV >0.29 (HR, 1.52; 95% CI 1.12–2.06; p=.006) but not the presence of hypoglycaemia were additively and independently associated with an increased risk of mortality. An MBG >140mg/dl with a CV >0.29 increased the mortality rates (123 vs. 317 per 1000 patient-year; p <.001) and the adjusted mortality risk (HR, 2.70; 95% CI 1.71–4.27; p<.001) compared with having an MBG ≤140mg/dl.ConclusionThe simultaneous presence of a high MBG level and CV constitutes a powerful tool for stratifying mortality risk after hospital discharge. (AU)

Effect of in-hospital glycemic variability on mortality in patients with diabetes.

INTRODUCTION: The aim of this study was to evaluate the impact of mean blood glucose (MBG) and glycaemic variability (GV) during hospitalisation on mortality after discharge. MATERIAL AND METHODS: We conducted a retrospective longitudinal analytical cohort study that included patients discharged form a department of internal medicine with a diabetes-related diagnosis. The evaluated prognosis was mortality. During hospitalisation, the patients' clinical, laboratory and glycaemic control-related variables were recorded (MBG, GV and hypoglycaemia). The GV was measured with the coefficient of variation (CV). We calculated the mortality rates for every 1000 patient-years and compared them with Kaplan-Meier curves. We determined the predictors of mortality by performing a Cox regression. RESULTS: The study included 276 patients with a mean age of 77.6 (SD, 10.2) years. The median outpatient follow-up duration was 2.7 years. In the multivariate analysis, an MBG > 140 mg/dL (HR = 1.72; 95% CI 1.14-2.61; p = .01) and a CV > 0.29 (HR = 1.52; 95% CI 1.12-2.06; p = .006), but not the presence of hypoglycaemia, were additively and independently associated with an increased risk of mortality. An MG > 140 mg/dL with a CV > 0.29 increased the mortality rates (123 vs. 317 per 1000 patient-year; p < .001) and the adjusted mortality risk (HR = 2.70; 95% CI 1.71-4.27; p < .001) compared with having an MBG ≤ 140 mg/dL. CONCLUSION: The simultaneous presence of a high MBG level and CV constitutes a powerful tool for stratifying mortality risk after hospital discharge.

Direct oral anticoagulants for the treatment and prevention of venous thromboembolism in patients with cancer: current evidence

Venous thromboembolic disease (VTED) is a common and clinically important complication in patients with cancer, contributing to its mortality and morbidity. Direct oral anticoagulant agents (DOACs), including direct thrombin inhibitors and direct factor Xa inhibitors, are as effective as vitamin K antagonists for the treatment of VTED and are associated with less frequent and severe bleeding. They have advantages over low-molecular-weight heparin, but comparative long-term efficacy and safety data are lacking for these compounds. Recent randomized clinical trials suggest a role for DOACs in the treatment of VTED in patients with cancer. This review will discuss the existing evidence and future perspectives on the role of DOACs in the treatment of VTE based on the current evidence about their overall efficacy and safety and the limited information in patients with cancer; in addition, we will briefly review their pharmacokinetic properties with special reference to potential interactions (AU)

False-positive fecal immunochemical test results in colorectal cancer screening and gastrointestinal drug use.

PURPOSE: The study aimed to determine the influence of drug treatments (proton pump inhibitors [PPIs] combined with other drugs) on the false-positive (FP) rate in the fecal immunochemical test (FIT). METHODS: Patients undergoing colonoscopy in the setting of a CRC screening program due to a positive FIT result were included prospectively. Demographic data and drug intake of PPIs, antiplatelet therapy (APA), anticoagulants, selective serotonin reuptake inhibitors (SSRIs), and nonsteroidal anti-inflammatory drugs (NSAIDs) were collected. An FP FIT result was considered normal colonoscopy or with nonneoplastic pathology (NNP). Logistic regression models were used to evaluate the effect of these drugs on the rate of FP FIT results. RESULTS: We included 515 patients, and 59% (304/515) were males. The rate of FP FIT results was 48% (249/515). Study drug use was higher in patients > 60 years old and females than in those < 60 years old and males (p < 0.001 and p = 0.049, respectively). Multivariate logistic regression revealed that female sex (OR = 2.7 95% CI 1.9-3.9), NNP (OR = 1.5 95% CI 1.1-2.2), and the use of any of the study drugs (OR = 1.4 95% CI 0.9-2.0) were independent risk factors for FP FIT results. The risk of FP FIT results was significantly higher in PPI users than in nonusers (OR = 1.8 95% CI 1.1-2.9), specifically when PPIs were combined with other drugs (OR = 2.01 95% CI 1.1-3.6) only in men. CONCLUSION: Female sex, NNP, and PPIs combined with other drugs in males were identified as independent risk factors for FP FIT results.

Clinical outcomes of FOLFIRINOX and gemcitabine–nab paclitaxel for metastatic pancreatic cancer in the real world setting

Background/objectives The incidence of pancreatic cancer is increasing in developed countries. The incorporation of new therapies, to the first-line treatment of patients with good performance status led to better survival in clinical trials. However, there is a wide variability in their use and some concerns about the treatment of elderly patients who were not included in the clinical trials. Methods This is a retrospective multicenter study. Data from consecutive patients diagnosed with metastatic pancreatic cancer (mPC) treated with FOLFIRINOX (FFX) or gemcitabine plus nab-paclitaxel (GnP) were analysed to evaluate efficacy (overall survival—OS) and toxicity. Results A total of 119 patients were included. 49.6% were treated with FFX and 50.4% with GNP in first-line. The median OS was 12 months with no statistically significant differences between both regimens (12.7 m for FFX vs 10.2 m for GnP). Elevated Ca 19.9 levels and neutrophil–lymphocyte ratio (NLR) increased the risk of death. Patients who received both regimens in first/second line had a median OS longer than 15 months whichever the sequence. 32 patients (27%) were older than 70-y. 54% patients received a second-line treatment, 56% in the FFX group and 44% in the GnP group. The median OS for patients older than 70 was 9.5 m versus 12.3 m for patients younger than 70. Progression of the disease was the cause of death in 67.6% of the patients. Conclusions In our setting, the use of FFX and GnP for treating mPC is quite similar, but superiority could not be demonstrated for any of the schemes in the first line. OS was determined by basal levels of Ca 19.9 and NLR. Patients receiving both regimens in first/second line whichever the sequence, exhibited the best survival rates. In our series, elderly patients had poorer survival rates (AU)

Clinical outcomes of FOLFIRINOX and gemcitabine-nab paclitaxel for metastatic pancreatic cancer in the real world setting.

BACKGROUND/OBJECTIVES: The incidence of pancreatic cancer is increasing in developed countries. The incorporation of new therapies, to the first-line treatment of patients with good performance status led to better survival in clinical trials. However, there is a wide variability in their use and some concerns about the treatment of elderly patients who were not included in the clinical trials. METHODS: This is a retrospective multicenter study. Data from consecutive patients diagnosed with metastatic pancreatic cancer (mPC) treated with FOLFIRINOX (FFX) or gemcitabine plus nab-paclitaxel (GnP) were analysed to evaluate efficacy (overall survival-OS) and toxicity. RESULTS: A total of 119 patients were included. 49.6% were treated with FFX and 50.4% with GNP in first-line. The median OS was 12 months with no statistically significant differences between both regimens (12.7 m for FFX vs 10.2 m for GnP). Elevated Ca 19.9 levels and neutrophil-lymphocyte ratio (NLR) increased the risk of death. Patients who received both regimens in first/second line had a median OS longer than 15 months whichever the sequence. 32 patients (27%) were older than 70-y. 54% patients received a second-line treatment, 56% in the FFX group and 44% in the GnP group. The median OS for patients older than 70 was 9.5 m versus 12.3 m for patients younger than 70. Progression of the disease was the cause of death in 67.6% of the patients. CONCLUSIONS: In our setting, the use of FFX and GnP for treating mPC is quite similar, but superiority could not be demonstrated for any of the schemes in the first line. OS was determined by basal levels of Ca 19.9 and NLR. Patients receiving both regimens in first/second line whichever the sequence, exhibited the best survival rates. In our series, elderly patients had poorer survival rates.

Direct oral anticoagulants for the treatment and prevention of venous thromboembolism in patients with cancer: current evidence.

Venous thromboembolic disease (VTED) is a common and clinically important complication in patients with cancer, contributing to its mortality and morbidity. Direct oral anticoagulant agents (DOACs), including direct thrombin inhibitors and direct factor Xa inhibitors, are as effective as vitamin K antagonists for the treatment of VTED and are associated with less frequent and severe bleeding. They have advantages over low-molecular-weight heparin, but comparative long-term efficacy and safety data are lacking for these compounds. Recent randomized clinical trials suggest a role for DOACs in the treatment of VTED in patients with cancer. This review will discuss the existing evidence and future perspectives on the role of DOACs in the treatment of VTE based on the current evidence about their overall efficacy and safety and the limited information in patients with cancer; in addition, we will briefly review their pharmacokinetic properties with special reference to potential interactions.

Hepatocarcinoma fibrolamelar. Revisión de sus características diferenciales a partir de nuestra serie / Fibrolamellar hepatocellular carcinoma. Differencial characteristics based on our own case series

Introducción. El hepatocarcinoma fibrolamelar (CHCFL) es un tumor infrecuente, de aparición en adultos jóvenes y sobre hígado sano. Clásicamente considerado una variante del carcinoma hepatocelular (CHC), difieren en tantos aspectos, que debieranconceptuarse como entidades diferentes. El objetivo de este trabajo es refrescar sus características, haciendo hincapié en las diferenciales, para ser tenido en consideración ante lesiones hepáticas sólidas ocupantes de espacio en pacientes jóvenes. Material ymétodo.Estudio descriptivo retrospectivo de las características de 5 casos de CHCFL intervenidos en la unidad de cirugía hepatobiliopancreática un hospital de tercer nivel. Resultados. Cinco casos, edad media 31.8 años, mujer/hombre 4/1. Todos ellos sobrehígado sano, con clínica inespecífica. Radiológicamente e histopatológicamente cumplen las características típicas de este tumor.Sometidos en todos los casos a resecciones quirúrgicas amplias, y reintervenidos, por recidiva, 2 casos, uno de ellos en forma detrasplante hepático. La tabla 1 recoge todas las características epidemiológicas y clínicas, datos operatorios y supervivencia globaly libre de enfermedad de los pacientes incluidos en el estudio. Discusión. De curso clínico insidioso y silente en muchas ocasiones,el diagnóstico suele ser tardío, con grandes masas tumorales en las pruebas de imagen. Actualmente el tratamiento quirúrgico esel único potencialmente curativo. Pese a una supervivencia prolongada, la tasa de recidiva es muy elevada, precisando en muchoscasos intervenciones reiteradas. Los resultados en nuestra serie son acordes con la literatura y podrían calificarse como paradigmade las características anatomoclínicas, terapéuticas y pronósticas de este tipo de tumor. (AU)

Introduction. Fibrolamellar hepatocellular carcinoma is an infrequent tumour, which appears in young adults and on healthy liver.It has been classically considered a subtype of hepatocellular carcinoma, but they differ in such many aspects they could be considered separately. The objective of this review is to refresh its differential characteristics in order to take into account in the differentialdiagnosis of hepatic solid lessions in young adults. Material and methods. Descriptive retrospective study of the principles characteristics of the five fibrolamellar hepatocellular carcinoma operated patients by the hepatobilliary surgery team of our hospital.Results. Five cases, medium age 31.8 years, women/men 4/1. All of them in healthy liver with inespecific symptoms and radiollogicaland hystopathological typical characteristics. All of them having enlarged hepatic ressections and reoperated two of them becauseof recurrence, in one case in form of hepatic transplantation. Table 1 collect all the epidemiological and clinical characteristics, operation reports, global and recurrence free survival of all patientes included in the study. Discussion. Having insidious and silentdevelopment in many cases, diagnosis can be delayed, appearing big tumoral masses on the imaging tests. Nowadays, surgery is the only curative treatment. Despite long survival periods, the recurrence rate is very high, needing sometimes being reoperated. Our results are in the line of the literature results and could be classified as the paradigm of anatomoclinic, therapeutic and prognostic characteristics of this type of tumour. (AU)

Effect of in-hospital glycemic variability on mortality in patients with diabetes. / Efecto de la variabilidad glucémica intrahospitalaria en la mortalidad de los pacientes con diabetes.

INTRODUCTION: The aim of this study was to evaluate the impact of mean blood glucose (MBG) and glycaemic variability (GV) during hospitalisation on mortality after discharge. MATERIAL AND METHODS: We conducted a retrospective longitudinal analytical cohort study that included patients discharged form a department of internal medicine with a diabetes-related diagnosis The evaluated prognosis was mortality. During hospitalisation, the patients' clinical, laboratory and glycaemic control-related variables were recorded (MBG, GV and hypoglycaemia). The GV was measured with the coefficient of variation (CV). We calculated the mortality rates for every 1000 patient-years and compared them with Kaplan-Meier curves. We determined the predictors of mortality by performing a Cox regression. RESULTS: The study included 276 patients with a mean age of 77.6 (SD, 10.2) years. The median outpatient follow-up duration was 2.7 years. In the multivariate analysis, an MBG >140mg/dl (HR, 1.72; 95% CI 1.14-2.61; p=.01) and a CV >0.29 (HR, 1.52; 95% CI 1.12-2.06; p=.006) but not the presence of hypoglycaemia were additively and independently associated with an increased risk of mortality. An MBG >140mg/dl with a CV >0.29 increased the mortality rates (123 vs. 317 per 1000 patient-year; p <.001) and the adjusted mortality risk (HR, 2.70; 95% CI 1.71-4.27; p<.001) compared with having an MBG ≤140mg/dl. CONCLUSION: The simultaneous presence of a high MBG level and CV constitutes a powerful tool for stratifying mortality risk after hospital discharge.

Pleiotropic effects of heparins: does anticoagulant treatment increase survival in cancer patients?

The association between venous thromboembolism (VTE) and cancer has been recognized for more than 100 years. Numerous studies have been performed to investigate strategies to decrease VTE incidence and to establish whether treating VTE impacts cancer progression and overall survival. Accordingly, it is important to understand the role of the hemostatic system in tumorigenesis and progression, as there is abundant evidence associating it with cell survival and proliferation, tumor angiogenesis, invasion, and dissemination, and metastasis formation. In attempts to further the scientific evidence, several studies examine survival benefits in cancer patients treated with anticoagulant therapy, specifically treatment with vitamin K antagonists, unfractionated heparin, and low-molecular-weight heparin. Several studies and meta-analyses have been conducted with a special focus on brain tumors. However, no definitive conclusions have been obtained, and more well-designed clinical trials are needed

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Respuesta de los autores: Onicomadesis en paciente adulto inmunocompetente / Author's reply: Onychomadesis in an immunocompetent adult patient

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Pleiotropic effects of heparins: does anticoagulant treatment increase survival in cancer patients?

The association between venous thromboembolism (VTE) and cancer has been recognized for more than 100 years. Numerous studies have been performed to investigate strategies to decrease VTE incidence and to establish whether treating VTE impacts cancer progression and overall survival. Accordingly, it is important to understand the role of the hemostatic system in tumorigenesis and progression, as there is abundant evidence associating it with cell survival and proliferation, tumor angiogenesis, invasion, and dissemination, and metastasis formation. In attempts to further the scientific evidence, several studies examine survival benefits in cancer patients treated with anticoagulant therapy, specifically treatment with vitamin K antagonists, unfractionated heparin, and low-molecular-weight heparin. Several studies and meta-analyses have been conducted with a special focus on brain tumors. However, no definitive conclusions have been obtained, and more well-designed clinical trials are needed.

Fitofotodermatitis diseminada, una entidad nosológica a conocer / Disseminated phytodermatitis: a nosological entity to know

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Tratamiento endoscópico de una urticaria recidivante / Endoscopic treatment of a recurrent urticaria

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