Impact of COVID-19 in the incidence of venous thromboembolism (VTE) and clinical outcomes in cancer patients: a cohort study.

PURPOSE: To determine the incidence of VTE and clinical outcomes in a cohort of cancer patients and COVID-19 infection, and to establish possible predictive factors of VTE. METHODS/PATIENTS: A single-center retrospective cohort study was performed to determine the incidence of VTE and mortality in 118 cancer patients with SARS-CoV-2 infection from March to August 2020. We calculated individual Khorana Risk and CATS-MICA scores in order to evaluate their utility to identify risk of VTE or death. Continuous variables were compared using Wilcoxon or Student's T test, and categorical variables were compared using the Chi-Square or Fisher's exact text among patients with and without VTE. A Log-Rank test was performed to detect mortality differences between the groups. RESULTS: A total of 118 patients were included. VTE global incidence was 4.2% (n = 5), and mortality 25.4% (n = 30). Obesity (p = 0.05), recent chemotherapy (p = 0.049) and use of steroids (p = 0.006) were related to higher risk of VTE in the univariate analysis, although they were not confirmed in the multivariate analysis as independent risk factors. Statistically significant differences in all-cause, COVID-19-related and cancer-related mortality according to the Khorana risk score (KRS) were observed. CATS-MICA score (CMS) also showed statistically significant differences in mortality between low- and high-risk patients. Prediction of risk of VTE development with these scores showed a tendency towards significance. CONCLUSIONS: In this cohort, VTE incidence was similar to previously reported in the general population with SARS-CoV-2 infection. KRS was associated with overall and specific-cause mortality, and might be a useful prognostic tool in this setting.

Sodium-glucose cotransporter 2 inhibition in primary and secondary glomerulonephritis.

BACKGROUND: The role of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in the management glomerular/systemic autoimmune diseases with proteinuria in real-world clinical settings is unclear. METHODS: This is a retrospective, observational, international cohort study. Adult patients with biopsy-proven glomerular diseases were included. The main outcome was the percentage reduction in 24-h proteinuria from SGLT2i initiation to 3, 6, 9 and 12 months. Secondary outcomes included percentage change in estimated glomerular filtration rate (eGFR), proteinuria reduction by type of disease and reduction of proteinuria ≥30% from SGLT2i initiation. RESULTS: Four-hundred and ninety-three patients with a median age of 55 years and background therapy with renin-angiotensin system blockers were included. Proteinuria from baseline changed by -35%, -41%, -45% and -48% at 3, 6, 9 and 12 months after SGLT2i initiation, while eGFR changed by -6%, -3%, -8% and -10.5% at 3, 6, 9 and 12 months, respectively. Results were similar irrespective of the underlying disease. A correlation was found between body mass index (BMI) and percentage proteinuria reduction at last follow-up. By mixed-effects logistic regression model, serum albumin at SGLT2i initiation emerged as a predictor of ≥30% proteinuria reduction (odds ratio for albumin <3.5 g/dL, 0.53; 95% CI 0.30-0.91; P = .02). A slower eGFR decline was observed in patients achieving a ≥30% proteinuria reduction: -3.7 versus -5.3 mL/min/1.73 m2/year (P = .001). The overall tolerance to SGLT2i was good. CONCLUSIONS: The use of SGLT2i was associated with a significant reduction of proteinuria. This percentage change is greater in patients with higher BMI. Higher serum albumin at SGLT2i onset is associated with higher probability of achieving a ≥30% proteinuria reduction.

Diffuse gastric adenocarcinoma during pregnancy and genetic counseling.

We present the case of a 38-year-old woman who, in the context of a 22-week gestation, was diagnosed with diffuse gastric adenocarcinoma. The age of the patient and the way in which the cancer presented itself, make genetic counseling mandatory to rule out hereditary diffuse gastric carcinoma syndrome. This rare entity, of autosomal dominant inheritance and closely linked to mutations in the CDH1 (in most cases) and CTNNA1 genes, is associated with a greater predisposition to develop malignant neoplasms of the breast and stomach. Genetic sequencing ruled out hereditary diffuse gastric cancer syndrome. Unfortunately, 24 months after the cesarean section, our patient dies.

Experiencia en angioplastia percutánea de recoartación de aorta en un solo centro. Resultados a corto, medio y largo plazo / Experience in percutaneous angioplasty of aortic recoartation in a single centre. Short, medium and long-term outcomes

Resumen Introducción: La angioplastia con balón es una técnica que ofrece buenos resultados, especialmente en los casos de recoartación tras cirugía correctora. Objetivo: Analizar los resultados de un centro hospitalario a partir de la introducción de la técnica. Método: Se analizaron 73 pacientes con una edad media de 3.3 años; el 74% eran menores de 1 año y el 72.6% estaban por debajo de 10 kg de peso. Todos los pacientes incluidos fueron casos de recoartación tras cirugía correctora. Resultados: Se observó un resultado efectivo en el 93.1% de los casos, con gradiente residual < 20 mmHg. Durante el seguimiento, el 20.5% precisaron reintervención, la cual fue más frecuente en caso de angioplastia sobre el arco, lesiones asociadas y menores de 1 año. Solo se objetivó una complicación grave relacionada con el procedimiento, que correspondió a una rotura aórtica que no pudo ser solventada con implante de stent cubierto. Conclusiones: La angioplastia percutánea de recoartación de aorta es una técnica segura y efectiva, en especial en los casos de recoartación tras cirugía correctora de lesiones circunscritas al istmo.

Abstract Introduction: Balloon angioplasty is a technique with good outcomes, specially in cases aortic recoartation after correcting surgery. Objective: To analyze our centre results since the introduction of the technique. Method: We analyzed 73 patients with medium age of 3,3 years; 74% were under 1 years old and 72,6% under 10 kg weight. All patients included were cases of recoartation after surgery. Results: Effective results was achieved in 93,1%, obtaining residual gradient less than 20 mmHg. During the following up 20,5% of patients required reintervention, being more frequent in case of aortic arch hypoplasia, associated lesions or patients under 1 year. Only a severe complication was referred, a case of aortic rupture that couldn’t be solved with a covered stent. Conclusions: Percutaneous angioplasty of aortic recoartation is a safe and effective technique, specially in discrete istmic lesions after correcting surgery.

Sacubitril-Valsartan Improves Anemia of Cardiorenal Syndrome (CRS).

BACKGROUND AND AIMS: Anemia is a common complication of heart failure and Chronic Kidney Disease (CKD). Sacubitril-valsartan is a novel therapy for the treatment of chronic Heart Failure with a reduced Ejection Fraction (HFrEF). We have evaluated the short-term effects of sacubitril- valsartan on the anemia of CRS. METHODS: The study group comprised 39 patients with HFrEF, who were followed-up for three months. The study is a retrospective analysis of clinical data. Data of 3 months' and baseline visits were recorded including plasmatic creatinine, glomerular filtration rate, cystatin C, kaliemia, haemoglobin, pro-BNP, and albuminuria. RESULTS: In all, 34 patients ended the follow-up. Mean sacubitril-valsartan dosage at baseline was 101 ± 62 mg/day and 126 ± 59 mg/day at end. Mean hemoglobin increased from 12.2 ± 1.1 g/dl at baseline to 12.9 ± 1.0 g/dl (p = 0.001,). Prevalence of anemia was 64.7% (95%CI, 47.9-78.5%) at baseline and 38.4 (95%CI, 23.9-55.0%) after the follow-up (p = 0.016). Serum cystatin C levels decreased from 2.71 ± 1.0 to 2.48 ± 1.0 mg/l (p = 0.028). Serum K levels remained unchanged (baseline 4.94 ± 0.60, three months visit 4.94 ± 0.61 mmol/l, p = 0.998). CONCLUSION: Sacubitril-valsartan improves anemia in CRS patients. An improvement in serum cystatin levels was observed. Few untoward effects were detected. These findings should be confirmed in wider clinical trials.

Vitamin A deficiency regulates the expression of ferritin in young male Wistar rats / A deficiência de vitamina A regula a expressão de ferritina em ratos Wistar machos jovens

ABSTRACT Objective Iron deficiency and vitamin A deficiency are two of the main micronutrient deficiencies. Both micronutrients are essential for human life and children's development. This study aimed to investigate the effects of vitamin A deficiency on ferritin and transferrin receptors' expression and its relationship with iron deficiency. Methods Five diets with different vitamin A-to-iron ratios were given to thirty five 21-day-old male Wistar rats (separated in groups of seven animals each). The animals received the diet for six weeks before being euthanized. Serum iron and retinol levels were measured as biochemical parameters. Their duodenums, spleens, and livers were analyzed for the expression of ferritin and transferrin receptors by Western Blotting. Results Regarding biochemical parameters, the results show that when both vitamin A and iron are insufficient, the serum iron content (74.74µg/dL) is significantly lower than the control group (255.86µg/dL). The results also show that vitamin A deficiency does not influence the expression of the transferrin receptor, but only of the ferritin one. Conclusion Vitamin A deficiency regulates the expression of ferritin in young male Wistar rats.

RESUMO Objetivo A deficiência de ferro e de vitamina A são duas das principais deficiências de micronutrientes, sendo que ambos são essenciais para a vida humana e o desenvolvimento das crianças. O objetivo deste estudo foi investigar o efeito da deficiência de vitamina A na expressão de ferritina e o receptor de transferrina e sua relação com a deficiência de ferro. Métodos Cinco dietas com diferentes proporções de vitamina A para ferro foram administradas a 35 ratos Wistar machos de 21 dias de vida (sete animais por grupo). Os animais receberam a dieta por seis semanas antes de serem eutanasiados. Os níveis séricos de ferro e retinol foram medidos como parâmetros bioquímicos. Duodeno, baço e fígado foram analisados quanto à expressão de ferritina e o receptor de transferrina por Western Blotting. Resultados Em relação aos parâmetros bioquímicos, os resultados mostram que quando a vitamina A e o ferro são insuficientes, o teor de ferro sérico (74.74µg/dL) é significativamente menor do que no grupo controle (255.86µg/dL). Os resultados também mostram que a deficiência de vitamina A não influencia a expressão do receptor da transferrina, mas da ferritina. Conclusão A deficiência de vitamina A regula a expressão de ferritina em ratos Wistar machos jovens.

mRNA Polyadenylation Machineries in Intestinal Protozoan Parasites.

In humans, mRNA polyadenylation involves the participation of about 20 factors in four main complexes that recognize specific RNA sequences. Notably, CFIm25, CPSF73, and PAP have essential roles for poly(A) site selection, mRNA cleavage, and adenosine residues polymerization. Besides the relevance of polyadenylation for gene expression, information is scarce in intestinal protozoan parasites that threaten human health. To better understand polyadenylation in Entamoeba histolytica, Giardia lamblia, and Cryptosporidium parvum, which represent leading causes of diarrhea worldwide, genomes were screened for orthologs of human factors. Results showed that Entamoeba histolytica and C. parvum have 16 and 12 proteins out of the 19 human proteins used as queries, respectively, while G. lamblia seems to have the smallest polyadenylation machinery with only six factors. Remarkably, CPSF30, CPSF73, CstF77, PABP2, and PAP, which were found in all parasites, could represent the core polyadenylation machinery. Multiple genes were detected for several proteins in Entamoeba, while gene redundancy is lower in Giardia and Cryptosporidium. Congruently with their relevance in the polyadenylation process, CPSF73 and PAP are present in all parasites, and CFIm25 is only missing in Giardia. They conserve the functional domains and predicted folding of human proteins, suggesting they may have the same roles in polyadenylation.

Embarazo y lesión hepática inducida por medicamentos. Reporte de un caso y revisión de la literatura / Pregnancy and drug-induced liver injury. Case report and literature review

La lesión hepática inducida por medicamentos o DILI (del inglés, Drug-Induced Liver Injury) es una condición relativamente rara, y más aún durante el embarazo. Usualmente es subdiagnosticada, y cuando se presenta en nuestro medio, pocas veces es notificada a los sistemas de registros nacionales, con un importante subregistro a nivel nacional y de Latinoamérica. Su forma de presentación clínica, tiempo de latencia, patrón de lesión hepática y reacciones idiosincráticas dificultan el diagnóstico oportuno, así como la ausencia tanto de pruebas diagnósticas objetivas, como de cambios histológicos patognomónicos que confirmen esta entidad. Se presenta el primer caso reportado en la literatura de una mujer en primer trimestre de gestación, quien cursó con DILI secundario al uso de tionamidas por sospecha clínica de hipertiroidismo.

Drug-induced liver injury (DILI) is a relative rare condition among general population and among pregnant women. It is usually underdiagnosed, and when identified, it is rarely notified to the national registry systems, especially locally, and in general in Latin America. Clinical presentation, time before symptom onset, patterns of liver injury and idiosyncratic reactions make an early diagnosis difficult, as well as the absence of diagnostic tests or histological changes that are unique to this pathology to confirm the diagnosis. We present the first case reported in the literature of a woman, who during the first trimester of pregnancy presented with DILI, secondary to the use of thionamides due to suspected hyperthyroidism.

Intrathecal baclofen as a treatment for spasticity: Review of the cases treated in our hospital. / Baclofeno intratecal para el tratamiento de la espasticidad: revisión de los casos presentes tratados en nuestro servicio.

INTRODUCTION: Spasticity represents a medical problem whose incidence is increasing during the last years due to pathologies such as cerebral palsy, stroke, multiple sclerosis, trauma or encephalopathy, affecting both adults and children. The treatments include rehabilitation, pharmacotherapy and surgery, among which we highlight intrathecal baclofen infusion devices. MATERIAL AND METHODS: Intrathecal baclofen devices implanted patients in Clinical Hospital of Santiago de Compostela from 2005 to 2018 were selected for retrospective analysis using assessment of spasticity scales, such as Ashworth scale. Complications are described. RESULTS: Surgery was performed in 17 patients for baclofen pump implant, achieving an improvement of 2 points on the Ashworth Scale in 88,2% of the patients and of 1 point on the Penn Scale in 94%. Complications were seen in 3 patients. CONCLUSIONS: Intrathecal baclofen is a simple technique with good results for improving the quality of life of patients with spasticity.

Clasificación de Neer. Variabilidad interobservador / Interobserver Variability Of Neer Classification

Introducción Hacer objetiva la variabilidad interobservador al evaluar una fractura de húmero proximal utilizando la clasificación de Neer y establecer su utilidad diagnóstica y terapéutica. Materiales y Métodos Formulario digital con 20 casos elegidos al azar de fracturas de húmero proximal, de un mismo hospital entre 2010 y 2014. Cada caso incluyó: edad, sexo, lateralidad y dos proyecciones radiográficas. Evaluado de forma anónima por Traumatólogos, con y sin práctica habitual en cirugía del hombro, de hospitales nacionales e internacionales, indicando estadío de Neer y opción terapéutica adecuada. Se estableció la variabilidad interobservador entre grupos y comparando a todos por igual, calculando el índice de Kappa de Fleiss e interpretándolo según los criterios de Landis y Koch. Resultados 40 respuestas de Traumatólogos, 15 con práctica habitual de cirugía de hombro y 25 no. El índice Kappa de Fleiss medio fue 0,173 en el grupo de Traumatólogos con práctica habitual en cirugía de hombro. Siendo 0,176 en el grupo sin práctica habitual. Al evaluarlos conjuntamente, 0,184. Existe gran variabilidad interobservador en la indicación terapéutica y dentro de la indicación quirúrgica. Discusión El grado de acuerdo obtenido, según los criterios de Landis y Koch, ha sido pobre en todos los grupos en lo que a estadío se refiere y débil en lo referente al tratamiento, no influyendo la experiencia del Traumatólogo. Sería necesaria una clasificación más reproducible ya que la clasificación de Neer presenta la suficiente variabilidad interobservador como para aceptarla como único medio en la toma de decisiones.

Background To study inter-observer variability by evaluating a fracture of the proximal humerus using Neer's classification and to establish its diagnostic and therapeutic utility. Methods A computerised form was used with 20 randomly selected cases of fractures of the proximal humerus, from the same hospital between 2010 and 2014. Each case included: age, gender, laterality, and two radiographic projections. They were anonymously evaluated by Traumatologists, for whom shoulder surgery was routine practice or not, from national and international hospitals. They indicated Neer stage and an appropriate therapeutic option. Interobserver variability was established between groups, and comparing all of them equally, calculating Fleap's Kappa index and interpreting it according to the Landis and Koch criteria. Results A total of 40 responses were obtained from the Traumatologists, 15 of them were shoulder surgery was usual practice and 25 where it was not. The mean Fleap Kappa index was 0.173 in the Traumatologists group were shoulder surgery was usual practice, being 0.176 in the group were it was not usual practice. The overall index was 0.184. There is wide interobserver variability in the therapeutic indication, as well as within the surgical indication. Discussion The level of agreement obtained, according to the criteria of Landis and Koch, was poor in all groups in terms of stage, and weak in terms of treatment. The experience of the Traumatologist had no influence. A more reproducible classification may be necessary since Neer's classification has sufficient interobserver variability to accept it as the sole means of decision making.

Estudio comparativo entre clavo endomedular y tratamiento conservador en fracturas de húmero proximal de 2 y 3 fragmentos / Comparative study between intramedullary nailing and conservative treatment in proximal humerus fractures of 2 and 3 fragments

Introducción Hacer objetivas las diferencias relativas a funcionalidad y calidad de vida entre pacientes con fracturas de húmero proximal de 2 y 3 fragmentos tratados de forma conservadora y mediante enclavado endomedular. Materiales y Métodos Estudio descriptivo-retrospectivo realizado en un mismo centro hospitalario entre junio de 2010 y mayo de 2014. Se incluyeron pacientes con fractura de húmero proximal de 2 y 3 fragmentos, excluyendo los menores de 60 años. Se evaluó la movilidad, test de Constant y ASES. El análisis estadístico se realizó con el programa SPSS. Resultados 71 pacientes seleccionados; 43 presentaban fractura de 2 fragmentos y 28 de 3. Mediante enclavado endomedular fueron tratados 15, con una media de edad de 76,7 años, y 38 recibieron tratamiento conservador, con una edad media de 79,8 años; en ambos grupos el número de mujeres fue mayor. Las puntuaciones de los cuestionarios Constant y ASES fueron superiores en el grupo que recibió tratamiento conservador, al igual que su grado de satisfacción y mejor movilidad y funcionalidad. Discusión En las fracturas de 2 y 3 fragmentos el tratamiento conservador es utilizado en gran parte de los casos. La edad no es un factor influyente a la hora de decantarse por una u otra opción terapéutica. La mayoría de los pacientes están satisfechos con el tratamiento recibido. En los test de Constant y ASES obtienen mejor resultado los pacientes tratados de forma conservadora. La abducción y la flexión son ligeramente superiores en pacientes que recibieron tratamiento conservador.

Background To study the differences related to functionality and quality of life between patients with proximal humerus fractures of 2 and 3 fragments treated conservatively and by using intramedullary nailing. Material and Methods Descriptive-retrospective study was conducted in the same hospital between June 2010 and May 2014. Patients with proximal humerus fractures of 2 and 3 fragments were included. Patients under 60 years were excluded. Mobility was evaluated, using the Constant and ASES (American Shoulder and Elbow Surgeons) test. Statistical analysis was performed using the SPSS program. Results Of the 71 selected patients, 43 had a 2 fragments fracture, and 28 had a 3 fragment fracture Intramedullary nailing was used to treat 15 cases (with a mean age of 76.7 years), and 38 (mean age 79.8 years) received conservative treatment. The number of women was higher in both groups. The scores of the Constant and ASES questionnaires were higher in the group that received conservative treatment. They also had a higher level of satisfaction and better mobility and functionality. Discussion In fractures of 2 and 3 fragments conservative treatment is used in a large majority of the cases. Age is not an influential factor when opting for one or another therapeutic option. Most patients are satisfied with the treatment received. Patients treated conservatively obtain better results in the Constant and ASES tests. Abduction and flexion are slightly higher in patients that received conservative treatment.

Inhibition of hepatitis B virus replication by N-hydroxyisoquinolinediones and related polyoxygenated heterocycles.

We previously reported low sensitivity of the hepatitis B virus (HBV) ribonuclease H (RNaseH) enzyme to inhibition by N-hydroxyisoquinolinedione (HID) compounds. Subsequently, our biochemical RNaseH assay was found to have a high false negative rate for predicting HBV replication inhibition, leading to underestimation of the number of HIDs that inhibit HBV replication. Here, 39 HID compounds and structurally related polyoxygenated heterocycles (POH), N-hydroxypyridinediones (HPD), and flutimides were screened for inhibition of HBV replication in vitro. Inhibiting the HBV RNaseH preferentially blocks synthesis of the positive-polarity DNA strand and causes accumulation of RNA:DNA heteroduplexes. Eleven HIDs and one HPD preferentially inhibited HBV positive-polarity DNA strand accumulation. EC50s ranged from 0.69 µM to 19 µM with therapeutic indices from 2.4 to 71. Neither the HIDs nor the HPD had an effect on the ability of the polymerase to elongate DNA strands in capsids. HBV RNaseH inhibition by the HIDs was confirmed with an improved RNaseH assay and by detecting accumulation RNA:DNA heteroduplexes in HBV capsids from cells treated with a representative HID. Therefore, the HID scaffold is more promising for anti-HBV drug discovery than we originally reported, and the HPD scaffold may hold potential for antiviral development. The preliminary structure-activity relationship will guide optimization of the HID/HPDs as HBV inhibitors.

Post-traumatic ventricular septal defect: a rare indication for extracorporeal membrane oxygenation as a bridge to transplant.

A ventricular septal defect (VSD) is a rare complication of blunt chest trauma. This report presents the case of a 44-year-old man who developed a VSD as a result of high-energy closed chest trauma. We describe the initial surgical and medical management of the cardiac rupture. After failed repair surgery, extracorporeal membrane oxygenation (ECMO) was used as a bridge to heart transplantation. We discuss the successful use of ECMO to improve the prognosis results in this rare and complex entity.

Minimally invasive spine surgery in spinal infections.

INTRODUCTION: Although spinal infections have always been present recently their incidence has increased, in partly fostered by the advances in medicine (i.e. compromised immunity, chronic diseases, increasingly complex spinal procedures, etc.) and increased life expectancy. EVIDENCE ACQUISITION: Using PubMed for this systematic review, the main spine infections types will be addressed focusing in the minimally invasive surgical techniques that can be used in their treatment. EVIDENCE SYNTHESIS: Spontaneous and iatrogenic pyogenic and non-pyogenic spine infections can be treated in many different ways depending on their extension and location as well as on their causative microorganisms. The indications of percutaneous image-guided, endoscopic and microsurgical treatment techniques will be updated. CONCLUSIONS: In spine infections minimally invasive surgical techniques show a great potential as to be safe, effective, with low surgical morbidity and fast patients' recovery.

Aptamers as a promising approach for the control of parasitic diseases

ABSTRACT Aptamers are short single-stranded RNA or DNA oligonucleotides that are capable of binding various biological targets with high affinity and specificity. Their identification initially relies on a molecular process named SELEX (Systematic Evolution of Ligands by EXponential enrichment) that has been later modified in order to improve aptamer sensitivity, minimize duration and cost of the assay, as well as increase target types. Several biochemical modifications can help to enhance aptamer stability without affecting significantly target interaction. As a result, aptamers have generated a large interest as promising tools to compete with monoclonal antibodies for detection and inhibition of specific markers of human diseases. One aptamer-based drug is currently authorized and several others are being clinically evaluated. Despite advances in the knowledge of parasite biology and host-parasite interactions from "omics" data, protozoan parasites still affect millions of people around the world and there is an urgent need for drug target discovery and novel therapeutic concepts. In this context, aptamers represent promising tools for pathogen identification and control. Recent studies have reported the identification of "aptasensors" for parasite diagnosis, and "intramers" targeting intracellular proteins. Here we discuss various strategies that have been employed for intracellular expression of aptamers and expansion of their possible application, and propose that they may be suitable for the clinical use of aptamers in parasitic infections.

Hepatitis B virus genetic diversity has minimal impact on sensitivity of the viral ribonuclease H to inhibitors.

Hepatitis B virus (HBV) causes hepatitis, cirrhosis, liver failure, and liver cancer, but the current therapies that employ either nucelos(t)ide analogs or (pegylated)interferon α do not clear the infection in the large majority of patients. Inhibitors of the HBV ribonuclease H (RNaseH) that are being developed with the goal of producing anti-HBV drugs are promising candidates for use in combination with the nucleos(t)ide analogs to improve therapeutic efficacy. HBV is genetically very diverse, with at least 8 genotypes that differ by ≥8% at the sequence level. This diversity is reflected in the viral RNaseH enzyme, raising the possibility that divergent HBV genotypes or isolates may have varying sensitivity to RNaseH inhibitors. To evaluate this possibility, we expressed and purified 18 patient-derived RNaseHs from genotypes B, C, and D. Basal RNaseH activity and sensitivity to three novel RNaseH inhibitors from three different chemotypes were assessed. We also evaluated four consensus HBV RNaseHs to determine if such sequences would be suitable for use in antiviral drug screening. The patient-derived enzymes varied by over 10-fold in their basal RNaseH activities, but they were equivalently sensitive to each of the three inhibitors. Similarly, all four consensus HBV RNaseH enzymes were active and were equally sensitive to an RNaseH inhibitor. These data indicate that a wide range of RNaseH sequences would be suitable for use in antiviral drug screening, and that genotype- or isolate-specific genetic variations are unlikely to present a barrier during antiviral drug development against the HBV RNaseH.

Plasmaféresis en rechazo agudo del injerto renal mediado por anticuerpos. Estudio realizado en el Hospital Pablo Tobón Uribe, Medellín, Colombia. Año 2005-2015 / Plasmapheresis in antibody-mediated renal allograft rejection. Experience of Pablo Tobon Uribe, Medellin, Colombia. Year 2005-2015

Introducción: el rechazo agudo mediado por anticuerpos es una complicación que se presenta luego del trasplante renal y es una causa importante de pérdida del injerto. La plasmaféresis es una de las terapias utilizadas para su tratamiento, algunos estudios sugieren mejor supervivencia del injerto renal con el uso de plasmaféresis; sin embargo su evidencia es débil. Objetivo: este estudio tiene como objetivo describir la experiencia del uso de plasmaféresis en el rechazo agudo mediado por anticuerpos. Materiales y Métodos: estudio descriptivo retrospectivo realizado en el Hospital Pablo Tobón Uribe entre agosto de 2005 y junio de 2015 en pacientes con diagnóstico de rechazo agudo mediado por anticuerpos, quienes recibieron entre tres y nueve sesiones de plasmaféresis. Resultados: se realizaron un total de 769 trasplantes renales; de los cuales 26 pacientes presentaron rechazo agudo mediado por anticuerpos y recibieron plasmaféresis como parte del tratamiento. Todos los pacientes recibieron terapia de inducción al momento del trasplante y en el 80,8% la terapia de mantenimiento utilizada fue tacrolimus-micofenolato-prednisolona. El rechazo mediado por anticuerpos se presentó en forma temprana en el 61,5% de los pacientes. A seis y doce meses el 44% y 53,8% de los pacientes respectivamente presentaron pérdida del injerto renal; las complicaciones se presentaron en el 53,8% de los pacientes, las cuales fueron hipocalcemia, hipotensión y anafilaxia. Conclusión: en esta cohorte el uso de plasmaféresis en el rechazo agudo mediado por anticuerpos no logró evitar la pérdida del injerto renal en el 50% de los pacientes; se sugiere adicionar a esta terapia otras alternativas de tratamiento entre ellas, la inmunoglobulinas intravenosas, rituximab, eculizumab y bortezomib. MÉD.UIS. 2016;29(2):41-8.

Background: antibody-mediated renal allograft rejection is a complication after kidney transplantation, and it has poor prognosis for graft survival. Plasmapheresis has been used with controversial results; few trials indicate a trend towards superior graft survival in patients receiving this treatment; however, the evidence remains weak. Objetive: the aim of this study was to describe the experience in treating Antibody-mediated renal allograft rejection with plasmapheresis in kidney transplant recipients. Methods: retrospective and descriptive study of the patients that underwent three to nine session of plasmapheresis as a treatment of severe Antibody-mediated renal allograft rejection in Pablo Tobón Uribe Hospital. Results: between August 2005 and June 2015, 769 patients underwent kidney transplantation at our institution; 26 patients received plasmapheresis as part of the treatment for Antibody-mediated renal allograft rejection. All patients received induction therapy. Maintenance therapy used was tacrolimus, mycophenolic acid and steroids in 80,8% of the patients and cyclosporine, micophenolic acid and steroids in 19,2%. Antibody mediated rejection had an early onset in 61,5% of the cases. At six and 12 months after therapy, 44% and 53,8% patients respectively were back on dialysis. Complications were reported in 53,8% of the patients (hypocalcaemia, hypotension and anaphylaxis). Conclusion: in this cohort, 50% of patients who received Plasmapheresis as therapy for severe Antibody-mediated renal allograft rejection presented loss graft after one year of follow up. It is necessary adding to this therapy new treatment alternatives, among them intravenous immunoglobulin, rituximab, eculizumab and bortezomib. MÉD.UIS. 2016;29(2):41-8.

Secondary forms of Takotsubo cardiomyopathy: A whole different prognosis.

BACKGROUND: Takotsubo syndrome (TKS) usually mimics an acute coronary syndrome. However, several clinical forms have been reported. Our aim was to assess if different stressful triggers had prognostic influence on TKS, and to establish a working classification. METHODS: We performed an analysis including patients with TKS between 2003-2013 from our prospective local database and the RETAKO National Registry, fulfilling Mayo criteria. Patients were divided in two groups regarding their potential triggers: (a) none/psychic stress as 'primary forms' and (b) physical factors (asthma, surgery, trauma, etc.) as 'secondary forms'. RESULTS: Finally, 328 patients were included, 90.2% women, with a mean age of 69.7 years. Patients were divided into primary TKS (n=265) and 63 secondary TKS groups. Age, gender, previous functional class and cardiovascular risk profile displayed no differences between groups before admission. However, primary-TKS patients suffered a main complaint of chest pain (89.4% vs 50.7%, p<0.0001) with frequent vegetative symptoms. Regarding treatment before admission, there were no differences either. During admission, differences were related to more intensive antithrombotic and anxiolytic drug use in the primary TKS group. Inotropic and mechanical ventilation use was higher in the secondary cohort. After discharge, a more frequent prescription of beta-blockers and statins in primary-TKS patients was seen. Secondary forms displayed more in-hospital stay and evolutive complications: death (hazard ratio (HR): 3.41; 95% confidence interval (CI): 1.14-10.16, p=0.02), combined event variable (MACE) (HR: 1.61; 95% CI: 1.01-2.6, p=0.04) and recurrences (HR: 1.85; 95% CI: 1.06-3.22, p=0.02). CONCLUSION: Secondary TKS could present or mark worse short and long-term prognoses in terms of mortality, recurrences and readmissions. We propose a simple working nomenclature for TKS.