Carcinogenic effect of human tumor-derived cell-free filtrates in nude mice.

Cancer remains a worldwide cause of morbidity and mortality. Investigational research efforts have included the administration of tumor-derived extracts to healthy animals. Having previously demonstrated that the administration of non-transmissible, human cancer-derived homogenates induced malignant tumors in mice, here, we examined the consequences of administering 50 or 100 µg of protein of crude homogenates from mammary carcinoma, pancreatic adenocarcinoma, and melanoma samples in 6 inoculations per week during 2 months. The concurrent control mice received homogenates of healthy donor-skin cosmetic surgery fragments. Mammary carcinoma homogenate administration did not provoke the deterioration or mortality of the animals. Multiple foci of lung adenocarcinomas with a broad expression of malignity histomarkers coexisting with small cell-like carcinomas were found. Disseminated cells, positive to classic epithelial markers, were detected in lymphoid nodes. The administration of pancreatic tumor and melanoma homogenates progressively deteriorated animal health. Pancreatic tumor induced poorly differentiated lung adenocarcinomas and pancreatic islet hyperplasia. Melanoma affected lungs with solid pseudopapillary adenocarcinomas. Giant atypical hepatocytes were also observed. The kidney exhibited dispersed foci of neoplastic cells within a desmoplastic matrix. Nuclear overlapping with hyperchromatic nuclei, mitotic figures, and prominent nuclear atypia was identified in epidermal cells. None of these changes were ever detected in the control mice. Furthermore, the incubation of zebrafish embryos with breast tumor homogenates induced the expression of c-Myc and HER-2 as tumor markers, contrasting to embryos exposed to healthy tissue-derived material. This study confirms and extends our hypothesis that tumor homogenates contain and may act as vectors for "malignancy drivers," which ultimately implement a carcinogenesis process in otherwise healthy mice.

Fatigue-Related Changes of Daily Function: Most Promising Measures for the Digital Age.

Background: Fatigue is a prominent symptom in many diseases and is strongly associated with impaired daily function. The measurement of daily function is currently almost always done with questionnaires, which are subjective and imprecise. With the recent advances of digital wearable technologies, novel approaches to evaluate daily function quantitatively and objectively in real-life conditions are increasingly possible. This also creates new possibilities to measure fatigue-related changes of daily function using such technologies. Summary: This review examines which digitally assessable parameters in immune-mediated inflammatory and neurodegenerative diseases may have the greatest potential to reflect fatigue-related changes of daily function. Key Messages: Results of a standardized analysis of the literature reporting about perception-, capacity-, and performance-evaluating assessment tools indicate that changes of the following parameters: physical activity, independence of daily living, social participation, working life, mental status, cognitive and aerobic capacity, and supervised and unsupervised mobility performance have the highest potential to reflect fatigue-related changes of daily function. These parameters thus hold the greatest potential for quantitatively measuring fatigue in representative diseases in real-life conditions, e.g., with digital wearable technologies. Furthermore, to the best of our knowledge, this is a new approach to analysing evidence for the design of performance-based digital assessment protocols in human research, which may stimulate further systematic research in this area.

Costo y porcentaje de gasto en salud por COVID-19 en primer nivel de atención / Cost and percentage of health spending by COVID-19 at the first level of care

Antecedentes. Ante la pandemia de COVID-19 el sistema de salud reasignó recursos económicos para la atención. Objetivo. Determinar el costo de la atención y el porcentaje del gasto en salud por COVID-19 en una unidad de medicina familiar de primer nivel de atención. Metodología. Estudio de costo y porcentaje de gasto en COVID-19 en una unidad de primer nivel de atención. Se identificaron los servicios generales y finales, para construir el costo fijo se utilizó la técnica de tiempos y movimientos, se identificaron el total de partidas presupuestales ejercidas en la unidad médica para cada uno de los servicios, para desagregar el gasto de los servicios generales a los finales se construyeron ponderadores. El costo variable se realizó con la técnica consenso de expertos y microcosteo. El costo promedio se relacionó con la productividad por servicio y con el total de pacientes atendidos por COVID-19, el resultado se relacionó con el presupuesto ejercido de la unidad. Resultados. El costo anual de la atención de COVID-19 en módulo respiratorio fue 158.597,25 dólares americanos, en medicina familiar fue 192.549,36 dólares americanos, el costo total ejercido en el año 2021 para atención de SARS COV 2 en una unidad de primera atención fue 351.146,61 dólares americanos. Esta cantidad representa el 9,6 % del gasto en salud. Conclusión. El costo en atención de COVID-19 y el porcentaje del gasto en salud en primer nivel de atención es elevado (AU)

Background. In the COVID-19 pandemic, the health system reallocated financial resources for care. Objetive. To determine the cost of care and the percentage of health spending due to COVID-19 in a first level care family medicine unit. Metodology. Study of the cost and percentage of spending on COVID-19 in a first-level care unit. The general and final services were identified, to construct the fixed cost, the technique of times and movements was used, the total budget items exercised in the medical unit for each of the services were identified, to disaggregate the expense of general services to the endings were constructed weights. Variable costing was performed using the expert consensus technique and microcosting. The average cost was related to productivity per service and to the total number of patients treated for COVID-19, the result was related to the budget used by the unit. Results. The annual cost of COVID-19 care in the respiratory module was 158.597,25 US dollars, in family medicine it was 192.549,36 US dollars, the total cost incurred in 2021 for SARS COV 2 care in a unit of first attention was 351.146,61 US dollars. This amount represents 9,6% of health spending. Conclusion. The cost of COVID-19 care and the percentage of health spending at the first level of care is high (AU)

Influencia de la NeuroEPO en el corazón fetal en un modelo de insuficiencia placentaria en ratas

Fundamento: la insuficiencia placentaria es la causa más común del retardo del crecimiento intrauterino, que puede provocar alteraciones cardiovasculares. Recientemente, se han desarrollado terapias con eritropoyetina que protegen los tejidos cardiacos con hipoxia. Objetivo: evaluar la influencia de la eritropoyetina recombinante humana con bajo contenido de ácido siálico (NeuroEPO) en el corazón fetal en un modelo de insuficiencia placentaria en ratas. Métodos: se utilizaron 14 ratas Wistar gestadas con ligadura unilateral de la arteria uterina derecha en el día 16 de la gestación. Ese mismo día, a siete ratas se le administró NeuroEPO (0,5 mg/kg/día subcutáneo por tres días) y al resto placebo. En el día 20 de la gestación los fetos se dividieron en cuatro grupos: un grupo control, un grupo con retardo del crecimiento intrauterino, un grupo control NeuroEPO y un grupo con retardo del crecimiento intrauterino y NeuroEPO. En los fetos se obtuvo el peso placentario, peso fetal y la eficacia placentaria. En el estudio histológico se cuantificó el número de cardiomiocitos, número de vasos sanguíneos y cantidad de las fibras de colágenos. Resultados: el grupo con retardo del crecimiento intrauterino presentó una disminución del peso fetal, del número de cardiomiocitos, del número de vasos sanguíneos y un aumento en la cantidad de fibras colágenas (p<0.05). Al tratar con NeuroEPO a los fetos con retardo en el crecimiento intrauterino, aumentó el peso fetal, aunque el peso no fue similar al control. El resto de las variables se comportaron semejantes al control. Conclusiones: la administración de esta molécula mejoró el peso fetal y permitió un equilibrio adecuado en el desarrollo del corazón fetal, quizás, debido a los efectos citoprotectores de esta molécula.

Foundation: placental insufficiency is the most common cause of intrauterine growth retardation, which can cause cardiovascular alterations. Recently, erythropoietin therapies have been developed that protect hypoxic cardiac tissues. Objective: To evaluate the influence of human recombinant erythropoietin with low sialic acid content (NeuroEPO) on the fetal heart in a rat model of placental insufficiency. Methods: 14 Wistar rats gestated with unilateral ligation of the right uterine artery on day 16 of gestation were used. That same day, seven rats were administered NeuroEPO (0.5 mg/kg/day subcutaneously for three days) and the rest received placebo. On day 20 of gestation, the fetuses were divided into four groups: a control group, a group with intrauterine growth retardation, a NeuroEPO control group, and a group with intrauterine growth retardation and NeuroEPO. In the fetuses, placental weight, fetal weight and placental efficiency were obtained. In the histological study, the number of cardiomyocytes, number of blood vessels and quantity of collagen fibers were quantified. Results: the group with intrauterine growth retardation presented a decrease in fetal weight, the number of cardiomyocytes, the number of blood vessels and an increase in the amount of collagen fibers (p<0.05). When fetuses with intrauterine growth retardation were treated with NeuroEPO, fetal weight increased, although the weight was not similar to the control. The rest of the variables behaved similar to the control. Conclusions: the administration of this molecule improved fetal weight and allowed an adequate balance in the development of the fetal heart, perhaps due to the cytoprotective effects of this molecule.

Oral administration of a recombinant modified RBD antigen of SARS-CoV-2 as a possible immunostimulant for the care of COVID-19.

BACKGROUND: Developing effective vaccines against SARS-CoV-2 that consider manufacturing limitations, equitable access, and acceptance is necessary for developing platforms to produce antigens that can be efficiently presented for generating neutralizing antibodies and as a model for new vaccines. RESULTS: This work presents the development of an applicable technology through the oral administration of the SARS-CoV-2 RBD antigen fused with a peptide to improve its antigenic presentation. We focused on the development and production of the recombinant receptor binding domain (RBD) produced in E. coli modified with the addition of amino acids extension designed to improve antigen presentation. The production was carried out in shake flask and bioreactor cultures, obtaining around 200 mg/L of the antigen. The peptide-fused RBD and peptide-free RBD proteins were characterized and compared using SDS-PAGE gel, high-performance chromatography, and circular dichroism. The peptide-fused RBD was formulated in an oil-in-water emulsion for oral mice immunization. The peptide-fused RBD, compared to RBD, induced robust IgG production in mice, capable of recognizing the recombinant RBD in Enzyme-linked immunosorbent assays. In addition, the peptide-fused RBD generated neutralizing antibodies in the sera of the dosed mice. The formulation showed no reactive episodes and no changes in temperature or vomiting. CONCLUSIONS: Our study demonstrated the effectiveness of the designed peptide added to the RBD to improve antigen immunostimulation by oral administration.

Tiempo transcurrido para la recuperación de la calidad de vida en pacientes que presentaron COVID-19 y fueron hospitalizados / Time elapsed for the recovery of the quality of life in patients who presented COVID-19 and were hospitalized

Introducción. El COVID-19 grave con foco neumónico se maneja en hospital, en esta población las secuelas físicas y funcionales posterior al egreso hospitalario son más frecuentes, involucran la calidad de vida y tienen repercusión en las actividades cotidianas, la autopercepción y el autocuidado.Objetivo. Identificar el tiempo transcurrido para la recuperación de la calidad de vida previa al evento COVID-19 en pacientes que requirieron hospitalización.Metodología. Diseño de cohorte antes-después en pacientes que requirieron hospitalización por cuadro de COVID-19. Se consideró expuesto a los pacientes después del evento COVID-19 y no expuesto al mismo paciente antes del evento. La calidad de vida relacionada con la salud se midió con el instrumento SF-36. El plan de análisis incluyó ecuación de regresión lineal y proyección del número de días transcurridos después de la hospitalización para recuperar la calidad de vida relacionada con la salud previa al evento COVID-19 a partir del egreso hospitalario. Resultados. La dimensión que tarda más días en recuperar la calidad de vida que poseía previa al evento COVID-19 es rol físico con 225 días, y la dimensión que menos días tarda en recuperar la calidad de vida que poseía previa el evento es vitalidad y función social, ambas con 44 días.Conclusión. El tiempo para la recuperación de la calidad de vida previo a la hospitalización es diferente en cada una de las dimensiones de la calidad de vida (AU)

Introduction. Severe COVID-19 with a pneumonic focus is managed in a hospital. In this population, the physical and functional sequelae after hospital discharge are more frequent, involve quality of life, and have an impact on daily activities, self-perception, and self-care.Aim. Identify the time elapsed for the recovery of the quality of life prior to the COVID-19 event in patients who required hospitalization.Methodology. Before-after cohort design in patients who required hospitalization due to COVID-19. Patients were considered exposed after the COVID-19 event and not exposed to the same patient before the event. Health-related quality of life was measured with the SF-36 instrument. The analysis plan included a linear regression equation and projection of the number of days elapsed after hospitalization to recover the health-related quality of life prior to the COVID-19 event from hospital discharge.Results. The dimension that takes the longest days to recover the quality of life that it had prior to the COVID-19 event is physical role with 225 days, and the dimension that takes the fewest days to recover the quality of life that it had prior to the event is vitality and social function, both with 44 days.Conclusion. The time for recovery of quality of life prior to hospitalization is different in each of the dimensions of quality of life (AU)

Experiencias en la realización de autopsias a puérperas fallecidas por la COVID-19

Introducción: El SARS-CoV-2 causa graves neumonías. Las gestantes experimentan cambios inmunológicos y fisiológicos, que pueden hacerlas más susceptibles a las infecciones respiratorias virales, incluida la COVID-19. Objetivo: Exponer las características de una serie de casos de muertes maternas, confirmadas con la COVID-19. Métodos: Se realizó un estudio de serie de autopsias parciales, a las puérperas confirmadas al SARS-CoV-2, revisadas por el grupo especial de trabajo de anatomía patológica para la COVID-19, en el año 2021. Se analizaron las variables edad, historia obstétrica y causas de muerte, en el Hospital Militar Central "Dr. Luis Díaz Soto". Resultados: En el 2021 fueron atendidas 425 gestantes confirmadas al SARS-CoV-2, de ellas 16 fallecieron (3,8 %). A todas se les realizó cesárea, por beneficio materno-fetal e ingresaron en la unidad de cuidados intensivos, con comorbilidades entre las cuales la obesidad y la diabetes fueron más frecuentes. La media de fecha de inicio de los síntomas fue 5,18 días, todas contacto de casos positivos; en las causas de muerte la hipoxia sistémica afectó a un tercio de las fallecidas; el edema pulmonar de permeabilidad se presentó en el 100 % de las puérperas y en todas las muertes maternas hubo daño múltiple de órganos. Conclusiones: El edema pulmonar de permeabilidad afecta a todos los casos, con impacto importante como causa de muerte, así como en la expresión de la hipoxia y la respuesta inflamatoria sistémica. La COVID-19 es la causa básica de muerte en todos los casos.

Introduction: SARS-CoV-2 causes severe pneumonias. Pregnant women experience immunological and physiological changes, which may make them more susceptible to viral respiratory infections, including COVID-19. Objective: To present the characteristics of a case series of maternal deaths confirmed with COVID-19. Methods: A serial study of partial autopsies of postpartum women confirmed with SARS-CoV-2, reviewed by the special working group of pathological anatomy for COVID-19, in the year 2021, was carried out. The variables age, obstetric history and causes of death were analyzed at the Central Military Hospital "Dr. Luis Díaz Soto". Results: In 2021, 425 pregnant women with confirmed SARS-CoV-2 were attended, 16 of them died (3.8%). All of them underwent cesarean section for maternal-fetal benefit and were admitted to the intensive care unit, with comorbidities among which obesity and diabetes were more frequent. The mean date of symptom onset was 5.18 days, all contact positive cases; in the causes of death systemic hypoxia affected one third of the deceased; permeability pulmonary edema was present in 100 % of the puerperal women and in all maternal deaths there was multiple organ damage. Conclusions: Permeability pulmonary edema affects all cases, with important impact as a cause of death, as well as in the expression of hypoxia and systemic inflammatory response. COVID-19 is the basic cause of death in all cases.

Plasma concentrations of lysophosphatidic acid and the expression of its receptors in peripheral blood mononuclear cells are altered in patients with cocaine use disorders.

We have recently reported alterations in the plasma concentrations of lysophosphatidic acid (LPA) in patients with substance use disorders. In order to further explore the potential role of the LPA signaling system as biomarker in cocaine use disorders (CUD) we conducted a cross-sectional study with 105 patients diagnosed with CUD and 92 healthy controls. Participants were clinically evaluated and blood samples were collected to determine plasma concentrations of total LPA and LPA species (16:0-, 18:0-, 18:1-, 18:2-, and 20:4-LPA), and the gene expression of LPA1 and LPA2 receptors in peripheral blood mononuclear cells. We found that patients with CUD had significantly lower plasma concentration of the majority of LPA species, while the mRNA expression of LPA1 receptor was found to be higher than controls. Moreover, we found a positive association between plasma concentration of 20:4-LPA and relevant CUD-related variables: age of onset cocaine use and length of cocaine abstinence. The statistical analysis revealed sex differences in concentrations of total LPA and LPA species, and women showed higher LPA concentrations than men. Furthermore, studies in rats of both sexes showed that plasma concentrations of total LPA were also altered after acute and chronic cocaine administration, revealing a sexual dimorphism in these effects. This study found alterations on the LPA signaling system in both, patients with CUD and rats treated with cocaine. Our results demonstrate that LPA signaling is impacted by CUD and sex, which must be taken into consideration in future studies evaluating LPA as a reliable biomarker for CUD.

Prediction of prostate cancer biochemical recurrence by using discretization supports the critical contribution of the extra-cellular matrix genes.

Due to its complexity, much effort has been devoted to the development of biomarkers for prostate cancer that have acquired the utmost clinical relevance for diagnosis and grading. However, all of these advances are limited due to the relatively large percentage of biochemical recurrence (BCR) and the limited strategies for follow up. This work proposes a methodology that uses discretization to predict prostate cancer BCR while optimizing the necessary variables. We used discretization of RNA-seq data to increase the prediction of biochemical recurrence and retrieve a subset of ten genes functionally known to be related to the tissue structure. Equal width and equal frequency data discretization methods were compared to isolate the contribution of the genes and their interval of action, simultaneously. Adding a robust clinical biomarker such as prostate specific antigen (PSA) improved the prediction of BCR. Discretization allowed classifying the cancer patients with an accuracy of 82% on testing datasets, and 75% on a validation dataset when a five-bin discretization by equal width was used. After data pre-processing, feature selection and classification, our predictions had a precision of 71% (testing dataset: MSKCC and GSE54460) and 69% (Validation dataset: GSE70769) should the patients present BCR up to 24 months after their final treatment. These results emphasize the use of equal width discretization as a pre-processing step to improve classification for a limited number of genes in the signature. Functionally, many of these genes have a direct or expected role in tissue structure and extracellular matrix organization. The processing steps presented in this study are also applicable to other cancer types to increase the speed and accuracy of the models in diverse datasets.

Multiplex assay for the simultaneous detection of antibodies against small ruminant lentivirus, Mycobacterium avium subsp. paratuberculosis, and Brucella melitensis in goats.

Background and Aim: Brucellosis, paratuberculosis (PTb), and infections caused by small ruminant lentivirus (SRLV), formerly known as caprine arthritis encephalitis virus (CAEV), adversely affect goat production systems. Nonetheless, commonly used diagnostic tests can only determine one analyte at a time, increasing disease surveillance costs, and limiting their routine use. This study aimed to design and validate a multiplex assay for antibody detection against these three diseases simultaneously. Materials and Methods: Two recombinant proteins from the SRLV (p16 and gp38), the native hapten of Brucella melitensis, and the paratuberculosis-protoplasmic antigen 3 from Mycobacterium avium subsp. paratuberculosis (MAP) were used to devise and assess a multiplex assay. Conditions for the Luminex® multiplex test were established and validated by sensitivity, specificity, repeatability, and reproducibility parameters. Cut-off points for each antigen were also established. Results: The 3-plex assay had high sensitivity (84%) and specificity (95%). The maximum coefficients of variation were 23.8% and 20.5% for negative and positive control samples, respectively. The p16 and gp38 SRLV antigens are 97% and 95%, similar to the CAEV sequence found in GenBank, respectively. Conclusion: The multiplex test can be effectively used for the simultaneous detection of antibodies against SRLV, MAP and B. melitensis in goats.

Efectividad de anticuerpos monoclonales anti-PRGC en el tratamiento preventivo de la migraña: estudio prospectivo de 63 pacientes / Effectiveness of anti-CGRP monoclonal antibodies in the preventive treatment of migraine: A prospective study of 63 patients

Introducción: El péptido relacionado con el gen de la calcitonina (PRGC) ha supuesto una revolución en el conocimiento de la fisiopatología de la migraña y ha llevado al desarrollo de nuevos fármacos específicos contra esta nueva diana.MétodosPresentamos un estudio prospectivo de 63 pacientes con migraña episódica (ME) y crónica (MC) tratados con anticuerpos monoclonales anti-PRGC y describimos su eficacia, seguridad y recaídas tras su suspensión. Se analizan predictores de respuesta que puedan ayudar a planificar mejor los tratamientos.ResultadosLa edad media fue de 48,3 ± 11,81 años, siendo 84,1% mujeres. La media de días de migraña al mes (DMM) fue de 15,59 días; 63,5% tenían MC. En todos se comenzó con erenumab 70 mg subcutáneo. Se aumentó la dosis a 140 mg en 47,6% de los pacientes. Se obtuvo una reducción entre 49,85 y 59,53% de DMM entre los tres primeros meses y el año de tratamiento; 17,5% presentó estreñimiento y 4,8% reacción en el lugar de la inyección. En cinco pacientes (17,9%) se cambió el tratamiento a galcanezumab. Tras suspender el tratamiento 23 pacientes sufrieron recaídas, con buena respuesta al reintroducirlo. No hemos podido establecer predictores de respuesta, pero sí observamos de forma estadísticamente significativa mayor número de días de mejora cuantos más DMM hubiera al inicio (p = 0,002).ConclusionesLos anticuerpos monoclonales anti-PRGC son fármacos eficaces, seguros y bien tolerados. Observamos que su interrupción, en algunos casos, puede conllevar recaídas frecuentes y precoces, por lo que recomendamos prolongar el tratamiento en aquellos pacientes con mayor DMM. (AU)

Introduction: Calcitonine Gen-Related Peptide (CGRP) established a revolution in migraine pathophysiology knowledge and has led to the development of new drugs specifically targeting this disease.MethodsWe present a prospective study in which 63 episodic and chronic migraine patients have been treated with anti-CGRP monoclonal antibodies describing their efficacy, security and relapses after their interruption. Response predictors have been analyzed such they can help us to create a better treatment plan.ResultsAverage age was 48.3 ± 11.81 years old, 84.1% of them being women. The average was of 15.59 migraine days per month (MDM). 63.5% of all patients suffered chronic migraine. The initial dose of Erenumab in all patient was 70 mg subcutaneous. This was increased to 140 mg in 47.6% of the patients. An MDM reduction between 49.85% and 59.53% was obtained within three to twelve months from the start of treatment. Constipation was present in 17.5% of the patients and 4.8% suffered injection site reaction. The treatment was changed to Galcanezumab in 17.9% of the patients. After interrupting the treatment, 23 patients relapsed with a good response on reintroduction of the treatment. It was not possible to establish a clear response predictor, however a statistically significant increase in the number of days of improvement was observed with more MDM at baseline level (p = 0.002).ConclusionsAnti-CGRP monoclonal antibodies are effective, safe, and well tolerated drugs. We have observed that their discontinuation, in some cases can lead to frequent and early relapses so we strongly recommend to extend the treatment in those patients with a higher MDM. (AU)

Meropenem allergy testing performed at the bedside of hospitalized patients labelled with a penicillin allergy.

BACKGROUND: Meropenem is a widely prescribed beta-lactam for hospitalized patients. There are few data on meropenem allergy assessments in inpatients with a reported history of penicillin allergy who require a treatment with meropenem. This can lead to the use of less effective second-line antibiotics that may increase antibiotic resistances. We aimed to evaluate the clinical outcomes of a meropenem allergy assessment in admitted patients with a reported history of penicillin allergy that required meropenem for the treatment of an acute infection. METHODS: A retrospective analysis was performed on 182 inpatients labelled with a penicillin-allergy who received meropenem after an allergy assessment. The allergy study was performed bedside if meropenem was required urgently. The study included skin prick tests (SPTs) followed by an intradermal skin test (IDT) to meropenem, and a meropenem drug challenge test (DCT). If a non-immediate reaction to a beta-lactam was suspected, it was initiated with patch tests. RESULTS: The median age of the patients was 59.7 years (range 28-95) and 80 (44%) were women. A total of 196 sets of diagnostic workups were performed, with 189 (96.4%) of them being tolerated. Only two patients had a positive meropenem IV DCT, both presenting a non-severe cutaneous reaction that completely resolved after treatment. CONCLUSIONS: This study evidenced that a bedside meropenem allergy assessment of hospitalized patients labelled with a 'penicillin allergy' who require a broad-spectrum antibiotic for empiric coverage is a safe and effective procedure, avoiding the use of second-line antimicrobial agents.

[Effectiveness of anti-CGRP monoclonal antibodies in the preventive treatment of migraine: A prospective study of 63 patients]. / Efectividad de anticuerpos monoclonales anti-PRGC en el tratamiento preventivo de la migraña: estudio prospectivo de 63 pacientes.

INTRODUCTION: Calcitonine Gen-Related Peptide (CGRP) established a revolution in migraine pathophysiology knowledge and has led to the development of new drugs specifically targeting this disease. METHODS: We present a prospective study in which 63 episodic and chronic migraine patients have been treated with anti-CGRP monoclonal antibodies describing their efficacy, security and relapses after their interruption. Response predictors have been analyzed such they can help us to create a better treatment plan. RESULTS: Average age was 48.3 ± 11.81 years old, 84.1% of them being women. The average was of 15.59 migraine days per month (MDM). 63.5% of all patients suffered chronic migraine. The initial dose of Erenumab in all patient was 70 mg subcutaneous. This was increased to 140 mg in 47.6% of the patients. An MDM reduction between 49.85% and 59.53% was obtained within three to twelve months from the start of treatment. Constipation was present in 17.5% of the patients and 4.8% suffered injection site reaction. The treatment was changed to Galcanezumab in 17.9% of the patients. After interrupting the treatment, 23 patients relapsed with a good response on reintroduction of the treatment. It was not possible to establish a clear response predictor, however a statistically significant increase in the number of days of improvement was observed with more MDM at baseline level (p = 0.002). CONCLUSIONS: Anti-CGRP monoclonal antibodies are effective, safe, and well tolerated drugs. We have observed that their discontinuation, in some cases can lead to frequent and early relapses so we strongly recommend to extend the treatment in those patients with a higher MDM.

Agave mapisaga aqueous extract shows in vitroand in vivoactivity on murine prostate cancer cells / El extracto acuoso del Agave mapisaga presenta actividad in vitro e in vivo sobre células de cáncer de próstata murino

Plants are a source of multiple antineoplastic treatments. However, the effect of many species used in traditional medicine has yet to be demonstrated. In this work, the taxonomic identification of Agave mapisaga was made and a high-performance liquid chromatography-mass spectrometry (HPLC-MS) study suggested the presence of the aglycone hecogenin, which is part of compounds such as agavoside C and cantalasaponin 4. The antineoplastic activity of an aqueous extract was tested in vitro and in vivo on PEC-Src epithelial murine prostate cancer cells. In vitro study revelead a significant chemosensivity at 0.125 mg/100 µL (p=0.0001). Also, in in vivo, using an isotransplantation model with 1x106 cells subcutaneously, it was observed that the group treated with 50 mg/kg presented a lower tumor implantation compared with the control without treatment (p=0.04).

Las plantas son fuente de múltiples tratamientos antineoplásicos. Sin embargo, aún falta demostrar el efecto de muchas especies usadas en la medicina tradicional. En este trabajo se realizó la identificación taxonómica del Agave mapisaga y un estudio de cromatografía líquida de alta definición­masas (HPLC-MS) que sugirió la presencia de la aglicona hecogenina, que forma parte de compuestos como el agavósido C y la cantalasaponina 4. Se probó la actividad antineoplásica de un extracto acuoso in vitro e in vivo sobre células de cáncer de próstata murino epitelial PEC-Src. En el estudio in vitro se observó una actividad citotóxica significativa a partir de 0.125 mg/100 µL (p=0.0001). Mientras que, en los experimentos in vivo, se isotransplantaron 1x106 células por vía subcutánea, se observó que el grupo tratado con 50 mg/kg presentó una menor implantación tumoral con respecto del testigo sin tratamiento (p=0.04).

Infección por SARS-CoV-2, endotelitis y ácidos biliares: una visión integradora / SARS-CoV-2 infection, endotheliitis and bile acids: an integrative view

Introducción: La endotelitis es causada por mecanismos complejos asociados a comorbilidades inmunitario-metabólicas como expresión del daño producido por diversos agentes, como el caso de las acciones proinflamatorias debidas a la interacción del virus SARS-CoV-2 con los ácidos biliares, que pueden estar implicadas en la mortalidad por la COVID-19. Objetivo: Describir las evidencias biomoleculares de la citotoxicidad de los ácidos biliares sobre el endotelio y la posible relación con la endotelitis de los cortes histológicos de tejidos de fallecidos por la COVID-19, asociada o no a las comorbilidades conocidas. Métodos: Se realizó una revisión sistemática y crítica de los artículos reportados sobre ácidos biliares y endotelitis desde 1963 hasta 2021 en los sitios web (PubMed, SciELO, Lilacs y Elservier). Se citó la histología del tejido pulmonar con daño endotelial en 34 fallecidos por COVID-19 en el Hospital Militar Central "Luis Díaz Soto", cuyos cortes histológicos fueron examinados en el Hospital Clínico Quirúrgico "Hermanos Ameijeiras". Asimismo, se describieron las acciones y las propiedades físico-químicas de los ácidos biliares que pudieran relacionarse con la endotelitis observada en dichos cortes histológicos. Conclusiones: Los ácidos biliares hidrofóbicos conjugados con glicinas, por sus propiedades e incrementos séricos hallados en las comorbilidades inmunitario-metabólicas y en las enfermedades hepato-intestinales, pudieran tener un papel en la endotelitis presente en pacientes de la COVID-19, con estadíos graves y críticos(AU)

Introduction: Endotheliitis is caused by complex mechanisms associated with immune-metabolic comorbidities as an expression of the damage produced by various agents, such as the case of proinflammatory actions due to the interaction of the SARS-CoV-2 virus with bile acids, which may be involved in mortality from COVID-19. Objective: To describe the biomolecular evidence of bile acid cytotoxicity on the endothelium and the possible relationship with endothelitis of histological sections of tissues from COVID-19 deaths, associated or not with known comorbidities. Methods: A systematic and critical review of the articles reported on bile acids and endothelitis from 1963 to 2021 was conducted on the websites (PubMed, SciELO, Lilacs and Elservier). It was cited the histology of lung tissue with endothelial damage in 34 deceased by COVID-19 at "Luis Díaz Soto" Central Military Hospital, whose histological sections were examined at "Hermanos Ameijeiras" Clinical Surgical Hospital. Likewise, the actions and physicochemical properties of bile acids that could be related to observed endothelitis in these histological sections were described. Conclusions: Hydrophobic bile acids conjugated with glycine, due to their properties and serum increases found in immune-metabolic comorbidities and hepato-intestinal diseases, could have a role in endothelitis present in COVID-19 patients, with severe and critical stages(AU)

Altered neutrophil-to-lymphocyte ratio in sepsis secondary to canine parvoviral enteritis treated with and without an immunomodulator in puppies.

Neutrophil-to-lymphocyte ratio (NLR) is a cheap and easy-to-obtain biomarker that mirrors the balance between innate and adaptive immunity. Cortisol and catecholamines have been identified as major drivers of NLR. High cortisol levels increase neutrophils while simultaneously decreasing lymphocyte counts. Likewise, endogenous catecholamines may cause leukocytosis and lymphopenia. Thus, NLR allows us to monitor patient severity in conditions such as sepsis. Twenty-six puppies with sepsis secondary to canine parvoviral enteritis were treated with and without an immunomodulator. Our group determined the NLR and the plasmatic cortisol levels by chemiluminescence, and norepinephrine (NE) and epinephrine (E) by HPLC during the first 72 h of clinical follow-up. Our results showed that at admission puppies presented an NLR value of 1.8, cortisol of 314.9 nmol/L, NE 3.7, and E 3.3 pmol/mL. Both treatments decreased admission NLR values after 24 h of treatment. However, only the puppies treated with the immunomodulator (I) remained without significant changes in NLR (0.7-1.4) compared to the CT group, and that showed a significant difference (P < 0.01) in their NLR value (0.4-4.6). In addition, we found significant differences in the slope values between the admission and final values of NLR (P < 0.005), cortisol (P < 0.02), and E (P < 0.05) between treatments. Then, our data suggest that the immunomodulator positively affects the number of lymphocytes and neutrophils involved in NLR as well as major drivers like cortisol and epinephrine, which is reflected in clinical parameters and survival.

A case of intestinal schwannoma initially suspected by transvaginal ultrasound.

Schwannomas are peripheral nerve sheath tumors. Due to their low incidence, few cases of colorectal schwannomas have been published, which increases the diagnostic challenge. The aim of this case report is to discuss the role of transvaginal ultrasound in different areas than the gynecological disorders, when on hands of properly trained professionals that perform systematized procedures. A 56-year-old woman consulted for postmenopausal genital bleeding. During transvaginal ultrasound, a colonic solid, hypervascularized mass of 23 × 26 mm was visualized. As a result of this incidental finding, the patient underwent a sigmoidectomy, with a final diagnosis of intestinal schwannoma. Transvaginal ultrasound is today one of the most useful and accurate diagnostic tools in the assessment of gynecological disorders. However, the proximity of other pelvic structures makes it possible to evaluate the presence of nongynecological conditions. This fact should encourage gynecologists to systematize the transvaginal ultrasound procedure.

Feasibility of targeted axillary dissection for de-escalation of surgical treatment after neoadjuvant chemotherapy in breast cancer.

BACKGROUND: Targeted axillary dissection, which combines sentinel lymph node biopsy with removal of the proven involved node noted during the staging process, has been shown to improve axillary staging and decrease false negative rates after neoadjuvant chemotherapy in patients with breast cancer. OBJECTIVE(S): The main goal of this study was to assess the ability to identify and remove the clipped node and the false negative rate of targeted axillary dissection. METHODS: We performed a prospective study among patients with biopsy-confirmed nodal metastases who received neoadjuvant chemotherapy. A clip was placed on the sample node prior systemic therapy. After neoadjuvant chemotherapy, all patients underwent sentinel lymph node biopsy (dual tracer), localization and excision of the clipped node and axillary lymph node dissection. The clipped node was preoperatively localized in all cases placing an iodine-125 seed guided by ultrasound. The pathology of the sentinel nodes and clipped node was compared with other nodes. RESULTS: A total of 455 patients with invasive breast cancer were studied. Of the 148 patients with NAC, 32 met the eligibility criteria and were enrolled in the study. Mean age at diagnosis was 52.3 years. Systematic lymphadenectomy was performed in all patients, with an average of 14.3 lymph nodes removed. Detection rate of the clipped node alone was 96.9%, and 100% for targeted axillary dissection. Ability of clipped node alone to predict nodal status showed a FNR of 10,5% while SLNB alone performed by dual tracer and targeted axillary dissection, showed FNRs of 5.3% and 5.0%, respectively. Sentinel lymph nodes matched clipped node in 23 patients (74.2%). CONCLUSION (S): In node positive breast cancer patients, targeted axillary dissection is a reliably approach for axillary staging after neoadjuvant chemotherapy. The preoperative location of the clipped node is mandatory to increase the detection rate and optimize the results of the technique.

Experiencias de autopsias a fallecidos por la COVID-19 / Autopsy experiences of deceased by COVID-19

RESUMEN Introducción: Se presenta un caso de paciente fallecido por la COVID-19, que los autores consideran prototipo de la mayor parte de los fallecidos por esta afección, que se le realizó a autopsia. Objetivo: Divulgar las experiencias en el estudio de la autopsia de este tipo de pacientes y contribuir a su aplicación en la práctica asistencial y científica. Caso clínico: Se presenta un paciente masculino de 78 años, con hipertensión arterial, diabetes mellitus y obesidad, que comenzó con tos, fiebre, secreción nasal, que ingresa con diagnóstico de la COVID-19, evoluciona hacia la gravedad y fallece 10 días después de su ingreso. Se presentan los elementos fundamentales de la historia clínica, los diagnósticos de causas de muerte pre mortem y post mortem. Se precisan los diagnósticos en la autopsia y los resultados de la evaluación de la calidad de los diagnósticos de causas de muerte clínicos. Conclusiones: Las experiencias del estudio de esta autopsia como prototipo, reafirman los daños ocasionados por el SARS-CoV-2 y aporta a los conocimientos de este campo.

ABSTRACT Introduction: A case of a patient who died from COVID-19 is presented, which the authors consider to be the prototype of most of those who died from this condition, which was performed at autopsy. Objective: Disseminate the experiences in the study of the autopsy of this type of patients and contribute to its application in clinical and scientific practice. Clinical case: A 78-year-old male patient is presented, with arterial hypertension, diabetes mellitus and obesity, who began with cough, fever, runny nose, who was admitted with a diagnosis of COVID-19, progressed to severity and died 10 days later. of his admittance. The fundamental elements of the clinical history, the diagnoses of causes of death pre-mortem and post-mortem are presented. Autopsy diagnoses and quality assessment results of clinical cause of death diagnoses are specified. Conclusions: The experiences of the study of this autopsy as a prototype, reaffirm the damage caused by SARS-CoV-2 and contribute to the knowledge of this field.