Impacto pronóstico de metformina en pacientes con diabetes mellitus tipo 2 e insuficiencia cardiaca aguda. Análisis combinado de los registros EAHFE y RICA / Prognostic impact of metformin in patients with type 2 diabetes mellitus and acute heart failure: Combined analysis of the EAHFE and RICA registries

Introducción Los pacientes con diabetes mellitus (DM) e insuficiencia cardiaca (IC) presentan peor pronóstico a pesar de los avances terapéuticos en ambas enfermedades. Los inhibidores del cotransportador sodio-glucosa tipo 2 y agonistas del receptor de GLP-1 han demostrado beneficios cardiovasculares y se han posicionado como primer escalón en el tratamiento de DM en pacientes con IC o elevado riesgo cardiovascular. Sin embargo, en los ensayos pivotales la mayoría de los pacientes recibe tratamiento concomitante con metformina. Todavía no se han desarrollado ensayos clínicos aleatorizados para evaluar el impacto pronóstico de la metformina a nivel cardiovascular. Nuestro objetivo fue analizar si los pacientes con DM e IC aguda que recibían tratamiento con metformina en el momento del alta podrían presentar mejor pronóstico al año de seguimiento. Métodos Ensayo de cohortes prospectivo mediante el análisis combinado de los 2 principales registros españoles de IC: el Registro Epidemiology of Acute Heart Failure in Emergency Departments –EAHFE– y el Registro Nacional de Pacientes con Insuficiencia Cardiaca –RICA–. Resultados De un total de 4.403 pacientes con DM tipo 2, recibió tratamiento con metformina el 33% (1.453). Este grupo presentó una mortalidad significativamente inferior al año de tratamiento (22 versus 32%; test de Log Rank p<0,001). En el análisis ajustado de mortalidad, los pacientes que recibieron tratamiento con metformina presentaron menor mortalidad al año de seguimiento independientemente del resto de las variables (RR 0,814; IC 95% 0,712-0,930; p<0,01). Conclusiones Los pacientes con DM tipo 2 e IC aguda que recibieron metformina presentaron mejor pronóstico al año de seguimiento, por lo que consideramos que este fármaco debe continuar siendo un pilar fundamental en el tratamiento de estos pacientes (AU)

Introduction Patients with diabetes mellitus (DM) and heart failure (HF) have a worse prognosis despite therapeutic advances in both diseases. Sodium-glucose co-transporter type 2 and GLP-1 receptor agonists have shown cardiovascular benefits and have been positioned as the first step in the treatment of DM in patients with HF or high cardiovascular risk. However, in the pivotal trials the majority of patients receives concomitant treatment with metformin. Randomized clinical trials have not yet been developed to assess the prognostic impact of metformin at the cardiovascular level. Our objective was to analyze whether patients with DM and acute HF who receive treatment with metformin at the time of discharge may have had a better prognosis at one year of follow-up. Methods Prospective cohort trial using the combined analysis of the 2 main Spanish HF registries: the Epidemiology of Acute Heart Failure in Emergency Departments registry –EAHFE– and the National Registry of Patients with Heart Failure –RICA–. Results 33% (1453) of a total of 4403 patients with DM type 2 received treatment with metformin. This group presented significantly lower mortality after one year of treatment (22 vs. 32%; Log Rank test, p<0.001). In the adjusted analysis of mortality, patients receiving treatment with metformin had lower mortality at one year of follow-up regardless of the rest of the variables (RR 0.814; 95% CI: 0.712–0.930; p<0.01). Conclusions Patients with DM type 2 and acute HF who received metformin had a better prognosis after one year of follow-up, so we believe that this drug should continue to be a fundamental pillar in the treatment of these patients (AU)

Prognostic impact of metformin in patients with type 2 diabetes mellitus and acute heart failure: Combined analysis of the EAHFE and RICA registries.

INTRODUCTION: Patients with diabetes mellitus (DM) and heart failure (HF) have a worse prognosis despite therapeutic advances in both diseases. Sodium-glucose co-transporter type 2 and GLP-1 receptor agonists have shown cardiovascular benefits and they have been positioned as the first step in the treatment of DM in patients with HF or high cardiovascular risk. However, in the pivotal trials the majority of patients receive concomitant treatment with metformin. Randomized clinical trials have not yet been developed to assess the prognostic impact of metformin at the cardiovascular level. Our objective has been centered in analyzing whether patients with DM and acute HF who receive treatment with metformin at the time of discharge may have a better prognosis at one year of follow-up. METHODS: Prospective cohort trial using the combined analysis of the two main Spanish HF registries, the EAHFE Registry (Epidemiology of Acute Heart Failure in Emergency Departments) and the RICA (National Registry of Patients with Heart Failure). RESULTS: 33% (1453) of a total of 4403 patients with DM type 2 received treatment with metformin. This group presents significantly lower mortality after one year of treatment (22 versus 32%; Log Rank test P < 0.001). In the adjusted analysis of mortality, patients receiving treatment with metformin have lower mortality at one year of follow-up regardless of the rest of the variables (RR 0,814; 95%IC 0,712-0,930; P < 0.01). CONCLUSIONS: Patients with DM type 2 and acute HF who receive metformin have a better prognosis after one year of follow-up, so we believe that this drug should continue to be a fundamental pillar in the treatment of these patients.

Músculo Esternal Bilateral, Descripción de un Caso e Implicancias Clínicas / Bilateral Sternal Muscle, Description of a Case and Clinical Implications

El músculo esternal corresponde a una variante muscular supernumeraria de la musculatura torácica, cuya descripción más antigua se remonta al año 1604. A lo largo de la historia ha sido denominado músculo "epiesternal", "preesternal", "recto torácico" o "recto esternal". Se ubica entre la fascia superficial y el músculo pectoral mayor, tiene una prevalencia de entre 3 % y 8 % en la población general, se presenta de forma unilateral o bilateral exhibiendo una alta variabilidad interracial y puede ser motivo de dilemas diagnósticos durante cirugías y exámenes de imagen. Disección en un cadáver adulto de sexo masculino. Se encontraron dos músculos esternales conectados superiormente por un tendón central. El músculo esternal derecho se extendía desde el manubrio esternal hasta el séptimo cartílago costal derecho. El músculo esternal izquierdo se extendía desde el manubrio esternal hasta el sexto cartílago costal izquierdo. Su inervación estaba dada por ramos cutáneos anteriores de los nervios intercostales y su vascularización por ramas perforantes provenientes de los vasos torácicos internos. El músculo esternal presenta una alta variabilidad morfológica y su prevalencia se ve influenciada por factores raciales. Conocer esta variación muscular enriquece la capacidad diagnóstica y quirúrgica reduciendo la posibilidad de iatrogenia.

SUMMARY: The sternal muscle corresponds to a supernumerary muscle variant of the thoracic musculature, whose oldest description dates to 1604. Throughout history it has been called the "episternal", "presternal", "rectus thoracis" or "rectus sternalis" muscle. It is located between the superficial fascia and the pectoralis major muscle, has a prevalence of between 3 % and 8 % in the general population, presents unilaterally or bilaterally, exhibits a high interracial variability and can be the cause of diagnostic dilemmas during surgery and imaging examinations. Dissection in an adult male cadaver. Two sternal muscles were found connected superiorly by a central tendon. The right sternal muscle extended from the sternal manubrium to the right seventh costal cartilage. The left sternal muscle extended from the sternal manubrium to the left sixth costal cartilage. The innervation was given by anterior cutaneous branches of the intercostal nerves and the vascularization by perforating branches coming from the internal thoracic vessels. The sternal muscle presents a high morphological variability and the prevalence is influenced by racial factors. Knowing this muscle variation enriches the diagnostic and surgical capacity, reducing the possibility of iatrogenesis.

Resultados del programa de cribado de enfermedad de Fabry en pacientes con córnea verticillata en el Hospital Universitario de Navarra / Results of the screening program for Fabry disease in patients with cornea verticillata at the University Hospital of Navarre

Introducción La cornea verticillata (CV) o queratopatía vortex se caracteriza por la presencia de depósitos en forma de espiral en el epitelio corneal. Las causas más frecuentes son los fármacos antipalúdicos y la amiodarona, y dentro de las causas sistémicas la enfermedad de Fabry (EF). Material y métodos Se realiza un estudio descriptivo prospectivo multidisciplinar en un centro de tercer nivel y de referencia en la Comunidad Foral de Navarra, tras la implementación de un programa de despistaje de la EF en los pacientes atendidos en consultas del servicio de oftalmología que eran diagnosticados de CV y posteriormente fueron remitidos a la consulta de enfermedades minoritarias del servicio de Medicina Interna del Hospital Universitario de Navarra para la realización del estudio de la EF. Resultados Dos mujeres y 4 varones, con una edad media de 76,8 años, se diagnosticaron de CV, de un total de 17.280 pacientes valorados en consultas externas por 3 especialistas de oftalmología durante el periodo de abril de 2018 a abril de 2020. Una paciente falleció antes de realizar el estudio de despistaje y en ningún paciente se diagnosticó la EF. Conclusiones A pesar de que el programa de despistaje de la EF en pacientes con CV en el Hospital Universitario de Navarra no confirmó ningún caso con EF, los especialistas en oftalmología deben tener en cuenta el posible diagnóstico de la EF en aquellos pacientes con CV en sus consultas rutinarias (AU)

Introduction Cornea verticillata (CV) or vortex keratopathy is characterized by the presence of spiral-shaped deposits in the corneal epithelium. The most frequent causes are antimalarial drugs and amiodarone and, among systemic causes, Fabry disease (FD). Material and methods A multidisciplinary, prospective, descriptive study was conducted in a tertiary reference center in Spain's Autonomous Community of Navarre after the implementation of a FD screening program for patients attended to in the Ophthalmology Department. The study analyzed those diagnosed with CV, who were subsequently referred to the rare disease clinic of the University Hospital of Navarre's Internal Medicine Department for an FD study. Results Two women and four men with a mean age of 76.8 years were diagnosed with CV out of a total of 17,280 patients evaluated in outpatient consultations by three ophthalmology specialists during the period from April 2018 to April 2020. One patient died before performing the screening study and no patients were diagnosed with FD. Conclusions Despite the fact that the University Hospital of Navarre's FD screening program for patients with CV did not confirm any cases of FD, ophthalmology specialists should consider the possible diagnosis of FD in patients with CV in their routine consultations (AU)

Results of the screening program for Fabry disease in patients with cornea verticillata at the University Hospital of Navarre.

INTRODUCTION: Cornea verticillata (CV) or vortex keratopathy is characterized by the presence of spiral-shaped deposits in the corneal epithelium. The most frequent causes are antimalarial drugs and amiodarone and, among systemic causes, Fabry disease (FD). MATERIAL AND METHODS: A multidisciplinary, prospective, descriptive study was conducted in a tertiary reference center in Spain's Autonomous Community of Navarre after the implementation of a FD screening program for patients attended to in the Ophthalmology Department. The study analyzed those diagnosed with CV, who were subsequently referred to the rare disease clinic of the University Hospital of Navarre's Internal Medicine Department for an FD study. RESULTS: Two women and four men with a mean age of 76.8 years were diagnosed with CV out of a total of 17,280 patients evaluated in outpatient consultations by three ophthalmology specialists during the period from April 2018 to April 2020. One patient died before performing the screening study and no patients were diagnosed with FD. CONCLUSIONS: Despite the fact that the University Hospital of Navarre's FD screening program for patients with CV did not confirm any cases of FD, ophthalmology specialists should consider the possible diagnosis of FD in patients with CV in their routine consultations.

Trajectories of Sugar Consumption and Dental Caries in Early Childhood.

This study verifies the association between the trajectory of sugar consumption and dental caries in the 2015 Pelotas Birth Cohort in Pelotas, Brazil. It was conducted with data from the follow-ups at 3, 12, 24, and 48 mo from the 2015 Birth Cohort, which included 4,275 children born alive in hospitals in Pelotas. Data collection included standardized questionnaires for first caregivers applied by trained interviewers at all follow-ups. Exposure was the trajectory of sugar consumption from 3 to 48 mo (always low, always intermediate, increasing, and always high), obtained by group-based trajectory modeling. The outcome of this study was dental caries, obtained through clinical examination performed by calibrated dentists at 48 mo of age. Socioeconomic conditions and oral health instruction from a health professional during the first 4 y of life were included in the analysis as potential confounders. Prevalence ratios and their 95% confidence intervals were provided from generalized estimating equations with a log-Poisson with robust variance specification. In total, 3,654 (91.1%) children participated in the survey at 48 mo, and 2,806 children had complete data for the analyzes performed. Of these, 1,012 (36.1%; 95% confidence interval [CI], 34.3-37.8) experienced caries, and 723 (25.8%; 95% CI, 24.2-27.4) had cavitated caries. Regarding cavitated caries, the prevalence was 1.48 times higher in the group with increasing sugar consumption than children with always low consumption. There is an association between the trajectory of sugar consumption and dental caries at 48 mo. Children with increasing and always high sugar consumption have the highest prevalence of caries.

Association of the length of time using computers and mobile devices with low back, neck and mid-back pains: findings from a birth cohort.

OBJECTIVES: Neck and low back pains are the leading causes of years lived with disability, and using computers or mobile devices in excess could be risk factors for back pain. Our aim was to evaluate the association of the length of time using computers and mobile devices with neck, mid-back and low back pains and the number of regions with pain. STUDY DESIGN: Cross-sectional study nested in the 1993 Pelotas birth cohort with young adults aged 22 years. METHODS: Outcomes analyzed were neck, mid-back and low back pains and the number of regions with pain. Exposures were the number of daily hours using computers and mobile devices. Crude and adjusted analyses were performed to estimate prevalence ratios using Poisson regression. RESULTS: Almost half of the sample reported having back pain, the low back pain being the most prevalent. Compared with individuals using mobile devices for less than one hour, the prevalence of neck pain was 1.41 and 1.81 times higher among individuals using mobile devices from three to seven hours and for seven or more hours per day, respectively. Neck pain prevalence was 1.47 times higher among individuals using computers for more than two hours than among those not using computers. Using mobile devices for seven hours or more was associated to 1.19 times higher prevalence of low back pain. CONCLUSION: Using mobile devices in excess was associated to neck and low back pains, while the use of computers in excess was associated only to neck pain. It is important that guidelines are developed to recommend the adequate length of time that computers and mobile devices should be used to prevent back pain.

Positional anomaly between the brachial plexus and the scalene muscles, concomitant with an anomalous path of the musculocutaneous nerve: case report and clinical implication / Anomalía posicional entre el plexo braquial y el músculo escaleno anterior, concomitante con un trayecto anómalo del nervio musculocutáneo: reporte de un caso e implicancia clínica

Anatomical variations of the scalene muscles are frequent, as are those of the brachial plexus and its terminal nerves. Nonetheless, these variations are reported separately in the literature. The aim of this work is to present a variation of scalene muscles, concomitant with an abnormal path of the musculocutaneous nerve. During a routine dissection of the cervical region, axilla and right anterior brachial region in an adult male cadaver, a supernumerary muscle fascicle was located in the anterior scalene muscle, altering the anatomical relations of C5 and C6 ventral branches of the brachial plexus. This variation was related to an anomalous path of the musculocutaneous nerve that did not cross the coracobrachialis muscle. It passed through the brachial canal along with the median nerve. It then sent off muscular branches to the anterior brachial region and likewise, communicating branches to the median nerve. The concomitant variations of the brachial plexus and scalene muscles they are not described frequently. Knowledge of these variations improves diagnosis, enhancing therapeutic and surgical approaches by reducing the possibility of iatrogenesis during cervical, axillary and brachial region interventions.

Las variaciones anatómicas de los músculos escalenos son frecuentes, así como también las del plexo braquial y sus nervios terminales. Sin embargo la literatura científica las presenta por separado. El propósito de este trabajo es presentar una variación de los músculos escalenos concomitante con un trayecto anómalo del nervio musculocutáneo. Disección de rutina de región cervical, axila y región braquial anterior derechas realizada en un cadáver adulto de sexo masculino. Se encontró un fascículo muscular supernumerario para el músculo escaleno anterior que alteraba las relaciones anatómicas de los ramos ventrales C5 y C6 del plexo braquial. Esta variación estaba acompañada por un trayecto anómalo del nervio musculocutáneo, el cual no atravesaba al músculo coracobraquial y transitaba por el conducto braquial acompañando al nervio mediano. Desde allí enviaba a la región braquial anterior ramos musculares y al nervio mediano ramos comunicantes. Las variaciones conjuntas del plexo braquial y los músculos escalenos no se presentan con frecuencia. Conocerlas enriquece la capacidad diagnóstica, terapéutica y quirúrgica. Reduciendo la posibilidad de iatrogenia al intervenir en las regiones cervical, axilar y braquial.

[Peripartum cardiomyopathy: clinical key to diagnosis]. / Miocardiopatía periparto: claves clínicas para su sospecha.

Peripartum cardiomyopathy (PPCM) is an idiopathic cardiomyopathy that is caused by heart failure secondary to a dysfunction of the left ventricle at the end of pregnancy or in the first months following childbirth. The diagnosis is performed by electrocardiogram, radiography of the thorax and increase of natriuretic peptides. Bedside radiography can contribute with data that help early diagnosis. Treatment is carried out following clinical guidelines for heart failure, taking into account potentially teratogenic drugs. The importance of this pathology lies in that it affects women at a fertile age and is potentially mortal, which is why there must be a high index of suspicion for its diagnosis and a differential diagnosis with other entities. In this clinical note we present a series of cases of PPCM with the goal of reviewing the diagnosis and treatment of this entity.

The cloning of the virus envelope glycoprotein F of canine distemper virus expressed in Pichia pastoris.

Canine distemper virus (CDV) is a pathogen which affects members of the Canidae family, causing an acute, often fatal, systemic disease. CDV is an RNA virus of the family Paramyxoviridae that contains two envelope glycoproteins: F and HA. In this study, we focused on the envelope glycoprotein F as the main target for neutralizing antibodies produced after infection or vaccination. The complete coding region of the protein (60 kDa) was expressed in the methylotrophic yeast Pichia pastoris, obtained in a recombinant form and secreted to the culture medium. Later, to analyze its immunogenicity, the protein was combined with an oily adjuvant and used to inoculate mice. The results provide evidence supporting a potential application of this recombinant protein as a subunit vaccine.

Detection and molecular characterization of porcine parvovirus in fetal tissues from sows without reproductive failure in Argentina.

Porcine parvovirus (PPV) is one of many pathogens responsible for reproductive failure in pregnant sows. Several studies have reported the appearance of new PPV strains that differ from previous isolates both genetically and antigenically. Thus, the protective effects of commercially inactivated vaccines could not be complete. In South America, the information about PPV is limited. Thus, the aim of the present study was to detect and characterize the PPV strains present in 131 mummies or stillbirths from normal deliveries in sows from a commercial swine farm of Argentina that uses the commercial vaccine. PCR results showed that 17/131 were positive to PPV. Ten of these viruses were isolated and sequenced. All viruses were related to the PPV1 sequence (NADL-2), maintaining the amino acid differences in positions 436 (S-P) and 565 (R-K). This study is the first to report the isolation of PPV in Argentina and the results suggest that PPV can cross the placenta even in vaccinated sows, thus affecting some of the fetuses and being able to cause fetal death in sows without reproductive failure. The results also suggest that vaccination only reduces clinical signs and reproductive disorders and may thus not be a perfect tool to manage PPV infection. This study provides information that needs to be studied in depth to improve strategies to prevent and control PPV infection in swine farms.

The dorsoepicondylar medial muscle a clinically relevant anatomical variation / El músculo dorsoepicondylar medial: una variación anatómica clínicamente relevante

Anatomical variations in the axillary region do not always appear in modern human anatomy texts, which leaves the risk of diagnostic and surgical errors by doctors unaware of these variations. This work presents an anatomical variation of muscular type in the axillary region that can potentially generate clinical manifestations or iatrogenic results during surgical procedures. Routine dissection of an upper limb in a male cadaver. An atypical muscle was found in the axillary region, located at the base of the right axilla, and conformed by three muscle fascicles that give rise to a common muscular belly. The three fascicles are joined at the base of the axilla, and form a thin flat muscle 120 mm long from this join to its tendon, with a cross-section diameter of 15 mm and a thickness of 2 mm. The common belly of the muscle establishes a posterior relationship with the neurovascular elements of the axillary fossa and partially covers them. The tendon 150 mm in length originates at the level of the union of the upper and middle thirds of the arm and ends inserted in the medial epicondyle of the humerus, relating in its path with muscular and neurovascular elements of the arm. Being familiar with this variation enriches diagnostic and surgical abilities and reduces the possibility of iatrogenia in surgery of the axillary and brachial regions.

Las variaciones anatómicas son frecuentes en la región axilar, sin embargo no siempre figuran en los textos modernos de anatomía humana, existiendo un potencial riesgo de error diagnóstico y quirúrgico para quienes no las consideren. Se presenta una variación anatómica en la región axilar de tipo muscular que potencialmente puede generar manifestaciones clínicas o inducir iatrogenias durante un abordaje quirúrgico. Disección de rutina de miembro superior realizada en un cadáver adulto de sexo masculino. Se detectó un músculo atípico en la región axilar ubicado en la base de la axila derecha, compuesto por 3 fascículos musculares que dieron origen a un vientre muscular común. Los 3 fascículos, se unían en la base de la axila, formando un músculo delgado y plano de 120 mm longitud desde la unión de los fascículos hasta su tendón, con un diámetro transversal de 15 mm y un grosor de 2 mm. El vientre común del músculo establecía una relación posterior con los elementos neurovasculares de la fosa axilar y los cubría parcialmente. A nivel de la unión de los tercios superior y medio del brazo, desde el vientre muscular común se originaba un delgado tendón de 150 mm de longitud, que terminaba insertándose en el epicóndilo medial del húmero, relacionándose en su trayecto con los elementos musculares y neurovasculares del brazo. Conocer esta variación enriquece la capacidad diagnóstica y quirúrgica reduciendo la posibilidad de iatrogenia en la cirugía de las regiones axilar y braquial.

SHOX Duplication and Tall Stature in a Patient with Xq Deletion and Vascular Disease.

The anomalies of X chromosome are classified as numerical or structural. Concomitant structural anomalies in this chromosome that associate partial loss of its long arm with duplications in its short arm are uncommon. Only a few cases have been published and in most of them the reported patients present ovarian dysfunction, tall stature, and overdosage of the SHOX gene with locus Xp22.33. Considering these reports, we evaluated the case of a woman with a deletion in the long arm of the X chromosome, premature ovarian failure, tall stature, and multiple arterial vascular disease. With the aim to find a relationship between karyotype and phenotype, we explored associated anomalies in Xp and certified the overdosage of the SHOX gene in this case by MLPA. Also, taking into account the fact that the gene locus of the angiotensin-converting enzyme type 2 (ACE2) is located in Xp, our goal was to investigate the influence of this gene in the development of cardiovascular disease. The detection of the gene product of ACE2 by ELISA was undetectable. We have proposed that cytogenetic anomalies in X chromosome could contribute to decrease this protein synthesis in this gender.

Evaluation of apoptosis markers in different cell lines infected with equine arteritis virus.

Equine arteritis virus (EAV) induces apoptosis in infected cells. Cell death caused by EAV has been studied mainly using three cell lines, BHK-21, RK-13 and Vero cells. The mechanism of apoptosis varies among cell lines and results cannot be correlated owing to differences in EAV strains used. We evaluated different markers for apoptosis in BHK-21, RK-13 and Vero cell lines using the Bucyrus EAV reference strain. Acridine orange/ethidium bromide staining revealed morphological changes in infected cells, while flow cytometry indicated the extent of apoptosis. We also observed DNA fragmentation, but the DNA ladder was detected at different times post-infection depending on the cell line, i.e., 48, 72 and 96 h post-infection in RK-13, Vero and BHK-21 cells, respectively. Measurement of viral titers obtained with each cell line indicated that apoptosis causes interference with viral replication and therefore decreased viral titers. As an unequivocal marker of apoptosis, we measured the expression of caspase-3 and caspases-8 and -9 as extrinsic and intrinsic markers of apoptosis pathways, respectively. Caspase-8 in BHK-21 cells was the only protease that was not detected at any of the times assayed. We found that Bucyrus EAV strain exhibited a distinctive apoptosis pathway depending on the cell line.