Cardiovascular Manifestations From Therapeutic Radiation: A Multidisciplinary Expert Consensus Statement From the International Cardio-Oncology Society.

Radiation therapy is a cornerstone of cancer therapy, with >50% of patients undergoing therapeutic radiation. As a result of widespread use and improved survival, there is increasing focus on the potential long-term effects of ionizing radiation, especially cardiovascular toxicity. Radiation therapy can lead to atherosclerosis of the vasculature as well as valvular, myocardial, and pericardial dysfunction. We present a consensus statement from the International Cardio-Oncology Society based on general principles of radiotherapy delivery and cardiovascular risk assessment and risk mitigation in this population. Anatomical-based recommendations for cardiovascular management and follow-up are provided, and a priority is given to the early detection of atherosclerotic vascular disease on imaging to help guide preventive therapy. Unique management considerations in radiation-induced cardiovascular disease are also discussed. Recommendations are based on the most current literature and represent a unanimous consensus by the multidisciplinary expert panel.

Role of cardiovascular magnetic resonance in early detection and treatment of cardiac dysfunction in oncology patients.

The purpose of this review is to provide an overview of the essential role that cardiovascular magnetic resonance (CMR) has in the field of cardio-oncology. Recent findings: CMR has been increasingly used for early identification of cancer therapy related cardiac dysfunction (CTRCD) due to its precision in detecting subtle changes in cardiac function and for myocardial tissue characterization. Summary: CMR is able to identify subclinical CTRCD in patients receiving potentially cardiotoxic chemotherapy and guide initiation of cardio protective therapy. Multiparametric analysis with myocardial strain, tissue characterization play a critical role in understanding important clinical questions in cardio-oncology.

Synthetic repertoires derived from convalescent COVID-19 patients enable discovery of SARS-CoV-2 neutralizing antibodies and a novel quaternary binding modality.

The ongoing evolution of SARS-CoV-2 into more easily transmissible and infectious variants has sparked concern over the continued effectiveness of existing therapeutic antibodies and vaccines. Hence, together with increased genomic surveillance, methods to rapidly develop and assess effective interventions are critically needed. Here we report the discovery of SARS-CoV-2 neutralizing antibodies isolated from COVID-19 patients using a high-throughput platform. Antibodies were identified from unpaired donor B-cell and serum repertoires using yeast surface display, proteomics, and public light chain screening. Cryo-EM and functional characterization of the antibodies identified N3-1, an antibody that binds avidly (Kd,app = 68 pM) to the receptor binding domain (RBD) of the spike protein and robustly neutralizes the virus in vitro. This antibody likely binds all three RBDs of the trimeric spike protein with a single IgG. Importantly, N3-1 equivalently binds spike proteins from emerging SARS-CoV-2 variants of concern, neutralizes UK variant B.1.1.7, and binds SARS-CoV spike with nanomolar affinity. Taken together, the strategies described herein will prove broadly applicable in interrogating adaptive immunity and developing rapid response biological countermeasures to emerging pathogens.

Interim Analysis of the Phase II Study: Noninferiority Study of Doxorubicin with Upfront Dexrazoxane plus Olaratumab for Advanced or Metastatic Soft-Tissue Sarcoma.

PURPOSE: To report the interim analysis of the phase II single-arm noninferiority trial, testing the upfront use of dexrazoxane with doxorubicin on progression-free survival (PFS) and cardiac function in soft-tissue sarcoma (STS). PATIENTS AND METHODS: Patients with metastatic or unresectable STS who were candidates for first-line treatment with doxorubicin were deemed eligible. An interim analysis was initiated after 33 of 65 patients were enrolled. Using the historical control of 4.6 months PFS for doxorubicin in the front-line setting, we tested whether the addition of dexrazoxane affected the efficacy of doxorubicin in STS. The study was powered so that a decrease of PFS to 3.7 months would be considered noninferior. Secondary aims included cardiac-related mortality, incidence of heart failure/cardiomyopathy, and expansion of cardiac monitoring parameters including three-dimensional echocardiography. Patients were allowed to continue on doxorubicin beyond 600 mg/m2 if they were deriving benefit and were not demonstrating evidence of symptomatic cardiac dysfunction. RESULTS: At interim analysis, upfront use of dexrazoxane with doxorubicin demonstrated a PFS of 8.4 months (95% confidence interval: 5.1-11.2 months). Only 3 patients were removed from study for cardiotoxicity, all on > 600 mg/m2 doxorubicin. No patients required cardiac hospitalization or had new, persistent cardiac dysfunction with left ventricular ejection fraction remaining below 50%. The median administered doxorubicin dose was 450 mg/m2 (interquartile range, 300-750 mg/m2). CONCLUSIONS: At interim analysis, dexrazoxane did not reduce PFS in patients with STS treated with doxorubicin. Involvement of cardio-oncologists is beneficial for the monitoring and safe use of high-dose anthracyclines in STS.See related commentary by Benjamin and Minotti, p. 3809.

Cardiac Amyloidosis for the Primary Care Provider: A Practical Review to Promote Earlier Recognition of Disease.

Cardiac amyloidosis is increasingly recognized as an underdiagnosed cause of heart failure. Diagnostic delays of up to 3 years from symptom onset may occur, and patients may be evaluated by more than 5 specialists prior to receiving the correct diagnosis. Newly available therapies improve clinical outcomes by preventing amyloid fibril deposition and are usually more effective in early stages of disease, making early diagnosis essential. Better awareness among primary care providers of the clinical presentation and modern treatment landscape is essential to improve timely diagnosis and early treatment of this disease. In this review, we provide practical guidance on the epidemiology, clinical manifestations, diagnostic evaluation, and treatment of transthyretin and light chain cardiac amyloidosis to promote earlier disease recognition among primary care providers.

Cardio-Oncology Education and Training: JACC Council Perspectives.

The innovative development of cancer therapies has led to an unprecedented improvement in survival outcomes and a wide array of treatment-related toxicities, including those that are cardiovascular in nature. Aging of the population further adds to the number of patients being treated for cancer, especially those with comorbidities. Such pre-existing and developing cardiovascular diseases pose some of the greatest risks of morbidity and mortality in patients with cancer. Addressing the complex cardiovascular needs of these patients has become increasingly important, resulting in an imperative for an intersecting discipline: cardio-oncology. Over the past decade, there has been a remarkable rise of cardio-oncology clinics and service lines. This development, however, has occurred in a vacuum of standard practice and training guidelines, although these are being actively pursued. In this council perspective document, the authors delineate the scope of practice in cardio-oncology and the proposed training requirements, as well as the necessary core competencies. This document also serves as a roadmap toward confirming cardio-oncology as a subspecialty in medicine.

Frecuencia de dermatomicosis y factores asociados en población vulnerable. Manizales, Colombia / Dermatomicosis frequency and associated factors in vulnerable population. Manizales, Colombia

RESUMEN Objetivo Determinar la frecuencia de las dermatomicosis en personas de diferentes instituciones de atención social en la ciudad de Manizales durante el año 2011. Método Mediante la toma de muestras de los sitios que presentaban algún tipo de lesión sospechosa de ser una micosis cutánea, se hizo un análisis directo con KOH y cultivo en medios de Saboureaud y Mycosel. Se aplicó un instrumento de recolección de información para establecer factores asociados con la presencia de estos microorganismos. Resultados Los hongos levaduriformes encontrados con mayor frecuencia fueron: Candida albicans, Trichosporon sp, y los mohos saprofitos Penicillium sp, fusarium sp; seguido de hongos dermatofitos como: Trichophyton mentagrophytes, Trichophyton rubrum, Epidermophyton floccosum y Microsporum gypseum. Las lesiones secas y descamativas se encontraron con mayor frecuencia. El compartir baños y vivir en hacinamiento y el uso de elementos comunes fueron los factores asociados más importantes en este estudio. Conclusiones Las dermatomicosis son frecuentes en poblaciones vulnerables y se asocian a diferentes factores muy similares a los encontrados en otros estudios de igual naturaleza.(AU)

ABSTRACT Objective To determine the frequency of ringworm in people of different social care institutions in the city of Manizales in 2011. Method Using the sampling sites that had some kind of suspicious lesion from a cutaneous mycosis, direct analysis with KOH and culture media was Saboureaud and Mycosel. An instrument of data collection was used to establish factors associated with the presence of these microorganisms. Results The yeast found most frequently were: Candida albicans, Trichosporon sp and Penicillium molds saprophytes sp, Fusarium sp, followed by dermatophyte fungi such as Trichophyton mentagrophytes, Trichophyton rubrum, Epidermophyton floccosum and Microsporum gypseum. Dry scaly lesions were found more frequently. The shared bathrooms and living in overcrowded and the use of common elements were the most important in this study associated factors. Conclusions Dermatomycoses are common in vulnerable populations and are associated with different very similar to those found in other studies of the same nature factors.(AU)

Determinación de VSG: comparación de los métodos de Wintrobe y microhematocrito / Determination of VSG: comparison of methods and microhaematocrit Wintrobe

RESUMEN Objetivo Establecer la correlación entre los métodos de Wintrobe y de micro-hematocrito Métodos Se tomaron 407 pacientes asistentes a un laboratorio de tercer nivel a quienes en forma simultánea se les realizó las dos pruebas en estudio. Resultados Mediante el un método estadístico de regresión lineal se encontró un coeficiente de correlación de 0,99. Conclusión Ambos métodos pueden contribuir al análisis clínico de los pacientes a quienes se les solicitó la prueba con fines de diagnóstico, control y seguimiento de diferentes patologías.(AU)

ABSTRACT Objective To establish the correlation between the methods of Wintrobe and micro-hematocrit Methods 407 patients attendees were taken laboratory to third level simultaneo usly tests were performed in the study. Results Using a statistical method of linear regression correlation coefficient of 0,99 was found. Conclusion Both methods can contribute to the clinical analysis of patients who were asked to test for diagnosis or control of different pathologies.(AU)

[Determination of VSG: comparison of methods and microhaematocrit Wintrobe]. / Determinación de VSG: comparación de los métodos de Wintrobe y microhematocrito.

OBJECTIVE: To establish the correlation between the methods of Wintrobe and micro-hematocrit. METHODS: 407 patients attendees were taken laboratory to third level simultaneo usly tests were performed in the study. RESULTS: Using a statistical method of linear regression correlation coefficient of 0,99 was found. CONCLUSION: Both methods can contribute to the clinical analysis of patients who were asked to test for diagnosis or control of different pathologies.

OBJETIVO: Establecer la correlación entre los métodos de Wintrobe y de micro-hematocrito. MÉTODOS: Se tomaron 407 pacientes asistentes a un laboratorio de tercer nivel a quienes en forma simultánea se les realizó las dos pruebas en estudio. RESULTADOS: Mediante el un método estadístico de regresión lineal se encontró un coeficiente de correlación de 0,99. CONCLUSIÓN: Ambos métodos pueden contribuir al análisis clínico de los pacientes a quienes se les solicitó la prueba con fines de diagnóstico, control y seguimiento de diferentes patologías.

[Dermatomicosis frequency and associated factors in vulnerable population. Manizales, Colombia]. / Frecuencia de dermatomicosis y factores asociados en población vulnerable. Manizales, Colombia.

OBJECTIVE: To determine the frequency of ringworm in people of different social care institutions in the city of Manizales in 2011. METHOD: Using the sampling sites that had some kind of suspicious lesion from a cutaneous mycosis, direct analysis with KOH and culture media was Saboureaud and Mycosel. An instrument of data collection was used to establish factors associated with the presence of these microorganisms. RESULTS: The yeast found most frequently were: Candida albicans, Trichosporon sp and Penicillium molds saprophytes sp, Fusarium sp, followed by dermatophyte fungi such as Trichophyton mentagrophytes, Trichophyton rubrum, Epidermophyton floccosum and Microsporum gypseum. Dry scaly lesions were found more frequently. The shared bathrooms and living in overcrowded and the use of common elements were the most important in this study associated factors. CONCLUSIONS: Dermatomycoses are common in vulnerable populations and are associated with different very similar to those found in other studies of the same nature factors.

OBJETIVO: Determinar la frecuencia de las dermatomicosis en personas de diferentes instituciones de atención social en la ciudad de Manizales durante el año 2011. MÉTODO: Mediante la toma de muestras de los sitios que presentaban algún tipo de lesión sospechosa de ser una micosis cutánea, se hizo un análisis directo con KOH y cultivo en medios de Saboureaud y Mycosel. Se aplicó un instrumento de recolección de información para establecer factores asociados con la presencia de estos microorganismos. RESULTADOS: Los hongos levaduriformes encontrados con mayor frecuencia fueron: Candida albicans, Trichosporon sp, y los mohos saprofitos Penicillium sp, fusarium sp; seguido de hongos dermatofitos como: Trichophyton mentagrophytes, Trichophyton rubrum, Epidermophyton floccosum y Microsporum gypseum. Las lesiones secas y descamativas se encontraron con mayor frecuencia. El compartir baños y vivir en hacinamiento y el uso de elementos comunes fueron los factores asociados más importantes en este estudio. CONCLUSIONES: Las dermatomicosis son frecuentes en poblaciones vulnerables y se asocian a diferentes factores muy similares a los encontrados en otros estudios de igual naturaleza.

Desenvolvimento e padronização do Dot-ELISA usando peptídeos recombinantes para o diagnóstico sorológico de Neospora caninum / Development and standardization of Dot-ELISA using recombinant peptides for serological diagnosis of Neospora caninum

A neosporose é reconhecida como uma das maiores causas de aborto e perdas neonatais em bovinos de leite e corte em todo o mundo. Nos últimos anos esta doença tem atraído o interesse de pesquisadores com foco na epidemiologia e métodos eficazes de diagnóstico desta doença. No presente estudo objetivou-se desenvolver e padronizar um teste Dot-ELISA para o diagnóstico sorológico de Neospora caninum com um peptídeo recombinate como antígeno, visando o desenvolvimento de um kit para diagnóstico a campo. O peptídeo recombinante (rNcGRA1) foi desenhado com base na metodologia de genética reversa de epítopos antigênicos originados de uma proteína de grânulos densos de N. caninum, e sintetizado pela GenScript (USA). Produzido mediante o processo fermentativo em leveduras Pichia pastoris KM71. Para a padronização do Dot-ELISA, membranas de nitrocelulose de 0.22µm foram sensibilizadas com 1µL do antígeno e posteriormente os soros foram diluídos em solução de lavagem e incubados durante 1 hora. A revelação foi feita mediante a adição de Proteína G marcada com peroxidase por 30 minutos, seguido da solução reveladora a base de 3,3’-Diaminobenzidine (DAB). Logo após a padronização foram testados 44 soros bovinos diagnosticados por imunofluorescência indireta (RIFI), obtendo-se uma concordância nos resultados do teste de 95,5% e uma sensibilidade e especificidade de 100% e 92% respectivamente. Quanto ao Kit para diagnóstico a campo na Plataforma Tecnológica RapidFlow-Through Miriad®, o peptídeo rNcGRA1 apresentou marcações visíveis ao reagir com os soros positivos, e não apresentou marcações usando os soros negativos. Este estudo é o primeiro a utilizar peptídeos recombinantes e mostrar-se eficiente para o diagnóstico sorológico de bovinos naturalmente infetados por N. caninum...

Neosporosis is recognized as a major cause of abortion and neonatal loss in cattle worldwide, both for dairy cattle and beef cattle. In recent years this disease has attracted the interest of researchers and studying the epidemiology and effective methods of diagnosis of this disease. The present study aimed to develop and standardize on a Dot-ELISA for the serological diagnosis of Neospora caninum by using recombinant peptide as antigen for the development of a diagnostic kit used on the field. The recombinant antigen (rNcGRA1) was designed based on the method of reverse genetics derived antigenic epitopes of dense granules protein of N. caninum and synthesized by GenScript (USA). It was produced by the fermentation in yeasts Pichiapastoris KM71. The serological technique was used for the Dot-ELISA detection of IgG specific for N. caninum in which 0.22μm nitrocellulose membranes were sensitized with 1μL of antigen and subsequently the plasmas were diluted in a washing solution and incubated for 1 hour. The results will revealed by the addition of Protein G labeled with peroxidasse for 30 minutes, followed by the developing solution based on 3,3’-Diaminobenzidine (DAB). Soon after standardization tested 44 bovine plasmas were diagnosed by indirect immunofluorescence assay (IFA), agreeing with the results on a 95.5% and a sensitivity and specificity of 100% and 92% respectively. In regard to the diagnostic kit for the Technology Platform Rapid Flow-Through Miriad®, the peptide presented rNcGRA1 visible markings to react with positive plasma, and showed no markings using the negative plasma. This study is the first to use recombinant peptides and prove to be efficient for the serological diagnosis of cattle naturally infected...

Hemodialysis catheter implantation in the axillary vein by ultrasound guidance versus palpation or anatomical reference.

BACKGROUND: WE COMPARED THE RESULTS OF FOUR DIFFERENT METHODS OF HEMODIALYSIS CATHETER INSERTION IN THE MEDIAL SEGMENT OF THE AXILLARY VEIN: ultrasound guidance, palpation, anatomical reference, and prior transient catheter. METHODS: All patients that required acute or chronic hemodialysis and for whom it was determined impossible or not recommended either to place a catheter in the internal jugular vein (for instance, those patients with a tracheostomy), or to practice arteriovenous fistula or graft; it was then essential to obtain an alternative vascular access. When the procedure of axillary vein catheter insertion was performed in the Renal Care Facility (RCF), ultrasound guidance was used, but in the intensive care unit (ICU), this resource was unavailable, so the palpation or anatomical reference technique was used. RESULTS: Two nephrologists with experience in the technique performed 83 procedures during a period lasting 15 years and 8 months (from January 1997-August 2012): 41 by ultrasound guidance; 19 by anatomical references; 15 by palpation of the contiguous axillary artery; and 8 through a temporary axillary catheter previously placed. The ultrasound-guided patients had fewer punctures than other groups, but the value was not statistically significant. Arterial punctures were infrequent in all techniques. Analyzing all the procedure-related complications, such as hematoma, pneumothorax, brachial-plexus injury, as well as the reasons for catheter removal, no differences were observed among the groups. The functioning time was longer in the ultrasound-guided and previous catheter groups. In 15 years and 8 months of surveillance, no clinical or image evidence for axillary vein stenosis was found. CONCLUSION: The ultrasound guide makes the procedure of inserting catheters in the axillary veins easier, but knowledge of the anatomy of the midaxillary region and the ability to feel the axillary artery pulse (for the palpation method) also allow relatively easy successful implant of catheters in the axillary veins.

Frequency of clinical parasitic otitis due to Rhabditiform nematodes (Rhabditis sp) in six Gyr breed cattle farms in Cordoba, Colombia / Frecuencia de otitis parasitaria clínica por nematodos Rhabditiformes (Rhabditis spp) en seis fincas de la raza Gyr en Córdoba, Colombia / Freqüência de otite parasitária clínica por nematóides Rhabditiformes (Rhabditis sp) em seis fazendas na raça Gir em Córdoba, Colômbia

Objective: to determine the frequency of presentation of clinical parasitic otitis due to rhabditiform nematode (Rhabditis sp) in six Gyr breed cattle farms in Córdoba, Colombia. Methods: a descriptive prospective study in animals of convenience, between June and October 2010 was performed. Cerumen samples were collected using sterile swabs from the external ear canals of 155 animals. Results: the frequency of occurrence of Rhabditis sp presenting clinical otitis in six Gyr breed farms in Córdoba was 63.2%. Conclusion: clinical manifestations and characteristics of the cerumen as well as microscopic observation of the parasites, reported a high number of Rhabditis sp causing clinical parasitic otitis in 6 Gyr cattle farms in the province of Córdoba, Colombia.

Objetivo: determinar la frecuencia de presentación de otitis parasitaria clínica por nematodos Rhabditiformes (Rhabditis spp) en seis explotaciones de la raza Gyr en Córdoba, Colombia. Métodos: se realizó un estudio descriptivo prospectivo en animales de conveniencia, entre los meses de junio y octubre de 2010. Se recolectaron muestras de cerumen con hisopos de los conductos auditivos externos de 155 bovinos. Resultados: la frecuencia de presentación de otitis parasitaria clínica causada por Rhabditis spp en seis fincas de la raza Gyr en Córdoba fue del 63.2%. Conclusión: las manifestaciones clínicas y características del cerumen, así como la observación microscópica del parásito, informan una elevada presencia de Rhabditis spp causante de otitis parasitaria clínica en bovinos de la raza Gyr en 6 explotaciones del departamento de Córdoba, Colombia.

Objetivo: determinar a freqüência de apresentação de otite parasitária clínica por nematóides Rhabditiformes (Rhabditis sp) em seis fazendas da raça Gir em Córdoba, Colômbia. Métodos: foi realizado um estudo descritivo, prospectivo em animais de conveniência, entre junho e outubro de 2010. As amostras de cerume foram obtidas com swab nos canais auditivos de 155 bovinos. Resultados: a freqüência de ocorrência de otite parasitária clínica causada por Rhabditis sp em seis fazendas da raça Gir em Córdoba foi de 63.2%. Conclusão: As manifestações clínicas e as características do cerume, assim como a observação microscópica do parasita, relatam uma alta freqüência do Rhabditis sp causando otite parasitária clínica em 6 fazendas de gado da raça Gir do departamento de Córdoba, Colômbia.

Kynurenic acid triggers firm arrest of leukocytes to vascular endothelium under flow conditions.

Recent studies have demonstrated that kynurenic acid (KYNA), a compound produced endogenously by the interferon-gamma-induced degradation of tryptophan by indoleamine 2,3-dioxygenase, activates the previously orphaned G protein-coupled receptor, GPR35. This receptor is expressed in immune tissues, although its potential function in immunomodulation remains to be explored. We determined that GPR35 was most highly expressed on human peripheral monocytes. In an in vitro vascular flow model, KYNA triggered the firm arrest of monocytes to both fibronectin and ICAM-1, via beta(1) integrin- and beta(2) integrin-mediated mechanisms, respectively. Incubation of monocytes with pertussis toxin prior to use in flow experiments significantly reduced the KYNA-induced monocyte adhesion, suggesting that adhesion is triggered by a G(i)-mediated process. Furthermore, KYNA-triggered adhesion of monocytic cells was reduced by short hairpin RNA-mediated silencing of GPR35. Although GPR35 is expressed at slightly lower levels on neutrophils, KYNA induced firm adhesion of these cells to an ICAM-1-expressing monolayer as well. KYNA also elicited neutrophil shedding of surface L-selectin, another indicator of leukocyte activation. Taken together, these data suggest that KYNA could be an important early mediator of leukocyte recruitment.