Analysis of tumor infiltrating CD4+ and CD8+ CDR3 sequences reveals shared features putatively associated to the anti-tumor immune response.

Introduction: Tumor-infiltrating lymphocytes (TILs) have predictive and prognostic value in breast cancer (BC) and exert a protective function against tumor growth, indicating that it is susceptible to treatment using adoptive cell transfer of TILs or T cell receptor (TCR)-based therapies. TCR can be used to identify naturally tumor-reactive T cells, but little is known about the differences in the TCR repertoires of CD4+ and CD8+ TILs. Methods: TCR high-throughput sequencing was performed using TILs derived from the initial cultures of 11 BC biopsies and expanded and sorted CD4+ and CD8+ TILs as well as using PBMCs from healthy donors expanded and sorted using the same methodology. Results: Physicochemical TCR differences between T cell subsets were observed, as CD4+ TILs presented larger N(D)Nnt TRB sequences and with a higher usage of positively charged residues, although only the latest was also observed in peripheral T cells from healthy individuals. Moreover, in CD4+ TILs, a more restricted TCR repertoire with a higher abundance of similar sequences containing certain amino acid motifs was observed. Discussion: Some differences between CD4+ and CD8+ TCRs were intrinsic to T cell subsets as can also be observed in peripheral T cells from healthy individuals, while other were only found in TILs samples and therefore may be tumor-driven. Notably, the higher similarity among CD4+ TCRs suggests a higher TCR promiscuity in this subset.

Epstein-Barr Virus+ B Cells in Breast Cancer Immune Response: A Case Report.

EBV-specific T cells have been recently described to be involved in fatal encephalitis and myocarditis in cancer patients after immune checkpoint therapies. Here, we report the study of a human triple-negative breast cancer tumor (TNBC) and EBV-transformed B cells obtained from a patient-derived xenograft (PDX) that progressed into a lymphocytic neoplasm named xenograft-associated B-cell lymphoma (XABCL). T-cell receptor (TCR) high-throughput sequencing was performed to monitor the T-cell clonotypes present in the different samples. Forty-three T-cell clonotypes were found infiltrating the XABCL tissue after three passes in mice along 6 months. Eighteen of these (42%) were also found in the TNBC biopsy. TCR infiltrating the XABCL tissue showed a very restricted T-cell repertoire as compared with the biopsy-infiltrating T cells. Consequently, T cells derived from the TNBC biopsy were expanded in the presence of the B-cell line obtained from the XABCL (XABCL-LCL), after which the TCR repertoire obtained was again very restricted, i.e., only certain clonotypes were selected by the B cells. A number of these TCRs had previously been reported as sequences involved in infection, cancer, and/or autoimmunity. We then analyzed the immunopeptidome from the XABCL-LCL, to identify putative B-cell-associated peptides that might have been expanding these T cells. The HLA class I and class II-associated peptides from XABCL-LCL were then compared with published repertoires from LCL of different HLA typing. Proteins from the antigen processing and presentation pathway remained significantly enriched in the XABCL-LCL repertoire. Interestingly, some class II-presented peptides were derived from cancer-related proteins. These results suggest that bystander tumor-infiltrating EBV+ B cells acting as APC may be able to interact with tumor-infiltrating T cells and influence the TCR repertoire in the tumor site.

Application of failure mode and effects analysis to intracranial stereotactic radiation surgery by linear accelerator.

PURPOSE: The aim of this study was to analyze the application of the failure modes and effects analysis (FMEA) to intracranial stereotactic radiation surgery (SRS) by linear accelerator in order to identify the potential failure modes in the process tree and adopt appropriate safety measures to prevent adverse events (AEs) and near-misses, thus improving the process quality. METHODS AND MATERIALS: A working group was set up to perform FMEA for intracranial SRS in the framework of a quality assurance program. FMEA was performed in 4 consecutive tasks: (1) creation of a visual map of the process; (2) identification of possible failure modes; (3) assignment of a risk probability number (RPN) to each failure mode based on tabulated scores of severity, frequency of occurrence and detectability; and (4) identification of preventive measures to minimize the risk of occurrence. RESULTS: The whole SRS procedure was subdivided into 73 single steps; 116 total possible failure modes were identified and a score of severity, occurrence, and detectability was assigned to each. Based on these scores, RPN was calculated for each failure mode thus obtaining values from 1 to 180. In our analysis, 112/116 (96.6%) RPN values were <60, 2 (1.7%) between 60 and 125 (63, 70), and 2 (1.7%) >125 (135, 180). The 2 highest RPN scores were assigned to the risk of using the wrong collimator's size and incorrect coordinates on the laser target localizer frame. CONCLUSION: Failure modes and effects analysis is a simple and practical proactive tool for systematic analysis of risks in radiation therapy. In our experience of SRS, FMEA led to the adoption of major changes in various steps of the SRS procedure.

Valoración subjetiva de los factores de riesgo de osteoporosis frente a su registro objetivo mediante la herramienta FRAX. Avance del estudio VALSUFRAX / Assessment of subjetive risk factors for osteoporosis in front of objetive registration by FRAX tool. VALSUFRAX study preview

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Escenas de tabaco en el cine y la televisión en España / No disponible

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Respuesta de los autores a la carta 'Valoración de hemoglobina glucosilada en sangre capilar frente a la obtenida en sangre venosa' / No disponible

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Sala de observación de un servicio de urgencias: un lugar adecuado para el manejo del flutter auricular / Emergency department observation unit: an adequate place for the management of atrial flutter

Introducción y objetivos: La sala de observación de urgencias (SOU) es uno de los pilares fundamentales para la atención y control de la patología urgente. Existe muy poca información acerca del manejo del flutter en urgencias. Nuestro objetivo es ver la eficacia del manejo en los pacientes con flutter ingresados en la SOU. Método: Durante 36 meses consecutivos se realizó un estudio observacional, descriptivo y prospectivo de los pacientes diagnosticados de flutter en urgencias y que posteriormente pasaron a la SOU. Resultados: Se incluyen 157 pacientes (edad media 70 años), de los que 110 (71%)son dados de alta, y el 79% de ellos en menos de 24 horas. Para restaurar el ritmo se emplea la flecainida en 6 casos (4%) con una efectividad del 67%, la propafenona en4 casos (3%), con una efectividad del 25% y la amiodarona en 77 casos (49%) con una efectividad del 53%. En 11 casos (7%) se realiza cardioversión eléctrica, y es efectiva en un 100% sin efectos secundarios. Cuando abandonaron la SOU, 61 casos(38,85%) presentaban un electrocardiograma con ritmo sinusal. Conclusiones: Un gran número de pacientes con flutter auricular reciben el alta desde la SOU. Sin embargo, la efectividad farmacológica en la restauración del ritmo es baja, siendo la amiodarona el fármaco más empleado y la flecainida el más efectivo. La cardioversión eléctrica en la SOU es baja (AU)

Background: The Emergency Observation Unit (EOU) plays a central role in the attention and monitorization of patients with urgent conditions. Nevertheless, data regarding the management of atrial flutter at emergency departments are scarce. Aim: The aim of the present study was to assess the effectiveness of flutter management in patients admitted to the EOU. Methods: A prospective, descriptive, observational study of all the patients who were initially diagnosed of atrial flutter at emergency department and later transferred to the EOU during 36 consecutive months was carried out. Results: Among 157 patients (mean age 70 years) included in the study, 110 (71%) were discharged from the EOU,79% of them within less than 24 hours. The normal heart rhythm was restored with flecainide in 6 cases (4%, effectiveness67%), propafenone in 4 cases (3%, effectiveness 25%) and amiodarone in 77 cases (49%, effectiveness 53%).Electrical cardioversion was used in 11 cases (7%) with effectiveness of 100% and absence of adverse effects. In 61 cases(38,85%) the electrocardiogram showed sinus rhythm when the patients left the EOU. Conclusions: The number of patients with atrial flutter discharged from the EOU was high. Pharmacological effectiveness to restore the heart rhythm was low being amiodarone and flecainide the most effective drugs. The number of electrical cardioversion procedures performed for the treatment of atrial flutter in the EOU was low (AU)