Efficient Identification of Patients With NTRK Fusions Using a Supervised Tumor-Agnostic Approach.

CONTEXT.­: The neurotrophic tropomyosin receptor kinase (NTRK) family gene rearrangements have been recently incorporated as predictive biomarkers in a "tumor-agnostic" manner. However, the identification of these patients is extremely challenging because the overall frequency of NTRK fusions is below 1%. Academic groups and professional organizations have released recommendations on the algorithms to detect NTRK fusions. The European Society for Medical Oncology proposal encourages the use of next-generation sequencing (NGS) if available, or alternatively immunohistochemistry (IHC) could be used for screening with NGS confirmation of all positive IHC results. Other academic groups have included histologic and genomic information in the testing algorithm. OBJECTIVE.­: To apply some of these triaging strategies for a more efficient identification of NTRK fusions within a single institution, so pathologists can gain practical insight on how to start looking for NTRK fusions. DESIGN.­: A multiparametric strategy combining histologic (secretory carcinomas of the breast and salivary gland; papillary thyroid carcinomas; infantile fibrosarcoma) and genomic (driver-negative non-small cell lung carcinomas, microsatellite instability-high colorectal adenocarcinomas, and wild-type gastrointestinal stromal tumors) triaging was put forward. RESULTS.­: Samples from 323 tumors were stained with the VENTANA pan-TRK EPR17341 Assay as a screening method. All positive IHC cases were simultaneously studied by 2 NGS tests, Oncomine Comprehensive Assay v3 and FoundationOne CDx. With this approach, the detection rate of NTRK fusions was 20 times higher (5.57%) by only screening 323 patients than the largest cohort in the literature (0.30%) comprising several hundred thousand patients. CONCLUSIONS.­: Based on our findings, we propose a multiparametric strategy (ie, "supervised tumor-agnostic approach") when pathologists start searching for NTRK fusions.

[Contribution of the occupational health to the COVID-19 pandemic control.] / Contribución de la salud laboral al control de la pandemia por covid-19 en España.

When the World Health Organization declared Covid-19 as a public health emergency of international concern, the Spanish Ministry of Health called the health, labor, social security authorities, Labor and Social Security Inspection, National Institute of Security and Occupational Health, employers, unions, occupational risk prevention services, mutual societies and scientific societies of occupational medicine and nursing, to collaborate in the control of the transmission of SARS-CoV-2 in companies. The Occupational Health Group of the Public Health Commission of the Interterritorial Council of the National Health System, developed the Procedure for the prevention of occupational risks in the face of exposure to SARS-CoV-2, which has been updated 15 times until the date. It contains the prevention measures to be implemented in the workplaces: organizational and collective protection, personal protection, especially vulnerable worker and risk level, study and management of cases and contacts that occurred in the company, collaboration in the management of temporary disability and, more recently, reincorporation and management of vaccinated workers. As a result of these cooperation and collaboration frameworks, a series of activities were deployed in the workplace, which are described in this article.

Cuando la Organización Mundial de la Salud declaró la Covid-19 como una emergencia de salud pública de importancia internacional, el Ministerio de Sanidad convocó a las autoridades sanitarias, laborales, de seguridad social, Inspección de Trabajo y Seguridad Social, Instituto Nacional de Seguridad y Salud en el Trabajo, empresarios, sindicatos, servicios de prevención de riesgos laborales, mutuas y sociedades científicas de la medicina y enfermería del trabajo, para colaborar en el control de la transmisión del SARS-CoV-2 en el ámbito de las empresas. La Ponencia de Salud Laboral de la Comisión de Salud Pública del Consejo Interterritorial del Sistema Nacional de Salud, elaboró el Procedimiento para los servicios de prevención de riesgos laborales frente a la exposición al SARS-CoV-2, que se ha actualizado 15 veces hasta la fecha. En él se recogen las medidas de prevención a implantar en los centros de trabajo: de carácter organizativo y de protección colectiva, de protección personal, de trabajador especialmente vulnerable y nivel de riesgo, de estudio y manejo de casos y contactos ocurridos en la empresa, de colaboración en la gestión de la incapacidad temporal y, más recientemente, de reincorporación y gestión de las y los trabajadores vacunados. Como resultado de esos marcos de cooperación y colaboración se desplegaron una serie de actividades en los lugares de trabajo que son descritas en este artículo.

Optimal lockdown in altruistic economies.

The recent COVID-19 crisis has revealed the urgent need to study the impact of an infectious disease on market economies and provide adequate policy recommendations. The present paper studies the optimal lockdown policy in a dynamic general equilibrium model where households are altruistic and they care about the share of infected individuals. The spread of the disease is modeled here using SIS dynamics, which implies that recovery does not confer immunity. To avoid non-convexity issues, we assume that the lockdown is constant in time. This strong assumption allows us to provide analytical solutions. We find that the zero lockdown is efficient when agents do not care about the share of infected, while a positive lockdown is recommended beyond a critical level of altruism. Moreover, the lockdown intensity increases in the degree of altruism. Our robust analytical results are illustrated by numerical simulations, which show, in particular, that the optimal lockdown never trespasses 60% and that eradication is not always optimal.

Pan-TRK Immunohistochemistry: An Example-Based Practical Approach to Efficiently Identify Patients With NTRK Fusion Cancer.

CONTEXT.­: Food and Drug Administration-approved TRK inhibitors with impressive overall response rates are now available for patients with multiple cancer types that harbor NTRK rearrangements, yet the identification of NTRK fusions remains a difficult challenge. These alterations are highly recurrent in extremely rare malignancies or can be detected in exceedingly small subsets of common tumor types. A 2-step approach has been proposed, involving a screening by immunohistochemistry (IHC) followed by a confirmatory method (fluorescence in situ hybridization, reverse transcriptase-polymerase chain reaction, or next-generation sequencing) in cases expressing the protein. However, there is no interpretation guide for any of the available IHC clones. OBJECTIVE.­: To provide a pragmatic update on the use of pan-TRK IHC. Selected examples of the different IHC staining patterns across multiple histologies are shown. DATA SOURCES.­: Primary literature review with PubMed, combined with personal diagnostic and research experience. CONCLUSIONS.­: In-depth knowledge of pan-TRK IHC will help pathologists implement a rational approach to the detection of NTRK fusions in human malignancies.

Assessment of a New ROS1 Immunohistochemistry Clone (SP384) for the Identification of ROS1 Rearrangements in Patients with Non-Small Cell Lung Carcinoma: the ROSING Study.

INTRODUCTION: The ROS1 gene rearrangement has become an important biomarker in NSCLC. The College of American Pathologists/International Association for the Study of Lung Cancer/Association for Molecular Pathology testing guidelines support the use of ROS1 immunohistochemistry (IHC) as a screening test, followed by confirmation with fluorescence in situ hybridization (FISH) or a molecular test in all positive results. We have evaluated a novel anti-ROS1 IHC antibody (SP384) in a large multicenter series to obtain real-world data. METHODS: A total of 43 ROS1 FISH-positive and 193 ROS1 FISH-negative NSCLC samples were studied. All specimens were screened by using two antibodies (clone D4D6 from Cell Signaling Technology and clone SP384 from Ventana Medical Systems), and the different interpretation criteria were compared with break-apart FISH (Vysis). FISH-positive samples were also analyzed with next-generation sequencing (Oncomine Dx Target Test Panel, Thermo Fisher Scientific). RESULTS: An H-score of 150 or higher or the presence of at least 70% of tumor cells with an intensity of staining of 2+ or higher by the SP384 clone was the optimal cutoff value (both with 93% sensitivity and 100% specificity). The D4D6 clone showed similar results, with an H-score of at least 100 (91% sensitivity and 100% specificity). ROS1 expression in normal lung was more frequent with use of the SP384 clone (p < 0.0001). The ezrin gene (EZR)-ROS1 variant was associated with membranous staining and an isolated green signal FISH pattern (p = 0.001 and p = 0.017, respectively). CONCLUSIONS: The new SP384 ROS1 IHC clone showed excellent sensitivity without compromising specificity, so it is another excellent analytical option for the proposed testing algorithm.

Intraosseous access EZ-IO in a prehospital emergency service.

BACKGROUND: Several scientific and professional associations have made reports and recommendations to regulate the use of intraosseous (IO) access as an alternative to conventional intravenous access (IA) in emergency situations when IA cannot be obtained. It has been well documented that IO access is safe and effective for fluid resuscitation, drug delivery, and blood collection. IO access is attainable in all age groups. OBJECTIVE: The objective of this prospective study was to test the use of a semi-automatic IO infusion system (EZ-IO) as an alternative to vascular access in critical patients treated in a prehospital emergency setting. METHOD: This prospective, cross-sectional study included patients who required immediate peripheral vascular access. This study was performed by reviewing clinical records and through a questionnaire (created by and for nurses who perform the insertion with the EZ-IO). RESULTS: During the study period we identified 107 patients who underwent EZ-IO insertion (114 insertions were performed). Patients were predominantly male (66%) and middle aged (mean age 56 years; range 3-94). Overall, insertion was performed via the proximal tibia (49.4%) distal tibia (25.2%), radius (14.9%), and humerus (10.5%). During the study period, 14 insertions were performed in 2007, 44 in 2008, and 56 in 2009. A majority of patients (50.9%) had medical cardiac arrest, (25.4%) were injured trauma patients, and 12.3% had traumatic cardiac arrest. All patients were transported to a hospital with 2 sites of peripheral vascular access. The first site of access in these patients was IO (100% of cases) and the second site (in 79% of cases) was peripheral intravenous access. All EZ-IO insertions were achieved within 30 seconds and were successful upon the first attempt. CONCLUSION: The use of the EZ-IO provides a quick (100% performed within 30 seconds), easy, and reliable alternative to conventional venous access in critically ill patients. Traditional peripheral venous access requires a minimal preparation that can delay initial treatment in critically ill patients and cause possible interference with resuscitation. The main advantage of using EZ-IO is to obtain secure, immediate, noncollapsible peripheral venous access in critically ill patients. It is possible to obtain a second site of access such as peripheral venous access to administer fluids and drugs, which can improve survival rates.

Participación activa de la mujer / Es

El proyecto participación activa de la mujer, trata de enfrentar la ausencia de la mujer boliviana en las estructuras de la decisión y poder de los ambitos socioeconomicos, educativos y politicos del desarrollo local, regional y nacional...