Factors influencing blood tumor marker concentrations in the absence of neoplasia.

BACKGROUND: Tumor markers (TMs) are a heterogeneous group of molecules used in the diagnosis, prognosis and follow-up of cancer patients. During neoplastic differentiation, cells can either directly synthesize or induce the synthesis of TMs, and the release of these molecules into the bloodstream allows their quantification in biological fluids. Although very small concentrations of TMs are usually present in the serum or plasma of healthy subjects, increased concentrations may also be found in the presence of benign diseases or due to technical interference, producing false positive results. MATERIAL AND METHODS AND RESULTS: Our review analyses the causes of false positives described between January 1970 to February 2023 for the TMs most frequently used in clinical practice: α-fetoprotein (AFP), ß2-microglobulin (ß2-M), cancer antigen 15-3 (CA 15-3), cancer antigen CA 19-9 (CA 19-9), cancer antigen CA 72-4 (CA 72-4), cancer antigen 125 (CA 125), carcinoembryonic antigen (CEA), chromogranin A (CgA), choriogonadotropin (hCG), cytokeratin 19 fragment (CYFRA 21-1), neuron-specific enolase (NSE), human epididymis protein 4 (HE4), serum HER2 (sHER2), squamous cell carcinoma antigen (SCCA), protein induced by vitamin K absence-II (PIVKA-II), Pro-gastrin-releasing peptide (Pro-GRP), prostate-specific antigen (PSA), Protein S-100 (S-100) and thyroglobulin (Tg). A total of 247 references were included. CONCLUSIONS: A better understanding of pathophysiological processes and other conditions that affect the concentration of TMs might improve the interpretation of results and their clinical application.

Variations in tumor growth, intra-individual biological variability, and the interpretation of changes.

OBJECTIVES: The identification of changes in tumor markers (TMs) in cancer patients that indicate response to treatment, stabilization or disease progression is a challenge for laboratory medicine. Several approaches have been proposed: assessing percentage increases, applying discriminant values, and estimating half-life (t1/2) or doubling time (DT). In all of them it is assumed that the TM is a surrogate of the variation in tumor size. In general this variation is time-dependent, but this is not the case of intraindividual biological variability (CVi), which can range from 6 % in CA15-3 to 22 % in CA125. When decisions are made on the basis of DT or t1/2, these values can be affected by the CVi; if it is very large, the growth rate very slow and the period of time between determinations very short, the result obtained for DT may be due mainly to the CVi. The aim of this study is to establish the relationship between the CVi and temporal variables. METHODS: We related equations for calculating DT and t1/2 to the reference change values in tumor markers. RESULTS: The application of the formula obtained allows the calculation of the optimal time between measurements to ensure that the influence of the CVi is minimal in different types of tumors and different scenarios. CONCLUSIONS: Intraindividual variation affects the calculation of DT and t1/2. It is necessary to establish the minimum time between two measurements to ensure that the CVi does not affect their calculation or lead to misinterpretation.

Uso del cigarrillo electronico y riesgo de padecer enfermedades respiratorias en adolescentes y adultos jóvenes

Objetivo: Determinar el riesgo de padecer enfermedades respiratorias por el uso del cigarrillo electrónico. Materiales y métodos: Revisión integrativa, basada en el análisis de artículos científicos completos en bases de datos como: PubMed, Scopus y SciELO utilizando el método PRISMA, en el periodo 2018-2023, en los idiomas inglés y español. Resultados: Se obtuvo 95 artículos científicos, de los cuales se excluyeron un total de 75 por no cumplir con los criterios de selección, quedando seleccionados 20 artículos científicos que responden a los objetivos planteados. Conclusiones: Este estudio identificó los riesgos de padecer enfermedades respiratorias por el uso del cigarrillo electrónico, siendo las más relevantes: enfermedad pulmonar obstructiva crónica, neumonía, lesión pulmonar asociada al cigarrillo electrónico o al vapeo, síndrome de distrés respiratorio, hipertensión pulmonar y asma, además de acompañarse de signos y síntomas como infección de las vías aéreas, el desarrollo de enfermedades cardiovasculares, gastrointestinales y el inicio de adicciones. El estudio identificó que el sexo masculino es el predominante en exponerse más al riesgo de enfermedades respiratorias y la edad oscila entre los 14 a 35 años, convirtiéndose en un problema de salud pública que cada año va en aumento.

Objective: To determine the risk of respiratory diseases due to the use of electronic cigarettes. Materials and Methods: Integrative review, based on the analysis of complete scientific articles in databases such as: PubMed, Scopus and SciELO, using the PRISMA method, in the period 2018-2023, in English and Spanish. Results: Of the 95 scientific articles that were obtained, 20 met the selection criteria and were selected to meet the stated objectives. The remaining 75 articles were excluded. Conclusions: This study identi fied the risks of suffering from respiratory diseases associated with the use of electronic cigarettes. The most significant risks include chronic obstructive pulmonary disease, pneumonia, lung injury associated with electronic cigarettes or vaping, respiratory distress syndrome, pulmonary hypertension, and asthma. Symptoms may also include signs and symptoms of respiratory infections, development of cardiovascular and gastrointestinal diseases, and the onset of addiction. The study found that males are more susceptible to respiratory diseases, with the 14-35 age group being particularly affected. This is becoming a growing public health concern.

Objetivo: Determinar o risco de doenças respiratórias devido ao uso de cigarros eletrônicos. Materiais e métodos: Revisão integrativa, baseada na análise de artigos científicos completos em bases de dados como: PubMed, Scopus e SciELO, utilizando o método PRISMA, no período de 2018 a 2023, em inglês e espanhol. Resultados: Foram obtidos 95 artigos científicos, dos quais um total de 75 foram excluídos por não atenderem aos critérios de seleção, restando 20 artigos científicos selecionados que respondem aos objetivos estabelecidos. Conclusões: Este estudo identificou os riscos de doenças respiratórias decorrentes do uso de cigarros eletrônicos, sendo as mais relevantes a doença pulmonar obstrutiva crônica, pneumonia, lesão pulmonar associada ao cigarro eletrônico ou vaping, síndrome do desconforto respiratório, hipertensão pulmonar e asma, além de serem acompanhadas de sinais e sintomas como infecção das vias aéreas, desenvolvimento de doença cardiovascular, doença gastrointestinal e início de dependência. O estudo identificou que o sexo masculino está predominantemente exposto ao risco de doenças respiratórias e a idade varia de 14 a 35 anos, tornando-se um problema de saúde pública que aumenta a cada ano.

Inmunoensayo quimioluminiscente para sífilis en donantes de sangre: ¿Los valores de lectura se correlacionan con el estado de la infección? / Chemiluminescent immunoassay for syphilis in blood donors: do signal strength values correlate with the infection status? / Imunoensaio quimioluminescente para sífilis em doadores de sangue: os valores de leitura estão correlacionados com o estado da infecção?

Resumen El objetivo del trabajo fue comparar el desempeño del tamizaje treponémico y no treponémico en dos períodos próximos en el tiempo en donantes de sangre y analizar la asociación de la intensidad de la señal de la prueba quimioluminiscente (QL) con la reactividad del enzimoinmunoanálisis (ELISA) y la reagina plasmática rápida (RPR). Se realizó el tamizaje con pruebas treponémicas. Se analizó la distribución de los valores de señal/valor de corte (S/CO) obtenidos por QL en función del ELISA y RPR y se evaluó su asociación entre dos grupos de resultados de laboratorio (1) ELISA+/RPR+ y (2): ELISA+/RPR-. Se procesaron 76 794 donaciones voluntarias. Al comparar las medianas entre grupos, se encontró que la relación S/CO de QL fue significativamente mayor para los donantes del Grupo 1 (19,5 vs. 8,10; p<0,001). Se concluye que la intensidad de la señal de la prueba cualitativa QL estaría asociada con la reactividad de la RPR y guardaría relación con el curso de la infección.

Abstract The objective of this work was to compare the performance of treponemal and non-treponemal screening in two periods close in time in blood donors and to analyse the association of the signal strength (signal-to-cutoff, S/ CO) of the chemiluminescent immunoassay (CIA) with the reactivity of the enzymeimmunoassay (EIA) and the rapid plasma reagin (RPR). Donors were screened with treponemal tests. The distribution of the S/CO values obtained by CIA was analysed based on EIA and RPR, and its association was evaluated. Group 1: ELISA+/RPR+ donors and Group 2: ELISA+/RPR-. A total of 76,794 voluntary donations were processed. Comparing the means between groups, it was found that the CIA S/CO ratio was significantly higher for Group 1 donors (19.5 vs. 8.10; p<0.001). In conclusion, the signal strength of the qualitative CIA test would be associated with the reactivity of the RPR and would be related to the course of the infection.

Resumo O objetivo do trabalho foi comparar o desempenho da triagem treponêmica e não treponêmica em dois períodos próximos no tempo em doadores de sangue e analisar a associação da intensidade do sinal da prova quimioluminescente (QL) com a reatividade da análise imunoenzimática (ELISA) e a reagina plasmática rápida (RPR). Foi realizada uma triagem com provas treponêmicas. Foi analisada a distribuição dos valores de sinal/valor de corte (S/CO) obtidos por QL em função da ELISA e RPR, e também a associação entre dois grupos de resultados laboratoriais (1): ELISA+/RPR+ e (2) ELISA+/ RPR-). Foram procesadas 76 794 doações de sangue voluntárias. Ao comparar as medianas entre os grupos, obteve-se que a relação S/CO de QL foi significativamente maior para os doadores de sangue do grupo 1 (19,5 vs. 8,10; p<0,001). Em conclusão, a intensidade do sinal da prova qualitativa QL estaria associada com a reatividade da RPR e guardaria relação com o curso da infecção.

Utility of human epididymis protein 4 in the differential diagnosis of ascites.

BACKGROUND AND AIMS: Human epididymal protein 4 (HE4) may be a useful tool in the differential diagnosis of malignant ascites. The aim of this study was to evaluate the diagnostic utility of HE4 for detecting malignant ascites, taking into account the possible false positives identified with adenosine deaminase (ADA), C-reactive protein (CRP), % polynuclear cells (%PMN) and glomerular filtration rate (eGFR). METHODS: Concentrations of HE4, ADA, %PMN and CRP were determined in 114 samples of peritoneal fluid and creatinine in serum in order to calculate eGFR. RESULTS: Concentrations of HE4 presented significant differences (P = 0.028) in benign [median (interquartile range)] [582(372)] pmol/L) and malignant ascites ([8241(367)] pmol/L. Sensitivity was 21.2% and specificity 100%. Significant differences were also observed for HE4 between tumors of gynecological origin ([3165(8769)] pmol/L) and others ([665(663)] pmol/L), with a sensitivity of 67% and a specificity of 100%. Classifying according to possible false positives (ADA > 45U/L, CRP > 50 mg/L, %PMN > 90 and eGFR < 30 mL/min/1.73 m2) at maximum specificity, a sensitivity of 33.3% was obtained for HE4, with a cut-off point of 2660 pmol/L. Without possible false positives (ADA < 45U/L, CRP < 50 mg/L, %PMN < 90 and eGFR ≥ 30 mL/min/1.73 m2), a sensitivity of 37.7% was obtained at 100% specificity for a cut-off point of 1041 pmol/L. Applying these criteria to the entire group, a sensitivity of 36.4% was obtained at maximum specificity. CONCLUSIONS: HE4 allows the identification of malignant ascites with moderate sensitivity at maximum specificity. HE4 levels can differentiate between tumors of gynecological origin and others. Classification according to possible false positives increases sensitivity without losing specificity.

Nivel de ansiedad en adolescentes con sobrepeso u obesidad

Objetivo: Conocer el nivel de ansiedad en los adolescentes con sobrepeso u obesidad. Material y Método: Estudio cuantitativo, no experimental, descriptivo y transversal, realizado entre abril y agosto 2023 en una Unidad Educativa del cantón Ambato, provincia de Tungurahua, Ecuador. De una población de 109 estudiantes, la muestra definitiva fueron 71 adolescentes con sobrepeso y obesidad pertenecientes al Octavo, Noveno y Décimo grado de Educación General Básica (EGB). Para medir la ansiedad se aplicó el cuestionario Beck Anxiety Inventory (BAI) validado y con alto nivel de confiabilidad (Alfa Cronbach: 0,82); para el estado nutricional se midieron la Circunferencia de Cintura (CC) y el Índice de Masa Corporal (IMC) junto a variables demográficas: sexo y edad. Resultados: 54% de sexo masculino, 38% en noveno año de EGB y un nivel moderado de ansiedad. Conclusión: Más de la mitad de los adolescentes presentan sobrepeso u obesidad, evidenciándose predominio del sexo masculino, específicamente en el noveno año de EGB y existe un nivel moderado de ansiedad en la mayoría de la muestra estudiada con mayor frecuencia en el sexo femenino. Es importante que el personal de enfermería eduque a la población sobre todo a los adolescentes sobre los beneficios que otorga a la salud el llevar un estilo de vida saludable.

Objective: To determine the level of anxiety in overweight or obese adolescents. Material and Method: Quantitative, non-experimental, descriptive and cross-sectional study, conducted from April to August 2023, in an educational unit of the canton of Ambato, Province of Tungurahua, Ecuador. From a population of 109 students, the final sample consisted of 71 adolescents with overweight or obesity belonging to the eighth, ninth and tenth grades of General Basic Education (GBS). To measure anxiety, the Beck Anxiety Inventory (BAI) questionnaire was used, which has been validated with high reliability (Cronbach's alpha: 0.82); for nutritional status, waist circumference (WC) and body mass index (BMI) were measured, along with the demographic variables sex and age. Results: 54% male, 38% in the ninth year of GBS and a moderate level of anxiety. Conclusions: More than half of the adolescents are overweight and obese, with a predominance of males, especially in the ninth year of GBS, and there is a moderate level of anxiety in most of the sample studied, with a higher frequency in females. It is important for nursing staff educate the population, especially adolescents, about the health benefits of a healthy lifestyle.

Objetivo: Determinar o nível de ansiedade em adolescentes com sobrepeso ou obesidade. Material e Método: Estudo quantitativo, não experimental, descritivo e transversal, realizado entre abril e agosto de 2023, em uma unidade educacional do cantão de Ambato, província de Tungurahua, Equador. De uma população de 109 estudantes, a amostra final foi composta por 71 adolescentes com sobrepeso ou obesidade pertencentes ao oitavo, nono e décimo anos do Ensino Básico Geral (EGB). Para mensurar a ansiedade foi utilizado o questionário Beck Anxiety Inventory (BAI), que foi validado com alta confiabilidade (alfa de Cronbach: 0,82); para o estado nutricional foram aferidos a circunferência da cintura (CC) e o índice de massa corporal (IMC), além das variáveis demográficas sexo e idade. Resultados: 54% do sexo masculino, 38% no nono ano de EBG e nível moderado de ansiedade. Conclusões: Mais da metade dos adolescentes apresentam excesso de peso e obesidade, com predominância do sexo masculino, sobretudo no nono ano de EGB, e existe um nível moderado de ansiedade na maior parte da amostra estudada, com maior frequência no sexo feminino. E importante que a equipe de enfermagem eduque a população, principalmente os adolescentes, sobre os benefícios para a saúde de um estilo de vida saudável.

Lung cancer tumor markers in serous effusions and other body fluids.

From its onset and during its progression, lung cancer may affect various extrapulmonary structures. These include the serous membranes, the pleura and pericardium, and less frequently the central nervous system, with leptomeningeal involvement. In these cases, fluid accumulates in the serous membranes which may contain substances secreted by the tumor. Measuring the concentrations of these substances can provide useful information for elucidating the origin of the fluid accumulation, either in pleural and pericardial effusions or in cerebrospinal fluid. This paper describes the histological types of lung cancer that most frequently affect the serosa and leptomeninges. It also reviews the literature on tumor markers in different fluids and makes recommendations for their interpretation.

Funcionalidad y personas mayores: ¿dónde estamos y hacia dónde ir? / Functionality and seniors: where are we and where should we be going? / Funcionalidade e pessoas idosas: onde estamos e para onde devemos ir?

RESUMEN El proceso de envejecimiento poblacional llevará a un aumento en problemas de salud en personas mayores, principalmente relacionados a su funcionalidad. En esta línea, los países de la Región de las Américas deben comenzar a actuar para hacer frente a este desafío. Una de las tareas fundamentales en este reto tiene que ver con la capacidad de medir y monitorear la funcionalidad de la población. Los instrumentos utilizados para evaluarla están enfocados principalmente en las actividades básicas de la vida diaria, lo que limita su capacidad preventiva por ser las actividades instrumentales las que permiten un mejor pronóstico. Usando el caso de Chile identificamos desafíos para la Región, principalmente relacionados con las ventajas de incorporar nuevas metodologías de evaluación de la capacidad funcional que no solo permitan las estrategias actuales sino, también, detectar precozmente su deterioro y monitorear sus estadios a lo largo de la dependencia en las personas mayores. Ello permitirá, a la vez, evaluar las iniciativas de prevención y manejo de la pérdida de la funcionalidad.

ABSTRACT The process of population aging will lead to an increase in health problems in older people, mainly related to their functionality. Accordingly, the countries of the Region of the Americas must begin to act to meet this challenge. One of the fundamental tasks involves the ability to measure and monitor functionality in the population. The tools used to evaluate functionality focus mainly on the basic activities of daily living, which limits their preventive capacity, since instrumental activities provide a better prognosis. Using the case of Chile, challenges for the Region were identified, mainly related to the advantages of adopting new methodologies that not only evaluate functional capacity, as current strategies do, but also detect its deterioration early and monitor its stages throughout the dependence stage in older people. This will also make it possible to evaluate initiatives for the prevention and management of loss of functionality.

RESUMO O processo de envelhecimento populacional levará a um aumento de problemas de saúde nas pessoas idosas, principalmente relacionados à sua funcionalidade. Nesse sentido, os países da Região das Américas devem começar a agir para enfrentar esse desafio. Uma das tarefas fundamentais está relacionada à capacidade de medir e monitorar a funcionalidade da população. Os instrumentos utilizados para avaliá-la estão voltados principalmente para as atividades básicas da vida diária, o que limita sua capacidade preventiva, já que são as atividades instrumentais que permitem um melhor prognóstico. Utilizando o caso do Chile, identificamos desafios para a Região, principalmente relacionados às vantagens de incorporar novas metodologias de avaliação da capacidade funcional que não só habilitem as estratégias atuais, mas também detectem precocemente a deterioração da funcionalidade e monitorem suas fases ao longo da dependência das pessoas idosas. Isso permitirá, ao mesmo tempo, avaliar as iniciativas de prevenção e manejo da perda de funcionalidade.

Tumour Markers in the Differential Diagnosis of Patients With Isolated Involuntary Weight Loss.

BACKGROUND/AIM: Paraneoplastic syndrome symptoms include isolated involuntary weight loss (IIWL). The differential diagnosis of cancer from other diseases may require a significant number of tests. Tumour markers (TMs) can be used for the diagnosis and stratification of patients according to cancer risk. PATIENTS AND METHODS: This study included 606 patients (48% females) seen at the rapid diagnostic unit for IIWL. We determined the levels of TMs carcinoembryonic antigen, carbohydrate antigen 19-9, soluble fragments of cytokeratin 19, carbohydrate antigen 15-3, carbohydrate antigen 125, neuron specific enolase, alpha-fetoprotein, prostatic specific antigen using the multiparametric analyser COBAS 601. Two cut-off points were established, the upper reference limit described by the manufacturer and a high cut-off point suggested by Molina et al., to stratify patients according to cancer risk. RESULTS: Patients were classified according to TM levels as follows: I) all TMs below the upper reference limit; II) highest number of TMs between the two cut-offs; III) at least one TM above the higher cut-off. The odds ratio for malignancy was 4.3 for group II and 248 for group III. These results indicate that when at least one TM is above the higher cut-off, neoplasia is highly probable. CONCLUSION: TM determination allowed to establish cancer risk in patients with IIWL.

Characterization of Total and Unprotonated (Free) Nicotine Content of Nicotine Pouch Products.

INTRODUCTION: Nicotine pouch products, oral smokeless products that contain nicotine but no tobacco leaf material, have recently entered the US marketplace. Available data indicate sales of these products in the United States have increased since 2018; however, the extent of use among US youth and adults is uncertain. METHODS: To assay the chemistry of these emerging tobacco products, we analyzed 37 nicotine pouch brands from six total manufacturers. Almost all of the products had flavor descriptors (36 of 37), such as mint, licorice, coffee, cinnamon, and fruit. The amount of free nicotine, the form most easily absorbed, was calculated for each product using total nicotine, product pH, the appropriate pKa, and the Henderson-Hasselbalch equation. RESULTS: Nicotine pouch products varied in pouch content mass, moisture content (1.12%‒47.2%), alkalinity (pH 6.86‒10.1), and % free nicotine (7.7%‒99.2%). Total nicotine content ranged from 1.29 to 6.11 mg/pouch, whereas free nicotine ranged from 0.166 to 6.07 mg/pouch. These findings indicate that nicotine and pH levels found in some of these nicotine pouches are similar to conventional tobacco products, such as moist snuff and snus, and that most of these pouch products are flavored. CONCLUSIONS: Although these products likely lack many tobacco-related chemicals, each product analyzed contained nicotine, which is both addictive and can harm human health. Given that nicotine pouches may appeal to a spectrum of users, from novice to experienced users, it is important to include these emerging tobacco products in tobacco control research, policy, and practice. IMPLICATIONS: These "tobacco-free" nicotine pouches have similar pH and nicotine content to conventional tobacco products, such as moist snuff and snus. Although they lack many tobacco-related chemicals, most are highly flavored which could increase experimentation from new users. Given that nicotine pouches may appeal to a spectrum of users, from novice to experienced users, in terms of their flavors and nicotine content, it is important to examine and include these emerging tobacco products as they relate to tobacco control research, policy, and practice.

Estilos de alimentación y su asociación con apreciación corporal, internalización del sesgo del peso y autocompasión / Eating styles and their association with body appreciation, weight bias internalization and self-compassion

Resumen Antecedentes: La valoración de la delgadez y sesgo hacia las personas con sobrepeso, pueden promover menor valoración del cuerpo y estilos de alimentación desadaptativos; la autocompasión podría actuar mitigando estas relaciones. Objetivo: comprender la asociación entre apreciación corporal, internalización del sesgo del peso y estilos de alimentación (EA), así como el rol que cumple una actitud autocompasiva en la apreciación corporal. Método: Estudio correlacional, transversal, en el que participaron 837 adultos residentes en Chile. En el análisis de datos se empleó regresión múltiple y análisis de mediación. Resultados: La apreciación corporal y la internalización del sesgo del peso predijeron EA emocional (β = -,126; p <,001 y β = ,146 p <,001, respectivamente), EA externo (β = -,095; p <,001 y β = ,064 p <,001, respectivamente) y EA restrictivo (β = ,134; p <,001 y β = ,258; p <,001, respectivamente). La autocompasión medió la relación entre internalización del sesgo del peso y apreciación corporal (β = -,133; IC:[-,157; −0,11]). Conclusiones: La valoración del cuerpo y la internalización del sesgo del peso influyen en los EA, y una actitud compasiva hacia sí mismo media en el efecto del sesgo del peso sobre la devaluación hacia el propio cuerpo.

Abstract Background: The assessment of thinness and bias towards overweight people can promote body appreciation and maladaptive eating styles; self-compassion could act mitigating these relationships. Objective: to understand the association between body appreciation, weight bias internalization and eating styles (ES), as well as the role of a self-compassionate attitude in body appreciation. Method: Correlational, cross-sectional study, with 837 adults living in Chile. In the data analysis, multiple regression and mediation analysis were used. Results: Body appreciation and internalization of weight bias predicted emotional ES (β = -.126; p < .001 and β = .146; p < .001, respectively), external ES (β = -.095; p < .001 and β = .064; p < .001, respectively) and restrictive ES (β = -.134; p < 001 and β = .258; p < .001, respectively). Self-compassion mediated the relationship between internalization of weight bias and body appreciation (β = -.133, CI: [- .157, -.11]). Conclusions: The assessment of the body and the weight bias internalization influence eating styles, and a compassionate attitude towards oneself intervenes in the effect of the weight bias on the devaluation towards the own body.

EMA Review of Acalabrutinib for the Treatment of Adult Patients with Chronic Lymphocytic Leukemia.

On November 5, 2020, a marketing authorization valid through the European Union (EU) was issued for acalabrutinib monotherapy or acalabrutinib in combination with obinutuzumab (AcalaObi) in adult patients with treatment-naïve (TN) chronic lymphocytic leukemia (CLL) and also for acalabrutinib monotherapy in adult patients with relapsed or refractory (RR) CLL. Acalabrutinib inhibits the Bruton tyrosine kinase, which plays a significant role in the proliferation and survival of the disease. Acalabrutinib was evaluated in two phase III multicenter randomized trials. The first trial (ACE-CL-007) randomly allocated acalabrutinib versus AcalaObi versus chlorambucil plus obinutuzumab (ChlObi) to elderly/unfit patients with TN CLL. The progression-free survival (PFS), as assessed by an independent review committee, was superior for both the AcalaObi (hazard ratio [HR], 0.1; 95% confidence interval [CI], 0.06-0.17) and acalabrutinib (HR, 0.2; 95% CI, 0.13-0.3) arms compared with the ChlObi arm. The second trial (ACE-CL-309) randomly allocated acalabrutinib versus rituximab plus idelalisib or bendamustine to adult patients with RR CLL. Also in this trial, the PFS was significantly longer in the acalabrutinib arm (HR, 0.31; 95% CI, 0.20-0.49). Adverse events for patients receiving acalabrutinib varied across trials, but the most frequent were generally headache, diarrhea, neutropenia, nausea, and infections. The scientific review concluded that the benefit-risk ratio of acalabrutinib was positive for both indications. This article summarizes the scientific review of the application leading to regulatory approval in the EU. IMPLICATIONS FOR PRACTICE: Acalabrutinib was approved in the European Union for the treatment of adult patients with chronic lymphocytic leukemia who have not received treatment before and for those who have received therapy but whose disease did not respond or relapsed afterward. Acalabrutinib resulted in a clinically meaningful and significant lengthening of the time from treatment initiation to further disease relapse or patient's death compared with standard therapy. The overall safety profile was considered acceptable, and the benefit-risk ratio was determined to be positive.

EMA Review of Daratumumab (Darzalex) for the Treatment of Adult Patients Newly Diagnosed with Multiple Myeloma.

The use of daratumumab in combination with established regimens for the treatment of newly diagnosed multiple myeloma has recently been authorized by the European Medicines Agency based on results from three separate phase III randomized, active controlled, open-label studies that have confirmed enhanced efficacy and tolerability in both transplant-ineligible (MMY3008 and MMY3007) and transplant-eligible (MMY3006) patients, without compromising transplant ability. Trial MMY3008 showed an improvement in progression-free survival (PFS) when daratumumab was added to lenalidomide and dexamethasone compared with lenalidomide and dexamethasone; the median PFS had not been reached in the daratumumab arm and was 31.9 months in the control arm (hazard ratio [HR], 0.56; 95% confidence interval [CI], 0.43-0.73; p < .0001). Trial MMY3007 showed an improvement in PFS when daratumumab was added to bortezomib, melphalan, and prednisone compared with bortezomib, melphalan, and prednisone; PFS had not been reached in the daratumumab arm and was 18.1 months in the control arm (HR, 0.5; 95% CI, 0.38-0.65; p < .0001). In trial MMY3006, daratumumab added to bortezomib, thalidomide, and dexamethasone was compared with bortezomib, thalidomide, and dexamethasone as induction and consolidation treatment prior to autologous stem cell transplant. The stringent complete response rate at day 100 after transplant in the daratumumab group was 29% compared with 20% in the control group (odds ratio, 1.60; 1.21-2.12 95% CI; p = .0010). Overall adverse events were manageable, with an increased rate of neutropenia and infections in the daratumumab arms. Regulatory assessment of efficacy and safety results from trials MMY3006, MMY3007, and MMY3008 confirmed a positive benefit-risk ratio leading to an approval of the extensions of indication. IMPLICATIONS FOR PRACTICE: A set of extensions of indication was recently approved for daratumumab (Darzalex) in the setting of newly diagnosed multiple myeloma in combination with established regimens. Results of the MMY3006, MMY3007, and MMY3008 trials have shown enhanced efficacy and a favorable side effect profile of several daratumumab-based combinations in patients both ineligible and eligible for transplant, without compromising transplant ability. The combinations of daratumumab with either lenalidomide and low-dose dexamethasone or bortezomib, melphalan, and prednisone were approved for transplant-ineligible patients. The combination of daratumumab with bortezomib, thalidomide, and dexamethasone was approved for transplant-eligible patients. These combinations are expected to improve the survival outlook for patients with multiple myeloma, without an unacceptable risk of increase in adverse events, and updated information on progression-free survival and overall survival is expected from the above trials.

BVDV-1 induces interferon-beta gene expression through a pathway involving IRF1, IRF7, and NF-κB activation.

The bovine viral diarrhea virus (BVDV-1) is a pathogen with the capacity to modulate the interferon type I system. To further investigate the effects of BVDV-1 on the production of the immune response, the Madin-Darby bovine kidney cell line was infected with the cytopathic CH001 field isolate of BVDV-1, and the IFNbeta expression profiles were analyzed. The results showed that cpBVDV-1 was able to induce the production of IFNbeta in a way similar to polyinosinic-polycytidylic acid, but with less intensity. Interestingly, all cpBVDV-1 activities were blocked by pharmacological inhibitors of the IRF-1, IRF-7, and NF-κB signaling pathway, and the level of IFNbeta decreased at the level of transcript and protein. These results, together with in silico analyses showing the presence of several regulatory consensus target motifs, suggest that cpBVDV-1 regulates IFNbeta expression in bovines through the activation of several key transcription factors. Collectively, the results suggest that during cpBVDV-1 infection, cross talk is evident between various signaling pathways involved in transcriptional activation of IFNbeta in cattle.

Comparative Assessment of Two Strategies for Interpreting Tumor Markers in Ascitic Effusions.

BACKGROUND/AIM: There are two strategies for the interpretation of tumor markers (TM) in fluid effusions: i) high cut-off and ii) fluid/serum ratio (F/S) and low cut-off. The objective of this study is to compare these two strategies and to determine whether diagnostic accuracy improves by the identification of possible false positives using Adenosine deaminase (ADA), C reactive protein (CRP) and % of polymorphonuclear cells (%PN). PATIENTS AND METHODS: We studied 157 ascitic fluids, 74 of which were malignant. ADA, CRP and %PN were determined in ascitic fluid, and Carcinoembryonic antigen (CEA), Cancer antigen 72-4 (CA72-4), Cancer antigen CA19-9 and Cancer antigen 15-3 (CA15-3) in both fluid and serum. RESULTS: The strategy of high cut-off showed 59.5% sensitivity at 100% specificity. The F/S strategy showed 75.7% sensitivity at 95.2% specificity. Subclassifying cases with ADA, CRP and %PN negative showed 67.5% sensitivity at 100% specificity for high cut-off and for the F/S strategy was 81.7% sensitivity at 98.7% specificity. CONCLUSION: The strategy of F/S with negative ADA, CRP and %PN allow the best interpretation for TM in the ascitic fluid.

Chemical analysis of snus products from the United States and northern Europe.

INTRODUCTION: Snus is an oral tobacco product that originated in Sweden. Snus products are available as fine-cut loose tobacco or in pre-portioned porous "pouches." Some snus products undergo tobacco pasteurization during manufacturing, a process that removes or reduces nitrite-forming microbes, resulting in less tobacco-specific nitrosamine content in the product. Some tobacco companies and researchers have suggested that snus is potentially less harmful than traditional tobacco and thus a potential smoking cessation aid or an alternative to continued cigarette consumption. Although snus is available in various countries, limited information exists on snus variants from different manufacturers. METHODS: Moisture, pH, nicotine, and tobacco-specific N'-nitrosamines (TSNAs) were quantified in 64 snus products made by 10 manufacturers in the United States and Northern Europe (NE). Reported means, standard errors, and differences are least-square (LS) estimates from bootstrapped mixed effects models, which accounted for correlation among repeated measurements. Minor alkaloids and select flavors were also measured. RESULTS: Among all product types, moisture (27.4%-59.5%), pH (pH 5.87-9.10), total nicotine (6.81-20.6 mg/g, wet), unprotonated nicotine (0.083-15.7 mg/g), and total TSNAs (390-4,910 ng/g) varied widely. The LS-mean unprotonated nicotine concentration of NE portion (7.72 mg/g, SE = 0.963) and NE loose (5.06 mg/g, SE = 1.26) snus were each significantly higher than US portion snus (1.00 mg/g, SE = 1.56). Concentrations of minor alkaloids varied most among products with the highest total nicotine levels. The LS-mean NNN+NNK were higher in snus sold in the US (1360 ng/g, SE = 207) than in NE (836 ng/g, SE = 132) countries. The most abundant flavor compounds detected were pulegone, eucalyptol, and menthol. CONCLUSION: Physical and chemical characteristics of US and NE products labeled as snus can vary considerably and should not be considered "equivalent". Our findings could inform public health and policy decisions pertaining to snus exposure and potential adverse health effects associated with snus.

Vitamin E Acetate in Bronchoalveolar-Lavage Fluid Associated with EVALI.

BACKGROUND: The causative agents for the current national outbreak of electronic-cigarette, or vaping, product use-associated lung injury (EVALI) have not been established. Detection of toxicants in bronchoalveolar-lavage (BAL) fluid from patients with EVALI can provide direct information on exposure within the lung. METHODS: BAL fluids were collected from 51 patients with EVALI in 16 states and from 99 healthy participants who were part of an ongoing study of smoking involving nonsmokers, exclusive users of e-cigarettes or vaping products, and exclusive cigarette smokers that was initiated in 2015. Using the BAL fluid, we performed isotope dilution mass spectrometry to measure several priority toxicants: vitamin E acetate, plant oils, medium-chain triglyceride oil, coconut oil, petroleum distillates, and diluent terpenes. RESULTS: State and local health departments assigned EVALI case status as confirmed for 25 patients and as probable for 26 patients. Vitamin E acetate was identified in BAL fluid obtained from 48 of 51 case patients (94%) in 16 states but not in such fluid obtained from the healthy comparator group. No other priority toxicants were found in BAL fluid from the case patients or the comparator group, except for coconut oil and limonene, which were found in 1 patient each. Among the case patients for whom laboratory or epidemiologic data were available, 47 of 50 (94%) had detectable tetrahydrocannabinol (THC) or its metabolites in BAL fluid or had reported vaping THC products in the 90 days before the onset of illness. Nicotine or its metabolites were detected in 30 of 47 of the case patients (64%). CONCLUSIONS: Vitamin E acetate was associated with EVALI in a convenience sample of 51 patients in 16 states across the United States. (Funded by the National Cancer Institute and others.).

Endocarditis infecciosa en válvula tricúspide: Presentación clínica y evolución en paciente sin factores de riesgo clásicos. Endocarditis infecciosa tricuspídea: a propósito de un caso / Infective endocarditis in the tricuspid valve: Clinical presentation and evolution in patient without classic risk factors. Tricuspid infectious endocarditis: a case report

Infective endocarditis (IE) correspond to a serious condition of the endocardium, with clinical and classic risk factors. Heart failure is described as the main complication and cause of mortality. A 58-year-old diabetic female patient, with fever, weight loss and history of 10 months of fatigue, is presented below. She is hospitalized in Hospital Regional de Talca, in Medicine Service, where she is diagnosed of right IE by blood cultures (Streptococcus Sanguis) and transthoracic echocardiogram, that showed vegetations in the tricuspid valve and severe insufficiency. Without clinical improvement despite antibiotic treatment, echocardiography is repeated, showing persistence of vegetations and insufficiency, so that surgical resolution is decided, taking place in Hospital Gustavo Grant Benavente Concepción, with clinical recovery after surgery. It highlights a classic and larval presentation of the disease, but without classic risk factors for right IE, also associated with glomerulonephritis. The antibiotic eliminated bacteremia, but the valve damage was already established.