Poziotinib treatment in patients with HER2-positive advanced breast cancer who have received prior anti-HER2 regimens.

PURPOSE: Poziotinib is an irreversible pan-inhibitor of the human epidermal growth factor receptor (HER) that has shown acceptable tolerability and antitumor activity in phase I and II trials in patients with advanced solid tumors. In the present open-label, multicenter phase II study, we demonstrate safety, tolerability, and preliminary efficacy data from two different dosing schedules in patients with HER2-positive advanced breast cancer. PATIENTS AND METHODS: Patients who had received at least two prior HER2-directed therapy lines for advanced disease, received 24 mg poziotinib on an intermittent dosing schedule (cohort 1) or 16 mg poziotinib once daily on a continuous dosing schedule (cohort 2). The primary endpoint was overall response rate (ORR). Secondary endpoints were progression-free survival (PFS), disease control rate (DCR), and time to progression (TTP). Secondary endpoints additionally included safety and pharmacokinetics. RESULTS: A total of 67 patients were enrolled. The ORR was 30% in both groups (p = 0.98). DCR was 60% vs 78% (p = 0.15) and median PFS and TTP were 4.1 vs 4.9 months (both p = 0.30) for cohorts 1 and 2, respectively. The most common treatment related adverse events (AEs) of any grade included diarrhea (88% vs 85%, p = 0.76), rash (88% vs 88%, p = 0.96), and stomatitis (64% vs 56%, p = 0.52), with grade 3-4 diarrhea occurring in 33% vs 32% of patients (p = 0.93) and grade 3-4 rash in 27% vs 35% of patients (p = 0.48) in cohort 1 vs cohort 2, respectively. CONCLUSION: Poziotinib demonstrated evidence of clinical activity in patients with pre-treated HER2-positive advanced breast cancer, although high levels of toxicity may preclude further studies at this time.

Grupo Científico Estudiantil Tecnología y Ciencia. Experiencias en la divulgación científica

Introducción: La divulgación científica no debe verse solo como una actividad propia del profesional de la comunicación o del periodismo. Saber divulgar una investigación científica es una forma de gestión del conocimiento adquirido. Objetivo: Describir las experiencias en la divulgación científica del Grupo Científico Estudiantil Tecnología y Ciencia. Método: Se realizó un estudio observacional, descriptivo y transversal. Durante el período comprendido de octubre de 2020 a mayo de 2023 en la Universidad de Ciencias Médicas de Cienfuegos, Cuba. La información se recopiló a partir del análisis de las evidencias de trabajo del Grupo Científico Estudiantil. Las experiencias se describieron teniendo en cuenta las acciones, actividades y espacios creados para el desarrollo de la divulgación científica. Resultados: El Grupo Científico Estudiantil está integrado por 14 estudiantes de las diferentes carreras de las ciencias médicas. De ellos: 7 son estudiantes de Medicina, 2 pertenecen a Estomatología, 3 a las Tecnologías de la Salud y 2 a la carrera de Enfermería. En cuanto al sexo el 57 % son masculinos y el 43 % femeninos. El trabajo sistemático con el Grupo Científico Estudiantil ha permitido avanzar considerablemente en cuanto a organización y desarrollo de eventos donde se socializan y divulgan resultados científicos, además la sostenibilidad del trabajo en equipo ha permitido que se publiquen en revistas científicas los aportes que se derivan de los resultados. Conclusiones: El trabajo del Grupo Científico Estudiantil Tecnología y Ciencia juega un papel decisivo en la comunidad universitaria, pues organiza actividades científicas y académicas en aras de incrementar el desarrollo científico estudiantil.

Introduction: Scientific dissemination should not be seen only as an activity of the communication or journalism professional. Knowing how to disseminate scientific research is a form of management of acquired knowledge. Objective: To describe the experiences in scientific dissemination of the Student Scientific Group: Technology and Science. Method: An observational, descriptive and cross-sectional study was carried out. During the period from October 2020 to May 2023 at the University of Medical Sciences of Cienfuegos, Cuba. The information was compiled from the analysis of the GCE's work evidence. The experiences were described taking into account the actions, activities and spaces created for the development of scientific dissemination. Results: The GCE is madeup of 14 students from different careers in medical sciences. Of them: seven are medical students, two belong to Stomatology, three to Health Technologies, and two to the Nursing career. Regarding sex, 57% are male and 43% female. The systematic work with the GCE has allowed for considerable progress in terms of organization and development of events where scientific results are socialized and disseminated, and the sustainability of team work has allowed the contributions derived from the results to be published in scientific journals. Conclusions: The work of the GCE: Technology and Science plays a decisive role in the university community, as it organizes scientific and academic activities in order to increase student scientific development.

Introdução: A divulgação científica não deve ser vista apenas como uma atividade do profissional de comunicação ou jornalismo. Saber divulgar pesquisas científicas é uma forma de gestão do conhecimento adquirido. Objetivo: Descrever as experiências de divulgação científica do Grupo Científico de Estudantes de Tecnologia e Ciências. Método: Foi realizado estudo observacional, descritivo e transversal. Durante o período de outubro de 2020 a maio de 2023 na Universidad de Cieências Médicas de Cienfuegos, Cuba. As informaçõ es foram compiladas a partir da análise das evidências de trabalho do Grupo Científico Estudantil. As experiências foram descritas levando em consideração as ações, atividades e espaços criados para o desenvolvimento da divulgação científica. Resultados: O Grupo Científico Estudantil é composto por 14 estudantes de diferentes carreiras das ciências médicas. Destes: 7 são estudantes de Medicina, 2 pertencem à Estomatologia, 3 às Tecnologias da Saúde e 2 à carreira de Enfermagem. Quanto ao sexo, 57% são homens e 43% mulheres. O trabalho sistemático com o Grupo Científico de Estudantes tempermitido avanços consideráveis em termos de organização e desenvolvimento de eventos onde os resultados científicos são socializados e divulgados, além disso a sustentabilidade do trabalho emequipe tem permitido que as contribuições derivadas dos estudos sejam publicadas em revistas científicas. Conclusões: A atuação do Grupo Científico de Estudantes de Tecnologia e Ciências desempenha um papel decisivo na comunidade universitária, pois organiza atividades científicas e acadêmicas com o objetivo de aumentar o desenvolvimento científico dos estudantes.

Twenty-Year Follow-Up of a Phase II Trial of Taxotere/Carboplatin/Herceptin in Patients With Metastatic HER2-Positive Breast Cancer.

BACKGROUND: As the implementation of trastuzumab, several studies have investigated new agents and regimens to treat human epidermal growth factor 2-positive (HER2+) metastatic breast cancer (MBC). However, long-term survival analyses from HER2-targeted therapies are lacking. This is a 20-year follow-up study of a phase II trial that evaluated the activity and safety of docetaxel in combination with carboplatin and trastuzumab (TCH) in patients with HER2+ MBC. MATERIALS AND METHODS: This is a follow-up of a phase II, single-arm, open-label study. The primary objective was the activity from the combination of TCH in terms of response rate (RR). Secondary objectives included the activity from TCH in terms of response duration (RD), time to progression (TTP), overall survival (OS), and percent one-year survival. RESULTS: Between 11/1999 and 10/2002, 40 women were enrolled. Most patients (67.5%) had visceral metastasis on enrollment. After 2 decades and 3 months from first enrollment, there were 4 (10%) survivors (median follow-up of 3.2 years). The RR for complete response (CR) or partial response (PR) was 72.5%. The RR for CR was 42.5%. RD was 8 months. Median TTP was 10.8 months. Participants achieved a median OS of 39.8 months. Percent one-year survival was 92.5%. CONCLUSION: A subset of patients (10%) receiving trastuzumab in the metastatic setting have achieved long-term survival beyond 20 years.

Evaluation of Viral Loads in Patients With SARS-CoV-2 Delta Variant Infection: Higher Loads Do Not Translate Into Different Testing Scenarios.

The Delta SARS-CoV-2 variant is very infectious, and it is spreading quickly during this pandemic. In the study, we compared viral loads estimated by means of the Ct values emerging from RT-PCR swab tests in surging cases infected with the SARS-CoV-2 Delta variant in the fourth wave of COVID-19 with the three prior waves. The data comprised viral loads from positive cases detected within the UPMC health care system in Allegheny County, Pennsylvania. A total of 2059 upper airway samples were collected and tested for SARS-CoV-2 positive by RT-PCR during March 2020 to September 2021. We did not observe significant difference in viral load difference between the third (December 2020 to January 2021) and fourth (June 2021 to September 2021) waves; however, they had the higher viral load than the first (March 2020 to June 2020) and second waves (June 2020 to August 2020). We did find an age-related effect with the elderly presenting with lower viral loads, which was also seen in the earlier waves. However, the level of the viral loads in the fourth wave in the respect of the previous ones was not sufficiently increased to change our testing strategies by means of increased use of rapid antigen tests (RAT).

Breast cancer mortality as a function of age.

BACKGROUND: Incidence of breast cancer (BC) in US women continues to increase with age as the strongest risk factor. We aimed to compare clinical, pathological and sociological variables associated to BC diagnosis, as well as the relative mortality rates of BC patients compared to the general US population. METHODS: We performed a retrospective, single-institution study evaluating 52,509 patients diagnosed with unilateral BC at the University of Pittsburgh Medical Center (UPMC) between 1990-2020. Primary outcome was death from any cause with cancer recurrence as a secondary outcome, evaluated for 4 age groups: 20-44, 45-55, 56-69, and 70-90. A dataset of expected mortality for women in the general population over a 10-year period was constructed using the Surveillance, Epidemiology, and End Results (SEER) Program. Observed vs. expected mortality and standardized mortality ratios (SMR) for each age group were calculated. RESULTS: Youngest patients with BC demonstrated the highest SMR at 10-year follow-up from time of diagnosis compared to the general US population (SMR 9.68, 95% CI: 8.99to 10.42), and remained highest compared to other age groups when analysis was limited to Stage 0/1 disease (10-year SMR 3.11, 95% CI: 2.54 to 3.76). SMRs decreased with increasing age at diagnosis with an SMR <1.0 in patients diagnosed with stage 0/1 at ages 70-90 at 5-year follow-up. CONCLUSIONS: Younger BC patients have the highest SMR which declines gradually with age. In the elderly, lower stage 0/1 SMR's are found compared to the general population, suggesting the possibility of an associated protective effect.

Machine Learning to Discern Interactive Clusters of Risk Factors for Late Recurrence of Metastatic Breast Cancer.

BACKGROUND: Risk of metastatic recurrence of breast cancer after initial diagnosis and treatment depends on the presence of a number of risk factors. Although most univariate risk factors have been identified using classical methods, machine-learning methods are also being used to tease out non-obvious contributors to a patient's individual risk of developing late distant metastasis. Bayesian-network algorithms can identify not only risk factors but also interactions among these risks, which consequently may increase the risk of developing metastatic breast cancer. We proposed to apply a previously developed machine-learning method to discern risk factors of 5-, 10- and 15-year metastases. METHODS: We applied a previously validated algorithm named the Markov Blanket and Interactive Risk Factor Learner (MBIL) to the electronic health record (EHR)-based Lynn Sage Database (LSDB) from the Lynn Sage Comprehensive Breast Center at Northwestern Memorial Hospital. This algorithm provided an output of both single and interactive risk factors of 5-, 10-, and 15-year metastases from the LSDB. We individually examined and interpreted the clinical relevance of these interactions based on years to metastasis and reliance on interactivity between risk factors. RESULTS: We found that, with lower alpha values (low interactivity score), the prevalence of variables with an independent influence on long-term metastasis was higher (i.e., HER2, TNEG). As the value of alpha increased to 480, stronger interactions were needed to define clusters of factors that increased the risk of metastasis (i.e., ER, smoking, race, alcohol usage). CONCLUSION: MBIL identified single and interacting risk factors of metastatic breast cancer, many of which were supported by clinical evidence. These results strongly recommend the development of further large data studies with different databases to validate the degree to which some of these variables impact metastatic breast cancer in the long term.

Covid-19-InfoCu: aplicación móvil para informar y orientar acerca de la pandemia originada por el SARS COV 2 / Covid-19-InfoCu: Mobile Application to Inform and Guide about the Pandemic Caused by SARS COV 2

La tecnología móvil o celular ha cambiado la forma en que vivimos, trabajamos y nos comunicamos, influyendo en todas las esferas de la vida diaria. El campo de la salud cada vez más es influido en todos los aspectos por esta tecnología cuyo desarrollo ha dado como resultado, entre otros, sistemas de gestión de información y conocimiento para la dirección en salud. El objetivo del presente trabajo es presentar el app Covid-19-InfoCu, accesible desde https://www.apklis.cu/application/cu.sld.COVID_19_InfoCU. La aplicación fue un encargo del Ministerio de Salud Cubano para informar de manera rápida y verídica a la población acerca de la pandemia que ha causado tantos contagios y muertes en todo el mundo, la COVID-19. Ha sido descargada por un gran número de usuarios y se ha extendido su uso en toda Cuba. El sitio Apklis (tienda de aplicaciones móviles de Cuba) reporta, hasta este momento, 183107 descargas. No se han contabilizado las descargas desde otros sitios cubanos, como la Empresa de Telecomunicaciones de Cuba (ETECSA) e Infomed, red telemática del sistema de salud cubano. En cuanto a la experiencia de usuarios, la aplicación ha recibido valoraciones positivas, que pueden ser verificadas en apklis(AU)

Mobile or cellular technology have changed the way we live, work and communicate, influencing all spheres of daily life. The health field is increasingly influenced in all aspects by technology whose development has resulted, among others, in information and knowledge systems for health management. The objective of this work is to present the Covid-19-InfoCu app, accessible from https://www.apklis.cu/application/cu.sld.COVID_19_InfoCU. This app was commissioned by the Cuban Ministry of Health to quickly and truthfully inform the population about the pandemic that has caused so many infections and deaths around the world, COVID-19. The app has been downloaded by a large number of users and its usage has spread nationwide. The Apklis site reports, so far, 183,107 downloads. Downloads from the ETECSA or Infomed FTP sites have not been counted. Regarding the user experience, the app has received positive evaluations, which can be verified in apklis(AU)

Atorvastatin facilitates chemotherapy effects in metastatic triple-negative breast cancer.

BACKGROUND: Metastatic triple-negative breast cancer (mTNBC) is treated mainly with chemotherapy. However, resistance frequently occurs as tumours enter dormancy. Statins have been suggested as effective against cancer but as they prolong and promote dormancy, it is an open question of whether the concomitant use would interfere with chemotherapy in primary and mTNBC. We examined this question in animal models and clinical correlations. METHODS: We used a xenograft model of spontaneous metastasis to the liver from an ectopic tumour employing a mTNBC cell line. Atorvastatin was provided to sensitise metastatic cells, followed by chemotherapy. The effects of statin usage on outcomes in women with metastatic breast cancer was assessed respectively by querying a database of those diagnosed from 1999 to 2019. RESULTS: Atorvastatin had limited influence on tumour growth or chemotherapy effects in ectopic primary tumours. Interestingly, atorvastatin was additive with doxorubicin (but not paclitaxel) when targeting liver metastases. E-cadherin-expressing, dormant, breast cancer cells were resistant to the use of either statins or chemotherapy as compared to wild-type cells; however, the combination of both did lead to increased cell death. Although prospective randomised studies are needed for validation, our retrospective clinical analysis suggested that patients on statin treatment could experience prolonged dormancy and overall survival; still once the tumour recurred progression was not affected by statin use. CONCLUSION: Atorvastatin could be used during adjuvant chemotherapy and also in conjunction with metastatic chemotherapy to reduce mTNBC cancer progression. These preclinical data establish a rationale for the development of randomised studies.

Statins and endocrine resistance in breast cancer.

Most breast cancers are hormone-receptor positive (HR+). However, more women eventually die from HR+ breast cancer than from either HER2+ or triple negative breast cancer. Endocrine therapies continue to be the mainstay of treatment. In 40% of these cases, recurrences in early-stage disease and progression in the metastatic setting are largely a function of the development of endocrine resistance. A multitude of mediators and pathways have been associated with endocrine resistance in breast cancer including the mevalonate pathway, which is integral to cholesterol biosynthesis. The mevalonate pathway and the downstream activation of associated cytoplasmic pathways including PI3K-AKT-mTOR and RAS-MEK-ERK have been known to affect cancer cell proliferation, cell survival, cell invasion, and metastasis. These are important mechanisms leading to the inevitable development of endocrine resistance in HR+ breast cancer. Statins are a class of drugs that inhibits HMG-CoA reductase, an enzyme in the mevalonate pathway that plays a central role in cholesterol production. In vitro and in vitro studies suggest that the role of statins in blocking the mevalonate pathway effectively disrupts downstream pathways involved in estrogen receptor expression and cellular processes such as cell survival, proliferation, stress, cell cycle, inhibition of apoptosis, and autophagy. Overcoming these key mechanisms heralds a role for statins in the prevention of endocrine resistance.

Dysregulation of the mevalonate pathway during SARS-CoV-2 infection: An in silico study.

SARS-CoV-2 triggers a dysregulated innate immune system activation. As the mevalonate pathway (MVP) prevents the activation of inflammasomes and cytokine release and regulates endosomal transport, compromised signaling could be associated with the pathobiology of COVID-19. Prior transcriptomic studies of host cells in response to SARS-CoV-2 infection have not reported to date the effects of SARS-CoV-2 on the MVP. In this study, we accessed public data sets to report in silico investigations into gene expression. In addition, we proposed candidate genes that are thought to have a direct association with the pathogenesis of COVID-19, and which may be dependent on signals derived from the MVP. Our results revealed dysregulation of genes involved in the MVP. These results were not found when investigating the gene expression data from host cells infected with H3N2 influenza virus, H1N1 influenza virus, or respiratory syncytial virus. Our manually curated gene set showed significant gene expression variability in A549 cells infected with SARS-CoV-2, as per Blanco-Melo et al. data set (GSE147507). In light of the present findings, SARS-CoV-2 could hijack the MVP, leading to hyperinflammatory responses. Prompt reconstitution of this pathway with available agents should be considered in future studies.

VATS Uniportal, masterclass Guatemala / VATS Uniportal, masterclass Guatemala

En las dos últimas décadas la evolución de la cirugía mínimamente invasiva del tórax ha transmutado de un abordaje de tres puertos, siguiendo dos puertos hasta llegar a puerto único, conocido también como VATS Uniportal, procurando un confort mucho mejor para el paciente y resultados quirúrgicos similares. Objetivos. Presentar la técnica quirúrgica de VATS Uniportal en un hospital nacional, efectuadas por un experto internacional en este campo. Pacientes y Métodos. Se presentan dos casos clínicos quirúrgicos: El de una paciente con Miastenia Gravis a quien se le realizó timectomía por abordaje sub-xifoideo y otra paciente, a quien se le completó una lobectomía inferior derecha por hallazgos de patología posterior a la resección de un nódulo pulmonar solitario, reportado como cáncer primario de pulmón. Conclusiones. La técnica de cirugía mínimamente invasiva, VATS Uniportal, ofrece grandes beneficios para el paciente, tanto estéticos como funcionales y su aprendizaje es posible con la transmisión de conocimientos y experiencias directa con la presencia del experto o indirectas a través de la información publicada. (AU)

In the last two decades, the evolution of minimally invasive chest surgery has transmuted from a three-port approach, following two ports until reaching a single port, also known as VATS Uniportal, seeking much better comfort for the patient and similar surgical results. Objective. Present the VATS Uniportal surgical technique in a national hospital, performed by an international expert in this field. Patients and Methods. Two surgical clinical cases are presented: that of a patient with Myasthenia Gravis who underwent thymectomy through the sub-xiphoid approach and another patient, who underwent a right lower lobectomy due to findings of pathology after the resection of a pulmonary nodule. solitary, reported as primary lung cancer. Conclusions. The minimally invasive surgery technique, VATS Uniportal, offers great benefits for the patient, both aesthetic and functional and its learning is possible with the transmission of knowledge and experiences directly with the presence of the expert or indirectly through published information. (AU)

Nontraumatic chylothorax secondary to lymphoma and filariasis.

Chylothorax is characterized by extravasation of chyle into the pleural space resulting from thoracic duct damage. The effusion is most commonly unilateral, with the right and left side being affected in 50% and 33.3% of the patients, respectively. Only 16.66% of cases present a bilateral effusion. The underlying etiology can be classified as spontaneous or traumatic. The diagnosis is made through pleural fluid analysis and imaging studies. The following article presents two cases of left spontaneous chylothorax: a 26-year-old male presenting with a chylous pleural effusion due to a non-Hodgkin lymphoma and a 47-year-old patient from a tropical area with a chylous pleural effusion attributed to filariasis. Filariasis as a cause of chylothorax is uncommon and there is not much literature on the topic. Alongside the case presentations, information on chylothorax etiology, mechanism, diagnosis and treatment options is provided.

The Evolving Landscape of HER2-Directed Breast Cancer Therapy.

OPINION STATEMENT: The management of patients with HER2+ breast cancer has evolved significantly over the preceding decades. HER2 targeting strategies have advanced beyond focusing on the receptor alone to encompass a range of approaches. Current standard of care practices in these patients relies upon dual HER2 blockade with trastuzumab and pertuzumab in the adjuvant and metastatic settings. T-DM1 has proven particularly efficacious in patients with residual disease status post neoadjuvant therapy, with additional therapies approved in the subsequent lines to address recurrent and resistant disease. Advances continue to be made in HER2+ breast cancer with multiple novel agents on the horizon, employing diverse mechanisms of action that are described in this review.

Boning up: amino-bisphophonates as immunostimulants and endosomal disruptors of dendritic cell in SARS-CoV-2 infection.

Amino-bisphosphonates such as zoledronic acid (ZA) can possibly ameliorate or prevent severe COVID-19 disease by at least three distinct mechanisms: (1) as immunostimulants which could boost γδ T cell expansion, important in the acute response in the lung; (2) as DC modulators, limiting their ability to only partially activate T cells; and (3) as prenylation inhibitors of small GTPases in the endosomal pathway of the DC to prevent expulsion of lysosomes containing SARS-CoV-2 virions. Use of ZA or other amino-bisphosphonates as modulators of COVID-19 disease should be considered.

Drenaje laparoscópico de linfocele post-trasplante renal / Laparoscopic drainage of lymphocele following renal transplantation

El trasplante renal es el tratamiento ideal para lospacientes con insuficiencia renal crónica, el cual, como todo procedimiento tiene una incidencia de complicaciones entre las que se mencionan el linfocele osea, la acumulación de líquido linfático peri-renal misma que se reporta entre el 2-10 por ciento. Complicación que si no se trata tempranamente puede causar disfunción del injerto. El presente reporte tiene como finalidzad presentar nuestra experiencia inicial en la Unidad de Trasplante Renal del Instituto Guatemalteco de Seguridad Social para el manejo de linfocele mediante una ventana peritoneal por videolaparoscopía. Se presentan 2 casos resueltos adecuadamente por esta vía; actualmente 1 año pos-trasplante con función renal adecuada