Molecular Tumor Board Improves Outcomes for Hispanic Patients With Advanced Solid Tumors.

PURPOSE: Multidisciplinary molecular tumor boards (MTBs) decode complex genomic data into clinical recommendations. Although MTBs are well-established in the oncology practice in developed countries, this strategy needs to be better explored in developing countries. Herein, we describe the possible benefits and limitations of the first MTB established in Colombia. METHODS: Demographic, clinical, and genomic information was collected between August 2020 and November 2021. By mid-2020, an MTB strategy was created to discuss clinical cases with one or more genomic alterations identified by next-generation sequencing using an open-access virtual platform. We characterized the patient population as benefiting from the recommended treatment option. We assessed the benefits and access to available targeted therapies that have the potential to change clinical management by making recommendations to treating oncologists on the basis of genomic profiling. However, we did not assess the treatment oncologists' compliance with MTB recommendations because they were not intended to replace clinical judgment/standard of care. RESULTS: A total of 146 patients were included in the discussions of the MTB. The median age was 59 years, and 59.6% were women. Genomic results prompting a change in therapeutic decisions were obtained in 53.1% of patients (95% CI, 44.9 to 61.3). The most prevalent malignancy was non-small-cell lung cancer (51%). Other malignancies represented 60%, 50%, and 30% of patients with soft-tissue sarcomas, brain tumors, and breast cancer, respectively. CONCLUSION: Using an open-access virtual platform, MTBs were feasible in low- and middle-income countries on the basis of the capability to provide the benefits and access to available targeted therapies that are not standard of care. Furthermore, MTB recommendations were made available to the treating oncologist in different locations across Colombia, providing the option to modify clinical management in most of these patients.

Uso terapéutico de los inhibidores de la enzima convertidora de angiotensina en pacientes con COVID-19: las «dos caras de la moneda¼ / Therapeutic use of angiotensin converting enzyme inhibitors in patients with COVID-19: the "two sides of the coin"

Resumen La evidencia actual es limitada para determinar el impacto del uso de los inhibidores de la enzima convertidora de angiotensina (IECA) en la predisposición al empeoramiento de la enfermedad del coronavirus 2019 (COVID-19). Inicialmente se reportó que en los pacientes con progresión grave de la COVID-19 existía una mortalidad elevada, los cuales tenían antecedentes de hipertensión arterial, diabetes mellitus, enfermedad cardiovascular y enfermedad renal crónica. Parte de estos pacientes también tenía en común que utilizaban IECA, lo cual alertó a la comunidad médica sobre su riesgo potencial en coexistencia con COVID-19. Sin embargo, estudios más recientes de casos-controles encontraron que los inhibidores del sistema renina-angiotensina, incluyendo los IECA, no incrementan el riesgo de COVID-19 o de requerir admisión hospitalaria por esta causa. Diferentes revistas científicas han facilitado el acceso a reportes preliminares, dejando a discreción de la comunidad médica y científica hacer uso de dicha información para promover el desarrollo de estudios que confirmen experimentalmente dichos hallazgos, preclínicos y epidemiológicos, que finalmente impacten en las decisiones de la práctica clínica para beneficiar a los pacientes con COVID-19. En esta revisión de la literatura se exploran los diferentes efectos mediados por los IECA que podrían estar relacionados con la respuesta inmune durante la infección y la transmisión de COVID-19, compilando evidencia disponible que evalúa si en realidad representan un riesgo o si, por el contrario, confieren un efecto protector.

Abstract There is limited evidence for determining the impact of the use of angiotensin converting enzyme inhibitors (ACE-I) in the tendency to worsening of coronavirus-19 disease (COVID-19). It was initially reported that, in patients with serious progression of COVID-19, there was an increased mortality in those that had a history of suffering arterial hypertension, diabetes mellitus, cardiovascular disease, and chronic kidney disease. A proportion of these patients also had in common that they used ACE-I, which alerted the medical community on the potential risk in coexisting with COVID-19. However, in more recent case-control studies, they found that inhibitors of the renin-angiotensin system, including ACE-I, does not increase the risk of COVID-19 or require hospital admission due to this cause. Several scientific journals have provided access to preliminary reports, leaving the use of such information at the discretion of the medical and scientific community for promoting the development of studies that might confirm these preclinical and epidemiological findings experimentally. These may finally have an impact on the clinical practice decisions, in order to benefit patients with COVID-19. In this literature review, the different effects mediated by ACE-I that could be related to the immune response during the infection and transmission of COVID-19 are examined, gathering available evidence that evaluates whether, in reality, they represent a risk or if on the other hand, they confer a protector effect.

Immunomodulatory effects of renin-angiotensin system inhibitors on T lymphocytes in mice with colorectal liver metastases.

BACKGROUND: It is now recognized that many anticancer treatments positively modulate the antitumor immune response. Clinical and experimental studies have shown that inhibitors of the classical renin-angiotensin system (RAS) reduce tumor progression and are associated with better outcomes in patients with colorectal cancer. RAS components are expressed by most immune cells and adult hematopoietic cells, thus are potential targets for modulating tumor-infiltrating immune cells and can provide a mechanism of tumor control by the renin-angiotensin system inhibitors (RASi). AIM: To investigate the effects of the RASi captopril on tumor T lymphocyte distribution in a mouse model of colorectal liver metastases. METHODS: Liver metastases were established in a mouse model using an autologous colorectal cancer cell line. RASi (captopril 750 mg/kg) or carrier (saline) was administered to the mice daily via intraperitoneal injection, from day 1 post-tumor induction to endpoint (day 15 or 21 post-tumor induction). At the endpoint, tumor growth was determined, and lymphocyte infiltration and composition in the tumor and liver tissues were analyzed by flow cytometry and immunohistochemistry (IHC). RESULTS: Captopril significantly decreased tumor viability and impaired metastatic growth. Analysis of infiltrating T cells into liver parenchyma and tumor tissues by IHC and flow cytometry showed that captopril significantly increased the infiltration of CD3+ T cells into both tissues at day 15 following tumor induction. Phenotypical analysis of CD45+ CD3+ T cells indicated that the major contributing phenotype to this influx is a CD4 and CD8 double-negative T cell (DNT) subtype, while CD4+ T cells decreased and CD8+ T cells remained unchanged. Captopril treatment also increased the expression of checkpoint receptor PD-1 on CD8+and DNT subsets . CONCLUSION: Captopril treatment modulates the immune response by increasing the infiltration and altering the phenotypical composition of T lymphocytes and may be a contributing mechanism for tumor control.

Renin-angiotensin inhibitors reprogram tumor immune microenvironment: A comprehensive view of the influences on anti-tumor immunity.

Renin-angiotensin system inhibitors (RASi) have shown potential anti-tumor effects that may have a significant impact in cancer therapy. The components of the renin-angiotensin system (RAS) including both, conventional and alternative axis, appear to have contradictory effects on tumor biology. The mechanisms by which RASi impair tumor growth extend beyond their function of modulating tumor vasculature. The major focus of this review is to analyze other mechanisms by which RASi reprogram the tumor immune microenvironment. These involve impairing hypoxia and acidosis within the tumor stroma, regulating inflammatory signaling pathways and oxidative stress, modulating the function of the non-cellular components and immune cells, and regulating the cross-talk between kalli krein kinin system and RAS.

Caso problema: retardo mental como secuela de enfermedad neurometabólica / Case discussion: mental retardation as sequel of neurometabolic disease

Los errores innatos del metabolismo representan un grupo paradigmático en el contexto de las enfermedades poco conocidas, aunque son más de 500 perfectamente definidas. Gracias a los avances de la biología molecular y la bioquímica, muchas de estas enfermedades no caracterizadas se han ido adicionando al grupo de errores innatos del metabolismo. El conocimiento de las bases moleculares de estas patologías, ha mejorado las posibilidades de diagnóstico prenatal y neonatal en la población a riesgo, lo que permite la posibilidad de implementar programas de manejo preventivo, así como, la aplicación del tratamiento y un consejo genético precoz. Se reporta el caso de un adolescente de 17 años con retardo mental y epilepsia mioclónica progresiva degenerativa, con hallazgos en neuroimágenes de enfermedad de sustancia blanca asociado a alteraciones metabólicas, lo cual es compatible con una impresión diagnóstica de Aciduria Glutárica tipo 1; lo cual es sustentado en el paciente, por la favorable respuesta terapéutica. Además del presente reporte, se busca analizar a través de una revisión de la literatura, el enfoque diagnóstico y terapéutico que permite considerar los errores innatos del metabolismo, como aquellas patologías cada vez más comunes en la práctica médica, que precisan de un manejo multidisciplinario. (MÉD.UIS. 2014;27(1):69-74).

Inborn errors of metabolism represent a paradigmatic group in the context of little known diseases, although more than 500 well-defined. Thanks to advances in molecular biology and biochemistry, many of these diseases have been characterized not adding to the group of inborn errors of metabolism. Knowledge of the molecular basis of these diseases, enhanced the possibilities of prenatal diagnosis and neonatal risk in the population, allowing the possibility of implementing preventive management programs, as well as the implementation of early treatment and genetic counseling. The case of a 17 -year mental retardation and myoclonic epilepsy progressive degenerative with findings in neuroimaging disease white matter associated with metabolic abnormalities are reported, which is consistent with a picture of glutaric aciduria type 1, this diagnosis is supported in the patient, by the favorable therapeutic response. In addition to this report, seeks to analyze through a review of literature, the diagnostic and therapeutic approach that allows considering the inborn errors of metabolism, such as those increasingly common diseases in medical practice, which require a multidisciplinary approach. (MÉD.UIS. 2014;27(1):69-74).

Estado actual del embarazo gemelar: Revisión de la literatura / Current status of twin pregnancy: A literature review

En la actualidad el diagnóstico de embarazo gemelar le confiere al binomio madre e hijo características específicas que los convierte en una población de alto riesgo para patologías que comprometen el estado de bienestar fetal como: prematurez, ruptura prematura de membranas, restricción de crecimiento intrauterino, malformaciones congénitas, problemas de entrecruzamiento del cordón, abruptio placentae, distocias de presentación y síndrome de trasfusión feto-fetal. Además de los determinantes de morbilidad materna, los cuales han incrementado su prevalencia según la etiología asociada, ya sean los trastornos de hipertensión asociados al embarazo, sepsis secundario a ruptura prematura de membranas y hemorragia postparto. En tanto así, recobra vital importancia realizar una revisión acuciosa dirigida por ejes temáticos sobre las patologías de mayor prevalencia asociadas al embarazo gemelar. Salud UIS 2012; 44 (3): 41-48.

Nowadays the diagnosis of twin pregnancy confers to the binomial mother and son specific characteristics that make them into a high risk population for pathologies that compromise the wellbeing of the fetus such as: prematurity, uterine overdistention, premature rupture of membranes and intrauterine growth restriction, congenital malformations, trouble with crossing over umbilical cord, abruptio placentae, presentation dystocia and twin-to-twin transfusion syndrome. Besides the risk determinants of maternal morbidity which have increased its prevalence accord to the etiology associated, such as hypertensive disorders associates with pregnancy, sepsis secondary to premature rupture of membranes and postpartum bleeding. Therefore, is really important to make an accurate review by thematic items about major prevalence pathologies associated with twin pregnancy. Salud UIS 2012; 44 (3): 41-48.