Analysis of the association of HER-2 low carcinomas and PAM50 assay in hormone receptor positive early-stage breast cancer.

BACKGROUND: HER2-low has emerged as a new predictive biomarker in metastatic breast cancer. However, its prognostic value in early-stage carcinomas needs to be revisited. We aimed to evaluate the association of HER2-low carcinomas with PAM50 risk groups combined with clinicopathological variables in early breast cancer. METHODS: We conducted a retrospective analysis of 332 patients with early-stage breast cancer that underwent PAM50 signature analysis between 2015 and 2021at Hospital Universitario 12 de Octubre (Madrid, Spain). Clinical and pathological variables were collected from medical records. After adjusting for potential confounders, we estimated Odds Ratio (OR) and 95% confidence interval for high-risk PAM50 subgroup, comparing HER2-low versus HER2-zero carcinomas by multivariable logistic regression. P values below 0.05 were deemed statistically significant. RESULTS: 192 (57%) patients were classified as HER2-low carcinomas. Median follow-up was 34 months. Adjusted OR for high-risk PAM50 when comparing HER2-low versus HER2-zero carcinomas was 1.31 (95% CI: 0.75-2.30, p = 0.33). The multivariable model detected significant associations for Ki-67% (≥20% vs. <20%: OR = 4.03, 95% CI: 2.15-7.56, p < 0.001), T staging category (T2/T3 vs. T1: OR = 3.44, 95% CI: 1.96-6.04, p < 0.001), progesterone receptor (PR ≥ 20% vs. <20%: OR = 0.44, 95% CI: 0.23-0.83, p = 0.01), nodal staging category (N+ vs. N0: OR = 3.8, 95% CI: 1.89-7.62, p < 0.001) and histological grade (grade 2 vs. 1: OR = 2.41, 95% CI: 1.01-5.73, p = 0.04; grade 3 vs 1: OR = 5.40, 95%CI: 1.98-14.60, p = 0.001). CONCLUSIONS: In this early-stage breast cancer cohort, HER2-low was not associated with a high-risk PAM50 compared to HER2-zero carcinomas. Ki-67 ≥ 20%, T2/T3, histological grade 2/3, N+ and PR<20% were significantly associated to a high-risk PAM50.

A Patient with an Ileocecal MiNEN and a Synchronous Squamous Non-Small-Cell Lung Cancer: Case Report and Review of the Literature.

Mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs) are rare tumors composed of two different histological components, one of which is of a neuroendocrine origin. Given its suggested underdiagnosis and consequent low prevalence, no clear diagnostic and treatment guidelines are available, and treatment usually follows regimens similar to that of the most aggressive component. On the other hand, multiple primary tumors (MPTs) are also rare neoplastic entities that usually confer a challenge regarding treatment options, for a regimen that comprises both the primary and the synchronous/metachronous malignancy should be used. Here, we discuss the challenging diagnostic and therapeutic management of a patient with an ileocecal MiNEN that presented along with a synchronous squamous non-small-cell lung cancer (SQ-NSCLC). The patient presented with intestinal obstruction symptoms for which he underwent an emergency resection of the ileocecal MiNEN. An initial CT scan showed an additional lung mass later identified as an SQ-NSCLC after bronchoscopy biopsy analysis. Given the rapid hepatic metastatic progression, palliative platinum-based chemotherapy was initiated, with an adequate response of the local and metastatic lesions of the MiNEN, but suggested platinum resistance and progression of the pulmonary neoplasm. Second-line treatment with pembrolizumab directed for the SQ-NSCLC was initiated; however, it was stopped after immune-mediated toxicities developed. A third-line chemotherapy scheme with carboplatin/gemcitabine was initiated, but central nervous system (CNS) progression developed, with the patient dying 11 months after initial diagnosis.

Treatment Eligibility and Therapeutic Responses of an Ecuadorian Population at High Cardiovascular Risk Based on the ATP III Guidelines

Abstract Background The Adult Treatment Panel III (ATPIII) guidelines aim to reduce cardiovascular morbidity and mortality. In Ecuador, 20% of people have high LDL cholesterol levels, and 39% have high triglyceride levels. Objective To analyze lipid-lowering regimens in Ecuadorian patients and determine the achievement rate of the ATPIII goals for lipid profile. Methods Using a retrospective analysis, 385 subjects older than 30 years, who received pharmacological treatment for dyslipidemia for at least three months was randomly selected from institutions at two large cities in Ecuador. Data were collected from patients' medical records and analyzed by chi-square test or paired t-test; p-values less than 0.05 were considered significant. Results Baseline total cholesterol values were above 200 mg/dL in 75% of subjects, LDL-c values above 129 mg/dL in 83% of subjects and triglycerides values above 150 mg/dL in 79% of subjects. Most (n = 253, 95.8%) patients at very high cardiovascular risk were taking statins, 50% of them atorvastatin. Considering the ATPIII guidelines' goals, only 24 subjects (19%) at high CV risk achieved an LDL-c < 100 mg/dl, while a significantly lower percentage (p = 0.04) of patients at very high risk reached an LDL-c < 70mg/dl (11%; n = 30). Conclusion These data indicate a low rate of compliance with the ATPIII guidelines, independent of the medication used or duration of the treatment. This may be attributed to the prescription of low doses of medication and a therapy targeting isolated lipid fractions rather than a complete lipid profile. (Int J Cardiovasc Sci. 2020; 33(4):371-376)

Increased incidences of noninfectious comorbidities among aging populations living with human immunodeficiency virus in Ecuador: a multicenter retrospective analysis.

Introduction: Besides the well-known increased risk of developing HIV-related infectious comorbidities; compared with the general population, people living with HIV (PLHIV) may also have an increased risk of developing noninfectious comorbidities (NICMs). This is the first study intended to determine the NICMs rates affecting PLHIV who were under cART regimen in Ecuador. Methods: A total of 503 HIV-positive patients were evaluated during the period June 2015-November 2016 and included in a multicenter retrospective, cross-sectional study conducted in seven main government and nongovernment community-based hospitals in Ecuador. Results: The average age of the participants was 39.2±11.9 years old and the majority of them were male (67.2%). The average age at HIV diagnosis was 34.1 years old and cART in average was started 15.9 months after HIV-diagnosis. Recruited patients were receiving cART for an average of 59.2±40.2 months. Only 9.9% (n=50) of the patients did not show any NICMs. Diabetes and pre-diabetes was found in 6% (n=30) and 16.3% (n=82) patients, respectively; however, dyslipidemia and overweight/obesity was frequent, as they affected 41.4% (n=208) and 36.4% (n=183) patients, respectively. Sixty patients (11.9%) were diagnosed with depression and 28.2% (n=142) of the studied subjects were found to have other NICMs. Conclusion: Prevalence of NICMs among subjects under cART was greater than that reported among the Ecuadorian general population, therefore specific public health actions are required to make patients aware of and prevent NICMs among PLHIV in Ecuador.

Use, knowledge, and effectiveness of nutritional traffic light label in an urban population from Ecuador: a pilot study.

BACKGROUND: The nutritional traffic light label (NTLL) has become one of the most used Front of Package labels (FOP's) around the world, for its simple and easy to understand graphical system. In Ecuador, this labelling system has recently been implemented; then, this research aims to evaluate the use and knowledge of NTLL and its effectiveness as a public health promotion strategy. METHOD: In a cross-sectional study at two different urban supermarkets in Quito-Ecuador, a survey was conducted in 73 participants to inquire about knowledge, perspectives and purchasing habits regarding the NTLL. Objective data obtained from pictures of the participants'purchase was compared with subjective data obtained from the survey. For categorical variables, Chi square or Fisher's Exact test were used and variables with a statistical significance at α = 0.1 were included in multivariate logistic regression models. RESULTS: 88.7% of participants knew about the NTTL. 27.4% reported using the NTLL, while 28.4% of participants were observed to really use it. Significant associations between self-knowledge of the NTLL and education level (p = 0.007) or knowledge level (p = 0.001) were found. A significant association was also found between the refered use of the NTLL and the shopping influencing factor (p = 0.02). In the multivariate analysis an association between knowledge of the NTLL and observed use was found only when adjusted for the supermarket (p = 0.038). CONCLUSION: This study found that the level of knowledge of the NTLL in the studied population was relatively high; however, both the referred and the observed use of the NTLL were low. Use and knowledge of the NTLL were associated with the socioeconomic and educational status of the participants. Thus, the change in nutritional patterns needs additional strategies to put the NTLL before the brand once customers make their purchases.

Mitochondria and Coenzyme Q10 in the Pathogenesis of Preeclampsia.

Hypertensive disorders during pregnancy constitute one of the main causes of maternal and perinatal morbidity and mortality across the world and particularly in developing countries such as Ecuador. However, despite its impact on public health, the primary pathophysiological processes involved are yet to be elucidated. It has been proposed, among other theories, that an abnormal placentation may induce an endothelial dysfunction, which is ultimately responsible for the final clinical manifestations. Mitochondria, particularly from trophoblastic cells, are responsible for the production of energy, which is extremely important for normal placentation. The malfunction in this supply of energy may produce higher levels of free radicals. In both production of energy and free radicals, coenzyme Q10 (CoQ10) plays a crucial role in electron transport. As such, the role of CoQ10 in the genesis and prevention of preeclampsia has become the focus of a number of research groups, including that of the authors. Developing an in-depth understanding of these mechanisms might allow us to design new and feasible strategies with which we can reduce preeclampsia, particularly in the Latin-American countries.

Adherencia al tratamiento en los pacientes de consulta externa de los centros de salud de Quito / Adherence to treatment in outpatient patients of health centers in Quito

La adherencia al tratamiento, según la OMS, es "La medida en que la conducta de una persona al tomar medicamentos, seguir una dieta y/o realizar cambios en su estilo de vida, corresponde con las recomendaciones acordadas por un proveedor de atención médica". Dicha adherencia puede estar comprometida por varios factores relacionados tanto con el paciente y su entorno, como con los proveedores de salud. Existe un gran problema mundial relacionado con esta falta de adherencia, que lleva a incrementar la morbi-mortalidad, errores diagnósticos y tratamiento, los costos de salud y otros. El objetivo del estudio fue determinar la adherencia al tratamiento en pacientes tomados de 3 centros de atención primaria de salud de Quito, Ecuador. Se realizó un estudio observacional y prospectivo. Se identificó a pacientes (n = 80) que recibieron algún tipo de tratamiento farmacológico ambulatorio y se realizó el seguimiento de su adherencia al tratamiento. Se encontró que 1 de cada 4 pacientes (25%) olvida tomar al menos 1 dosis de su tratamiento y, 2 de cada 5 (40%) no cumplen los horarios establecidos para la toma de medicación, independientemente de la patología o la duración del tratamiento. Por tanto, resulta indispensable implementar nuevos y diferentes instrumentos que permitan, al personal de salud, contribuir activamente a cambiar esta realidad

Adherence to treatment according to the WHO refers to "the extent to which a person's behaviour ­ taking medication, following a diet or executing lifestyle changes, corresponds with agreed recommendations from a health care provider. Such adherence might be compromised by several factors related to both the patient and its environment, as well as health providers. There is a large global problem related to this lack of adherence, which leads to an increase in morbidity and mortality, errors in diagnosis and treatment, increased costs of health, etc. The aim of this study was to determine adherence to treatment in patients from three primary health care centers in Quito, Ecuador. An observational and prospective study was carried out. Patients (n = 80) who received some kind of outpatient pharmacological treatment were identified and their adherence to the treatment was monitored. One out of four patients (25%) stated to have forgotten at least one dose of their treatment, and two out of five patients (40%) did not follow the established medication schedules, regardless of the pathology and duration of treatment. Therefore, it is essential to implement new and different instruments that allow health personnel to actively contribute to change this reality.

Risk Factors Associated With HIV Among Men Who Have Sex With Men (MSM) in Ecuador.

The Joint United Nations Program on HIV/AIDS estimates that between 0.3% and 0.7% of adults aged 15 to 49 years were living with HIV in Ecuador in 2013. However, very little is known about the HIV prevalence rate among men who have sex with men (MSM) in that country. A cross-sectional survey was conducted to investigate the knowledge, attitudes, and practices regarding HIV/AIDS as well as to estimate the prevalence of HIV among MSM in one of the cities with high HIV prevalence rates in Ecuador. In this study, questionnaires were administered to 307 adult MSM. An HIV prevalence of 10% was observed. Knowledge about HIV was high; 91% of participants could identify how HIV is transmitted. Although consistent condom use for anal sex was relatively high (89%) among participants who reported having pay-for-service clients, only 64% reported using a condom during oral sex with a client. Participants who had multiple male sexual partners (i.e., their stable male partners plus other partner[s]) had 3.7 times higher odds of testing positive for HIV compared with those who did not. They also had reduced odds of condom use. Participants who were forced to have anal receptive sex had 3 times higher odds of testing positive for HIV. Despite the finding that participants exhibited high knowledge about HIV/AIDS, a high prevalence rate of HIV was observed, which warrants targeted behavioral interventions. These data are consistent with MSM being one of the highest at-risk population groups for HIV in this region of Ecuador.

Syphilis and HIV/Syphilis Co-infection Among Men Who Have Sex With Men (MSM) in Ecuador.

There is a reemergence of syphilis in the Latin American and Caribbean region. There is also very little information about HIV/Syphilis co-infection and its determinants. The aim of this study is to investigate knowledge, attitudes, and practices regarding sexually transmitted infections (STIs), in particular syphilis infection and HIV/Syphilis co-infection, as well as to estimate the prevalence of syphilis among men who have sex with men (MSM) in a city with one of the highest HIV prevalence rates in Ecuador. In this study, questionnaires were administered to 291 adult MSM. Questions included knowledge about STIs and their sexual practices. Blood samples were taken from participants to estimate the prevalence of syphilis and HIV/syphilis co-infection. In this population, the prevalence of HIV/syphilis co-infection was 4.8%, while the prevalence of syphilis as mono-infection was 6.5%. Participants who had syphilis mono-infection and HIV/syphilis co-infection were older. Men who had multiple partners and those who were forced to have sex had increased odds of syphilis and HIV/syphilis co-infection. A high prevalence of syphilis and self-reported STI was observed, which warrants targeted behavioral interventions. Co-infections are a cause for concern when treating a secondary infection in a person who is immunocompromised. These data suggest that specific knowledge, attitudes, and behaviors among MSM are associated with increased odds of STIs (including HIV/syphilis co-infections) in this region of Ecuador.

To Genotype or Phenotype for Personalized Medicine? CYP450 Drug Metabolizing Enzyme Genotype-Phenotype Concordance and Discordance in the Ecuadorian Population.

Genetic variations within the cytochrome P450 (CYP450) superfamily of drug metabolizing enzymes confer substantial person-to-person and between-population differences in pharmacokinetics, and by extension, highly variable clinical effects of medicines. In this context, "personalized medicine," "precision medicine," and "stratified medicine" are related concepts attributed to what is essentially targeted therapeutics and companion diagnostics, aimed at improving safety and effectiveness of health interventions. We report here, to the best of our knowledge, the first comparative clinical pharmacogenomics study, in an Ecuadorian population sample, of five key CYP450s involved in drug metabolism: CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. In 139 unrelated, medication-free, and healthy Ecuadorian subjects, we measured the phenotypic activity of these drug metabolism pathways using the CEIBA multiplexed phenotyping cocktail. The subjects were genotyped for each CYP450 enzyme gene as well. Notably, based on the CYP450 metabolic phenotypes estimated by the genotype data, 0.75% and 3.10% of the subjects were genotypic poor metabolizers (gPMs) for CYP2C19 and CYP2D6, respectively. Additionally, on the other extreme, genotype-estimated ultrarapid metabolizer (gUMs) phenotype was represented by 15.79% of CYP2C19, and 5.43% of CYP2D6. There was, however, considerable discordance between directly measured phenotypes (mPMs and mUMs) and the above genotype-estimated enzyme phenotypes. For example, among individuals genotypically carrying enhanced activity alleles (gUMs), many showed a lower actual drug metabolism capacity than expected by their genotypes, even lower than individuals with reduced or no activity alleles. In conclusion, for personalized medicine in the Ecuadorian population, we recommend CYP450 multiplexed phenotyping, or genotyping and phenotyping in tandem, rather than CYP450 genotypic tests alone. Additionally, we recommend, in consideration of equity, ethical, and inclusive representation in global science, further precision medicine research and funding in support of neglected or understudied populations worldwide.

Multiplex Phenotyping for Systems Medicine: A One-Point Optimized Practical Sampling Strategy for Simultaneous Estimation of CYP1A2, CYP2C9, CYP2C19, and CYP2D6 Activities Using a Cocktail Approach.

Phenotyping of the CYP450 enzyme activities contributes to personalized medicine, but the past phenotyping approaches have followed a piecemeal strategy measuring single enzyme activities in vivo. A barrier to phenotyping of populations in rural and remote areas is the limited time and resources for sample collection. The CEIBA cocktail approach allows metabolic capacity estimation of multiple CYP450 enzymes in a single sample analysis, but the attendant sample collection schemes for applications in diverse global settings are yet to be optimized. The present study aimed to select an optimal matrix to simultaneously analyze CYP450 enzyme activities so as to simplify the sampling schemes in the phenotyping protocol to enhance its throughput and feasibility in native populations or in remote and underserviced geographies and social contexts. We evaluated 13 Ecuadorian healthy volunteers for CYP1A2, CYP2C9, CYP2C19, and CYP2D6 genotypes and their metabolic phenotypes, including CYP3A4, in plasma and urine after administering one reduced dose of caffeine, losartan, omeprazole, and dextromethorphan. Pharmacokinetic analyses were performed, and the correlation between AUC parent/AUC metabolite and the ratio between concentrations of probe drugs and their corresponding metabolites at timepoints ranging from 0 to 12 hours post-dose were analyzed. A single sampling timepoint, 4 hours post-dose in plasma, was identified as optimal to reflect the metabolic activity of the attendant CYP450 enzymes. This study optimizes the CEIBA multiplexed phenotyping approach and offers new ways forward for integrated drug metabolism analyses, in the pursuit of global personalized medicine applications in resource-limited regions, be they in developed or developing countries.