Predictors of Endocrine Resistance in a Cohort of Mexican Breast Cancer Patients.

Purpose: This study aimed to determine the prevalence of endocrine resistance in a cohort of Hispanic Mexican breast cancer (BC) patients receiving care at Instituto Nacional de Cancerología (INCan). Additionally, the clinical-pathological factors associated with endocrine resistance were identified, and their impact on patient survival was explored. Methods: A retrospective analysis of 200 BC patients who attended INCan between 2012 and 2016 with estrogen receptor (ER) and progesterone receptor (PR) positive tumors was made. Endocrine resistance was defined according to the International Consensus Guidelines for Advance Breast Cancer 2 definition. Their clinicopathological characteristics were analyzed to determine the association with endocrine resistance presence. We used sensitivity analyses and multivariate-adjusted logistic regressions, Kaplan-Meier curves, and multivariate-adjusted Cox regressions. P-value < 0.05 was considered as statistically significant. Results: Endocrine resistance was observed in 32.5% of patients included in this study. The distinction between hormone resistance and sensitivity was influenced by tumor size and node status. It had a mean diameter of 7.15 cm in endocrine resistance cases compared to 5.71 cm in non-endocrine, with N3 status present in 20% of endocrine resistance cases versus only 2.2% in non-endocrine (p-value < 0.001). The clinical stage exhibited a strong association with endocrine resistance (Risk Ratio [RR] 4.39, 95% confidence interval [95%CI] 1.50, 11.43). Furthermore, endocrine resistance significantly impacted mortality during the follow-up, with a Hazard Ratio [HR] of 23.7 (95%CI 5.20, 108.42) in multivariable-adjusted models. However, a complete pathological response reduced the endocrine resistance risk, as demonstrated by a Risk Ratio (RR) of 0.15 (95% CI 0.03, 0.75). Conclusions: Advanced clinical stage at diagnosis predicted endocrine resistance in Hispanic Mexican BC patients. Complete pathologic response in locally advanced disease patients was also a key predictor of endocrine resistance. These results indicated that endocrine resistance was a critical factor in BC during follow-up.

Antimicrobial and antitumor activities of an alginate-based membrane loaded with bismuth nanoparticles and cetylpyridinium chloride.

OBJECTIVE: To evaluate the antitumor and antimicrobial properties of an alginate-based membrane (ABM) loaded with bismuth lipophilic nanoparticles (BisBAL NPs) and cetylpyridinium chloride (CPC) on clinically isolated bacteria and a pancreatic cancer cell line. MATERIAL AND METHODS: The BisBAL NP-CPC ABM was characterized using optical and scanning electron microscopy (SEM). The antimicrobial potential was measured using the disk-diffusion assay, and antibiofilm activity was determined through the live/dead assay and fluorescence microscopy. The antitumor activity was analyzed on the pancreatic cell line (Panc 03.27) using the MTT assay and live/dead assay with fluorescence microscopy. RESULTS: After a 24-h exposure (37°C, aerobic conditions), 5 µM BisBAL NP reduced the growth of K. pneumoniae by 77.9%, while 2.5 µM BisBAL NP inhibited the growth of Salmonella, E. faecalis and E. faecium by 82.9%, 82.6%, and 78%, respectively (p < 0.0001). The BisBAL NPs-CPC ABM (at a ratio of 10:1; 500 and 50 µM, respectively) inhibited the growth of all isolated bacteria, producing inhibition halos of 9.5, 11.2, 7, and 10.3 mm for K. pneumoniae, Salmonella, E. faecalis, and E. faecium, respectively, in contrast to the 6.5, 9.5, 8.5, and 9.8 mm obtained with 100 µM ceftriaxone (p < 0.0001). The BisBAL NPs-CPC ABM also reduced bacterial biofilms, with 81.4%, 74.5%, 97.1%, and 79.5% inhibition for K. pneumoniae, E. faecium, E. faecalis, and Salmonella, respectively. Furthermore, the BisBAL NPs-CPC ABM decreased Panc 03.27 cell growth by 76%, compared to 18% for drug-free ABM. GEM-ABM reduced tumoral growth by 73%. The live/dead assay confirmed that BisBAL NPs-CPC-ABM and GEM-ABM were cytotoxic for the turmoral Panc 03.27 cells. CONCLUSION: An alginate-based membrane loaded with BisBAL NP and CPC exhibits dual antimicrobial and antitumoral efficacy. Therefore, it could be applied in cancer treatment and to diminish the occurrence of surgical site infections.

Sampling, composition, and biological effects of Mexico City airborne particulate matter from multiple periods.

Air pollution is a worldwide environmental problem with an impact on human health. Particulate matter of ten micrometers or less aerodynamic diameter (PM10) as well as its fine fraction (PM2.5) is related to multiple pulmonary diseases. The impact of air pollution in Mexico City, and importantly, particulate matter has been studied and considered as a risk factor for two decades ago. Previous studies have reported the composition of Mexico City particulate matter, as well as the biological effects induced by this material. However, material collected and used in previous studies is a limited resource, and sampling and particle recovery techniques have been improved. In this study, we describe the methods used in our laboratory for Mexico City airborne particulate matter PM10 and PM2.5 sampling, considering the years 2017, 2018 and 2019. We also analyzed the PM10 and PM2.5 samples obtained to determine their composition. Finally, we exposed lung cell line cultures to PM10 and PM2.5 to evaluate the biological effect of the material in terms of cell viability, cell death, inflammatory response, and cytogenetic alterations. Our results showed that PM10 composition includes inorganic, organic and biological compounds, while PM2.5 is a mixture of more enriched organic compounds. PM10 and PM2.5 treatment in lung cells does not significantly impact cell viability/cell death. However, PM10 and PM2.5 increase the secretion levels of IL-6. Moreover, PM10 as well as PM2.5 induce cytogenetic alterations, such as micronuclei, anaphase bridges, trinucleated cells and apoptotic cells in lung cells. Our results update the evidence of the composition and biological effects of Mexico City particulate matter and provide us a reliable basis for future approaches.

Cytotoxicity Activity of Some meso-Dihydroguaiaretic Acid Derivatives and Mode of Action of the Most Active Compound.

The aim of this study was to screen sixteen meso-1 semi-synthetic derivatives bearing ether, esther, carbamate, phosphate or aminoether functional groups against five cancer cell lines: MCF-7 (breast), A549 (lung), HepG2 (liver), HeLa (cervix), and DU145 (prostate) at 25 µM using the MTT assay. Results from the screening showed that two derivatives had the lowest percentage of cell viability at 25 µM, the aminoether derivative meso-11 and the esther derivative meso-20 against A549 (44.15±0.78 %) and MCF-7 (41.60±0.92 %), respectively. Then, it was determined the IC50 value of each compound against their most sensitive cancer cell line. Results showed that aminoether derivative meso-11 showed potent cytotoxicity against A549 (IC50 =17.11±2.11 µM), whereas it resulted more cytotoxic against the LL-47 lung normal cell line (IC50 =9.49±1.19 µM) having a Selective Index (SI) of 0.55. On the other hand, the esther derivative meso-20 exhibited potent activity against MCF-7 (IC50 =18.20±1.98 µM), whereas it displayed moderate cytotoxicity against the MCF-10 breast normal cell line (IC50 =41.22±2.17 µM) with a SI of 2.2. Finally, studies on the mechanism of action of meso-20 indicated disruption of MCF-7 plasma membrane in vitro and the AMPK activation in silico.

Geographical approach analysis of the impact of air pollution on newborn intrauterine growth and cord blood DNA damage in Mexico City.

BACKGROUND: Few epidemiologic studies have focused on the specific source of ambient air pollution and adverse health effects in early life. Here, we investigated whether air pollutants from different emission sources were associated with decreased birth anthropometry parameters and increased DNA adduct formation in mother-child pairs residing in the Mexico City Metropolitan Area (MCMA). METHODS: This cross-sectional study included 190 pregnant women recruited during their last trimester of pregnancy from two hospitals at MCMA, and a Modeling Emissions Inventory (MEI) to calculate exposure to ambient air pollutants from different emissions sources (area, point, mobile, and natural) for two geographical buffers 250 and 750 m radii around the participants households. RESULTS: Contaminants were positively correlated with umbilical cord blood (UCB) adducts, but not with maternal blood (MB) adducts. PM10 emissions (area and point sources, overall emissions), PM2.5 (point sources), volatile organic compounds (VOC), total organic compounds (TOC) from point sources were positively correlated with UCB adducts. Air pollutants emitted from natural sources were correlated with a decrease in MB and UCB adducts. PM10 and PM2.5 were correlated (p < 0.05) with a decrease in birth weight (BW), birth length (BL) and gestational age at term (GA). In multivariate analyses adjusted for potential confounders, PM10 was associated with an increase in UCB adducts. PM10 and PM2.5 from overall emissions were associated with a decrease in BW, BL and GA at term. IMPACT: Results suggested higher susceptibility of newborns compared to mothers to damage related to ambient air pollution. PMs are associated with birth anthropometry parameters and DNA damage in adjusted models, highlighting the need for more strict regulation of PM emissions.

Multivariate Prognostic Models for Patients with Stages I and Ii Colon Carcinoma: a Strobe-Compliant Retrospective Cohort Study.

Background: Colorectal cancer is the most frequent gastrointestinal malignancy worldwide. The value of adjuvant treatment is controversial in Stages I and II. Objective: The aim of this study was to construct post-operative prognostic models applicable to patients with stages I-II colon carcinoma (CC). Methods: This is a retrospective cohort study of patients with Stage I-II CC treated over a 25-year period. Exposure was defined as clinical, histopathological, and immunohistochemical factors (including CDX2 and MUC2 expression). Patients were randomly allocated to either a "modeling set" or a "validation set". Factors associated with recurrence, disease-free survival (DFS), and overall survival (OS) were defined in the "modeling set". Their performances were tested in the "validation set". Results: From a total of 556 recruited patients, 339 (61%) were allocated to the "modeling set" and 217 (39%) to the "validation set". Three models explaining recurrence, DFS, and OS were described. Tumor location in the left colon (Hazards ratio [HR] = 1.57; 95% Confidence interval [CI] 0.99-2.48), lymphocyte (HR = 0.46; 96% CI 0.27-0.88) and monocyte (HR = 0.99; 95% CI 0.99-1) counts, neutrophil/platelet ratio (HR = 1.3; 95% CI 0.74-2.3, and HR = 2.3; 95% CI 1.3-4.1; for second and third category, respectively), albumin/monocyte ratio (HR = 0.43; 95% CI 0.21-0.87), and microscopic residual disease after surgery (HR = 8.7; 95% CI 3.1-24) were independently associated with OS. T classification and expression of CDX2 and/or MUC2 were not independently associated with recurrence or prognosis. Conclusion: These models are simple and readily available, and distinguish the risk and prognosis in patients with CC stages I and II; these models require cheaper processes than the use of more sophisticated molecular biology techniques. They may guide either the need for adjuvant therapy versus post-operative surveillance only, as well as aid in the design of clinical trials.

Multivariate Prognostic Models for Patients with Stages I and Ii Colon Carcinoma: a Strobe-Compliant Retrospective Cohort Study

ABSTRACT Background: Colorectal cancer is the most frequent gastrointestinal malignancy worldwide. The value of adjuvant treatment is controversial in Stages I and II. Objective: The aim of this study was to construct post-operative prognostic models applicable to patients with stages I-II colon carcinoma (CC). Methods: This is a retrospective cohort study of patients with Stage I-II CC treated over a 25-year period. Exposure was defined as clinical, histopathological, and immunohistochemical factors (including CDX2 and MUC2 expression). Patients were randomly allocated to either a "modeling set" or a "validation set". Factors associated with recurrence, disease-free survival (DFS), and overall survival (OS) were defined in the "modeling set". Their performances were tested in the "validation set". Results: From a total of 556 recruited patients, 339 (61%) were allocated to the "modeling set" and 217 (39%) to the "validation set". Three models explaining recurrence, DFS, and OS were described. Tumor location in the left colon (Hazards ratio [HR] = 1.57; 95% Confidence interval [CI] 0.99-2.48), lymphocyte (HR = 0.46; 96% CI 0.27-0.88) and monocyte (HR = 0.99; 95% CI 0.99-1) counts, neutrophil/platelet ratio (HR = 1.3; 95% CI 0.74-2.3, and HR = 2.3; 95% CI 1.3-4.1; for second and third category, respectively), albumin/monocyte ratio (HR = 0.43; 95% CI 0.21-0.87), and microscopic residual disease after surgery (HR = 8.7; 95% CI 3.1-24) were independently associated with OS. T classification and expression of CDX2 and/or MUC2 were not independently associated with recurrence or prognosis. Conclusion: These models are simple and readily available, and distinguish the risk and prognosis in patients with CC stages I and II; these models require cheaper processes than the use of more sophisticated molecular biology techniques. They may guide either the need for adjuvant therapy versus post-operative surveillance only, as well as aid in the design of clinical trials.

Ion Channels as Potential Tools for the Diagnosis, Prognosis, and Treatment of HPV-Associated Cancers.

The human papilloma virus (HPV) group comprises approximately 200 genetic types that have a special affinity for epithelial tissues and can vary from producing benign symptoms to developing into complicated pathologies, such as cancer. The HPV replicative cycle affects various cellular and molecular processes, including DNA insertions and methylation and relevant pathways related to pRb and p53, as well as ion channel expression or function. Ion channels are responsible for the flow of ions across cell membranes and play very important roles in human physiology, including the regulation of ion homeostasis, electrical excitability, and cell signaling. However, when ion channel function or expression is altered, the channels can trigger a wide range of channelopathies, including cancer. In consequence, the up- or down-regulation of ion channels in cancer makes them attractive molecular markers for the diagnosis, prognosis, and treatment of the disease. Interestingly, the activity or expression of several ion channels is dysregulated in HPV-associated cancers. Here, we review the status of ion channels and their regulation in HPV-associated cancers and discuss the potential molecular mechanisms involved. Understanding the dynamics of ion channels in these cancers should help to improve early diagnosis, prognosis, and treatment in the benefit of HPV-associated cancer patients.

Gait speed according to cognitive status in older adults: a cross-sectional study in a resource-limited country.

OBJECTIVE: We aimed to investigate the association between gait speed and cognitive status in outpatient older adults from a resource-limited setting in Peru. METHODS: We performed a cross-sectional study including older adults aged ≥60 years attending a geriatrics outpatient clinic between July 2017 and February 2020. Gait speed was measured over a 10-meters distance without considering the first and last meter traveled. Cognitive status was assessed through the Short Portable Mental Status Questionnaire (SPMSQ) and the Mini-Mental State Examination (MMSE). We used a multivariate binomial logistic regression to conduct both an epidemiological and fully adjusted models. RESULTS: We included 519 older adults (mean age: 75 years; IQR = 10), of whom 95 (18.3%) and 151 (31.5%) were cognitively impaired according to the SPMSQ and MMSE, respectively. Gait speed was slower among patients with poorer cognitive status as assessed by both tools (p < 0.001). Malnutrition (PR: 1.74; CI: 1.45-2.08) and functional dependency (PR: 4.35; CI: 2.68-7.08) were associated with a greater prevalence of cognitive impairment according to the SPMSQ, whereas a faster gait speed (PR: 0.27, CI: 0.14-0.52) and longer years of education (PR: 0.83, CI: 0.77-0.88) were associated with a less prevalence. CONCLUSIONS: Slower gait speed was associated with poorer cognitive status in outpatient older adults. Gait speed may be a complementary tool in the cognitive assessment of older adults from resource-limited settings.

Current and novel approaches in the pharmacological treatment of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most lethal malignant tumours worldwide. The mortality-to-incidence ratio is up to 91.6% in many countries, representing the third leading cause of cancer-related deaths. Systemic drugs, including the multikinase inhibitors sorafenib and lenvatinib, are first-line drugs used in HCC treatment. Unfortunately, these therapies are ineffective in most cases due to late diagnosis and the development of tumour resistance. Thus, novel pharmacological alternatives are urgently needed. For instance, immune checkpoint inhibitors have provided new approaches targeting cells of the immune system. Furthermore, monoclonal antibodies against programmed cell death-1 have shown benefits in HCC patients. In addition, drug combinations, including first-line treatment and immunotherapy, as well as drug repurposing, are promising novel therapeutic alternatives. Here, we review the current and novel pharmacological approaches to fight HCC. Preclinical studies, as well as approved and ongoing clinical trials for liver cancer treatment, are discussed. The pharmacological opportunities analysed here should lead to significant improvement in HCC therapy.

High level of infection prevention and control in surveyed hospitals in Colombia, 2021.

Objective: This study aimed to determine the performance of infection prevention and control (IPC) programs in eight core components in level 2 and level 3 hospitals across all provinces in Colombia. Methods: This cross-sectional study used self-assessed IPC performance data voluntarily reported by hospitals to the Ministry of Health and Social Protection during 2021. Each of the eight core components of the World Health Organization's checklist in the Infection Prevention and Control Assessment Framework contributes a maximum score of 100, and the overall IPC performance score is the sum of these component scores. IPC performance is graded according to the overall score as inadequate (0-200), basic (201-400), intermediate (401-600) or advanced (601-800). Results: Of the 441 level 2 and level 3 hospitals, 267 (61%) reported their IPC performance. The median (interquartile range [IQR]) overall IPC score was 672 (IQR: 578-715). Of the 267 hospitals reporting, 187 (70%) achieved an advanced level of IPC. The median overall IPC score was significantly higher in private hospitals (690, IQR: 598-725) than in public hospitals (629, IQR: 538-683) (P < 0.001). Among the core components, scores were highest for the category assessing IPC guidelines (median score: 97.5) and lowest for the category assessing workload, staffing and bed occupancy (median score: 70). Median overall IPC scores varied across the provinces (P < 0.001). Conclusions: This countrywide assessment showed that 70% of surveyed hospitals achieved a self-reported advanced level of IPC performance, which reflects progress in building health system resilience. Since only 61% of eligible hospitals participated, an important next step is to ensure the participation of all hospitals in future assessments.

Adherence to guidelines on the use of amoxicillin for treatment of ambulatory pneumonia in children younger than 5 years, Colombia, 2017-2019.

Objectives: To determine the level of adherence to clinical guidelines in prescribing amoxicillin to children younger than 5 years with pneumonia in outpatient settings in Colombia from 2017 to 2019, and assess the factors associated with adherence. Methods: This was a cross-sectional study of secondary data from the Colombian Integrated Social Protection Information System database. Adherence was defined as prescription of oral amoxicillin for bacterial and unspecified pneumonia and non-prescription for viral pneumonia. Variables examined included: age (< 1 year, 1-4 years) of child; sex; cause of pneumonia (bacterial, viral, unspecified); region (Andean, Amazonian, Pacific, Caribbean, Insular, Orinoquian); and payment mechanism (without prior authorization, capitation, direct payment, pay per case, pay for event). Results: Of 215 925 cases of community-acquired pneumonia reported during 2017-2019, 64.8% were from the Andean region, 73.9% were bacterial pneumonia and 1.8% were viral pneumonia. Adherence to guidelines was observed in 5.8% of cases: this was highest for children diagnosed with viral (86.0%) compared with bacterial (2.0%) pneumonia. For children diagnosed with bacterial pneumonia, 9.4% were prescribed any antibiotic. A greater proportion of children covered by capitated payments (22.3%) were given treatment consistent with the guidelines compared with payment for event (1.3%). Conclusion: In this first study from Colombia, adherence to guidelines for outpatient treatment of children with bacterial pneumonia was low and was better for viral pneumonia. Further qualitative studies are needed to explore the reasons for this lack of adherence and why bacterial pneumonia was the most commonly reported etiology.

High level of infection prevention and control in surveyed hospitals in Colombia, 2021

[ABSTRACT]. Objective. This study aimed to determine the performance of infection prevention and control (IPC) programs in eight core components in level 2 and level 3 hospitals across all provinces in Colombia. Methods. This cross-sectional study used self-assessed IPC performance data voluntarily reported by hospi- tals to the Ministry of Health and Social Protection during 2021. Each of the eight core components of the World Health Organization’s checklist in the Infection Prevention and Control Assessment Framework contributes a maximum score of 100, and the overall IPC performance score is the sum of these component scores. IPC performance is graded according to the overall score as inadequate (0–200), basic (201–400), intermediate (401–600) or advanced (601–800). Results. Of the 441 level 2 and level 3 hospitals, 267 (61%) reported their IPC performance. The median (interquartile range [IQR]) overall IPC score was 672 (IQR: 578–715). Of the 267 hospitals reporting, 187 (70%) achieved an advanced level of IPC. The median overall IPC score was significantly higher in private hospitals (690, IQR: 598–725) than in public hospitals (629, IQR: 538–683) (P < 0.001). Among the core components, scores were highest for the category assessing IPC guidelines (median score: 97.5) and lowest for the cate- gory assessing workload, staffing and bed occupancy (median score: 70). Median overall IPC scores varied across the provinces (P < 0.001). Conclusions. This countrywide assessment showed that 70% of surveyed hospitals achieved a self-reported advanced level of IPC performance, which reflects progress in building health system resilience. Since only 61% of eligible hospitals participated, an important next step is to ensure the participation of all hospitals in future assessments.

[RESUMEN]. Objetivo. El objetivo de este estudio es determinar el desempeño de los programas de prevención y control de infecciones (PCI) en relación con ocho componentes básicos en hospitales de nivel 2 y 3 de todas las provincias de Colombia. Métodos. En este estudio transversal se emplearon datos de autoevaluación del desempeño de los programas de PCI informados voluntariamente al Ministerio de Salud y Protección Social por parte de los hospitales durante el 2021. Cada uno de los ocho componentes básicos de la lista de verificación de la Organización Mundial de la Salud incluidos en el Marco de evaluación de prevención y control de infecciones al nivel de establecimientos de atención de salud recibe una puntuación máxima de 100, y la puntuación general del desempeño del programa es la suma de las puntuaciones de estos componentes. Este desempeño se califica según la puntuación general como inadecuado (0-200), básico (201-400), intermedio (401-600) o avanzado (601-800). Resultados. De los 441 hospitales de nivel 2 y nivel 3, 267 (61%) informaron datos sobre su desempeño. La mediana (rango intercuartil [IQR]) de la puntuación general fue de 672 (IQR: 578–715). De los 267 hospi- tales que proporcionaron información, 187 (70%) alcanzaron el nivel avanzado. La mediana de la puntuación general fue significativamente mayor en los hospitales privados (690, IQR: 598-725) que en los hospitales públicos (629, IQR: 538-683) (p < 0,001). En el caso de los componentes básicos, las puntuaciones más altas fueron para la categoría que evalúa las directrices de PCI (puntuación mediana: 97,5) y más bajas para la categoría que evalúa la carga de trabajo, la dotación de personal y la ocupación de camas (puntuación mediana: 70). La mediana de las puntuaciones generales de PCI varió entre las provincias (p < 0,001). Conclusiones. Esta evaluación a nivel nacional mostró que el 70% de los hospitales encuestados lograron un nivel avanzado autoinformado del desempeño en cuanto a la PCI, lo que refleja el progreso en fortalec- imiento de la resiliencia del sistema de salud. Dado que solo participó el 61% de los hospitales que reunían las condiciones, el siguiente paso importante es garantizar la participación de todos los hospitales en futuras evaluaciones.

[RESUMO]. Objetivo. Este estudo teve o objetivo de determinar o desempenho de programas de prevenção e controle de infecções (PCI) quanto a oito componentes centrais em hospitais secundários e terciários de todas as províncias da Colômbia. Métodos. Este estudo transversal utilizou dados de desempenho autoavaliado de PCI enviados voluntaria- mente pelos hospitais ao Ministério da Saúde e Proteção Social em 2021. Cada um dos oito componentes centrais da lista de verificação na Estrutura de Avaliação de Prevenção e Controle de Infecções da Organi- zação Mundial da Saúde contribui com uma pontuação máxima de 100. A pontuação total de desempenho de PCI é a soma das pontuações nesses componentes. De acordo com a pontuação total, o desempenho de PCI é classificado nas seguintes categorias: inadequado (0-200), básico (201-400), intermediário (401-600) ou avançado (601-800). Resultados. Dos 441 hospitais secundários e terciários, 267 (61%) informaram o desempenho de PCI. A mediana (intervalo interquartil [IIQ]) da pontuação total de PCI foi 672 (IIQ: 578-715). Dos 267 hospitais que disponibilizaram informações, 187 (70%) alcançaram um nível de PCI avançado. A mediana da pontuação total de PCI foi significativamente maior nos hospitais privados (690, IIQ: 598-725) do que nos públicos (629, IIQ: 538-683) (p < 0,001). Entre os componentes centrais, as pontuações mais altas foram observadas na cat- egoria de avaliação das diretrizes de PCI (pontuação mediana: 97,5), ao passo que as mais baixas ocorreram na categoria de avaliação da carga de trabalho, dotação de pessoal e taxa de ocupação de leitos (pontuação mediana: 70). As medianas das pontuações totais de PCI variaram entre províncias (p < 0,001). Conclusões. Esta avaliação nacional mostrou que 70% dos hospitais pesquisados alcançaram um nível avançado de desempenho autorrelatado de PCI, o que demonstra progresso no desenvolvimento de resiliência no sistema de saúde. Como apenas 61% dos hospitais elegíveis participaram, um próximo passo importante é assegurar a participação de todos os hospitais em futuras avaliações.

Adherence to guidelines on the use of amoxicillin for treatment of ambulatory pneumonia in children younger than 5 years, Colombia, 2017–2019

[ABSTRACT]. Objectives. To determine the level of adherence to clinical guidelines in prescribing amoxicillin to children younger than 5 years with pneumonia in outpatient settings in Colombia from 2017 to 2019, and assess the factors associated with adherence Methods. This was a cross-sectional study of secondary data from the Colombian Integrated Social Protec- tion Information System database. Adherence was defined as prescription of oral amoxicillin for bacterial and unspecified pneumonia and non-prescription for viral pneumonia. Variables examined included: age (< 1 year, 1–4 years) of child; sex; cause of pneumonia (bacterial, viral, unspecified); region (Andean, Amazonian, Pacific, Caribbean, Insular, Orinoquian); and payment mechanism (without prior authorization, capitation, dir- ect payment, pay per case, pay for event). Results. Of 215 925 cases of community-acquired pneumonia reported during 2017–2019, 64.8% were from the Andean region, 73.9% were bacterial pneumonia and 1.8% were viral pneumonia. Adherence to guide- lines was observed in 5.8% of cases: this was highest for children diagnosed with viral (86.0%) compared with bacterial (2.0%) pneumonia. For children diagnosed with bacterial pneumonia, 9.4% were prescribed any antibiotic. A greater proportion of children covered by capitated payments (22.3%) were given treatment consistent with the guidelines compared with payment for event (1.3%). Conclusion. In this first study from Colombia, adherence to guidelines for outpatient treatment of children with bacterial pneumonia was low and was better for viral pneumonia. Further qualitative studies are needed to explore the reasons for this lack of adherence and why bacterial pneumonia was the most commonly reported etiology.

[RESUMEN]. Objetivos. Determinar el nivel de adherencia a las directrices clínicas al momento de prescribir amoxicilina a menores de 5 años con neumonía en entornos de atención ambulatoria en Colombia entre el 2017 y el 2019, así como evaluar los factores asociados con la adherencia. Métodos. Este fue un estudio transversal de datos secundarios de la base de datos del Sistema Integral de Información de la Protección Social de Colombia. La adherencia se definió como la prescripción de amox- icilina por vía oral para las neumonías bacterianas y no especificadas, y la ausencia de prescripción para las neumonías virales. Las variables examinadas incluyeron: edad (< 1 año, 1 a 4 años); sexo; causa de la neumonía (bacteriana, viral, no especificada); región (andina, amazónica, Pacífico, Caribe, insular, Orinoco); y mecanismo de pago (sin autorización previa, capitación, pago directo, pago por caso, pago por evento). Resultados. De 215 925 casos de neumonía adquirida en la comunidad notificados durante el período 2017- 2019, el 64,8% correspondieron a la región andina, el 73,9% a neumonía bacteriana y el 1,8% a neumonía viral. Se observó la adherencia a las directrices en el 5,8% de los casos: esta cifra fue más alta para la población infantil diagnosticada con neumonía viral (86,0%) que para la diagnosticada con neumonía bacte- riana (2,0%). En el caso de la población infantil diagnosticada con neumonía bacteriana, al 9,4% se le recetó algún antibiótico. La proporción de población infantil cubierta por pagos capitados (22,3%) que recibió un tratamiento en consonancia con las directrices fue mayor que la de la población cubierta por pagos por evento (1,3%). Conclusión. En este primer estudio de Colombia, la adherencia a las directrices sobre el tratamiento ambula- torio de la población infantil con neumonía bacteriana fue bajo, en tanto que resultó superior en el caso de la neumonía viral. Se necesitan más estudios cualitativos para indagar sobre los motivos de esta falta de adher- encia y las razones por las cuales la neumonía bacteriana fue la etiología notificada con mayor frecuencia.

[RESUMO]. Objetivos. Determinar o nível de adesão às diretrizes clínicas para prescrição de amoxicilina em regime ambulatorial para crianças menores de 5 anos com pneumonia na Colômbia, de 2017 a 2019, e avaliar os fatores associados à adesão. Métodos. Estudo transversal de dados secundários do banco de dados do Sistema Integrado de Informação sobre Proteção Social da Colômbia. Definiu-se adesão como prescrição de amoxicilina oral para pneumonia bacteriana e não especificada, e não prescrição para pneumonia viral. As variáveis examinadas incluíram: idade da criança (< 1 ano, 1–4 anos), sexo, etiologia da pneumonia (bacteriana, viral, não especificada), região (Andina, Amazônica, Pacífica, Caribenha, Insular, Orinoco) e mecanismo de pagamento (sem autor- ização prévia, capitação, pagamento direto, pay-per-case, pay-for-event). Resultados. Dos 215.925 casos de pneumonia adquirida na comunidade notificados nos anos 2017-2019, 64,8% ocorreram na região Andina, 73,9% foram pneumonia bacteriana e 1,8% foram pneumonia viral. A adesão às diretrizes foi observada em 5,8% dos casos. Foi maior para crianças com diagnóstico de pneu- monia viral (86,0%) em comparação com pneumonia bacteriana (2,0%). Para as crianças com diagnóstico de pneumonia bacteriana, 9,4% receberam algum antibiótico. Uma proporção maior de crianças cobertas por pagamentos capitados (22,3%) recebeu tratamento compatível com as diretrizes, contra apenas 1,3% no esquema de pay-for-event. Conclusão. Neste primeiro estudo da Colômbia, a adesão às diretrizes para tratamento ambulatorial de cri- anças com pneumonia bacteriana foi baixa, sendo melhor para pneumonia viral. Mais estudos qualitativos são necessários para explorar as razões dessa falta de adesão e por qual motivo a pneumonia bacteriana foi a etiologia mais comumente notificada.

Cumulative antitumor effect of bismuth lipophilic nanoparticles and cetylpyridinium chloride in inhibiting the growth of lung cancer.

OBJECTIVE: To determine the combined antitumor effect of bismuth lipophilic nanoparticles (BisBAL NP) and cetylpyridinium chloride (CPC) on human lung tumor cells. MATERIAL AND METHODS: The human lung tumor cells A549 were exposed to 1-100 µM BisBAL NP or CPC, either separately or in a 1:1 combination. Cell viability was measured with the PrestoBlue assay, the LIVE/DEAD assay, and fluorescence microscopy. The integrity and morphology of cellular microtubules were analyzed by immunofluorescence. RESULTS: A 24-h exposure to 1 µM solutions reduced A549 growth with 21.5% for BisBAL NP, 70.5% for CPC, and 92.4% for the combination (p < 0.0001), while a 50 µM BisBAL NP/CPC mixture inhibited cell growth with 99% (p < 0.0001). BisBAL NP-curcumin conjugates were internalized within 30 min of exposure and could be traced within the nucleus of tumor cells within 2 h. BisBAL NP, but not CPC, interfered with microtubule organization, thus interrupting cell replication, similar to the action mechanism of docetaxel. CONCLUSION: The growth inhibition of A549 human tumor cells by BisBAL NP and CPC was cumulative as of 1 µM. The BisBAL NP/CPC combination may constitute an innovative and cost-effective alternative for treating human lung cancer.

The Road to Malignant Cell Transformation after Particulate Matter Exposure: From Oxidative Stress to Genotoxicity.

In cells, oxidative stress is an imbalance between the production/accumulation of oxidants and the ability of the antioxidant system to detoxify these reactive products. Reactive oxygen species (ROS), cause multiple cellular damages through their interaction with biomolecules such as lipids, proteins, and DNA. Genotoxic damage caused by oxidative stress has become relevant since it can lead to mutation and play a central role in malignant transformation. The evidence describes chronic oxidative stress as an important factor implicated in all stages of the multistep carcinogenic process: initiation, promotion, and progression. In recent years, ambient air pollution by particulate matter (PM) has been cataloged as a cancer risk factor, increasing the incidence of different types of tumors. Epidemiological and toxicological evidence shows how PM-induced oxidative stress could mediate multiple events oriented to carcinogenesis, such as proliferative signaling, evasion of growth suppressors, resistance to cell death, induction of angiogenesis, and activation of invasion/metastasis pathways. In this review, we summarize the findings regarding the involvement of oxidative and genotoxic mechanisms generated by PM in malignant cell transformation. We also discuss the importance of new approaches oriented to studying the development of tumors associated with PM with more accuracy, pursuing the goal of weighing the impact of oxidative stress and genotoxicity as one of the main mechanisms associated with its carcinogenic potential.

Airborne particulate matter (PM10) induces cell invasion through Aryl Hydrocarbon Receptor and Activator Protein 1 (AP-1) pathway deregulation in A549 lung epithelial cells.

BACKGROUND: Particulate matter with an aerodynamic size ≤ 10 µm (PM10) is a risk factor for lung cancer development, mainly because some components are highly toxic. Polycyclic aromatic hydrocarbons (PAHs) are present in PM10, such as benzo[a]pyrene (BaP), which is a well-known genotoxic and carcinogenic compound to humans, capable of activating AP-1 transcription factor family genes through the Aryl Hydrocarbon Receptor (AhR). Because effects of BaP include metalloprotease 9 (MMP-9) activation, cell invasion, and other pathways related to carcinogenesis, we aimed to demonstrate that PM10 (10 µg/cm2) exposure induces the activation of AP-1 family members as well as cell invasion in lung epithelial cells, through AhR pathway. METHODS AND RESULTS: The role of the AhR gene in cells exposed to PM10 (10 µg/cm2) and BaP (1µM) for 48 h was evaluated using AhR-targeted interference siRNA. Then, the AP-1 family members (c-Jun, Jun B, Jun D, Fos B, C-Fos, and Fra-1), the levels/activity of MMP-9, and cell invasion were analyzed. We found that PM10 increased AhR levels and promoted its nuclear localization in A549 treated cells. Also, PM10 and BaP deregulated the activity of AP-1 family members. Moreover, PM10 upregulated the secretion and activity of MMP-9 through AhR, while BaP had no effect. Finally, we found that cell invasion in A549 cells exposed to PM10 and BaP is modulated by AhR. CONCLUSION: Our results demonstrated that PM10 exposure induces upregulation of the c-Jun, Jun B, and Fra-1 activity, the expression/activity of MMP-9, and the cell invasion in lung epithelial cells, effects mediated through the AhR. Also, the Fos B and C-Fos activity were downregulated. In addition, the effects induced by PM10 exposure were like those induced by BaP, which highlights the potentially toxic effects of the PM10 mixture in lung epithelial cells.

Adherence to guidelines on the use of amoxicillin for treatment of ambulatory pneumonia in children younger than 5 years, Colombia, 2017-2019 / Adherencia a las directrices sobre el uso de amoxicilina para el tratamiento ambulatorio de la neumonía en menores de 5 años, Colombia, 2017-2019 / Adesão às diretrizes sobre uso de amoxicilina para tratamento de pneumonia ambulatorial em crianças menores de 5 anos, Colômbia, 2017-2019

ABSTRACT Objectives. To determine the level of adherence to clinical guidelines in prescribing amoxicillin to children younger than 5 years with pneumonia in outpatient settings in Colombia from 2017 to 2019, and assess the factors associated with adherence Methods. This was a cross-sectional study of secondary data from the Colombian Integrated Social Protection Information System database. Adherence was defined as prescription of oral amoxicillin for bacterial and unspecified pneumonia and non-prescription for viral pneumonia. Variables examined included: age (< 1 year, 1-4 years) of child; sex; cause of pneumonia (bacterial, viral, unspecified); region (Andean, Amazonian, Pacific, Caribbean, Insular, Orinoquian); and payment mechanism (without prior authorization, capitation, direct payment, pay per case, pay for event). Results. Of 215 925 cases of community-acquired pneumonia reported during 2017-2019, 64.8% were from the Andean region, 73.9% were bacterial pneumonia and 1.8% were viral pneumonia. Adherence to guidelines was observed in 5.8% of cases: this was highest for children diagnosed with viral (86.0%) compared with bacterial (2.0%) pneumonia. For children diagnosed with bacterial pneumonia, 9.4% were prescribed any antibiotic. A greater proportion of children covered by capitated payments (22.3%) were given treatment consistent with the guidelines compared with payment for event (1.3%). Conclusion. In this first study from Colombia, adherence to guidelines for outpatient treatment of children with bacterial pneumonia was low and was better for viral pneumonia. Further qualitative studies are needed to explore the reasons for this lack of adherence and why bacterial pneumonia was the most commonly reported etiology.

RESUMEN Objetivos. Determinar el nivel de adherencia a las directrices clínicas al momento de prescribir amoxicilina a menores de 5 años con neumonía en entornos de atención ambulatoria en Colombia entre el 2017 y el 2019, así como evaluar los factores asociados con la adherencia. Métodos. Este fue un estudio transversal de datos secundarios de la base de datos del Sistema Integral de Información de la Protección Social de Colombia. La adherencia se definió como la prescripción de amoxicilina por vía oral para las neumonías bacterianas y no especificadas, y la ausencia de prescripción para las neumonías virales. Las variables examinadas incluyeron: edad (< 1 año, 1 a 4 años); sexo; causa de la neumonía (bacteriana, viral, no especificada); región (andina, amazónica, Pacífico, Caribe, insular, Orinoco); y mecanismo de pago (sin autorización previa, capitación, pago directo, pago por caso, pago por evento). Resultados. De 215 925 casos de neumonía adquirida en la comunidad notificados durante el período 2017-2019, el 64,8% correspondieron a la región andina, el 73,9% a neumonía bacteriana y el 1,8% a neumonía viral. Se observó la adherencia a las directrices en el 5,8% de los casos: esta cifra fue más alta para la población infantil diagnosticada con neumonía viral (86,0%) que para la diagnosticada con neumonía bacteriana (2,0%). En el caso de la población infantil diagnosticada con neumonía bacteriana, al 9,4% se le recetó algún antibiótico. La proporción de población infantil cubierta por pagos capitados (22,3%) que recibió un tratamiento en consonancia con las directrices fue mayor que la de la población cubierta por pagos por evento (1,3%). Conclusión. En este primer estudio de Colombia, la adherencia a las directrices sobre el tratamiento ambulatorio de la población infantil con neumonía bacteriana fue bajo, en tanto que resultó superior en el caso de la neumonía viral. Se necesitan más estudios cualitativos para indagar sobre los motivos de esta falta de adherencia y las razones por las cuales la neumonía bacteriana fue la etiología notificada con mayor frecuencia.

RESUMO Objetivos. Determinar o nível de adesão às diretrizes clínicas para prescrição de amoxicilina em regime ambulatorial para crianças menores de 5 anos com pneumonia na Colômbia, de 2017 a 2019, e avaliar os fatores associados à adesão. Métodos. Estudo transversal de dados secundários do banco de dados do Sistema Integrado de Informação sobre Proteção Social da Colômbia. Definiu-se adesão como prescrição de amoxicilina oral para pneumonia bacteriana e não especificada, e não prescrição para pneumonia viral. As variáveis examinadas incluíram: idade da criança (< 1 ano, 1-4 anos), sexo, etiologia da pneumonia (bacteriana, viral, não especificada), região (Andina, Amazônica, Pacífica, Caribenha, Insular, Orinoco) e mecanismo de pagamento (sem autorização prévia, capitação, pagamento direto, pay-per-case, pay-for-event). Resultados. Dos 215.925 casos de pneumonia adquirida na comunidade notificados nos anos 2017-2019, 64,8% ocorreram na região Andina, 73,9% foram pneumonia bacteriana e 1,8% foram pneumonia viral. A adesão às diretrizes foi observada em 5,8% dos casos. Foi maior para crianças com diagnóstico de pneumonia viral (86,0%) em comparação com pneumonia bacteriana (2,0%). Para as crianças com diagnóstico de pneumonia bacteriana, 9,4% receberam algum antibiótico. Uma proporção maior de crianças cobertas por pagamentos capitados (22,3%) recebeu tratamento compatível com as diretrizes, contra apenas 1,3% no esquema de pay-for-event. Conclusão. Neste primeiro estudo da Colômbia, a adesão às diretrizes para tratamento ambulatorial de crianças com pneumonia bacteriana foi baixa, sendo melhor para pneumonia viral. Mais estudos qualitativos são necessários para explorar as razões dessa falta de adesão e por qual motivo a pneumonia bacteriana foi a etiologia mais comumente notificada.

High level of infection prevention and control in surveyed hospitals in Colombia, 2021 / Nivel avanzado de prevención y control de infecciones en hospitales de Colombia en el 2021 / Alto nível de prevenção e controle de infecções em hospitais da Colômbia, 2021

ABSTRACT Objective. This study aimed to determine the performance of infection prevention and control (IPC) programs in eight core components in level 2 and level 3 hospitals across all provinces in Colombia. Methods. This cross-sectional study used self-assessed IPC performance data voluntarily reported by hospitals to the Ministry of Health and Social Protection during 2021. Each of the eight core components of the World Health Organization's checklist in the Infection Prevention and Control Assessment Framework contributes a maximum score of 100, and the overall IPC performance score is the sum of these component scores. IPC performance is graded according to the overall score as inadequate (0-200), basic (201-400), intermediate (401-600) or advanced (601-800). Results. Of the 441 level 2 and level 3 hospitals, 267 (61%) reported their IPC performance. The median (interquartile range [IQR]) overall IPC score was 672 (IQR: 578-715). Of the 267 hospitals reporting, 187 (70%) achieved an advanced level of IPC. The median overall IPC score was significantly higher in private hospitals (690, IQR: 598-725) than in public hospitals (629, IQR: 538-683) (P < 0.001). Among the core components, scores were highest for the category assessing IPC guidelines (median score: 97.5) and lowest for the category assessing workload, staffing and bed occupancy (median score: 70). Median overall IPC scores varied across the provinces (P < 0.001). Conclusions. This countrywide assessment showed that 70% of surveyed hospitals achieved a self-reported advanced level of IPC performance, which reflects progress in building health system resilience. Since only 61% of eligible hospitals participated, an important next step is to ensure the participation of all hospitals in future assessments.

RESUMEN Objetivo. El objetivo de este estudio es determinar el desempeño de los programas de prevención y control de infecciones (PCI) en relación con ocho componentes básicos en hospitales de nivel 2 y 3 de todas las provincias de Colombia. Métodos. En este estudio transversal se emplearon datos de autoevaluación del desempeño de los programas de PCI informados voluntariamente al Ministerio de Salud y Protección Social por parte de los hospitales durante el 2021. Cada uno de los ocho componentes básicos de la lista de verificación de la Organización Mundial de la Salud incluidos en el Marco de evaluación de prevención y control de infecciones al nivel de establecimientos de atención de salud recibe una puntuación máxima de 100, y la puntuación general del desempeño del programa es la suma de las puntuaciones de estos componentes. Este desempeño se califica según la puntuación general como inadecuado (0-200), básico (201-400), intermedio (401-600) o avanzado (601-800). Resultados. De los 441 hospitales de nivel 2 y nivel 3, 267 (61%) informaron datos sobre su desempeño. La mediana (rango intercuartil [IQR]) de la puntuación general fue de 672 (IQR: 578-715). De los 267 hospitales que proporcionaron información, 187 (70%) alcanzaron el nivel avanzado. La mediana de la puntuación general fue significativamente mayor en los hospitales privados (690, IQR: 598-725) que en los hospitales públicos (629, IQR: 538-683) (p < 0,001). En el caso de los componentes básicos, las puntuaciones más altas fueron para la categoría que evalúa las directrices de PCI (puntuación mediana: 97,5) y más bajas para la categoría que evalúa la carga de trabajo, la dotación de personal y la ocupación de camas (puntuación mediana: 70). La mediana de las puntuaciones generales de PCI varió entre las provincias (p < 0,001). Conclusiones. Esta evaluación a nivel nacional mostró que el 70% de los hospitales encuestados lograron un nivel avanzado autoinformado del desempeño en cuanto a la PCI, lo que refleja el progreso en fortalecimiento de la resiliencia del sistema de salud. Dado que solo participó el 61% de los hospitales que reunían las condiciones, el siguiente paso importante es garantizar la participación de todos los hospitales en futuras evaluaciones.

RESUMO Objetivo. Este estudo teve o objetivo de determinar o desempenho de programas de prevenção e controle de infecções (PCI) quanto a oito componentes centrais em hospitais secundários e terciários de todas as províncias da Colômbia. Métodos. Este estudo transversal utilizou dados de desempenho autoavaliado de PCI enviados voluntariamente pelos hospitais ao Ministério da Saúde e Proteção Social em 2021. Cada um dos oito componentes centrais da lista de verificação na Estrutura de Avaliação de Prevenção e Controle de Infecções da Organização Mundial da Saúde contribui com uma pontuação máxima de 100. A pontuação total de desempenho de PCI é a soma das pontuações nesses componentes. De acordo com a pontuação total, o desempenho de PCI é classificado nas seguintes categorias: inadequado (0-200), básico (201-400), intermediário (401-600) ou avançado (601-800). Resultados. Dos 441 hospitais secundários e terciários, 267 (61%) informaram o desempenho de PCI. A mediana (intervalo interquartil [IIQ]) da pontuação total de PCI foi 672 (IIQ: 578-715). Dos 267 hospitais que disponibilizaram informações, 187 (70%) alcançaram um nível de PCI avançado. A mediana da pontuação total de PCI foi significativamente maior nos hospitais privados (690, IIQ: 598-725) do que nos públicos (629, IIQ: 538-683) (p < 0,001). Entre os componentes centrais, as pontuações mais altas foram observadas na categoria de avaliação das diretrizes de PCI (pontuação mediana: 97,5), ao passo que as mais baixas ocorreram na categoria de avaliação da carga de trabalho, dotação de pessoal e taxa de ocupação de leitos (pontuação mediana: 70). As medianas das pontuações totais de PCI variaram entre províncias (p < 0,001). Conclusões. Esta avaliação nacional mostrou que 70% dos hospitais pesquisados alcançaram um nível avançado de desempenho autorrelatado de PCI, o que demonstra progresso no desenvolvimento de resiliência no sistema de saúde. Como apenas 61% dos hospitais elegíveis participaram, um próximo passo importante é assegurar a participação de todos os hospitais em futuras avaliações.

Perception about vaccines and level of knowledge, attitudes and practices towards COVID-19 in older adults in Lima, Peru. / Percepción sobre las vacunas y nivel de conocimientos, actitudes y prácticas hacia la COVID-19 en adultos mayores de Lima, Perú.

This study aimed to describe the perception about vaccines and the level of knowledge, attitudes and practices towards COVID-19 in older adults from a hospital in Lima, Peru. Descriptive and cross-sectional study carried out from March to November 2021. An instrument was adapted and validated to measure the level of knowledge, attitudes and practices; the perception about vaccines was evaluated with an exploratory questionnaire. Eighty-three older adults were surveyed, the mean age was 74.0 years and 62.7% were women. Most of the participants knew the cause and symptoms, and 50.6% believed that it could be transmitted by contaminated food. Additionally, 61.7% used traditional medicine to prevent it, and 65.4% considered that the level of social awareness was insufficient; 91.5% were vaccinated against COVID-19, and 65.4% considered these vaccines to be safe. In conclusion, most older adults showed a high level of knowledge, attitudes and practices and a positive perception about the vaccine against COVID-19.

El objetivo fue describir la percepción sobre las vacunas y el nivel de conocimientos, actitudes y prácticas hacia la COVID-19 en adultos mayores que acuden a un hospital en Lima, Perú. Estudio descriptivo y transversal de marzo a noviembre del 2021. Se adaptó y validó un instrumento para medir el nivel de conocimientos, actitudes y prácticas, y se evaluó la percepción sobre vacunas con un cuestionario exploratorio. Se encuestaron a 83 adultos mayores, la media de edad fue 74,0 años y el 62,7% fueron mujeres. La mayoría conoce la causa y síntomas, y el 50,6% cree que puede transmitirse por alimentos contaminados. El 61,7% usa medicina tradicional para prevenirla, y el 65,4% considera insuficiente el nivel de conciencia social. El 91,5% se vacunó contra la COVID-19, y el 65,4% considera que estas vacunas son seguras. En conclusión, la mayoría de los adultos mayores presenta un alto nivel de conocimientos, actitudes y prácticas y una percepción positiva sobre la vacuna contra la COVID-19.