Repositorio Institucional
Nuestra plataforma Reúne, conserva y difunde la producción intelectual en formato digital de estudiantes, académicos e investigadores de la Universidad del Desarrollo. Es una plataforma web colaborativa diseñada y administrada por el Sistema de Bibliotecas, en el que participan las unidades académicas como proveedoras de contenido, ejerciendo el rol de editor en su respectiva “comunidad” Leer Más...
¿Qué estás buscando?
Recent Submissions
Daily compliance of the ABCDEF liberation bundle for patients in the intensive care unit: A retrospective descriptive study
(2024) Muñoz, Felipe; Leppe Zamora, Jaime; González Seguel, Felipe; Castro-Avila, Ana Cristina
Introduction Implementing the ABCDEF bundle has demonstrated improved outcomes in patients with critical illness. This study aims to describe the daily compliance of the ABCDEF bundle in a Chilean intensive care unit.
Methods Retrospective observational study of electronic clinical records of nursing, physiotherapy, and medical professionals who cared for patients over 18 years of age, admitted to an intensive care unit for at least 24 hours, with or without mechanical ventilation. Daily bundle compliance was determined by considering the daily records for each element: Assess pain (element A), both spontaneous awakening trials (element B1) and spontaneous breathing trials (element B2), choice of sedation (element C), delirium assessment (element D), early mobilization (element E), and family engagement (element F).
Results 4165 registered bundle elements were obtained from nursing (47%), physiotherapy (44%), and physicians (7%), including 1134 patient/days (from 133 patients). Elements E and C showed 67 and 40% compliance, while D, A, and B2 showed 24, 14 and 11%, respectively. For B1 and F, 0% compliance was achieved. Compliance was higher in patients without mechanical ventilation for A and E, while it was similar for D.
Conclusions Early mobilization had the highest compliance, while spontaneous awakening trials and family engagement had absolute non-compliance. Future studies should explore the reasons for the different degrees of compliance per bundle element in clinical practice.
Integration of T-cell clonality screening using TRBC-1 in lymphoma suspect samples by flow cytometry
(2024) Castillo, Felipe; Morales, Constanza; Spralja, Biserka; Díaz Schmidt, Joaquín Andrés; Iruretagoyena, Mirentxu; Ernst, Daniel
Background: The diagnosis of T-cell non-Hodgkin lymphomas (NHL) is challenging. The development of a monoclonal antibody specific for T-cell receptor β constant region 1 (TRBC1) provides an alternative to discriminate clonal T cells. The aim of this study was to evaluate the diagnostic potential of an anti-TRBC1 mAb for the identification of T-NHL.
Methods: We performed a cross-sectional diagnostic analytic study of samples tested for lymphoma. All samples sent for lymphoma screening were first evaluated using the standard Euroflow LST, to which a second additional custom-designed T-cell clonality assessment tube was added CD45/TRBC1/CD2/CD7/CD4/TCRγδ/CD3. Flow cytometry reports were compared with morphological and molecular tests.
Results: Fifty-nine patient samples were evaluated. Within the T-cell population, cut-off percentages in the CD4+ cells were from 29.4 to 54.6% and from 23.9 to 52.1% in CD8+ cells. Cut-off ratios in CD4+ T cells were from 0.33 to 1.1, and in CD8+ cells between 0.22 and 1.0. Using predefined normal cut-off values, 18 of 59 (30.5%) samples showed a restricted expression of TRBC1. A final diagnosis of a T-NHL was confirmed clinically and/or by histopathological studies in 15 of the 18 cases (83.3%). There were no cases of T-NHL by morphology/IHC with normal TRBC1 expression. Non-neoplastic patient samples behaved between predefined TRBC1 cut-off values.
Conclusions: Expression of TRBC1 provides a robust method for T-cell clonality assessment, with very high sensitivity and good correlation with complementary methods. TRBC1 can be integrated into routine lymphoma screening strategies via flow cytometry.
Cognitive telerehabilitation: an expert consensus paper on current evidence and future perspective
(2024) Maggio, Maria Grazia; Baglio, Francesca; Arcuri, Francesco; Borgnis, Francesca; Contrada, Marianna; Maldonado Diaz, Marcos Daniel; Leochico, Carl Froilan; Jimenez Neira, Nicolas; Laratta, Stefania; Suchan, Boris; Tonin, Paolo; Calabrò, Rocco Salvatore
The progressive improvement of the living conditions and medical care of the population in industrialized countries has led to improvement in healthcare
interventions, including rehabilitation. From this perspective, Telerehabilitation (TR) plays an important role. TR consists of the application of telemedicine to
rehabilitation to offer remote rehabilitation services to the population unable to reach healthcare. TR integrates therapy-recovery-assistance, with continuity
of treatments, aimed at neurological and psychological recovery, involving the patient in a family environment, with an active role also of the caregivers. This
leads to reduced healthcare costs and improves the continuity of specialist care, as well as showing efficacy for the treatment of cognitive disorders, and
leading to advantages for patients and their families, such as avoiding travel, reducing associated costs, improving the frequency, continuity, and comfort
of performing the rehabilitation in its own spaces, times and arrangements.
The aim of this consensus paper is to investigate the current evidence on the use and effectiveness of TR in the cognitive field, trying to also suggest some
recommendations and future perspectives. To the best of our knowledge, this is the first consensus paper among multiple expert researchers that
comprehensively examines TR in different neurological diseases. Our results supported the efficacy and feasibility of TR with good adherence and no adverse
events among patients. Our consensus summarizes the current evidence for the application of cognitive TR in neurological populations, highlighting the
potential of this tool, but also the limitations that need to be explored further.
Columnas de Opinión: explorando las dimensiones filosóficas del tiempo en la actualidad
(Universidad del Desarrollo. Centro de Innovación Docente, 2024) Gerias Inostroza, Mariana; Fossa, Pablo
El proyecto buscó fortalecer las habilidades de lecto-escritura de los estudiantes del curso Track, mediante la creación de columnas de opinión sobre el concepto de tiempo. Implementado el segundo semestre de 2024, incluyó actividades prácticas con retroalimentación constante, guiadas por una docente experta permitió a los 40 participantes mejorar su capacidad de argumentación escrita, vinculando teorías filosóficas del tiempo con temas actuales, intereses y experiencias personales.
The impact of education level and socioeconomic status on the association between depressive symptoms and memory in an older population in Latin America: An exploratory analysis from the Brazilian Longitudinal Study of Aging (ELSI-BRAZIL)
(2024) Loss, Karla; Fandino, Wilson; Almarie, Bassel; Bazan-Perkins, Blanca; Minetto, Julia; Nadine Aranis, Nadine; Monaco, Thiago; Aladab, Aisha; Pacheco-Barrios, Kevin; Fregni, Felipe
Purpose: The globally increasing older population raises concerns about age-related conditions, including cognitive impairment and depressive symptoms. In Latin America, nearly one-third of the population is affected by either of these conditions. However, data investigating the association between cognitive impairment and depressive symptoms, particularly in Brazil, are limited to small-scale studies that have not carefully examined the critical effects of variables such as education level and socioeconomic status on this relationship. We aimed at exploring this association in a representative population-based cohort.
Methods: We used the Brazilian Longitudinal Study of Aging (ELSI-BRAZIL) database to examine the relationship between depressive symptoms and cognitive impairment in Brazilian older adults, adjusted for potential confounders. Direct acyclic graphs and multivariable linear regression were used to build our model. Depressive symptoms were measured using a short version of the Center for Epidemiologic Studies Scale (CES D-8), and combined memory recall test as a surrogate of cognitive impairment.
Results: The study included 8280 participants. Only education level was identified as a confounder for the relationship between memory loss and depressive symptoms. After adjusting for age, sex, and education level, there was strong evidence for a negative association between depressive symptoms and memory performance. For every 5-unit increase in the CES D-8 score, there was a reduction in memory capacity, translating to a loss of approximately one word in the combined words recall test (mean - 0.18, 95% CI -0.22; -0.15, P < 0.001). In addition, we found strong evidence for an interaction between socioeconomic status and depressive symptoms. Subjects belonging to medium socioeconomic status (SES) showed more pronounced memory decline, when compared to those with lower SES (mean - 0.28, 95% CI -0.42 to -0.14, P < 0.001).
Conclusions: In adults aged over 50, after adjusting for sex, age, and educational level, a 5-unit increase in CES D-8 score is associated with loss of one point in the combined memory recall test. This association seems to be confounded by educational level and significantly modified by socioeconomic status.
Health conditions of migrant children and adolescents from Latin America and the Caribbean: A narrative review
(2024) CARREÑO CALDERON, ALEJANDRA; Blukacz, Alice; Cabieses, Báltica; Obach, Alexandra
The presence of children and adolescents in migratory flows is growing in Latin America and the Caribbean. Little is known about migration's effects on these groups' health. This article aims to investigate the evidence available on the access and use of healthcare services by migrant children and adolescents in Latin America and the Caribbean. We seek to explore the role of social determinants of health at different levels in the health conditions of these groups. Also, to identify potential recommendations for healthcare systems and public policy to address them. For this purpose, a narrative review of 52 publications was carried out based on a search of scientific literature in the Web of Science and Google Scholar databases. Five relevant topics were identified: use of emergency care associated with lack of healthcare access, preventive services, and other social determinants of health; exposure to preventable infectious diseases; mental health; sexual and reproductive health; and vaccinations and dental health. We conclude that the evidence shows the need to address the inequities and disadvantages faced by migrant children from a perspective of social determinants of health and policies that consider health as a human right regardless of the migratory status of children and adolescents, as well as that of their parents or primary caregivers.
Humoral immune response in people living with HIV after administration of SARS-CoV-2 vaccine CoronaVac or BNT162b2 or CoronaVac/BNT162b2 booster sequence: A cross-sectional study
(2024) Wolff, Marcelo; Charpentier, Paulo; Canals, Andrea; Vial Cox, María Cecilia; Hormazabal, Juan; Cortes Salinas, Lina Jimena; Silva, Macarena
Background: The evidence of SARS-CoV-2 vaccine effectiveness in people living with HIV (PLWH) is limited. This study evaluated the humoral immune response to CoronaVac™ (virus inactivated) and BNT162b2 (mRNA- based) vaccines in PLWH and HIV-negative controls, with and without a booster sequence.
Methods: We conducted a cross-sectional study on PLWH and HIV-negative controls who received CoronaVac or BNT162b2, with a subgroup receiving a CoronaVac/BNT162b2 booster. Blood samples were collected 4-6 months after primary vaccination and tested for anti-SARS-CoV-2 protein S (aSAb) and neutralizing antibodies (NtAb) using validated assays. Immune response was evaluated by age, sex, previous COVID-19 history, and CD4 + cell count.
Findings: One hundred and eighty nine participants were enrolled with 161 (85%) being PLWH. Among participants without previous known COVID-19, median aSAb levels were significantly lower in PLWH who received CoronaVac compared to BNT162b2 (32 U/mL vs. 587 U/mL, p < 0.001), with similar results in HIV-negative controls. NtAb presence was also significantly lower after CoronaVac compared to BNT162b2 (30% vs. 93%, p < 0.001). The booster sequence group showed a significant increase in aSAb titers in both PLWH and HIV-negative controls (from 33 U/ml to 2500 U/ml, p < 0.001), and NtAb positivity increased from 20% to 95 % in PLWH, and 27% to 100% in HIV-negative controls. Prior COVID-19 led to significantly higher post-vaccine antibody titers particularly in the BNT162b2 group. PLWH with CD4 + count < 200 cells/mL showed a weaker immune response to both vaccines.
Interpretation: CoronaVac resulted in a weaker immune response in both PLWH and HIV-negative controls compared to BNT162b2, particularly in immunosuppressed PLWH without prior COVID-19. Hybrid immunity and heterologous booster vaccination increased antibody levels.
Funding: Local funding.
Propiedades psicométricas de la versión chilena del cuestionario de calidad de vida para mieloma múltiple
(2024) Lorca, Luz Alejandra; Sacomori, Cinara; Peña, Camila; Barrera, Claudia; Salazar, Melissa; Leão, Ivana; Valladares, Ximena; Rojas, Christine
Objetivos: Evaluar consistencia interna y validez de constructo del QLQ-MY20 para valoración de calidad de vida en sobrevivientes de mieloma múltiple en Chile.
Métodos: Estudio transversal, realizado entre marzo 2020 y diciembre 2022. Participaron 118 personas de dos hospitales públicos. Se utilizaron los cuestionarios QLQ-C30 y QLQ-MY20. Fueron evaluadas la consistencia interna con alfa de Cronbach (α) y validez de constructo mediante pruebas de hipótesis (Mann Whitney y correlación de Spearman).
Resultados: El promedio de edad de los participantes era 67,2 (DE=9,2) años. Consistencia interna para escala completa (α=0,779), dimensión “síntomas de la enfermedad” (α=0,671), dimensión “efectos secundarios de los tratamientos” (α=0,538) y dimensión “perspectiva de futuro” (α=0,670). Se comprobaron cuatro de las cinco hipótesis de la validez de constructo: presentaron más síntomas las mujeres, personas con peor performance estatus, con dolor y con peor fatiga.
Conclusiones: La versión chilena del QLQ-MY20 presenta adecuada consistencia interna y validez de constructo.
Validación del cuestionario EORTC QLQ -CR29 para evaluación de la calidad de vida relacionada a la salud de personas adultas con cáncer colorrectal en Chile
(2024) Lorca Parraguez, Luz Alejandra; Sacomori, Cinara; Pizarro, Marta; Leao Ribeiro, Ivana; Vidal, Rodrigo; Rebolledo, Gonzalo
Introducción: Personas con cáncer colorrectal (CCR) pueden presentar efectos adversos, perjudicando la calidad de vida relacionada a la salud (CVRS).
Objetivo: Validar el módulo QLQ CR2-9 para evaluación de la CVRS, en Chile.
Materiales y método: Estudio transversal que incluyó 170 personas con CCR. Se analizaron la consistencia interna y validez de constructo del instrumento con test de hipótesis.
Resultados: 117 personas (68,8%) fueron evaluadas antes de la cirugía y 53 (31,2%) después de la cirugía. La consistencia interna del QLQ CR-29 fue α=0,838. Fueron comprobadas las hipótesis planteadas: Los pacientes evaluados antes de la cirugía se quejaron más de “sangre/mucosidad en las heces”, “dolor abdominal”, “pérdida de cabello” e “hinchazón abdominal”, mientras que los pacientes evaluados después presentaron más “incontinencia fecal” (p<0,05). Antes de la cirugía, los pacientes con CCR presentaron mayores valores de “frecuencia urinaria”, “frecuencia de deposiciones”, “dolor en las nalgas”, “problemas con el gusto” y “vergüenza”; mientras que aquellos con cáncer de colon que se quejaban más de “sangre/mucosidad en las heces” (p<0,05). Después de la cirugía, los pacientes con cáncer de recto tenían mayor “frecuencia de deposiciones”, “eliminación de gases” y “vergüenza” (p=0,004) en comparación con los con cáncer de colon (p<0,05). Los pacientes ostomizados presentaron más “incontinencia fecal” y “vergüenza” (p<0,001). Fueron observadas correlaciones positivas y negativas bajas entre la mayoría de las dimensiones del QLQ C-29 con las dimensiones del QLQ C-30.
Conclusión: La versión chilena del módulo QLQ CR-29 es adecuada para evaluar la CVRS en personas con CCR.
Protocol for a systematic mapping review of surgical and pharmacological interventions for the treatment of trigeminal neuralgia
(2024) Ladevig, Dominga; Veloso, Valentina; Ávila-Oliver, Camila
INTRODUCTION Trigeminal neuralgia is a painful neuropathic disorder characterized by sudden electric shock–like pain that significantly impacts patients' quality of life. Multiple treatment alternatives are available, including medical and surgical options but establishing the optimal course of action can be challenging. To enhance clinical decision-making for trigeminal neuralgia treatment, it is imperative to organize, describe and map the available systematic reviews and randomized trials. This will help identify the best treatment alternatives supported by evidence and acknowledge potential knowledge gaps where future research is needed.
OBJECTIVE This systematic mapping review aims to provide up-to-date evidence on the different surgical and pharmacological treatment alternatives used for trigeminal neuralgia.
METHODS A search will be systematically conducted on the Epistemonikos database to identify potentially eligible systematic reviews. Additionally, a search will be made in PubMed, CENTRAL, and EBSCO to identify randomized controlled trials assessing pharmacological and surgical treatment interventions for trigeminal neuralgia. Two independent reviewers will screen and select the studies. Data on the different treatment alternatives and reported outcomes in the included studies will be extracted using standardized forms. Following extraction, descriptive statistical methods will be used to analyze the data. The final output of this study will include an evidence map that will illustrate the connections between different treatments and their respective outcomes,
providing a clear depiction of the evidence landscape.
EXPECTED RESULTS This study expects to map, describe and assess the methodological quality of the available systematic reviews and trials on pharmacological interventions and neurosurgical procedures for treating trigeminal neuralgia. It will present the results in an evidence map that organizes the available evidence based on their different interventions and outcomes. This evidence map will serve as a visual tool to assist healthcare professionals and patients to understand evidence-based treatment options and their implications for managing this medical condition.
¿Cambió la pandemia la imagen de las enfermeras españolas? Identidad enfermera y voz como fuentes informativas
(2024) González-Luis, Hildegart; Beatriz Gómez-Baceiredo; Begoña Errasti-Ibarrondo; Ana Choperena; Isabel Díaz-Suárez; Amaranta Alfaro; Pérez, Claudia
Introducción: Los medios de comunicación son claves en la configuración de la imagen social de las enfermeras. La difusión de una imagen de enfermería incoherente con su identidad profesional tiene consecuencias adversas para las enfermeras, para el conjunto del sistema sanitario y para la sociedad.
Objetivo: Comparar la imagen de las enfermeras y su papel como fuentes informativas en 2019-2020 tomando como marco para el análisis la identidad profesional consensuada por ISPIN. Estudiar si durante pandemia por COVID-19 la imagen de las enfermeras en los medios fue más completa y si se les dio un mayor protagonismo como fuentes informativas.
Material y Método: Análisis cuantitativo mediante instrumento que evalúa la coherencia entre la imagen publicada y la identidad profesional enfermera definida por ISPIN en las 468 noticias publicadas en El País y El Mundo en 2019-2020, que incluían la palabra enfermera/s, enfermeros/s o enfermería.
Resultados: La presencia mediática de las enfermeras aumentó en 2020. Las temáticas principales en las que se las mencionó durante los dos años estuvieron relacionadas con cuestiones problemáticas del ejercicio de la profesión. El número de informaciones publicadas en las que se describe su trabajo diario aumentó en 2020. El rol más difundido fue el asistencial, pero la visibilidad de su función como gestoras creció durante la pandemia. Los estereotipos para representarlas se redujeron y la presencia de hombres enfermeros fue mayor.
Conclusión: Aunque se incrementó la presencia de las enfermeras y de sus asociaciones como fuentes informativas, no fueron fuentes principales en la mayoría de las noticias.
Exploring HLA-C methylation patterns and nutritional status in Kichwa mothers and infants from Tena, Ecuador
(2024) Velastegui, Erick; Falconí, Isaac; Garcia, Valeria; Munizaga, Gabriela; Matias, Carmen; Segura, Yaritza; Alcivar, Kerly; Valencia, Luz; Vera, Edwin; Muñoz, Mindy; Vanden Berghe, Wim; Lebeer, Sarah; Orellana, Andrea
Environment and lifestyle can affect the epigenome passed down from generation to generation. A mother's nutrition can impact the methylation levels of her offspring's epigenome, but it's unclear which genes may be affected by malnutrition during gestation or early development. In this study, we examined the levels of methylated GC in the promoter region of HLA-C in mothers and infants from the Kichwa community in Ecuador. To do this, we analyzed saliva samples using bisulfite DNA sequencing. While we did not observe any significant differences in the mean methylation percentages in exon 1 of HLA-C between mothers and their infants after the first two years of lactation and life, respectively, we did find that infants tended to increase their methylation level during the first two years of life, while mothers tended to decrease it after the first two years of breastfeeding. When we compared methylation levels between mothers and infants using an ANOVA/posthoc Tukey test, we found that the average methylation for the entire population was less than 3% at T1 and T2. Although there was a tendency for infants to have higher methylation levels during their first two years of life and for mothers to have lower methylation levels after the first two years of breastfeeding, the mean values were not significantly different. However, we found a significant difference when we contrasted the data using a Kruskal-Wallis test at 0.05 for T1 AND T2 (p-value: 0.0148). Specifically, mothers had an average of X̅ = 2.06% and sons had X̅ = 1.57% at T2 (p-value: 0.7227), while the average for mothers was X̅ = 1.83% and for sons X̅ =1.77%. Finally, we identified three CpG motif nucleotide positions (32-33, 43-44, and 96-97) along the 122 bp analysis of HLA-C exon one, which was found to retain methylation patterns over time and is inherited from mother to offspring. Finally, our small pilot study did not reveal significant correlations between maternal and offspring nutritional status and DNA methylation levels of HLA-C exon one.
Antiviral drugs prolong survival in murine recessive dystrophic epidermolysis bullosa
(2024) Tartaglia, Grace; Fuentes, María; Pate,Neil; Varughese, Abigail; Pyung, Lauren; Pyung, Israel; Alexander, Michael; Poojan, Shiv; Cao, Qingqing; Solomon, Brenda; Padron, Zachary; Dyer, Jonathan; Mellerio, Jemima; McGrath, John; Palisson, Francis; Salas, Julio; Han, Lin; South, Andrew
Recessive dystrophic epidermolysis bullosa (RDEB) is a rare inherited skin disease characterized by defects in type VII collagen leading to a range of fibrotic pathologies resulting from skin fragility, aberrant wound healing, and altered dermal fibroblast physiology. Using a novel in vitro model of fibrosis based on endogenously produced extracellular matrix, we screened an FDA-approved compound library and identified antivirals as a class of drug not previously associated with anti-fibrotic action. Preclinical validation of our lead hit, daclatasvir, in a mouse model of RDEB demonstrated significant improvement in fibrosis as well as overall quality of life with increased survival, weight gain and activity, and a decrease in pruritus-induced hair loss. Immunohistochemical assessment of daclatasvir-treated RDEB mouse skin showed a reduction in fibrotic markers, which was supported by in vitro data demonstrating TGFβ pathway targeting and a reduction of total collagen retained in the extracellular matrix. Our data support the clinical development of antivirals for the treatment of patients with RDEB and potentially other fibrotic diseases.
Challenges in surveillance of all cancer cases: The Chilean National Cancer Registry
(2024) Taramasco, Carla; Rimassa, Carla; Acevedo, Johanna
Cancer causes millions of deaths worldwide, making its registration essential. There are clinical, hospital, and population-based registries in place. The latter is the gold standard for information on cancer incidence and survival in a defined region. Chile has five population-based registries located in specific areas of the country. The Chilean National Cancer Registry emerged with the challenge of creating a tool encompassing all three types of registries to identify the number of cancer cases by type. Its design involved a series of actions to achieve consensus among various actors regarding information, validation, and events to be registered. Four stages were identified in the care and registration process: suspected diagnosis, morphological confirmation (biopsy), clinical resolution (oncology committee, including treatment recommendations), treatment, and oncological follow-up. The platform's development (from 2018 to 2021) involved gathering information and agreements on the requirements for co-designing the registry, including a successful pilot program with over 20 public and private healthcare facilities that recorded nearly 7500 cancer cases. The deployment and use of the National Cancer Registry at a national level depends on the healthcare authority. It is an information system that continuously and systematically collects, stores, processes, and analyzes data on all cancer cases and types occurring in the country. This work presents the design and development of the tool, the challenges addressed, as well as its strengths and weaknesses.
Antimigratory Effect of Lipophilic Cations Derived from Gallic and Gentisic Acid and Synergistic Effect with 5-Fluorouracil on Metastatic Colorectal Cancer Cells: A New Synthesis Route
(2024) Suárez, Cristian; Jara, José; Cortés, Gonzalo; Rojas, Diego; Araya, Gabriel; Molina, Alfredo; González, Fabiola; Fuentes, Sebastián; Aránguiz, Pablo; Campodónico, Paola; Maya, Juan; Vivar, Raúl; Catalán, Mabel
Colorectal cancer (CRC) is the third leading cause of cancer deaths in the world. Standard drugs currently used for the treatment of advanced CRC-such as 5-fluorouracil (5FU)-remain unsatisfactory in their results due to their high toxicity, high resistance, and adverse effects. In recent years, mitochondria have become an attractive target for cancer therapy due to higher transmembrane mitochondrial potential. We synthesized gallic acid derivatives linked to a ten-carbon aliphatic chain associated with triphenylphosphonium (TPP+C10), a lipophilic cationic molecule that induces the uncoupling of the electron transport chain (ETC). Other derivatives, such as gentisic acid (GA-TPP+C10), have the same effects on colorectal cancer cells. Although part of our group had previously reported preparing these structures by a convergent synthesis route, including their application via flow chemistry, there was no precedent for a new methodology for preparing these compounds. In this scenario, this study aims to develop a new linear synthesis strategy involving an essential step of Steglich esterification under mild conditions (open flask) and a high degree of reproducibility. Moreover, the study seeks to associate GA-TPP+C10 with 5FU to evaluate synergistic antineoplastic effects. In addition, we assess the antimigratory effect of GA-TPP+C10 and TPP+C10 using human and mouse metastatic CRC cell lines. The results show a new and efficient synthesis route of these compounds, having synergistic effects in combination with 5FU, increasing apoptosis and enhancing cytotoxic properties. Additionally, the results show a robust antimigratory effect of GATPP+C10 and TPP+C10, reducing the activation pathways linked to tumor progression and reducing the expression of VEGF and MMP-2 and MMP-9, common biomarkers of advanced CRC. Moreover, TPP+C10 and GA-TPP+C10 increase the activity of metabolic signaling pathways through AMPK activation. The data allow us to conclude that these compounds can be used for in vivo evaluations and are a promising alternative associated with conventional therapies for advanced colorectal cancer. Additionally, the reported intermediates of the new synthesis route could give rise to analog compounds with improved therapeutic activity.
Ceftazidime/avibactam resistance is associated with PER-3-producing ST309 lineage in Chilean clinical isolates of non-carbapenemase producing Pseudomonas aeruginosa
(2024) Soto, Katherine; Alcalde, Manuel; Ugalde, Juan; Olivares, Jorge; Quiroz, Valeria; Brito, Bárbara; Rivas Jiménez, Lina María; Munita, Jose M.; García, Patricia; Wozniak, Aniela
Introduction: Ceftazidime/avibactam (CZA) is indicated against multidrug-resistant Pseudomonas aeruginosa, particularly those that are carbapenem resistant. CZA resistance in P. aeruginosa producing PER, a class A extended-spectrum β-lactamase, has been well documented in vitro. However, data regarding clinical isolates are scarce. Our aim was to analyze the contribution of PER to CZA resistance in non-carbapenemase-producing P. aeruginosa clinical isolates that were ceftazidime and/or carbapenem non-susceptible.
Methods: Antimicrobial susceptibility was determined through agar dilution and broth microdilution, while bla PER gene was screened through PCR. All PER-positive isolates and five PER-negative isolates were analyzed through Whole Genome Sequencing. The mutational resistome associated to CZA resistance was determined through sequence analysis of genes coding for PBPs 1b, 3 and 4, MexAB-OprM regulators MexZ, MexR, NalC and NalD, AmpC regulators AmpD and AmpR, and OprD porin. Loss of bla PER-3 gene was induced in a PER-positive isolate by successive passages at 43°C without antibiotics.
Results: Twenty-six of 287 isolates studied (9.1%) were CZA-resistant. Thirteen of 26 CZA-resistant isolates (50%) carried bla PER. One isolate carried bla PER but was CZA-susceptible. PER-producing isolates had significantly higher MICs for CZA, amikacin, gentamicin, ceftazidime, meropenem and ciprofloxacin than non-PER-producing isolates. All PER-producing isolates were ST309 and their bla PER-3 gene was associated to ISCR1, an insertion sequence known to mobilize adjacent DNA. PER-negative isolates were classified as ST41, ST235 (two isolates), ST395 and ST253. PER-negative isolates carried genes for narrow-spectrum β-lactamases and the mutational resistome showed that all isolates had one major alteration in at least one of the genes analyzed. Loss of bla PER-3 gene restored susceptibility to CZA, ceftolozane/tazobactam and other β-lactamsin the in vitro evolved isolate.
Discussion: PER-3-producing ST309 P. aeruginosa is a successful multidrug-resistant clone with blaPER-3 gene implicated in resistance to CZA and other β-lactams.
Pseudomonas aeruginosa Bloodstream Infections Presenting with Septic Shock in Neutropenic Cancer Patients: Impact of Empirical Antibiotic Therapy
(2024) Royo, Cristina; Laporte, Julia; Peña, Marta; Ruiz, Isabel; Garcia, Carolina; Abdala, Edson; Oltolini, Chiara; Akova, Murat; Montejo, Miguel; Mikulska, Malgorzata; Martín, Pilar; Herrera, Fabián; Gasch, Oriol; Drgona, Lubos; Paz, Hugo; Brunel, Anne; García, Estefanía; Isler, Burcu; Kern, Winfried; Palacios, Zaira; Maestr de la Calle, Guillermo; Montero, Maria; Kanj, Souha; Sipahi, Oguz; Calik, Sebnem; Márquez, Ignacio; Marin, Jorge; Gomes, Marisa; Hemmatii, Philipp; Araos Bralic, Rafael Ignacio; Peghin, Maddalena; Del Pozo, Jose; Yáñez, Lucrecia; Tilley, Robert; Manzur, Adriana; Novo, Andrés; Carratalà, Jordi; Gudiol, Carlota; IRONIC Study Group
This large, multicenter, retrospective cohort study including onco-hematological neutropenic patients with Pseudomonas aeruginosa bloodstream infection (PABSI) found that among 1213 episodes, 411 (33%) presented with septic shock. The presence of solid tumors (33.3% vs. 20.2%, p < 0.001), a high-risk Multinational Association for Supportive Care in Cancer (MASCC) index score (92.6% vs. 57.4%; p < 0.001), pneumonia (38% vs. 19.2% p < 0.001), and infection due to multidrug-resistant P. aeruginosa (MDRPA) (33.8% vs. 21.1%, p < 0.001) were statistically significantly higher in patients with septic shock compared to those without. Patients with septic shock were more likely to receive inadequate empirical antibiotic therapy (IEAT) (21.7% vs. 16.2%, p = 0.020) and to present poorer outcomes, including a need for ICU admission (74% vs. 10.5%; p < 0.001), mechanical ventilation (49.1% vs. 5.6%; p < 0.001), and higher 7-day and 30-day case fatality rates (58.2% vs. 12%, p < 0.001, and 74% vs. 23.1%, p < 0.001, respectively). Risk factors for 30-day case fatality rate in patients with septic shock were orotracheal intubation, IEAT, infection due to MDRPA, and persistent PABSI. Therapy with granulocyte colony-stimulating factor and BSI from the urinary tract were associated with improved survival. Carbapenems were the most frequent IEAT in patients with septic shock, and the use of empirical combination therapy showed a tendency towards improved survival. Our findings emphasize the need for tailored management strategies in this high-risk population.
Interventional solutions for post-surgical problems: a lymphatic leaks review
(2024) Gómez, Fernando M.; Baetens, Tarik R.; Santos, Ernestos; Rocha, Leon; Horwitz, Benjamín; Lojo-Lendoiro, Sara; Vargas, Patricio; Patel, Premal; Beets-Tan, Regina; Martinez-Rodrigo, José J.; Marti Bonmati, Luis
The lymphatic circulation plays a crucial role in maintaining fluid balance and supporting immune responses by returning serum proteins and lipids to the systemic circulation. Lymphatic leaks, though rare, pose significant challenges post-radical neck surgery, oesophagectomy, and thoracic or retroperitoneal oncological resections, leading to heightened morbidity and mortality. Managing lymphatic leaks necessitates consideration of aetiology, severity, and volume of leakage.
Traditionally, treatment involved conservative measures such as dietary restrictions, drainage, and medical management, with surgical intervention reserved for severe cases, albeit with variable outcomes and extended recovery periods. Lymphography, introduced in the 1950s, initially served as a diagnostic tool for lymphoedema, lymphoma, tumour staging, and monitoring chemotherapy response. However, its widespread adoption was impeded by alternative techniques like Computed Tomography, learning curves, and its associated complications. Contemporary lymphatic interventions have evolved, favouring nodal lymphangiography over pedal lymphangiography for its technical simplicity and reduced complexity.
Effective management of chylous leaks mandates a multimodal approach encompassing clinical evaluation and imaging techniques. In cases where conservative management proves ineffective, embolization through conventional lymphangiography by bipedal dissection or intranodal injection emerges as a viable option. This review underscores the importance of a comprehensive approach to diagnosing and treating lymphatic leaks, highlighting advancements in imaging and therapeutic interventions that enhance patient outcomes.
Molecular dynamics simulations reveal molecular mechanisms for the gain and loss of function effects of four SCN2A variants
(2024) Bhattarai, Nisha; Montanucci, Ludovica; Brünger, Tobias; Pérez Palma, Eduardo; Martin, William; Smith, Iris; Eng, Charis; Cheng, Feixiong; Helbig, Ingo; Müller, Rikke; Brunklaus, Andreas; Schorge, Stephanie; Lal, Dennis
SCN2A gene disorders cover a wide range of medical conditions, from epileptic encephalopathies to neurodevelopmental disorders. The variants of these disorders, studied through electrophysiology, show complex behaviors that go beyond simple classification as either gain or loss of function. In our study, we simulated the biophysical effects of variants (R937C, V208E, S1336Y, and R853Q) to understand their impact. Our findings reveal that all these variants negatively affect the structural stability of the gene, with R937C being the most unstable. Specifically, R937C disrupts important charged interactions affecting sodium ion flow, while S1336Y introduces a new interaction that impacts the channel’s inactivation gate. Conversely, the variants V208E and R853Q, which are located in the voltage-sensing domains, have opposite effects: R853Q increases compactness and interaction, whereas V208E shows a decrease. Our computer-based method offers a scalable way to gain crucial insights into how genetic variants influence channel dysfunction and contribute to neurodevelopmental disorders.
Atención sanitaria intercultural desde la perspectiva de estudiantes, docentes y autoridades de enfermería: estudio fenomenográfico
(2024) Pérez, Claudia; Medina, José
Objetivo principal:
comprender el significado que se otorga a la atención sanitaria basada en interculturalidad desde la perspectiva de estudiantes, docentes de enfermería y autoridades de la facultad de medicina.
Metodología:
Estudio cualitativo fenomenográfico, mediante entrevistas semiestructuradas, participaron 17 agentes claves, entre estudiantes, docentes y autoridades de carrera y facultad, elegidas por muestreo opinático a estudiantes y docentes e invitación a autoridades.
Resultados principales:
Se descubrieron tres formas cualitativamente diferentes de concebir la Atención Sanitaria Basada en Intrculturalidad (ASBI): (a) Atributos que componen ASBI; (b) Concepción teórica ASBI; (c) Enfoque integrativo de la ASBI.
Conclusión principal:
Destaca la importancia de la intercultural en la formación de enfermeras. Enfatiza la aplicación práctica de este conocimiento en ASBI en la atención sanitaria, promoviendo el respeto, la empatía y la comunicación efectiva para una atención más humana y sensible a la diversidad cultural.