Matrix Metalloproteinase-9 Expression Is Associated with the Absence of Response to Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer Patients

Biomarkers; Neoadjuvant chemotherapy; Triple-negative breast cancerBiomarcadores; Quimioterapia neoadyuvante; Cáncer de mama triple negativoBiomarcadors; Quimioteràpia neoadjuvant; Càncer de mama triple negatiuTriple-negative breast cancer (TNBC) is particularly challenging due to the weak or absent response to therapeutics and its poor prognosis. The effectiveness of neoadjuvant chemotherapy (NAC) response is strongly influenced by changes in elements of the tumor microenvironment (TME). This work aimed to characterize the residual TME composition in 96 TNBC patients using immunohistochemistry and in situ hybridization techniques and evaluate its prognostic implications for partial responders vs. non-responders. Compared with non-responders, partial responders containing higher levels of CD83+ mature dendritic cells, FOXP3+ regulatory T cells, and IL-15 expression but lower CD138+ cell concentration exhibited better OS and RFS. However, along with tumor diameter and positive nodal status at diagnosis, matrix metalloproteinase-9 (MMP-9) expression in the residual TME was identified as an independent factor associated with the impaired response to NAC. This study yields new insights into the key components of the residual tumor bed, such as MMP-9, which is strictly associated with the lack of a pathological response to NAC. This knowledge might help early identification of TNBC patients less likely to respond to NAC and allow the establishment of new therapeutic targets.This research was supported by grants from the Instituto de Salud Carlos III (PI13/02501 and PI11/0488) co-financed by the European Regional Development Fund (ERDF). ML acknowledges support from the “PATH-IMAGE” project, which was funded by ERDF (agreement 2903/335-41)

Prognostic Implications of the Residual Tumor Microenvironment after Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer Patients without Pathological Complete Response

Neoadjuvant therapy; Relapse; Triple-negative breast cancerTerapia neoadyuvante; Recaída; Cáncer de mama triple negativoTeràpia neoadjuvant; Recaiguda; Càncer de mama triple negatiuWith a high risk of relapse and death, and a poor or absent response to therapeutics, the triple-negative breast cancer (TNBC) subtype is particularly challenging, especially in patients who cannot achieve a pathological complete response (pCR) after neoadjuvant chemotherapy (NAC). Although the tumor microenvironment (TME) is known to influence disease progression and the effectiveness of therapeutics, its predictive and prognostic potential remains uncertain. This work aimed to define the residual TME profile after NAC of a retrospective cohort with 96 TNBC patients by immunohistochemical staining (cell markers) and chromogenic in situ hybridization (genetic markers). Kaplan–Meier curves were used to estimate the influence of the selected TME markers on five-year overall survival (OS) and relapse-free survival (RFS) probabilities. The risks of each variable being associated with relapse and death were determined through univariate and multivariate Cox analyses. We describe a unique tumor-infiltrating immune profile with high levels of lymphocytes (CD4, FOXP3) and dendritic cells (CD21, CD1a and CD83) that are valuable prognostic factors in post-NAC TNBC patients. Our study also demonstrates the value of considering not only cellular but also genetic TME markers such as MUC-1 and CXCL13 in routine clinical diagnosis to refine prognosis modelling.This research was supported by grants from the Instituto de Salud Carlos III (PI13/02501 and PI11/0488) co-financed by the European Regional Development Fund (ERDF). ML acknowledges support from the “PATH-IMAGE” project, which was funded by ERDF (agreement 2903/335-41)

Psychological Well-Being in Nursing Students: A Multicentric, Cross-Sectional Study

In addition to complying with strict academic standards, nursing students must acquire relevant knowledge and skills, and learn how to carry themselves in different and often stressful professional settings. These obligations could severely affect their mental health. The purpose of this study was to examine the mental health status of undergraduate nursing students and related factors. A total of 1368 nursing students from different universities in Spain and Chile were included in this study, which took place over the 2018-2019 academic year. We assessed their levels of stress related to specific learning methodologies and determined their mental health status using the General Health Questionnaire (GHQ-28). The results revealed that the more advanced the course was, the lower the total GHQ-28 score. The stress generated by different types of training activities had a significant effect on the total GHQ-28 score. These results suggest that nursing education could act as a protective factor against mental health disorders. Although a heavy academic workload could lead to higher levels of stress, overall, it seems that mental health is better in more advanced courses than in initial academic years

Matrix Metalloproteinase-9 Expression Is Associated with the Absence of Response to Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer Patients

Triple-negative breast cancer (TNBC) is particularly challenging due to the weak or absent response to therapeutics and its poor prognosis. The effectiveness of neoadjuvant chemotherapy (NAC) response is strongly influenced by changes in elements of the tumor microenvironment (TME). This work aimed to characterize the residual TME composition in 96 TNBC patients using immunohistochemistry and in situ hybridization techniques and evaluate its prognostic implications for partial responders vs. non-responders. Compared with non-responders, partial responders containing higher levels of CD83+ mature dendritic cells, FOXP3+ regulatory T cells, and IL-15 expression but lower CD138+ cell concentration exhibited better OS and RFS. However, along with tumor diameter and positive nodal status at diagnosis, matrix metalloproteinase-9 (MMP-9) expression in the residual TME was identified as an independent factor associated with the impaired response to NAC. This study yields new insights into the key components of the residual tumor bed, such as MMP-9, which is strictly associated with the lack of a pathological response to NAC. This knowledge might help early identification of TNBC patients less likely to respond to NAC and allow the establishment of new therapeutic targets

Prognostic Implications of the Residual Tumor Microenvironment after Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer Patients without Pathological Complete Response

Simple Summary Triple-negative breast cancer (TNBC) is currently in the clinical research spotlight because of the tumor's aggressive and invasive nature and the scarcity of therapeutic targets. Despite recent advances in identifying reliable prognostic biomarkers in the tumor microenvironment (TME), rigorous evaluation of their predictive capacity remains challenging. We describe the immune cellular and genetic profile of the residual tumor of TNBC that does not achieve a pathological complete response (pCR) after neoadjuvant chemotherapy (NAC). A high concentration of lymphocytes and dendritic cells, as well as genetic TME markers such as MUC-1 and CXCL13 in the residual tumor, are valuable prognostic factors of survival and relapse in TNBC patients. From a clinical health perspective, a thorough understanding of the composition of the TME and its prognostic implications might yield relevant immunological information and reveal key predictive biomarkers. This could ultimately help substantially improve the outcomes of residual cancer-burdened TNBC patients after NAC. With a high risk of relapse and death, and a poor or absent response to therapeutics, the triple-negative breast cancer (TNBC) subtype is particularly challenging, especially in patients who cannot achieve a pathological complete response (pCR) after neoadjuvant chemotherapy (NAC). Although the tumor microenvironment (TME) is known to influence disease progression and the effectiveness of therapeutics, its predictive and prognostic potential remains uncertain. This work aimed to define the residual TME profile after NAC of a retrospective cohort with 96 TNBC patients by immunohistochemical staining (cell markers) and chromogenic in situ hybridization (genetic markers). Kaplan-Meier curves were used to estimate the influence of the selected TME markers on five-year overall survival (OS) and relapse-free survival (RFS) probabilities. The risks of each variable being associated with relapse and death were determined through univariate and multivariate Cox analyses. We describe a unique tumor-infiltrating immune profile with high levels of lymphocytes (CD4, FOXP3) and dendritic cells (CD21, CD1a and CD83) that are valuable prognostic factors in post-NAC TNBC patients. Our study also demonstrates the value of considering not only cellular but also genetic TME markers such as MUC-1 and CXCL13 in routine clinical diagnosis to refine prognosis modelling

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

RNA-Seq Transcriptome Analysis for the Study of Prostate Cancer Development and Evolution

Int. J. Mol. Sci.2019, 20, x; doi: FOR PEER REVIEWwww.mdpi.com/journal/ijmsMaster ThesisRNA-Seq Transcriptome Analysis for the Study of Prostate Cancer Development and EvolutionEstherSauras Colón 1*, María Jesús Álvarez Cubero2,3*and Eduardo Andrés León4*1Master in Translational Research and Personalized Medicine. Faculty of Medicine, University of Granada. Granada, Spain.2GENYO. Centre for Genomics and Oncological Research.Pfizer / University of Granada /Andalusian Regional Government. Granada, Spain.3Department of Biochemistry and Molecular Biology III.Faculty of Medicine, University of Granada.Granada, Spain.4Bioinformatics Unit,Institute of Parasitology and Biomedicine “López-Neyra” (IPBLN).Spanish National Research Council (CSIC).Granada, Spain.*Correspondence: Esther Sauras Colón: [email protected]. María Jesús Álvarez Cubero: [email protected]. Eduardo Andrés León: [email protected] 2019Abstract: Prostate cancer (PCa) is one of the most common cancers worldwide.Even though prostate specific antigen (PSA) testis thenon-invasive routine blood test for the detection of asymptomatic disease, itcanresultinproblemsofdiagnostic accuracyandoverdiagnosis.Thus, it is necessary to continue investigating newefficientbiomarkers for the prevention, diagnosis and prognosis of PCa.Here, we analyse the transcriptome of seven individuals by the use of next-generation sequencing (NGS)techniqueto identify differentially expressed genes, which can help to better understand PCa aggressiveness. Presentanalysis show that there are two upregulated genes in PCa regarding to controls: HP(Haptoglobin)and HLA-G(Human Leukocyte Antigen-G). On the other hand, there are seven downregulated genes, where TP53TG3 and their transcripts should be highlighted.Also, we make a comparison between amoreaggressive PCa phenotype and the rest of PCa samples to investigate about genes implicated in aggressiveness, obtaining a high number of upregulated genesincludingCENPF, DLGAP5 and RRM2, among others.These genescould serve as predictive, diagnosticand prognosticbiomarkers, as well as molecular targets. Nevertheless, further studies would be needed to confirm the obtained results

Ictus isquémico y factores de riesgo vascular en el adulto joven y el adulto mayor. Estudio retrospectivo de base comunitaria (2011-2020)

Resumen: Objetivo: Analizar la presencia de factores de riesgo vascular (FRV) entre pacientes adultos jóvenes y adultos mayores con ictus isquémico, con y sin seguimiento en atención primaria tras el alta hospitalaria. Diseño: Estudio observacional, retrospectivo y multicéntrico. Emplazamiento: Centros de salud de atención primaria y hospital Verge de la Cinta, Tortosa, España. Participantes: Pacientes con ictus isquémico de dos grupos de edad (≤ 55 y ≥ 65 años) distribuidos en dos grupos (grupo A: sin seguimiento en atención primaria; grupo B: con seguimiento en atención primaria), entre 2011 y 2020. Mediciones principales: Datos sociodemográficos, clínicos y de FRV codificados según la Clasificación Internacional de Enfermedades (CIE-10). Estadística descriptiva e inferencial. Resultados: Se analizaron datos de 2.054 participantes. En el grupo de adulto joven, el 94,9% de los participantes del grupo A presentaban entre 1-2 FRV, frente al 60% del grupo B. En el adulto mayor, el 84,4% del grupo A presentaban entre 1-2 FRV, frente al 43,9% del grupo B. Los FRV más frecuentes entre pacientes adultos jóvenes y mayores con ictus isquémico fueron la hipertensión y la dislipemia en ambos grupos de seguimiento. No había registros sobre obesidad, ni tabaquismo ni consumo de alcohol en el grupo A. Se observó una asociación significativa entre realizar seguimiento en atención primaria tras el ictus y ser adulto joven y presentar entre 3 y 4 FRV (p < 0,001). Conclusiones: Los resultados refuerzan la necesidad de continuidad asistencial y seguimiento en las personas con ictus agudo en la atención primaria y la mejora de la calidad de los registros. Abstract: Objective: To analyze the presence of vascular risk factors (VRF) among young adult and older adult patients with ischemic stroke, with and without follow-up in primary care after hospital discharge. Design: Observational, retrospective, multicenter study. Setting: Primary care health centers and Hospital Verge de la Cinta, Tortosa, Spain. Participants: Patients with ischemic stroke of two age groups (≤ 55 and ≥ 65 years) distributed in two groups (Group A: without follow-up in primary care; and Group B: with follow-up in primary care), between 2011-2020. Main measurements: Sociodemographic, clinical, and VRF data coded according to the International Classification of Diseases (ICD-10). Descriptive, and inferential statistics. Results: Data from 2054 participants were analyzed. In the young adult group, 94.9% of the participants in group A had between 1-2 VRFs, compared to 60% in group B. In the older adult group, 84.4% of group A had between 1-2 VRFs, compared to 43,9% of group B. The most frequent VRFs among younger and older adult patients with ischemic stroke were hypertension and dyslipidemia in both follow-up groups. There were no records of obesity, smoking, or alcohol consumption in group A. There was a significant association between being followed up in primary care after stroke and being a young adult and presenting between 3-4 VRFs (P < 0.001). Conclusions: The results reinforce the need for continuity of care and follow-up in people with acute stroke in primary care and the need to improve the quality of registries

Prognostic implications of the residual tumor microenvironment after neoadjuvant chemotherapy in triple-negative breast cancer patients without pathological complete response

With a high risk of relapse and death, and a poor or absent response to therapeutics, the triple-negative breast cancer (TNBC) subtype is particularly challenging, especially in patients who cannot achieve a pathological complete response (pCR) after neoadjuvant chemotherapy (NAC). Although the tumor microenvironment (TME) is known to influence disease progression and the effectiveness of therapeutics, its predictive and prognostic potential remains uncertain. This work aimed to define the residual TME profile after NAC of a retrospective cohort with 96 TNBC patients by immunohistochemical staining (cell markers) and chromogenic in situ hybridization (genetic markers). Kaplan–Meier curves were used to estimate the influence of the selected TME markers on five-year overall survival (OS) and relapse-free survival (RFS) probabilities. The risks of each variable being associated with relapse and death were determined through univariate and multivariate Cox analyses. We describe a unique tumor-infiltrating immune profile with high levels of lymphocytes (CD4, FOXP3) and dendritic cells (CD21, CD1a and CD83) that are valuable prognostic factors in post-NAC TNBC patients. Our study also demonstrates the value of considering not only cellular but also genetic TME markers such as MUC-1 and CXCL13 in routine clinical diagnosis to refine prognosis modelling

Vascular Risk Factors in Ischemic Stroke Survivors: A Retrospective Study in Catalonia, Spain

Background: The distribution of vascular risk factors (VRFs) and stroke management vary by geographic area. Our aim was to examine the percentage of the VRFs according to age and sex in ischemic stroke survivors in a geographical area on the Mediterranean coast of Southern Catalonia, Spain. Methods: This was a multicenter, observational, retrospective, community-based study of a cohort, the data of which we obtained from digital clinical records of the Catalan Institute of Health. The study included all patients with a confirmed diagnosis of ischemic stroke who were treated between 1 January 2011 and 31 December 2020. Patients met the following inclusion criteria: residing in the study area, age ≥ 18 years, and presenting ≥1 modifiable vascular risk factor. The exclusion criteria were as follows: death patients (non-survivors) and patients without modifiable VRFs. We collected the demographic, clinical, and VRF variables of the total of 2054 cases included, and we analyzed the data according to age groups, sex, and number of VRFs. Results: Most of the patients included were in the 55–80 age group (n = 1139; 55.45%). Of the patients, 56.48% (n = 1160) presented ≤ 2 modifiable VRFs, and the age group 80 years old (38.82%)) and dyslipidemia (4 VRF (5.35%)). Conclusions: These results suggest the presence of many VRFs in people diagnosed with ischemic stroke—although with a lower percentage compared to other studies—and the need for specific individualized interventions for the control of modifiable RFs related to primary and secondary prevention of stroke