Metabolomics unravels subtype-specific characteristics related to neoadjuvant therapy response in breast cancer patients.

INTRODUCTION: Breast cancer is the most diagnosed tumor and the leading cause of cancer death in women worldwide. Metabolomics allows the quantification of the entire set of metabolites in blood samples, making it possible to study differential metabolomics patterns related to neoadjuvant treatment in the breast cancer neoadjuvant setting. OBJECTIVES: Characterizing metabolic differences in breast cancer blood samples according to their response to neoadjuvant treatment. METHODS: One hundred and three plasma samples of breast cancer patients, before receiving neoadjuvant treatment, were analyzed through UPLC-MS/MS metabolomics. Then, metabolomics data were analyzed using probabilistic graphical models and biostatistics methods. RESULTS: Metabolomics data allowed the identification of differences between groups according to response to neoadjuvant treatment. These differences were specific to each breast cancer subtype. Patients with HER2+ tumors showed differences in metabolites related to amino acids and carbohydrates pathways between the two pathological response groups. However, patients with triple-negative tumors showed differences in metabolites related to the long-chain fatty acids pathway. Patients with Luminal B tumors showed differences in metabolites related to acylcarnitine pathways. CONCLUSIONS: It is possible to identify differential metabolomics patterns between complete and partial responses to neoadjuvant therapy, being this metabolomic profile specific for each breast cancer subtype.

A Novel Molecular Analysis Approach in Colorectal Cancer Suggests New Treatment Opportunities.

Colorectal cancer (CRC) is a molecular and clinically heterogeneous disease. In 2015, the Colorectal Cancer Subtyping Consortium classified CRC into four consensus molecular subtypes (CMS), but these CMS have had little impact on clinical practice. The purpose of this study is to deepen the molecular characterization of CRC. A novel approach, based on probabilistic graphical models (PGM) and sparse k-means-consensus cluster layer analyses, was applied in order to functionally characterize CRC tumors. First, PGM was used to functionally characterize CRC, and then sparse k-means-consensus cluster was used to explore layers of biological information and establish classifications. To this aim, gene expression and clinical data of 805 CRC samples from three databases were analyzed. Three different layers based on biological features were identified: adhesion, immune, and molecular. The adhesion layer divided patients into high and low adhesion groups, with prognostic value. The immune layer divided patients into immune-high and immune-low groups, according to the expression of immune-related genes. The molecular layer established four molecular groups related to stem cells, metabolism, the Wnt signaling pathway, and extracellular functions. Immune-high patients, with higher expression of immune-related genes and genes involved in the viral mimicry response, may benefit from immunotherapy and viral mimicry-related therapies. Additionally, several possible therapeutic targets have been identified in each molecular group. Therefore, this improved CRC classification could be useful in searching for new therapeutic targets and specific therapeutic strategies in CRC disease.

Sorting Transcriptomics Immune Information from Tumor Molecular Features Allows Prediction of Response to Anti-PD1 Therapy in Patients with Advanced Melanoma.

Immunotherapy based on anti-PD1 antibodies has improved the outcome of advanced melanoma. However, prediction of response to immunotherapy remains an unmet need in the field. Tumor PD-L1 expression, mutational burden, gene profiles and microbiome profiles have been proposed as potential markers but are not used in clinical practice. Probabilistic graphical models and classificatory algorithms were used to classify melanoma tumor samples from a TCGA cohort. A cohort of patients with advanced melanoma treated with PD-1 inhibitors was also analyzed. We established that gene expression data can be grouped in two different layers of information: immune and molecular. In the TCGA, the molecular classification provided information on processes such as epidermis development and keratinization, melanogenesis, and extracellular space and membrane. The immune layer classification was able to distinguish between responders and non-responders to immunotherapy in an independent series of patients with advanced melanoma treated with PD-1 inhibitors. We established that the immune information is independent than molecular features of the tumors in melanoma TCGA cohort, and an immune classification of these tumors was established. This immune classification was capable to determine what patients are going to respond to immunotherapy in a new cohort of patients with advanced melanoma treated with PD-1 inhibitors Therefore, this immune signature could be useful to the clinicians to identify those patients who will respond to immunotherapy.

Proteomics Characterization of Clear Cell Renal Cell Carcinoma.

PURPOSE: To explore the tumor proteome of patients diagnosed with localized clear cell renal cancer (ccRCC) and treated with surgery. MATERIAL AND METHODS: A total of 165 FFPE tumor samples from patients diagnosed with ccRCC were analyzed using DIA-proteomics. Proteomics ccRCC subtypes were defined using a consensus cluster algorithm (CCA) and characterized by a functional approach using probabilistic graphical models and survival analyses. RESULTS: We identified and quantified 3091 proteins, including 2026 high-confidence proteins. Two proteomics subtypes of ccRCC (CC1 and CC2) were identified by CC using the high-confidence proteins only. Characterization of molecular differences between CC1 and CC2 was performed in two steps. First, we defined 514 proteins showing differential expression between the two subtypes using a significance analysis of microarrays analysis. Proteins overexpressed in CC1 were mainly related to translation and ribosome, while proteins overexpressed in CC2 were mainly related to focal adhesion and membrane. Second, a functional analysis using probabilistic graphical models was performed. CC1 subtype is characterized by an increased expression of proteins related to glycolysis, mitochondria, translation, adhesion proteins related to cytoskeleton and actin, nucleosome, and spliceosome, while CC2 subtype showed higher expression of proteins involved in focal adhesion, extracellular matrix, and collagen organization. CONCLUSIONS: ccRCC tumors can be classified in two different proteomics subtypes. CC1 and CC2 present specific proteomics profiles, reflecting alterations of different molecular pathways in each subtype. The knowledge generated in this type of studies could help in the development of new drugs targeting subtype-specific deregulated pathways.

MiRNAs in renal cell carcinoma

MicroRNAs (miRNAs) are small RNA sequences that act as post-transcriptional regulatory genes to control many cellular processes through pairing bases with a complementary messenger RNA (mRNA). A single miRNA molecule can regulate more than 200 different transcripts and the same mRNA can be regulated by multiple miRNAs. In this review, we highlight the importance of miRNAs and collect the existing evidence on their relationship with kidney cancer. (AU)

Complicaciones posquirúrgicas en un programa de cribado poblacional de cáncer colorrectal: incidencia y factores asociados / Surgical complications in a population-based colorectal cancer screening program: Incidence and associated factors

Introducción: Los programas de cribado de cáncer colorrectal (CCR) producen riesgos, entre ellos los derivados de las cirugías colorrectales. El objetivo de este análisis es evaluar las complicaciones asociadas a la cirugía. Pacientes y métodos: Análisis retrospectivo de los pacientes que requirieron cirugía colorrectal dentro del programa poblacional de cribado de CCR de Galicia (mayo de 2013-junio de 2019). Analizamos la indicación de la cirugía y la tasa de complicaciones intrahospitalarias (levesI-II, gravesIII-V, clasificación Clavien-Dindo) y al alta. Determinamos mediante un análisis multivariante las variables asociadas a su aparición. Resultados: En el periodo analizado, 1.092 pacientes fueron intervenidos (lesión benigna 16,5%, CCR pT1 18,2%, resto CCR 64,6%), por vía laparoscópica en el 69,8% de los casos. Se detectaron complicaciones intrahospitalarias en el 19,2% de los pacientes (leves: 13,4%; graves: 5,9%; fallecimientos: 0,2%) y al alta en 159 (14,6%) pacientes. El sexo masculino se asoció a las complicaciones intrahospitalarias (OR: 2,0; IC95%: 1,3-3,0). Las variables asociadas a las complicaciones graves fueron: sexo masculino (OR: 2,6; IC95%: 1,2-5,5), hospital terciario (OR: 0,5; IC95%: 0,2-0,9) y ECOGI (OR: 0,2; IC95%: 0,05-0,6). Los factores asociados a las complicaciones tras el alta fueron edad ≥60años (OR: 1,5; IC95%: 1,0-2,3), la ubicación rectal (OR: 1,6; IC95%: 1,1-2,3) y complicaciones intrahospitalarias (OR: 2,2; IC95%: 1,5-3,2). Conclusiones: La cirugía es la principal causa de morbimortalidad asociada a un programa de cribado de CCR. Estos resultados deben ser tenidos en cuenta en la toma de decisiones en lesiones candidatas a resección endoscópica.(AU)

Introduction: Colorectal cancer (CRC) screening programs produce risks, including those derived from colorectal surgeries. The objective of this analysis is to evaluate the complications associated with the surgery. Patients and methods: Retrospective analysis including patients who required colorectal surgery within the population-based CRC screening program in Galicia (May 2013-June 2019). We analyzed the indication for surgery and the rate of in-hospital (mildI-II, severeIII-V, Clavien-Dindo classification) and at discharge complications. We performed a multivariate analysis to determine the variables independently associated. Results: In the analyzed period, 1092 patients underwent surgery (benign lesion 16.5%, pT1 CRC 18.2%, rest of CRC 64.6%) laparoscopic approach in 69.8% of the cases. In-hospital complications were detected in 19.2% of patients (mild: 13.4%; severe: 5.9%; deaths: 0.2%) and at discharge in 159 (14.6%) patients. Male sex was associated with in-hospital complications (OR: 2.0; 95%CI: 1.3-3.0). The variables associated with severe complications were: male sex (OR: 2.6; 95%CI: 1.2-5.5), tertiary hospital (OR: 0.5; 95%CI: 0.2-0.9) and ECOGI (OR: 0.2; 95%CI: 0.05-0.6). The factors associated with complications after discharge were age ≥60years (OR: 1.5; 95%CI: 1.0-2.3), rectal location (OR: 1.6; 95%CI: 1.1-2.3) and in-hospital complications (OR: 2.2; 95%CI: 1.5-3.2). Conclusions: Surgery is the main cause of morbidity and mortality associated with a CRC screening program. These results must be taken into account in the decision making of lesions that are candidates for endoscopic resection.(AU)

Factors associated with lesion detection in colonoscopy among different indications.

BACKGROUND AND OBJECTIVE: Different factors may influence colonoscopy performance measures. We aimed to analyze procedure- and endoscopist-related factors associated with detection of colorectal lesions and whether these factors have a similar influence in the context of different colonoscopy indications: positive fecal immunochemical test (+FIT) and post-polypectomy surveillance colonoscopies. METHODS: This multicenter cross-sectional study included adults aged 40-80 years. Endoscopists (N = 96) who had performed ≥50 examinations were assessed for physician-related factors. Adenoma detection rate (ADR), adenomas per colonoscopy rate (APCR), advanced ADR, serrated polyp detection (SDR), and serrated polyps per colonoscopy rate (SPPCR) were calculated. RESULTS: We included 12,932 procedures, with 4810 carried out after a positive FIT and 1967 for surveillance. Of the 96 endoscopists evaluated, 43.8% were women, and the mean age was 41.9 years. The ADR, advanced ADR, and SDR were 39.7%, 17.7%, and 12.8%, respectively. Adenoma detection rate was higher in colonoscopies after a +FIT (50.3%) with a more than doubled advanced ADR compared to non-FIT procedures (27.6% vs. 13.0%) and similar results in serrated lesions (14.7% vs. 13.5%). Among all the detection indicators analyzed, withdrawal time was the only factor independently related to improvement (p < 0.001). Regarding FIT-positive and surveillance procedures, for both indications, withdrawal time was also the only factor associated with a higher detection of adenomas and serrated polyps (p < 0.001). Endoscopist-related factors (i.e., weekly hours dedicated to endoscopy, annual colonoscopy volume and lifetime number of colonoscopies performed) had also impact on lesion detection (APCR, advanced ADR and SPPCR). CONCLUSIONS: Withdrawal time was the factor most commonly associated with improved detection of colonic lesions globally and in endoscopies for + FIT and post-polypectomy surveillance. Physician-related factors may help to address strategies to support training and service provision. Our results can be used for establishing future benchmarking and quality improvement in different colonoscopy indications.

MiRNAs in renal cell carcinoma.

MicroRNAs (miRNAs) are small RNA sequences that act as post-transcriptional regulatory genes to control many cellular processes through pairing bases with a complementary messenger RNA (mRNA). A single miRNA molecule can regulate more than 200 different transcripts and the same mRNA can be regulated by multiple miRNAs. In this review, we highlight the importance of miRNAs and collect the existing evidence on their relationship with kidney cancer.

Identification of Carcinogenesis and Tumor Progression Processes in Pancreatic Ductal Adenocarcinoma Using High-Throughput Proteomics.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with an overall 5-year survival rate of just 5%. A better understanding of the carcinogenesis processes and the mechanisms of the progression of PDAC is mandatory. Fifty-two PDAC patients treated with surgery and adjuvant therapy, with available primary tumors, normal tissue, preneoplastic lesions (PanIN), and/or lymph node metastases, were selected for the study. Proteins were extracted from small punches and analyzed by LC-MS/MS using data-independent acquisition. Proteomics data were analyzed using probabilistic graphical models, allowing functional characterization. Comparisons between groups were made using linear mixed models. Three proteomic tumor subtypes were defined. T1 (32% of patients) was related to adhesion, T2 (34%) had metabolic features, and T3 (34%) presented high splicing and nucleoplasm activity. These proteomics subtypes were validated in the PDAC TCGA cohort. Relevant biological processes related to carcinogenesis and tumor progression were studied in each subtype. Carcinogenesis in the T1 subtype seems to be related to an increase of adhesion and complement activation node activity, whereas tumor progression seems to be related to nucleoplasm and translation nodes. Regarding the T2 subtype, it seems that metabolism and, especially, mitochondria act as the motor of cancer development. T3 analyses point out that nucleoplasm, mitochondria and metabolism, and extracellular matrix nodes could be involved in T3 tumor carcinogenesis. The identified processes were different among proteomics subtypes, suggesting that the molecular motor of the disease is different in each subtype. These differences can have implications for the development of future tailored therapeutic approaches for each PDAC proteomics subtype.

Surgical complications in a population-based colorectal cancer screening program: Incidence and associated factors. / Complicaciones posquirúrgicas en un programa de cribado poblacional de cáncer colorrectal: incidencia y factores asociados.

INTRODUCTION: Colorectal cancer (CRC) screening programs produce risks, including those derived from colorectal surgeries. The objective of this analysis is to evaluate the complications associated with the surgery. PATIENTS AND METHODS: Retrospective analysis including patients who required colorectal surgery within the population-based CRC screening program in Galicia (May 2013-June 2019). We analyzed the indication for surgery and the rate of in-hospital (mildI-II, severeIII-V, Clavien-Dindo classification) and at discharge complications. We performed a multivariate analysis to determine the variables independently associated. RESULTS: In the analyzed period, 1092 patients underwent surgery (benign lesion 16.5%, pT1 CRC 18.2%, rest of CRC 64.6%) laparoscopic approach in 69.8% of the cases. In-hospital complications were detected in 19.2% of patients (mild: 13.4%; severe: 5.9%; deaths: 0.2%) and at discharge in 159 (14.6%) patients. Male sex was associated with in-hospital complications (OR: 2.0; 95%CI: 1.3-3.0). The variables associated with severe complications were: male sex (OR: 2.6; 95%CI: 1.2-5.5), tertiary hospital (OR: 0.5; 95%CI: 0.2-0.9) and ECOGI (OR: 0.2; 95%CI: 0.05-0.6). The factors associated with complications after discharge were age ≥60years (OR: 1.5; 95%CI: 1.0-2.3), rectal location (OR: 1.6; 95%CI: 1.1-2.3) and in-hospital complications (OR: 2.2; 95%CI: 1.5-3.2). CONCLUSIONS: Surgery is the main cause of morbidity and mortality associated with a CRC screening program. These results must be taken into account in the decision making of lesions that are candidates for endoscopic resection.

Synergistic effect of antimetabolic and chemotherapy drugs in triple-negative breast cancer.

The triple-negative breast cancer (TNBC) subtype comprises approximately 15% of all breast cancers and is associated with poor long-term outcomes. Classical chemotherapy remains the standard of treatment, with toxicity and resistance being major limitations. TNBC is a high metabolic group, and antimetabolic drugs are effective in inhibiting TNBC cell growth. We analyzed the combined effect of chemotherapy and antimetabolic drug combinations in MDA-MB-231, MDA-MB-468 and HCC1143 human TNBC cell lines. Cells were treated with each drug or with drug combinations at a range of concentrations to establish the half-maximal inhibitory concentrations (IC50). The dose-effects of each drug or drug combination were calculated, and the synergistic or antagonistic effects of drug combinations were defined. Chemotherapy and antimetabolic drugs exhibited growth inhibitory effects on TNBC cell lines. Antimetabolic drugs targeting the glycolysis pathway had a synergistic effect with chemotherapy drugs, and antiglycolysis drug combinations also had a synergistic effect. The use of these drug combinations could lead to new therapeutic strategies that reduce chemotherapy drug doses, decreasing their toxic effect, or that maintain the doses but enhance their efficacy by their synergistic effect with other drugs.

Molecular characterization of triple negative breast cancer formaldehyde-fixed paraffin-embedded samples by data-independent acquisition proteomics.

Triple negative breast cancer accounts for 15%-20% of all breast carcinomas and is clinically characterized by an aggressive phenotype and poor prognosis. Triple negative tumors do not benefit from targeted therapies, so further characterization is needed to define subgroups with potential therapeutic value. In this work, the proteomes of 125 formalin-fixed paraffin-embedded samples from patients diagnosed with non-metastatic triple negative breast cancer were analyzed using data-independent acquisition + in a LTQ-Orbitrap Fusion Lumos mass spectrometer coupled to an EASY-nLC 1000. 1206 proteins were identified in at least 66% of the samples. Hierarchical clustering, probabilistic graphical models and Significance Analysis of Microarrays were combined to characterize proteomics-based molecular groups. Two molecular groups were defined with differences in biological processes such as glycolysis, translation and immune response. These two molecular groups showed also several differentially expressed proteins. This clinically homogenous dataset may serve to design new therapeutic strategies in the future.

Risk of Colorectal Cancer and Advanced Polyps One Year After Excision of High-Risk Adenomas.

BACKGROUND: Patients with multiple or large adenomas are considered to be high-risk for metachronous colorectal cancer. OBJECTIVE: Evaluate the risks of detecting colorectal cancer, advanced adenoma, and advanced serrated polyps at 1-year surveillance colonoscopy in patients with >5 adenomas or adenomas >20 mm. DESIGN: Descriptive, retrospective, multicentric, cohort study. We calculated the absolute risk of developing colorectal cancer, advanced adenomas, and advanced serrated polyps at the 1-year surveillance colonoscopy. Potential risk factors for advanced neoplasia at follow-up were evaluated with univariable and multivariable logistic regression analyses. SETTINGS: This study included data from a multicenter cohort colorectal cancer screening program, conducted from January 2014 to December 2015, based on fecal immunochemical tests in Spain. PATIENTS: We included 2119 participants with at least 1 adenoma ≥20 mm or ≥5 adenomas of any size. MAIN OUTCOME MEASURES: We calculated the absolute risk of developing colorectal cancer, advanced adenomas, and advanced serrated polyps at the 1-year surveillance colonoscopy. Potential risk factors for advanced neoplasia at follow-up were evaluated with univariable and multivariable logistic regression analyses. RESULTS: At 1 year, participants displayed 6 colorectal cancers (0.3%), 228 advanced adenomas (10.5%), and 58 advanced serrated polyps (2.7%). The adjusted analysis identified 2 factors associated with advanced neoplasia: >5 adenomas (odds ratio 1.53; 95% CI: 1.15-2.03; p = 0.004) and polyps in a proximal location (OR 1.52; 95% CI: 1.15-2.02; p = 0.004). LIMITATIONS: First, the sample size was relatively small compared to other studies with similar aims. Another limitation was the lack of a comparison group, which could have provided more practical results in terms of surveillance recommendations. CONCLUSIONS: The colorectal cancer detection rate at a 1-year colonoscopy surveillance was low among patients classified at high risk of advanced neoplasia. The risk factors for advanced neoplasia were ≥5 adenomas and proximal polyps at baseline. See Video Abstract at http://links.lww.com/DCR/B820 . RIESGO DE CNCER COLORRECTAL Y DE PLIPOS AVANZADOS UN AO DESPUS DE LA RESECCIN DE ADENOMAS DE ALTO RIESGO: ANTECEDENTES:Los pacientes con adenomas múltiples o grandes se consideran de alto riesgo para desarrollar cáncer colorrectal metacrónico.OBJETIVO:Evaluar los riesgos de detectar cáncer colorrectal, adenoma avanzado y pólipos serrados avanzados en la colonoscopia de seguimiento al año, en pacientes con un número mayor o igual a 5 adenomas o adenomas de 20 mm o más.DISEÑO:Estudio descriptivo, retrospectivo, multicéntrico, de cohortes. Calculamos el riesgo absoluto de desarrollar cáncer colorrectal, adenomas avanzados y pólipos serrados avanzados en la colonoscopia de vigilancia al año. Los factores de riesgo potenciales para el desarrollo de una neoplasia avanzada en el seguimiento, fueron evaluados mediante un análisis de regresión logística univariable y multivariable.AJUSTES:Este estudio incluyó datos de un programa de cribado de cáncer colorrectal de cohorte multicéntrico, realizado entre enero de 2014 y diciembre de 2015, con base en pruebas inmunoquímicas de materia fecal, en España.PACIENTES:Incluimos 2119 participantes con al menos un adenoma ≥20 mm o con cinco o más adenomas de cualquier tamaño.PRINCIPALES MEDIDAS DE RESULTADO:Calculamos el riesgo absoluto de desarrollar cáncer colorrectal, adenomas avanzados y pólipos serrados avanzados en la colonoscopia de vigilancia al año. Los potenciales factores de riesgo para desarrollar una neoplasia avanzada en el seguimiento, se evaluaron mediante un análisis de regresión logística univariable y multivariable.RESULTADOS:Al año se encontraron en los pacientes participantes, 6 cánceres colorrectales (0,3%), 228 adenomas avanzados (10,5%) y 58 pólipos serrados avanzados (2,7%). Mediante el análisis ajustado se identificaron dos factores asociados con el desarrollo de neoplasia avanzada: un número igual o mayor a 5 adenomas (razón de probabilidades 1,53; IC del 95%: 1,15-2,03; p = 0,004) y la presencia de pólipos en una ubicación proximal (razón de probabilidades 1,52; IC del 95%: 1,15-2,02; p = 0,004).LIMITACIONES:Primero, el tamaño de la muestra fue relativamente pequeño en comparación con otros estudios con objetivos similares. Otra limitación fue la falta de un grupo comparativo, que podría haber proporcionado resultados más prácticos, en términos de recomendaciones de vigilancia.CONCLUSIÓNES:La tasa de detección de cáncer colorrectal mediante una colonoscopia de vigilancia al año, fue baja entre los pacientes clasificados como de alto riesgo de neoplasia avanzada. Los factores de riesgo para desarrollar una neoplasia avanzada fueron; un número igual o mayor a 5 adenomas y la presencia de pólipos proximales en la colonoscopia inicial de base. Consulte Video Resumen en http://links.lww.com/DCR/B820 . ( Traducción-Eduardo Londoño-Schimmer ).

Evaluation of an educational intervention (edworkcases) involving clinical cases and Nursing students: a cross-sectional observational study.

OBJECTIVE: to evaluate the impact of the (edworkcases) educational intervention on students' evaluation outcomes in their clinical practices, their attitudes towards Nursing diagnoses, and their satisfaction. METHOD: this study used a cross-sectional observational design. The participants were 69 third-year Nursing students from a public university in Madrid, Spain. The data analysed in the study were the grades obtained by students for their clinical practices, as well as pre-post intervention scores on the Positions on Nursing Diagnosis Scale and a satisfaction survey. A means comparison by participation in the project (yes/no) was carried out using Student's t-test. A means comparison by professor was conducted using Kruskal-Wallis tests. RESULTS: participation rate: 72.4%; 92% of the participants were women; median age = 21 years old. Statistically significant differences were found between participants and non-participants in terms of mean score in the Overall Evaluation and in the Case Study Evaluation, with higher scores found among the group of participants. The mean score for attitudes towards Nursing diagnoses was 99.9 (SD=2.8) before the intervention and 111.1 (SD=2.9) after the intervention [95% CI: 3.3-19.2]. CONCLUSION: the use of (edworkcases) as part of the practical training was considered satisfactory, enabling theory and practice to be combined and improving students' attitudes towards Nursing diagnoses.

Evaluation of an educational intervention (edworkcases) involving clinical cases and Nursing students: a cross-sectional observational study / Avaliação de uma intervenção educacional (edworkcases) envolvendo casos clínicos e estudantes de Enfermagem: um estudo observacional transversal / Evaluación de una intervención educativa (edworkcases) que involucra casos clínicos y estudiantes de Enfermería: estudio transversal y observacional

Abstract Objective: to evaluate the impact of the (edworkcases) educational intervention on students' evaluation outcomes in their clinical practices, their attitudes towards Nursing diagnoses, and their satisfaction. Method: this study used a cross-sectional observational design. The participants were 69 third-year Nursing students from a public university in Madrid, Spain. The data analysed in the study were the grades obtained by students for their clinical practices, as well as pre-post intervention scores on the Positions on Nursing Diagnosis Scale and a satisfaction survey. A means comparison by participation in the project (yes/no) was carried out using Student's t-test. A means comparison by professor was conducted using Kruskal-Wallis tests. Results: participation rate: 72.4%; 92% of the participants were women; median age = 21 years old. Statistically significant differences were found between participants and non-participants in terms of mean score in the Overall Evaluation and in the Case Study Evaluation, with higher scores found among the group of participants. The mean score for attitudes towards Nursing diagnoses was 99.9 (SD=2.8) before the intervention and 111.1 (SD=2.9) after the intervention [95% CI: 3.3-19.2]. Conclusion: the use of (edworkcases) as part of the practical training was considered satisfactory, enabling theory and practice to be combined and improving students' attitudes towards Nursing diagnoses.

Resumo Objetivo: avaliar o impacto da intervenção educacional (edworkcases) nos resultados da avaliação dos alunos em suas práticas clínicas, suas atitudes em relação aos diagnósticos de Enfermagem e sua satisfação. Método: estudo observacional transversal, realizado com 69 estudantes do terceiro ano de Enfermagem de uma universidade pública de Madri, Espanha. Os dados analisados foram obtidos das notas dos alunos em suas práticas clínicas, bem como, os escores pré- e pós-intervenção na Escala de Posições frente ao Diagnóstico de Enfermagem e uma pesquisa de satisfação. A comparação de médias por participação no projeto (sim/não) foi realizada por meio do teste t de Student. A comparação de médias por professor foi realizada por meio de testes de Kruskal-Wallis. Resultados: taxa de participação: 72,4%; 92% dos participantes eram mulheres; mediana de idade de 21 anos. Foram encontradas diferenças estatisticamente significativas entre participantes e não participantes em termos de pontuação média na Avaliação Geral e na Avaliação do Estudo de Caso, com maiores pontuações encontradas entre o grupo de participantes. A pontuação média das atitudes em relação aos diagnósticos de Enfermagem foi de 99,9 (DP=2,8) antes da intervenção e 111,1 (DP=2,9) após a intervenção [IC 95%: 3,3-19,2]. Conclusão: a utilização de edworkcases como parte do treinamento prático foi considerada satisfatória, permitindo a articulação teoria e prática e melhorando as atitudes dos alunos em relação aos diagnósticos de Enfermagem.

Resumen Objetivo: evaluar el efecto de la intervención educativa (edworkcases) sobre los resultados de la evaluación de los estudiantes en sus prácticas clínicas, sus actitudes hacia los diagnósticos de Enfermería y su nivel de satisfacción. Método: en este estudio se empleó un diseño transversal y observacional. Los participantes fueron 68 estudiantes de tercer año de la carrera de Enfermería de una universidad pública de Madrid, España. Los datos que se analizaron en el estudio fueron las calificaciones obtenidas por los estudiantes en sus prácticas clínicas, al igual que las puntuaciones antes y después de la intervención en la Escala de Posicionamiento ante el Diagnóstico de Enfermería y en una encuesta de satisfacción. Se utilizó la prueba t de Student para realizar una comparación de valores medios por participación en el proyecto (sí/no). La comparación de valores medios por profesor se llevó a cabo por medio de pruebas Kruskal-Wallis. Resultados: índice de participación: 72,4%; el 92% de los participantes eran mujeres, con una mediana de edad de 21 años. Se encontraron diferencias estadísticamente significativas entre participantes y no participantes en cuanto a la puntuación media en la Evaluación General y en la Evaluación de Estudios de Caso, con puntuaciones más elevadas en el grupo de participantes. Las puntuaciones medias correspondientes a las actitudes con respecto a los diagnósticos de Enfermería fueron 99,9 (SD=2,8) y 111.1 (SD=2.9) antes y después de la intervención, respectivamente [IC 95%: 3,3-19,2]. Conclusión: se consideró satisfactorio utilizar edworkcases como parte te la capacitación práctica, lo que permitió combinar teoría y práctica y mejorar las actitudes de los estudiantes con respecto a los diagnósticos de Enfermería.

Polyprev: Randomized, Multicenter, Controlled Trial Comparing Fecal Immunochemical Test with Endoscopic Surveillance after Advanced Adenoma Resection in Colorectal Cancer Screening Programs: A Study Protocol.

Colorectal cancer (CRC) screening programs have been implemented to reduce the burden of the disease. When an advanced colonic lesion is detected, clinical practice guidelines recommend endoscopic surveillance with different intervals between explorations. Endoscopic surveillance is producing a considerable increase in the number of colonoscopies, with a limited effect on the CRC incidence. Instead, participation in CRC screening programs based on the fecal immunochemical test (FIT) could be a non-inferior alternative to endoscopic surveillance to reduce 10-year CRC incidence. Based on this hypothesis, we have designed a multicenter and randomized clinical trial within the Spanish population CRC screening programs to compare FIT surveillance with endoscopic surveillance. We will include individuals aged from 50 to 65 years with complete colonoscopy and advanced lesions resected within the CRC screening programs. Patients will be randomly allocated to perform an annual FIT and colonoscopy if fecal hemoglobin concentration is ≥10 µg/g, or to perform endoscopic surveillance. On the basis of the non-superior CRC incidence, we will recruit 1894 patients in each arm. The main endpoint is 10-year CRC incidence and the secondary endpoints are diagnostic yield, participation, adverse effects, mortality and cost-effectiveness. Our results may modify the clinical practice after advanced colonic resection in CRC screening programs.

Overtreatment in nonmalignant lesions detected in a colorectal cancer screening program: a retrospective cohort study.

BACKGROUND: Although colorectal cancer (CRC) screening programs reduce CRC incidence and mortality, they are associated with risks in healthy subjects. However, the risk of overtreatment and overdiagnosis has not been determined yet. The aim of this study was to report the surgery rates in patients with nonmalignant lesions detected within the first round of a fecal immunochemical test (FIT) based CRC screening program and the factors associated with it. METHODS: We included in this analysis all patients with nonmalignant lesions detected between May 2013 and June 2019 in the Galician (Spain) CRC screening program. We calculated surgery rate according to demographic variables, the risk classification according to the colonoscopy findings (European guidelines for quality assurance), the endoscopist's adenoma detection rate (ADR) classified into quartiles and the hospital's complexity level. We determined which variables were independently associated with surgery rate and expressed the association as Odds Ratio and its 95% confidence interval (CI). RESULTS: We included 15,707 patients in the analysis with high (19.9%), intermediate (26.9%) low risk (23.3%) adenomas and normal colonoscopy (29.9%) detected in the analyzed period. Colorectal surgery was performed in 162 patients (1.03, 95% CI 0.87-1.19), due to colonoscopy complications (0.02, 95% CI 0.00-0.05) and resection of colorectal benign lesions (1.00, 95% CI 0.85-1.16). Median hospital stay was 6 days with 17.3% patients developing minor complications, 7.4% major complications and one death. After discharge, complications developed in 18.4% patients. In benign lesions, an endoscopic resection was performed in 25.4% and a residual premalignant lesion was detected in 89.9%. The variables independently associated with surgery in the multivariable analysis were age (≥60 years = 1.57, 95% CI 1.11-2.23), sex (female = 2.10, 95% CI 1.52-2.91), the European guidelines classification (high risk = 67.94, 95% CI 24.87-185.59; intermediate risk = 5.63, 95% CI 1.89-16.80; low risk = 1.43; 95% CI 0.36-5.75), the endoscopist's ADR (Q4 = 0.44, 95% CI 0.28-0.68; Q3 = 0.44, 95% CI 0.27-0.71; Q2 = 0.71, 95% CI 0.44-1.14) and the hospital (tertiary = 0.54, 95% CI 0.38-0.79). CONCLUSIONS: In a CRC screening program, the surgery rate and the associated complications in patients with nonmalignant lesions are low, and related to age, sex, endoscopic findings, endoscopist's ADR and the hospital's complexity.

In vivo cholinergic basal forebrain degeneration and cognition in Parkinson's disease: Imaging results from the COPPADIS study.

INTRODUCTION: We aimed to assess associations between multimodal neuroimaging measures of cholinergic basal forebrain (CBF) integrity and cognition in Parkinson's disease (PD) without dementia. METHODS: The study included a total of 180 non-demented PD patients and 45 healthy controls, who underwent structural MRI acquisitions and standardized neurocognitive assessment through the PD-Cognitive Rating Scale (PD-CRS) within the multicentric COPPADIS-2015 study. A subset of 73 patients also had Diffusion Tensor Imaging (DTI) acquisitions. Volumetric and microstructural (mean diffusivity, MD) indices of CBF degeneration were automatically extracted using a stereotactic CBF atlas. For comparison, we also assessed multimodal indices of hippocampal degeneration. Associations between imaging measures and cognitive performance were assessed using linear models. RESULTS: Compared to controls, CBF volume was not significantly reduced in PD patients as a group. However, across PD patients lower CBF volume was significantly associated with lower global cognition (PD-CRStotal: r = 0.37, p < 0.001), and this association remained significant after controlling for several potential confounding variables (p = 0.004). Analysis of individual item scores showed that this association spanned executive and memory domains. No analogue cognition associations were observed for CBF MD. In covariate-controlled models, hippocampal volume was not associated with cognition in PD, but there was a significant association for hippocampal MD (p = 0.02). CONCLUSIONS: Early cognitive deficits in PD without dementia are more closely related to structural MRI measures of CBF degeneration than hippocampal degeneration. In our multicentric imaging acquisitions, DTI-based diffusion measures in the CBF were inferior to standard volumetric assessments for capturing cognition-relevant changes in non-demented PD.

Resumption of endoscopy in the Galician colorectal cancer screening programme after the COVID-19 lock down: patient safety results.

The COVID-19 pandemic meant that the population-based colorectal cancer (CRC) screening programs had to be suspended. Modifications were made to the organization in order to reduce SARS-CoV-2 transmission. We report the experience of the Galician CRC screening program and patient safety results. Endoscopy was suspended between 13/03/2020 and 11/05/2020. After resumption, a total of 3,310 colonoscopies were performed (1,702 positive fecal occult blood tests and 1,608 endoscopy monitoring) and no SARS-CoV-2 infections were detected in the subsequent two weeks. Thus, resumption of activity associated with population screening was safe.

pT1 Colorectal Cancer Detected in a Colorectal Cancer Mass Screening Program: Treatment and Factors Associated with Residual and Extraluminal Disease.

The aim of this study is to describe the treatment of pT1 colorectal cancer (CRC) in a mass screening program, the surgery-related complications and the factors associated with residual disease after endoscopic resection and extraluminal disease after surgery. We included in this retrospective analysis all the pT1 CRC detected in the Galician CRC screening program between May 2013 and June 2019. We determined which variables were independently associated with the outcomes of the study through a multivariable logistic regression analysis. We included 370-354 pT1 N0(X), 16 pT1N1- out of the 971 CRC detected; 277 (74.9%) were resected endoscopically and 162 (43.8%) were not referred to surgery. There were surgical complications in 30.7% and 16.3% of the patients during hospitalization and after discharge. Residual disease was detected in 12 (4.3%) after endoscopic resection and extraluminal disease in 18 (8.6%) patients after surgery. The variables independently associated with initial endoscopic resection were a pedunculated morphology (OR 33.1, 95% CI 4.3-254), a diameter ≥ 20 mm (OR 3.94, 95% CI 1.39-11.18) and a Site-Morphology-Size-Access score < 9 (OR 428, 95% CI 42-4263). The variables related with surgery rescue were a piecemeal resection (OR 4.48, 95% CI 1.48-13.6), an infiltrated/nonevaluable resection border (OR 7.44, 95% CI 2.12-26.0), a non-well-differentiated histology (OR 4.76, 95% CI 1.07-20.0), vascular infiltration (OR 8.24, 95% CI 2.72-25.0) and a Haggitt 4 infiltration of the submucosa (OR 5.68, 95% CI 2.62-12.3). Residual disease after endoscopic resection was associated with an infiltrated/nonevaluable resection border (OR 34.9, 95% CI 4.08-298), a non-well-differentiated histology (OR 6.67, 95% CI 1.05-50.0), and the vascular infiltration of the submucosa (OR 7.61, 95% CI 1.55-37.4). The variables related with extraluminal disease after surgical resection were no endoscopic resection (OR 4.34, 95% CI 1.26-14.28), a non-well-differentiated histology (OR 4.35, 95% CI 1.39-14.29) and the lymphatic infiltration of the submucosa (OR 4.8, 95% CI 1.32-17.8). In a CRC screening program, although most of pT1 CRC are candidates for endoscopic treatment, surgery is a safe procedure. We have defined some easy to evaluate variables that can be used in the decision-making process.