Genomic profiling of uterine aspirates and cfDNA as an integrative liquid biopsy strategy in endometrial cancer

The incidence and mortality of endometrial cancer (EC) have risen in recent years, hence more precise management is needed. Therefore, wecombined di erent types of liquid biopsies to better characterize the genetic landscape of EC in a non-invasive and dynamic manner. Uterine aspirates (UAs) from 60 patients with EC were obtained during surgery and analyzed by next-generation sequencing (NGS). Blood samples, collected at surgery, were used for cell-free DNA (cfDNA) and circulating tumor cell (CTC) analyses. Finally, personalized therapies were tested in patient-derived xenografts (PDXs) generated from the UAs. NGS analyses revealed the presence of genetic alterations in 93% of the tumors. Circulating tumor DNA (ctDNA) was present in 41.2% of cases, mainly in patients with high-risk tumors, thus indicating a clear association with a more aggressive disease. Accordingly, the results obtained during the post-surgery follow-up indicated the presence of ctDNA in three patients with progressive disease. Moreover, 38.9% of patients were positive for CTCs at surgery. Finally, the e cacy of targeted therapies based on the UA-specific mutational landscape was demonstrated in PDX models. Our study indicates the potential clinical applicability of a personalized strategy based on a combination of different liquid biopsies to characterize and monitor tumor evolution, and to identify targeted therapiesThis work was supported by grants and support from the Instituto de Salud Carlos III (ISCIII) and FEDER (PI17/01919, PI17/02071), CIBERONC (CB16/12/00328), and the AECC (Grupos Estables de Investigacion 2018-AECC) to A.G.-M. and M.A.; Instituto de Salud Carlos III (ISCIII) and FEDER (PI16/00134), CIBERONC (CB16/12/00295), and the AECC (Grupos Estables de Investigacion 2018-AECC) to G.M.-B.; and the AECC to L.M.-R

Extracellular vesicles-based biomarkers represent a promising liquid biopsy in endometrial cancer

Tumor-derived extracellular vesicles (EVs) are secreted in large amounts into biological fluids of cancer patients. The analysis of EVs cargoes has been associated with patient´s outcome and response to therapy. However, current technologies for EVs isolation are tedious and low cost-e cient for routine clinical implementation. To explore the clinical value of circulating EVs analysis we attempted a proof-of-concept in endometrial cancer (EC) with ExoGAG, an easy to use and highly e cient new technology to enrich EVs. Technical performance was first evaluated using EVs secreted by Hec1A cells. Then, the clinical value of this strategy was questioned by analyzing the levels of two well-known tissue biomarkers in EC, L1 cell adhesion molecule (L1CAM) and Annexin A2 (ANXA2), in EVs purified from plasma in a cohort of 41 EC patients and 20 healthy controls. The results demonstrated the specific content of ANXA2 in the purified EVs fraction, with an accurate sensitivity and specificity for EC diagnosis. Importantly, high ANXA2 levels in circulating EVs were associated with high risk of recurrence and non-endometrioid histology suggesting a potential value as a prognostic biomarker in EC. These results also confirmed ExoGAG technology as a robust technique for the clinical implementation of circulating EVs analysesThis research was funded by Instituto de Salud Carlos III, grant PI17/01919, co-financed by the European Regional Development Fund (FEDER), and by Fundación Científica de la Asociación Española Contra el Cáncer (AECC), Grupos Clínicos Coordinados 2018. Carolina Herrero is supported by a predoctoral i-PFIS fellowship from Instituto de Salud Carlos III (IFI17/00047); Laura Muinelo is supported by Asociación Española Contra el Cáncer (AECC)

Circulating Tumor Cells Characterization Revealed TIMP1 as a Potential Therapeutic Target in Ovarian Cancer

Background: Recent studies showed a relevant role of hematogenous spread in ovarian cancer and the interest of circulating tumor cells (CTCs) monitoring as a prognosis marker. The aim of the present study was the characterization of CTCs from ovarian cancer patients, paying special attention to cell plasticity characteristics to better understand the biology of these cells. Methods: CTCs isolation was carried out in 38 patients with advanced high-grade serous ovarian cancer using in parallel CellSearch and an alternative EpCAM-based immunoisolation followed by RT-qPCR analysis to characterize these cells. Results: Epithelial CTCs were found in 21% of patients, being their presence higher in patients with extraperitoneal metastasis. Importantly, this population was characterized by the expression of epithelial markers as MUC1 and CK19, but also by genes associated with mesenchymal and more malignant features as TIMP1, CXCR4 and the stem markers CD24 and CD44. In addition, we evidenced the relevance of TIMP1 expression to promote tumor proliferation, suggesting its interest as a therapeutic target. Conclusions: Overall, we evidenced the utility of the molecular characterization of EpCAM+ CTCs from advanced ovarian cancer patients to identify biomarkers with potential applicability for disseminated disease detection and as therapeutic targets such as TIMP1Part of this research was supported by CIBERONC funds (CB16/12/00328)S

Relationship among Streptococcus gallolyticus Subsp. gallolyticus, Enterococcus faecalis and Colorectal Neoplasms in Recurrent Endocarditis: A Historical Case Series.

Objectives: The role of colorectal neoplasms (CRN) as a common potential source of recurrent Streptococcus gallolyticus subsp. gallolyticus (SGG) and Enterococcus faecalis (EF) endocarditis remains unstudied. We aimed to investigate what proportion of episodes of recurrent endocarditis are caused by a succession of SGG and EF, or vice versa, and to assess the role of a colonic source in such recurrent episodes. Methods: we conducted a retrospective analysis of two prospective endocarditis cohorts (1979-2019) from two Spanish hospitals, providing descriptive analyses of the major features of the endocarditis episodes, colonoscopy findings, and histologic results. Results: among 1552 IE episodes, 204 (13.1%) were caused by EF and 197 (12.7%) by SGG, respectively. There were 155 episodes (10%) of recurrent IE, 20 of which (12.9%) were due to a succession of SGG/EF IE in 10 patients (the first episode caused by SGG in eight cases, and by EF in two cases). The median follow-up was 86 (interquartile range 34-156) months. In 8/10 initial episodes, the causative microorganism was SGG, and all patients were diagnosed with CRN either during the initial episode or during follow-up. During the second episode of IE or follow-up, colonoscopies revealed CRN in six patients. Conclusions: There seems to be an association between SGG and EF in recurrent endocarditis that warrants further investigation. Our findings reinforce the need for systematically performing colonoscopy in the event of endocarditis caused by both microorganisms

Molecular profiling of circulating tumor cells links plasticity to the metastatic process in endometrial cancer

Background About 20% of patients diagnosed with endometrial cancer (EC) are considered high-risk with unfavorable prognosis. In the framework of the European Network for Individualized Treatment in EC (ENITEC), we investigated the presence and phenotypic features of Circulating Tumor Cells (CTC) in high-risk EC patients. Methods CTC isolation was carried out in peripheral blood samples from 34 patients, ranging from Grade 3 Stage IB to Stage IV carcinomas and recurrences, and 27 healthy controls using two methodologies. Samples were subjected to EpCAM-based immunoisolation using the CELLection™ Epithelial Enrich kit (Invitrogen, Dynal) followed by RTqPCR analysis. The phenotypic determinants of endometrial CTC in terms of pathogenesis, hormone receptor pathways, stem cell markers and epithelial to mesenchymal transition (EMT) drivers were asked. Kruskal-Wallis analysis followed by Dunn’s post-test was used for comparisons between groups. Statistical significance was set at p < 0.05. Results EpCAM-based immunoisolation positively detected CTC in high-risk endometrial cancer patients. CTC characterization indicated a remarkable plasticity phenotype defined by the expression of the EMT markers ETV5, NOTCH1, SNAI1, TGFB1, ZEB1 and ZEB2. In addition, the expression of ALDH and CD44 pointed to an association with stemness, while the expression of CTNNB1, STS, GDF15, RELA, RUNX1, BRAF and PIK3CA suggested potential therapeutic targets. We further recapitulated the EMT phenotype found in endometrial CTC through the up-regulation of ETV5 in an EC cell line, and validated in an animal model of systemic dissemination the propensity of these CTC in the accomplishment of metastasis. Conclusions Our results associate the presence of CTC with high-risk EC. Gene-expression profiling characterized a CTC-plasticity phenotype with stemness and EMT features. We finally recapitulated this CTC-phenotype by over-expressing ETV5 in the EC cell line Hec1A and demonstrated an advantage in the promotion of metastasis in an in vivo mouse model of CTC dissemination and homing

Relationship among Streptococcus gallolyticus Subsp. gallolyticus, Enterococcus faecalis and Colorectal Neoplasms in Recurrent Endocarditis: A Historical Case Series

Objectives: The role of colorectal neoplasms (CRN) as a common potential source of recurrent Streptococcus gallolyticus subsp. gallolyticus (SGG) and Enterococcus faecalis (EF) endocarditis remains unstudied. We aimed to investigate what proportion of episodes of recurrent endocarditis are caused by a succession of SGG and EF, or vice versa, and to assess the role of a colonic source in such recurrent episodes. Methods: we conducted a retrospective analysis of two prospective endocarditis cohorts (1979&ndash;2019) from two Spanish hospitals, providing descriptive analyses of the major features of the endocarditis episodes, colonoscopy findings, and histologic results. Results: among 1552 IE episodes, 204 (13.1%) were caused by EF and 197 (12.7%) by SGG, respectively. There were 155 episodes (10%) of recurrent IE, 20 of which (12.9%) were due to a succession of SGG/EF IE in 10 patients (the first episode caused by SGG in eight cases, and by EF in two cases). The median follow-up was 86 (interquartile range 34&ndash;156) months. In 8/10 initial episodes, the causative microorganism was SGG, and all patients were diagnosed with CRN either during the initial episode or during follow-up. During the second episode of IE or follow-up, colonoscopies revealed CRN in six patients. Conclusions: There seems to be an association between SGG and EF in recurrent endocarditis that warrants further investigation. Our findings reinforce the need for systematically performing colonoscopy in the event of endocarditis caused by both microorganisms

Health Perception among Female COVID-19 Patients. Comment on Fern&aacute;ndez-de-las-Pe&ntilde;as et al. Female Sex Is a Risk Factor Associated with Long-Term Post-COVID Related-Symptoms but Not with COVID-19 Symptoms: The LONG-COVID-EXP-CM Multicenter Study. J. Clin. Med. 2022, 11, 413

We read with interest the original paper by Fern&aacute;ndez-de-las-Pe&ntilde;as et al. [...

Análisis de un modelo de asistencia clínica compartida con internistas en un servicio de cirugía vascular

Objetivo: valorar si la asistencia clínica compartida entre cirujanos vasculares e internistas mejora la calidad de la atención médica prestada a pacientes ingresados en un servicio de cirugía vascular. Material y método: se analizaron diversas características clínicas relativas a la atención de una muestra de pacientes con patología arterial y con TVP ingresados en el servicio de cirugía vascular del hospital universitario Lucus Augusti de Lugo, tras la implantación de un modelo de asistencia multidisciplinar con internistas durante el año 2013. Los datos de los enfermos con TVP se compararon con los de controles históricos del año anterior. Por otra parte, se realizó una encuesta de satisfacción al personal sanitario del servicio de cirugía vascular sobre sus preferencias respecto al modelo de atención. Resultados: se estudiaron 50 pacientes con patología arterial y 75 con TVP (25 casos y 50 controles). Entre los primeros, su edad fue 71.9 años (DE 14), 60% hombres. Recibían una media de 8.2 fármacos (DE 4.4), su índice de Charlson fue 4.1 (DE 2.7) y el índice de Barthel 85.9 (DE 20). El 70% tenía anemia al ingreso y el 86% presentó alguna complicación durante el ingreso, con una mortalidad del 10%. Los pacientes con TVP atendidos por el modelo de asistencia compartida presentaron una mayor frecuencia de identificación de factores de riesgo de trombosis (76% vs 38%; p=0.002), de ajuste correcto de dosis de HBPM al peso y función renal (92% vs 18%; p=0.0001) y de registro completo de comorbilidad (100% vs 50%; p=0.0001), sin diferencias en la estancia media hospitalaria. Tanto el personal facultativo como el de enfermería prefirieron el modelo de asistencia compartida con internistas respecto al estándar. Conclusiones: los enfermos con patología arterial y venosa presentan una comorbilidad y riesgo de complicaciones que justifica la participación de internistas en su atención. El modelo de asistencia compartida puede mejorar la calidad de la asistencia prestada, con un elevado grado de satisfacción entre el personal del equipo quirúrgico. Objective: to assess whether clinical comanagement between vascular surgeons and internists improves the quality of care provided to patients admitted to a vascular surgery service. Material and method: several clinical features related to the clinical care provided to a sample of patients with arterial disease and DVT admitted to the vascular surgery at Lucus Augusti University Hospital of Lugo were analyzed, after implementation of a comanagement model of care involving internists during the year 2013. Data of patients with DVT were compared with historical controls of the year before. Moreover, we conducted a satisfaction survey to the medical staff and nursing of the vascular surgery service about their preferences regarding the model of clinical care. Results: 50 patients with arterial disease and 75 with DVT (25 cases and 50 controls) were studied. Among the former, mean age was 71.9 years (SD 14), 60% male. They received an average of 8.2 drugs (SD 4.4), the Charlson index was 4.1 (SD 2.7) and the Barthel index 85.9 (SD 20). 70% had anemia at admission and 86% experienced in-hospital complications, with a mortality of 10%. DVT patients attended by the comanagement model showed a higher frequency of identified risk factors for thrombosis (76% vs 38%, p = 0.002), proper adjustment of the dose of LMWH to weight and renal function (92% vs 18%, p = 0.0001) and complete record of comorbidity (100% vs 50%, P = 0.0001), with no differences in length of hospital stay. Both medical staff and the nursing preferred the comanagement model with respect to the standard model. Conclusions: patients with arterial and venous disease have a risk of complications and comorbidity that justify the participation of internists in their clinical care. The comanagement model can improve the quality of care provided, with a high degree of satisfaction among the staff of the surgical team

Análisis de un modelo de asistencia clínica compartida con internistas en un servicio de cirugía vascular

Objective: to assess whether clinical comanagement between vascular surgeons and internists improves the quality of care provided to patients admitted to a vascular surgery service. Material and method: several clinical features related to the clinical care provided to a sample of patients with arterial disease and DVT admitted to the vascular surgery at Lucus Augusti University Hospital of Lugo were analyzed, after implementation of a comanagement model of care involving internists during the year 2013. Data of patients with DVT were compared with historical controls of the year before. Moreover, we conducted a satisfaction survey to the medical staff and nursing of the vascular surgery service about their preferences regarding the model of clinical care. Results: 50 patients with arterial disease and 75 with DVT (25 cases and 50 controls) were studied. Among the former, mean age was 71.9 years (SD 14), 60% male. They received an average of 8.2 drugs (SD 4.4), the Charlson index was 4.1 (SD 2.7) and the Barthel index 85.9 (SD 20). 70% had anemia at admission and 86% experienced in-hospital complications, with a mortality of 10%. DVT patients attended by the comanagement model showed a higher frequency of identified risk factors for thrombosis (76% vs 38%, p = 0.002), proper adjustment of the dose of LMWH to weight and renal function (92% vs 18%, p = 0.0001) and complete record of comorbidity (100% vs 50%, P = 0.0001), with no differences in length of hospital stay. Both medical staff and the nursing preferred the comanagement model with respect to the standard model. Conclusions: patients with arterial and venous disease have a risk of complications and comorbidity that justify the participation of internists in their clinical care. The comanagement model can improve the quality of care provided, with a high degree of satisfaction among the staff of the surgical team.Objetivo: valorar si la asistencia clínica compartida entre cirujanos vasculares e internistas mejora la calidad de la atención médica prestada a pacientes ingresados en un servicio de cirugía vascular. Material y método: se analizaron diversas características clínicas relativas a la atención de una muestra de pacientes con patología arterial y con TVP ingresados en el servicio de cirugía vascular del hospital universitario Lucus Augusti de Lugo, tras la implantación de un modelo de asistencia multidisciplinar con internistas durante el año 2013. Los datos de los enfermos con TVP se compararon con los de controles históricos del año anterior. Por otra parte, se realizó una encuesta de satisfacción al personal sanitario del servicio de cirugía vascular sobre sus preferencias respecto al modelo de atención. Resultados: se estudiaron 50 pacientes con patología arterial y 75 con TVP (25 casos y 50 controles). Entre los primeros, su edad fue 71.9 años (DE 14), 60% hombres. Recibían una media de 8.2 fármacos (DE 4.4), su índice de Charlson fue 4.1 (DE 2.7) y el índice de Barthel 85.9 (DE 20). El 70% tenía anemia al ingreso y el 86% presentó alguna complicación durante el ingreso, con una mortalidad del 10%. Los pacientes con TVP atendidos por el modelo de asistencia compartida presentaron una mayor frecuencia de identificación de factores de riesgo de trombosis (76% vs 38%; p=0.002), de ajuste correcto de dosis de HBPM al peso y función renal (92% vs 18%; p=0.0001) y de registro completo de comorbilidad (100% vs 50%; p=0.0001), sin diferencias en la estancia media hospitalaria. Tanto el personal facultativo como el de enfermería prefirieron el modelo de asistencia compartida con internistas respecto al estándar. Conclusiones: los enfermos con patología arterial y venosa presentan una comorbilidad y riesgo de complicaciones que justifica la participación de internistas en su atención. El modelo de asistencia compartida puede mejorar la calidad de la asistencia prestada, con un elevado grado de satisfacción entre el personal del equipo quirúrgic