Implicaciones clínicas de la implementación de la biopsia selectiva del ganglio centinela en el manejo quirúrgico del cáncer de endometrio

Tesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Obstetricia y Ginecología. Fecha de Lectura: 13-06-2024La presente tesis doctoral engloba como objetivo principal demostrar los beneficios derivados de la inclusión de la biopsia selectiva del ganglio centinela en el tratamiento quirúrgico del cáncer de endometrio en estadio inicial. Durante el desarrollo de este trabajo de investigación se han realizado tres artículos científicos originales que han seguido esta línea de investigación. El objetivo del primer artículo ha sido demostrar que la biopsia selectiva del ganglio centinela permite la detección de un mayor número de metástasis ganglionares, sobre todo, de metástasis de bajo volumen, y estudiar el impacto pronóstico de las mismas en nuestras pacientes. El segundo artículo ha demostrado que la biopsia selectiva del ganglio centinela sustituye de forma segura a la linfadenectomía completa en la estadificación ganglionar del cáncer de endometrio de riesgo intermedio de recurrencia. Finalmente, el tercer artículo ha evaluado el impacto que supone en la calidad de vida de las pacientes la sustitución de la linfadenectomía completa por la biopsia selectiva del ganglio centinela, estableciendo que este cambio de paradigma mejora el estatus funcional y la escala sintomática de nuestras pacientesThe main aim of this thesis is to demonstrate the benefits of including the selective sentinel lymph node biopsy in the surgical management of early-stage endometrial cancer. During the development of this research, three original scientific articles were performed following this line of research. The aim of the first original article was to demonstrate that selective sentinel lymph node biopsy allows the detection of a greater number of lymph node metastases, particularly low volume metastases, and to investigate the prognostic impact of these metastases in our patients. The second original article showed that selective sentinel lymph node biopsy can safely replace complete lymphadenectomy in the lymph node staging of endometrial cancer at intermediate risk of recurrence. Finally, the third original article evaluated the impact of replacing complete lymphadenectomy with selective sentinel lymph node biopsy on patient quality of life and found that this paradigm shift improved the functional status and symptom sphere of our patient

Accuracy and Survival Outcomes after National Implementation of Sentinel Lymph Node Biopsy in Early Stage Endometrial Cancer

Accuracy; Sentinel lymph node biopsy; Endometrial cancerPrecisión; Biopsia del ganglio linfático centinela; Cáncer de endometrioPrecisió; Biòpsia del gangli limfàtic sentinella; Càncer d'endometriBackground Sentinel lymph node (SLN) biopsy has recently been accepted to evaluate nodal status in endometrial cancer at early stage, which is key to tailoring adjuvant treatments. Our aim was to evaluate the national implementation of SLN biopsy in terms of accuracy to detect nodal disease in a clinical setting and oncologic outcomes according to the volume of nodal disease. Patients and Methods A total of 29 Spanish centers participated in this retrospective, multicenter registry including patients with endometrial adenocarcinoma at preoperative early stage who had undergone SLN biopsy between 2015 and 2021. Each center collected data regarding demographic, clinical, histologic, therapeutic, and survival characteristics. Results A total of 892 patients were enrolled. After the surgery, 12.9% were suprastaged to FIGO 2009 stages III–IV and 108 patients (12.1%) had nodal involvement: 54.6% macrometastasis, 22.2% micrometastases, and 23.1% isolated tumor cells (ITC). Sensitivity of SLN biopsy was 93.7% and false negative rate was 6.2%. After a median follow up of 1.81 years, overall surivial and disease-free survival were significantly lower in patients who had macrometastases when compared with patients with negative nodes, micrometastases or ITC. Conclusions In our nationwide cohort we obtained high sensitivity of SLN biopsy to detect nodal disease. The oncologic outcomes of patients with negative nodes and low-volume disease were similar after tailoring adjuvant treatments. In total, 22% of patients with macrometastasis and 50% of patients with micrometastasis were at low risk of nodal metastasis according to their preoperative risk factors, revealing the importance of SLN biopsy in the surgical management of patients with early stage EC.Open Access Funding provided by Universitat Autonoma de Barcelona

Adsorción de impurezas del jugo clarificado de la industria azucarera mediante biomasa pirolizada.

En este trabajo se prepararon dos adsorbentes a partir de la cáscara del fruto de Jatropha curcas, para evaluar su efectividad en la remoción de impurezas coloreadas presentes en el jugo clarificado obtenido del proceso de fabricación de azúcar de caña. Partiendo de la cáscara molida y tamizada (diámetro<2 mm) del fruto de Jatropha curcas se fabricaron dos pirolizados mediante deshidratación inicial con ácido concentrados (ácido sulfúricoy ácido fosfórico), y posterior pirólisis a 500 ºC. Se verificó, mediante análisis estadístico, que el PAF (elaborado por deshidratación con ácido fosfórico) eliminó el 47,4±1,8 % de las impurezas coloreadas, con respecto al 36,8±1,6 % eliminado por el PAS (elaborado por deshidratación con ácido sulfúrico). Los parámetros de calidad del PAF se encuentran dentro de los intervalos establecidos para este tipo de material adsorbente. Ninguno de los pirolizados contaminó el jugo clarificado. Teniendo en cuenta los resultados, se sugiere la introducción de estos materiales en el proceso productivo de la industria azucarera. Palabras clave: Jatropha curcas, pirolizado, remoción de color, jugo clarificado

Whole body correction of mucopolysaccharidosis IIIA by intracerebrospinal fluid gene therapy

For most lysosomal storage diseases (LSDs) affecting the CNS, there is currently no cure. The BBB, which limits the bioavailability of drugs administered systemically, and the short half-life of lysosomal enzymes, hamper the development of effective therapies. Mucopolysaccharidosis type IIIA (MPS IIIA) is an autosomic recessive LSD caused by a deficiency in sulfamidase, a sulfatase involved in the stepwise degradation of glycosaminoglycan (GAG) heparan sulfate. Here, we demonstrate that intracerebrospinal fluid (intra-CSF) administration of serotype 9 adenoassociated viral vectors (AAV9s) encoding sulfamidase corrects both CNS and somatic pathology in MPS IIIA mice. Following vector administration, enzymatic activity increased throughout the brain and in serum, leading to whole body correction of GAG accumulation and lysosomal pathology, normalization of behavioral deficits, and prolonged survival. To test this strategy in a larger animal, we treated beagle dogs using intracisternal or intracerebroventricular delivery. Administration of sulfamidase-encoding AAV9 resulted in transgenic expression throughout the CNS and liver and increased sulfamidase activity in CSF. High-titer serum antibodies against AAV9 only partially blocked CSF-mediated gene transfer to the brains of dogs. Consistently, anti-AAV antibody titers were lower in CSF than in serum collected from healthy and MPS IIIA-affected children. These results support the clinical translation of this approach for the treatment of MPS IIIA and other LSDs with CNS involvement

Whole body correction of mucopolysaccharidosis IIIA by intracerebrospinal fluid gene therapy

For most lysosomal storage diseases (LSDs) affecting the CNS, there is currently no cure. The BBB, which limits the bioavailability of drugs administered systemically, and the short half-life of lysosomal enzymes, hamper the development of effective therapies. Mucopolysaccharidosis type IIIA (MPS IIIA) is an autosomic recessive LSD caused by a deficiency in sulfamidase, a sulfatase involved in the stepwise degradation of glycosaminoglycan (GAG) heparan sulfate. Here, we demonstrate that intracerebrospinal fluid (intra-CSF) administration of serotype 9 adenoassociated viral vectors (AAV9s) encoding sulfamidase corrects both CNS and somatic pathology in MPS IIIA mice. Following vector administration, enzymatic activity increased throughout the brain and in serum, leading to whole body correction of GAG accumulation and lysosomal pathology, normalization of behavioral deficits, and prolonged survival. To test this strategy in a larger animal, we treated beagle dogs using intracisternal or intracerebroventricular delivery. Administration of sulfamidase-encoding AAV9 resulted in transgenic expression throughout the CNS and liver and increased sulfamidase activity in CSF. High-titer serum antibodies against AAV9 only partially blocked CSF-mediated gene transfer to the brains of dogs. Consistently, anti-AAV antibody titers were lower in CSF than in serum collected from healthy and MPS IIIA-affected children. These results support the clinical translation of this approach for the treatment of MPS IIIA and other LSDs with CNS involvement

Evaluation of a real time pcr system for detection of Escherichia coli O157:H7 in ground beef

La infección por Escherichia coli O157:H7 es causa de diarrea con o sin sangre, colitis hemorrágica y síndrome urémico hemolítico (SUH) en humanos. El principal reservorio animal de E. coli O157:H7 son los bovinos y la carne bovina molida es una potencial fuente de infección. El objetivo de este trabajo fue evaluar un sistema comercial de PCR en tiempo real para la detección de E. coli O157:H7. Se determinó límite de detección, selectividad y robustez. Se contaminaron experimentalmente 50 muestras de carne molida bovina con 10 cepas de E. coli O157:H7 (10, 100 y 1000 UFC/25 g) y 20 cepas de bacterias no-E. coli O157:H7 (1000 UFC/25 g). El límite de detección dependió de la cepa analizada, el valor mínimo fue 6,1 UFC/25 g. La robustez fue óptima al modificar diferentes variables. Se obtuvo 100% de inclusividad y 100% de exclusividad. La técnica evaluada es una alternativa apropiada para la detección de E. coli O157:H7 a partir de carne bovina molida.Shiga toxin-producing Escherichia coli (STEC) cause non-bloody or bloody diar- rhea, hemorrhagic colitis and hemolytic uremic syndrome (HUS) in humans. Cattle are a major animal reservoir for E. coli O157:H7 and the ground beef are a potential source of infection. The aim of the present study was to evaluate a real time PCR commercial system for detection of E. coli O157:H7. Detection limit, selectivity and robustness were established. Fifty samples of ground beef were experimentally contaminated with 10 E. coli O157:H7 strains (10, 100 y 1000 CFU/25 g) and 20 non-E. coli O157:H7 strains (1000 CFU/25 g). The detection limit depended on the strain analyzed, the minimum values was 6,1 cfu/15 g. A good robustness was observed when different variables were introduced. Inclusivity and exclusivity were of 100%. The evaluated technique is an appropriate alternative for detection of E. coli O157:H7 from ground beef.Facultad de Ciencias Veterinaria

Evaluation of a real time pcr system for detection of Escherichia coli O157:H7 in ground beef

La infección por Escherichia coli O157:H7 es causa de diarrea con o sin sangre, colitis hemorrágica y síndrome urémico hemolítico (SUH) en humanos. El principal reservorio animal de E. coli O157:H7 son los bovinos y la carne bovina molida es una potencial fuente de infección. El objetivo de este trabajo fue evaluar un sistema comercial de PCR en tiempo real para la detección de E. coli O157:H7. Se determinó límite de detección, selectividad y robustez. Se contaminaron experimentalmente 50 muestras de carne molida bovina con 10 cepas de E. coli O157:H7 (10, 100 y 1000 UFC/25 g) y 20 cepas de bacterias no-E. coli O157:H7 (1000 UFC/25 g). El límite de detección dependió de la cepa analizada, el valor mínimo fue 6,1 UFC/25 g. La robustez fue óptima al modificar diferentes variables. Se obtuvo 100% de inclusividad y 100% de exclusividad. La técnica evaluada es una alternativa apropiada para la detección de E. coli O157:H7 a partir de carne bovina molida.Shiga toxin-producing Escherichia coli (STEC) cause non-bloody or bloody diar- rhea, hemorrhagic colitis and hemolytic uremic syndrome (HUS) in humans. Cattle are a major animal reservoir for E. coli O157:H7 and the ground beef are a potential source of infection. The aim of the present study was to evaluate a real time PCR commercial system for detection of E. coli O157:H7. Detection limit, selectivity and robustness were established. Fifty samples of ground beef were experimentally contaminated with 10 E. coli O157:H7 strains (10, 100 y 1000 CFU/25 g) and 20 non-E. coli O157:H7 strains (1000 CFU/25 g). The detection limit depended on the strain analyzed, the minimum values was 6,1 cfu/15 g. A good robustness was observed when different variables were introduced. Inclusivity and exclusivity were of 100%. The evaluated technique is an appropriate alternative for detection of E. coli O157:H7 from ground beef.Facultad de Ciencias Veterinaria

Potential relation of cardiovascular risk factors to disease activity in patients with axial spondyloarthritis

Background: Axial spondyloarthritis (axSpA) patients are known to have a higher prevalence of several comorbidities, including, among others, an increased risk of atherosclerosis, hypertension, dyslipidemia, and diabetes. The purpose of the present study was to determine whether the sum of traditional cardiovascular (CV) risk factors is related to disease characteristics, such as disease activity, in patients with axSpA. Methods: A cross-sectional study that encompassed 804 patients with axSpA was conducted. Patients were assessed for the presence of five traditional CV risk factors (diabetes mellitus, dyslipidemia, hypertension, obesity, and smoking status), and disease activity measurements. A multivariable regression analysis was performed to evaluate whether the number of classic CV risk factors was independently associated with specific features of the disease, to include disease activity. Results: A multivariable analysis showed that Ankylosing Spondylitis Disease Activity Score-C reactive protein (ASDAS-CRP) activity score was significantly higher in patients with 1 [beta coefficient 0.3 (95% confidence interval (CI) 0.1-0.5), p = 0.001] and ?2 [beta coefficient 0.5 (95% CI 0.3-0.7), p = 0.000] CV risk factors compared with those without CV risk factors. Similarly, patients with 1 [OR 2.00 (95%CI 0.99-4.02), p = 0.053] and ?2 [OR 3.39 (95%CI 1.82-6.31), p = 0.000] CV risk factors had a higher odds ratio for the presence of high disease activity compared with the zero CV category. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) activity score was significantly associated with the number of CV risk factors, being higher in patients with more CV risk factors. These relationships showed a CV risk factor-dependent effect being beta coefficients and ORs higher for the effect of ?2 over 1 CV risk factor. Conclusion: Among patients with axSpA, as the number of traditional CV risk factors increased, disease activity similarly increases in an independent manner.Funding: The authors disclosed receipt of the following financial support for the research, authorship, and/ or publication of this article: This research was funded by a grant to MAG-G from the Instituto de Salud Carlos III (ISCIII) (Fondo de Investigación Sanitaria grants PI06/0024, PI09/00748, PI12/00060, PI15/00525, PI18/00043) and the ISCIII RETICS programs (RD12/0009 and RD16/0012)

Accuracy and Survival Outcomes after National Implementation of Sentinel Lymph Node Biopsy in Early Stage Endometrial Cancer

Background. Sentinel lymph node (SLN) biopsy has recently been accepted to evaluate nodal status in endometrial cancer at early stage, which is key to tailoring adjuvant treatments. Our aim was to evaluate the national implementation of SLN biopsy in terms of accuracy to detect nodal disease in a clinical setting and oncologic outcomes according to the volume of nodal disease. Patients and Methods. A total of 29 Spanish centers participated in this retrospective, multicenter registry including patients with endometrial adenocarcinoma at preoperative early stage who had undergone SLN biopsy between 2015 and 2021. Each center collected data regarding demographic, clinical, histologic, therapeutic, and survival characteristics. Results. A total of 892 patients were enrolled. After the surgery, 12.9% were suprastaged to FIGO 2009 stages III-IV and 108 patients (12.1%) had nodal involvement: 54.6% macrometastasis, 22.2% micrometastases, and 23.1% isolated tumor cells (ITC). Sensitivity of SLN biopsy was 93.7% and false negative rate was 6.2%. After a median follow up of 1.81 years, overall surivial and disease-free survival were significantly lower in patients who had macrometastases when compared with patients with negative nodes, micrometastases or ITC. Conclusions. In our nationwide cohort we obtained high sensitivity of SLN biopsy to detect nodal disease. The oncologic outcomes of patients with negative nodes and low-volume disease were similar after tailoring adjuvant treatments. In total, 22% of patients with macrometastasis and 50% of patients with micrometastasis were at low risk of nodal metastasis according to their preoperative risk factors, revealing the importance of SLN biopsy in the surgical management of patients with early stage EC

Temas Socio-Jurídicos. Volumen 17 No. 37 Diciembre 1999

Al cierre de la edición número 37 de la Revista Temas Socio- Jurídicos, registramos la desaparición de la profesora de la Universidad Nacional de Colombia Virginia Gutierrez De Pineda, antropóloga santandereana, profesora, quien en varias oportunidades honró con su presencia y su prestancia a la Universidad Autónoma de Bucaramanga, en especial la Maestría en Derecho de Familia, en la cual atendió el área relacionada con los conflictos entre los géneros, la pareja y la familia. Gus enseñanzas, su acción vital, su permanente indagación de la realidad del país han de servir de ejemplo a quienes deseen seguir la senda de la ciencia y conquistar horizontes de conocimiento. Como homenaje a esta mujer pionera, la revista publica una de sus últimas conferencias pronunciadas en la Universidad, denominada el conflicto en la relación de los géneros. Dos escritos salidos de la pluma del profesor Alfonso Gómez Gómez, el primero sobre el resurgimiento de las provincias, el segundo sobre las Asambleas Departamentales, incitan a la reflexión cobre la necesidad de una reconfiguración de la estructura político-administrativa de las regiones en el País. Proseguimos con la divulgación del ensayo sobre Institutos Jurídicos Básicos, la segunda parte, donde se exponen los fundamentos económico-sociales de las instituciones jurídicas y sus expresiones abstractas en el orden de los conceptos.At the close of the 37th edition of the Socio-Legal Issues Magazine, we recorded the disappearance of the professor at the National University of Colombia, Virginia Gutierrez De Pineda, an anthropologist from Santander, professor, who on several occasions honored the Autonomous University of Bucaramanga, especially the Master's Degree in Family Law, in which he dealt with the area related to conflicts between genders, couples and family. Gus teachings, his vital action, his permanent investigation of the reality of the country must serve as an example to those who wish to follow the path of science and conquer horizons of knowledge. As a tribute to this pioneering woman, the magazine publishes one of her last lectures given at the University, called the conflict in the relationship between genders. Two writings from the pen of Professor Alfonso Gómez Gómez, the first on the resurgence of the provinces, the second on the Departmental Assemblies, encourage reflection on the need for a reconfiguration of the political-administrative structure of the regions in the Country . We continue with the disclosure of the essay on Basic Legal Institutes, the second part, where the socio-economic foundations of legal institutions and their abstract expressions in the order of concepts are exposed