The "Twin Peaks" method of automated Spike-Wave detection: A two-step, two-criteria Matlab application.

BACKGROUND: There are many automated spike-wave discharge detectors, but the known weaknesses of otherwise good methods and the varying working conditions of different research groups (mainly the access to hardware and software) invite further exploration into alternative approaches. NEW METHOD: The algorithm combines two criteria, one in the time-domain and one in the frequency-domain, exploiting morphological asymmetry and the presence of harmonics, respectively. The time-domain criterion is additionally adjusted by normal modelling between the first and second iterations. RESULTS: We report specificity, sensitivity and accuracy values for 20 recordings from 17 mature, male WAG/Rij rats. In addition, performance was preliminary tested with different hormones, pharmacological injections and species (mice) in a smaller sample. Accuracy and specificity were consistently above 91 %. The number of automatically detected spike-wave discharges was strongly correlated with the numbers derived from visual inspection. Sensitivity varied more strongly than specificity, but high values were observed in both rats and mice. COMPARISON WITH EXISTING METHODS: The algorithm avoids low-voltage movement artifacts, displays a lower false positive rate than many predecessors and appears to work across species, i.e. while designed initially with data from the WAG/Rij rat, the algorithm can pick up seizure activity in the mouse of considerably lower inter-spike frequency. Weaknesses of the proposed method include a lower sensitivity than several predecessors. CONCLUSION: The algorithm excels in being a selective and flexible (based on e.g. its performance across rats and mice) spike-wave discharge detector. Future work could attempt to increase the sensitivity of this approach.

Cefalea e hipertensión como forma de presentación de un feocromocitoma y simulando un síndrome post-COVID-19 / Headache and hypertension as a form of presentation of pheochromocytoma and simulating a post-COVID-19 syndrome

El síndrome post-COVID-19 es un conjunto de síntomas y signos que persisten durante más de 12 semanas después de una infección por COVID-19 y actualmente carece de una definición clínica estandarizada. Únicamente se ha informado un caso en el que un feocromocitoma se confundió con un síndrome post-COVID-19. La sintomatología de este síndrome es variable y abarca desde la cefalea y la fatiga hasta la disnea persistente y las alteraciones neurocognitivas. Además, el SARS-CoV-2 puede afectar al sistema nervioso autónomo, contribuyendo a síntomas que se asemejan a los del feocromocitoma. Se recalca la importancia y la necesidad de discernir entre síntomas relacionados con la COVID-19 y otras afecciones, ya que la especificidad de las manifestaciones clínicas del síndrome post-COVID-19 es muy baja y puede ser confundido con otras enfermedades vitales. Se presenta un caso en el que un feocromocitoma fue confundido con un síndrome post-COVID-19 en una paciente sin antecedentes médicos.(AU)

Post-COVID-19 syndrome is a set of symptoms and signs that persist for more than 12 weeks after COVID-19 infection and currently lacks a standardised clinical definition. Only one case has been reported in which a pheochromocytoma was mistaken for post-COVID-19 syndrome. The symptomatology of this syndrome is variable and ranges from headache and fatigue to persistent dyspnoea and neurocognitive disturbances. In addition, SARS-CoV-2 can affect the autonomic nervous system, contributing to symptoms resembling those of pheochromocytoma. The importance and need to discern between COVID-19-related symptoms and other conditions is emphasised, as the specificity of the clinical manifestations of post-COVID-19 syndrome is very low and can be confused with other vital pathologies. A case is presented in which a pheochromocytoma was mistaken for post-COVID-19 syndrome in a patient with no medical history.(AU)

[Headache and hypertension as a form of presentation of pheochromocytoma and simulating a post-COVID-19 syndrome]. / Cefalea e hipertensión como forma de presentación de un feocromocitoma y simulando un síndrome post-COVID-19.

Post-COVID-19 syndrome is a set of symptoms and signs that persist for more than 12 weeks after COVID-19 infection and currently lacks a standardised clinical definition. Only one case has been reported in which a pheochromocytoma was mistaken for post-COVID-19 syndrome. The symptomatology of this syndrome is variable and ranges from headache and fatigue to persistent dyspnoea and neurocognitive disturbances. In addition, SARS-CoV-2 can affect the autonomic nervous system, contributing to symptoms resembling those of pheochromocytoma. The importance and need to discern between COVID-19-related symptoms and other conditions is emphasised, as the specificity of the clinical manifestations of post-COVID-19 syndrome is very low and can be confused with other vital pathologies. A case is presented in which a pheochromocytoma was mistaken for post-COVID-19 syndrome in a patient with no medical history.

Validación de los modelos de impresión 3D paciente-específicos para cirugía ortopédica oncológica pélvica / Validation of patient-specific 3D impression models for pelvic oncological orthopedic surgery

Introducción: Los tumores del anillo pélvico suponen un reto por la dificultad de obtener márgenes quirúrgicos adecuados. Herramientas como la navegación quirúrgica o la impresión 3D para la fabricación de plantillas de posicionamiento quirúrgico paciente-específicas ayudan en la planificación preoperatoria y la ejecución intraoperatoria. Su correcta colocación es fundamental en localizaciones complejas como la pelvis, por lo que es necesario identificar los errores de posicionamiento. El objetivo de este estudio es demostrar la fiabilidad en la colocación de plantillas 3D para la realización de osteotomías en el anillo pélvico. Material y métodos: Estudio experimental en cadáver con 10 hemipelvis. Se realiza TC para la obtención del modelo tridimensional, planificación de osteotomías, diseño de plantillas de posicionamiento en rama isquiopubiana (I), iliopubiana (P), supracetabular (S) y cresta iliaca (C); y un marcador de posicionamiento (rigid-body) sobre las plantillas C y S para la navegación. Las plantillas y el rigid-body son impresos en 3D y se colocan según planificación previa. La navegación permite comprobar la posición final de las plantillas y de las osteotomías. Resultados: El posicionamiento de las plantillas respecto a la planificación preoperatoria varió dependiendo de la localización, siendo mayor el error en las de cresta iliaca. Utilizando la navegación, la media de error de distancia al plano de corte está en 3,5mm, excepto en pubis (5-8mm), estando condicionado por la posición del rigid body. Conclusión: El uso de plantillas paciente-específicas impresas en 3D es una herramienta fiable para la realización de osteotomías en cirugía oncológica pélvica.(AU)

Introduction: Pelvic ring tumors pose a challenge due to the difficulty in obtaining adequate surgical margins. Tools such as surgical navigation or 3D printing for the fabrication of patient-specific surgical positioning templates help in preoperative planning and intraoperative execution. Their correct positioning is essential in complex locations such as the pelvis, so it is necessary to identify positioning errors. The aim of this study is to demonstrate the reliability of 3D template placement for pelvic ring osteotomies. Material and methods: Experimental study in cadaver with 10 hemipelvis. CT was performed to obtain the three-dimensional model, planning of osteotomies, design of positioning templates in ischiopubic (I), iliopubic (P), supracetabular (S) and iliac crest (C) branches; and a positioning marker (rigid-body) on the C and S templates for navigation. The templates and rigid-body are 3D printed and positioned according to pre-planning. Navigation allows the final position of the inserts and osteotomies to be checked. Results: The positioning of the templates with respect to the preoperative planning varied depending on the location, being greater the error in those of the iliac crest. Using navigation the mean error of distance to the cutting plane is 3.5mm, except in pubis 5-8mm), being conditioned by the position of the rigid body. Conclusion: The use of patient-specific templates printed in 3D is a reliable tool for performing osteotomies in pelvic cancer surgery.(AU)

[Translated article] Validation of patient-specific 3D impression models for pelvic oncological orthopedic surgery / Validación de los modelos de impresión 3D paciente-específicos para cirugía ortopédica oncológica pélvica

Introducción: Los tumores del anillo pélvico suponen un reto por la dificultad de obtener márgenes quirúrgicos adecuados. Herramientas como la navegación quirúrgica o la impresión 3D para la fabricación de plantillas de posicionamiento quirúrgico paciente-específicas ayudan en la planificación preoperatoria y la ejecución intraoperatoria. Su correcta colocación es fundamental en localizaciones complejas como la pelvis, por lo que es necesario identificar los errores de posicionamiento. El objetivo de este estudio es demostrar la fiabilidad en la colocación de plantillas 3D para la realización de osteotomías en el anillo pélvico. Material y métodos: Estudio experimental en cadáver con 10 hemipelvis. Se realiza TC para la obtención del modelo tridimensional, planificación de osteotomías, diseño de plantillas de posicionamiento en rama isquiopubiana (I), iliopubiana (P), supracetabular (S) y cresta iliaca (C); y un marcador de posicionamiento (rigid-body) sobre las plantillas C y S para la navegación. Las plantillas y el rigid-body son impresos en 3D y se colocan según planificación previa. La navegación permite comprobar la posición final de las plantillas y de las osteotomías. Resultados: El posicionamiento de las plantillas respecto a la planificación preoperatoria varió dependiendo de la localización, siendo mayor el error en las de cresta iliaca. Utilizando la navegación, la media de error de distancia al plano de corte está en 3,5mm, excepto en pubis (5-8mm), estando condicionado por la posición del rigid body. Conclusión: El uso de plantillas paciente-específicas impresas en 3D es una herramienta fiable para la realización de osteotomías en cirugía oncológica pélvica.(AU)

Introduction: Pelvic ring tumors pose a challenge due to the difficulty in obtaining adequate surgical margins. Tools such as surgical navigation or 3D printing for the fabrication of patient-specific surgical positioning templates help in preoperative planning and intraoperative execution. Their correct positioning is essential in complex locations such as the pelvis, so it is necessary to identify positioning errors. The aim of this study is to demonstrate the reliability of 3D template placement for pelvic ring osteotomies. Material and methods: Experimental study in cadaver with 10 hemipelvis. CT was performed to obtain the three-dimensional model, planning of osteotomies, design of positioning templates in ischiopubic (I), iliopubic (P), supracetabular (S) and iliac crest (C) branches; and a positioning marker (rigid-body) on the C and S templates for navigation. The templates and rigid-body are 3D printed and positioned according to pre-planning. Navigation allows the final position of the inserts and osteotomies to be checked. Results: The positioning of the templates with respect to the preoperative planning varied depending on the location, being greater the error in those of the iliac crest. Using navigation the mean error of distance to the cutting plane is 3.5mm, except in pubis 5-8mm), being conditioned by the position of the rigid body. Conclusion: The use of patient-specific templates printed in 3D is a reliable tool for performing osteotomies in pelvic cancer surgery.(AU)

[Translated article] Validation of patient-specific 3D impression models for pelvic oncological orthopedic surgery.

INTRODUCTION: Pelvic ring tumours pose a challenge due to the difficulty in obtaining adequate surgical margins. Tools such as surgical navigation or 3D printing for the fabrication of patient-specific surgical positioning templates help in preoperative planning and intraoperative execution. Their correct positioning is essential in complex locations such as the pelvis, so it is necessary to identify positioning errors. The aim of this study is to demonstrate the reliability of 3D template placement for pelvic ring osteotomies. MATERIAL AND METHODS: Experimental study in cadaver with 10 hemipelvis. CT was performed to obtain the three-dimensional model, planning of osteotomies, design of positioning templates in ischiopubic (I), iliopubic (P), supracetabular (S) and iliac crest (C) branches; and a positioning marker (rigid-body) on the C and S templates for navigation. The templates and rigid-body are 3D printed and positioned according to pre-planning. Navigation allows the final position of the inserts and osteotomies to be checked. RESULTS: The positioning of the templates with respect to the preoperative planning varied depending on the location, being greater the error in those of the iliac crest. Using navigation the mean error of distance to the cutting plane is 3.5mm, except in pubis (5-8mm), being conditioned by the position of the rigid body. CONCLUSION: The use of patient-specific templates printed in 3D is a reliable tool for performing osteotomies in pelvic cancer surgery.

Validation of patient-specific 3D impression models for pelvic oncological orthopedic surgery. / Validación de los modelos de impresión 3D paciente-específicos para cirugía ortopédica oncológica pélvica.

INTRODUCTION: Pelvic ring tumors pose a challenge due to the difficulty in obtaining adequate surgical margins. Tools such as surgical navigation or 3D printing for the fabrication of patient-specific surgical positioning templates help in preoperative planning and intraoperative execution. Their correct positioning is essential in complex locations such as the pelvis, so it is necessary to identify positioning errors. The aim of this study is to demonstrate the reliability of 3D template placement for pelvic ring osteotomies. MATERIAL AND METHODS: Experimental study in cadaver with 10 hemipelvis. CT was performed to obtain the three-dimensional model, planning of osteotomies, design of positioning templates in ischiopubic (I), iliopubic (P), supracetabular (S) and iliac crest (C) branches; and a positioning marker (rigid-body) on the C and S templates for navigation. The templates and rigid-body are 3D printed and positioned according to pre-planning. Navigation allows the final position of the inserts and osteotomies to be checked. RESULTS: The positioning of the templates with respect to the preoperative planning varied depending on the location, being greater the error in those of the iliac crest. Using navigation the mean error of distance to the cutting plane is 3.5mm, except in pubis (5-8mm), being conditioned by the position of the rigid body. CONCLUSION: The use of patient-specific templates printed in 3D is a reliable tool for performing osteotomies in pelvic cancer surgery.

A Chemical Biology Toolbox Targeting the Intracellular Binding Site of CCR9: Fluorescent Ligands, New Drug Leads and PROTACs.

A conserved intracellular allosteric binding site (IABS) has recently been identified at several G protein-coupled receptors (GPCRs). Starting from vercirnon, an intracellular C-C chemokine receptor type 9 (CCR9) antagonist and previous phase III clinical candidate for the treatment of Crohn's disease, we developed a chemical biology toolbox targeting the IABS of CCR9. We first synthesized a fluorescent ligand enabling equilibrium and kinetic binding studies via NanoBRET as well as fluorescence microscopy. Applying this molecular tool in a membrane-based setup and in living cells, we discovered a 4-aminopyrimidine analogue as a new intracellular CCR9 antagonist with improved affinity. To chemically induce CCR9 degradation, we then developed the first PROTAC targeting the IABS of GPCRs. In a proof-of-principle study, we succeeded in showing that our CCR9-PROTAC is able to reduce CCR9 levels, thereby offering an unprecedented approach to modulate GPCR activity.

Result of the implementation of telematic consultations in orthopaedic surgery and traumatology during COVID-19 laparoscopic surgery. / Resultado de la implantación de consultas telemáticas en cirugía ortopédica y traumatología durante la pandemia COVID-19.

The COVID pandemic has made telematic consultations a basic tool in daily practice. AIMS: The main objective of the study is to assess the results of the application of telematic consultations to limit the mobility of patients. The operational objectives are; to propose a consultation plan, to know how attendance limits consultations and to define which pathologies benefit the most from this plan. METHODS: A scheme is proposed with the creation of pre-scheduled clinic to assess suitability and the possibility of carrying them out in a single non face-to-face act. RESULTS: Phone call to 5,619 patients were made with a lack of response of 19%. The cases of 74% of the patients that answered were resolved virtually. There is a difference between units, obtaining a higher answering rate from patients appointed to specific clinic units, OR = 0.60, or to general trauma ones, OR = 0.67. The lowest answering rate was obtained from those derived from the emergency department. Twenty per cent of the consultations were not accompanied by complementary tests that would have favored the resolution in a single act. The general trauma consultations, OR = 0.34, postoperative control, OR = 0.49, and specific unit ones, OR = 0.40, were the ones that better met this requirement. Out of the remaining patients, the general trauma consultations, OR = 0.50, and those referred to units, OR = 0.54, were the ones that had a higher resolution rate without in- person consultation. CONCLUSIONS: The cases of 74% of the patients who answered the phone call were resolved virtually. Cases of 20% of the patients cannot be solved in a single act because they are derived without complementary tests. Osteosynthesis and postoperative arthroscopic follow-up consultations are the ones that need to be carried out in person the most.