Concordancia entre SPECT portátil y la gammagrafía convencional para detección de ganglio centinela en cáncer de mama / Concordance between freehand SPECT and conventional scintigraphy for sentinel lymph node detection in breast cancer

Introducción: La SPECT portátil puede ser una técnica de imagen útil para la planificación preoperatoria de la biopsia selectiva del ganglio centinela (BSGC) ya que permite la localización del ganglio centinela (GC) mediante imágenes tomográficas en 3D y en tiempo real y determina su profundidad, después de unos minutos de exploración. El objetivo del estudio fue evaluar la correlación entre el número de GC detectados entre las imágenes de la SPECT portátil y la linfogammagrafía (LG). Materiales y métodos: Cien pacientes con diagnóstico de cáncer de mama infiltrante y sin evidencia clínica de afectación ganglionar, se sometieron prospectivamente a una BSGC. El estudio preoperatorio incluyó imágenes de SPECT portátil a los 15 min tras la inyección y de LG a los 25 y 60-90 min (precoz y tardía). Se analizó el acuerdo observado y se realizó un estudio de concordancia entre el número de GC detectados con SPECT portátil y LG. Resultados: El acuerdo observado en la detección de GC entre SPECT portátil y LG precoz fue del 72%; entre SPECT portátil y LG tardía del 85%, y entre la LG precoz y la tardía de un 87%. En el estudio de concordancia se registró una concordancia moderada entre la SPECT portátil y la LG precoz (coeficiente kappa: 0,42); una concordancia moderada-alta entre la SPECT portátil y la LG tardía (coeficiente kappa: 0,60), y una concordancia de moderada-alta entre la LG precoz y la tardía (coeficiente kappa: 0,70), sin diferencias significativas entre ellos (valor p=0,16). Conclusión: La SPECT portátil presentó una concordancia moderada-alta con los estudios de imagen convencional y podría ser una alternativa válida para el estudio prequirúrgico de la BSGC en el cáncer de mama.(AU)

Introduction: Freehand SPECT can be a useful imaging technique for preoperative planning of sentinel lymph node biopsy (SLNB) as it allows localization of the sentinel node by 3D and real-time tomographic imaging and determines its depth after a few minutes of scanning. The aim of the study was to evaluate the correlation between the number of detected SNs between freehand SPECT images and lymphoscintigraphy (LS). Materials and methods: One hundred patients with a diagnosis of invasive breast cancer and no clinical evidence of lymph node involvement prospectively underwent SLNB. The preoperative study included freehand SPECT imaging at 15min after injection and LS imaging at 25 and 60–90min after injection (early and late). The observed agreement was analyzed and a concordance study was performed between the number of SNs detected with freehand SPECT and LS. Results: The observed agreement in the detection of SNs between freehand SPECT and early LS was 72%; between freehand SPECT and late LS was 85%; and between early and late LS was 87%. In the concordance study, there was moderate concordance between freehand SPECT and early LS (kappa coefficient: 0.42); moderate-high concordance between freehand SPECT and late LS (kappa coefficient: 0.60); and moderate-high concordance between early and late LS (kappa coefficient: 0.70), with no significant differences between them (p-value=0.16). Conclusion: Freehand SPECT showed a moderate-high concordance with conventional imaging studies and could be a valid alternative for the presurgical study of SLNB in breast cancer.(AU)

Concordance between freehand SPECT and conventional scintigraphy for sentinel lymph node detection in breast cancer.

INTRODUCTION: Freehand SPECT can be a useful imaging technique for preoperative planning of sentinel lymph node biopsy (SLNB) as it allows localization of the sentinel node by 3D and real-time tomographic imaging and determines its depth after a few minutes of scanning. The aim of the study was to evaluate the correlation between the number of detected SNs between freehand SPECT images and lymphoscintigraphy (LS). MATERIALS AND METHODS: 100 patients with a diagnosis of invasive breast cancer and no clinical evidence of lymph node involvement prospectively underwent SLNB. The preoperative study included freehand SPECT imaging at 15min after injection and LS imaging at 25 and 60-90min after injection (early and late). The observed agreement was analyzed and a concordance study was performed between the number of SNs detected with freehand SPECT and LS. RESULTS: The observed agreement in the detection of SNs between freehand SPECT and early LS was 72%; between freehand SPECT and late LS was 85%; and between early and late LS was 87%. In the concordance study, there was moderate concordance between freehand SPECT and early LS (kappa coefficient: 0.42); moderate-high concordance between freehand SPECT and late LS (kappa coefficient: 0.60); and moderate-high concordance between early and late LS (kappa coefficient: 0.70), with no significant differences between them (p-value=0.16). CONCLUSION: Freehand SPECT showed a moderate-high concordance with conventional imaging studies and could be a valid alternative for the presurgical study of SLNB in breast cancer.

Síndrome post-cuidados intensivos al mes del alta hospitalaria de pacientes críticos supervivientes a COVID-19 / Post-intensive care syndrome at one month after hospital discharge in critically ill patients surviving COVID-19

Objetivos: Incidencia del síndrome post-cuidados intensivos al mes del alta hospitalaria en pacientes críticos supervivientes de COVID-19 e identificar factores asociados. Diseño: Estudio de cohortes prospectivo. Ámbito: Dos unidades de críticos polivalentes del Hospital Universitario Araba. Pacientes ingresados en unidades de críticos por insuficiencia respiratoria aguda grave secundaria a COVID-19. Intervención: Ninguna. Variables de interés: Variables demográficas, estancias, índice de Charlson, APACHEII, SOFA, días de ventilación mecánica, traqueotomía, delirio, tetraparesia del paciente crítico, EuroQol 5D5L, Minimental Test. Resultados: Se objetiva un deterioro en el índice de salud (IS) del EuroQol, que pasa de 90,9 ±16,9 a 70,9 ±24,7 (p<0,001). La afectación de los cinco dominios del EuroQol es de: movilidad (46,1%), actividades habituales (44,7%), malestar/dolor (30,7%), dominio psicológico (27,3%) y autocuidado (20,3%). El 61,5% sufren un descenso significativo de su índice de salud. El análisis multivariante mediante regresión logística nos muestra que el delirio (OR=3,01; IC95%: 1,01-8,9; p=0,047) y la traqueotomía (OR=2,37; IC95%: 1,09-5,14; p=0,029) muestran asociación con la caída en el IS del EuroQol 5D5L. El área bajo la curva ROC del modelo es del 67,3%, con un intervalo de confianza entre el 58% y el 76%. Se calibra el modelo mediante el test de Hosmer-Lemeshow:(χ2=0,468; p=0,792). Solamente el 1,2% de los pacientes mostraban una puntuación ≤24, claramente patológica, en el Minimental Test de Folstein. Conclusiones: El delirio y la necesidad de traqueostomía se asocian a síndrome post-cuidados intensivos evaluado mediante EuroQol 5D5L. (AU)

Objectives: Incidence of post-intensive care syndrome at one month after hospital discharge in surviving critically ill COVID-19 patients and to identify associated factors. Design: Prospective cohort study. Setting: Two multipurpose critical care units of the Araba University Hospital. Patients admitted to critical care units for severe acute respiratory failure secondary to COVID-19. Intervention: None. Variables of interest: Demographic variables, length of stay, Charlson index, APACHEII, SOFA, days of mechanical ventilation, tracheotomy, delirium, tetraparesis of the critical patient, EuroQol 5D5L, Minimental Test. Results: A deterioration in the EuroQol health index (HI) from 90.9 ±16.9 to 70.9 ±24.7 (P<.001) was observed. The impairment of the five EuroQol domains is: mobility (46.1%), usual activities (44.7%), discomfort/pain (30.7%), psychological domain (27.3%) and self-care (20.3%). The 61.5% suffer a significant decrease in their health index. Multivariate analysis by logistic regression shows us that delirium (OR=3.01; 95%CI: 1.01-8.9; P=.047) and tracheostomy (OR=2.37; 95%CI: 1.09-5.14; P=.029) show association with drop in EuroQol 5D5L SI. The area under the ROC curve of the model is 67.3%, with a confidence interval between 58% and 76%. The model is calibrated using the Hosmer-Lemeshow test (χ2=0.468; P=.792). Only 1.2% of patients showed a score ≤24, clearly pathological, on the Folstein's Minimental Test. Conclusions: Delirium and need for tracheostomy are associated with post-intensive care syndrome assessed by EuroQol 5D5L. (AU)

Explorando la opinión de los especialistas españoles acerca de la utilidad de la radiómica en el área oncológica / Exploring the opinion of Spanish medical specialists about the usefulness of radiomics in oncology

Objetivo Describir el conocimiento y la opinión de los profesionales sanitarios relacionados con la oncología acerca de la radiómica. Métodos Se elaboró un cuestionario de 12 preguntas (respuestas de selección múltiple, de escala tipo Likert y respuesta abierta), dirigido a profesionales relacionados con el diagnóstico/tratamiento de enfermedades oncológicas (oncología, radiodiagnóstico, medicina nuclear, oncología-radioterápica, hematooncología, radiofísica y anatomía patológica). Los participantes se clasificaron en dos grupos según su grado de formación: adjuntos y residentes. Resultados Un total de 114 profesionales completaron la encuesta (54% residentes, principalmente de las especialidades medicina nuclear y radiodiagnóstico). Los adjuntos obtuvieron un mejor desempeño en el área de conocimiento respecto a los residentes. En ambos grupos los encuestados respondieron estar de acuerdo con la utilidad de la radiómica para ayudar a realizar diagnósticos más precisos, facilitando el trabajo de los equipos médicos. Las ideas más frecuentes relacionadas con las desventajas del uso de la radiómica se relacionaron con la falta de sistematización en la adquisición de imágenes y la extracción de parámetros, la necesidad de entrenamiento de los profesionales y la inquietud sobre el reemplazo del trabajo humano por herramientas tecnológicas. Conclusiones La radiómica es un campo de estudio novedoso, cuyos aspectos más generales son conocidos por los profesionales sanitarios. Los profesionales encuestados son optimistas en cuanto a los beneficios que entregan esta y otros tipos de herramientas. El principal problema detectado fue la falta de sistematización en su implementación. El reemplazo de los profesionales y la pérdida de trabajo es una preocupación presente, pero menos prevalente y que puede responder a un fenómeno generacional (AU)

Aim To describe the knowledge and opinion of health professionals regarding the usefulness of radiomics in oncology. Methods A 12-question questionnaire (multiple-choice responses, Likert-type scale, and open response) was developed and sent to professionals related to diagnosis/treatment of oncological diseases (Oncology, Radiodiagnosis, Nuclear Medicine, Radiation Oncology, Hematology-Oncology, Radiophysics and Pathology). Participants were classified into two groups according to their level of training: attending physicians and residents. Results 114 professionals completed the survey (54% residents, mostly from Nuclear Medicine and Radiodiagnostic specialties). Attending physicians obtained a better performance in the area pf knowledge compared to residents. Both groups of respondents agreed regarding the usefulness of radiomics to help make more accurate diagnoses and promoting the work of medical teams and the most frequent disadvantages were related to the lack of systematization in the acquisition of images and extraction of parameters, the need for the training of professionals and concern about the replacement of human work by technological tools. Conclusions Radiomics is a novel field and the most general aspects are known by health professionals. The professionals surveyed were optimistic about the benefits provided by radiomics and other types of tools. The main problem detected was the lack of systematization in its implementation. The replacement of professionals and job loss is a concern, albeit less prevalent, and may respond to a generational phenomenon (AU)

Progreso y utilidad actual de la radiómica dentro del estudio PET/TC en cáncer de mama no metastásico: una revisión sistemática / Progress and current utility of radiomics in PET/CT study of non-metastatic breast cancer: A systematic review

Objetivo Sintetizar la evidencia actual sobre la utilidad de la radiómica en el análisis de la imagen PET/TC en cáncer de mama local o localmente avanzado y evaluar la calidad metodológica de los estudios radiómicos publicados al respecto. Material y métodos Revisión sistemática de artículos en distintas bases de datos hasta 2021 utilizando los términos «PET», «radiomics», «texture», «breast». Se seleccionaron solo artículos con datos humanos y que incluyeran una imagen de PET en su análisis. Se excluyeron estudios con datos de pruebas y menos de 20 pacientes. De cada artículo se extrajo el tamaño muestral, el radiotrazador utilizado, la técnica de imagen y las características de imagen extraídas. Se determinó la calidad metodológica de los estudios mediante el instrumento QUADAS-2. Resultados Se seleccionaron 18 artículos. El diseño retrospectivo fue el más utilizado. La característica radiómica más estudiada fue el SUVmax. Diversos parámetros radiómicos se correlacionaron con la caracterización tumoral, y la heterogeneidad tumoral demostró utilidad para predecir el curso de la enfermedad y la respuesta al tratamiento. La mayoría de los artículos mostraron un alto riesgo de sesgo, derivado principalmente de la selección de pacientes. Conclusiones Se observó una alta probabilidad de sesgo en los artículos publicados. La radiómica es un campo aún en desarrollo y son necesarios más estudios para demostrar su utilidad en la práctica clínica habitual. La herramienta QUADAS-2 permite la valoración crítica de la calidad metodológica de la evidencia disponible. Pese a las limitaciones, la radiómica se muestra como una herramienta que puede ayudar a conseguir un manejo oncológico personalizado en el cáncer de mama (AU)

Aim To synthesize the current evidence of the usefulness of radiomics in PET/CT image analysis in local and locally advanced breast cancer. Also, to evaluate the methodological quality of the radiomic studies published. Methods Systematic review of articles in different databases until 2021 using the terms «PET», «radiomics», «texture», «breast». Only articles with human data and that included a PET image were included. Studies with simulated data and with less than 20 patients were excluded. The sample size, radiotracer used, imaging technique, and radiomics characteristics were extracted from each article. The methodological quality of the studies was determined using the QUADAS-2 tool. Results Eighteen articles were selected. The retrospective design was the most used. The most studied radiomic characteristic was SUVmax. Several radiomic parameters were correlated with tumor characterization, and tumor heterogeneity proved useful for predicting disease course and response to treatment. Most articles showed a high risk of bias, mainly from the patient selection. Conclusions A high probability of bias was observed in most of the published articles. Radiomics is a developing field and more studies are needed to demonstrate its usefulness in routine clinical practice. The QUADAS-2 tool allows critical assessment of the methodological quality of the available evidence. Despite its limitations, radiomics is shown to be an instrument that can help to achieve personalized oncologic management of breast cancer (AU)

Exploring the opinion of Spanish medical specialists about the usefulness of radiomics in oncology.

AIM: To describe the knowledge and opinion of health professionals regarding the usefulness of radiomics in oncology. METHODS: A 12-question questionnaire (multiple-choice responses, Likert-type scale, and open response) was developed and sent to professionals related to diagnosis/treatment of oncological diseases (Oncology, Radiodiagnosis, Nuclear Medicine, Radiation Oncology, Hematology-Oncology, Radiophysics and Pathology). Participants were classified into two groups according to their level of training: attending physicians and residents. RESULTS: 114 professionals completed the survey (54% residents, mostly from Nuclear Medicine and Radiodiagnostic specialties). Attending physicians obtained a better performance in the area pf knowledge compared to residents. Both groups of respondents agreed regarding the usefulness of radiomics to help make more accurate diagnoses and promoting the work of medical teams and the most frequent disadvantages were related to the lack of systematization in the acquisition of images and extraction of parameters, the need for the training of professionals and concern about the replacement of human work by technological tools. CONCLUSIONS: Radiomics is a novel field and the most general aspects are known by health professionals. The professionals surveyed were optimistic about the benefits provided by radiomics and other types of tools. The main problem detected was the lack of systematization in its implementation. The replacement of professionals and job loss is a concern, albeit less prevalent, and may respond to a generational phenomenon.

Progress and current utility of radiomics in PET/CT study of non-metastatic breast cancer: A systematic review.

AIM: To synthesize the current evidence of the usefulness of radiomics in PET/CT image analysis in local and locally advanced breast cancer. Also, to evaluate the methodological quality of the radiomic studies published. METHODS: Systematic review of articles in different databases until 2021 using the terms "PET", "radiomics", "texture", "breast". Only articles with human data and that included a PET image were included. Studies with simulated data and with less than 20 patients were excluded. Were extracted sample size, radiotracer used, imaging technique, and radiomics characteristics from each article. The methodological quality of the studies was determined using the QUADAS-2 tool. RESULTS: 18 articles were selected. The retrospective design was the most used. The most studied radiomic characteristic was SUVmax. Several radiomic parameters were correlated with tumor characterization, and tumor heterogeneity proved useful for predicting disease course and response to treatment. Most articles showed a high risk of bias, mainly from the patient selection. CONCLUSIONS: A high probability of bias was observed in most of the published articles. Radiomics is a developing field and more studies are needed to demonstrate its usefulness in routine clinical practice. The QUADAS-2 tool allows critical assessment of the methodological quality of the available evidence. Despite its limitations, radiomics is shown to be an instrument that can help to achieve personalized oncologic management of breast cancer.

Post-intensive care syndrome one month after discharge in surviving critically ill COVID-19 patients.

OBJECTIVES: Incidence of post-intensive care syndrome at one month after hospital discharge in surviving critically ill COVID 19 patients and to identify associated factors. DESIGN: Prospective cohort study. SETTING: Two multipurpose critical care units of the Araba University Hospital. Patients admitted to critical care units for severe acute respiratory failure secondary to COVID 19. INTERVENTION: None. VARIABLES OF INTEREST: Demographic variables, length of stay, Charlson index, APACHE II, SOFA, days of mechanical ventilation, tracheotomy, delirium, tetraparesis of the critical patient, EuroQol 5D5L, Minimental Test. RESULTS: A deterioration in the EuroQol health index (HI) from 90.9±16.9 to 70.9±24.7 (p<0.001) was observed. The impairment of the five EuroQol domains is: mobility (46.1%), usual activities (44.7%), discomfort/pain (30.7%), psychological domain (27.3%) and self-care (20.3%). The 61.5% suffer a significant decrease in their health index. Multivariate analysis by logistic regression shows us that delirium (OR=3.01; 95%CI: 1.01-8.9; p=0.047) and tracheostomy (OR=2.37; 95%CI: 1.09-5.14; p=0.029) show association with drop in EuroQoL 5D5L SI. The area under the ROC curve of the model is 67.3%, with a confidence interval between 58% and 76%. The model is calibrated using the Hosmer-Lemeshow test (χ2=0.468; p=0.792). Only 1.2% of patients showed a score ≤ 24, clearly pathological, on the Folstein's Minimental Test. CONCLUSIONS: Delirium and need for tracheostomy are associated with post-intensive care syndrome assessed by EuroQol 5D5L.

Mechanisms of action of vitamin B1 (thiamine), B6 (pyridoxine), and B12 (cobalamin) in pain: a narrative review.

Pain is a complex sensory and emotional experience with nociceptive, nociplastic, and neuropathic components. An involvement of neurotropic B vitamins (B1 - thiamine, B6 - pyridoxine, and B12 - cyanocobalamin) as modulators of inflammation and pain has been long discussed. New evidence suggests their therapeutic potential in different pain conditions. In this review, we discuss the main role of neurotropic B vitamins on different nociceptive pathways in the nervous system and to describe their analgesic action mechanisms. The performed literature review showed that, through different mechanisms, these vitamins regulate several inflammatory and neural mediators in nociceptive and neuropathic pain. Some of these processes include aiming the activation of the descending pain modulatory system and in specific intracellular pathways, anti-inflammatory, antioxidative and nerve regenerative effects. Moreover, recent data shows the antinociceptive, antiallodynic, and anti-hyperalgesic effects of the combination of these vitamins, as well as their synergistic effects with known analgesics. Understanding how vitamins B1, B6, and B12 affect several nociceptive mechanisms can therefore be of significance in the treatment of various pain conditions.

[Post-intensive care syndrome one month after hospital discharge of critical patients surviving COVID 19.] / Síndrome post-cuidados intensivos al mes del alta hospitalaria de pacientes críticos supervivientes a COVID 19.

OBJECTIVES: incidence of post-intensive care syndrome at one month after hospital discharge in surviving critically ill COVID 19 patients and to identify associated factors. DESIGN: prospective cohort study. SETTING: two multipurpose critical care units of the Araba University Hospital.Patients admitted to critical care units for severe acute respiratory failure secondary to COVID 19. INTERVENTION: none. VARIABLES OF INTEREST: demographic variables, length of stay, Charlson index, APACHE II, SOFA, days of mechanical ventilation, tracheotomy, delirium, tetraparesis of the critical patient, EuroQol 5D5L, Minimental Test. RESULTS: a deterioration in the EuroQol health index (HI) from 90.9 ± 16.9 to 70.9 ± 24.7 (p < 0.001) was observed. The impairment of the five EuroQol domains is: mobility (46.1%), usual activities (44.7%), discomfort/pain (30.7%), psychological domain (27.3%) and self-care (20.3%). The 61.5% suffer a significant decrease in their health index. Multivariate analysis by logistic regression shows us that delirium (OR= 3.01; 95%CI: 1.01-8.9; p= 0.047) and tracheostomy (OR= 2.37; 95%CI: 1.09-5.14; p= 0.029) show association with drop in EuroQoL 5D5L SI. The area under the ROC curve of the model is 67.3%, with a confidence interval between 58% and 76%. The model is calibrated using the Hosmer-Lemeshow test:(χ2=0.468; p=0.792). Only 1.2% of patients showed a score ≤ 24, clearly pathological, on the Folstein's Minimental Test. CONCLUSIONS: delirium and need for tracheostomy are associated with post-intensive care syndrome assessed by EuroQol 5D5L.

Remarkably Low KIR and HLA Diversity in Amerindians Reveals Signatures of Strong Purifying Selection Shaping the Centromeric KIR Region.

The killer-cell immunoglobulin-like receptors (KIR) recognize human leukocyte antigen (HLA) molecules to regulate the cytotoxic and inflammatory responses of natural killer cells. KIR genes are encoded by a rapidly evolving gene family on chromosome 19 and present an unusual variation of presence and absence of genes and high allelic diversity. Although many studies have associated KIR polymorphism with susceptibility to several diseases over the last decades, the high-resolution allele-level haplotypes have only recently started to be described in populations. Here, we use a highly innovative custom next-generation sequencing method that provides a state-of-art characterization of KIR and HLA diversity in 706 individuals from eight unique South American populations: five Amerindian populations from Brazil (three Guarani and two Kaingang); one Amerindian population from Paraguay (Aché); and two urban populations from Southern Brazil (European and Japanese descendants from Curitiba). For the first time, we describe complete high-resolution KIR haplotypes in South American populations, exploring copy number, linkage disequilibrium, and KIR-HLA interactions. We show that all Amerindians analyzed to date exhibit the lowest numbers of KIR-HLA interactions among all described worldwide populations, and that 83-97% of their KIR-HLA interactions rely on a few HLA-C molecules. Using multiple approaches, we found signatures of strong purifying selection on the KIR centromeric region, which codes for the strongest NK cell educator receptors, possibly driven by the limited HLA diversity in these populations. Our study expands the current knowledge of KIR genetic diversity in populations to understand KIR-HLA coevolution and its impact on human health and survival.

An international evaluation of biosecurity management capacity in the seaweed aquaculture industry.

Seaweeds form the second largest global aquaculture product in volume, and despite rapid growth of the sector over the last 25 years, production and quality in top producing regions is becoming increasingly limited due to disease and pest outbreaks, the spread of non-native cultivars and the degradation of genetic health due to inbreeding. Most notably, the lack of biosecurity measures leading to disease and pest outbreaks are reported to cause the most significant production losses in the seaweed industry. This study uses the Knowledge, Attitude and Practice (KAP) survey tool to quantify and compare biosecurity cross-culturally, in two major red seaweed producing countries, the Philippines and Tanzania. Both countries have significantly different political contexts and the seaweed sector sits within two very different value chains. Seaweed-based commodities from these countries, however, enters the same international market for carrageenan, a thickening agent used for a variety of products globally. This study uses the KAP survey tool to assess currently-adopted biosecurity control measures and understand how potential policy strategies could be developed on an international scale. Farmers from both producing countries have good biosecurity knowledge. In Tanzania 64% farmers scored Fair or Good, and in the Philippines this was 95%. Corresponding scores in practices were lower, 85% Poor for Tanzania, and 88% Fair for the Philippines, indicating there is a lack of resources for farmers to implement additional practices. The information gathered using the KAP tool in the context of the global seaweed industry can be used to facilitate compromise between science, policy and practice whilst taking into consideration smaller-scale regional challenges. Given the results from the seaweed industry were similar to that of smallholder agricultural sectors, it is suggested that governmental programs to incentivise biosecurity in smallholder rural agriculture could be adapted for the seaweed industry. This study also demonstrates the potential use of the KAP survey, as a tool to accurately compare biosecurity challenges faced by farmers in different aquaculture sectors globally, and to encourage alignment in international approaches to aquaculture biosecurity policies.

Precision Medicine and Obesity.

The highly variable response to obesity therapies justifies the search for treatment strategies that are best suited to individual patients to enhance their effectiveness and tolerability via precision medicine. Precision medicine development in recent years has been driven by the emergence of powerful methods to characterize patients ("omic" assays). Current available information has revealed that there are numerous intermediary processes that contribute to obesity and have provided a framework for partially comprehending the mechanisms behind the heterogeneity of obesity and its clinical consequences. Some of these processes have or are currently being targeted to individualize obesity therapy with some success.

Precision Medicine for Obesity.

Obesity is a multifactorial disease with a variable and underwhelming weight loss response to current treatment approaches. Precision medicine proposes a new paradigm to improve disease classification based on the premise of human heterogeneity, with the ultimate goal of maximizing treatment effectiveness, tolerability, and safety. Recent advances in high-throughput biochemical assays have contributed to the partial characterization of obesity's pathophysiology, as well as to the understanding of the role that intrinsic and environmental factors, and their interaction, play in its development and progression. These data have led to the development of biological markers that either are being or will be incorporated into strategies to develop personalized lines of treatment for obesity. There are currently many ongoing initiatives aimed at this; however, much needs to be resolved before precision obesity medicine becomes common practice. This review aims to provide a perspective on the currently available data of high-throughput technologies to treat obesity.

Asociación entre penfigoide ampolloso e inhibidores de la dipeptidilpeptidasa-4: estudio de cohortes retrospectivo / Association Between Bullous Pemphigoid and Dipeptidyl Peptidase 4 Inhibitors: A Retrospective Cohort Study

ANTECEDENTES: La asociación entre los inhibidores de la dipeptidil peptidasa 4 (iDPP-4) y el penfigoide ampolloso (PA) se ha demostrado en varios estudios. El objetivo principal de este estudio era estimar el uso del tratamiento con iDPP-4i en pacientes diagnosticados de PA en nuestro entorno. MATERIAL Y MÉTODOS: Seleccionamos pacientes diagnosticados histológicamente de PA en nuestro departamento entre octubre de 2015 y octubre de 2018. Realizamos una revisión retrospectiva para evaluar los datos clínicos-epidemiológicos y los patrones de inmunofluorescencia directa (IFD). RESULTADOS: De los 70 pacientes diagnosticados con PA durante el período de estudio, el 50% eran diabéticos y el 88,57% de ellos estaban siendo tratados con un iDPP-4 en el momento del diagnóstico de PA. El iDPP-4 más frecuente era la linagliptina (utilizada en el 18,6% de los pacientes), seguida de la vildagliptina (el 17,1%). La mediana de tiempo de latencia entre el inicio del tratamiento con iDPP-4 y el diagnóstico de PA fue de 27,5 meses, siendo de 16 meses para la linagliptina y 39 meses para la vildagliptina (log Rank < 0,01). La IFD fue negativaUn resultado negativo de DIF fue significativamente más común en pacientes que no fueron tratados con un DPP-4i. El patrón DIF más fuertemente (y significativamente) asociado con el tratamiento con DPP-4i fueron los depósitos lineales de inmunoglobulina G a lo largo de la unión dermoepidérmica. El tratamiento con DPP-4i se retiró en el 87% de los pacientes y el 96% de ellos logró una respuesta completa. CONCLUSIÓN: El tratamiento con DPP-4i es muy común en pacientes con BP en nuestro entorno. El período de latencia entre el inicio del tratamiento y el inicio de la PA parece ser más corto con linagliptina que con otros tipos de gliptinas. Los pacientes que reciben tratamiento con DPP-4i pueden mostrar patrones DIF diferentes a los que no reciben tratamiento

BACKGROUND: The association between dipeptidyl peptidase 4 inhibitors (DPP-4i) and bullous pemphigoid (BP) has been demonstrated in several studies. The main aim of this study was to estimate the use of DPP-4i treatment in patients diagnosed with BP in our setting. METHODS: We selected patients histologically diagnosed with BP in our department between October 2015 and October 2018 and performed a retrospective chart review to assess clinical and epidemiological data and direct immunofluorescence (DIF) patterns. RESULTS: Of the 70 patients diagnosed with BP during the study period, 50% were diabetic and 88.57% of these were being treated with a DPP-4i when diagnosed with BP. The most common DPP-4i was linagliptin (used in 18.6% of patients), followed by vildagliptin (17.1%). The median latency period between initiation of DPP-4i treatment and diagnosis of BP was 27.5 months for all treatments, 16 months for linagliptin, and 39 months for vildagliptin (log rank < 0.01). A negative DIF result was significantly more common in patients not being treated with a DPP-4i. The DIF pattern most strongly (and significantly) associated with DPP-4i treatment was linear immunoglobulin G deposits along the dermal-epidermal junction. DPP-4i treatment was withdrawn in 87% of patients and 96% of these achieved a complete response. CONCLUSIONS: DPP-4i treatment is very common in patients with BP in our setting. The latency period between start of treatment and onset of BP seems to be shorter with linagliptin than with other types of gliptins. Patients receiving DPP-4i treatment may show different DIF patterns to those not receiving treatment

Autophagy lipidation machinery regulates axonal microtubule dynamics but is dispensable for survival of mammalian neurons.

Neurons maintain axonal homeostasis via employing a unique organization of the microtubule (MT) cytoskeleton, which supports axonal morphology and provides tracks for intracellular transport. Abnormal MT-based trafficking hallmarks the pathology of neurodegenerative diseases, but the exact mechanism regulating MT dynamics in axons remains enigmatic. Here we report on a regulation of MT dynamics by AuTophaGy(ATG)-related proteins, which previously have been linked to the autophagy pathway. We find that ATG proteins required for LC3 lipid conjugation are dispensable for survival of excitatory neurons and instead regulate MT stability via controlling the abundance of the MT-binding protein CLASP2. This function of ATGs is independent of their role in autophagy and requires the active zone protein ELKS1. Our results highlight a non-canonical role of ATG proteins in neurons and suggest that pharmacological activation of autophagy may not only promote the degradation of cytoplasmic material, but also impair axonal integrity via altering MT stability.

Optimal duration of first-line chemotherapy for advanced gastric cancer: data from the AGAMENON registry.

BACKGROUND: The optimal duration of first-line chemotherapy for patients with advanced gastric cancer is unknown. Diverse clinical trials have proposed different strategies including limited treatment, maintenance of some drugs, or treatment until progression. METHOD: The sample comprises patients from the AGAMENON multicenter registry without progression after second evaluation of response. The objective was to explore the optimal duration of first-line chemotherapy. A frailty multi-state model was conducted. RESULTS: 415 patients were divided into three strata: discontinuation of platinum and maintenance with fluoropyrimidine until progression (30%, n = 123), complete treatment withdrawal prior to progression (52%, n = 216), and full treatment until progression (18%, n = 76). The hazard of tumor progression decreased by 19% per month with the full treatment regimen. However, we found no evidence that fluoropyrimidine maintenance (hazard ratio [HR] 1.07, confidence interval [CI] 95%, 0.69-1.65) worsened progression-free survival (PFS) with respect to treatment until progression. Predictive factors for PFS were ECOG performance status, ≥ 3 metastatic sites, prior tumor response, and bone metastases. Toxicity grade 3/4 was more common in those who continued the full treatment until progression vs fluoropyrimidine maintenance (16% vs 6%). CONCLUSION: The longer duration of the full initial regimen exerted a protective effect on the patients of this registry. Platinum discontinuation followed by fluoropyrimidine maintenance yields comparable efficacy to treatment up to PD, with a lower rate of serious adverse events.

Association Between Bullous Pemphigoid and Dipeptidyl Peptidase 4 Inhibitors: A Retrospective Cohort Study. / Asociación entre penfigoide ampolloso e inhibidores de la dipeptidilpeptidasa-4: estudio de cohortes retrospectivo.

BACKGROUND: The association between dipeptidyl peptidase 4 inhibitors (DPP-4i) and bullous pemphigoid (BP) has been demonstrated in several studies. The main aim of this study was to estimate the use of DPP-4i treatment in patients diagnosed with BP in our setting. METHODS: We selected patients histologically diagnosed with BP in our department between October 2015 and October 2018 and performed a retrospective chart review to assess clinical and epidemiological data and direct immunofluorescence (DIF) patterns. RESULTS: Of the 70 patients diagnosed with BP during the study period, 50% were diabetic and 88.57% of these were being treated with a DPP-4i when diagnosed with BP. The most common DPP-4i was linagliptin (used in 18.6% of patients), followed by vildagliptin (17.1%). The median latency period between initiation of DPP-4i treatment and diagnosis of BP was 27.5 months for all treatments, 16 months for linagliptin, and 39 months for vildagliptin (log rank < 0.01). A negative DIF result was significantly more common in patients not being treated with a DPP-4i. The DIF pattern most strongly (and significantly) associated with DPP-4i treatment was linear immunoglobulin G deposits along the dermal-epidermal junction. DPP-4i treatment was withdrawn in 87% of patients and 96% of these achieved a complete response. CONCLUSIONS: DPP-4i treatment is very common in patients with BP in our setting. The latency period between start of treatment and onset of BP seems to be shorter with linagliptin than with other types of gliptins. Patients receiving DPP-4i treatment may show different DIF patterns to those not receiving treatment.