Prognostic value of brain perfusion by MRI in the initial study of high grade gliomas.

OBJECTIVES: To evaluate if the tumour perfusion at the initial MRI scan is a marker of prognosis for survival in patients diagnosed with High Grade Gliomas (HGG). To analyse the risk factors which influence on the mortality from HGG to quantify the overall survival to be expected in patients. PATIENTS AND METHODS: The patients diagnosed with HGG through a MRI scan in a third-level hospital between 2017 and 2019 were selected. Clinical and tumour variables were collected. The survival analysis was used to determine the association between the tumour perfusion and the survival time. The relation between the collected variables and the survival period was assessed through Wald's statistical method, measuring the relationship via Cox's regression model. Finally, the type of relationship that exists between the tumour perfusion and the survival was analysed through the Lineal Regression method.Those statistical analysis were carried out using the software SPSS v.17. RESULTS: 38 patients were included (average age: 61.1 years old). The general average survival period was 20.6 months. A relationship between the tumour perfusion at the MRI scan and the overall survival has been identified, in detail, a group with intratumor values of relative cerebral blood volume (rCBV)>3.0 has shown a significant decline in the average survival period with regard to the average survival period of the group with values <3.0 (14.6 months vs. 22.8 months, p = 0.046). It has also been proved that variables like Karnofsky's scale and the response time since the intervention significantly influence on the survival period. CONCLUSIONS: It has become evident that the tumour perfusion via MRI scan has a prognostic value in the initial analysis of HGG. The average survival period of patients with rCBV less than or equal to 3.0 is significantly higher than those patients whose values are higher, which allows to be more precise with the prognosis of each patient.

Valor pronóstico de la perfusión cerebral por RM en el estudio inicial de los gliomas de alto grado / Prognostic value of brain perfusion by MRI in the initial study of high grade gliomas

Objetivos: Valorar si la perfusión tumoral en el estudio diagnóstico inicial de RM es un marcador pronóstico para la supervivencia en pacientes diagnosticados de gliomas de alto grado. Analizar los factores de riesgo que influyen en la mortalidad por gliomas de alto grado para poder cuantificar la supervivencia global esperada del paciente. Pacientes y métodos: Se seleccionaron las RM de todos los pacientes diagnosticados de glioma de alto grado en un hospital de tercer nivel entre los años 2017 y 2019. Se recogieron variables clínicas y tumorales. Se usó el análisis de supervivencia para determinar la asociación entre la perfusión tumoral y el tiempo de supervivencia. Se estudió la relación entre las variables recogidas y la supervivencia mediante el estadístico de Wald, cuantificando esta relación mediante la regresión de Cox. Por último, se analizó el tipo de relación existente entre la perfusión tumoral y la supervivencia a través del estudio de regresión lineal. Estos análisis estadísticos se realizaron con el software SPSS v.17. Resultados: Se incluyeron 38 pacientes (media de edad 61,1años). La supervivencia media global fue de 20,6meses. Se observó asociación entre la perfusión tumoral en la RM diagnóstica y la supervivencia global, mostrando el grupo con valores intratumorales de volumen sanguíneo cerebral relativo (rVSC) >3,0 una disminución significativa en el tiempo medio de supervivencia respecto al grupo con valores <3,0 (14,6meses vs 22,8meses, p=0,046). También han demostrado influir significativamente en la supervivencia media variables como la escala de Karfnosky y el tiempo de recidiva desde la intervención. Conclusiones: Se ha evidenciado que la perfusión tumoral por RM tiene valor pronóstico en el estudio inicial de los gliomas de alto grado.(AU)

Objectives: To evaluate if the tumour perfusion at the initial MRI scan is a marker of prognosis for survival in patients diagnosed with high grade gliomas (HGG). To analyse the risk factors which influence on the mortality from HGG to quantify the overall survival to be expected in patients. Patients and methods: The patients diagnosed with HGG through a MRI scan in a third-level hospital between 2017 and 2019 were selected. Clinical and tumour variables were collected. The survival analysis was used to determine the association between the tumour perfusion and the survival time. The relation between the collected variables and the survival period was assessed through Wald's statistical method, measuring the relationship via Cox's regression model. Finally, the type of relationship that exists between the tumour perfusion and the survival was analysed through the lineal regression method.Those statistical analysis were carried out using the software SPSS v.17. Results: Thirty-eight patients were included (average age: 61.1years old). The general average survival period was 20.6months. A relationship between the tumour perfusion at the MRI scan and the overall survival has been identified, in detail, a group with intratumor values of relative cerebral blood volume (rCBV) >3.0 has shown a significant decline in the average survival period with regard to the average survival period of the group with values <3.0 (14.6months vs. 22.8months, P=.046). It has also been proved that variables like Karnofsky's scale and the response time since the intervention significantly influence on the survival period. Conclusions: It has become evident that the tumour perfusion via MRI scan has a prognostic value in the initial analysis of HGG. The average survival period of patients with rCBV less than or equal to 3.0 is significantly higher than those patients whose values are higher, which allows to be more precise with the prognosis of each patient.(AU)

Tunable structure of TiO2 deposited by DC magnetron sputtering to adsorb Cr (VI) and Fe (III) from water.

TiO2 thin films with mixtures of the anatase, rutile, and brookite phases were deposited on glass substrates via magnetron sputtering. Based on XRD and Raman results, the TiO2-0.47 and TiO2-3.47 films principally contained the brookite phase, while the TiO2-1.27 and TiO2-2.13 films were primarily anatase. The capacities of the TiO2 films to adsorb heavy metals were tested with Cr(VI) and Fe(III) solutions, and the maximum Cr(VI) and Fe(III) adsorption capacities were realized with the TiO2-0.47 film (334.5 mg/g) and TiO2-3.47 film (271.3 mg/g), respectively. SEM‒EDS results revealed the presence of Cr and Fe on the surfaces of the films, thus corroborating the ability of the TiO2 films to adsorb and remove heavy metals. They are strong candidates for use in wastewater treatment plants.

Ejecución neuropsicológica y carga de enfermedad en sujetos en riesgo de desarrollar enfermedad de Huntington / Neuropsychological performance and disease burden in individuals at risk of developing Huntington disease

Introducción La enfermedad de Huntington (EH) es un trastorno neurodegenerativo y hereditario. Gracias al diagnóstico predictivo se han descrito características clínicas incipientes en la fase prodrómica. Objetivo Comparar la ejecución en tareas cognitivas de portadores (PEH) del gen de la huntingtina y no portadores (NPEH) y observar la variabilidad en la ejecución, dependiendo de la carga de la enfermedad y cercanía a la etapa manifiesta (edad de inicio de los síntomas). Método Los 146 participantes de un Programa de Diagnóstico Predictivo de EH (PDP-EH) fueron divididos en PEH (41,1%) y NPEH (58,9%). Mediante fórmulas matemáticas se obtuvo la carga de enfermedad y cercanía a la etapa manifiesta en el grupo PEH y se correlacionó con la ejecución neuropsicológica. Resultados Se observaron diferencias significativas entre los grupos con las pruebas Mini-Mental State Examination (MMSE), Stroop-B, SDMT y fluidez fonológica. En el grupo PEH se observaron correlaciones entre la carga de enfermedad con la MMSE, Stroop-B y SDMT. El grupo «Cerca» de la etapa manifiesta es el que obtuvo la puntuación más baja en las pruebas MMSE, Stroop-B, Stroop-C, SDMT y fluidez verbal semántica. De acuerdo al MANCOVA, el efecto MMSE evidencia diferencias estadísticamente significativas entre carga de la enfermedad y la cercanía de inicio de los síntomas. Conclusiones Se observa un nivel menor de desempeño en el grupo PEH con probabilidad de inicio cercano de la fase manifiesta en pruebas que evalúan la velocidad de procesamiento y atención. La disfunción cognitiva prefrontal se altera de manera precoz varios años antes del diagnóstico motor de la EH. (AU)

Introduction Huntington disease (HD) is a hereditary neurodegenerative disorder. Thanks to predictive diagnosis, incipient clinical characteristics have been described in the prodromal phase. Objective To compare performance in cognitive tasks of carriers (HDC) and non-carriers (non-HDC) of the huntingtin gene and to analyse the variability in performance as a function of disease burden and proximity to the manifest stage (age of symptom onset). Method A sample of 146 participants in a predictive diagnosis of HD programme were divided into the HDC (41.1%) and non-HDC groups (58.9%). Mathematical formulae were used to calculate disease burden and proximity to the manifest stage in the HDC group; these parameters were correlated with neuropsychological performance. Results Significant differences were observed between groups in performance on the Mini-Mental State Examination (MMSE), Stroop-B, Symbol-Digit Modalities Test (SDMT), and phonological fluency. In the HDC group, correlations were observed between disease burden and performance on the MMSE, Stroop-B, and SDMT. The group of patients close to the manifest stage scored lowest on the MMSE, Stroop-B, Stroop-C, SDMT, and semantic verbal fluency. According to the multivariate analysis of covariance, the MMSE effect shows statistically significant differences in disease burden and proximity to onset of symptoms. Conclusions Members of the HDC group close to the manifest phase performed more poorly on tests assessing information processing speed and attention. Prefrontal cognitive dysfunction appears early, several years before the motor diagnosis of HD. (AU)

Evaluation of the expression of growth hormone and its receptor during the resumption of postpartum ovarian follicle development in dairy cows.

Growth hormone is a key endocrine factor for metabolic adaptations to lactation and optimal reproductive function of the dairy cow. This study aimed to analyze the expression of GH and its receptor (GHR) in ovarian follicles, along with metabolic biomarkers, during the resumption of the postpartum follicular development, and to analyze the immunolocalization and protein expression of GH and GHR in preovulatory follicles. Thirty-six dairy cows were grouped according to the postpartum days (PPD) until the establishment of the first dominant follicle in: cows that established their first dominant follicle at fewer postpartum days (FPPD group; n = 15) and cows that established their first dominant follicle at more postpartum days (MPPD group; n = 22). For a second analysis, the same cows were regrouped according to the calving season (S), into cows calving in autumn (n = 20) and cows calving in winter (n = 17). During the PP, blood and follicular aspirates were obtained at two timepoints (T): when the first dominant follicle was established (T1, day 9 ± 2), and when the preovulatory follicle was established (T2, day 45 ± 2). Also, six dairy cows were ovariectomized in proestrus and ovarian histological sections were obtained. Growth hormone mRNA was detected in granulose cells from ovarian follicle sampled during PP. A PPD × T interaction was observed for GHR mRNA, where it was greater in the FPPD cows than in the MPPD cows at T1. Metabolic biomarkers and reproductive hormones showed differences or interaction between PPD, T, S, depending on the case. Also, GH and GHR were immunolocalized in granulosa and theca interna cells of preovulatory follicles. These results confirm the expression of GH and GHR in the mature ovarian follicles of dairy cows and show a possible association between greater GHR expression and an earlier resumption of postpartum follicular development.

Neuropsychological performance and disease burden in individuals at risk of developing Huntington disease.

INTRODUCTION: Huntington disease (HD) is a hereditary neurodegenerative disorder. Thanks to predictive diagnosis, incipient clinical characteristics have been described in the prodromal phase. OBJECTIVE: To compare performance in cognitive tasks of carriers (HDC) and non-carriers (non-HDC) of the huntingtin gene and to analyse the variability in performance as a function of disease burden and proximity to the manifest stage (age of symptom onset). METHOD: A sample of 146 participants in a predictive diagnosis of HD programme were divided into the HDC (41.1%) and non-HDC groups (58.9%). Mathematical formulae were used to calculate disease burden and proximity to the manifest stage in the HDC group; these parameters were correlated with neuropsychological performance. RESULTS: Significant differences were observed between groups in performance on the Mini-Mental State Examination (MMSE), Stroop-B, Symbol-Digit Modalities Test (SDMT), and phonological fluency. In the HDC group, correlations were observed between disease burden and performance on the MMSE, Stroop-B, and SDMT. The group of patients close to the manifest stage scored lowest on the MMSE, Stroop-B, Stroop-C, SDMT, and semantic verbal fluency. According to the multivariate analysis of covariance, the MMSE effect shows statistically significant differences in disease burden and proximity to onset of symptoms. CONCLUSIONS: Members of the HDC group close to the manifest phase performed more poorly on tests assessing information processing speed and attention. Prefrontal cognitive dysfunction appears early, several years before the motor diagnosis of HD.

Consideraciones anestésicas en el manejo perioperatorio del paciente con síndrome de Jarcho-Levin / Anesthetic considerations in the perioperative management of the patient with Jarcho-Levin syndrome

El síndrome de Jarcho-Levin es un epónimo usado para describir un espectro de displasias esqueléticas de tórax pequeño con el compromiso variable de vertebras y costillas. Inicialmente considerado letal, actualmente es compatible con la vida en sus presentaciones más leves. Las alteraciones óseas que conllevan un patrón respiratorio restrictivo, las infecciones respiratorias de repetición y el fenotipo particular pueden dificultar el manejo anestésico perioperatorio. Es de especial interés la adecuada valoración de la vía aérea por presentar predictores de vía aérea difícil, así como la prevención, el diagnóstico precoz y el tratamiento adecuado de la insuficiencia respiratoria. Presentamos el caso de un paciente con síndrome de Jarcho-Levin intervenido de distracción vertebral, con sus implicaciones más destacables en el manejo anestésico.(AU)

Jarcho-Levin syndrome is an eponym used to describe a spectrum of small thoracic skeletal dysplasias with variable involvement of vertebrae and ribs. Initially considered lethal, it is currently compatible with life in its mildest forms. Bone alterations that lead to a restrictive respiratory pattern, recurrent respiratory infections and particular phenotype can make perioperative anesthetic management difficult. The proper assessment of the airway is of special interest because it presents predictors of a difficult airway, as well as the prevention, early diagnosis and adequate treatment of respiratory failure. We present the case of a patient with Jarcho-Levin syndrome who underwent vertebral distraction surgery, with its most notable implications in anesthetic management.(AU)

Anesthetic considerations in the perioperative management of the patient with Jarcho-Levin Syndrome.

Jarcho-Levin syndrome is an eponym used to describe a spectrum of small thoracic skeletal dysplasias with variable involvement of vertebrae and ribs. Initially considered lethal, it is currently compatible with life in its mildest forms. Bone alterations that lead to a restrictive respiratory pattern, recurrent respiratory infections and particular phenotype, can make perioperative anesthetic management difficult. The proper assessment of the airway is of special interest because it presents predictors of a difficult airway, as well as the prevention, early diagnosis and adequate treatment of respiratory failure. We present the case of a patient with Jarcho-Levin Syndrome who underwent vertebral distraction surgery, with its most notable implications in anesthetic management.

The influence of Amazon River connectivity to littoral meanders on long-term carbon accumulation: A case study of Lake Yahuarcaca.

The objective of this investigation is to evaluate the recent changes in the accumulation of organic matter and carbon on the Yahuarcaca lake system, by means of a multiproxy paleolimnological study. The methodology based on lithological descriptions of 210Pb/137Cs-dated cores allowed us to infer the centennial sedimentation processes and carbon accumulation rates. Sedimentary facies, grain size, magnetic susceptibility, loss on ignition, carbonate, chlorophyll derivatives, stable isotopes of δ13C/δ15N, and carbon accumulation rate were analyzed. LANDSAT and photographic record of satellite images were used to reconstruct the historical geomorphological evolution of the Lake. Sediment cores yielded basal ages of 1827 and 1828 Common Era, representing the formation of lakes as a consequence of the Amazon meandering process. Two main paleolimnological stages were identified, with a boundary transition set at 1980-1984 Common Era, attributed to the geomorphological closure and complete lake separation from the Amazon and the onset of full lentic conditions. This inference was mainly based on both sharp increases in the sedimentation rate from 0.2 to >1 cm yr-1 and carbon accumulation that increased seven-fold (from 2 to 14 g m-2 yr-1) from 1980 to 1984 Common Era. The flood-pulse and connection to the Amazon defined the magnitude of organic inputs, where areas more distant/isolated from the river showed higher accumulation of carbon from autochthonous production, with an average of 8.9 % and 1.10 g m-2 yr-1 (carbon accumulation rate). Those areas closer and connected to the river were strongly related to the interannual hydrological variability, with a lower mean carbon content (5.9 %) and 0.73 g m-2 yr-1 (carbon accumulation rate). We concluded that carbon burial was highest within the most distant spot from the Amazon River because of the weaker connection to the river itself and the more stable lentic conditions for net sedimentation.

Gaussian and Gaussian-pulsed-like Fermi velocity graphene structures.

Gaussian and Gaussian-related structures are quite attractive due to its versatility to modulate the electronic transport, including its possibility as electron filters. Here, we show that these non-conventional profiles are not the exception when dealing with Fermi velocity barriers in monolayer graphene. In particular, we show that Gaussian Fermi velocity graphene barriers (G-FVGBs) and Gaussian-pulsed-like Fermi velocity graphene superlattices (GPL-FVGSLs) can serve as electron band-pass filters and oscillating conductance structures. We reach this conclusion by theoretically studying the transmission and transport properties of the mentioned structures. The study is based on the continuum model, the transfer matrix method and the Landauer-Büttiker formalism. We find nearly flat transmission bands or pass bands for G-FVGBs modulable through the system parameters. The pass bands improve as the maximum ratio of Fermi velocities (ξmax) increases, however its omnidirectional range is reduced. These characteristics result in a decaying conductance (integrated transmission) withξmax. The integrated transmission remains practically unaltered with the size of the system due to the saturation of the electron pass band filtering. In the case of GPL-FVGSLs the GPL profile results in regions of high transmission probability that can merge as flat transmission minibands if the pulse fraction and the superlattice parameters are appropriately tuned. The GPL profile also results in conductance (integrated transmission) oscillations that can be multiplied or reduced in number by adjusting the pulse fraction as well as the superlattice parameters.

Association of glucocorticoid receptor expression with key members of the insulin signaling pathway and heat shock proteins in the bovine ovary.

Glucocorticoids (GCs) act through their receptor (GR) as regulators in different biological processes such as reproduction. In the absence of GCs, the GR remains inactive in the cytoplasm by associating with heat shock proteins (HSPs), which act as molecular chaperones, among which the most relevant are HSP90 and HSP70. Cytoplasmic GC-activated GR mediates non-genomic effects, interacting with members of signaling pathways such as PI3K/Akt, which participates in several metabolic processes, including the insulin signaling pathway. The aim of the present study was to evaluate possible associations between the cytoplasmic GR and the main intermediates of the insulin signaling pathway and HSP90 and HSP70 in ovaries of dairy cows. To this end, the protein expression of cytoplasmic GR, key members of the insulin signaling pathway, and HSPs was evaluated in ovarian preovulatory follicles of non-lactating Holstein cows in proestrus. Positive associations were observed between protein expression of GR and HSP90, IRS1, pIRS1, PI3K and pAkt (p < 0.05; ß > 0) in granulosa cells of dominant follicles of dairy cows. Instead, in theca cells, no associations were observed between protein expression of GR and members of the insulin signaling pathway or HSPs. These data provide evidence of the possible association between the non-genomic mechanisms of action of the GR and the insulin signaling pathway in the bovine ovary.

Recomendaciones para la coordinación de los servicios de Neurología y Neurorradiología en la atención a pacientes con esclerosis múltiple / Recommendations for the coordination of Neurology and Neuroradiology Departments in the management of patients with multiple sclerosis

Introducción: El uso de la resonancia magnética (RM) está ampliamente extendido en el diagnóstico y el seguimiento de los pacientes con esclerosis múltiple (EM). La coordinación entre los servicios de Neurología y Neurorradiología es clave para la realización e interpretación de estudios radiológicos de la manera más eficaz posible. Sin embargo, esta coordinación es susceptible de mejoras en una gran parte de los hospitales nacionales. Métodos: Un panel de 17 neurólogos y neurorradiólogos de 8 hospitales españoles, presencialmente y a través de comunicación online, consensuaron una guía de buenas prácticas en la coordinación en EM. La guía se estableció en 4 fases: 1) definición del alcance de la guía y metodología del estudio; 2) revisión bibliográfica sobre buenas prácticas o recomendaciones en el uso de la RM en EM; 3) discusión y búsqueda de consenso entre los expertos; y 4) formalización y validación de los contenidos para elaborar el documento de consenso. Resultados: Se consensuaron un total de 9 recomendaciones dirigidas a la mejora de la coordinación entre los servicios de Neurología y Neurorradiología, que se pueden resumir en: 1) estandarizar las solicitudes de RM, informes y planificación; 2) crear protocolos compartidos para los estudios de RM; 3) establecer comités multidisciplinares y sesiones de coordinación, y 4) generar canales de comunicación formales entre los profesionales de ambos departamentos. Conclusiones: Se espera que las recomendaciones consensuadas sirvan de guía para optimizar la coordinación entre neurólogos y neurorradiólogos y que repercutan en la mejora del diagnóstico y seguimiento de los pacientes con EM.(AU)

Introduction: Magnetic resonance imaging (MRI) is widely used for the diagnosis and follow-up of patients with multiple sclerosis (MS). Coordination between Neurology and Neuroradiology departments is crucial for performing and interpreting radiological studies as efficiently and as accurately as possible. However, improvements can be made in the communication between these departments in many Spanish hospitals. Methods: A panel of 17 neurologists and neuroradiologists from 8 Spanish hospitals held in-person and online meetings to draft a series of good practice guidelines for the coordinated management of MS. The drafting process included 4 phases: 1) establishing the scope of the guidelines and the methodology of the study; 2) literature review on good practices or recommendations on the use of MRI in MS; 3) discussion and consensus between experts; and 4) validation of the contents. Results: The expert panel agreed a total of 9 recommendations for improving coordination between neurology and neuroradiology departments. The recommendations revolve around 4 main pillars: 1) standardising the process for requesting and scheduling MRI studies and reports; 2) designing common protocols for MRI studies; 3) establishing multidisciplinary committees and coordination meetings; and 4) creating formal communication channels between both departments. Conclusions: These consensus recommendations are intended to optimise coordination between neurologists and neuroradiologists, with the ultimate goal of improving the diagnosis and follow-up of patients with MS.(AU)

Environmental vs psychosocial barriers to active commuting to university: which matters more?

OBJECTIVES: The aims of this study were (1) to examine the differences in the mode of commuting and barriers to active commuting to university between the sexes (men and women) and in different countries (Chile and Spain); and (2) to analyse the association between the mode of commuting and the perceived barriers for male and female university students in Chile and Spain. STUDY DESIGN: This cross-sectional study took place between April 2017 and May 2018 in Chile and Spain. METHODS: The study population included 2269 university students (53.0% women). The mode of commuting and barriers to active commuting to university were assessed by a self-reported questionnaire. Multinomial logistic regression analysis was used to examine the associations. RESULTS: In both sexes, public and private transport were the main modes of commuting used in Chile and Spain, respectively, followed by active commuting in all participants, except for female students in Spain. Women perceived more environmental and psychosocial barriers compared to men (Chile: P < 0.001; Spain: P = 0.006). Perceived environmental barriers showed higher significant differences between students in Chile and Spain (P < 0.05). Private commuters reported a larger proportion of psychosocial barriers compared to active commuters (Chile: men P = 0.001, women P < 0.001; Spain: men P < 0.001, women P = 0.036). CONCLUSIONS: The study findings suggest that the mode of commuting and the barriers to active commuting to university may be influenced by sex and country.

Percutaneous transhepatic cholangioscopy for benign and malignant biliary disease using a novel short single-operator cholangioscope.

BACKGROUND: The length of conventional single-use cholangioscopes poses a challenge for percutaneous or laparoscopic approaches for direct visualization of the biliary tract. The aim of this retrospective observational clinical study was to assess the use of a dedicated percutaneous short single-operator cholangioscope (PSSOC) for diagnosis and treatment of benign or malignant biliary diseases. METHODS: Retrospective analysis of a prospectively maintained database including all consecutive patients undergoing percutaneous transhepatic cholangioscopy with the PSSOC between 06/2021 and 01/2023. RESULTS: Forty patients were included (22F/18 M, age 58.7 ± 16.7 years). The diagnostic and therapeutic management plan was based on procedural findings. Indications were bile duct obstruction associated with complex anatomy (n = 13), choledocholithiasis (n = 11), suspected malignant stenosis of the biliary tract (n = 11), biliary stent placement (n = 2) and removal (n = 1), and failed endoscopic retrograde cholangiopancreatography (n = 2). The cholangioscopies were diagnostic (n = 5), therapeutic (n = 20) or both simultaneously (n = 15). The most frequent procedures were electrohydraulic lithotripsy (n = 25) and biopsy sampling (n = 12). Complications occurred in 7 cases (17.5%), including cholangitis (n = 4, B2), pleural perforation (n = 1, B2), portal bleeding (n = 1, B3), and Tako-Tsubo syndrome (n = 1, B3), classified according to the Society of Interventional Radiology classification. Intraprocedural visual diagnosis was confirmed by the histopathologic result in 11/12 patients in which biopsies were performed (91.7%). PSSOC was relevant to avoid surgery in 2 patients (5%) with indeterminate strictures, allowing to rule out malignancy and treat the lithiasis. CONCLUSIONS: Direct visualization of the biliary tract enabled targeted biopsies for histopathological diagnosis. The visual and histopathological diagnoses were concordant in all but one case. Percutaneous cholangioscopy with a dedicated PSSOC allows to optimize identification and treatment of complex biliary disease including biliary lithiasis while assessing bile duct patency. The clinical use of the novel PSSOC system was safe and effective and could prevent surgical exploration in select patients.

Genomic instability in long-term culture of human adipose-derived mesenchymal stromal cells.

Mesenchymal stromal/stem cells stem (MSC) have been widely studied due to their great potential for application in tissue engineering and regenerative and translational medicine. In MSC-based therapy for human diseases, cell proliferation is required to obtain a large and adequate number of cells to ensure therapeutic efficacy. During in vitro culture, cells are under an artificial environment and manipulative stress that can affect genetic stability. Several regulatory agencies have established guidelines to ensure greater safety in cell-based regenerative and translational medicine, but there is no specific definition about the maximum number of passages that ensure the lowest possible risk in MSC-based regenerative medicine. In this context, the aim of this study was to analyze DNA damage and chromosome alterations in adipose-derived mesenchymal stromal cells (ADMSC) until the eleventh passage and to provide additional subsidies to regulatory agencies related to number of passages in these cells. Thus, two methods in genetic toxicology were adopted: comet assay and micronucleus test. The comet assay results showed an increase in DNA damage from the fifth passage onwards. The micronucleus test showed a statistically significant increase of micronucleus from the seventh passage onwards, indicating a possible mutagenic effect associated with the increase in the number of passages. Based on these results, it is important to emphasize the need to assess genetic toxicology and inclusion of new guidelines by regulatory agencies to guarantee the safety of MSC-based therapies for human diseases.

Association between prehospital lactate categories with short- and long-term mortality: a prospective, observational multicenter study.

BACKGROUND: Lactate is an already recognized biomarker for short-term mortality in emergency medical services (EMS). However, how different levels of lactate are associated with short-, mid- and long-term outcomes should be unveiled. AIM: To determine how different categories of hyperlactatemia are associated with mortality. We also aim to clinically characterize hyperlactatemia groups. DESIGN: A multicenter, prospective, observational study performed between January 2019 and February 2022, considering 48 basic life support units and 5 advanced life support units referring to 4 tertiary care hospitals (Spain). Patients were recruited from phone requests for emergency assistance in adults, evacuated to emergency departments. The primary outcome was in-hospital mortality from any cause within the first to the 365-day period following EMS attendance. The main measures were demographical and biochemical variables, prehospital advanced life support techniques used and patient condition categorized in 24 diseases. METHODS: Univariate and Cox regression analysis. RESULTS: A total of 5072 participants fulfilled inclusion criteria. Group #1 (non-hyperlactatemia) was composed of 2389 subjects (47.1%), Group #2 (mild hyperlactatemia) of 1834 (36.1%), Group #3 (hyperlactatemia) of 333 (6.6%) and, finally, Group #4 (severe hyperlactatemia) of 516 (10.2%). The 1-day mortality was 0.2%, 1.1%, 9% and 22.3% in the four lactate groups, respectively. Long-term mortality (365 days) was 10.2%, 22.7%, 38.7% and 46.7% in the four lactate groups, respectively. Differences between patients' conditions of lactatemia groups were also found. CONCLUSIONS: Our results demonstrated that prehospital lactate categories were associated with short- and long-term outcomes in a different manner. These results will allow EMS to establish different risk states according to the prehospital lactate categories.

IL1R1+ cancer-associated fibroblasts drive tumor development and immunosuppression in colorectal cancer.

Fibroblasts have a considerable functional and molecular heterogeneity and can play various roles in the tumor microenvironment. Here we identify a pro-tumorigenic IL1R1+, IL-1-high-signaling subtype of fibroblasts, using multiple colorectal cancer (CRC) patient single cell sequencing datasets. This subtype of fibroblasts is linked to T cell and macrophage suppression and leads to increased cancer cell growth in 3D co-culture assays. Furthermore, both a fibroblast-specific IL1R1 knockout and IL-1 receptor antagonist Anakinra administration reduce tumor growth in vivo. This is accompanied by reduced intratumoral Th17 cell infiltration. Accordingly, CRC patients who present with IL1R1-expressing cancer-associated-fibroblasts (CAFs), also display elevated levels of immune exhaustion markers, as well as an increased Th17 score and an overall worse survival. Altogether, this study underlines the therapeutic value of targeting IL1R1-expressing CAFs in the context of CRC.