Position paper on retinal arterial occlusion. SEMI-SERV.

The retina is an organ frequently affected by ischemic changes. Retinal arterial occlusion can be considered the equivalent of stroke, in terms of presentation, management and treatment. In addition to a specific ophthalmological treatment systemic management is essential with an appropriate study and control of cardiovascular risk factors considering these patients of a very high cardiovascular risk. In this consensus document we aim to provide an update on this relatively frequent pathology in our practices, considering the importance of an early and systematic action.

Analysis of intra-fractional positioning correction performed by cone beam computed tomography in SBRT treatments.

PURPOSE: This study aims to evaluate the positioning correction extracted from Intra-fraction Cone Beam (IF-CBCT) images obtained during Stereotactic Body Radiotherapy (SBRT) treatments, and to assess whether its magnitude justifies its acquisition. In addition, the results obtained in lung, liver, and pancreas SBRTs with two deep inspiration breath-hold systems (DIBH), and for prostate with/without ultrasound (US) monitoring were compared. METHODS: 1449 treatments, performed with two linear accelerators (LINACs) were retrospectively analyzed. DIBH were performed either with a spirometry-based device or a surface-guidance system and one LINAC was equipped with US monitoring system for prostate. Significance tests were used to account for differences between units. RESULTS: Group systematic error (M) was approximately -0.7 mm for DIBH treatments in superior-inferior (SI) direction with no difference (p > 0.7) between LINACs. Moreover, there was a SI difference of 0.5 mm for prostate treatments (p = 0.008), in favor of the US monitored one. In anterior-posterior (AP) direction, only liver treatments exhibited differences between LINACs, with the spirometer-based system being 0.8 mm inferior (p = 0.003). M<0.4 mm in left-right (LR) direction was found for all locations and LINACs. The spirometer-based system resulted in lower standard deviation of systematic and random errors in most components and locations, with a greater effect observed in liver SBRTs. CONCLUSIONS: The corrections made with IF-CBCT during SBRT treatments were not negligible. Both DIBH systems were effective in managing respiratory movements. However, the spirometry-based system was slightly more accurate. In addition, US monitoring of the prostate appeared to be useful in reducing target shift.

Different Mutational Profiles of Subcutaneous Panniculitis-like T-cell Lymphoma and Lupus Panniculitis: An Additional Case Series.

BACKGROUND: Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare cytotoxic T-cell lymphoma with indolent behavior, mostly present in women and associated with immunological diseases whose pathogenic background is still poorly understood. SPTCL is associated with lupus erythematosus panniculitis (LEP) and histologically misdiagnosed. OBJECTIVES: The aim of our study was to identify mutations affecting the pathogenesis of both SPTCL and LEP. MATERIALS AND METHODS: We studied a total of 10 SPTCL and 10 LEP patients using targeted next-generation sequencing and pyrosequencing. Differences in gene expression between molecular subgroups were investigated using NanoString technology. Clinical data were collected, and correlations sought with the molecular data obtained. RESULTS: The mutational profile of SPTCL and LEP is different. We identified fewer pathogenic mutations than previously reported in SPTCL, noting a single HAVCR2-mutated SPTCL case. Interestingly, 40% of our SPTCL cases showed the pathogenic TP53 (p.Pro72Arg) (P72R) variant. Although cases showing HAVCR2 mutations or the TP53 (P72R) variant had more severe symptomatic disease, none developed hemophagocytic syndrome (HPS). Furthermore, TP53 (P72R)-positive cases were characterized by a lower metabolic signaling pathway and higher levels of CD28 expression and Treg signaling genes. In addition, 30% of our cases featured the same mutation (T735C) of the epigenetic modificatory gene DNMT3A. None of the LEP cases showed mutations in any of the studied genes. CONCLUSIONS: The mutational landscape of SPTCL is broader than previously anticipated. We describe, for the first time, the involvement of the TP53 (P72R) pathogenic variant in this subgroup of tumors, consider the possible role of different genetic backgrounds in the development of SPTCL, and conclude that LEP does not follow the same pathogenic pathway as SPTCL.

Insights on kraft lignin degradation in an anaerobic environment.

Lignin is an aromatic macromolecule and one of the main constituents of lignocellulosic materials. Kraft lignin is generated as a residual by-product of the lignocellulosic biomass industrial process, and it might be used as a feedstock to generate low molecular weight aromatic compounds. In this study, we seek to understand and explore the potential of ruminal bacteria in the degradation of kraft lignin. We established two consortia, KLY and KL, which demonstrated significant lignin-degrading capabilities. Both consortia reached maximum growth after two days, with KLY showing a higher growth and decolorization rate. Additionally, SEM analysis revealed morphological changes in the residual lignin from both consortia, indicating significant degradation. This was further supported by FTIR spectra, which showed new bands corresponding to the C-H vibrations of guaiacyl and syringyl units, suggesting structural transformations of the lignin. Taxonomic analysis showed enrichment of the microbial community with members of the Dickeya genus. Seven metabolic pathways related to lignin metabolism were predicted for the established consortia. Both consortia were capable of consuming aromatic compounds such as 4-hydroxybenzoic acid, syringaldehyde, acetovanillone, and syringic acid, highlighting their capacity to convert aromatic compounds into commercially valuable molecules presenting antifungal activity and used as food preservatives as 4-hydroxyphenylacetic, 3-phenylacetic, and phenylacetic acids. Therefore, the microbial consortia shown in the present work are models for understanding the process of lignin degradation and consumption in bacterial anaerobic communities and developing biological processes to add value to industrial processes based on lignocellulosic biomass as feedstock.

[National competitive bidding analysis of osteosynthesis materials in pediatric patients with femur fractures]. / Análisis de licitación pública nacional de materiales de osteosíntesis en los pacientes pediátricos con fracturas de fémur.

INTRODUCTION: health promotion policy requires the identification of barriers to the adoption of public policies. Paraguay's national healthcare system is inequitable, expensive, and inefficient. The Ministry of Public Health and Social Welfare (MSPyBS) is the entity responsible for covering the needs of a significant portion of the population. In January 2022, the MSPyBS financed the purchase of titanium elastic nails through a National Public Tender for Osteosynthesis Materials (LPN 02/22) to provide them for free in the pediatric service. Using research as a tool, we seek to analyze the impact of the implementation of LPN 02/22 at the Trauma Hospital, believing that this action would help streamline administrative and bureaucratic processes, making them more efficient with the assistance of the hospital's human resources. MATERIAL AND METHODS: a retrospective, analytical, and comparative study conducted at a high-complexity trauma center in Asunción, Paraguay. Patients aged 4 to 14 years with an indication for stabilization with elastic nails were included. Demographic data, the mechanism of injury, time elapsed from hospital arrival to surgical treatment, length of hospital stay, and the average hospital cost were analyzed based on the daily expense of pediatric patient hospitalization. RESULTS: 52 patients, divided into 25 cases in 2021 before implementation and 27 cases after implementation. The time elapsed from hospital arrival to definitive treatment was six days in the pre-implementation period, with an average stay from admission to discharge of 7.4 days. After implementation, the time from hospital arrival to definitive treatment was 4.3 days, and the average discharge time for the Post group was six days. The potential savings per patient amount to 332 dollars, offset by the institution's implant supply cost of 197 dollars, resulting in an approximate savings of 135 dollars per patient for the ministry. CONCLUSIONS: we view the implementation of free titanium elastic nails for pediatric femur fracture patients positively. We encourage the institution to continue with similar policies and strive to achieve even greater benefits for users.

INTRODUCCIÓN: la política de promoción de la salud requiere la identificación de los obstáculos para la adopción de políticas públicas. El sistema nacional de salud de Paraguay es inequitativo, caro e ineficiente. El Ministerio de Salud Pública y Bienestar Social (MSPyBS) es el ente que cubre las necesidades de gran parte de la población. El MSPyBS en Enero del 2022 financió, mediante la Licitación Pública Nacional de Materiales de Osteosíntesis (LPN 02/22), la compra de clavos elásticos de titanio para disponer de su uso gratuito en el Servicio de Pediatría; usando a la investigación como herramienta, buscamos analizar el impacto de la implementación de la LPN 02/22 en el Hospital de Trauma, creyendo que esta acción ayudaría a dinamizar los procesos administrativos y burocráticos, haciéndolos más eficientes con la ayuda de los recursos humanos del hospital. MATERIAL Y MÉTODOS: estudio retrospectivo, analítico y comparativo, realizado en un centro de trauma de alta complejidad de Asunción, Paraguay. Fueron incluidos los pacientes con edad comprendidas entre cuatro y 14 años, con indicación de estabilización con clavos elásticos. Se analizaron los datos demográficos, el mecanismo de trauma, el tiempo transcurrido desde la llegada al hospital hasta el tratamiento quirúrgico, así como el tiempo de estadía hospitalaria. Se evaluó el costo hospitalario promedio, basados en el gasto diario de la internación de un paciente pediátrico. RESULTADOS: cincuenta y dos pacientes, separados en 25 casos en el 2021 previo a la implementación y 27 casos posterior a la implementación. El tiempo transcurrido desde la llegada al hospital hasta el tratamiento definitivo fue de seis días para la etapa previa a la implementación; el promedio desde el ingreso hasta el alta fue de 7.4 días. Desde la implementación se tuvo un transcurso de 4.3 días desde la llegada al hospital hasta el tratamiento definitivo. El egreso del grupo Post tuvo un promedio de seis días. El ahorro probable en relación con cada paciente es de 332 dólares; a esto debemos contrarrestar el monto que paga la institución para la provisión del implante (197 dólares), por lo que el ahorro del ministerio sería de aproximadamente 135 dólares por cada paciente. CONCLUSIONES: vemos como positiva la implementación de la gratuidad de los clavos elásticos de titanio en los pacientes en edad pediátrica con fractura de fémur. Alentamos a la institución a seguir con políticas similares y tratar de lograr mayores beneficios para los usuarios.

[Comorbidities in multiple sclerosis and their influence on the choice of treatment]. / Comorbilidades en la esclerosis múltiple y su influencia en la elección del tratamiento.

Clinical trials of disease-modifying therapies (DMTs) for people with multiple sclerosis (pMS) are conducted in selected populations, excluding patients with comorbidities or concomitant medications. However, a large percentage of pMS have some additional disease, which could affect the response and choice of the DMT. The objective of this review is to assess how concurrent pathologies can impact the choice of DMTs. Relevant articles were selected through a systematic search in PubMed. Comorbidities were grouped for better classification into autoimmune, chronic infections, cardiovascular and metabolic, oncological and neuropsychiatric. In autoimmune pathologies, it is key to take into account the effects of TME on them and the possibility of interaction with their specific treatments. Immunomodulatory therapies are safe for people with chronic infections. Immunosuppressive treatments are generally contraindicated in people with active infections. In cardiovascular and metabolic comorbidities, infusion reactions associated with monoclonal antibodies, and the phenomena of starting treatment with S1P modulators, must be taken into account. DMTs with an immunosuppressive effect are contraindicated in people with active malignancies. Although psychiatric pathology per se does not preclude the use of DMTs, caution should be exercised when new psychiatric symptoms appear. For these reasons, among the multiple factors that must be considered when starting or changing a DMT in pMS, comorbidities constitute a decisive element.

TITLE: Comorbilidades en la esclerosis múltiple y su influencia en la elección del tratamiento.Los estudios clínicos de tratamientos para personas con esclerosis múltiple (pEM) se realizan en poblaciones seleccionadas, que excluyen a pacientes que presenten comorbilidades o medicaciones concomitantes. Sin embargo, un gran porcentaje de las pEM tiene alguna enfermedad adicional, que podría afectar a la respuesta y la elección del tratamiento. El objetivo de esta revisión es valorar cómo pueden las diferentes patologías concurrentes impactar en la elección de las terapias modificadoras de la enfermedad (TME) en las pEM. Se seleccionaron artículos relevantes mediante búsqueda en PubMed. Las comorbilidades se agruparon, a los fines de mejor ordenamiento de los artículos encontrados, en patologías diversas: autoinmunes, infecciones crónicas, cardiovasculares, respiratorias, metabólicas, oncológicas, neuropsiquiátricas y epilepsia. En cuanto a las patologías autoinmunes, es clave tener en cuenta los efectos de las TME sobre ellas y la posibilidad de interacción con sus tratamientos específicos. Las terapias inmunomoduladoras son seguras para personas con infecciones crónicas. Los tratamientos inmunosupresores, en general, están contraindicados en personas con infecciones activas. En las comorbilidades cardiovasculares y metabólicas deben tenerse en cuenta las potenciales reacciones de infusión asociadas a anticuerpos monoclonales, y los fenómenos asociados al inicio de tratamiento con moduladores del receptor de la esfingosina-1-fosfato. Las TME con efecto inmunosupresor están contraindicadas en personas con malignidades activas. Aunque la patología psiquiátrica de por sí no impide el uso de TME, debería tenerse precaución cuando aparecen nuevos síntomas psiquiátricos, y siempre tenerse en cuenta su monitorización y tratamiento. Por este motivo, entre los múltiples factores que deben considerarse a la hora de iniciar o cambiar una TME en pEM, las comorbilidades constituyen un elemento muchas veces decisivo.

[Core data set for real world data in multiple sclerosis: customization for latin america from a global task force recommendation]. / Core data set para la generación de datos de la vida real en esclerosis múltiple: adaptación de una iniciativa global para América Latina.

INTRODUCTION: The primary objective of the core data set is to reduce heterogeneity and promote harmonization among data sources in EM, thereby reducing the time needed to execute real life data collection efforts. Recently, a group led by the Multiple Sclerosis Data Alliance has developed a core data set for collecting real-world data on multiple sclerosis (MS) globally. Our objective was to adapt this global data set to the needs of Latin America, so that it can be implemented by the registries already developed and in the process of development in the region. MATERIAL AND METHODS: A working group was formed regionally, the core data set created globally was adapted (translation process into Spanish, incorporation of regional variables and consensus on variables to be used). Consensus was obtained through the remote Delphi methodology of a round of questionnaires and remote discussion of the core data set variables. RESULTS: A total of 25 professionals from Latin America carried out the adaptation process between November 2022 and July 2023. Agreement was established on a core data set of nine categories and 45 variables, version 2023 to suggest its implementation in developed or developing registries, and MS cohorts in the region. CONCLUSION: The core data set seeks to harmonize the variables collected by registries and cohorts in MS in Latin America in order to facilitate said collection and allow collaboration between sources. Its implementation will facilitate real life data collection and collaboration in the region.

TITLE: Core data set para la generación de datos de la vida real en esclerosis múltiple: adaptación de una iniciativa global para América Latina.Introducción. Los objetivos primarios del core data set son reducir la heterogeneidad y promover la armonización entre las fuentes de datos en la esclerosis múltiple (EM), reduciendo así el tiempo necesario para ejecutar esfuerzos en la recolección de datos de vida real. Recientemente, un grupo liderado por la Multiple Sclerosis Data Alliance ha desarrollado un core data set para la recolección de datos del mundo real en EM a nivel global. Nuestro objetivo ha sido adaptar y consensuar este conjunto de datos globales a las necesidades de América Latina para que pueda ser implementado por los registros ya desarrollados y en proceso de desarrollo en la región. Material y métodos. Se conformó un grupo de trabajo regionalmente y se adaptó el core data set creado globalmente (proceso de traducción al español, incorporación de variables regionales y consenso sobre variables que se iban a utilizar). El consenso se obtuvo a través de la metodología Delphi remoto de ronda de cuestionarios y discusión a distancia de las variables del core data set. Resultados. Veinticinco profesionales de América Latina llevaron adelante el proceso de adaptación entre noviembre de 2022 y julio de 2023. Se estableció un acuerdo sobre un core data set de nueve categorías y 45 variables, versión 2023, con la sugerencia de implementarlo en registros desarrollados o en vías de desarrollo y cohortes de EM en la región. Conclusión. El core data set busca armonizar las variables recolectadas por los registros y las cohortes de EM en América Latina con el fin de facilitar dicha recolección y permitir una colaboración entre fuentes. Su implementación facilitará la recolección de datos de vida real y la colaboración en la región.

Presence of Epstein-Barr virus (EBV) antigens detected by sensitive methods has no influence on local immune environment in diffuse large B cell lymphoma.

EBV+ diffuse large B cell lymphoma (DLBCL) not otherwise specified (NOS) is a new entity confirmed by the World Health Organization (WHO) in 2017. In this new entity, the virus may contribute to a tolerogenic microenvironment. Traces of the virus have been described in DLBCL with more sensitive methods, in cases that were originally diagnosed as negative. The aim of this study was to analyze the expression of immune response genes in the tumor microenvironment to disclose the role of the virus and its traces in DLBCL. In 48 DLBCL cases, the expression of immune response genes and the presence of molecules that induce tolerance, such as TIM3, LAG3 and PDL1 by immunohistochemistry (IHC), were studied. To broaden the study of the microenvironment, tumor-associated macrophages (TMAs) were also explored. No significant differences were observed in the expression of immune response genes in the EBV+ DLBCL and those cases that were EBV- DLBCL but that exhibited viral traces, assessed by ViewRNA assay. Only the EBV+ DLBCL cases displayed a significantly higher increase in the expression of CD8 and cytotoxic T cells detected by gene expression analysis, and of PDL1 in tumor cells and in the expression of CD68 in the tumor microenvironment detected by IHC, not observed in those cases with viral traces. The increase in CD8 and cytotoxic T cells, PDL1 and CD68 markers only in EBV+ DLBCL may indicate that traces of viral infection might not have influence in immune response markers.

Validation of machine-learning model for first-trimester prediction of pre-eclampsia using cohort from PREVAL study.

OBJECTIVE: Effective first-trimester screening for pre-eclampsia (PE) can be achieved using a competing-risks model that combines risk factors from the maternal history with multiples of the median (MoM) values of biomarkers. A new model using artificial intelligence through machine-learning methods has been shown to achieve similar screening performance without the need for conversion of raw data of biomarkers into MoM. This study aimed to investigate whether this model can be used across populations without specific adaptations. METHODS: Previously, a machine-learning model derived with the use of a fully connected neural network for first-trimester prediction of early (< 34 weeks), preterm (< 37 weeks) and all PE was developed and tested in a cohort of pregnant women in the UK. The model was based on maternal risk factors and mean arterial blood pressure (MAP), uterine artery pulsatility index (UtA-PI), placental growth factor (PlGF) and pregnancy-associated plasma protein-A (PAPP-A). In this study, the model was applied to a dataset of 10 110 singleton pregnancies examined in Spain who participated in the first-trimester PE validation (PREVAL) study, in which first-trimester screening for PE was carried out using the Fetal Medicine Foundation (FMF) competing-risks model. The performance of screening was assessed by examining the area under the receiver-operating-characteristics curve (AUC) and detection rate (DR) at a 10% screen-positive rate (SPR). These indices were compared with those derived from the application of the FMF competing-risks model. The performance of screening was poor if no adjustment was made for the analyzer used to measure PlGF, which was different in the UK and Spain. Therefore, adjustment for the analyzer used was performed using simple linear regression. RESULTS: The DRs at 10% SPR for early, preterm and all PE with the machine-learning model were 84.4% (95% CI, 67.2-94.7%), 77.8% (95% CI, 66.4-86.7%) and 55.7% (95% CI, 49.0-62.2%), respectively, with the corresponding AUCs of 0.920 (95% CI, 0.864-0.975), 0.913 (95% CI, 0.882-0.944) and 0.846 (95% CI, 0.820-0.872). This performance was achieved with the use of three of the biomarkers (MAP, UtA-PI and PlGF); inclusion of PAPP-A did not provide significant improvement in DR. The machine-learning model had similar performance to that achieved by the FMF competing-risks model (DR at 10% SPR, 82.7% (95% CI, 69.6-95.8%) for early PE, 72.7% (95% CI, 62.9-82.6%) for preterm PE and 55.1% (95% CI, 48.8-61.4%) for all PE) without requiring specific adaptations to the population. CONCLUSIONS: A machine-learning model for first-trimester prediction of PE based on a neural network provides effective screening for PE that can be applied in different populations. However, before doing so, it is essential to make adjustments for the analyzer used for biochemical testing. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

A resonant sextuplet of sub-Neptunes transiting the bright star HD 110067.

Planets with radii between that of the Earth and Neptune (hereafter referred to as 'sub-Neptunes') are found in close-in orbits around more than half of all Sun-like stars1,2. However, their composition, formation and evolution remain poorly understood3. The study of multiplanetary systems offers an opportunity to investigate the outcomes of planet formation and evolution while controlling for initial conditions and environment. Those in resonance (with their orbital periods related by a ratio of small integers) are particularly valuable because they imply a system architecture practically unchanged since its birth. Here we present the observations of six transiting planets around the bright nearby star HD 110067. We find that the planets follow a chain of resonant orbits. A dynamical study of the innermost planet triplet allowed the prediction and later confirmation of the orbits of the rest of the planets in the system. The six planets are found to be sub-Neptunes with radii ranging from 1.94R⊕ to 2.85R⊕. Three of the planets have measured masses, yielding low bulk densities that suggest the presence of large hydrogen-dominated atmospheres.

Radiographic evaluation of the bicipital groove morphology does not predict intraarticular changes in the long head of biceps tendon.

INTRODUCTION AND OBJECTIVES: This study aimed to examine the clinical utility of the radiographic evaluation of the bicipital groove in predicting long head of biceps tendon (LHBT) pathology. MATERIAL AND METHODS: A prospective study was conducted, and sixty consecutive patients proposed to shoulder arthroscopic surgery were selected. Before surgery, a radiographic evaluation was performed with a supine and a Fisk radiograph. Most supine radiographs (>75%) were non-interpretable and were excluded from the study. As some Fisk radiographs (26.7%) were also non-interpretable, that left 44 interpretable radiographs in the study. These were measured for medial opening angle, total opening angle, width and depth of the bicipital groove. The radiographic measurements and the presence of LHBT pathology, as assessed at arthroscopy, were correlated. RESULTS: Radiographic evaluation of the bicipital groove showed a mean medial opening angle of 53 ±â€¯15° (23-90), a mean total opening angle of 80 ±â€¯26° (30-135), a mean width of 10.3 ±â€¯2.5 mm (6-19) and a mean depth of 4.1 ±â€¯1.5 mm (1-8). Men had higher medial opening angle (60 vs 50°, p = 0.044) and wider grooves (11.9 vs 9.7 mm, p = 0.019). Twenty-five patients (56.8%) were found to have an abnormal LHBT. No correlation was found between the radiographic measurements and LHBT pathology. Only age was correlated with a LHBT lesion (61.8 vs 46.3 years, p < 0.001). CONCLUSIONS: Our results show that there is no correlation between radiographic morphologic evaluation of the bicipital groove and LHBT pathology.

Dual-energy CT in the differentiation between adrenal adenomas and metastases: Usefulness of material density maps and monochromatic images.

OBJECTIVE: To evaluate the behavior of adrenal adenomas and metastases with dual-energy CT, analyzing the attenuation coefficient in monochromatic images at three different levels of energy (45, 70, and 140 keV) and the tissue concentrations of fat, water, and iodine in material density maps, with the aim of establishing optimal cutoffs for differentiating between these lesions and comparing our results against published evidence. MATERIALS AND METHODS: This retrospective case-control study included oncologic patients diagnosed with adrenal metastases in the 6-12 months prior to the study who were followed up in our hospital between January and June 2020. For each case (patient with metastases) included in the study, we selected a control (patient with an adrenal adenoma) with a nodule of similar size. All patients were studied with a rapid-kilovoltage-switching dual-energy CT scanner, using a biphasic acquisition protocol. We analyzed the concentration of iodine in paired water-iodine images, the concentration of fat in the paired water-fat images, and the concentration of water in the paired iodine-water and fat-water images, in both the arterial and portal phases. We also analyzed the attenuation coefficient in monochromatic images (at 55, 70, and 140 keV) in the arterial and portal phases. RESULTS: In the monochromatic images, in both the arterial and portal phases, the attenuation coefficient at all energy levels was significantly higher in the group of patients with metastases than in the group of patients with adenomas. This enabled us to calculate the optimal cutoffs for classifying lesions as adenomas or metastases, except for the arterial phase at 55 KeV, where the area under the receiver operating characteristic curve (AUC) for the estimated threshold (0.68) was not considered accurate enough to classify the lesions. For the arterial phase at 70 keV, the AUC was 0.76 (95% CI: 0.663‒0.899); the optimal cutoff (42.4 HU) yielded 92% sensitivity and 60% specificity. For the arterial phase at 140 keV, the AUC was 0.94 (95% CI: 0.894‒0.999); the optimal cutoff (18.9 HU) yielded 88% sensitivity and 94% specificity). For the portal phase at 55 keV, the AUC was 0.76 (95% CI: 0.663‒0.899); the optimal cutoff (95.4 HU) yielded 68% sensitivity and 84% specificity. For the portal phase at 70 keV, the AUC was 0.82 (95% CI: 0.757‒0.955); the optimal cutoff (58.4 HU) yielded 80% sensitivity and 84% specificity. For the portal phase at 140 keV, the AUC was 0.9 (95% CI: 0.834‒0.987); the optimal cutoff (16.35 HU) yielded 96% sensitivity and 84% specificity. In the material density maps, in the arterial phase, significant differences were found only for the iodine-water pair, where the concentration of water was higher in the group with metastases (1018.8 ±â€¯7.6 mg/cm3 vs. 998.6 ±â€¯8.0 mg/cm3 for the group with adenomas, p < 0.001). The AUC was 0.97 (95% CI: 0.893‒0.999); the optimal cutoff (1012.5 mg/cm3) yielded 88% sensitivity and 96% specificity. The iodine-water pair was also significantly higher in metastases (1019.7 ±â€¯12.1 mg/cm3 vs. 998.5 ±â€¯9.1 mg/cm3 in adenomas, p < 0.001). The AUC was 0.926 (95% CI: 0.807‒0.977); the optimal cutoff (1009.5 mg/cm3) yielded 92% sensitivity and 92% specificity. Although significant results were also observed for the fat-water pair in the portal phase, the AUC was insufficient to enable a sufficiently accurate cutoff for classifying the lesions. No significant differences were found in the fat-water maps or iodine-water maps in the arterial or portal phase or in the water-fat map in the arterial phase. CONCLUSIONS: Monochromatic images show differences between the behavior of adrenal adenomas and metastases in oncologic patients studied with intravenous-contrast-enhanced CT, where the group of metastases had higher attenuation than the group of adenomas in both the arterial and portal phases; this pattern is in line with the evidence published for adenomas. Nevertheless, to our knowledge, no other publications report cutoffs for this kind of differentiation in contrast-enhanced monochromatic images obtained in rapid-kilovoltage-switching dual-energy CT scanners, and this is the first new contribution of our study. Regarding the material density maps, our results suggest that the water-iodine pair is a good tool for differentiating between adrenal adenomas and metastases, in both the arterial and portal phases. We propose cutoffs for differentiating these lesions, although to our knowledge no cutoffs have been proposed for portal-phase contrast-enhanced images obtained with rapid-kilovoltage-switching dual-energy CT scanners.

Real-world effectiveness and safety of stereotactic body radiotherapy for liver metastases with different respiratory motion management techniques.

PURPOSE: Stereotactic body radiotherapy (SBRT) has been firmly established as a treatment choice for patients with oligometastases, as it has demonstrated both safety and efficacy by consistently achieving high rates of local control. Moreover, it offers potential survival benefits for carefully selected patients in real-world clinical settings. METHODS: Between January 2008 and May 2020, a total of 149 patients (with 414 liver metastases) received treatment. The Active Breathing Coordinator device was used for 68 patients, while respiratory gating was used for 65 and abdominal compression was used for 16 patients. The most common histological finding was colorectal adenocarcinoma, with 37.6% of patients having three or more metastases, and 18% having two metastases. The prescribed dose ranged from 36 to 60 Gy, delivered in 3-5 fractions. RESULTS: Local control rates at 2 and 3 years were 76.1% and 61.2%, respectively, with no instances of local recurrence after 3 years. Factors negatively impacting local control included colorectal histology, lower prescribed dose, and the occurrence of new liver metastases. The median overall survival from SBRT was 32 months, with the presence of metastases outside the liver and the development of new liver metastases after SBRT affecting survival. The median disease-free survival was 10 months. No substantial differences in both local control and survival were observed between the respiratory motion control techniques employed. Treatment tolerance was excellent, with only one patient experiencing acute grade IV thrombocytopenia and two patients suffering from ≥ grade II chronic toxicity. CONCLUSION: For radical management of single or multiple liver metastases, SBRT is an effective and well-tolerated treatment option. Regardless of the technology employed, experienced physicians can achieve similarly positive outcomes. However, additional studies are required to elucidate prognostic factors that can facilitate improved patient selection.

Myotonic dystrophy type 1: 13 years of experience at a tertiary hospital. Clinical and epidemiological study and genotype-phenotype correlation.

INTRODUCTION: The incidence of myotonic dystrophy type 1 (DM1), a disease with great phenotypic variety, in our region is unknown. This study aims to estimate the incidence of DM1 at our hospital (a reference centre in Aragon, Spain) and to identify the characteristics of our population (genotype-phenotype correlation). METHODS: Retrospective, descriptive study of 459 patients classified according to the number of CTG repeats, as follows: normal (5-35), premutation (36-50), protomutation (51-80), small expansions (81-150), intermediate expansions (151-1000), and large expansions (> 1000). Furthermore, according to clinical phenotype, patients were categorised as unaffected (5-50 CTG repeats), mild form or asymptomatic (51-150), classical form (151-1000), and severe form (> 1000). RESULTS: The incidence of DM1 was 20.61 cases per million person-years (95% CI, 19.59-21.63). An inverse correlation was observed between the number of CTG repeats and the age at genetic diagnosis (ρ = -0.547; 95% CI, -0.610 to -0.375; P < .001). CTG5 was the most frequent polymorphic allele in healthy individuals. Of all patients with DM1, 28.3% presented the mild or asymptomatic form, 59.1% the classical form, and 12.6% the severe form. Inheritance was maternal in 35.1% of cases, paternal in 59.4%, and uncertain in 5.5%. In mild forms, frontal balding in men was the most prevalent phenotypic trait, as well as myotonia and cataracts, while in the classical form, ptosis, facial weakness, voice and pronunciation alterations, myotonia, and fatigue/sleepiness were most frequent. CONCLUSIONS: The incidence of DM1 in Aragon is significant. Multidisciplinary study of the phenotype of patients with DM1 is key to early diagnosis and personalised management.

Large-scale real-life analysis of survival and usage of therapies in multiple myeloma.

Survival in multiple myeloma has improved significantly in recent years, especially in young patients. We reviewed the evolution of the survival of patients with MM in three groups based on age at MM diagnosis over three time periods between 1999 and 2020 at our 12 de Octubre Hospital institution (H12O). Then, to confirm our results, we used data from TriNetx, a global health research platform that includes patients from Europe to US. Finally, we analysed differences in the patterns of treatment between networks across the world. Kaplan‒Meier analysis was used to estimate survival probabilities, and between-group differences were tested using the log-rank test and hazard ratio. For patients from H12O, the median OS was 35.61, 55.59 and 68.67 months for the 1999-2009, 2010-2014 and 2015-2020 cohorts, respectively (p = 0.0001). Among all patients included in the EMEA network, the median OS was 20.32 months versus 34.75 months from 1999-2009 versus 2010-2014. The median OS from the 2010-2014 versus 2015-2020 time cohorts was 34.75 months versus 54.43 months, respectively. In relation to the US cohort, the median OS from before 2010 versus 2010-2014 was not reached in either time cohort and neither when comparing the 2010-2014 versus 2015-2019 time cohorts. Bortezomib is the most commonly used drug in the EMEA cohort, while lenalidomide is the most commonly used drug in the US cohort. This large-scale study based on real-world data confirms the previous finding that MM patients have increased their survival in the last two decades.

Seiðr: Efficient calculation of robust ensemble gene networks.

Gene regulatory and gene co-expression networks are powerful research tools for identifying biological signal within high-dimensional gene expression data. In recent years, research has focused on addressing shortcomings of these techniques with regard to the low signal-to-noise ratio, non-linear interactions and dataset dependent biases of published methods. Furthermore, it has been shown that aggregating networks from multiple methods provides improved results. Despite this, few useable and scalable software tools have been implemented to perform such best-practice analyses. Here, we present Seidr (stylized Seiðr), a software toolkit designed to assist scientists in gene regulatory and gene co-expression network inference. Seidr creates community networks to reduce algorithmic bias and utilizes noise corrected network backboning to prune noisy edges in the networks. Using benchmarks in real-world conditions across three eukaryotic model organisms, Saccharomyces cerevisiae, Drosophila melanogaster, and Arabidopsis thaliana, we show that individual algorithms are biased toward functional evidence for certain gene-gene interactions. We further demonstrate that the community network is less biased, providing robust performance across different standards and comparisons for the model organisms. Finally, we apply Seidr to a network of drought stress in Norway spruce (Picea abies (L.) H. Krast) as an example application in a non-model species. We demonstrate the use of a network inferred using Seidr for identifying key components, communities and suggesting gene function for non-annotated genes.

Demographic, clinical and microbiological characteristics of the first 30 human monkeypox confirmed cases attended in a tertiary hospital in Madrid (Spain), during the May-June 2022 international outbreak.

The present outbreak of Human Monkeypox (HMPX) that has begun in May 2022 and has spread across all continents in less than two months has qualitative and quantitative characteristics that make it different from the pattern of human disease previously caused by this virus. It has spread with enormous ease, affects almost exclusively adults, behaves as a sexually transmitted disease and focuses on very specific groups and transmission conditions. The high incidence in the city of Madrid in males that have sex with males (MSM) has allowed us to observe and report the experience with the first 30 cases diagnosed in our institution. Patients presented with febrile symptoms, genital and paragenital skin lesions reminiscent of smallpox, but less extensive and severe. The disease may also cause proctitis, pharyngitis and perioral lesions. The PCR test for diagnostic confirmation has been shown to be very sensitive and effective, not only in skin lesions but also in blood and other fluids such as pharyngeal, rectal exudates and blood. A very high proportion of patients with HMPX also have other sexually transmitted diseases that must be actively detected in this context. The spontaneous evolution of our patients has been good and hospitalization has been practically unnecessary. Transmission to non-sexual cohabitants and health personnel has been nonexistent and the lesions have disappeared in less than 30 days without leaving sequelae and no need for specific antiviral treatment.

Anti-endotoxin antibodies consumption in cardiovascular collapse: Pathophysiological concerns.

OBJECTIVE: Abnormal endotoxin activity in critically ill patients has been described in the absence of Gram-negative bacterial (GNB) infection. As disease severity seems to be crucial in the detection of this phenomenon, we decided to assess and compare endotoxin exposure in those patients representing the critical situation: septic shock and cardiogenic shock. DESIGN: Prospective, observational non intervention study. SETTING: Critical Care Department of a University tertiary hospital. PATIENTS: Cardiogenic shock (CS) and septic shock (SS) patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Follow-up was performed for the first three days. Inflammatory biomarkers (C-reactive protein, procalcitonin and interleuquin-6) and IgM antiendotoxin-core antibodies titter (IgM EndoCAb) were daily analyzed. Sixty-two patients were included; twenty-five patients with SS and thirty-seven with CS. Microbial etiology was established in 23 SS patients (92%) and GNB were present in 13 cases (52%). Although infection was suspected and even treated in 30 CS patients (81%), any episode could be finally confirmed. EndoCAb consumption was more intense in SS patients, although twenty-two CS patients (59.5%) had IgM anti-endotoxin value below 10th percentile range for healthy people. No statistically significant difference in endotoxin exposure was detected between Gram-positive and Gram-negative infections in the SS group. Endotoxin exposure ability to distinguish between SS and CS was moderate (AUC 0.7892, 95% IC: 0.6564-0.9218). CONCLUSIONS: In the severely ill patient some mechanisms take place allowing endotoxin incursion and therefore blurring the limits of diseases pathophysiology. Our work representatively shows how exposure to endotoxin was not fully capable of distinguishing between CS and SS.