Ibero-American Consensus for the Management of Peritoneal Sarcomatosis: Updated Review and Clinical Recommendations.

Peritoneal sarcomatosis is a rare malignant disease with a poor prognosis, secondary to peritoneal dissemination of abdominopelvic soft tissue sarcomas. Its rarity, together with the characteristic histological heterogeneity and the historically poor response to systemic treatments, has prevented the establishment of widely accepted treatment criteria with curative intent. In this sense, radical cytoreductive surgery (CRS) with peritonectomy procedures and hyperthermic intraperitoneal chemotherapy (HIPEC), widely used in peritoneal carcinomatosis with excellent results, have not had the same evolutionary development in patients with peritoneal sarcomatosis. A multidisciplinary working group of experts in sarcomas and peritoneal oncological surgery established a series of recommendations based on current scientific evidence for the management of peritoneal sarcomatosis, taking into account the different histological subgroups of abdominopelvic sarcomas that can cause it depending on their origin: retroperitoneal sarcomas, uterine sarcomas, and visceral/peritoneal sarcomas of GIST (gastrointestinal stromal tumor) and non-GIST origin. This article shows the results of sarcoma experts' voting on the recommendations presented during the I Ibero-American Consensus on the Management of Peritoneal Sarcomatosis, which took place during the recent celebration of the III Hispanic-Portuguese Meeting for Updates on the Treatment of Sarcomas.

Relationship between neck kinematics and neck dissability index. An approach based on functional regression.

Numerous studies use numerical variables of neck movement to predict the level of severity of a pathology. However, the correlation between these numerical variables and disability levels is low, less than 0.4 in the best cases, even less in subjects with nonspecific neck pain. This work aims to use Functional Data Analysis (FDA), in particular scalar-on-function regression, to predict the Neck Disability Index (NDI) of subjects with nonspecific neck pain using the complete movement as predictors. Several functional regression models have been implemented, doubling the multiple correlation coefficient obtained when only scalar predictors are used. The best predictive model considers the angular velocity curves as a predictor, obtaining a multiple correlation coefficient of 0.64. In addition, functional models facilitate the interpretation of the relationship between the kinematic curves and the NDI since they allow identifying which parts of the curves most influence the differences in the predicted variable. In this case, the movement's braking phases contribute to a greater or lesser NDI. So, it is concluded that functional regression models have greater predictive capacity than usual ones by considering practically all the information in the curve while allowing a physical interpretation of the results.

Infecciones de la vias urinarias en pacientes diabéticos / Urinary tract infections in diabetic patients

Las infecciones del tracto urinario se encuentran entre las enfermedades infecciosas más comunes en todo el mundo, Los pacientes con diabetes mellitus suelen presentar una función inmune deteriorada y enfermedades infecciosas agravadas. La infección del tracto urinario es una de las principales complicaciones de la diabetes mellitus, aumenta la susceptibilidad a las infecciones, en parte debido a la alteración de la función de los granulocitos, un control glucémico inadecuado e hiperglucemia crónica que condiciona la presencia de microangiopatía diabética.

Urinary tract infections are among the most common infectious diseases worldwide. Patients with diabetes mellitus sometimes presented with impaired immune function and aggravated infectious diseases. Urinary tract infection is one of the main complications of diabetes mellitus; it increases susceptibility to infections, partly due to altered granulocyte function, inadequate glycemic control and chronic hyperglycemia that conditions the presence of diabetic microangiopathy.

A cell abundance analysis based on efficient PAM clustering for a better understanding of the dynamics of endometrial remodelling.

BACKGROUND: Single-cell RNA sequencing (scRNA-seq) is a powerful tool for investigating cell abundance changes during tissue regeneration and remodeling processes. Differential cell abundance supports the initial clustering of all cells; then, the number of cells per cluster and sample are evaluated, and the dependence of these counts concerning the phenotypic covariates of the samples is studied. Analysis heavily depends on the clustering method. Partitioning Around Medoids (PAM or k-medoids) represents a well-established clustering procedure that leverages the downstream interpretation of clusters by pinpointing real individuals in the dataset as cluster centers (medoids) without reducing dimensions. Of note, PAM suffers from high computational costs and memory requirements. RESULTS: This paper proposes a method for differential abundance analysis using PAM as a clustering method and negative binomial regression as a statistical model to relate covariates to cluster/cell counts. We used this approach to study the differential cell abundance of human endometrial cell types throughout the natural secretory phase of the menstrual cycle. We developed a new R package -scellpam-, that incorporates an efficient parallel C++ implementation of PAM, and applied this package in this study. We compared the PAM-BS clustering method with other methods and evaluated both the computational aspects of its implementation and the quality of the classifications obtained using distinct published datasets with known subpopulations that demonstrate promising results. CONCLUSIONS: The implementation of PAM-BS, included in the scellpam package, exhibits robust performance in terms of speed and memory usage compared to other related methods. PAM allowed quick and robust clustering of sets of cells with a size ranging from 70,000 to 300,000 cells. https://cran.r-project.org/web/packages/scellpam/index.html . Finally, our approach provides important new insights into the transient subpopulations associated with the fertile time frame when applied to the study of changes in the human endometrium during the secretory phase of the menstrual cycle.

Genetic interaction in the association between oxidative stress and diabetes in the Spanish population.

Oxidative stress (OS) is a relevant intermediate mechanism involved in Type 2 Diabetes Mellitus (T2D) development. To date, the interaction between OS parameters and variations in genes related to T2D has not been analyzed. AIMS: To study the genetic interaction of genes potentially related to OS levels (redox homeostasis, renin-angiotensin-aldosterone system, endoplasmic stress response, dyslipidemia, obesity and metal transport) and OS and T2D risk in a general population from Spain (the Hortega Study) in relation to the risk of suffering from T2D. MATERIALS AND METHODS: One thousand five hundred and two adults from the University Hospital Rio Hortega area were studied and 900 single nucleotide polymorphisms (SNPs) from 272 candidate genes were analyzed. RESULTS: There were no differences in OS levels between cases and controls. Some polymorphisms were associated with T2D and with OS levels. Significant interactions were observed between OS levels and two polymorphisms in relation to T2D presence: rs196904 (ERN1 gene) and rs2410718 (COX7C gene); and between OS levels and haplotypes of the genes: SP2, HFF1A, ILI8R1, EIF2AK2, TXNRD2, PPARA, NDUFS2 and ERN1. CONCLUSIONS: Our results indicate that genetic variations of the studied genes are associated with OS levels and that their interaction with OS parameters may contribute to the risk of developing T2D in the Spanish general population. These data support the importance of analyzing the influence of OS levels and their interaction with genetic variations in order to establish their real impact in T2D risk. Further studies are required to identify the real relevance of interactions between genetic variations and OS levels and the mechanisms involved in them.

Biomarcadores tempranos en nefropatia diabética / Early biomarkers in diabetic nephropathy

La enfermedad renal diabética es una patología de presentación frecuente y una costosa complicación de la diabetes. Se considera una de las principales causas de insuficiencia renal e ingreso a Terapia de Reemplazo renal. En la práctica clínica, la enfermedad renal diabética se diagnostica por albuminuria, una disminución de la tasa de filtración glomerular estimada (eGFR), o ambos. Actualmente existe la posibilidad de detectar varios marcadores tempranos, como el CKD273, el mismo que se asoció con un mayor riesgo de progresión a microalbuminuria, siendo una alerta temprana de presentación de nefropatía diabetica, varios años antes de su presentación.

SUMMARY Diabetic kidney disease is a common presenting condition and a costly complication of diabetes. It is considered one of the main causes of renal failure and admission to renal replacement therapy. In clinical practice, diabetic kidney disease is diagnosed by albuminuria, a decrease in estimated glomerular filtration rate (eGFR), or both. Currently, there is the possibility of detecting early markers such as CKD273, which was associated with an increased risk of progression to microalbuminuria, being an early warning of the presentation of diabetic nephropathy, several years before its presentation.

Uso de inhibidores de sglt 2 en pacientes con nefropatía diabética / Use of SGLT-2 inhibitors in patients with diabetic nephropathy

El tratamiento antidiabético oral ha sido un reto en el manejo de la diabetes mellitus. Los pacientes con algún grado de enfermedad renal crónica corren serios riesgos de hipoglucemia, sin embargo, los inhibidores del transportador de glucosa SGLT2 suponen un nuevo abordaje terapéutico de la diabetes mellitus tipo 2. Estudios en modelos experimentales de diabetes han demostrado que la inducción de glucosuria revierte la glucotoxicidad, restaura la normoglucemia, y mejora el funcionamiento de la célula beta y la sensibilidad a la insulina. Por lo tanto, se constituyen en una alternativa segura en estos pacientes.

Oral antidiabetic treatment has been a challenge in the management of diabetes mellitus in patients with some degree of chronic kidney disease due to the constant risks of hypoglycemia; however, glucose transporter SGLT2 inhibitors represent a new therapeutic approach to diabetes mellitus. Type 2, studies in experimental models of diabetes have shown thatthe induction of glycosuria reverses glucotoxicity, restores normoglycemia, and improves beta cell function and insulin sensitivity.

Assessment of mental workload across cognitive tasks using a passive brain-computer interface based on mean negative theta-band amplitudes.

Brain-computer interfaces (BCI) can provide real-time and continuous assessments of mental workload in different scenarios, which can subsequently be used to optimize human-computer interaction. However, assessment of mental workload is complicated by the task-dependent nature of the underlying neural signals. Thus, classifiers trained on data from one task do not generalize well to other tasks. Previous attempts at classifying mental workload across different cognitive tasks have therefore only been partially successful. Here we introduce a novel algorithm to extract frontal theta oscillations from electroencephalographic (EEG) recordings of brain activity and show that it can be used to detect mental workload across different cognitive tasks. We use a published data set that investigated subject dependent task transfer, based on Filter Bank Common Spatial Patterns. After testing, our approach enables a binary classification of mental workload with performances of 92.00 and 92.35%, respectively for either low or high workload vs. an initial no workload condition, with significantly better results than those of the previous approach. It, nevertheless, does not perform beyond chance level when comparing high vs. low workload conditions. Also, when an independent component analysis was done first with the data (and before any additional preprocessing procedure), even though we achieved more stable classification results above chance level across all tasks, it did not perform better than the previous approach. These mixed results illustrate that while the proposed algorithm cannot replace previous general-purpose classification methods, it may outperform state-of-the-art algorithms in specific (workload) comparisons.

Tiempo de aislamiento y periodo infeccioso en pacientes con covid 19 hospitalizados / Isolation time and infectious period in patients with covid 19 hospitalized

RESUMEN: Se revisan las recomendaciones actuales de aislamiento y los criterios que se deben conocer para considerar a los pacientes que cursan con COVID, como potencialmente contagiosos. Se debe continuar utilizando las tasas de transmisión y seguir las recomendaciones de control y prevención de infecciones de los CDC para entornos de atención médica. El aislamiento ayuda a prevenir la transmisión del virus al separar a las personas infectadas con el virus de las que no lo están. Es básico por lo tanto discriminar esas situaciones clínicas y tener claros los criterios laboratoriales para tomar decisiones respecto al tiempo de aislamiento de los pacientes. Considerando la exposición del personal de salud y los pacientes hospitalizados se concluye que no necesaria la cuarentena para los asintomáticos que están al día con todas las dosis recomendadas de la vacuna contra el COVID-19 o que se han recuperado de la infección por SARS-CoV-2 en los 90 días anteriores, las posibles excepciones y el grupo de pacientes que deben someterse a pruebas, se describen en el desarrollo de este artículo.

ABSTRACT: It reviews the current isolation recommendations and the criteria that must be known to consider patients who are with COVID, as potentially contagious. Transmission rates should continue to be used and CDC infection prevention and control recommendations for health care settings should be followed. Isolation helps prevent transmission of the virus by separating people infected with the virus from those who are not. It is therefore essential to discriminate these clinical situations and to be clear about the laboratory criteria to make decisions regarding the isolation time of patients. Considering the exposure of health personnel and hospitalized patients; it is concluded that quarantine is not necessary for asymptomatic patients who are up to date with all recommended doses of COVID-19 vaccine or who have recovered from SARS-CoV-2 infection in the previous 90 days, possible exceptions and the group of patients to be tested, are described in the development of this article.

Motherhood-induced gene expression in the mouse medial amygdala: Changes induced by pregnancy and lactation but not by pup stimuli.

During lactation, adult female mice display aggressive responses toward male intruders, triggered by male-derived chemosensory signals. This aggressive behavior is not shown by pup-sensitized virgin females sharing pup care with dams. The genetic mechanisms underlying the switch from attraction to aggression are unknown. In this work, we investigate the differential gene expression in lactating females expressing maternal aggression compared to pup-sensitized virgin females in the medial amygdala (Me), a key neural structure integrating chemosensory and hormonal information. The results showed 197 genes upregulated in dams, including genes encoding hormones such as prolactin, growth hormone, or follicle-stimulating hormone, neuropeptides such as galanin, oxytocin, and pro-opiomelanocortin, and genes related to catecholaminergic and cholinergic neurotransmission. In contrast, 99 genes were downregulated in dams, among which we find those encoding for inhibins and transcription factors of the Fos and early growth response families. The gene set analysis revealed numerous Gene Ontology functional groups with higher expression in dams than in pup-sensitized virgin females, including those related with the regulation of the Jak/Stat cascade. Of note, a number of olfactory and vomeronasal receptor genes was expressed in the Me, although without differences between dams and virgins. For prolactin and growth hormone, a qPCR experiment comparing dams, pup-sensitized, and pup-naïve virgin females showed that dams expressed higher levels of both hormones than pup-naïve virgins, with pup-sensitized virgins showing intermediate levels. Altogether, the results show important gene expression changes in the Me, which may underlie some of the behavioral responses characterizing maternal behavior.

Incidencia de infecciones en pacientes con artritis reumatoide en tratamiento corticoideo e inmunosupresor / Incidence of infections in patients with rheumatoid arthritis in corticosteroid and immunosuppressive treatment

Introducción La artritis reumatoide (AR) es una enfermedad inflamatoria autoinmune, que requiere tratamiento farmacológico por tiempo muy prolongado. Se prescribe para su tratamiento fármacos con capacidad antiinflamatoria y potencial efecto inmunosupresor. Con estos fármacos los pacientes presentan menor intensidad inflamatoria, pero a la vez existe el riesgo de procesos infecciosos, siendo éstos, una importante causa de morbilidad y mortalidad. Objetivo Analizar la incidencia de infección durante el tratamiento corticoideo vs inmunosupresor en la terapia crónica en pacientes con artritis reumatoide. Material y métodos Estudio de tipo analítico, observacional, retrospectivo, con selección por intención, no controlado, de cohorte, con estudio de riesgo, incidencia y asociación cruzada, realizado en el Servicio de Reumatología del Hospital de Clínicas de La Paz, Bolivia; en pacientes con diagnóstico de AR entre las gestiones 2010 - 2020, tanto en consultorio externo y sala de internación. Se seleccionaron pacientes con adultos, ambos sexos, con edad mayor a 18 años, con diagnóstico de artritis reumatoide según clasificación ACR 2010, clinimetría CDAI en grado de actividad, con indicación de tratamiento asociado (corticoide + metotrexato o incluso adición de cloroquina / hidroxicloroquina) de acuerdo a guías ACR/EULAR, que realice control regular (bimensual). Resultados La incidencia de procesos infecciosos asociada al uso de prednisona con dosis >7,5mg/día, tras 6 meses de tratamiento es de 19,39% y de 18,88% a los 12 meses. La incidencia de procesos infecciosos asociada al uso de metotrexate (dosis >12,5mg/semana), es de 12,76% a 6 meses de tratamiento y de 13,27% a 12 meses. Conclusiones En pacientes adultos de ambos sexos, sin factores de riesgo asociados, la corticoterapia prolongada (Prednisona en dosis mayor a 7.5mg/día durante más de 6 meses de tratamiento) produce el desarrollo de procesos infecciosos con mayor frecuencia y gravedad que la terapia con metotrexate incluso a dosis intermedia-alta (MTX >12.5mg / semana).

Introduction Rheumatoid arthritis is an autoimmune inflammatory disease, which requires pharmacological treatment for a very long time. It is prescribed for its treatment drugs with anti-inflammatory capacity and potential immunosuppressive effect. With these drugs patients present lower inflammatory intensity, but at the same time there is a risk of infectious processes, these being an important cause of morbidity and mortality. Objective To analyze the risk of infection with corticosteroid vs. immunosuppressive treatment in chronic therapy in patients with rheumtaoid arthritis. Material and methods Analytical, observational, retrospective study, with selection by intention, uncontrolled, cohort, with study of risk, incidence and cross association, carried out in the Rheumatology Service of the Hospital de Clínicas, La Paz, Bolivia, in patients who were diagnosed with RA between the 2010 - 2020 management, both in the outpatient clinic and the hospitalization room. Patients were selected with adults, both sexes, aged over 18 years, with a diagnosis of rheumatoid arthritis according to ACR 2010 classification, CDAI clinimetry in degree of activity, with indication of associated treatment (corticoid + methoroxate or even addition of chloroquine / hydroxychloroquine) according to ACR/EULAR guidelines, which perform regular control (bi monthly). Results: The incidence of infectious processes associated with the use of prednisone with doses >7.5mg/day, after 6 months of treatment is 19.39% and 18.88% at 12 months. The incidence of infectious processes associated with the use of metotrexate (dose >12.5mg/week), is 12.76% at 6 months of treatment and 13.27% at 12 months. Conclusions In adult patients of both sexes, without associated risk factors, prolonged corticotherapy (Prednisone in doses greater than 7.5mg/day for more than 6 months of treatment) produces the development of infectious processes with greater frequency and severity than therapy with metotrexate even at intermediate-high dose (MTX >12.5mg / week).

Utilidad de los reactantes de fase agua en el diagnóstico clínico / Usefulness of water phase reactants in clinical diagnosis

Los reactantes de fase aguda son proteínas plasmáticas que sufren alteraciones durante la inflamación. Las variadas reacciones del huésped a la infección, inflamación o trauma abarcan como respuesta una amplia gama de respuestas patofisiológicas tales como la pirexia, leucocitosis, las alteraciones hormonales entre otros

OMICfpp: a fuzzy approach for paired RNA-Seq counts.

BACKGROUND: RNA sequencing is a widely used technology for differential expression analysis. However, the RNA-Seq do not provide accurate absolute measurements and the results can be different for each pipeline used. The major problem in statistical analysis of RNA-Seq and in the omics data in general, is the small sample size with respect to the large number of variables. In addition, experimental design must be taken into account and few tools consider it. RESULTS: We propose OMICfpp, a method for the statistical analysis of RNA-Seq paired design data. First, we obtain a p-value for each case-control pair using a binomial test. These p-values are aggregated using an ordered weighted average (OWA) with a given orness previously chosen. The aggregated p-value from the original data is compared with the aggregated p-value obtained using the same method applied to random pairs. These new pairs are generated using between-pairs and complete randomization distributions. This randomization p-value is used as a raw p-value to test the differential expression of each gene. The OMICfpp method is evaluated using public data sets of 68 sample pairs from patients with colorectal cancer. We validate our results through bibliographic search of the reported genes and using simulated data set. Furthermore, we compared our results with those obtained by the methods edgeR and DESeq2 for paired samples. Finally, we propose new target genes to validate these as gene expression signatures in colorectal cancer. OMICfpp is available at http://www.uv.es/ayala/software/OMICfpp_0.2.tar.gz . CONCLUSIONS: Our study shows that OMICfpp is an accurate method for differential expression analysis in RNA-Seq data with paired design. In addition, we propose the use of randomized p-values pattern graphic as a powerful and robust method to select the target genes for experimental validation.

Hiperparatiroidismo primario: caso clínico y revisión de la literatura / Primary Hyperparathyroidism: Clinical case and review of the Literature

El adenoma de paratiroides es un tumor benigno de las gládulas paratiroides, que se caracteriza por un incremento de los niveles de la para hormona. Esta hormona tiene como objetivo prinicipal de regulación de los niveles de calcio, fosforo y vitamina D en la sangre y en los huesos. Puede deberse a un problema genético, a la radiación en el cuello o por consumo de litio. La triada caracteristica es un aumento de niveles de parathormona, hipercalcemia e hipofosfatemia. Esta enfermedad afecta a uno entre 500-1000 habitantes y es la prinicipal causa de hiperparatiroidismo primario. Se presenta el caso de un paciente masculino de 42 años, el cual es ingresado por presentar fractura de antebrazo y pierna derecha, causada por hiperparatiroidismo primario originado por adenoma paratiroideo, con identificación precisa de la lesión inicial y resolución quirúrgica satisfactoria

Resistencia Bacteriana por beta lactamasas de epectro extendido: un problema creciente / BACTERIAL RESISTANCE BY EXTENDED SPECTRUM BETA LACTAMASE: A GROWING PROBLEM

Las ß-lactamasas de espectro extendido (BLEE) son enzimas que generan resistencia a la mayoría de los b-lactámicos, incluyendo a penicilinas, cefalosporinas de primera, segunda, tercera generación, monobactámicos, excepto a la cefamicina y carbapenémicos. Esta resistencia se vio incrementada por el indiscriminado uso de cefalosporinas para infecciones incluso leves. También cuentan con frecuencia con genes para otros antimicrobianos como ser aminoglucosidos, tetraciclinas y cotrimoxazol. Además, las cepas BLEE (+) son más frecuentemente resistentes a quinolonas que las cepas no productoras de BLEE. La resistencia actual que existe a las betalactamasas de espectro extendido aumenta las tasas de mortalidad, ya que en pacientes con infecciones se inician tratamientos empíricos, que al no tener buena respuesta ocasionan que el cuadro clínico llegue a evolucionar hasta la sepsis. El tratamiento de elección en estos casos es el uso de carbapenémicos, recomendación que se basa principalmente en el resultado de resistencia observada in vitro. Los nuevos carbapenémicos, como ertapenem o doripenem parecen tener una excelente actividad. Se realiza una revisión de los aspectos básicos de la aparición de cepas BLEE y su importancia en el manejo de pacientes con cuadros infecciosos, que son de frecuente presentación en los Hospitales de referencia

Probabilistic liver atlas construction.

BACKGROUND: Anatomical atlases are 3D volumes or shapes representing an organ or structure of the human body. They contain either the prototypical shape of the object of interest together with other shapes representing its statistical variations (statistical atlas) or a probability map of belonging to the object (probabilistic atlas). Probabilistic atlases are mostly built with simple estimations only involving the data at each spatial location. RESULTS: A new method for probabilistic atlas construction that uses a generalized linear model is proposed. This method aims to improve the estimation of the probability to be covered by the liver. Furthermore, all methods to build an atlas involve previous coregistration of the sample of shapes available. The influence of the geometrical transformation adopted for registration in the quality of the final atlas has not been sufficiently investigated. The ability of an atlas to adapt to a new case is one of the most important quality criteria that should be taken into account. The presented experiments show that some methods for atlas construction are severely affected by the previous coregistration step. CONCLUSION: We show the good performance of the new approach. Furthermore, results suggest that extremely flexible registration methods are not always beneficial, since they can reduce the variability of the atlas and hence its ability to give sensible values of probability when used as an aid in segmentation of new cases.