Defining the first bona fide cell model for SMARCA4-deficient, undifferentiated tumor.

The World Health Organization's tumor classification guidelines are frequently updated and renewed as knowledge of cancer biology advances. For instance, in 2021, a novel lung tumor subtype named SMARCA4-deficient, undifferentiated tumor (SMARCA4-dUT, code 8044/3) was included. To date, there is no defined cell model for SMARCA4-dUT that could be used to help thoracic clinicians and researchers in the study of this newly defined tumor type. As this tumor type was recently described, it is feasible that some cell models formerly classified as lung adenocarcinoma (LUAD) could now be better classified as SMARCA4-dUT. Thus, in this work, we aimed to identify a bona fide cell model for the experimental study of SMARCA4-dUT. We compared the differential expression profiles of 36 LUAD-annotated cell lines and 38 cell lines defined as rhabdoid in repositories. These comparative results were integrated with the mutation and expression profiles of the SWI/SNF complex members, and they were surveyed for the presence of the SMARCA4-dUT markers SOX2, SALL4, and CD34, measured by RT-qPCR and western blotting. Finally, the cell line with the paradigmatic SMARCA4-dUT markers was engrafted into immunocompromised mice to assess the histological morphology of the formed tumors and compare them with those formed by a bona fide LUAD cancer cell line. NCI-H522, formerly classified as LUAD, displayed expression profiles nearer to rhabdoid tumors than LUAD tumors. Furthermore, NCI-H522 has most of the paradigmatic features of SMARCA4-dUT: hemizygous inactivating mutation of SMARCA4, severe SMARCA2 downregulation, and high-level expression of stem cell markers SOX2 and SALL4. In addition, the engrafted tumors of NCI-H522 did not display a typical differentiated glandular structure as other bona fide LUAD cell lines (A549) do but had rather a largely undifferentiated morphology, characteristic of SMARCA4-dUT. Thus, we propose the NCI-H522 as the first bona fide cell line model of SMARCA4-dUT. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Durable ventricular assist device in Spain (2007-2020). First report of the REGALAD registry.

INTRODUCTION AND OBJECTIVES: This report presents the clinical characteristics, outcomes and complications of all consecutive patients implanted with a long-term mechanical circulatory support device in Spain between 2007 and 2020. METHODS: Analysis of the Spanish Registry of durable ventricular assist devices (REGALAD) including data form Spanish centers with a mechanical circulatory support program. RESULTS: During the study period, 263 ventricular assist devices were implanted in 22 hospitals. The implanted device was an isolated continuous-flow left ventricular assist device in 182 patients (69%), a pulsatile-flow device (58 isolated left ventricular and 21 biventricular) in 79 (30%), and a total artificial heart in 2 patients (1%). The strategy of the implant was as bridge to heart transplant in 78 patients (30%), bridge to candidacy in 110 (42%), bridge to recovery in 3 (1%) and destination therapy in 72 patients (27%). Overall survival at 6, 12 and 24 months was 79%, 74% and 69%, respectively, and was better in continuous-flow left ventricular assist devices (84%, 80%, and 75%). The main adverse events related to this therapy were infections (37% of patients), bleeding (35%), neurological (29%), and device malfunction (17%). CONCLUSIONS: Durable ventricular assist devices have emerged in Spain in the last few years as a useful therapy for patients with advanced heart failure. As in other international registries, the current trend is to use continuous-flow intracorporeal left ventricular devices, which are associated with better results. Adverse events continue to be frequent and severe.

Behavior of echocardiographic parameters of right ventricular function after tricuspid surgery.

Evaluation of right ventricular (RV) function after tricuspid valve surgery is complex. The objective was to identify the most appropriate RV function parameters for this purpose. This prospective study included 70 patients undergoing cardiac and tricuspid valve (TV) surgery. RV size and function parameters were determined at 3 months and 1-year post-surgery. Categorical variables were analyzed with the McNemar test and numerical variables with the Student's t-test for related samples or, when non-normally distributed, the Wilcoxon test. Spearman's rho was used to determine correlations between variables at 3 months and 1 year. RV diameters were reduced at 3 months post-surgery and were then unchanged at 1 year. Tricuspid annular plane systolic excursion (TAPSE) and S' wave values were worse at 3 months and then improved at 1 year (t-score-2.35, p 0.023; t-score-2.68; p 0.010). There was no significant reduction in free wall longitudinal strain (LS) or shortening fraction (SF) at 3 months (t-score 1.421 and - 1.251; p 0.218 and 0.172), and they were only slightly below pre-surgical values at 1 year. No relationship was found between RV function parameters and mortality or major complications. During the first few months after TV surgery, LS may be a more appropriate parameter to evaluate global ventricular function in comparison to TAPSE. At 1 year, good correlations are observed between TAPSE, S' wave, and LS values.

Surgical management of tricuspid regurgitation: a new algorithm to minimise recurrent tricuspid regurgitation.

INTRODUCTION: Recurrent tricuspid regurgitation (TR) is frequently observed after cardiac surgery; however, the correct approach remains controversial. We developed an algorithm for action on the tricuspid valve (TV) and conducted a 1-year follow-up study. The aim was to assess the efficacy of the algorithm to minimise residual TR after TV surgery. The hypothesis was that the TR rate at 1 year would be reduced by selecting the surgical approach in accordance with a set of preoperative clinical and echocardiographic variables. METHODS: A prospective, observational, single-centre study was performed in 76 consecutive patients with TV involvement. A protocol was designed for their inclusion, and data on their clinical and echocardiographic characteristics were gathered at 3 months and 1-year postsurgery. The treatment of patients depended on the degree of TR. Surgery was performed in all patients with severe or moderate-to-severe TR and in those with mild or moderate TR alongside the presence of certain clinical or echocardiographic factors. They underwent annuloplasty or extended valve repair when the TV was distorted. If repair techniques were not feasible, a prosthesis was implanted. Residual TR rates were compared with published reports, and predictors of early/late mortality and residual TR were evaluated. RESULTS: TR was functional in 69.9% of patients. Rigid ring annuloplasty was performed in 35.7% of patients, De Vega annuloplasty in 27.1%, extended repair in 11.4% and prosthetic replacement in 25.7%. TR was moderate or worse in 8.19% of patients (severe in 3.27%) at 1 year postintervention. No clinical, surgical or epidemiological variables were significantly associated with residual TR persistence, although annulus diameter showed a close-to-significant association. Total mortality was 12.85% for all causes and 10% for cardiovascular causes. In multivariate analysis, left ventricular ejection fraction was related to both early and late mortality. CONCLUSIONS: Severe residual TR was significantly less frequent than reported in other series, being observed in less than 4% of patients at 1-year postsurgery.

Machine learning techniques for mortality prediction in critical traumatic patients: anatomic and physiologic variables from the RETRAUCI study.

BACKGROUND: Interest in models for calculating the risk of death in traumatic patients admitted to ICUs remains high. These models use variables derived from the deviation of physiological parameters and/or the severity of anatomical lesions with respect to the affected body areas. Our objective is to create different predictive models of the mortality of critically traumatic patients using machine learning techniques. METHODS: We used 9625 records from the RETRAUCI database (National Trauma Registry of 52 Spanish ICUs in the period of 2015-2019). Hospital mortality was 12.6%. Data on demographic variables, affected anatomical areas and physiological repercussions were used. The Weka Platform was used, along with a ten-fold cross-validation for the construction of nine supervised algorithms: logistic regression binary (LR), neural network (NN), sequential minimal optimization (SMO), classification rules (JRip), classification trees (CT), Bayesian networks (BN), adaptive boosting (ADABOOST), bootstrap aggregating (BAGGING) and random forest (RFOREST). The performance of the models was evaluated by accuracy, specificity, precision, recall, F-measure, and AUC. RESULTS: In all algorithms, the most important factors are those associated with traumatic brain injury (TBI) and organic failures. The LR finds thorax and limb injuries as independent protective factors of mortality. The CT generates 24 decision rules and uses those related to TBI as the first variables (range 2.0-81.6%). The JRip detects the eight rules with the highest risk of mortality (65.0-94.1%). The NN model uses a hidden layer of ten nodes, which requires 200 weights for its interpretation. The BN find the relationships between the different factors that identify different patient profiles. Models with the ensemble methodology (ADABOOST, BAGGING and RandomForest) do not have greater performance. All models obtain high values ​​in accuracy, specificity, and AUC, but obtain lower values ​​in recall. The greatest precision is achieved by the SMO model, and the BN obtains the best recall, F-measure, and AUC. CONCLUSION: Machine learning techniques are useful for creating mortality classification models in critically traumatic patients. With clinical interpretation, the algorithms establish different patient profiles according to the relationship between the variables used, determine groups of patients with different evolutions, and alert clinicians to the presence of rules that indicate the greatest severity.

A propósito del “Return to play” en futbolistas lesionados / About the Return to Play on injured football players

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Capacidad inmunomoduladora de cepas potencialmente probióticas de Lactobacillus aisladas de leche materna y heces de lactante / Immunomodulating capacity of potentially probiotic Lactobacillus strains isolated from human breast milk and lactating children feces

El objetivo del estudio fue evaluar la capacidad inmunomoduladora de dos cepas de L. paracasei (66 y 71) y una de L. rhamnosus (75) aisladas de leche materna y heces de lactante, en Mérida, Venezuela, caracterizadas como potencialmente probióticas en estudios previos. Las bacterias fueron administradas a ratones BALB/c en el agua de bebida durante 7 días. Con los fluidos intestinales se realizaron pruebas de ELISA para determinar los valores de las citoquinas IFN-γ e IL-10. Se realizó la coloración de hematoxilina-eosina a cortes histológicos del intestino delgado para observar posibles reacciones inflamatorias. Para el análisis estadístico, se utilizó la prueba de ANOVA de una vía, seguido del test post hoc de Tukey, considerando a p<0,05 como significativo. Se observaron incrementos significativos, por encima del grupo control, en las concentraciones de IFN-γ e IL-10 en el fluido intestinal de los ratones alimentados con las cepas 71 y 75. No se observaron reacciones inflamatorias en el intestino delgado. Al inducir un aumento en la producción de las citoquinas, estas cepas fueron capaces de estimular el sistema inmune manteniendo la homeostasis, por lo que pueden ser utilizadas como adyuvantes del sistema inmune intestinal, sin producir efectos secundarios indeseables.

The objective of this study was to evaluate the immunomodulating capacity of two L. paracasei strains (66 and 71), and one L. rhamnosus (75) isolated from breast milk and lactating children feces in Mérida, Venezuela, characterized as potentially probiotic in previous studies. The bacteria were administered to BALB/c mice in their drinking water during 7 days. Intestinal fluids were tested by ELISA to determine IFN-γ and IL-10 cytokines values. Histological sections of the small intestine were stained with hematoxilin-eosin to detect possible inflammatory reactions. The statistical analysis was done by a one way ANOVA, followed by the Tukey post hoc test, considering p<0.05 as significant. There were significant increases, as compared with the control group, of INF-γ and IL.10 concentrations in the intestinal fluid of mice fed with strains 71 and 75. There were no inflammatory reactions of the small intestine tissue. By inducing an increase in cytokine production, these strains were capable of stimulating the immune system maintaining homeostasis, due to which they can be used as adjuvant of the immune intestinal system, without producing undesirable side effects.

Early markers of acute respiratory distress syndrome development in severe trauma patients.

PURPOSE: The aim of the study was to identify early risk factors for development of acute respiratory distress syndrome (ARDS) in severe trauma patients. MATERIALS AND METHODS: This was a prospective observational study of 693 severe trauma patients (Injury Severity Score >or=16 and/or Revised Trauma Score or=2) of long bone fractures, and with chest injuries (rib/sternal fracture [ICD-9 code 807] and hemo/pneumothorax [ICD-9 code 860/861]). Patients with ARDS required more colloids (P = .005) and red blood cell units (P = .02) than patients without ARDS during the first 24 hours. Multivariate analysis showed that ARDS was related to chest trauma diagnosis (ICD-9 code 807) (odds ratio [OR], 3.85), femoral fracture (OR, 3.16), APACHE II score (OR, 1.05), and blood transfusion during resuscitation (OR, 1.32). CONCLUSIONS: Risk of ARDS development is related to the first 24-hour admission variables, including severe physiologic derangements and specific ICD-9-classified injuries. Blood transfusion may play an independent role.