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BACKGROUND: Over recent decades, splenic angioembolization (SAE) as an adjunct to non-operative management (NOM) has emerged as a prominent intervention for patients with blunt splenic injuries (BSI). SAE improves patient outcomes, salvages the spleen, and averts complications associated with splenectomy. This systematic review aimed to evaluate the failure rate and complications related to SAE in patients with BSI. METHODS: A systematic literature search (PubMed, SCOPUS, and Cochrane Library) focused on studies detailing splenic angioembolization in blunt trauma cases. Articles that fulfilled the predetermined inclusion criteria were included. This review examined the indications, outcomes, failure rate, and complications of SAE. RESULTS: Among 599 identified articles, 33 met the inclusion criteria. These comprised 29 retrospective studies, three prospective studies, and one randomized control trial. The analysis encompassed 25,521 patients admitted with BSI and 3,835 patients who underwent SAE. The overall failure rate of SAE was 5.3 %. Major complications predominantly were rebleeding (4.8 %), infarction (4.6 %), and abscess formation (4 %). Minor complications were fever (18.4 %), pleural effusion (13.1 %), and coil migration (3.9 %). Other complications included splenic atrophy, splenic cyst, hematoma, and access site complications such as splenic/femoral dissection. Overall, post embolization mortality was 0.08 %. CONCLUSION: SAE is a valuable adjunct in managing BSI, with a low failure rate. However, this treatment modality is not without the risk of potentially serious complications.
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Crohn's disease (CD) is a complex chronic inflammatory disorder with both gastrointestinal and extra-intestinal manifestations associated immune dysregulation. Analyzing 202,359 cells from 170 specimens across 83 patients, we identify a distinct epithelial cell type in both terminal ileum and ascending colon (hereon as 'LND') with high expression of LCN2, NOS2, and DUOX2 and genes related to antimicrobial response and immunoregulation. LND cells, confirmed by in-situ RNA and protein imaging, are rare in non-IBD controls but expand in active CD, and actively interact with immune cells and specifically express IBD/CD susceptibility genes, suggesting a possible function in CD immunopathogenesis. Furthermore, we discover early and late LND subpopulations with different origins and developmental potential. A higher ratio of late-to-early LND cells correlates with better response to anti-TNF treatment. Our findings thus suggest a potential pathogenic role for LND cells in both Crohn's ileitis and colitis.
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Colon , Enfermedad de Crohn , Oxidasas Duales , Células Epiteliales , Íleon , Lipocalina 2 , Enfermedad de Crohn/patología , Enfermedad de Crohn/genética , Enfermedad de Crohn/inmunología , Humanos , Células Epiteliales/metabolismo , Células Epiteliales/patología , Colon/patología , Íleon/patología , Lipocalina 2/metabolismo , Lipocalina 2/genética , Oxidasas Duales/genética , Oxidasas Duales/metabolismo , Masculino , Óxido Nítrico Sintasa de Tipo II/metabolismo , Óxido Nítrico Sintasa de Tipo II/genética , Femenino , Adulto , Factor de Necrosis Tumoral alfa/metabolismo , Mucosa Intestinal/patología , Mucosa Intestinal/metabolismo , Persona de Mediana EdadRESUMEN
This is an interim analysis of the Beta-blocker (Propranolol) use in traumatic brain injury (TBI) based on the high-sensitive troponin status (BBTBBT) study. The BBTBBT is an ongoing double-blind placebo-controlled randomized clinical trial with a target sample size of 771 patients with TBI. We sought, after attaining 50% of the sample size, to explore the impact of early administration of beta-blockers (BBs) on the adrenergic surge, pro-inflammatory cytokines, and the TBI biomarkers linked to the status of high-sensitivity troponin T (HsTnT). Patients were stratified based on the severity of TBI using the Glasgow coma scale (GCS) and HsTnT status (positive vs negative) before randomization. Patients with positive HsTnT (non-randomized) received propranolol (Group-1; n = 110), and those with negative test were randomized to receive propranolol (Group-2; n = 129) or placebo (Group-3; n = 111). Propranolol was administered within 24 h of injury for 6 days, guided by the heart rate (> 60 bpm), systolic blood pressure (≥ 100 mmHg), or mean arterial pressure (> 70 mmHg). Luminex and ELISA-based immunoassays were used to quantify the serum levels of pro-inflammatory cytokines (Interleukin (IL)-1ß, IL-6, IL-8, and IL-18), TBI biomarkers [S100B, Neuron-Specific Enolase (NSE), and epinephrine]. Three hundred and fifty patients with comparable age (mean 34.8 ± 9.9 years) and gender were enrolled in the interim analysis. Group 1 had significantly higher baseline levels of IL-6, IL-1B, S100B, lactate, and base deficit than the randomized groups (p = 0.001). Group 1 showed a significant temporal reduction in serum IL-6, IL-1ß, epinephrine, and NSE levels from baseline to 48 h post-injury (p = 0.001). Patients with severe head injuries had higher baseline levels of IL-6, IL-1B, S100B, and HsTnT than mild and moderate TBI (p = 0.01). HsTnT levels significantly correlated with the Injury Severity Score (ISS) (r = 0.275, p = 0.001), GCS (r = - 0.125, p = 0.02), and serum S100B (r = 0.205, p = 0.001). Early Propranolol administration showed a significant reduction in cytokine levels and TBI biomarkers from baseline to 48 h post-injury, particularly among patients with positive HsTnT, indicating the potential role in modulating inflammation post-TBI.Trial registration: ClinicalTrials.gov NCT04508244. It was registered first on 11/08/2020. Recruitment started on 29 December 2020 and is ongoing. The study was partly presented at the 23rd European Congress of Trauma and Emergency Surgery (ECTES), April 28-30, 2024, in Estoril, Lisbon, Portugal.
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Antagonistas Adrenérgicos beta , Biomarcadores , Lesiones Traumáticas del Encéfalo , Propranolol , Troponina T , Humanos , Lesiones Traumáticas del Encéfalo/tratamiento farmacológico , Lesiones Traumáticas del Encéfalo/sangre , Antagonistas Adrenérgicos beta/administración & dosificación , Antagonistas Adrenérgicos beta/uso terapéutico , Biomarcadores/sangre , Masculino , Femenino , Adulto , Persona de Mediana Edad , Troponina T/sangre , Propranolol/administración & dosificación , Propranolol/uso terapéutico , Método Doble Ciego , Escala de Coma de Glasgow , Citocinas/sangre , Subunidad beta de la Proteína de Unión al Calcio S100/sangreRESUMEN
Hypusine is an amino acid synthesized by the enzyme deoxyhypusine synthase (DHPS). It is critical for the activity of eukaryotic translation initiation factor 5A (EIF5A). We reported that hypusination i) in macrophages supports the innate response towards pathogenic bacteria and ii) in epithelial cells maintains intestinal homeostasis. Herein, we investigated the effect of myeloid hypusination on the outcome of colitis and colitis-associated cancer. We found that patients with Crohn's disease exhibit increased levels of DHPS and EIF5AHyp in cells infiltrating the colon lamina propria. However, the specific deletion of Dhps in myeloid cells had no impact on clinical, histological, or inflammatory parameters in mice treated with dextran sulfate sodium (DSS). Further, tumorigenesis and level of dysplasia were not affected by myeloid deletion of Dhps in the azoxymethane-DSS model. The composition of the fecal and the mucosa-associated microbiome was similar in animals lacking or not DHPS in myeloid cells. Thus, hypusination in myeloid cells does not regulate colitis associated with epithelial injury and colitis-associated cancer. Enhancement of the DHPS/hypusine pathway in patients with inflammatory bowel disease could have therapeutic impact through epithelial effects, but modulation of hypusination in myeloid cells will be unlikely to affect the disease.
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Background: Body contouring surgery removes excess skin and fat, often after massive weight loss. Some reports suggest that patients who have previously undergone obesity (bariatric) surgery are at excess risk of subsequent bleeding, possibly due to complex nutritional and metabolic sequelae of massive weight loss. Methods: A retrospective cohort study of intraoperative blood loss and postoperative bleeding indicators were examined for patients who had undergone abdominoplasty. Participants were categorized based on their history of previous obesity surgery, and outcome variables were compared using odds ratio, followed by subgroup comparison between a history of restrictive versus malabsorptive obesity surgery. Results: The study included 472 patients, of which 171 (36.2 %) had a history of obesity surgery. Mean age was 40.4 years, and 402 (85.1%) participant were women. Fifty-five (11.6%) patients were smokers whereas 65 (13.7%) were hypertensive. Mean body mass index before surgery was 30.2 kg per m2, and average time between obesity and body contouring surgery (if applicable) was 35.8 months. Patients with a history of obesity surgery exhibited greater intraoperative blood loss (162.2 mL versus 132.1 mL; P = 0.001), drainage volume at 24 h (155 mL versus 135 mL; P = 0.001), and total drainage volume (300ml versus 220 mL; P = 0.001). Postoperative hematoma requiring surgical re-exploration was almost three times higher following a history of obesity surgery (4.7% versus 1.7 %; P = 0.05). Conclusions: History of obesity surgery increases intraoperative blood loss, postoperative serosanguinous drainage volumes, and the risk of postoperative hematoma requiring surgical evacuation after abdominal body contouring procedures.
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BACKGROUND: The effective management of trauma patients necessitates efficient triaging, timely activation of Massive Blood Transfusion Protocols (MTP), and accurate prediction of in-hospital outcomes. Machine learning (ML) algorithms have emerged as up-and-coming tools in the domains of optimizing triage decisions, improving intervention strategies, and predicting clinical outcomes, consistently outperforming traditional methodologies. This study aimed to develop, assess, and compare several ML models for the triaging processes, activation of MTP, and mortality prediction. METHODS: In a 10-year retrospective study, the predictive capabilities of seven ML models for trauma patients were systematically assessed using on-admission patients' hemodynamic data. All patient's data were randomly divided into training (80 %) and test (20 %) sets. Employing Python for data preprocessing, feature scaling, and model development, we evaluated K-Nearest Neighbors (KNN), Logistic Regression (LR), Decision Tree (DT), Support Vector Machines (SVM) with RBF kernels, Random Forest (RF), Extreme Gradient Boosting (XGBoost), and Artificial Neural Network (ANN). We employed various imputation techniques and addressed data imbalance through down-sampling, up-sampling, and synthetic minority for the over-sampling technique (SMOTE). Hyperparameter tuning, coupled with 5-fold cross-validation, was performed. The evaluation included essential metrics like sensitivity, specificity, F1 score, accuracy, Area Under the Receiver Operating Curve (AUC ROC), and Area Under the Precision recall Curve (AUC PR), ensuring robust predictive capability. RESULT: This study included 17,390 adult trauma patients; of them, 19.5 % (3385) were triaged at a critical level, 3.8 % (664) required MTP, and 7.7 % (1335) died in the hospital. The model's performance improved using imputation and balancing techniques. The overall models demonstrated notable performance metrics for predicting triage, MTP activation, and mortality with F1 scores of 0.75, 0.42, and 0.79, sensitivities of 0.73, 0.82, and 0.9, and AUC ROC values of 0.89, 0.95 and 0.99 respectively. CONCLUSION: Machine learning, especially RF models, effectively predicted trauma triage, MTP activation, and mortality. Featured critical hemodynamic variables include shock indices, systolic blood pressure, and mean arterial pressure. Therefore, models can do better than individual parameters for the early management and disposition of patients in the ED. Future research should focus on creating sensitive and interpretable models to enhance trauma care.
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Transfusión Sanguínea , Hemodinámica , Aprendizaje Automático , Triaje , Heridas y Lesiones , Humanos , Triaje/métodos , Heridas y Lesiones/mortalidad , Heridas y Lesiones/fisiopatología , Hemodinámica/fisiología , Masculino , Femenino , Estudios Retrospectivos , Adulto , Persona de Mediana EdadRESUMEN
BACKGROUND: Upper extremity injuries (UEIs) are common in the emergency departments, yet they are under-reported in developing countries. This study examined the frequency, injury characteristics, and treatment approaches of upper extremity fractures (UEFs) among hospitalized trauma patients in a nationally representative population. METHODS: We conducted a retrospective, observational study including all the hospitalized patients with UEFs in the only level 1 trauma center in Qatar between July 2015 and August 2020. Comparative analyses were performed according to injury mechanisms, severity, and management approach. RESULTS: A total of 2,023 patients sustained UEIs with an average age of 34.4 ± 12.9 years, and 92% were males. Motor vehicle crashes (MVCs; 42.3%) were the primary cause of shoulder girdle injuries in 48.3% of cases. Fractures of the radius, ulna, and hands occurred in 30.8, 16.5 and 14.5%, respectively. Young adults were more involved in MVCs and motorcycle crashes (MCCs), while pedestrians who were typically older had a higher rate of humerus fractures. Patients with MCCs had a higher rate of clavicle and ulna fractures. Pedestrians were at risk of serious injuries, with a higher mean injury severity score and lower Glasgow Coma Scale. CONCLUSION: Most UEFs patients were young males and mainly affected by MVCs. Shoulder girdle, particularly clavicle and scapula/glenoid fractures, emerged as common injury sites. The study highlighted the potential risk of pedestrian injuries, as reflected in higher injury severity, concomitant injuries, and higher mortality. Future studies are needed to optimize preventive measures by incorporating insights into specific injury mechanisms and patterns of UEIs.
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Background: Grade (III-V) blunt splenic injuries (BSI) in hemodynamically stable patients represent clinical challenges for successful non-operative management (NOM). In 2014, Our institution proposed a treatment protocol requiring splenic angiography and embolization for stable, intermediate, and high-grade BSI. It also included a follow-up CT scan for grade III BSI. We sought to assess the success rate of NOM in treating intermediate and high-grade BSI, following a standardized treatment protocol at a level 1 trauma center. Methods: An observational retrospective study was conducted. Data of patients with BSI from June 2011 to September 2019 were reviewed using the Qatar National Trauma Registry. Patients' demographics, CT scan and angiographic findings, grade of splenic injuries, and outcomes were analyzed. The pre- and post-implementation of treatment protocol periods were compared. Results: During the study period, a total of 552 hemodynamically stable patients with BSI were admitted, of which 240 had BSI with grade III to V. Eighty-one patients (33.8%) were admitted in the pre-protocol implementation period and 159 (66.2%) in the post-protocol implementation period. The NOM rate increased from 50.6% in the pre-protocol group to 65.6% in the post-protocol group (p = 0.02). In addition, failure of the conservative treatment did not significantly differ in the two periods, while the requirement for blood transfusion dropped from 64.2% to 45.9% (p = 0.007). The frequency of CT scan follow-up (55.3% vs. 16.3%, p = 0.001) and splenic arterial embolization (32.7% vs. 2.5%, p = 0.001) in NOM patients increased significantly in the post-protocol group compared to the pre-protocol group. Overall mortality was similar between the two periods. However, hospital and ICU length of stay and ventilatory days were higher in the post-protocol group. Conclusions: NOM is an effective and safe treatment option for grade III-V BSI patients. Using standardized treatment guidelines for intermediate-to high-grade splenic injuries could increase the success rate for NOM and limit unnecessary laparotomy. Moreover, angioembolization is a crucial adjunct to NOM that could improve the success rate.
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Introduction: Phenytoin is one of the commonly used anti.seizure medications in nontraumatic seizures. However, its utility and safety in young patients with traumatic brain injury (TBI) for the prevention of early-onset seizures (EOS) are debatable. We sought to explore the use of phenytoin as a seizure prophylaxis following TBI. We hypothesized that administering phenytoin is not effective in preventing EOS after TBI. Methods: This was a retrospective observational study conducted on adult TBI patients. EOS was defined as a witnessed seizure within a week postinjury. Data were compared as phenytoin versus no-phenytoin use, EOS versus no-EOS, and among TBI severity groups. Results: During 1 year, 639 TBI patients were included with a mean age of 32 years; of them, 183 received phenytoin as seizure prophylaxis, and 453 received no prophylaxis medication. EOS was documented in 13 (2.0%) patients who received phenytoin, and none had EOS among the nonphenytoin group. The phenytoin group was more likely to have a higher Marshall Score (P = 0.001), lower Glasgow Coma Scale (GCS) (P = 0.001), EOS (P = 0.001), and higher mortality (P = 0.001). Phenytoin was administrated for 15.2%, 43.2%, and 64.5% of mild, moderate, and severe TBI patients, respectively. EOS and no-EOS groups were comparable for age, gender, mechanism of injury, GCS, Marshall Score, serum phenytoin levels, liver function levels, hospital stay, and mortality. Multivariable logistic regression analysis showed that low serum albumin (odds ratio [OR] 0.81; 95% confidence interval [CI] 0.676.0.962) and toxic phenytoin level (OR 43; 95% CI 2.420.780.7) were independent predictors of EOS. Conclusions: In this study, the prophylactic use of phenytoin in TBI was ineffective in preventing EOS. Large-scale matched studies and well-defined hospital protocols are needed for the proper utility of phenytoin post-TBI.
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BACKGROUND: During the COVID-19 pandemic, there was a boom in the delivery sector, with a significant increase in the demand and number of motorcycle delivery drivers in Qatar, which made them vulnerable to injury. We aimed to evaluate the incidence, pattern, and outcome of patients injured by motorcycle-related crashes (MCC) before and during the pandemic. METHODS: A retrospective observational study included all adult patients admitted with motorcycle-related injuries before the pandemic (March 2018 to February 2020) and during the pandemic (March 2020 to March 2022). Comparative analyses were performed based on (work versus non-work related MCCs) and (pre- versus during the pandemic injuries). RESULTS: 510 patients with MCC were identified, of which 172 (33.7 %) were admitted in the pre-pandemic and 338 (66.3 %) during the pandemic. The mean age of patients was 29.2±7.8 years; 56 % were aged 20-29 years, and 99.4 % were males. Work-related MCCs were more frequent among the younger age group (60.9 % vs. 52.1 %; p=0.001) during the early evening, i.e., 6:00 to 9:00 p.m. (21.9 % vs. 13.9 %; p=0.004). However, non-work related MCC occurred more frequently between midnight and 3:00 am (20.2 % vs. 10.9 %; p=0.004), and such patients were more likely non-compliant for protective devices use (19.3 % vs. 6.1 %; p=0.001) and ride under the influence of alcohol (13.2 % vs. 7.4 %; p=0.03). During the pandemic, the proportion of alcohol consumers (13 % vs. 5.8 %; p=0.01) and work-related MCC (50.9 % vs. 22.7 %; p=0.001) increased significantly compared to the pre-pandemic period. CONCLUSION: The overall burden of MCC increased during the pandemic, and the frequency of MCC involving commercial drivers surged significantly during the pandemic period as opposed to the non-work MCC, which predominated in the pre-pandemic period. Work-related MCCs were more frequent among younger age groups, mainly involving South Asians with frequent accidents in the evening time. However, recreation-related MCCs occurred more frequently at midnight, and victims were non-compliant with the protective gear. Furthermore, there is a need for prospective studies to examine the broader scope of risk factors that are associated with the work-related MCC, especially involving food deliveries, and for focused safety programs for motorcycle delivery drivers and recreational motorcyclists.
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COVID-19 , Heridas y Lesiones , Adulto , Masculino , Humanos , Adulto Joven , Femenino , Motocicletas , Accidentes de Tránsito/prevención & control , Pandemias , COVID-19/epidemiología , COVID-19/prevención & control , Medio Oriente , Dispositivos de Protección de la Cabeza , Heridas y Lesiones/epidemiologíaRESUMEN
Background: We aimed to analyze in-hospital timing and risk factors for mortality in a level 1 trauma center. Methods: This is a retrospective analysis of all trauma-related mortality between 2013 and 2018. Patients were divided and analyzed based on the time of mortality (early (≤48â h) vs late (>48â h)), and within different age groups. Multivariate regression analysis was performed to predict in-hospital mortality. Results: 8624 trauma admissions and 677 trauma-related deaths occurred (47.7% at the scene and 52.3% in-hospital). Among in-hospital mortality, the majority were males, with a mean age of 35.8 ± 17.2 years. Most deaths occurred within 3-7 days (35%), followed by 33% after 1 week, 20% on the first day, and 12% on the second day of admission. Patients with early mortality were more likely to have a lower Glasgow coma scale, a higher shock index, a higher chest and abdominal abbreviated injury score, and frequently required exploratory laparotomy and massive blood transfusion (P < .005). The injury severity scores and proportions of head injuries were higher in the late mortality group than in the early group. The severity of injuries, blood transfusion, in-hospital complications, and length of intensive care unit stay were comparable among the age groups, whereas mortality was higher in the age group of 19 to 44. The higher proportions of early and late in-hospital deaths were evident in the age group of 24 to 29. In multivariate analysis, the shock index (OR 2.26; 95%CI 1.04-4.925; P = .04) was an independent predictor of early death, whereas head injury was a predictor of late death (OR 4.54; 95%CI 1.92-11.11; P = .001). Conclusion: One-third of trauma-related mortalities occur early after injury. The initial shock index appears to be a reliable hemodynamic indicator for predicting early mortality. Therefore, timely hemostatic resuscitation and appropriate interventions for bleeding control may prevent early mortality.
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Mortalidad Hospitalaria , Centros Traumatológicos , Heridas y Lesiones , Humanos , Estudios Retrospectivos , Masculino , Femenino , Centros Traumatológicos/estadística & datos numéricos , Adulto , Factores de Riesgo , Persona de Mediana Edad , Heridas y Lesiones/mortalidad , Factores de Tiempo , Adulto Joven , Puntaje de Gravedad del Traumatismo , Escala de Coma de Glasgow , Transfusión Sanguínea/estadística & datos numéricos , Anciano , Tiempo de Internación/estadística & datos numéricos , AdolescenteRESUMEN
Trauma is a serious public health issue, and remains a major cause of mortality and disability worldwide. The notion that genetic factors contribute to an individual's response to traumatic injury has advanced significantly. Genetic variations in severely injured patients have been linked to mortality, morbidity, and psychological outcomes. We conducted a comprehensive review of beta-adrenergic receptor polymorphisms and their impact on the pathogenetics of traumatic injuries, which could pave the way for a transformational frontier of personalized medicine in neurotrauma. It remains unclear why some individuals are vulnerable to worse outcomes, whereas others are resilient. Although genetic factors may be significant, the intricate interplay between environmental and genetic factors may be responsible for variations in the presentation and outcome after injury. Recent advancements in genetic analysis and molecular physiology have helped to shed light on the causes of such variability. Although exposure to trauma can initiate a cascade of stress-related responses, these responses alone are insufficient to explain etiopathogenesis. Therefore, gaining insights into how trauma and genetic predispositions to adrenergic variations interact at the molecular level to affect an individual's susceptibility and recuperation could provide an essential understanding of the molecular pathogenesis of traumatic injuries. Therefore, it is imperative to identify potential genetic and physiological markers to guide early management and prognosis of trauma. Such knowledge could pave the way for the discovery of novel biomarkers that can identify a transdiagnostic subgroup that is at high risk and requires early intervention. This could lead to the adoption of personalized medical approaches in neurotrauma care.
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Medicina de Precisión , Receptores Adrenérgicos beta , Humanos , Receptores Adrenérgicos beta/genética , Polimorfismo Genético , Pronóstico , Predisposición Genética a la Enfermedad , BiomarcadoresRESUMEN
The Coronavirus disease 2019 (COVID-19) caused by the SARS-CoV-2 virus led to over 626 million infections and 6.5 million deaths worldwide and forced to cancel or postpone several sporting events. Effective control techniques are therefore urgently required to avoid COVID-19 spread at these local and global events. This narrative review addressed the healthcare and research efforts on the intersections between COVID-19 and major professional sports leagues worldwide, with special reference to the FIFA World Cup football 2022. This explained how the broader transformation of COVID-19 from being a potential risk to an urgent pandemic public health emergency, caused the world of Football to halt between February and March 2020. This review could add to the growing literature on the importance of scientific research in understanding the relationship between mass sports events and COVID-19 trajectory, concerning studies conducted globally and particularly for the recommencement of major professional football competitions. The information outlined in the article may help sports organizations understand the risks associated with sports and their settings and improve their preparedness for future events under unprecedented circumstances. There were tremendous global healthcare and research efforts to deal with this unprecedented pandemic. The successful FIFA World Cup football tournament was an indicator of the success of these efforts.
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The intestinal immune response is crucial in maintaining a healthy gut, but the enhanced migration of macrophages in response to pathogens is a major contributor to disease pathogenesis. Integrins are ubiquitously expressed cellular receptors that are highly involved in immune cell adhesion to endothelial cells while in the circulation and help facilitate extravasation into tissues. Here we show that specific deletion of the Tln1 gene encoding the protein talin-1, an integrin-activating scaffold protein, from cells of the myeloid lineage using the Lyz2-cre driver mouse reduces epithelial damage, attenuates colitis, downregulates the expression of macrophage markers, decreases the number of differentiated colonic mucosal macrophages, and diminishes the presence of CD68-positive cells in the colonic mucosa of mice infected with the enteric pathogen Citrobacter rodentium. Bone marrow-derived macrophages lacking expression of Tln1 did not exhibit a cell-autonomous phenotype; there was no impaired proinflammatory gene expression, nitric oxide production, phagocytic ability, or surface expression of CD11b, CD86, or major histocompatibility complex II in response to C. rodentium. Thus, we demonstrate that talin-1 plays a role in the manifestation of infectious colitis by increasing mucosal macrophages, with an effect that is independent of macrophage activation.
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Colitis , Infecciones por Enterobacteriaceae , Animales , Ratones , Citrobacter rodentium , Colitis/genética , Colitis/prevención & control , Colon/patología , Células Endoteliales/metabolismo , Infecciones por Enterobacteriaceae/metabolismo , Inflamación/patología , Mucosa Intestinal/metabolismo , Macrófagos/metabolismo , Ratones Endogámicos C57BL , Talina/genética , Talina/metabolismoRESUMEN
Background: Loss of muscle mass, and its strength, is associated with adverse outcomes in many medical and surgical conditions. Trauma patients may get malnourished during their hospital course due to many interrelated contributing factors. However, there is insufficient knowledge on the acute muscle and fat changes in young trauma patients in the early days post-admission. Objective: to explore the diagnosis, feeding status, and outcome of muscle mass loss among young abdominal polytrauma patients. Methods: It was a retrospective study including hospitalized abdominal trauma patients who underwent an abdominal computerized tomographic (CT) examination initially and a follow-up one week later. CT scan-based automatic and manual analysis of the muscles and fat of the abdominal region was calculated and compared. Also, we evaluated the feeding and nutritional values to explore the adequacy of the provided calories and proteins and the potential influence of enteral feeding on the CT-based parameters for muscle loss and fat depletion. Results: There were 138 eligible subjects with a mean age of 32.8 ± 13.5 years; of them, 92% were males. Operative interventions were performed on two-thirds of the patients, including abdominal surgery (43%), orthopedic surgeries (34%), and neurosurgical procedures (8.1%). On admission, 56% received oral feeding, and this rate slightly increased to 58.4% after the first week. Enteral feed was prescribed for the remaining, except for two patients. The percentage of change in the total psoas muscle area was significantly reduced after one week of admission in patients on enteral feed as compared to those in the oral feeding group (p = 0.001). There were no statistically significant differences in the percentages of changes in the CT scan findings except for the total psoas muscle area (p = 0.001) and para-spinal muscle area (p = 0.02), which reduced significantly in the those who underwent laparotomy as compared to those who did not need laparotomy. Trauma patients who underwent emergency abdominal surgery lost muscle and fat over time. Conclusions: Loss of muscle mass and body fat is not uncommon among young trauma patients. Patients who underwent laparotomy are more likely to be affected. Further larger studies are needed to assess the specific features in the younger trauma population and how far this can be influenced by the nutrition status and its impact on the clinical outcomes. It could be early or impending stages of sarcopenia linked to trauma patients, or just acute changes in the muscle and fat, that need further investigation and follow-up after hospital discharge.
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Lung cancer remains the leading cause of cancer-related deaths globally, and the survival rate remains low despite advances in diagnosis and treatment. The progression of lung cancer is a multifaceted and dynamic phenomenon that encompasses interplays among cancerous cells and their microenvironment, which incorporates immune cells. Exosomes, which are small membrane-bound vesicles, are released by numerous cell types in normal and stressful situations to allow communication between cells. Tumor-derived exosomes (TEXs) possess diverse neo-antigens and cargoes such as proteins, RNA, and DNA and have a unique molecular makeup reflecting tumor genetic complexity. TEXs contain both immunosuppressive and immunostimulatory factors and may play a role in immunomodulation by influencing innate and adaptive immune components. Moreover, they transmit signals that contribute to the progression of lung cancer by promoting metastasis, epithelial-mesenchymal transition (EMT), angiogenesis, and immunosuppression. This makes them a valuable resource for investigating the immune environment of tumors, which could pave the way for the development of non-invasive biomarkers that could aid in the prognosis, diagnosis, and immunotherapy of lung cancer. While immune checkpoint inhibitor (ICI) immunotherapy has shown promising results in treating initial-stage cancers, most patients eventually develop adaptive resistance over time. Emerging evidence demonstrates that TEXs could serve as a prognostic biomarker for immunotherapeutic response and have a significant impact on both systemic immune suppression and tumor advancement. Therefore, understanding TEXs and their role in lung cancer tumorigenesis and their response to immunotherapies is an exciting research area and needs further investigation. This review highlights the role of TEXs as key contributors to the advancement of lung cancer and their clinical significance in lung immune-oncology, including their possible use as biomarkers for monitoring disease progression and prognosis, as well as emerging shreds of evidence regarding the possibility of using exosomes as targets to improve lung cancer therapy.
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Exosomas , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/terapia , Biomarcadores , Transducción de Señal , Inmunosupresores , Microambiente TumoralRESUMEN
BACKGROUND & AIMS: The amino acid hypusine, synthesized from the polyamine spermidine by the enzyme deoxyhypusine synthase (DHPS), is essential for the activity of eukaryotic translation initiation factor 5A (EIF5A). The role of hypusinated EIF5A (EIF5AHyp) remains unknown in intestinal homeostasis. Our aim was to investigate EIF5AHyp in the gut epithelium in inflammation and carcinogenesis. METHODS: We used human colon tissue messenger RNA samples and publicly available transcriptomic datasets, tissue microarrays, and patient-derived colon organoids. Mice with intestinal epithelial-specific deletion of Dhps were investigated at baseline and in models of colitis and colon carcinogenesis. RESULTS: We found that patients with ulcerative colitis and Crohn's disease exhibit reduced colon levels of DHPS messenger RNA and DHPS protein and reduced levels of EIF5AHyp. Similarly, colonic organoids from colitis patients also show down-regulated DHPS expression. Mice with intestinal epithelial-specific deletion of Dhps develop spontaneous colon hyperplasia, epithelial proliferation, crypt distortion, and inflammation. Furthermore, these mice are highly susceptible to experimental colitis and show exacerbated colon tumorigenesis when treated with a carcinogen. Transcriptomic and proteomic analysis on colonic epithelial cells demonstrated that loss of hypusination induces multiple pathways related to cancer and immune response. Moreover, we found that hypusination enhances translation of numerous enzymes involved in aldehyde detoxification, including glutathione S-transferases and aldehyde dehydrogenases. Accordingly, hypusination-deficient mice exhibit increased levels of aldehyde adducts in the colon, and their treatment with a scavenger of electrophiles reduces colitis. CONCLUSIONS: Hypusination in intestinal epithelial cells has a key role in the prevention of colitis and colorectal cancer, and enhancement of this pathway via supplementation of spermidine could have a therapeutic impact.
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Colitis , Espermidina , Humanos , Animales , Ratones , Espermidina/farmacología , Espermidina/metabolismo , Proteómica , Factores de Iniciación de Péptidos/genética , Factores de Iniciación de Péptidos/metabolismo , Carcinogénesis/genética , Colitis/inducido químicamente , Colitis/genética , Colitis/prevención & control , Homeostasis , InflamaciónRESUMEN
Background: There is a gap in knowledge on the epidemiology of pediatric trauma in the developing countries. We aimed to describe the injury pattern, mechanism of injury (MOI), and outcomes of pediatric trauma in a level 1 trauma centre in one of the Arab Middle Eastern countries. Methods: A retrospective analysis of pediatric injury data was conducted. All trauma patients (<18 years old) requiring hospitalization between 2012 and 2021 were included. Patients were categorized and compared based on the MOI, age-group and injury severity. Results: A 3,058 pediatric patients (20% of the total trauma admissions) were included in the study. The incidence rate in 2020 was 86 cases per 100,000 pediatric population in Qatar. The majority were male (78%) and the mean age was 9.3 ± 5.7 years. Nearly 40% had head injuries. The in-hospital mortality rate was 3.8%. The median injury severity score (ISS) (interquartile range; IQR) was 9 (4-14) and Glasgow coma scale (GCS) was 15 (IQR 15-15). Almost 18% required Intensive Care admission. Road Traffic Injuries (RTI) were more frequent in 15-18 years old whereas ≤4 years group was mostly injured by falling objects. The case fatality rate was higher among females (5.0%), and in 15-18 years (4.6%) and <4 years (4.4%) group. Pedestrian injuries were more lethal among the MOI. One fifth had severe injury with a mean age of 11 ± 6 and 9.5% had ISS of ≥25. Predictors of severe injury were age (10 years old and above) and RTI. Conclusion: Almost one-fifth of the trauma admissions at the level 1 trauma centre in Qatar is due to traumatic injuries among the pediatric population. Developing strategies that are based on understanding the age- and mechanism-specific patterns of traumatic injuries among the pediatric population remains crucial.
RESUMEN
Colorectal cancer (CRC) is a major health problem worldwide. Dicarbonyl electrophiles, such as isolevuglandins (isoLGs), are generated from lipid peroxidation and form covalent adducts with amine-containing macromolecules. We have shown high levels of adducts of isoLGs in colonic epithelial cells of patients with CRC. We thus investigated the role of these reactive aldehydes in colorectal cancer development. We found that 2-hydroxybenzylamine (2-HOBA), a natural compound derived from buckwheat seeds that acts as a potent scavenger of electrophiles, is bioavailable in the colon of mice after supplementation in the drinking water and does not affect the colonic microbiome. 2-HOBA reduced the level of isoLG adducts to lysine as well as tumorigenesis in models of colitis-associated carcinogenesis and of sporadic CRC driven by specific deletion of the adenomatous polyposis coli gene in colonic epithelial cells. In parallel, we found that oncogenic NRF2 activation and signaling were decreased in the colon of 2-HOBA-treated mice. Additionally, the growth of xenografted human HCT116 CRC cells in nude mice was significantly attenuated by 2-HOBA supplementation. In conclusion, 2-HOBA represents a promising natural compound for the prevention and treatment of CRC.