Pre- and post-implementation protocol for non-operative management of grade III-V splenic injuries: An observational study.

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.

Seizure Prophylaxis in Young Patients Following Traumatic Brain Injury.

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.

Motorcycle-related crashes before and during the COVID-19 pandemic: A comparative retrospective observational study from the Middle East.

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.

Time and Risk Factors of Trauma-Related Mortality: A 5-Year Retrospective Analysis From a National Level I Trauma Center.

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 (≤48 h) vs late (>48 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.

Beta-Adrenergic Receptor Polymorphism and Patho-Genetics of Trauma: A Transformational Frontier of Personalized Medicine in Neurotrauma.

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.

Academic and healthcare efforts from Cessation to complete resumption of professional football tournaments during COVID-19 pandemic: A narrative review.

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.

Myeloid deletion of talin-1 reduces mucosal macrophages and protects mice from colonic inflammation.

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.

Acute Changes in Body Muscle Mass and Fat Depletion in Hospitalized Young Trauma Patients: A Descriptive Retrospective Study.

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.

Exosome nanovesicles as potential biomarkers and immune checkpoint signaling modulators in lung cancer microenvironment: recent advances and emerging concepts.

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.

Hypusination Maintains Intestinal Homeostasis and Prevents Colitis and Carcinogenesis by Enhancing Aldehyde Detoxification.

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.

Patterns, mechanism of injury and outcome of pediatric trauma at a level 1 trauma centre: a descriptive retrospective analysis.

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.

Electrophilic reactive aldehydes as a therapeutic target in colorectal cancer prevention and treatment.

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.

The impact of emergency department length of stay on the outcomes of trauma patients requiring hospitalization: a retrospective observational study.

BACKGROUND: We aimed to explore the impact of the emergency department length of stay (EDLOS) on the outcome of trauma patients. METHODS: A retrospective study was conducted on all trauma patients requiring hospitalization between 2015 and 2019. Patients were categorized into 4 groups based on the EDLOS (<4 h, 4-12 h,12-24 h, and >24 h). Data were analyzed using Chi-square test (categorical variables), Student's t-test (continuous variables), correlation coefficient, analysis of variance and multivariate logistic regression analysis for identifying predictors of short EDLOS and hospital mortality. RESULTS: The study involved 7,026 patients with a mean age of 32.1±15.6 years. One-fifth of patients had a short EDLOS (<4 h) and had higher level trauma team T1 activation (TTA-1), higher Injury Severity Score (ISS), higher shock index (SI), and more head injuries than the other groups (P=0.001). Patients with an EDLOS >24 h were older (P=0.001) and had more comorbidities (P=0.001) and fewer deaths (P=0.001). Multivariate regression analysis showed that the predictors of short EDLOS were female gender, GCS, SI, hemoglobin level, ISS, and blood transfusion. The predictors of mortality were TTA-1 (odds ratio [OR]=4.081, 95%CI: 2.364-7.045), head injury (OR=3.920, 95%CI: 2.413-6.368), blood transfusion (OR=2.773, 95%CI: 1.668-4.609), SI (OR=2.132, 95%CI: 1.364-3.332), ISS (OR=1.077, 95%CI: 1.057-1.096), and age (OR=1.040, 95%CI: 1.026-1.054). CONCLUSIONS: Patients with shorter EDLOS had different baseline characteristics and hospital outcomes compared with patients with longer EDLOS. Patients with prolonged EDLOS had better outcomes; however, the burden of prolonged boarding in the ED needs further elaboration.

A compendium of Androgen Receptor Variant 7 target genes and their role in Castration Resistant Prostate Cancer.

Persistent androgen receptor (AR) signalling is the main driver of prostate cancer (PCa). Truncated isoforms of the AR called androgen receptor variants (AR-Vs) lacking the ligand binding domain often emerge during treatment resistance against AR pathway inhibitors such as Enzalutamide. This review discusses how AR-Vs drive a more aggressive form of PCa through the regulation of some of their target genes involved in oncogenic pathways, enabling disease progression. There is a pressing need for the development of a new generation of AR inhibitors which can repress the activity of both the full-length AR and AR-Vs, for which the knowledge of differentially expressed target genes will allow evaluation of inhibition efficacy. This review provides a detailed account of the most common variant, AR-V7, the AR-V7 regulated genes which have been experimentally validated, endeavours to understand their relevance in aggressive AR-V driven PCa and discusses the utility of the downstream protein products as potential drug targets for PCa treatment.

Management of Traumatic Femur Fractures: A Focus on the Time to Intramedullary Nailing and Clinical Outcomes.

BACKGROUND: Femur shaft factures (FSF) are common injuries following high-energy mechanisms mainly involving motor vehicle crashes (MVC). We evaluated the timings of nailing management and analyzed the pattern of fracture union and outcome in a level 1 trauma center. METHODS: This was a retrospective observational study of all the admitted trauma patients who sustained femoral fractures between January 2016 and September 2020. Data were analyzed and compared based on time to Intramedullary Nailing (IMN) (<12 h, 12-24 h and >24 h) and outcomes of FSF (union, delayed union and nonunion). RESULTS: A total of 668 eligible patients were included in the study, of which the majority were males (90.9%) with a mean age of 34.5 ± 15.8, and 54% of the injuries were due to MVCs. The chest (35.8%) was the most commonly associated injured body region, followed by the pelvis (25.9%) and spine (25.4%). Most of femur fractures (93.3%) were unilateral, and 84.4% were closed fractures. The complete union of fractures was observed in 76.8% of cases, whereas only 4.2% and 3.3% cases had delayed union and nonunion, respectively, on the clinical follow-up. Patients in the delayed IMN (>24 h) were severely injured, had bilateral femur fracture (p = 0.001) and had higher rate of external fixation, blood transfusion, pulmonary complications and prolonged hospitalization. Non-union proportion was greater in those who had IMN <24 h, whereas a delayed union was greater in IMN done after 24 h (p = 0.5). Those with a nonunion femur fracture were more likely to have bilateral fracture (p = 0.003), frequently had retrograde nailing (p = 0.01), and high-grade femur fracture (AO type C; p = 0.04). CONCLUSION: This study showed that femur fracture is not uncommon (8.9%), which is manifested with the variety of clinical characteristics, depending on the mechanism, management and outcome in our center. Bilateral fracture, retrograde nailing and AO classification type C were the significant risk factors of non-union in patients with diaphyseal fractures. The timing of IMN has an impact on the fracture union; however, it is not a statistically significant difference. Therefore, the treating physicians should consider the potential risk factors for a better outcome by careful selection of treatment in sub-groups of patients.

Bio-secure bubble during the COVID-19 pandemic to host the Asian Football Confederation (AFC) Champions League: A retrospective observational study.

Background and Aims: To describe the COVID-19 positivity rate among football players, team staff, and local organizing committee members participated in the Asian Football Confederation (AFC) Champions League (West) tournament organized with the Bio-secure bubble protocol in place. Methods: A retrospective observational study was carried out to include a total of 2184 participants during the AFC-West tournament in Qatar, which was a 3-week event (September 14-October 3, 2020). This event was undertaken under the Bio-secure bubble protocol, which was developed and implemented for sports events in Qatar during the pandemic. Within 72 h of departure and upon arrival in Qatar, all participants underwent reverse-transcriptase polymerase chain reaction testing (RT-PCR) to diagnose COVID-19. The test was considered positive based on the cycle threshold (cT) value which was <30, whereas, reactive if cT value was ≥30 and <40, and negative (cT > 40). Results: Of the 2184 participants (528 players, 388 team staff, and 1268 local staff), 916 international participants were tested for COVID-19 PCR upon arrival at the Hamad International Airport, whereas the local staff (n = 1268) were tested 2 days before entering the bubble. The mean age of the players was 27.5 ± 9.8. Fifteen teams participated and as many as 60 matches were played over 3 weeks. Most participants tested negative (95.3%) and 3.9% tests were inconclusive. During the entire tournament, the positivity rate was 2.7% among all participants. Of the total positive cases, 0.8% were positive before entering the bubble system. The remaining (1.9%) tested positive during the tournament phase (19 players, 16 team officials, and 8 organizing committee staff). Conclusion: Bio-secure bubble protocol operated in a controlled environment presents a minimal risk of COVID-19 infection for hosting international football events. This framework could be benchmarked to resume professional football competitions under unprecedented pandemic situations.

Shock Index for the Prediction of Interventions and Mortality in Patients With Blunt Thoracic Trauma.

INTRODUCTION: Shock index (SI) is a bedside simple scoring tool; however, it has not yet been tested in blunt thorax trauma (BTT). We sought to evaluate the prognostic value of SI for chest interventions (thoracostomy tube or thoracotomy), blood transfusion, and mortality in patients with BTT. We hypothesized that high SI is associated with worse outcomes in patients with BTT. METHODS: We conducted a retrospective analysis of all BTT patients (chest Abbreviated Injury Score [AIS] > 1) hospitalized in a level 1 trauma center between 2011 and 2020. Patients with AIS >1 for head or abdominal injuries and patients undergoing open reduction and internal fixation surgery or penetrating injuries were excluded. Patients were categorized into two groups (low SI <0.80 versus high SI ≥0.80) based on the receiver operating characteristic curve analysis. Multivariable regression analysis was performed to identify the predictors of mortality. RESULTS: A total of 1645 patients were admitted with BTT; of them, 24.5% had high SI. The mean age was 39.2 ± 15.2 y, and most were males (91%). Patients with high SI were younger, had sustained severer injuries, and required more chest interventions (P = 0.001), blood transfusion (P = 0.001), and massive transfusion protocol activation (P = 0.001) compared with low SI group. The overall in-hospital mortality rate was 2.6%, which was more in the high SI group (8.2% versus 0.8%; P = 0.001). SI significantly correlated with age (r = -0.281), injury severity score (r = 0.418), Glasgow Come Score on arrival (r = -0.377), Trauma and Injury Severity Score (r = -0.144), Revised Trauma Score (r = -0.219), serum lactate (r = 0.434), blood transfusion units (r = 0.418), and chest AIS (r = 0.066). SI was an independent predictor of mortality (odds ratio 3.506; 95% confidence interval 1.389-8.848; P = 0.008), and this effect persisted after adjustment for chest intervention (odds ratio 2.923; 95% confidence interval 1.146-7.455; P = 0.02). CONCLUSIONS: The present study highlights the prognostic value of SI as a rapid bedside tool to predict the use of interventions and the risk of mortality in patients with BTT. The study findings help the emergency physicians for early and appropriate risk stratification and triaging of patients with BTT.

Predisposing Factors and Outcome of Acute Kidney Injury After Blunt Trauma: A 10-Year Study.

INTRODUCTION: Acute kidney injury (AKI) indicates an impairment of the renal function following blunt trauma. It is multifactorial and associated with an increased risk of morbidity and mortality. The incidence and risk factors of AKI in young patients with trauma are not well-described. This study aimed to evaluate the incidence, clinical characteristics, and outcomes of post-traumatic AKI. We hypothesized that AKI is associated with worse outcomes in patients with trauma. METHODS: This was a retrospective study of all adult trauma patients admitted to a level 1 trauma center between 2011 and 2021. AKI was diagnosed on the basis of the Kidney Disease Improving Global Outcomes criteria. Data were collected and analyzed for patients with and without AKI using chi-square test and Student's t-test. Multivariate logistic regression analysis and Kaplan-Meier curves were performed. RESULTS: A total of 17,341 patients with trauma were evaluated, of which 140 (0.8%) developed AKI. Patients with AKI were older (40 ± 20 versus 32 ± 16 y), had more comorbidities, and had a higher injury severity score (ISS) and in-hospital mortality (65% versus 3.2%) than non-AKI patients. Direct trauma to the kidney was reported in only nine (6.4%) patients in the AKI group. Among patients with AKI, nonsurvivors had a higher ISS and were more likely to have hypotension, elevated serum lactate, positive troponin, and a lower platelet-to-lymphocyte ratio than survivors. Multiple logistic regression analyses showed that age, ISS, acute respiratory distress syndrome, blood transfusion, diabetes mellitus, onadmission Glasgow coma scale score, and shock index were predictors of AKI in trauma patients, whereas ISS (odds ratio (OR) = 1.05; 95% confidence interval (CI):1.003-1.100; P = 0.03), serum lactate level (OR = 1.25; 95% CI: 1.019-1.533; P = 0.03), and hypotension (OR = 3.22; 95% CI: 1.044-9.945; P = 0.04) were independent predictors of mortality in patients with posttraumatic AKI. Kaplan-Meier survival analysis showed significant differences in mortality among the three stages of AKI (P = 0.03), with the worst outcome in stage III. However, after adjusting for age, hypotension, and ISS, the Cox regression model showed that only stage I had better survival than stages II and III, whereas no survival difference was noted between stages II and III (P = 0.06). CONCLUSIONS: AKI in young trauma patients is uncommon and associated with a prolonged hospital course and higher mortality. This study identified factors that independently predicted the development of AKI and its outcomes in patients with trauma. However, further prospective and multicenter studies are required to minimize the incidence and complications of posttraumatic AKI.

Hybrid Androgen Receptor Inhibitors Outperform Enzalutamide and EPI-001 in in†vitro Models of Prostate Cancer Drug Resistance.

Androgen receptor targeted therapies for prostate cancer have serious limitations in advanced stages of the disease. While resistance to the FDA-approved enzalutamide is extensively documented, novel therapies based on epichlorohydrin scaffolds (EPI) are currently in clinical trials, but display suboptimal pharmacokinetics. Herein, we report the synthesis and biological characterisation of a novel class of compounds designed through covalently linking enzalutamide and EPI-001 through various triazole based linkers. The compounds display an 18 to 53 fold improvement in the cell killing potency towards C4-2b prostate cancer (PCa) cells compared to the gold standards of therapy, enzalutamide and EPI-001. The most promising compounds were proven to exhibit their toxicity exclusively through androgen receptor (AR) mediated pathways. This work sets the basis for the first class of hybrid AR inhibitors which successfully combine two drug moieties - EPI-001 and enzalutamide - into the same molecule.