Cholinergic regulation of vascular endothelial function by human ChAT+ T cells.

Endothelial dysfunction and impaired vasodilation are linked with adverse cardiovascular events. T lymphocytes expressing choline acetyltransferase (ChAT), the enzyme catalyzing biosynthesis of the vasorelaxant acetylcholine (ACh), regulate vasodilation and are integral to the cholinergic antiinflammatory pathway in an inflammatory reflex in mice. Here, we found that human T cell ChAT mRNA expression was induced by T cell activation involving the PI3K signaling cascade. Mechanistically, we identified that ChAT mRNA expression was induced following the attenuation of RE-1 Silencing Transcription factor REST-mediated methylation of the ChAT promoter, and that ChAT mRNA expression levels were up-regulated by GATA3 in human T cells. In functional experiments, T cell-derived ACh increased endothelial nitric oxide-synthase activity, promoted vasorelaxation, and reduced vascular endothelial activation and promoted barrier integrity by a cholinergic mechanism. Further, we observed that survival in a cohort of patients with severe circulatory failure correlated with their relative frequency of ChAT +CD4+ T cells in blood. These findings on ChAT+ human T cells provide a mechanism for cholinergic immune regulation of vascular endothelial function in human inflammation.

Transarterial Radioembolization for Management of Hepatocellular Carcinoma.

Transarterial radioembolization (TARE) with Yttrium-90 (Y90) is a growing area of study due to its benefits in early-, intermediate-, and late-stage hepatocellular carcinoma. Treatment intent, including curative therapy, bridging to transplant, and downstaging disease, informs treatment approach and dosimetry goals. Radiation lobectomy (RL) and radiation segmentectomy (RS) are the 2 main forms of Y90 administration which have shown improved survival outcomes with the development of personalized dosimetry. RS aims to achieve complete pathological necrosis with dose escalation and RL aims for local disease control as well as induction of contralateral lobe hypertrophy to improve hepatic reserve. Furthermore, TARE has been validated in head-to-head comparison to other locoregional and systemic therapies. Lastly, early potential exists for combination therapy between TARE and immune checkpoint inhibitors for advanced stage disease.

Selective internal radiation therapy using yttrium-90 microspheres for treatment of localized and locally advanced intrahepatic cholangiocarcinoma.

OBJECTIVES: To evaluate safety and effectiveness of selective internal radiation therapy (SIRT) using yttrium-90 for localized and locally advanced intrahepatic cholangiocarcinoma (iCCA). METHODS: A retrospective review was performed of patients with localized iCCA treated with SIRT at a single institution. Overall survival (OS), local tumor response, progression-free survival (PFS), and toxicity were collected. Stratified analysis was performed based on surgical resection. Predictor analysis of OS was performed using the Fine-Grey regression analysis model with patients bridged to surgery regarded as competing events. RESULTS: A total of 28 consecutive patients with localized iCCA were treated with a total of 38 sessions of SIRT (17 segmental, 13 lobar, and 8 combined deliveries) and a mean dominant target dose per session of 238.4 ± 130.0 Gy. The cumulative radiologic response rate was 16/28 (57.1%) with a median PFS of 265 days. Median survival time (MST) was 22.9 months for the entire cohort with 1-year and 3-year survival of 78.4% and 45.1%, respectively. Ten patients (34.5%) were downstaged to surgical intervention (7 resection, 3 transplant) and showed longer OS (p = 0.027). The 1-year and 3-year OS for patients who received surgery were 100% and 62.5% (95% CI: 14.2-89.3%), respectively. Age (p = 0.028), Eastern Cooperative Oncology Group performance status (p = 0.030), and objective radiologic response (p=0.014) are associated with OS. Two ≥grade 3 hyperbilirubinemia, anemia, and one pleuro-biliary fistula occurred post-SIRT. CONCLUSIONS: SIRT for localized iCCA is safe and effective in achieving radiological response, downstaging to surgery and transplant, and resulting in pathologic necrosis. CLINICAL RELEVANCE STATEMENT: Selective internal radiation therapy should be considered for patients with localized and locally advanced intrahepatic cholangiocarcinoma. KEY POINTS: • The effectiveness of radioembolization for intrahepatic cholangiocarcinoma (iCCA) can be underestimated given the inclusion of extrahepatic disease. • Radioembolization is safe and effective for local and locally advanced iCCA. Age, Eastern Cooperative Oncology Group performance status, and radiologic response are associated with survival. • Radioembolization should be considered for patients with localized and locally advanced iCCA.

15 Year Trend in Inferior Vena Cava Filter Utilization Before and After FDA Communications: Data from the National Inpatient Sample 2005-2019.

The purpose of this study was to evaluate the contemporary trends in IVC filter utilization in the inpatient setting following the FDA safety communications and to compare those trends in relation to incidence of hospital admissions involving venous thromboembolism. The National Inpatient Sample was queried between 2005-2019. There was an increasing trend in the utilization of IVC filters between 2005-2010 (P < 0.01). Following the FDA communication in 2010, this trend reversed to a decreasing trend (P < 0.001) which persisted following the second FDA communication in 2014, though there was no significant change in the rate of decline (P = 0.67). Throughout the entirety of the study period, the proportion of IVC filters placed in patients with venous thromboembolism increased from 70.8% to 82.2%.

Modified Radiation Lobectomy Strategy of Radioembolization for Right-Sided Unresectable Primary Liver Tumors.

PURPOSE: To assess the safety and effectiveness of using modified radiation lobectomy (mRL) to treat primary hepatic tumors located in the right hepatic lobe (Segments V-VIII) and to determine future liver remnant (FLR) hypertrophy. MATERIALS AND METHODS: A retrospective review was performed at a single institution to include 19 consecutive patients (7 females, 12 males) who underwent single-session mRL for right-sided primary hepatic tumors: 15 received segmentectomy plus lobectomy (segmental dose of >190 Gy and lobar dose of >80 Gy); 4 were treated with the double-segmental approach (dominant segments of >190 Gy and nondominant segments of >80 Gy). Treated tumors included 13 hepatocellular carcinoma (HCC), 4 cholangiocarcinoma (CCA), and 2 mixed-type HCC-CCA with a median dominant tumor size of 5.3 cm (interquartile range [IQR], 3.7-7.3 cm). FLR of the left hepatic lobe was measured at baseline, T1 (4-8 weeks), T2 (2-4 months), T3 (4-6 months), and T4 (9-12 months). RESULTS: Objective tumor response and tumor control were achieved in 17 of the 19 (89.5%) and 18 of the 19 (94.7%) patients, respectively. FLR hypertrophy was observed at T1 (median, 47.8%; P = .025), T2 (median, 48.4%; P = .012), T3 (median, 50.4%; P = .015), and T4 (median, 59.1%; P < .001). Patients without cirrhosis demonstrated greater hypertrophy by 6 months (median, 55.8% vs 47.2%; P = .031). One patient developed a Grade 3 adverse event (ascites requiring paracentesis) at 1-month follow-up. Grade ≥2 serum toxicities were associated with worse baseline Child-Pugh Score, serum albumin, and total bilirubin (P < .05). Among 7 patients who underwent neoadjuvant mRL, 2 underwent resection and 1 received liver transplant. CONCLUSIONS: mRL appears safe and effective for treatment of right-sided primary hepatic tumors with the benefit of promoting FLR hypertrophy.

Tumor Size and Watershed Area Correlate with Incomplete Treatment and Tumor Progression after Selective Radioembolization for Hepatocellular Carcinoma.

PURPOSE: To identify factors of incomplete treatment after segmental transarterial radioembolization (TARE) for treatment-naive and solitary hepatocellular carcinoma (HCC). MATERIALS AND METHODS: A total of 75 consecutive patients (age, 68.5 years [SD ± 8.0]; 25/75 [33.3%] women) with treatment-naive, solitary HCC underwent segmental or subsegmental TARE with glass microspheres (tumor size, 3.8 cm [SD ± 2.2]; administered dose, 222.6 Gy [SD ± 123.9]) at a single institution from November 2015 to June 2022. Radiologic response and progression-free survival (PFS) were assessed as per modified Response Evaluation Criteria in Solid Tumors. RESULTS: Complete treatment was achieved in 48 of 75 (64.0%) patients (mean follow-up, 33.2 months [SD ± 27.4]). Patients with incomplete treatment (27/75, 36%) presented with larger tumor size (5.0 [SD ± 2.5] vs 3.1 [SD ± 1.6] cm; P = .0001), with more tumors located in the watershed zone (81.5% vs 41.7%; P = .001). These patients were less likely to be bridged to transplant or resection (22.2% vs 52.1%; P = .015). Watershed tumors demonstrated worse target tumor PFS (median PFS, 19 months vs not reached; P = .0104) and overall PFS (9.1 months vs not reached; P = .0077). Watershed location was associated with worse PFS among tumors >3 cm in size (8.4 months vs not reached; P = .035) but not in tumors ≤3 cm in size (52.2 months vs not reached; P = .915). CONCLUSIONS: Tumor size and watershed location were associated with incomplete treatment after segmental TARE for HCC. Watershed tumors were associated with worse PFS, particularly tumors larger than 3 cm. These tumors may require careful treatment planning and repeated treatments to ensure a durable response.

Society of Interventional Radiology Research Reporting Standards for Genicular Artery Embolization.

Genicular artery embolization (GAE) is an emerging, minimally invasive therapy to address the global burden of knee osteoarthritis (OA) and the unmet needs for medically refractory disease. Although total knee arthroplasty has been a standard intervention for severe cases, GAE is developing into a promising alternative, particularly for patients ineligible for or unwilling to undergo surgery. GAE targets the inflammatory cascade underlying OA pathophysiology by arresting neoangiogenesis and preventing pathological neoinnervation, offering potential pain relief. Although early studies have established safety and short-term effectiveness, ensuing studies are needed to validate long-term safety, durability, and comparative effectiveness and to optimize patient selection, embolic agent selection, and administration techniques. Standardized reporting guidelines are therefore essential to enhance transparency and reproducibility across clinical trials, facilitating data aggregation and comparison. This Society of Interventional Radiology (SIR)-endorsed reporting standards consensus document provides a framework to harmonize future research efforts and to improve the interpretation of outcomes.

Evaluation of the SCAT 5 tool in the assessment of concussion in Para athletes: a Delphi study.

OBJECTIVES: To investigate if the sport concussion assessment tool version 5 (SCAT5) could be suitable for application to Para athletes with a visual impairment, a spinal cord injury, or a limb deficiency. METHODS: A 16-member expert panel performed a Delphi technique protocol. The first round encompassed an open-ended questionnaire, with round 2 onwards being composed of a series of closed-ended statements requiring each expert's opinion using a five-point Likert scale. A predetermined threshold of 66% was used to decide whether agreement had been reached by the panel. RESULTS: The Delphi study resulted in a four-round process. After round 1, 92 initial statements were constructed with 91 statements obtaining the targeted level of agreement by round 4. The expert panellist completion rate of the full four-round process was 94%. In the case of athletes with a suspected concussion with either limb deficiencies or spinal cord injuries, the panel agreed that a baseline assessment would be needed on record is ideal before a modified SCAT5 assessment. With respect to visual impairments, it was conceded that some tests were either difficult, infeasible or should be omitted entirely depending on the type of visual impairment. CONCLUSION: It is proposed that the SCAT5 could be conducted on athletes with limb deficiencies or spinal cord injuries with some minor modifications and by establishing a baseline assessment to form a comparison. However, it cannot be recommended for athletes with visual impairment in its current form. Further research is needed to determine how potential concussions could be more effectively evaluated in athletes with different impairments.

Solar desalination system for fresh water production performance estimation in net-zero energy consumption building: A comparative study on various machine learning models.

This study employs diverse machine learning models, including classic artificial neural network (ANN), hybrid ANN models, and the imperialist competitive algorithm and emotional artificial neural network (EANN), to predict crucial parameters such as fresh water production and vapor temperatures. Evaluation metrics reveal the integrated ANN-ICA model outperforms the classic ANN, achieving a remarkable 20% reduction in mean squared error (MSE). The emotional artificial neural network (EANN) demonstrates superior accuracy, attaining an impressive 99% coefficient of determination (R2) in predicting freshwater production and vapor temperatures. The comprehensive comparative analysis extends to environmental assessments, displaying the solar desalination system's compatibility with renewable energy sources. Results highlight the potential for the proposed system to conserve water resources and reduce environmental impact, with a substantial decrease in total dissolved solids (TDS) from over 6,000 ppm to below 50 ppm. The findings underscore the efficacy of machine learning models in optimizing solar-driven desalination systems, providing valuable insights into their capabilities for addressing water scarcity challenges and contributing to the global shift toward sustainable and environmentally friendly water production methods.

A Review of Professional Liability in IR: Sweeping the Mines.

Medical professional liability (MPL) is becoming a substantial issue in interventional radiology (IR), with both impact on health care costs and negative psychological effects on physicians. MPL presents special challenges within IR because of the field's complex and innovative therapies that are provided to a diverse group of patients and complicated by the off-label use of devices and drugs that is pervasive in the field. This review discusses the principles and practices to avoid and manage MPLs that are specific to the field of IR.

Quantifying Change in Perfusion after Genicular Artery Embolization with Parametric Analysis of Intraprocedural Digital Subtraction Angiograms.

PURPOSE: To quantify perfusion changes during genicular artery embolization (GAE) with the qualitatively described "pruning" technique using parametric analysis. MATERIALS AND METHODS: A total of 12 patients underwent unilateral GAE with a total of 36 vessels embolized. Among 34 of the 36 vessels embolized, regions of interest (ROIs) were placed on parent vessels (PVs) and hyperemic target vessels (TVs) before and after GAE. For each ROI, peak intensity (PI), time to arrival (TTA), and area under the curve (AUC) were computed and compared between PV and TV. Volume of embolic administered was correlated with adverse events. RESULTS: No change was seen in PI, TTA, and AUC in the PV after GAE. Reduction in AUC (1,495.7 ± 521.5 vs 1,667.4 ± 574.0; P << .01) and PI (195.1 ± 43.8 vs 224.3 ± 49.2; P << .01) with increase in TTA (3.42 s ± 1.70 vs 1.92 s ± 1.45; P << .01) within the TV were observed after GAE. Median follow-up time was 89 days (range, 21-254 days). Reduction in clinical symptoms was also noted based on the Western-Ontario and McMaster Universities Arthritis Index total and pain scale at 1 month (total, 42.9% ± 23.0; pain, 54.4% ± 9.8; P << .01) and 3 months (total, 42.5% ± 14.9; pain, 57.8% ± 10.6; P << .01). Eight total mild adverse events (minor/self-limiting) were noted per Society of Interventional Radiology guidelines. A larger volume of embolic was observed in knees with skin changes (3.4 mL ± 0.4 vs 1.7 mL ± 0.4; P << .001). Furthermore, all skin changes were seen with embolic volumes >3.0 mL. CONCLUSIONS: Quantification of intraprocedural perfusion changes with GAE demonstrated reduced flow to the TV with maintained flow in the PV and acceptable clinical outcomes. A potential relationship between embolic volume and nontarget embolization was also highlighted.

Unplanned 30-Day Readmissions after Management of Submassive and Massive Acute Pulmonary Embolism: Catheter-Directed versus Systemic Thrombolysis.

PURPOSE: To compare 30-day readmission and in-hospital outcomes from the Nationwide Readmissions Database (NRD) for catheter-directed thrombolysis (CDT) versus systemic intravenous thrombolysis (IVT) as treatments for acute submassive or massive pulmonary embolism (PE). MATERIALS AND METHODS: The NRD was queried from 2016 to 2019 for adult patients with nonseptic acute PE who underwent IVT or CDT. Massive PE was distinguished from submassive PE if patients had concurrent International Classification of Diseases (ICD-10) codes corresponding to mechanical ventilation, vasopressors, or shock. Propensity score-matched analysis was conducted to infer the association of CDT versus IVT in unplanned 30-day readmissions, nonroutine discharge, gastrointestinal bleeding (GIB), and intracranial hemorrhage (ICH). These results are demonstrated as average treatment effects (ATEs) of IVT compared with those of CDT. RESULTS: A total of 37,116 patients with acute PE were studied; 18,702 (50.3%) underwent CDT, and 18,414 (49.7%) underwent IVT. A total of 2,083 (11.1%) and 3,423 (18.6%) were massive PEs in the 2 groups, respectively (P < .001). The ATE of IVT was higher than that of CDT regarding unplanned 30-day readmissions (ATE, 0.019; P < .001), GIB (ATE, 0.012; P < .001), ICH (ATE, 0.003; P = .017), and nonroutine discharge (ATE, 0.022; P = .006). The subgroup analysis of patients with submassive PE demonstrated that IVT had a higher ATE regarding unplanned 30-day readmission (ATE, 0.028; P < .001), GIB (ATE, 0.008; P = .003), ICH (ATE, 0.002; P = .035), and nonroutine discharge (ATE, 0.019; P = .022) than CDT. CONCLUSIONS: CDT had a lower likelihood of unplanned 30-day readmissions, including when stratified by a submassive PE subtype. Additionally, adverse events, including ICH and GIB, were more likely among patients who received IVT than among those who received CDT.

Yttrium-90 Radioembolization and Concomitant Systemic Gemcitabine, Cisplatin, and Capecitabine as the First-Line Therapy for Locally Advanced Intrahepatic Cholangiocarcinoma.

PURPOSE: To determine the safety and effectiveness of yttrium-90 transarterial radioembolization (TARE) combined with systemic gemcitabine, cisplatin, and capecitabine for the first-line treatment of locally advanced intrahepatic cholangiocarcinoma (iCCA). MATERIALS AND METHODS: Data of 13 patients with treatment-naïve, locally advanced iCCA treated with a downstaging protocol using gemcitabine, cisplatin, TARE, and capecitabine were retrospectively reviewed. Overall survival (OS), local tumor response (modified Response Evaluation Criteria in Solid Tumors), progression-free survival (PFS), technical adverse events, and toxicity were measured. RESULTS: Calculated from the time of diagnosis, the median OS was 29 months (95% confidence interval [CI], 15 to not reached), with a 1-year OS of 84.6% (95% CI, 52.2%-95.9%) and 2-year OS of 52.9% (95% CI, 20.3%-77.5%). The median OS values were 24 months (95% CI, 8 to not reached) and 21 months (95% CI, 5 to not reached) from the time of initial cycle of chemotherapy and TARE, respectively. Patients who were downstaged to surgery (n = 7, 53.8%) had a more favorable OS (median OS, not reached vs 15 months; P = .0221). Complete and partial radiologic responses were achieved in 5 (38.5%) and 6 (46.2%) patients, respectively. The median PFS was 13 months (95% CI, 12 to not reached). Although no serum toxicity with Grade >2 occurred within 3 months after TARE, 1 patient was no longer a surgical candidate given suboptimal nutrition status despite successful downstage on imaging studies. Two patients required a reduced dose or delay of post-TARE chemotherapy. CONCLUSIONS: First-line combination therapy with TARE and systemic gemcitabine, cisplatin, and capecitabine is an effective treatment with an acceptable safety profile for iCCA with a high rate of downstaging to resection.

Segmental Yttrium-90 Radioembolization Using Glass Microspheres Greater than 400 Gray for the Treatment of Intrahepatic Cholangiocarcinoma: A Preliminary Experience.

Radiation segmentectomy with a dose of >190 Gy using yttrium-90 (90Y) glass microspheres for intrahepatic cholangiocarcinoma (iCCA) has been shown to be safe and effective. The present study further increased the dose to >400 Gy for treatment of iCCA as complete pathologic necrosis has been shown in hepatocellular carcinoma using this ablative approach. A total of 10 patients with 13 tumors (median size, 5.3 cm; range, 1.5-13.6 cm) at a single institution underwent >400-Gy segmental radioembolization. Objective response was achieved in all tumors (13 of 13, 100%). One patient developed a Grade 3 or greater major adverse event (stroke and hepatic decompensation). One patient was bridged to transplant (>95% pathologic necrosis), whereas another underwent resection (>99% necrosis). Contralateral hypertrophy was observed in 6 out of 6 patients treated with modified lobectomy dosing, with a functional liver reserve increase from a median of 31.5% to 57.1%. The present report suggests that segmental transarterial radioembolization with >400 Gy is feasible in terms of safety and effectiveness for treating iCCA.

Technical outcomes of below-the-elbow revascularization for upper extremity critical limb ischemia.

OBJECTIVES: This study aims to report the technical results of below-the-elbow arterial revascularization in patients with critical hand ischemia. METHODS: We retrospectively identified upper extremity critical limb ischemia patients treated with below-the-elbow arterial intervention between 2013 and 2017. Patient demographics, comorbidities, and procedural data were reviewed and technical success was evaluated. RESULTS: Seven patients with 12 arteries that were affected by critical hand ischemia were treated. All patients had a history of end-stage renal disease. The technical success rate was 83.3%. There were no major or minor complications. The average follow-up duration was 9 months (2-26 months). One patient underwent a digital amputation at 8 months. CONCLUSION: Arterial revascularization of the below-the-elbow arteries for critical hand ischemia is safe and technically feasible.

Concussion through my eyes: a qualitative study exploring concussion experiences and perceptions of male English blind footballers.

OBJECTIVES: Athletes with impairments play sports with a risk of sustaining head injuries and concussions. However, the scientific knowledge needed to improve care is lacking. This qualitative study explores English blind 5-a-side footballers' perceptions of concussion, concussion risks and prevention to improve para concussion care. METHODS: Nine semi-structured interviews were conducted with male English blind footballers (six current and three retired). Data were analysed by thematic analysis using a six-stage approach. RESULTS: Blind footballers were not sure about the number of concussions they had sustained. They lacked an understanding of what to experience when concussed, and they perceived the diagnosis and experience of a concussion to be different for a person without vision. Perceived concussion severity and previous concussion experiences were key concepts affecting their concussion reporting behaviours. Participants mentioned spatial orientation and sleep are important to function in daily life and were affected by concussions. However, these factors are not adequately included in current assessment tools or clinical guidance for sports-related concussions. CONCLUSION: Blind footballers suggested the quality and accuracy of reported concussions were impacted by lack of concussion experience, knowledge and concomitant impairment. A better understanding of concussion symptoms and injury mechanisms will improve concussion reporting for athletes with visual impairments. These athlete insights should guide future studies and para sports governing body initiatives to improve concussion reporting, diagnosis and management in para athletes.

Endovascular thrombectomy and repair of suprarenal inferior vena cava thrombosis: A case series.

OBJECTIVES: The objective of this study is to document the combined use of catheter-based thrombectomy/thrombolysis with endovascular repair of high-risk segments of the inferior vena cava in the setting of iatrogenic and traumatic injuries. While the use of endovascular techniques to treat caval thrombosis is well documented and often preferred due to its minimally invasive nature, there is still little literature that focuses on the nuances related to injury of high mortality areas of the IVC as a result of major trauma, transplant, and other surgical interventions. METHODS: An IRB-approved retrospective review of all patients undergoing IVC thrombectomy was performed at a single tertiary care academic center between January 2018 and July 2021. Cases were subsequently selected based on those who underwent primary mechanical thrombectomy followed by endovascular stenting (or angioplasty). Among this cohort, four patients who underwent this procedure in the context of iatrogenic and traumatic injuries were included. RESULTS: All four patients undergoing primary mechanical thrombectomy followed by endovascular stenting (or angioplasty) due to IVC thrombus and/or stenosis were technically successful with immediate positive clinical outcomes. CONCLUSIONS: Mechanical thrombectomy in conjunction with IVC recanalization via stenting may be a useful intervention with promising technical success and positive clinical outcomes for occlusive thrombosis and IVC stenosis.

Amsterdam 2022 process: A summary of the methodology for the Amsterdam International Consensus on Concussion in Sport.

The purpose of this paper is to summarise the consensus methodology that was used to inform the International Consensus Statement on Concussion in Sport (Amsterdam 2022). Building on a Delphi process to inform the questions and outcomes from the 5th International Conference on Concussion in Sport, the Scientific Committee identified key questions, the answers to which would help encapsulate the current science in sport-related concussion and help guide clinical practice. Over 3½ years, delayed by 2 years due to the pandemic, author groups conducted systematic reviews on each selected topic. The 6th International Conference on Concussion in Sport was held in Amsterdam (27-30 October 2022) and consisted of 2 days of systematic review presentations, panel discussions, question and answer engagement with the 600 attendees, and abstract presentations. This was followed by a closed third day of consensus deliberations by an expert panel of 29 with observers in attendance. The fourth day, also closed, was dedicated to a workshop to discuss and refine the sports concussion tools (Concussion Recognition Tool 6 (CRT6), Sport Concussion Assessment Tool 6 (SCAT6), Child SCAT6, Sport Concussion Office Assessment Tool 6 (SCOAT6) and Child SCOAT6). We include a summary of recommendations for methodological improvements for future research that grew out of the systematic reviews.

Consensus statement on concussion in sport: the 6th International Conference on Concussion in Sport-Amsterdam, October 2022.

For over two decades, the Concussion in Sport Group has held meetings and developed five international statements on concussion in sport. This 6th statement summarises the processes and outcomes of the 6th International Conference on Concussion in Sport held in Amsterdam on 27-30 October 2022 and should be read in conjunction with the (1) methodology paper that outlines the consensus process in detail and (2) 10 systematic reviews that informed the conference outcomes. Over 3½ years, author groups conducted systematic reviews of predetermined priority topics relevant to concussion in sport. The format of the conference, expert panel meetings and workshops to revise or develop new clinical assessment tools, as described in the methodology paper, evolved from previous consensus meetings with several new components. Apart from this consensus statement, the conference process yielded revised tools including the Concussion Recognition Tool-6 (CRT6) and Sport Concussion Assessment Tool-6 (SCAT6, Child SCAT6), as well as a new tool, the Sport Concussion Office Assessment Tool-6 (SCOAT6, Child SCOAT6). This consensus process also integrated new features including a focus on the para athlete, the athlete's perspective, concussion-specific medical ethics and matters related to both athlete retirement and the potential long-term effects of SRC, including neurodegenerative disease. This statement summarises evidence-informed principles of concussion prevention, assessment and management, and emphasises those areas requiring more research.

Soat2 ties cholesterol metabolism to ß-oxidation and glucose tolerance in male mice.

BACKGROUND: Sterol O-acyltransferase 2 (Soat2) encodes acyl-coenzyme A:cholesterol acyltransferase 2 (ACAT2), which synthesizes cholesteryl esters in hepatocytes and enterocytes fated either to storage or to secretion into nascent triglyceride-rich lipoproteins. OBJECTIVES: We aimed to unravel the molecular mechanisms leading to reduced hepatic steatosis when Soat2 is depleted in mice. METHODS: Soat2-/- and wild-type mice were fed a high-fat, a high-carbohydrate, or a chow diet, and parameters of lipid and glucose metabolism were assessed. RESULTS: Glucose, insulin, homeostatic model assessment for insulin resistance (HOMA-IR), oral glucose tolerance (OGTT), and insulin tolerance tests significantly improved in Soat2-/- mice, irrespective of the dietary regimes (2-way ANOVA). The significant positive correlations between area under the curve (AUC) OGTT (r = 0.66, p < 0.05), serum fasting insulin (r = 0.86, p < 0.05), HOMA-IR (r = 0.86, p < 0.05), Adipo-IR (0.87, p < 0.05), hepatic triglycerides (TGs) (r = 0.89, p < 0.05), very-low-density lipoprotein (VLDL)-TG (r = 0.87, p < 0.05) and the hepatic cholesteryl esters in wild-type mice disappeared in Soat2-/- mice. Genetic depletion of Soat2 also increased whole-body oxidation by 30% (p < 0.05) compared to wild-type mice. CONCLUSION: Our data demonstrate that ACAT2-generated cholesteryl esters negatively affect the metabolic control by retaining TG in the liver and that genetic inhibition of Soat2 improves liver steatosis via partitioning of lipids into secretory (VLDL-TG) and oxidative (fatty acids) pathways.