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Objectives: Trauma-induced coagulopathy remains a significant contributor to mortality in severely injured patients. Fibrinogen is essential for early hemostasis and is recognized as the first coagulation factor to fall below critical levels, compromising the coagulation cascade. Recent studies suggest that early administration of fibrinogen concentrate is feasible and effective to prevent coagulopathy. We conducted a scoping review to characterize the existing quantity of literature and to explore the usage of prehospital fibrinogen concentrate products in improving clinical outcomes in trauma patients., Methods: A search strategy was developed and underwent Peer Review of Electronic Search Strategies (PRESS) review in consultation with an information specialist. We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and Scopus from inception to May 6, 2024. English studies evaluating prehospital civilian and military usage of fibrinogen concentrate in trauma patients were included. Studies were assessed by three independent reviewers for meeting inclusion and exclusion criteria. A hand search of the reference lists of included articles was conducted to identify additional studies meeting inclusion criteria. Clinical endpoints regarding fibrinogen were extracted and synthesized., Results: The literature search returned 1,301 articles with six studies meeting the inclusion criteria. Five studies (83%) were conducted in civilian settings and one study (17%) was conducted in a military setting. Of the included studies, two related studies (29%) utilized a randomized control trial design. We identified five outcomes that compared fibrinogen concentrate to a placebo group. The outcomes included thromboembolic events, clotting time, maximum clot firmness, clot stability at emergency department (ED) admission, and fibrinogen concentration at ED admission. Apart from thromboembolic events, all other reported outcomes showed statistically significant differences in group comparisons, determined using p values. The four (67%) non-clinical studies underscored the robustness, practicality, and degree of fibrinogen concentrate utilization in military environments and retrieval services., Conclusions: Preliminary research suggests that prehospital fibrinogen concentrate administration in traumatic bleeding patients is both feasible and effective, improving clotting parameters. While implementing a time-saving and proactive approach with fibrinogen holds potential for enhancing trauma care, the current evidence is limited. Further studies in this novel field are warranted.

Background: Immune tolerance induction (ITI) is the gold standard for inhibitor eradication to restore the clinical efficacy of factor replacement therapy in haemophilia. However, as ITI often requires frequent administration over extended periods, it can be considered burdensome for patients and healthcare resources. Therefore, there is a need to optimise ITI treatment, particularly in patients who failed previous ITI attempts., Objectives: The ReITIrate study aimed to prospectively evaluate rescue ITI with efmoroctocog alfa, an extended half-life recombinant FVIII Fc fusion protein (herein rFVIIIFc), within a limited 60-week timeframe in patients with severe haemophilia A and inhibitors who failed previous ITI attempts., Design: ReITIrate was a phase IV, open-label, single-arm, interventional, multicentre study., Methods: Primary endpoint was ITI success (negative titre, <0.6 BU/mL; incremental recovery >66%; elimination half-life ⩾7 hours) within 60 weeks. Exploratory immunophenotype analyses were performed to characterise anti-drug antibodies (ADA) and cellular immune responses., Results: Nine of 16 enrolled subjects completed the ITI period during ReITIrate, of which one subject attained all 3 ITI success criteria after 46 weeks with no relapse. Two subjects achieved partial success (one subject met 2/3 success criteria; one met all criteria, but not simultaneously, with inhibitor recurrence). One additional subject (ITI failure) achieved negative inhibitor titre. Across these four subjects, median (range) time to negative titre was 19 (11-60) weeks. No new safety concerns were identified. IgG4 was the major contributor to the ADA IgG response. Subjects with partial/complete ITI success had fewer IgG subclasses involved than those who failed/withdrew. Immunophenotyping indicated an increase in regulatory T-cells (CD4 + CD25 + CD127 low ), supporting the ability to perform sensitive blood sampling to identify immune tolerance markers., Conclusion: This study demonstrates that ITI with rFVIIIFc given within a limited timeframe has potential benefit in a difficult-to-treat inhibitor haemophilia population who failed previous ITI attempts., Trial Registration: NCT03103542., (© The Author(s), 2024.)

Study Design: Systematic review., Objective: To systematically review the use of intraoperative methadone in spine surgery and examine its effects on postoperative opioid use, pain, length of stay, and operative time., Summary of Background Data: Spine surgery patients commonly have a history of chronic pain and opioid use, and as a result, they are at an increased risk of severe postoperative pain. While pure mu opioids remain the standard for acute surgical pain management, they are associated with significant short-term and long-term adverse events. Methadone presents an alternative to pure mu opioids which may improve postoperative management of pain following intraoperative use., Methods: A systematic review of MEDLINE, Embase, and Web of Science databases was conducted to review existing literature detailing operating time, postoperative pain, opioid usage, and hospital length of stay (LOS) following intraoperative methadone administration in spine surgery., Results: Following screening of 994 articles and application of inclusion criteria, 8 articles were included, 4 of which were retrospective. Conventional spine surgery intraoperative analgesic strategies used as comparators for intraoperative methadone included hydromorphone, ketamine, and sufentanil. Considering patient outcomes, included studies observed that patients treated with intraoperative methadone had statistically similar or significantly reduced pain scores, opioid usage, and LOS compared with comparator analgesics. However, one study observed that intraoperative methadone used in a multimodal analgesia regimen strategy with ketamine resulted in a shortened LOS compared with the use of intraoperative methadone alone. Differences in operating time between cases that used intraoperative methadone and cases that used comparator analgesics were not statistically significant among included studies., Conclusion: Methadone may present an alternative option for both intraoperative and postoperative analgesia in spine surgery recovery protocols and may reduce postoperative pain, opioid use, and LOS while maintaining consistent operating time and reduced side effects of pure mu opioids., Level of Evidence: Level II., Competing Interests: M.K. reports stock and honorarium with Globus Medical Inc., and is a consultant for Sanara MedTech. The remaining authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Migraine prevalence has been estimated to be as high as 25% during reproductive years. Despite this, and the known significantly lower odds of acute stroke being correctly diagnosed among women versus men, little is known about the migraine-stroke connection in this vulnerable population. Our study seeks to provide a consolidated examination of cerebrovascular and obstetric complications of migraines in pregnant women and to evaluate the role of concurrent comorbidities. Methods: We utilized the 2016-2020 Healthcare Cost and Utilization Project's National Inpatient Sample with the International Classification of Diseases, 10th Revision diagnostic codes to compare pregnant patients with migraines with those without migraines. Multivariable logistic regression was used to examine the incidence of subtypes of stroke while controlling for confounding variables. Results: Overall, 19,825,525 pregnant patients were evaluated; 219,175 (1.1%) had a concomitant diagnosis of migraine. Pregnant patients with migraines were more likely to suffer ischemic (0.1% versus 0.0%) or hemorrhagic stroke (0.3% versus 0.1%). On multivariate analysis, acute ischemic stroke was most strongly associated with migraine with aura (odds ratio [OR], 23.26; 95% confidence interval [CI], 18.46-29.31), followed by migraine without aura (OR, 8.15; 95% CI, 4.79-13.88). Conclusions: Pregnant women with migraine are at a significantly increased risk for both ischemic and hemorrhagic stroke. Pregnant women with migraines should be cautioned that they may be at an increased risk of stroke, particularly if they are experiencing an aura, and encouraged to contact their medical providers to rule out neurological complications.

Purpose: This study aimed to understand current prehospital trauma air-ambulance policies and triage guidelines across Canada. The research question centered on understanding the guidelines used by provinces and territories and identifying potential regional variations in air-ambulance triage., Methods: We conducted a cross-sectional survey from November 2022 to May 2023, involving trauma leaders from Canada's 13 provinces and territories. Participants were identified via the Trauma Association of Canada and professional networks. The survey, developed with expert input and pilot tested for clarity, focused on prehospital trauma-triage guidelines, level of adoption of Center for Disease Control and Prevention (CDC) triage guidelines, and auto-launch air-ambulance policies. Data were collected using an 18-item electronic survey. Potential response bias was considered, and confidentiality was maintained. A cross-sectional qualitative analysis was used to evaluate the guidelines' adoption and variations, with responses compared across regions., Results: The analysis revealed a nationwide adoption (11 of 11 respondents) of the CDC guidelines, indicating a standardized approach to patient transportation. Notably, many provinces and territories (5 of 11) endorse auto-launch protocols for air ambulances in specific scenarios. These policies offer advantages in geographically vast regions weighed against the cost of over-triage and inefficient resource allocation. Each province and territory tailors its approach based on factors such as geographic areas served, and available resources., Conclusion: This study provides a snapshot of the current state of prehospital trauma-triage guidelines in Canada. With some differences in nomenclature, Canadian provinces and territories widely apply the CDC guidelines to serve their populations. There is some regional variation on how transport is initiated within their borders. The findings underscore the delicate balance required for optimizing air-ambulance policies, considering factors such as timely access, resource allocation, and the local application of guidelines., Competing Interests: Declarations Conflict of interest There are no conflicts of interest to declare., (© 2024. The Author(s), under exclusive licence to the Canadian Association of Emergency Physicians (CAEP)/ Association Canadienne de Médecine d'Urgence (ACMU).)

Objective: This study utilizes the latest data from the Vascular Quality Initiative (VQI), which now encompasses over 50,000 transcarotid artery revascularization (TCAR) procedures, to offer a sizeable dataset for comparing the effectiveness and safety of TCAR, transfemoral carotid artery stenting (tfCAS), and carotid endarterectomy (CEA). Given this substantial dataset, we are now able to compare outcomes overall and stratified by symptom status across revascularization techniques., Methods: Utilizing VQI data from September 2016 to August 2023, we conducted a risk-adjusted analysis by applying inverse probability of treatment weighting to compare in-hospital outcomes between TCAR vs tfCAS, CEA vs tfCAS, and TCAR vs CEA. Our primary outcome measure was in-hospital stroke/death. Secondary outcomes included myocardial infarction and cranial nerve injury., Results: A total of 50,068 patients underwent TCAR, 25,361 patients underwent tfCAS, and 122,737 patients underwent CEA. TCAR patients were older, more likely to have coronary artery disease, chronic kidney disease, and undergo coronary artery bypass grafting/percutaneous coronary intervention as well as prior contralateral CEA/CAS compared with both CEA and tfCAS. TfCAS had higher odds of stroke/death when compared with TCAR (2.9% vs 1.6%; adjusted odds ratio [aOR], 1.84; 95% confidence interval [CI], 1.65-2.06; P < .001) and CEA (2.9% vs 1.3%; aOR, 2.21; 95% CI, 2.01-2.43; P < .001). CEA had slightly lower odds of stroke/death compared with TCAR (1.3% vs 1.6%; aOR, 0.83; 95% CI, 0.76-0.91; P < .001). TfCAS had lower odds of cranial nerve injury compared with TCAR (0.0% vs 0.3%; aOR, 0.00; 95% CI, 0.00-0.00; P < .001) and CEA (0.0% vs 2.3%; aOR, 0.00; 95% CI, 0.0-0.0; P < .001) as well as lower odds of myocardial infarction compared with CEA (0.4% vs 0.6%; aOR, 0.67; 95% CI, 0.54-0.84; P < .001). CEA compared with TCAR had higher odds of myocardial infarction (0.6% vs 0.5%; aOR, 1.31; 95% CI, 1.13-1.54; P < .001) and cranial nerve injury (2.3% vs 0.3%; aOR, 9.42; 95% CI, 7.78-11.4; P < .001)., Conclusions: Although tfCAS may be beneficial for select patients, the lower stroke/death rates associated with CEA and TCAR are preferred. When deciding between CEA and TCAR, it is important to weigh additional procedural factors and outcomes such as myocardial infarction and cranial nerve injury, particularly when stroke/death rates are similar. Additionally, evaluating subgroups that may benefit from one procedure over another is essential for informed decision-making and enhanced patient care in the treatment of carotid stenosis., (Copyright © 2024 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

The neuronal nucleus houses a meticulously organized genome. Within this structure, genetic material is not simply compacted but arranged into a precise and functional 3D chromatin landscape essential for cellular regulation. This mini-review highlights the importance of this chromatin landscape in healthy neurodevelopment, as well as the diseases that occur with aberrant chromatin architecture. We discuss insights into the fundamental mechanistic relationship between histone modifications, DNA methylation, and genome organization. We then discuss findings that reveal how these epigenetic features change throughout normal neurodevelopment. Finally, we highlight single-gene neurodevelopmental disorders that illustrate the interdependence of epigenetic features, showing how disruptions in DNA methylation or genome architecture can ripple across the entire epigenome. As such, we emphasize the importance of measuring multiple chromatin architectural aspects, as the disruption of one mechanism can likely impact others in the intricate epigenetic network. This mini-review underscores the vast gaps in our understanding of chromatin structure in neurodevelopmental diseases and the substantial research needed to understand the interplay between chromatin features and neurodevelopment., (© 2024 Nolan et al.; Published by Cold Spring Harbor Laboratory Press.)

Background Half of Americans will have obesity, and a quarter will have severe obesity by the year 2030. Postoperative acute renal failure (ARF) is associated with increased morbidity and mortality. Given the increase in the number of patients with obesity undergoing elective surgery, we investigated the relationship between obesity and postoperative ARF after elective general surgery procedures. Methods We performed a retrospective cohort study of patients in the 2015-2019 National Surgical Quality Improvement Program database who underwent elective general surgery procedures. The primary outcome was the presence of postoperative ARF. The patient body mass index (BMI) was categorized as normal (BMI 18.5-24.9), overweight (BMI 25-29.9), obesity class 1 and 2 (BMI 30-39.9), severe obesity (BMI 40-49.9), and extreme obesity (BMI³50). Descriptive statistics and unadjusted comparisons were performed for patients who developed postoperative ARF and those who did not. Multivariable regression analyses were used to model BMI categories and postoperative ARF, adjusting for patient- and surgical-level covariates. Results Among 424,527 patients included in the study, 3638 patients (0.8%) developed ARF. Patients who developed ARF were older, had a higher BMI, and had more serious comorbidities. After risk adjustment, there was a stepwise rise in odds of developing postoperative ARF with increasing BMI categories compared to normal BMI: (overweight: OR 1.11 (95% CI 1.0-1.23), obesity class 1 and 2: OR 1.32 (95% CI 1.2-1.46), severe obesity: OR 1.45 (95% CI 1.27-1.66), and extreme obesity: OR 1.78 (95% CI 1.47-2.15)). Conclusion Obesity is independently associated with ARF after elective general surgery procedures., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Research Ethics Board at Unity Health (Toronto, ON) issued approval REB ID 00042883. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Srivastava et al.)

Competing Interests: The author certifies that there are no funding or commercial associations (consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article related to the author or any immediate family members. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research® editors and board members are on file with the publication and can be viewed on request.

Competing Interests: The author certifies that there are no funding or commercial associations (consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article related to the author or any immediate family members. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research® editors and board members are on file with the publication and can be viewed on request.

The propensity for individuals to experience problem gambling (PG) varies depending on their motivation to gamble. The present meta-analysis assessed the effect sizes associated with various gambling motives identified in representative population samples. Studies were sourced through PsycINFO, PudMed, and databases maintained by the Alberta Gambling Research Institute and the Greo Evidence Insights. Quantitative studies and technical studies were included if they reported on gambling motivation as a correlate of PG; were published in English, French, or Spanish; used valid and reliable measures PG as an outcome variable; and targeted the general adult population. A random effects meta-analysis was conducted to estimate pooled odds ratios. A total of 26 studies were included from 17 jurisdictions, with most studies conducted in Canadian provinces (k = 17) or specific states of the United States (k = 7). Number of participants varied, depending on the gambling motivation analyzed, and ranged from 2,835 to 51,685. Fourteen unique motives were identified with odds ratios ranging from 0.53 (95% CI, 0.45, 0.63) for gambling for charity to 6.20 (95% CI, 3.83, 10.05) for the motive "to be alone", with high study heterogeneity being observed for many gambling motives, given variability in important study characteristics. The results generally indicate that coping motives were associated with large effect sizes, enhancement motives with medium effect sizes, and all other motives with small or nil effects. Coping motives are on par with other strong risk factors such as participation in online gambling or electronic gaming machines, and are therefore important elements to consider when screening for PG or designing public health messages., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Despite being recognized as a safe procedure with minimal reported complications, injecting autologous bone marrow aspirate concentrate (BMAC) as an adjuvant to arthroscopic partial meniscectomy (APM) for symptomatic patients with meniscal tears and concomitant knee osteoarthritis (OA) has not been studied in randomized controlled trials., Purpose: To compare patient-reported outcome measure (PROM) scores and radiographic outcomes in symptomatic patients with meniscal tears and concomitant mild knee OA who underwent APM with and without an autologous BMAC injection administered at the time of surgery., Study Design: Randomized controlled trial; Level of evidence, 1., Methods: Enrolled patients aged ≥18 years determined to have a symptomatic meniscal tear with concomitant mild knee OA suitable for APM and meeting inclusion and exclusion criteria were randomized into 2 groups: BMAC and control (no BMAC). The primary endpoint of the study was the International Knee Documentation Committee (IKDC) score at 1 year postoperatively. Secondary endpoints included radiographic outcomes (Kellgren-Lawrence grade) at 1 year postoperatively and various PROM scores, including those for the IKDC, Knee injury and Osteoarthritis Outcome Score (KOOS), visual analog scale, and Veterans RAND 12-Item Health Survey, at 3 months, 6 months, 1 year, and 2 years after meniscectomy., Results: Of the 95 enrolled patients, 83 (87.4%) were included for final analysis. No significant differences were found between the groups with regard to patient characteristics, intraoperative variables, concomitant procedures, preoperative PROM scores, or preoperative radiographic findings. At 1 year postoperatively, the BMAC group failed to demonstrate significantly better IKDC scores ( P = .687) or radiographic outcomes ( P > .05 for all radiographic measures) compared with the control group. Secondary PROM scores also did not significantly differ between the groups ( P > .05 for all PROMs). However, there were higher achievement rates of the minimal clinically important difference for the KOOS Sport (100.0% vs 80.0%, respectively; P = .023) and KOOS Symptoms (92.3% vs 68.0%, respectively; P = .038) at 1 year postoperatively in the BMAC group than in the control group. All PROMs, excluding the VR-12 mental score, showed significant improvements compared with baseline at all postoperative time points for both the BMAC and control groups., Conclusion: The addition of an autologous BMAC injection during APM did not result in significant changes in IKDC scores or radiographic outcomes at the 1-year postoperative mark. Secondary PROM scores were generally comparable between the 2 groups, but there was higher minimal clinically important difference achievement for the KOOS Sport and KOOS Symptoms at 1 year postoperatively in the BMAC group. In patients with symptoms consistent with a meniscal tear who had concomitant mild OA, the addition of BMAC to arthroscopic debridement did not affect the outcome., Registration: NCT02582489 (ClinicalTrials.gov)., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: This study was supported by internal departmental funding. A.B.Y. has received consulting fees from AlloSource, the Joint Restoration Foundation, Olympus America, and Stryker; has received research support from Arthrex and Organogenesis; has received support for education from Medwest Associates; is an unpaid consultant for and holds stock or stock options in PatientIQ and Sparta Biomedical; and holds stock or stock options in Icarus. J.D. has received support for education from Kairos Surgical, Smith & Nephew, and Elite Orthopedics; consulting fees from Encore Medical; grants from Arthrex; and hospitality payments from Wright Medical Technology and Synthes. R.M.D. has received support for education from SouthTech Orthopedics. B.F. has received research support from Arthrex, Smith & Nephew, and Sparta Biopharma; has received consulting fees from Smith & Nephew and Sparta Biopharma; has received speaking fees from Medwest Associates; and holds stock or stock options in i-BrainTech, Sparta Biopharma, and Zuno Medical. N.N.V. has received consulting fees from Arthrex and Stryker; research support from Breg and Ossur; hospitality payments from Spinal Simplicity; and royalties from Arthrex, Smith & Nephew, and Graymont Professional Products. B.J.C. has received research support from Aesculap/B. Braun and Arthrex; has received consulting fees from Arthrex, Ossio, Vericel, Bioventus, Acument, DJO, Anika Therapeutics, Endo Pharmaceuticals, Flexion Therapeutics, and Pacira Pharmaceuticals; has received royalties from Arthrex; has received support for education from Endo Pharmaceuticals and Medwest Associates; has received speaking fees from Terumo Blood and Cell Technologies; has received hospitality payments from GE Healthcare; and holds stock or stock options in BandGrip and Ossio. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.

Objective: To assess the impact of vagus nerve stimulation (VNS) on quality of life contributors such as rescue medications., Methods: Using the seizure diary application SeizureTracker™ database, we examined trends in rescue administration frequency before and after the first recorded VNS magnet swipe in patients with drug-resistant epilepsy who had 1) At least one VNS magnet swipe recorded in the diary, and 2) Recorded usage of a benzodiazepine rescue medication (RM) within 90 days prior to the first swipe. A paired Wilcoxon rank-sum test was used to assess changes in RM usage frequency between 30-, 60-, 90-, 180- and 360-day intervals beginning 30 days after first magnet swipe. Longitudinal changes in RM usage frequency were assessed with a generalized estimating equation model., Results: We analyzed data of 95 patients who met the inclusion criteria. Median baseline seizure frequency was 8.3 seizures per month, with median baseline rescue medication usage frequency of 2.1 administrations per month (SD 3.3). Significant reductions in rescue medication usage were observed in the 91 to 180 day interval after first VNS magnet swipe, and at 181 to 360 days and at 361 to 720 days, with the magnitude of reduction increasing over time. Decreases in rescue medication usage were sustained when controlling for patients who did not record rescue medication use after the first VNS magnet swipe (N=91). Significant predictors of reductions in rescue medication included baseline frequency of rescue medication usage and time after first VNS magnet swipe., Significance: This retrospective analysis suggests that usage of rescue medications is reduced following the start of VNS treatment in patients with epilepsy, and that the magnitude of reduction may progressively increase over time., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [SW, CRM & PM reported personal fees (speakers bureau) from LivaNova outside the submitted work. R.M. is the cofounder/owner of Seizure Tracker, LLC, which has received funding from Courtagen, Engage Therapeutics, Greenwich Biosciences, Neurelis, UCB, Xenon Pharmaceuticals, and grants from TuberousSclerosis Alliance. SC is the co-founder/owner of EpilepsyAI, LLC, which has received funding from Neurelis. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential Competing Interest.]., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: Haemophilia B (HB), characterised by deficient factor IX (FIX), leads to spontaneous bleeds. Severe cases require prophylactic FIX replacement. This post hoc analysis assessed the first spontaneous bleeds among previously untreated patients (PUPs) with HB treated with recombinant FIX Fc fusion protein (rFIXFc) (NCT02234310) to identify factors influencing bleeds., Methods: Subjects included paediatric PUPs with HB (≤2 IU/dL endogenous FIX). Analyses described treatment patterns (on demand [OD] vs. prophylaxis) and prophylaxis type (started on vs. switched to prophylaxis). Kaplan-Meier analyses assessed the time to first spontaneous bleed, including median time to event and fitting models with predictors for treatment regimen and/or baseline age., Results: PUPs B-LONG enrolled 33 subjects. Baseline age did not influence the time to first spontaneous bleed for any rFIXFc regimen. Those who started on prophylaxis with rFIXFc (n = 11), compared with those treated OD (n = 22), had an extended time to first spontaneous bleed. Starting prophylaxis afforded a 93% reduced risk of first spontaneous bleed versus starting OD (hazard ratio [95% confidence interval]: 0.071 [0.009-0.592]) (p = .015)., Conclusion: rFIXFc prophylaxis, particularly starting early, reduced the risk of bleeding and delayed time to first spontaneous bleed compared with rFIXFc OD. Hence, initial treatment regimens impact bleed patterns in paediatric PUPs., (© 2024 Sanofi and The Author(s). European Journal of Haematology published by John Wiley & Sons Ltd.)

The osteocutaneous radial forearm (OCRFF) is a versatile free flap option for bony defects of the head and neck, given the thinness and pliability of the forearm cutaneous paddle, pedicle length, reliability, lack of atherosclerosis, and functional concerns common to other osseous donor sites. The OCRFF was once associated with a high risk of radial fracture, in addition to concerns about the quality and durability of bone stock for osseous reconstruction, particularly for the mandible. Following the introduction of prophylactic plating of the radius, the incidence of symptomatic radial fracture has drastically decreased. Furthermore, modifications of the bony osteotomies and other evolutions of this flap harvest have increased the use of the OCRFF throughout the head and neck. Despite these advantages, the OCRFF is not widely utilized by microvascular reconstructive surgeons due to perceived limitations and risks. Herein, we present a multidisciplinary, contemporary review of the harvest technique, outcomes, and perioperative management for the OCRFF., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objectives: Fenestrated-branched endovascular technology (F/B-EVAR) is increasingly used to repair complex aortic aneurysms. While reintervention, morbidity and mortality after F/B-EVAR have been well-characterized, studies on patient-reported quality of life (QOL) after F/B-EVAR have been limited in their use of non-specific instruments and measures. We report on disease-specific QOL in patients that underwent F/B-EVAR using a validated QOL survey for aortic aneurysms., Methods: Prospectively maintained databases were used to contact living patients that underwent F/B-EVAR for pararenal or thoracoabdominal aortic aneurysms at two institutions. Eligible patients (n = 286) were asked to complete a disease-specific QOL survey previously validated in patients that underwent repair of an infrarenal abdominal aortic aneurysm. An emotional impact score (EIS) from 0-100 was derived from the survey with higher scores indicating more emotional impact and worse QOL. Respondent behavior change following F/B-EVAR was evaluated in four domains (strenuous activity, travel, heavy lifting, and sexual activity) previously identified by patients to be most impacted by an aortic aneurysm., Results: In total, 234 patients (82%) completed surveys. Mean post-operative interval to survey completion was 3.4 ± 2.8 years. Mean EIS was 16 (range 0-91) for all patients surveyed, with higher mean EIS among those within the first year after F/B-EVAR (20 vs 14). Most respondents demonstrated limited adverse emotional impact after F/B-EVAR. However, the 4 th quartile of EIS was broad (22-91), indicating that a subset of respondents had significantly worse QOL after repair. While most patients reported no post-procedure change in each of the activity domains, over 40% of patients did report decrease in strenuous activity and heavy lifting after F/B-EVAR. Those with decreased activity after repair had corresponding deficiencies in disease-specific knowledge for the domains of heavy lifting (P <.001) and sexual activity (P = .17)., Conclusions: The majority of patients who underwent F/B-EVAR in this cohort had low emotional impact on their QOL after repair. One-quarter of patients did report significant post-procedure anxiety about their aneurysm, with improvement observed beyond one year after repair. Most patients reported unchanged or decreased activity levels following F/B-EVAR, and less aneurysm-specific patient knowledge was associated with decreased activity after repair. These findings are similar to those seen in prior work using this survey instrument in patients that underwent infrarenal aneurysm repair. This work confirms the feasibility of using this survey to evaluate QOL in patients with complex aortic disease. Longitudinal evaluation in these patients may identify those at high-risk for worse QOL after F/B-EVAR., Competing Interests: Disclosures The authors have no competing interests., (Copyright © 2024 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Advanced airway management (AAM) is a critical component of prehospital critical care. Airway management in flight can be more challenging because of spatial, ergonomic, and environmental factors. This study examines the frequency of in-flight intubation (IFI), first-pass success (FPS) rates, and definitive airway sans hypoxia/hypotension on first attempt (DASH-1A) across different locations of airway management., Methods: We conducted a retrospective database analysis of all patients transported between January 2016 and July 2021 who received AAM from a single air medical service. Patient records were reviewed for location of intubation, patient characteristics, and FPS and DASH-1A rates. The primary outcome was the frequency of IFI. The secondary outcomes included FPS and DASH-1A rates by location and type of transport asset., Results: During the study period, 473 patients required AAM. Three percent (15/473) of patients were intubated in an in-flight setting, 28% (130/473) were intubated on scene, and 70% (328/473) were intubated in a health care facility. The primary reason for IFI was unanticipated cardiac arrest or clinical deterioration. The overall FPS rate was 69% (328/473), and the DASH-1A rate was 49% (194/399). Based on the location of AAM, the FPS and DASH-1A rates were the lowest for on-scene intubations (56% [74/130] and 27% [20/74], respectively). Most of the on-scene AAM took place with rotor wing flight crews., Conclusion: Airway management occurs infrequently in an in-flight setting and is necessary because of patient deterioration or cardiac arrest. Based on our results, we identified opportunities for targeted AAM quality improvement and clinical governance., Competing Interests: Declaration of competing interest The author(s) have no relevant disclosures. There was no grant funding or financial support for this manuscript., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: Cerebral venous thrombosis (CVT) is associated with a high degree of morbidity and mortality. Our objective is to elucidate characteristics, treatments, and outcomes of patients with cancer and CVT (CA-CVT)., Methods: The 2016-2019 National Inpatient Sample (NIS) database was queried for patients with a primary diagnosis of CVT. Patients with a currently active diagnosis of malignancy (CA-CVT) were then identified. Demographics and comorbidities were compared between CA-CVT and CVT patients. Subgroup analyses explored patients with hematopoietic cancer and non-hematopoietic cancers. Stroke severity and treatment were explored. Inpatient outcomes studied were discharge disposition, length of stay, and mortality., Results: Between 2016 and 2019, 6,140 patients had a primary diagnosis code of CVT, and 370 (6.0%) patients had a coexisting malignancy. The most common malignancy was hematopoietic (n=195, 52.7%), followed by central nervous system (n=40, 10.8%), respiratory (n=40, 10.8%), and breast (n=40, 10.8%). These patients tended to be older than non-CA-CVT and were more likely to have coexisting comorbidities. CA-CVT patients had higher severity scores on the International Study of Cerebral Vein and Dural Sinus Thrombosis Risk Score (ISCVT-RS) and increased complications. In a propensity-score matched cohort, there were no differences in inpatient outcomes., Conclusion: Malignancy occurs in 6% of patients presenting with CVT and should be considered a potential comorbidity in instances where clear causes of hypercoagulabilty have not been identified. Malignancy was linked to higher mortality rates. Nonetheless, after adjusting for the severity of CVT, the outcomes for inpatients with cancer-associated CVT were comparable to those without cancer, indicating that the increased mortality associated with malignancy is probably due to more severe CVT conditions.

Objective: To comprehensively analyze reported cases of nasolacrimal squamous cell carcinoma (NLSCC), focusing on risk factors, treatment modalities, and outcomes. Additionally, investigate the impact of human Papillomavirus (HPV) status and histopathological subtypes' impact on prognosis., Data Sources: Pubmed, Embase., Review Methods: We conducted a systematic literature review to identify relevant studies reporting cases of NLSCC. The review methods adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The final update was performed on May 31, 2023., Results: The 72 studies included a total of 313 participants (mean age: 55; 60% male). Longer symptom duration (44.1 ± 59.2 months) correlated with recurrence (p = 0.004), and males exhibited higher mortality rates (19.6% vs. 2.4% in females, p = 0.01). The overall survival (OS) rate among all patients was 87.1%. Basaloid NLSCC had a worse death outcome (p ≤ 0.001). HPV-positive cases showed comparable OS, recurrence, and metastasis rates to the general population (p = 0.917, 0.851, 0.07, respectively). Comparing treatment approaches (surgery, surgery with adjuvant radiation, chemoradiotherapy [CRT] followed by surgery), no significant differences in 5 and 10-year OS rates or recurrence were observed (p = 0.4, 0.24, respectively), but 5-year metastasis events were significant (p = 0.024). Eye exenteration rates were 31.1%, 20%, and 0% for the respective treatments (p = 0.089). Induction chemotherapy saved four cases from potential exenteration with favorable prognosis., Conclusion: Early detection and diagnosis are of utmost importance in the management of NLSCC. Regardless of the treatment approach, HPV-related NLSCC demonstrated similar outcomes to the general population. Basaloid histology represents the worst subtype in terms of prognosis. Limited adjuvant CRT cases showed improved outcomes and induction chemotherapy's importance was emphasized in recent literature and our shared experience. Laryngoscope, 134:3892-3902, 2024., (© 2024 The Authors. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Recent years have seen increased attention given to identifying and describing the levels of gambling participation that confer a risk of harm in order to generate public health advice regarding lower-risk gambling. However, most of the existing literature has failed to explicitly assess these limits in a prospective manner. The purpose of this study is to employ a methodology consistent with prior investigations to evaluate the level of gambling participation associated with an increased risk of future gambling-related harm. Using data from the Alberta Gambling Research Institute's National Project Online Panel Survey, risk ratios and Receiver Operating Characteristic (ROC) analyses were used to determine the relative risk of gambling-related harm associated with participating in a greater number of gambling formats, gambling more days per month, and spending a greater proportion of income gambling. Prospective lower-risk limits were largely consistent with those identified in previous cross-sectional analyses (e.g., no more than two gambling formats, no more than once a week), with the exception that higher limits were found for the percent of household income spent gambling (3.4-6.4% vs. 1%). We advise that future research on lower-risk gambling limits consider the use of more granular assessment instruments and prospective methods to more closely evaluate the association between gambling participation and gambling harm., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: Subarachnoid hemorrhage (SAH) from spontaneous aneurysm rupture is a debilitating condition with high morbidity and mortality. Patients with SAH remain understudied, particularly concerning the evaluation of incidence and consequences of subsequent acute kidney injury (AKI). In this study, we aim to explore the risk factors and outcomes of AKI in SAH patients., Materials and Methods: International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) and International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes were used to query the National Inpatient Sample (NIS) for patients with a diagnosis of SAH between 2010-2019. Subgroup analysis was stratified by AKI diagnosis during the same hospitalization. AKI and non-AKI groups were assessed for baseline clinical characteristics, interventions, complications, and outcomes. Descriptive statistics, multivariate regressions, and propensity score-matching were performed using IBM SPSS 28., Results: Of 76,553 patients diagnosed with nontraumatic SAH between 2010-2019, 10,634 (13.89 %) had a comorbid diagnosis of AKI. SAH patients with AKI were older (p < 0.01) and more often obese (p < 0.01) compared to the non-AKI group. A multivariate regression found the diagnosis of AKI to be independently correlated with poor functional outcome (p < 0.001), above average length of stay (p < 0.001), and in-hospital mortality (p < 0.001) when controlling for age, SAH severity, and other comorbidities., Conclusions: This study showed significant association between AKI and adverse outcomes in SAH patients, and a correlation between AKI and heightened complication rates, poor functional outcome, extended hospital stays, and elevated mortality rates. Early detection of AKI in SAH patients is vital to improve their chances of recovery., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Objectives: Large language model (LLM)-based chatbots such as ChatGPT have been publicly available and increasingly utilized by the general public since late 2022. This study sought to investigate ChatGPT responses to common patient questions regarding Human Papilloma Virus (HPV) positive oropharyngeal cancer (OPC)., Methods: This was a prospective, multi-institutional study, with data collected from high volume institutions that perform >50 transoral robotic surgery cases per year. The 100 most recent discussion threads including the term "HPV" on the American Cancer Society's Cancer Survivors Network's Head and Neck Cancer public discussion board were reviewed. The 11 most common questions were serially queried to ChatGPT 3.5; answers were recorded. A survey was distributed to fellowship trained head and neck oncologic surgeons at 3 institutions to evaluate the responses., Results: A total of 8 surgeons participated in the study. For questions regarding HPV contraction and transmission, ChatGPT answers were scored as clinically accurate and aligned with consensus in the head and neck surgical oncology community 84.4% and 90.6% of the time, respectively. For questions involving treatment of HPV+ OPC, ChatGPT was clinically accurate and aligned with consensus 87.5% and 91.7% of the time, respectively. For questions regarding the HPV vaccine, ChatGPT was clinically accurate and aligned with consensus 62.5% and 75% of the time, respectively. When asked about circulating tumor DNA testing, only 12.5% of surgeons thought responses were accurate or consistent with consensus., Conclusion: ChatGPT 3.5 performed poorly with questions involving evolving therapies and diagnostics-thus, caution should be used when using a platform like ChatGPT 3.5 to assess use of advanced technology. Patients should be counseled on the importance of consulting their surgeons to receive accurate and up to date recommendations, and use LLM's to augment their understanding of these important health-related topics., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

As the incidence of subdural hematoma is increasing, it is important to understand symptomatology and clinical variables associated with treatment outcomes and mortality in this population; patients with subdural hematoma were selected from the National Inpatient Sample (NIS) Database between 2016 and 2020 using International Classification of Disease 10th Edition (ICD10) codes. Moderate-to-severe subdural hematoma patients were identified using the Glasgow Coma Scale (GCS). Multivariate regression was first used to identify predictors of in-hospital mortality and then beta coefficients were used to create a weighted mortality score. Of 29,915 patients admitted with moderate-to-severe subdural hematomas, 12,135 (40.6%) died within the same hospital admission. In a multivariate model of relevant demographic and clinical covariates, age greater than 70, diabetes mellitus, mechanical ventilation, hydrocephalus, and herniation were independent predictors of mortality ( p < 0.001 for all). Age greater than 70, diabetes mellitus, mechanical ventilation, hydrocephalus, and herniation were assigned a "1" in a weighted mortality score. The ROC curve for our model showed an area under the curve of 0.64. Age greater than 70, diabetes mellitus, mechanical ventilation, hydrocephalus, and herniation were predictive of mortality. We created the first clinically relevant weighted mortality score that can be used to stratify risk, guide prognosis, and inform family discussions.

Background: Canadian Armed Forces (CAF) operate in environments that challenge patient care, especially trauma. Military personnel often find themselves in remote settings without conventional healthcare facilities. Treating traumatic injuries, particularly hemorrhagic shock, often necessitates prehospital blood transfusion. This study aims to present an overview of the current CAF prehospital transfusion practices. Furthermore, the study compared current and developing protocols against expert-recommended guidelines., Methods: A cross-sectional survey design was employed to describe and compare CAF prehospital blood transfusion practices and protocols against expert recommendations. Topics included protocols, equipment, and procedures. An online survey targeted medical leadership and providers within CAF, with data collected from August 15 to December 15, 2023. Results were summarized descriptively. This study received approval from the Unity Health Toronto Research Ethics Board (REB 23-087)., Results: Units and teams with prehospital blood transfusion capabilities were contacted, achieving a 100 % response rate. Within CAF, Canadian Special Operations Forces Command (CANSOFCOM), Mobile Surgical Resuscitation Team (MSRT), and Canadian Medical Emergency Response Team (CMERT) possess these capabilities, established between 2013 and 2018. These programs are crucial for military operations. CAF has access to standard blood components, cold Leuko-Reduced Whole Blood (LrWB), and factor concentrates from Canadian Blood Services (CBS), available for both domestic and international missions given adequate planning and favorable conditions. Key findings indicate high adherence to recommended practices, some variability in the transfusion process, and potential benefits of standardizing prehospital transfusion practices., Conclusions: This study provided insights into CAF's implementation of prehospital transfusion practices, highlighting high adherence to national expert recommendations and the importance of structured protocols in military prehospital trauma management., Implications of Key Findings: CAF's approach and adoption of prehospital transfusion protocols lay a strong foundation for managing trauma patients in remote settings and for expanding prehospital transfusion capabilities across CFHS deployed assets. Further research is needed to advance military trauma care by adapting prehospital blood transfusion to dynamic tactical landscapes and evolving technologies., Competing Interests: Declaration of competing interest The work has not been previously published. This study is not sponsored or funded. None of the authors have any conflicts of interest to disclose., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: This study aimed to investigate adverse events (AEs) in trauma resuscitation, evaluate contributing factors, and assess methods, such as trauma video review (TVR), to mitigate AEs., Background: Trauma remains a leading cause of global mortality and morbidity, necessitating effective trauma care. Despite progress, AEs during trauma resuscitation persist, impacting patient outcomes and the healthcare system. Identifying and analyzing AEs and their determinants are crucial for improving trauma care., Methods: This narrative review explored the definition, identification, and assessment of AEs associated with trauma resuscitation within the trauma system. It includes various studies and assessment tools such as STAT Taxonomy and T-NOTECHs. Additionally, it assessed the role of TVR in detecting AEs and strategies to enhance patient safety., Conclusion: Integrated with standardized tools, TVR shows promise for identifying AEs. Challenges include ensuring reporting consistency and integrating approaches into existing protocols. Future research should prioritize linking trauma team performance to patient outcomes, and develop sustainable TVR programs to enhance patient safety., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Artificial intelligence (AI) has emerged as a potentially transformative force, particularly in the realm of emergency medicine (EM). The implementation of AI in emergency departments (ED) has the potential to improve patient care through various modalities. However, the implementation of AI in the ED presents unique challenges that influence its clinical adoption. This scoping review summarizes the current literature exploring the barriers and facilitators of the clinical implementation of AI in the ED., Methods: We systematically searched Embase (Ovid), MEDLINE (Ovid), Web of Science, and Engineering Village. All articles were published in English through November 20th, 2023. Two reviewers screened the search results, with disagreements resolved through third-party adjudication., Results: A total of 8172 studies were included in the preliminary search, with 22 selected for the final data extraction. 10 studies were reviews and the remaining 12 were primary quantitative, qualitative, and mixed-methods studies. Out of the 22, 13 studies investigated a specific AI tool or application. Common barriers to implementation included a lack of model interpretability and explainability, encroachment on physician autonomy, and medicolegal considerations. Common facilitators to implementation included educating staff on the model, efficient integration into existing workflows, and sound external validation., Conclusion: There is increasing literature on AI implementation in the ED. Our research suggests that the most common barrier facing AI implementation in the ED is model interpretability and explainability. More primary research investigating the implementation of specific AI tools should be undertaken to help facilitate their successful clinical adoption in the ED., Competing Interests: Declaration of competing interest All authors declare no conflicts of interest. No funding was provided for this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Vital signs are important factors in assessing injury severity and guiding trauma resuscitation, especially among severely injured patients. Despite this, physiological data are frequently missing from trauma registries. This study aimed to evaluate the extent of missing prehospital data in a hospital-based trauma registry and to assess the associations between prehospital physiological data completeness and indicators of injury severity., Methods: A retrospective review was conducted on all adult trauma patients brought directly to a level 1 trauma center in Toronto, Ontario by paramedics from January 1, 2015, to December 31, 2019. The proportion of missing data was evaluated for each variable and patterns of missingness were assessed. To investigate the associations between prehospital data completeness and injury severity factors, descriptive and unadjusted logistic regression analyses were performed., Results: A total of 3,528 patients were included. We considered prehospital data missing if any of heart rate, systolic blood pressure, respiratory rate or oxygen saturation were incomplete. Each individual variable was missing from the registry in approximately 20 % of patients, with oxygen saturation missing most frequently (n = 831; 23.6 %). Over 25 % (n = 909) of patients were missing at least one prehospital vital sign, of which 69.1 % (n = 628) were missing all four of these variables. Patients with incomplete data were more severely injured, had higher mortality, and more frequently received lifesaving interventions such as blood transfusion and intubation. Patients were most likely to have missing prehospital physiological data if they died in the trauma bay (unadjusted OR: 9.79; 95 % CI: 6.35-15.10), did not survive to discharge (unadjusted OR: 3.55; 95 % CI: 2.76-4.55), or had a prehospital GCS less than 9 (OR: 3.24; 95 % CI: 2.59-4.06)., Conclusion: In this single center trauma registry, key prehospital variables were frequently missing, particularly among more severely injured patients. Patients with missing data had higher mortality, more severe injury characteristics and received more life-saving interventions in the trauma bay, suggesting an injury severity bias in prehospital vital sign missingness. To ensure the validity of research based on trauma registry data, patterns of missingness must be carefully considered to ensure missing data is appropriately addressed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Introduction: Direct transport from the scene of injury to a trauma centre reduces saves lives. In Ontario, paramedics use the field trauma triage standard (FTTS) to determine if a patient meets trauma bypass criteria. Recent studies have questioned the efficacy of the FTTS in identifying severely injured patients. The objective of this study was to determine the predictive performance of the FTTS on the need for trauma center care in patients who were transported to a trauma center., Methods: This was a single-center health records study of patients transported by ambulance directly to a level 1 trauma center. Hospital based trauma center need and injury severity score-based need were defined. Bivariate associations with one or more FTTS criteria were tested using the Wilcoxon two-sample test for continuous variables, and the Chi-square or Fisher's exact test for categorical indicators. The sensitivity and specificity of each category of the FTTS were calculated., Results: There were 1427 patients included in the study, with 76% men, mean age of 40, and 76% had a blunt mechanism. The overall sensitivity and specificity of the FTTS was 90.9% and 20.8% for hospital-based need and 91.6% and 20.3 for injury severity need. The most sensitive variable for hospital-based need was physiologic criteria (53.7). Mechanism of injury was the most sensitive criteria for injury severity need (54.8). Physiological criteria had the highest association with hospital-based and injury severity need (adjusted odds ratios 7.5 [95% CI 5.8-9.8] and 5.1 [95% CI 3.9-6.7])., Conclusions: The FTTS has fair performance in identifying the need for hospital-based and injury severity need. Systolic blood pressure less than 90 mmHg, Glasgow Coma Scale (motor) less than 6, and falls greater than 6 m were most predictive of trauma center need. Improving prehospital trauma triage is critical to ensure timely transport to a trauma centre., (© 2024. The Author(s), under exclusive licence to the Canadian Association of Emergency Physicians (CAEP)/ Association Canadienne de Médecine d'Urgence (ACMU).)

Objective: Simulation education and assessment are increasingly used in prehospital curriculums. The objective of this study was to assess the challenges and feasibility of correlating evaluation data from an airway management simulation assessment with clinical performance., Methods: This study was undertaken in Ontario, the most populous province in Canada, where 13 bases are distributed in geographically diverse areas, from urban to rural and remote locations. This is a retrospective cohort study of paramedics who had completed simulation education and assessment in rapid sequence intubation. Logistic regression was used to assess for correlation between assessment scores (ie, the global score and the overall score and the definitive airway sans hypoxia/hypotension on the first attempt [DASH-1A] success in the field)., Results: DASH-1A success when grouped by base varied from 25% to 100%. The odds of DASH-1A success increased for paramedics who had a higher overall score (odds ratio [OR]: 1.03; 95% confidence interval [CI], 0.96-1.11) and for paramedics who had a higher global rating (OR: 1.27; CI, 0.73-2.21) when accounting for base intubation frequency. The odds of DASH-1A success increased for paramedics who had a higher overall score (OR: 1.01; CI, 0.93-1.09) and decreased for paramedics who had a higher global rating (OR: 0.96; CI, 0.47-1.96) when accounting for base geography., Conclusion: Although this study lacked a sample size large enough to draw conclusions, it provides a foundation and areas to improve in future work exploring the relationship between simulation assessments and clinical performance., Competing Interests: Declaration of Competing Interest The author(s) have no relevant disclosures. There was no grant funding or financial support for this manuscript., (Copyright © 2024 Air Medical Journal Associates. Published by Elsevier Inc. All rights reserved.)

Central retinal artery occlusion (CRAO) is a rare and visually debilitating vascular condition characterized by sudden and severe vision loss. CRAO is a compelling target for intravenous alteplase (tPA) and endovascular mechanical thrombectomy (MT) due to pathophysiological similarities with acute ischemic stroke; however, the utility of these interventions in CRAO remains dubious due to limited sample sizes and potential risks. To assess usage and outcomes of tPA and MT in CRAO, we queried the National Inpatient Sample database using International Classification of Disease, Ninth and Tenth edition for patients with CRAO and acute ischemic stroke between 2010 and 2019. Our cohort of 5009 CRAO patients were younger with higher rates of obesity, hypertension, long-term anticoagulant use, and tobacco use compared to acute ischemic stroke patients. CRAO patients had lower rates of tPA administration (3.41% vs 6.21%) and endovascular MT (0.38% vs 1.31%) but fewer complications, including deep vein thrombosis, pneumonia, urinary tract infection, acute kidney injury, and acute myocardial infarction (all P < 0.01). CRAO patients had lower rates of poor functional outcome (31.74% vs 58.1%) and in-hospital mortality (1.2% vs 5.64%), but higher rates of profound blindness (9.24% vs 0.58%). A multivariate regression showed no relationship between tPA and MT and profound blindness, although the limited sample size of patients receiving interventions may have contributed to this apparent insignificance. Further investigation of larger patient cohorts and alternative treatment modalities could provide valuable insights for revascularization therapies in CRAO to optimize visual restoration and clinical outcomes., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

While better management of loco-regional prostate cancer (PC) has greatly improved survival, advanced PC remains a major cause of cancer deaths. Identification of novel targetable pathways that contribute to tumor progression in PC could open new therapeutic options. The di-ganglioside GD2 is a target of FDA-approved antibody therapies in neuroblastoma, but the role of GD2 in PC is unexplored. Here, we show that GD2 is expressed in a small subpopulation of PC cells in a subset of patients and a higher proportion of metastatic tumors. Variable levels of cell surface GD2 expression were seen on many PC cell lines, and the expression was highly upregulated by experimental induction of lineage progression or enzalutamide resistance in CRPC cell models. GD2 high cell fraction was enriched upon growth of PC cells as tumorspheres and GD2 high fraction was enriched in tumorsphere-forming ability. CRISPR-Cas9 knockout (KO) of the rate-limiting GD2 biosynthetic enzyme GD3 Synthase (GD3S) in GD2 high CRPC cell models markedly impaired the in vitro oncogenic traits and growth as bone-implanted xenograft tumors and reduced the cancer stem cell and epithelial-mesenchymal transition marker expression. Our results support the potential role of GD3S and its product GD2 in promoting PC tumorigenesis by maintaining cancer stem cells and suggest the potential for GD2 targeting in advanced PC., (© 2024. The Author(s).)

Purpose: Early administration and protocolization of massive hemorrhage protocols (MHP) has been associated with decreases in mortality, multiorgan system failure, and number of blood products used. Various prediction tools have been developed for the initiation of MHP, but no single tool has demonstrated strong prediction with early clinical data. We sought to develop a massive transfusion prediction model using machine learning and early clinical data., Methods: Using the National Trauma Data Bank from 2013 to 2018, we included severely injured trauma patients and extracted clinical features available from the pre-hospital and emergency department. We subsequently balanced our dataset and used the Boruta algorithm to determine feature selection. Massive transfusion was defined as five units at 4 h and ten units at 24 h. Six machine learning models were trained on the balanced dataset and tested on the original., Results: A total of 326,758 patients met our inclusion with 18,871 (5.8%) requiring massive transfusion. Emergency department models demonstrated strong performance characteristics with mean areas under the receiver-operating characteristic curve of 0.83. Extreme gradient boost modeling slightly outperformed and demonstrated adequate predictive performance with pre-hospital data only, as well as 4-h transfusion thresholds., Conclusions: We demonstrate the use of machine learning in developing an accurate prediction model for massive transfusion in trauma patients using early clinical data. This research demonstrates the potential utility of artificial intelligence as a clinical decision support tool., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Gambling-related harm is a public health issue requiring market regulation and efforts aimed at prevention and treatment. An important consideration for the regulation of gambling is whether certain types of gambling are intrinsically more harmful than others. The present study was a comprehensive investigation of this issue in a nationwide sample of 10,199 Canadian adult gamblers that included 1346 individuals with problem gambling. We investigated (a) the univariate cross-sectional association between individual types of gambling and problem gambling; (b) the cross-sectional association between individual gambling types and problem gambling when controlling for breadth of gambling involvement; (c) the prospective/lagged relationship between participation in different gambling types and future problem gambling; and (d) the self-reports of people with gambling problems concerning the types and modalities they consider to be most problematic. Our collective results indicate that breadth of gambling involvement is a stronger predictor of gambling problems than involvement in any particular type, but that involvement in certain types (electronic gambling machines in particular, and casino table games and online gambling to a lesser extent) does confer additional risk., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To determine among infants born very preterm (VPT) or with very low birth weight (VLBW) the incidence of alterations in thyroid function and associated comorbidities; the incidence of atypical congenital hypothyroidism (CH) requiring thyroxine therapy; and reference ranges for rescreening at 1 month of age., Study Design: A retrospective review of infants born VPT or with VLBW and admitted to UC Irvine Medical Center between January 1, 2012, and December 31, 2020. Repeat thyroid screening was obtained at 1 month of life (+10 days). Infants with thyroid-stimulating hormone (TSH) >5 μIU/mL or free thyroxine <0.8 ng/dL underwent follow-up testing and endocrinology consultation. Initial newborn screening (NBS) and repeat thyroid screening data were collected via chart review. Demographic data and short-term outcomes were abstracted from the California Perinatal Quality Care Collaborative database., Results: In total, 430 patients were included; 64 of 429 patients (14.9%) had TSH >5 μIU/mL and 20 of 421 patients (4.8%) had free thyroxine <0.8 ng/dL. Logistic regression analysis identified small for gestational age (P = .044), patent ductus arteriosus (P = .013), and late-onset sepsis (P = .026) as risk factors associated with delayed TSH rise. Atypical CH requiring treatment through neonatal intensive care unit discharge was diagnosed in 6 patients (incidence of 1.4%); none were identified by NBS. The 90th percentile TSH for infants with extremely low birth weight (<1000 g) was 7.2 μIU/mL, and the 95th percentile for those with birth weight of 1000-1500 g was 6.1 μIU/mL; using these cutoff values identified all infants diagnosed with atypical CH with 100% sensitivity and 90%-95% specificity., Conclusions: Abnormal thyroid function is common in infants born preterm. Those infants, including some with atypical CH, are missed by NBS. We recommend repeat thyroid screening with TSH at 1 month of age in infants born VPT or infants with VLBW to identify CH that may require therapy., Competing Interests: Declaration of Competing Interest This study was funded through an intramural funding provided by the Division of Neonatology, Department of Pediatrics, University of CaliforniaIrvine. The authors reported no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The osteocutaneous radial forearm free flap (OCRFFF) is a versatile flap with the ability to reconstruct complex defects. We detail the techniques necessary to harvest an OCRFFF, including an outline on making 90-degree osteotomies to maximize bone harvest. In this pictorial essay, we provide illustrations of the anatomy and surgical techniques necessary for OCRFFF harvest. Detailed discussion is provided on how to protect the perforators to the bone and the approach to making osteotomies in a 90-degree fashion. The approach for prophylactic plating of the radius to prevent radius fractures is outlined. A case presentation on the real-life utilization of this flap is included. The OCRFFF is an excellent head and neck reconstructive option. While there are limitations to its use for patients requiring dental rehabilitation or long/anterior mandibular defects, for the right patient and indication it has shown great success in reconstructive efforts., (© 2024 The Authors. Head & Neck published by Wiley Periodicals LLC.)

Abstract: Fitusiran, a subcutaneous investigational small interfering RNA therapeutic, targets antithrombin to rebalance hemostasis in people with hemophilia A or B (PwHA/B), irrespective of inhibitor status. This phase 3, open-label study evaluated the efficacy and safety of fitusiran prophylaxis in males aged ≥12 years with hemophilia A or B, with or without inhibitors, who received prior bypassing agent (BPA)/clotting factor concentrate (CFC) prophylaxis. Participants continued their prior BPA/CFC prophylaxis for 6 months before switching to once-monthly 80 mg fitusiran prophylaxis for 7 months (onset and efficacy periods). Primary end point was annualized bleeding rate (ABR) in the BPA/CFC prophylaxis and fitusiran efficacy period. Secondary end points included spontaneous ABR (AsBR) and joint ABR (AjBR). Safety and tolerability were assessed. Of 80 enrolled participants, 65 (inhibitor, n = 19; noninhibitor, n = 46) were eligible for ABR analyses. Observed median ABRs were 6.5 (interquartile range [IQR], 2.2-19.6)/4.4 (IQR, 2.2-8.7) with BPA/CFC prophylaxis vs 0.0 (IQR, 0.0-0.0)/0.0 (IQR, 0.0-2.7) in the corresponding fitusiran efficacy period. Estimated mean ABRs were substantially reduced with fitusiran by 79.7% (P = .0021) and 46.4% (P = .0598) vs BPA/CFC prophylaxis, respectively. Forty-one participants (63.1%) experienced 0 treated bleeds with fitusiran vs 11 (16.9%) with BPAs/CFCs. Median AsBR and AjBR were both 2.2 with BPA/CFC prophylaxis and 0.0 in the fitusiran efficacy period. Two participants (3.0%) experienced suspected or confirmed thromboembolic events with fitusiran. Once-monthly fitusiran prophylaxis significantly reduced bleeding events vs BPA/CFC prophylaxis in PwHA/B, with or without inhibitors, and reported adverse events were generally consistent with previously identified risks of fitusiran. This trial was registered at www.ClinicalTrials.gov as #NCT03549871., (© 2024 American Society of Hematology. Published by Elsevier Inc. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Background: Mucosal melanoma, an aggressive type of malignancy different from the cutaneous melanomas commonly seen in the head and neck region, represents < 1% of all malignant melanomas. The pathogenesis of mucosal melanoma is unknown. Targetable mutations commonly seen in cutaneous melanoma, such as in the BRAF and NRAS genes, have a lower incidence in mucosal melanoma. Mucosal melanoma carries a distinct mutational pattern from cutaneous melanoma. Surgery with negative margins is the first-line treatment for mucosal melanoma, and systemic therapy is not well defined. Talimogene laherparepvec, an oncolytic viral immunotherapy, is United States Food and Drug Administration approved for the treatment of advanced malignant cutaneous melanoma, with local therapeutic benefits. Mucosal melanoma was initially excluded from talimogene laherparepvec's initial phase III clinical trial., Case Presentation: We present the case of a white female patient in her 40s with past medical history of systemic lupus erythematous, scleroderma, and estrogen-receptor-positive invasive ductal breast carcinoma. Following a bilateral mastectomy, the patient was found to have BRAF-negative mucosal melanoma of her hard palate with a soft palate skip lesion. Owing to the presence of a skip mucosal lesion as well as the anticipated defect and need for free-flap reconstructive surgery, nonsurgical management was considered. The patient was referred to medical oncology, where-based on the patient's complicated medical history and the risk of immunotherapy possibly worsening her prior autoimmune diseases-local talimogene laherparepvec injections were chosen as the primary therapy for her mucosal lesions. Though talimogene laherparepvec is approved for the treatment of cutaneous melanoma, there are limited data available on the use of talimogene laherparepvec in mucosal melanomas., Conclusion: The patient had a complete local tumor response at both the primary lesion as well as the skip lesion with the local injections. She had no side effects and maintained a high quality of life during treatment., (© 2024. The Author(s).)

Introduction: Despite the rapid uptake of emicizumab in the paediatric haemophilia A (HA) population, real-world data on the safety and efficacy is limited., Aim: To report on bleeding and safety in paediatric patients receiving emicizumab prophylaxis., Methods: Data were extracted from the multicentre prospective observational PedNet Registry (NCT02979119). Children with haemophilia A, and ≥50 FVIII exposures or inhibitors present receiving emicizumab maintenance therapy were analysed. Data were summarized as medians with interquartile range (IQR, P25-P75). Mean (95% confidence interval (CI)), annualized (joint) bleeding rate (A(J)BR) during emicizumab and ≤2 years before emicizumab prophylaxis were modelled and compared using negative binomial regression., Results: Total of 177 patients started emicizumab at median 8.6 years (IQR 4.8-13.1), most had no FVIII inhibitors (64%). Follow up before emicizumab was median: 1.68 years (IQR: 1.24-1.90) and during emicizumab: 1.32 years (IQR: .94-2.11). In patients without inhibitors, mean ABR reduced after starting emicizumab from 2.41 (CI 1.98-2.95) to 1.11 (CI .90-1.36, p < .001), while AJBR reduced from.74 (CI .56-.98) to.31 (CI .21-.46, p < .001). Concordantly, in patients with inhibitors, mean ABR reduced from 5.08 (CI 4.08-6.38) to .75 (CI .56-1.01, p < .001), while AJBR reduced from 1.90 (CI 1.42-2.58) to .34 (CI .21-.56, p < .001). Five emicizumab-related adverse events were reported (3% of the cohort), including one patient with antidrug antibodies., Conclusion: This study showed improved bleeding control compared to previous treatment and a favourable safety profile during emicizumab therapy in paediatric haemophilia A patients., (© 2024 The Authors. Haemophilia published by John Wiley & Sons Ltd.)

Objective: Effective flipped classroom (FC) education fosters learner engagement, promoting higher-level cognitive skills. FC learning in graduate medical education (GME) has increased, but few educators have significant experience with FC facilitation. There are no evidence-based practices to support professional development of FC facilitation skills in GME. The objective of this study is to identify best practices for effective FC facilitation in GME., Study Design: We conducted a mixed-methods, cross-sectional study of faculty educators who participated in a randomized controlled trial (RCT) using FC for physiology education in neonatal-perinatal medicine. Educators completed a 25-question survey about effective strategies for FC facilitation. A subset of educators participated in interviews to share their FC facilitation experiences and strategies to maximize learner engagement. Quantitative survey data were analyzed with descriptive statistics. Qualitative survey and interview data were coded and analyzed inductively to identify themes., Results: Seventy-five educators completed the survey (75/136, 55% response rate), and 11 participated in semistructured interviews. While educators facilitated a median of two FC sessions (interquartile range: 1, 5) during the RCT, 43 (57%) had not received prior training in FC facilitation. Qualitative data analyses generated five themes that aligned with quantitative survey results: (1) educator preferences, (2) unique FC facilitation skills, (3) learning environment optimization, (4) subject matter expertise, and (5) learner behavior management. Sixty-two educators (83%) felt they were well prepared to lead FC sessions. Thirty-six educators (48%) reported that unprepared learners disrupt the learning environment, and the provision of clear expectations and adequate time to prepare for FCs improves learner preparation. Strategies to facilitate effective FC sessions included creating a safe learning environment and engaging learners in critical thinking., Conclusion: Educators highlighted faculty development needs, strategies, and actions to promote effective FC facilitation. Further exploration through learner interviews will provide additional evidence for the development of best practices and resources for FC facilitation., Key Points: · Educators prefer the FC educational modality over traditional didactic lectures.. · Prior experiences in simulation debriefing provide foundational skills for new FC facilitators.. · Setting learner expectations and ensuring safe space in the classroom encourage learner engagement.. · Educator and learner preparation for FC is essential to optimize the learning experience.. · Unique approaches in facilitation are required to support all types of learners.., Competing Interests: None declared., (Thieme. All rights reserved.)

Intracerebral hemorrhage (ICH) is the second most common type of stroke, accounting for approximately 10-20% of all strokes, and is linked to severe neurological disability and death. Since the most accurate predictor of outcome in patients with ICH is hematoma volume, there is a great need for pharmacologic therapy that can reduce hematoma expansion and resultant mass effect and edema. This is especially critical within the ultra-early window of 3-4 hours after the presentation. Hemostatic therapies are exceptionally important for those patients taking antiplatelet or anticoagulant medications to reverse the effects of these medications and therefore prevent hematoma expansion. Furthermore, the recent publication of the 2023 Guideline for the Management of Patients with Aneurysmal Subarachnoid Hemorrhage by the American Heart Association/American Stroke Association, the first update to the guidelines since 2012, underscores the importance of optimizing anticoagulation reversal for this population. The purpose of this selective, nonsystematic review is to examine current literature regarding the use of hemostatic therapies in ICH, with particular attention paid to antiplatelet, anticoagulation, and antifibrinolytic therapies., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction  Limited data relating to treatment burden, quality of life, and mental health burden of hemophilia A (HA) are currently available. Aim  To provide a comprehensive overview of unmet needs in people with HA (PwHA) using data generated from the Cost of Haemophilia in Europe: a Socioeconomic Survey-II (CHESS II) and CHESS in the pediatric population (CHESS PAEDs) studies. Methods  CHESS II and CHESS PAEDs are cross-sectional surveys of European males with HA or hemophilia B (HB) aged ≥18 and ≤17 years, respectively. Participants with FVIII inhibitors, mild HA, or HB were excluded from this analysis, plus those aged 18 to 19 years. Annualized bleeding rates (ABRs), target joints, and other patient-reported outcomes were evaluated. Results  Overall, 468 and 691 PwHA with available data for the outcomes of interest were stratified by hemophilia severity and treatment regimen in CHESS II and CHESS PAEDs, respectively. In these studies, 173 (37.0%) and 468 (67.7%) participants received FVIII prophylaxis, respectively; no participants received the FVIII mimetic emicizumab or gene therapy. ABRs of 2.38 to 4.88 were reported across disease severity and treatment subgroups in both studies. Target joints were present in 35.7 and 16.6% of participants in CHESS II and CHESS PAEDS; 43.8 and 23.0% had problem joints. Chronic pain was reported by a large proportion of PwHA (73.9% in CHESS II; 58.8% in CHESS PAEDs). Participants also reported low EQ-5D scores (compared with people without HA), anxiety, depression, and negative impacts on their lifestyles due to HA. Conclusions  These analyses suggest significant physical, social, and mental burdens of HA, irrespective of disease severity. Optimization of prophylactic treatment could help reduce the burden of HA on patients., Competing Interests: Conflict of Interest P.C. has served on advisory boards for Bayer, Boehringer Ingelheim, Apcintex, CSL Behring, Chugai, Freeline, Novo Nordisk, Pfizer, F. Hoffmann-La Roche Ltd, Sanofi, Spark, Sobi, and Takeda and has received research funding from Bayer, CSL Behring, Freeline, Novo Nordisk, Pfizer, Takeda and Sobi. R.O. is a previous employee of F. Hoffmann-La Roche Ltd and current employee of AstraZeneca Plc. F.N. reports employment for F. Hoffmann-La Roche Ltd and Kite Pharma. E.F.G. is an employee of HCD Economics and has served on a Haemophilia Patient Council organized by BMRN on behalf of an advocacy organization representative and participated in an advisory board organized by Roche as a patient representative. M.A. is an employee and shareholder of F. Hoffmann-La Roche Ltd. K.M. is an employee and shareholder of F. Hoffmann-La Roche Ltd. T.B. is an employee of HCD Economics. B.N. reports speaker's fees from Sobi and sponsor-led clinical trials for CSL Behring, Sobi, Biogen, Biomnis, Sanofi, Bayer, and Alnylam. J.O.H. is an employee of HCD Economics. K.K. is an employee and shareholder of Haemnet Ltd., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).)

Background: Atlantoaxial subluxation (AAS) is a diagnosis describing misalignment of the C1 vertebra relative to C2. Excessive translation of this joint, located adjacent to the medullary brain stem, can lead to devastating neurological consequences. A higher prevalence of AAS within the Down syndrome (DS) population has been well-established. This study aims to establish a prevalence rate of DS in patients hospitalized for AAS and compare outcomes between AAS patients with and without DS., Methods: This study utilized the National Inpatient Sample (NIS) provided by the Healthcare Cost and Utilization Project (HCUP). In accordance with HCUP 2023 Clinical Classifications Software Refined files, data were queried using the International Classification of Diseases 10 th Edition codes for DS and AAS. Demographics, comorbidities, hospital course, and outcomes were examined and compared using binary and linear multivariate regression. IBM SPSS software was used for data analysis., Results: Of the 213,095 patients in the NIS database admitted between 2016 and 2020 with AAS as their primary diagnosis, 7.2% were DS patients. DS patients were significantly younger (26.56 ± 20.81 vs. 49.39 ± 27.63, P < 0.01), less likely to be female (33.30% vs. 52.10%), and had fewer comorbidities (diabetes mellitus, hypertension, and hyperlipidemia) than non-DS patients. There was no significant difference in likelihood to undergo surgical fusion between DS patients and non-DS patients with AAS., Conclusion: This large-scale study using NIS data determined that 7.2% of all patients admitted to hospitals for AAS are DS patients. The analysis of demographics, hospital course, and outcomes can influence the development of treatment protocols for AAS in the DS population., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Craniovertebral Junction and Spine.)

Purpose: The STAT (Safety Threats and Adverse Events in Trauma) taxonomy was developed through expert consensus, and groups 65 identified trauma resuscitation adverse events (AEs) into nine distinct categories. It provides a framework for standardized analysis of trauma resuscitations and creates a foundation for targeted quality improvement and patient safety initiatives. This study aims to evaluate the reliability of the STAT taxonomy in identifying AEs during video-recorded trauma resuscitations., Methods: High-definition audiovisual data from 30 trauma resuscitations were reviewed. Videos were assessed and scored by four independent reviewers (two trainees and two staff). The STAT taxonomy was used to identify AEs based on binary responses: yes and no. Inter-rater reliability was calculated using Gwet's AC1. The frequencies of AEs were tallied and reported as counts and percentages., Results: The most common AEs identified in the videos were failure to measure temperature (86.7%) and inadequate personal protective equipment (86.7%), followed by inability to use closed-loop communication (76.7%). The agreement on all AEs between reviewers was 0.94 (95% CI: 0.93-0.95). The Gwet's AC1 agreement across the 9 AE categories was paramedic handover (0.82), airway and breathing (0.99), circulation (0.95), assessment of injuries (0.91), management of injuries (0.96), procedure-related (0.97), patient monitoring and IV access (0.99), disposition (0.98), team communication and dynamics (0.87)., Conclusion: The STAT taxonomy demonstrated excellent inter-rater reliability between reviewers and can be used to identify AEs in video-recorded trauma resuscitations. These results provide a foundation for adapting video review to objectively quantify and assess AEs in the trauma bay., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: Salivary duct carcinomas (SDC) are a rare and aggressive subtype of salivary gland neoplasm. They can present with distinct immunoprofiles, such as androgen receptor (AR) and HER-2/Neu-positivity. To date, no consensus exists on how to best manage this entity., Methods: All patients diagnosed with nonmetastatic AR+ SDC of the parotid from 2013 to 2019 treated with curative intent were included. Immunologic tumor profiling was conducted using 24 distinct markers. Kaplan-Meier analyses were used to estimate locoregional recurrence (LRR), distant control, and overall survival (OS)., Results: Fifteen patients were included. Nine (60%) patients presented with T4 disease and eight (53%) had positive ipsilateral cervical lymphadenopathy. Ten (67%) patients underwent trimodality therapy, including surgery followed by adjuvant radiation and concurrent systemic therapy. The median follow-up was 5.5 years (interquartile range, 4.8-6.1). The estimated 5-year rates of LRR, distant progression, and OS were 6%, 13%, and 87%, respectively., Conclusion: Despite only including AR+ SDC of the parotid, immunoprofiles, such as expression of HER-2, were highly variable, highlighting the potential to tailor systemic regimens based on individual histologic profiles in the future. Studies with larger patient numbers using tumor-specific molecular profiling and tumor heterogeneity analyses are justified to better understand the biology of these tumors. Molecularly informed treatment approaches, including the potential use of AR- and HER-2/Neu-directed therapies upfront in the definitive setting, may hold future promise to further improve outcomes for these patients.

Objective: Timely access to a lead trauma hospital (LTH) saves lives; however, the vast geography of Northern Ontario creates a barrier to equitable access to an LTH. Paramedics in Ontario follow the field trauma triage standard (FTTS) to identify which patients should be directly brought to an LTH. A pilot project was launched using a fixed wing modified scene response (MSR) to transport patients from Northern Ontario who met the FTTS directly to an LTH. This study aimed to 1) explore the impact of the fixed wing MSR pilot program on the time to LTH arrival for injured patients in Northern Ontario compared with the traditional interfacility transfer (IFT) process and 2) determine the frequency and specific FTTS criteria that were fulfilled., Methods: This was a retrospective cohort study of injured patients in Northern Ontario who were emergently transported to an LTH by the provincial air ambulance service between January 2016 and October 2021. Electronic patient care records were manually reviewed, and patient cases were grouped by their sending and receiving facilities to evaluate time differences between MSR and IFT., Results: For same-distance transports, the average time from injury to trauma center arrival was reduced with MSR (292.8 minutes) compared with IFT (507.8 minutes), with a mean difference of 130.3 minutes. All MSR cases and 90% of IFT cases met at least 1 FTTS criterion., Conclusion: Fixed wing MSR improves access to timely definitive care for injured patients in Northern Ontario, and all patients transported in this pilot project met the trauma bypass criteria., Competing Interests: Declaration of Competing Interest The author(s) have no relevant disclosures. There was no grant funding or financial support for this manuscript., (Copyright © 2023 Air Medical Journal Associates. Published by Elsevier Inc. All rights reserved.)

Objective: To identify factors influencing volume change in non-osseous oral free flap reconstruction using postoperative cross-sectional imaging and 3-dimensional segmentation of the free flap's muscular and adipose tissue content., Methods: Oral tongue free flap reconstruction cases (2014-2019) were reviewed with inclusion of patients with 3 postoperative, cross-sectional imaging studies with 1 within 6 months, 1 within 1 year, and 1 that spanned 2 years post-reconstruction. Exclusion criteria included recurrence, significant dental artifact, bony reconstruction, and flap failure. Demographics, risk factors, and surgical/clinical treatments were identified. Flap volumes were measured using Materialise MIMICS., Results: Twenty-two patients met strict inclusion criteria. Four flaps were anterolateral thighs and 18 radial forearms. Median percent volume loss greater than 2 years post-reconstruction was 53.2% overall, 58.1% for radial forearms, and 45.4% for ALTs (21.4% for adipose tissue and 57.4% for muscular tissue). Univariate analysis revealed glossectomy amount was associated with percent volume loss ( P  = .0417). Each successive postoperative month, the flap decreased by 1.54% ( P  < .0001). Checking for the interaction effect, the percent of flap loss across time was different for glossectomy amount ( P  = .0093), obesity status ( P  = .0431), and base of tongue involvement ( P  = .0472)., Conclusion: Glossectomy type, and thus flap size, is a positive predictor for flap atrophy. Obesity and base of tongue involvement are negative predictors for flap atrophy. The amount of tissue loss may differ from classical teachings with median atrophy 53.2% greater than 2 years post-reconstruction., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.