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Background: Calcific aortic stenosis (CAS) is more prevalent, occurs earlier, progresses faster and has worse outcomes in patients with chronic kidney disease (CKD). The uremic toxin indoxyl sulfate (IS) is powerful predictor of cardiovascular mortality in these patients and a strong promoter of ectopic calcification whose role in CAS remains poorly studied. The objective of this study was to evaluate whether IS influences the mineralization of primary human valvular interstitial cells (hVICs) from the aortic valve., Methods: Primary hVICs were exposed to increasing concentrations of IS in osteogenic medium (OM). The hVICs' osteogenic transition was monitored by qRT-PCRs for BMP2 and RUNX2 mRNA. Cell mineralization was assayed using the o-cresolphthalein complexone method. Inflammation was assessed by monitoring NF-κB activation using Western blots as well as IL-1β, IL-6 and TNF-α secretion by ELISAs. Small interfering RNA (siRNA) approaches enabled us to determine which signaling pathways were involved., Results: Indoxyl-sulfate increased OM-induced hVICs osteogenic transition and calcification in a concentration-dependent manner. This effect was blocked by silencing the receptor for IS (the aryl hydrocarbon receptor, AhR). Exposure to IS promoted p65 phosphorylation, the blockade of which inhibited IS-induced mineralization. Exposure to IS promoted IL-6 secretion by hVICs, a phenomenon blocked by silencing AhR or p65. Incubation with an anti-IL-6 antibody neutralized IS's pro-calcific effects., Conclusion: IS promotes hVIC mineralization through AhR-dependent activation of the NF-κB pathway and the subsequent release of IL-6. Further research should seek to determine whether targeting inflammatory pathways can reduce the onset and progression of CKD-related CAS., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Simulation-based education can augment residents' skills and knowledge. We assessed the effectiveness of a simulation-based course for surgery interns designed to improve their comfort, knowledge, and ability to manage common surgical critical care (SCC) conditions., Materials and Methods: For 2 y, all first year residents (n = 31) in general surgery, urology, interventional radiology, and the integrated plastics, vascular, and cardiothoracic surgery training programs at our institution participated in a simulation-based course emphasizing evidence-based management of SCC conditions. Precourse and postcourse surveys and multiple-choice tests, as well as summative simulation tests, assessed interns' comfort, knowledge, and ability to manage SCC conditions. Changes in these measures were assessed with Wilcoxon matched-pairs signed rank tests. Factors associated with summative performance were determined by linear regression., Results: The course consisted of four simulation-based teaching sessions in year 1 and six in year 2. The course taught seven of the 18 core SCC conditions in the Surgical Council on Resident Education general surgery curriculum in year 1 and 10 in year 2. Interns' self-reported comfort, knowledge, and ability to manage each condition taught in the course increased (P < 0.02). Their knowledge of each condition, as assessed by written tests, also increased (P < 0.02). Their summative simulation test performance correlated with the number of course sessions attended (P < 0.03) and status as general surgery residents (P < 0.01)., Conclusions: A simulation-based SCC training course for surgery interns that emphasizes evidence-based management of SCC conditions improves interns' comfort, knowledge, and ability to manage these conditions., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Trauma systems in resource-rich countries have decreased mortality for trauma patients through centralizing resources and standardizing treatment. Rapid industrialization and urbanization have increased the demand for formalized emergency medical services and trauma services (EMS and TS) in low- and middle-income countries (LMICs). This systematic review examines initiatives to develop EMS and TS systems in LMICs to inform the development of comprehensive prehospital care systems in resource-poor settings., Materials and Methods: EMS and TS system development publications were identified using MEDLINE, PubMed, and Scopus databases. Articles addressing subspecialty skill sets, public policy, or physicians were excluded. Two independent reviewers assessed titles, abstracts, and full texts in a hierarchical manner., Results: A total of 12 publications met inclusion criteria, and 10 unique LMIC EMS and TS programs were identified. Common initiatives included the integration of existing EMS and TS services and provision of standardized training and formalized certification processes for prehospital care providers, as well as the construction of a conceptual framework for system development through the public health model., Conclusions: There is no single model of EMS and TS systems, and successful programs are heterogeneous across regions. Successful EMS and TS systems share common characteristics. A predevelopment needs assessment is critical in identifying existing EMS and TS resources as a foundation for further development. Implementation requires coordination of preexisting resources with cost-effective initiatives that involve local stakeholders. High-impact priority areas are identified to focus improvements. Financial stresses and mismatching of resources in LMICs are common and are more commonly encountered when implementing a high-income model EMS and TS in an LMIC. Preimplementation and postimplementation evaluations can determine the efficacy of initiatives to strengthen EMS and TS systems., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Prehospital trauma systems are rudimentary in many low- and middle-income countries (LMICs) and require laypersons to stabilize and transport injured patients. The World Health Organization recommends educating layperson first responders as an essential step in the development of Emergency Medical Services systems in LMICs. This systematic review examines trauma educational initiatives for layperson first responders in resource-poor settings., Materials and Methods: Layperson first-responder training and education program publications were identified using PubMed MEDLINE and Scopus databases. Articles addressing physicians, professional Emergency Medical Services training, or epidemiologic descriptions were excluded. Publications were assessed by independent reviewers, and those included underwent thematic analysis., Results: Thirteen publications met inclusion criteria. Four themes emerged regarding the development of layperson first-responder training programs: (1) An initial needs assessment of a region's existing trauma system of care and laypersons' baseline emergency care knowledge focuses subsequent educational interventions; (2) effective programs adapt to and leverage existing resources; (3) training methods should anticipate participants with low levels of education and literacy; and (4) postimplementation evaluation allows for curriculum improvement. Technology, such as online and remote learning platforms, can be used to operationalize each theme., Conclusions: Successful training programs for layperson first responders in LMICs identify and maximize existing resources are adaptable to learners with little formal education and are responsive to postimplementation evaluation. Educational platforms that leverage technology to deliver content may facilitate first-responder trauma education in underresourced areas. Themes identified can inform the development of trauma systems of care to decrease mortality and physiological severity scores in trauma patients in LMICs., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Compartment syndrome of the thigh is a surgical emergency rarely reported in the literature. The most common etiologies include blunt trauma, vascular injuries from penetrating trauma, and hematoma formation. Thigh compartment syndrome (TCS) is important as it is often associated with concomitant severe injury with mortality rates as high as 47%. This study aims to identify mechanisms of injury, clinical presentation, and outcomes associated with TCS in the urban trauma patient population., Methods: Demographic and clinical information for all patients with a diagnosis of TCS at a level 1 urban trauma center over a 10.5-y period were reviewed. Collected data included age, sex, mechanism of injury, method of diagnosis, time taken for diagnosis and management, methods of decompression, wound management, lengths of stay in the intensive care unit and hospital, amputation rate, and hospital disposition., Results: Ten patients were identified with diagnosis of TCS. The mechanism of injury was penetrating in six patients and blunt in four. The mean time from injury to diagnosis was 23.4 h. Intensive care unit and hospital lengths of stay were significantly increased among patients sustaining penetrating injuries compared with blunt injuries. Two of the six penetrating injury patients underwent an amputation. Eight of 10 patients were ambulatory on discharge. There were no mortalities., Conclusions: Among urban trauma patients, penetrating injuries of the thigh and adjacent vascular structures and the need for decompressive fasciotomy of the lower leg are the major risk factors for TCS. Clinical diagnosis and early intervention with fasciotomy remain the mainstay of treatment., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Prior work using simulation for assessing intubation skills has largely focused on the use of observer-generated performance measures in the form of checklists and global ratings scales., Purpose: The purpose of our work was to investigate whether patient-centered simulation data could be used to quantify learner's performance during direct laryngoscopy., Methods: We designed a pretest/posttest prospective intervention study of residents' (n = 25) intubation skills., Results: When assessing validity, all of the patient-centered simulation variables showed significant correlations with the previously validated observer-generated performance measures (r = 0.331-0.463, P ≤ 0.001). When assessing reliability, there were significant correlations between all of the sensor variables, confirming moderate to high inter-item reliability (r = 0.259-0.794, P ≤ 0.05). The observer-generated performance measures showed significant improvement in use of the Macintosh blade (T1 = 2.10/5.00, T2 = 3.64/5.00, P = 0.001). However, this was not the case for the Miller blade (T1 = 1.30/5.00, T2 = 1.75/5.00, P = 0.119). Overall, the patient-centered simulation variables provided a high level of detail regarding performance improvement areas., Conclusion: This study presents a multilevel analysis of sensor-generated simulation data. As the sensors provide sound, formative data regarding patient contact, the outputs may be used for specific criterion measures and detailed performance feedback., (Copyright © 2012 Elsevier Inc. All rights reserved.)