Glutathione synthesis in the mouse liver supports lipid abundance through NRF2 repression.

Cells rely on antioxidants to survive. The most abundant antioxidant is glutathione (GSH). The synthesis of GSH is non-redundantly controlled by the glutamate-cysteine ligase catalytic subunit (GCLC). GSH imbalance is implicated in many diseases, but the requirement for GSH in adult tissues is unclear. To interrogate this, we have developed a series of in vivo models to induce Gclc deletion in adult animals. We find that GSH is essential to lipid abundance in vivo. GSH levels are highest in liver tissue, which is also a hub for lipid production. While the loss of GSH does not cause liver failure, it decreases lipogenic enzyme expression, circulating triglyceride levels, and fat stores. Mechanistically, we find that GSH promotes lipid abundance by repressing NRF2, a transcription factor induced by oxidative stress. These studies identify GSH as a fulcrum in the liver's balance of redox buffering and triglyceride production.

Transforming remediation for competency-based medical education.

We care about the future experiences of all health professions trainees as competency-based medical education evolves. It is an exciting new era with many possibilities for progress in learning and competency development. Yet we are concerned that remediation remains a troubled and stigmatized detour from routine learning that can persist as a feared off-ramp from competency development rather than a central avenue for improvement and competency achievement. We believe that it is time to acknowledge that all trainees struggle and to recognize that remediation is an essential aspect of individualized learning. Decisive steps are possible to revitalize remediation and to launch its transformation towards growth-oriented pathways for change.

Advances and challenges in regenerative therapies for abdominal aortic aneurysm.

Abdominal aortic aneurysm (AAA) is a significant source of mortality worldwide and carries a mortality of greater than 80% after rupture. Despite extensive efforts to develop pharmacological treatments, there is currently no effective agent to prevent aneurysm growth and rupture. Current treatment paradigms only rely on the identification and surveillance of small aneurysms, prior to ultimate open surgical or endovascular repair. Recently, regenerative therapies have emerged as promising avenues to address the degenerative changes observed in AAA. This review briefly outlines current clinical management principles, characteristics, and pharmaceutical targets of AAA. Subsequently, a thorough discussion of regenerative approaches is provided. These include cellular approaches (vascular smooth muscle cells, endothelial cells, and mesenchymal stem cells) as well as the delivery of therapeutic molecules, gene therapies, and regenerative biomaterials. Lastly, additional barriers and considerations for clinical translation are provided. In conclusion, regenerative approaches hold significant promise for in situ reversal of tissue damages in AAA, necessitating sustained research and innovation to achieve successful and translatable therapies in a new era in AAA management.

Narrow bandwidth, low-emittance positron beams from a laser-wakefield accelerator.

The rapid progress that plasma wakefield accelerators are experiencing is now posing the question as to whether they could be included in the design of the next generation of high-energy electron-positron colliders. However, the typical structure of the accelerating wakefields presents challenging complications for positron acceleration. Despite seminal proof-of-principle experiments and theoretical proposals, experimental research in plasma-based acceleration of positrons is currently limited by the scarcity of positron beams suitable to seed a plasma accelerator. Here, we report on the first experimental demonstration of a laser-driven source of ultra-relativistic positrons with sufficient spectral and spatial quality to be injected in a plasma accelerator. Our results indicate, in agreement with numerical simulations, selection and transport of positron beamlets containing N e + ≥ 10 5 positrons in a 5% bandwidth around 600 MeV, with femtosecond-scale duration and micron-scale normalised emittance. Particle-in-cell simulations show that positron beams of this kind can be guided and accelerated in a laser-driven plasma accelerator, with favourable scalings to further increase overall charge and energy using PW-scale lasers. The results presented here demonstrate the possibility of performing experimental studies of positron acceleration in a laser-driven wakefield accelerator.

Validation of dual energy X-ray absorptiometry for longitudinal quantification of tumor burden in a murine model of pancreatic ductal adenocarcinoma.

Noninvasive imaging is central to preclinical, in vivo models of pancreatic ductal adenocarcinoma (PDAC). While bioluminescent imaging (BLI) is a gold standard, its signal is dependent on the metabolic activity of tumor cells. In contrast, dual energy X-ray absorptiometry (DEXA) is a direct measure of body composition. Thus, we aimed to assess its potential for longitudinal quantification of tumor burden versus BLI. We utilized the KCKO murine model of PDAC and subjected tumor-bearing (n = 20) and non-tumor control (NTC) (n = 10) animals to weekly BLI and DEXA measurements for up to 10 weeks. While BLI detected tumors at 1-week, it failed to detect tumor growth, displayed a decreasing trend overtime (slope = -9.0x108; p = 0.0028), and terminal signal did not correlate with ex vivo tumor mass (r = 0.01853; p = 0.6286). In contrast, DEXA did not detect elevated changes in abdominal cavity lean mass until week 2 post inoculation and tumors were not visible until week 3, but successfully quantified a tumor growth trend (slope = 0.7322; p<0.0001), and strongly correlated with final tumor mass (r = 0.9351; p<0.0001). These findings support the use of BLI for initial tumor engraftment and persistence but demonstrate the superiority of DEXA for longitudinal tumor burden studies. As tumor detection by DEXA is not restricted to luciferase expressing models, future studies to assess its value in various cancer models and as an in vivo outcome measure of treatment efficacy are warranted.

Bilateral Spontaneous Retrobulbar Hemorrhage due to Warfarin Misuse After Sinus Lavage.

While warfarin has historically played an important role in anticoagulation, direct oral anticoagulants have largely supplanted warfarin due to their improved safety profile and reduced need for monitoring. Herein, the authors report the case of a 64-year-old male who developed severe, bilateral retrobulbar hemorrhage following aggressive nasal lavage due to a supratherapeutic international normalized ratio from warfarin misuse. Visual acuity on arrival was hand-motion OD and no-light-perception OS. He underwent bilateral canthotomy with upper and lower lid cantholysis before transfer to a trauma center where his international normalized ratio was greater than 12. Reversal with vitamin K and prothrombin complex concentrate was initiated. Over the course of hospitalization, vision and swelling continued to improve and at 2-month follow-up his visual acuity was 20/20 OD and no-light-perception OS. This case outlines the risk of bleeding associated with warfarin misuse and advocates for the transition of patients to direct oral anticoagulants when possible.

Pembrolizumab-Induced Nodular Posterior Scleritis.

Purpose: To report a case of painless posterior scleritis presenting as a choroidal nodule in a patient with history of a tumor being treated with pembrolizumab. Methods: A case and its findings were analyzed, and a relevant literature review was performed. Results: A 20-year-old woman with a history of ependymoma presented with painless blurred vision in the right eye after being started on pembrolizumab for a tumor recurrence. Fundoscopy showed a solitary amelanotic choroidal lesion with surrounding subretinal fluid in the affected eye. Ultrasonography showed moderate internal reflectivity and fluid in Tenon capsule consistent with nodular posterior scleritis. After a course of systemic steroids and discontinuation of the pembrolizumab, the choroidal lesion completely resolved. Conclusions: Clinicians should be aware of posterior scleritis as an ocular complication of this class of medications.

The LINC complex regulates Achilles tendon elastic modulus, Achilles and tail tendon collagen crimp, and Achilles and tail tendon lateral expansion during early postnatal development.

There is limited understanding of how mechanical signals regulate tendon development. The nucleus has emerged as a major regulator of cellular mechanosensation, via the linker of nucleoskeleton and cytoskeleton (LINC) protein complex. Specific roles of LINC in tenogenesis have not been explored. In this study, we investigate how LINC regulates tendon development by disabling LINC-mediated mechanosensing via dominant negative (dn) expression of the Klarsicht, ANC-1, and Syne Homology (KASH) domain, which is necessary for LINC to function. We hypothesized that LINC regulates mechanotransduction in developing tendon, and that disabling LINC would impact tendon mechanical properties and structure in a mouse model of dnKASH. We used Achilles (AT) and tail (TT) tendons as representative energy-storing and limb-positioning tendons, respectively. Mechanical testing at postnatal day 10 showed that disabling the LINC complex via dnKASH significantly impacted tendon mechanical properties and cross-sectional area, and that effects differed between ATs and TTs. Collagen crimp distance was also impacted in dnKASH tendons, and was significantly decreased in ATs, and increased in TTs. Overall, we show that disruption to the LINC complex specifically impacts tendon mechanics and collagen crimp structure, with unique responses between an energy-storing and limb-positioning tendon. This suggests that nuclear mechanotransduction through LINC plays a role in regulating tendon formation during neonatal development.

Validation of Dual Energy X-ray Absorptiometry for longitudinal quantification of tumor burden in a murine model of pancreatic ductal adenocarcinoma.

Noninvasive imaging is central to preclinical, in vivo models of pancreatic ductal adenocarcinoma (PDAC). While bioluminescent imaging (BLI) is a gold standard, its signal is dependent on the metabolic activity of tumor cells. In contrast, dual energy X-ray absorptiometry (DEXA) is a direct measure of body composition. Thus, we aimed to assess its potential for longitudinal quantification of tumor burden versus BLI. We utilized the KCKO murine model of PDAC and subjected tumor-bearing (n = 20) and non-tumor control (NTC) (n = 10) animals to weekly BLI and DEXA measurements for up to 10 weeks. While BLI detected tumors at 1-week, it failed to detect tumor growth, displayed a decreasing trend overtime (slope = -9.0×108; p = 0.0028), and terminal signal did not correlate with ex vivo tumor mass (r = 0.01853; p = 0.6286). In contrast, DEXA did not detect elevated changes in abdominal cavity lean mass until week 2 post inoculation and tumors were not visible until week 3, but successfully quantified a tumor growth trend (slope = 0.7322; p<0.0001), and strongly correlated with final tumor mass (r = 0.9351; p<0.0001). These findings support the use of BLI for initial tumor engraftment and persistence but demonstrate the superiority of DEXA for longitudinal tumor burden studies. As tumor detection by DEXA is not restricted to luciferase expressing models, future studies to assess its value in various cancer models and as an in vivo outcome measure of treatment efficacy are warranted.

Influence of high altitude after a prior ascent on physical exhaustion during cardiopulmonary resuscitation: a randomised crossover alpine field experiment.

BACKGROUND: Performing cardiopulmonary resuscitation (CPR) inevitably causes significant physical, as well as psychological stress for rescuers. Physical activity at high altitude, a hypobaric and hypoxic environment, similarly adds to the level of stress and causes multiple physiological changes. Continuous measurement of pulse rate serves as an objective measure of fatigue during CPR. We therefore aimed to investigate rescuers' heart rates as a measure of physical strain during CPR in a high-altitude alpine environment to provide a better understanding of the physiological changes under these very special conditions. METHODS: Twenty experienced mountaineers performed basic life support (BLS) on a manikin for 16 min, both at baseline altitude and at high altitude (3454 m) following a quick and exhausting ascent over 1200 m. Sequence of scenarios was randomised for analysis. Heart rate was continuously measured and compared between baseline and high altitude by absolute differences and robust confidence intervals. RESULTS: During CPR at baseline, the average heart rate increased from 87 bpm (SD 16 bpm) to 104 bpm [increase 17 bpm (95% CI 8.24-24.76)], compared to an increase from 119 bpm (SD 12 bpm) to 124 bpm [increase 5 bpm (95% CI - 1.59 to 12.19)] at high altitude [difference between two groups 32 bpm (95% CI 25-39)]. Differences between periods of chest compressions and ventilations were very similar at baseline [19 bpm (95%CI 16.98-20.27)] and at high altitude [20 bpm 95% CI 18.56-21.44)], despite starting from a much higher level at high altitude. The average heart rates of rescuers at high altitude at any point were higher than those at baseline at any other point. CONCLUSION: Performing BLS CPR causes exhaustion both at base level and at a high altitude. A further increase during CPR might imply a physiological reserve for adapting to additional physical exertion at high altitude. Phases of ventilation are much needed recovery-periods, but heart rates remain very high. Subjective measures of exhaustion, such as the BORG-scale, might lead to rescuers' overestimation of their own performance.

Diabetes, gaps in care coordination, and preventable adverse events.

OBJECTIVES: To compare the frequency of self-reported gaps in care coordination and self-reported preventable adverse events among adults with vs without diabetes. STUDY DESIGN: Cross-sectional analysis of REasons for Geographic And Racial Differences in Stroke (REGARDS) study participants 65 years and older who completed a survey on health care experiences in 2017-2018 (N = 5634). METHODS: We analyzed the association of diabetes with self-reported gaps in care coordination and with preventable adverse events. Gaps in care coordination were assessed using 8 validated questions. Four self-reported adverse events were studied (drug-drug interactions, repeat medical tests, emergency department visits, and hospitalizations). Respondents were asked if they thought these events could have been prevented with better communication among providers. RESULTS: Overall, 1724 (30.6%) participants had diabetes. Among participants with and without diabetes, 39.3% and 40.7%, respectively, reported any gap in care coordination. The adjusted prevalence ratio (aPR) for any gap in care coordination for participants with vs without diabetes was 0.97 (95% CI, 0.89-1.06). Any preventable adverse event was reported by 12.9% and 8.7% of participants with and without diabetes, respectively. The aPR for any preventable adverse event for participants with vs without diabetes was 1.22 (95% CI, 1.00-1.49). Among participants with and without diabetes, the aPRs for any preventable adverse event associated with any gap in care coordination were 1.53 (95% CI, 1.15-2.04) and 1.50 (95% CI, 1.21-1.88), respectively (P comparing aPRs = .922). CONCLUSIONS: Interventions to improve quality of care for patients with diabetes could incorporate patient-reported gaps in care coordination to aid in preventing adverse events.

Partnering With Patients and Caregivers in Cancer Care: Lessons From Experiences With Transgender, Hispanic, and Pediatric Populations.

A cancer diagnosis thrusts patients and caregivers into a foreign world of health care with systems, protocols, and norms that can leave little room for individual needs and circumstances. Quality and efficacious oncology care requires clinicians to partner with patients and caregivers to understand and incorporate their needs, values, and priorities into information sharing, decision making, and care provision. This partnership is necessary for effective patient- and family-centered care and access to individualized and equitable information, treatment, and research participation. Partnering with patients and families also requires oncology clinicians to see that our personal values, preconceived ideas, and established systems exclude certain populations and potentially lead to poorer care for all patients. Furthermore, inequitable access to participation in research and clinical trials can contribute to an unequal burden of cancer morbidity and mortality. Leveraging the expertise of the authorship team with transgender, Hispanic, and pediatric populations, this chapter provides insights and suggestions for oncology care that are applicable across patient populations to mitigate stigma and discrimination and improve the quality of care for all patients.

Organizational readiness to implement task-strengthening strategy for hypertension management among people living with HIV in Nigeria.

BACKGROUND: Hypertension (HTN) is highly prevalent among people living with HIV (PLHIV), but there is limited access to standardized HTN management strategies in public primary healthcare facilities in Nigeria. The shortage of trained healthcare providers in Nigeria is an important contributor to the increased unmet need for HTN management among PLHIV. Evidence-based TAsk-Strengthening Strategies for HTN control (TASSH) have shown promise to address this gap in other resource-constrained settings. However, little is known regarding primary health care facilities' capacity to implement this strategy. The objective of this study was to determine primary healthcare facilities' readiness to implement TASSH among PLHIV in Nigeria. METHODS: This study was conducted with purposively selected healthcare providers at fifty-nine primary healthcare facilities in Akwa-Ibom State, Nigeria. Healthcare facility readiness data were measured using the Organizational Readiness to Change Assessment (ORCA) tool. ORCA is based on the Promoting Action on Research Implementation in Health Services (PARIHS) framework that identifies evidence, context, and facilitation as the key factors for effective knowledge translation. Quantitative data were analyzed using descriptive statistics (including mean ORCA subscales). We focused on the ORCA context domain, and responses were scored on a 5-point Likert scale, with 1 corresponding to disagree strongly. FINDINGS: Fifty-nine healthcare providers (mean age 45; standard deviation [SD]: 7.4, 88% female, 68% with technical training, 56% nurses, 56% with 1-5 years providing HIV care) participated in the study. Most healthcare providers provide care to 11-30 patients living with HIV per month in their health facility, with about 42% of providers reporting that they see between 1 and 10 patients with HTN each month. Overall, staff culture (mean 4.9 [0.4]), leadership support (mean 4.9 [0.4]), and measurement/evidence-assessment (mean 4.6 [0.5]) were the topped-scored ORCA subscales, while scores on facility resources (mean 3.6 [0.8]) were the lowest. CONCLUSION: Findings show organizational support for innovation and the health providers at the participating health facilities. However, a concerted effort is needed to promote training capabilities and resources to deliver services within these primary healthcare facilities. These results are invaluable in developing future strategies to improve the integration, adoption, and sustainability of TASSH in primary healthcare facilities in Nigeria. TRIAL REGISTRATION: NCT05031819.

Engineering Cell-ECM-Material Interactions for Musculoskeletal Regeneration.

The extracellular microenvironment regulates many of the mechanical and biochemical cues that direct musculoskeletal development and are involved in musculoskeletal disease. The extracellular matrix (ECM) is a main component of this microenvironment. Tissue engineered approaches towards regenerating muscle, cartilage, tendon, and bone target the ECM because it supplies critical signals for regenerating musculoskeletal tissues. Engineered ECM-material scaffolds that mimic key mechanical and biochemical components of the ECM are of particular interest in musculoskeletal tissue engineering. Such materials are biocompatible, can be fabricated to have desirable mechanical and biochemical properties, and can be further chemically or genetically modified to support cell differentiation or halt degenerative disease progression. In this review, we survey how engineered approaches using natural and ECM-derived materials and scaffold systems can harness the unique characteristics of the ECM to support musculoskeletal tissue regeneration, with a focus on skeletal muscle, cartilage, tendon, and bone. We summarize the strengths of current approaches and look towards a future of materials and culture systems with engineered and highly tailored cell-ECM-material interactions to drive musculoskeletal tissue restoration. The works highlighted in this review strongly support the continued exploration of ECM and other engineered materials as tools to control cell fate and make large-scale musculoskeletal regeneration a reality.

Glutathione supports lipid abundance in vivo.

Cells rely on antioxidants to survive. The most abundant antioxidant is glutathione (GSH). The synthesis of GSH is non-redundantly controlled by the glutamate-cysteine ligase catalytic subunit (GCLC). GSH imbalance is implicated in many diseases, but the requirement for GSH in adult tissues is unclear. To interrogate this, we developed a series of in vivo models to induce Gclc deletion in adult animals. We find that GSH is essential to lipid abundance in vivo. GSH levels are reported to be highest in liver tissue, which is also a hub for lipid production. While the loss of GSH did not cause liver failure, it decreased lipogenic enzyme expression, circulating triglyceride levels, and fat stores. Mechanistically, we found that GSH promotes lipid abundance by repressing NRF2, a transcription factor induced by oxidative stress. These studies identify GSH as a fulcrum in the liver's balance of redox buffering and triglyceride production.

Implementation of automated behavior metrics to evaluate voluntary wheel running effects on inflammatory-erosive arthritis and interstitial lung disease in TNF-Tg mice.

BACKGROUND: Although treatment options and algorithms for rheumatoid arthritis (RA) have improved remarkably in recent decades, there continues to be no definitive cure or pharmacologic intervention with reliable long-term efficacy. For this reason, the combination of medications and healthy lifestyle modifications are essential for controlling joint disease, and extra-articular manifestations of RA, such as interstitial lung disease (ILD) and other lung pathologies, which greatly impact morbidity and mortality. Generally, exercise has been deemed beneficial in RA patients, and both patients and clinicians are motivated to incorporate effective non-pharmacologic interventions. However, there are limited evidence-based and specific exercise regimens available to support engagement in such activities for RA patients. Here, we provided the continuous opportunity for exercise to mice and implemented automated recording and quantification of wheel running behavior. This allowed us to describe the associated effects on the progression of inflammatory-erosive arthritis and ILD in the tumor necrosis factor transgenic (TNF-Tg) mouse model of RA. METHODS: Wild-type (WT; males, n=9; females, n=9) and TNF-Tg (males, n=12; females, n=14) mice were singly housed with free access to a running wheel starting at 2 months until 5 to 5.5 months of age. Measures of running included distance, rate, length, and number of run bouts, which were derived from continuously recorded data streams collected automatically and in real-time. In vivo lung, ankle, and knee micro-computed tomography (micro-CT), along with terminal micro-CT and histology were performed to examine the association of running behaviors and disease progression relative to sedentary controls. RESULTS: TNF-Tg males and females exhibited significantly reduced running distance, rate, length, and number of run bouts compared to WT counterparts by 5 months of age (p<0.0001). Compared to sedentary controls, running males and females showed increased aerated lung volumes (p<0.05) that were positively correlated with running distance and rate in female mice (WT: Distance, ρ=0.705/rate, ρ=0.693 (p<0.01); TNF-Tg: ρ=0.380 (p=0.06)/ρ=0.403 (p<0.05)). Talus bone volumes were significantly reduced in running versus sedentary males and negatively correlated with running distance and rate in TNF-Tg mice (male: ρ=-903/ρ=-0.865; female: ρ=-0.614/ρ=-0.594 (p<0.001)). Histopathology validated the lung and ankle micro-CT findings. CONCLUSIONS: Implementation of automated wheel running behavior metrics allows for evaluation of longitudinal activity modifications hands-off and in real-time to relate with biomarkers of disease severity. Through such analysis, we determined that wheel running activity increases aerated lung volumes, but exacerbates inflammatory-erosive arthritis in TNF-Tg mice. To the end of a clinically relevant model, additional functional assessment of these outcomes and studies of pain behavior are warranted.

Automated feedback modestly improves perioperative treatment adherence of postoperative nausea and vomiting.

STUDY OBJECTIVE: Extensive evidence demonstrates that medical record modernization and a vast amount of available data have not overcome the gap between recommended and delivered care. This study aimed to evaluate the use of clinical decision support (CDS) in conjunction with feedback (post-hoc reporting) to improve PONV medication administration compliance and postoperative nausea and vomiting (PONV) outcomes. DESIGN: Single center, prospective observational study between January 1, 2015, and June 30, 2017. SETTING: Perioperative care at a university-affiliated tertiary care center. PATIENTS: 57,401 adult patients who received general anesthesia in a non-emergency setting. INTERVENTION: A multi-phased intervention that consisted of post-hoc reporting for individual providers by email about PONV occurrences in their patients, followed by directive CDS through preoperative daily case emails that provided therapeutic PONV prophylaxis recommendations based on patients' PONV risk scores. MEASUREMENT: Compliance with PONV medication recommendations, as well as hospital rates of PONV were measured. MAIN RESULT: Over the study period, there was a 5.5% (95% CI, 4.2% to 6.4%; p < 0.001) improvement in the compliance of PONV medication administration along with an 8.7% (95% CI, 7.1% to 10.2%, p < 0.001) reduction in PONV rescue medication administration in the PACU. However, there was no statistically or clinically significant reduction in the prevalence of PONV in the PACU. The prevalence of PONV rescue medication administration decreased during the Intervention Rollout Period (odds ratio 0.95 [per month]; 95% CI, 0.91 to 0.99; p = 0.017), and during the Feedback with CDS Recommendation Period (odds ratio, 0.96 [per month]; 95% CI, 0.94 to 0.99; p = 0.013). CONCLUSION: PONV medication administration compliance modestly improves with CDS in conjunction with post-hoc reporting; however, no improvement in PACU rates of PONV occurred.

Ambulatory Care Fragmentation, Emergency Department Visits, and Race: a Nationwide Cohort Study in the U.S.

BACKGROUND: It is unclear whether highly fragmented ambulatory care (i.e., care spread across multiple providers without a dominant provider) increases the risk of an emergency department (ED) visit. Whether any such association varies with race is unknown. OBJECTIVE: We sought to determine whether highly fragmented ambulatory care increases the risk of an ED visit, overall and by race. DESIGN AND PARTICIPANTS: We analyzed data for 14,361 participants ≥ 65 years old from the nationwide prospective REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort study, linked to Medicare claims (2003-2016). MAIN MEASURES: We defined high fragmentation as a reversed Bice-Boxerman Index ≥ 0.85 (≥ 75th percentile). We used Poisson models to determine the association between fragmentation (as a time-varying exposure) and ED visits, overall and stratified by race, adjusting for demographics, medical conditions, medications, health behaviors, psychosocial variables, and physiologic variables. KEY RESULTS: The average participant was 70.5 years old; 53% were female, and 33% were Black individuals. Participants with high fragmentation had a median of 9 visits to 6 providers, with 29% of visits by the most frequently seen provider; participants with low fragmentation had a median of 7 visits to 3 providers, with 50% of visits by the most frequently seen provider. Overall, high fragmentation was associated with more ED visits than low fragmentation (adjusted risk ratio [aRR] 1.31, 95% confidence interval [CI] 1.29, 1.34). The magnitude of this association was larger among Black (aRR 1.48, 95% CI 1.44, 1.53) than White participants (aRR 1.23, 95% CI 1.20, 1.25). CONCLUSIONS: Highly fragmented ambulatory care was an independent predictor of ED visits, especially among Black individuals.

Arterial stiffness in acute coronary syndrome as a potential triage tool: a prospective observational study.

BACKGROUND: Diagnosis and percutaneous coronary intervention (PCI) in acute coronary syndrome (ACS) are time-sensitive. Triage and algorithms identify patients at high-risk. However, additional prediction tools are warranted for prioritized care based on predicted coronary pathologies and PCI complexity. Pulse-wave velocity (PWV) is a non-invasive measurement related to cardiovascular morbidity, and their exact value in ACS evaluation is unclear. METHODS: In patients undergoing coronary angiography (CA) and - if warranted - PCI for ACS evaluation at a tertiary university hospital in Vienna, Austria, brachial-ankle (ba)PWV and carotid-femoral (cf)PWV were prospectively measured from January 2020 to January 2021. RESULTS: PWV was measured in 58 patients (60.3% male; 65 [61-69] years). Risk prediction scores (GRACE, CRUSADE, TIMI), cardiac enzymes, and fraction of patients with a three-vessel disease were significantly higher in the pathological PWV ranges. Adjusted for age and comorbidities, baPWV independently predicted the LAD being relevantly stenotic (crude OR=1.416 [1.143-1.755], P=0.001; adjusted OR=1.340 [1.039-1.727], P=0.024; cut-off 15.5 m/s in CART-analysis), being the culprit lesion (crude OR=1.320 [1.094-1.594], P=0.004; adjusted OR=1.311 [1.037-1.657], P=0.024; cut-off 15.5 m/s), and being totally occluded (crude OR=1.422 [1.113-1.818], P=0.005; adjusted OR=1.677 [1.189-2.366], P=0.003; cut-off 19.6 m/s). Moreover, CA or PCI complexity were associated with higher PWV. CONCLUSIONS: Pathological PWV as a surrogate for arterial stiffness, polyvascular disease and a larger atherosclerotic burden was associated with GRACE, CRUSADE, and TIMI scores, and PCI duration and complexity. BaPWV independently predicted relevant LAD pathologies, and is suggested as a potential novel triage and prioritization tool for suspected NSTE-ACS in emergency departments.

Efficacy and safety of sonographer discretion to terminate a venous duplex ultrasound for diagnosis of deep vein thrombosis in coronavirus disease 2019 patients.

OBJECTIVE: Sonographers performing venous duplex ultrasound (VDUS) of patients with coronavirus disease 2019 (COVID-19) have an increased risk of exposure owing to their close contact with these patients for an extended period. The objective of the present study was to evaluate the efficacy of a modified COVID-19 VDUS protocol to reduce sonographer exposure to COVID-19 patients. METHODS: We performed a single-center retrospective review. Patients who had undergone VDUS under the modified COVID-19 protocol between March 1, 2020, and June 30, 2020, with a confirmed or presumed COVID-19 diagnosis at the VDUS were included. The modified COVID-19 protocol was defined as the ability of the sonographer to terminate the examination on detection of an acute deep vein thrombosis (DVT). The primary outcome measures were the number of anatomic deep venous segments recorded by the sonographer, which was used as a surrogate measure for sonographer exposure time, and the number of acute DVTs found on follow-up examinations in segments not visualized at the index VDUS. RESULTS: A total of 160 lower extremity VDUS (LEVDUS) scans and 72 upper extremity VDUS (UEVDUS) scans were performed using the modified COVID-19 protocol. The index VDUS had found an acute DVT for 44 of 160 patients (27.5%) who had undergone LEVDUS and 26 of 72 (36.6%) who had undergone UEVDUS. On follow-up imaging, 7 of 38 LEVDUS scans (17.9%) and 1 of 10 UEVDUS scans (10%) had demonstrated a new acute DVT. Malignancy and surgery 30 days before imaging were significantly associated with acute lower extremity DVT, and mechanical ventilation and extracorporeal membrane oxygenation were associated with acute upper extremity DVT. On the index VDUS, the average was 10.6 of 12 total visualized segments on LEVDUS and 6.4 of 10 total segments on UEVDUS. Of the index VDUS scans, 35.6% of the LEVDUS and 78.6% of the UEVDUS scans had been abbreviated. The index VDUS scans that were positive for acute DVT had had significantly fewer visualized segments for both lower (8.4 vs 11.5; P < .0001) and upper (4.2 vs 7.6) extremities (P < .0001). On the follow-up examinations, only one of eight new acute DVTs had been found in a patient whose index VDUS had been abbreviated and the corresponding segment not assessed. These findings did not affect the patient's clinical course. CONCLUSIONS: The modified COVID-19 VDUS protocol reduced sonographers' potential exposure time to COVID-19. Additionally, the clinical efficacy was maintained, with no missed DVTs, despite the abbreviation of the VDUS examinations.