Ultrasound elastography to quantify average percent pressure-normalized strain reduction associated with different aortic endografts in 3D-printed hydrogel phantoms.

Objective: Strain has become a viable index for evaluating abdominal aortic aneurysm stability after endovascular aneurysm repair (EVAR). In addition, literature has shown that healthy aortic tissue requires a degree of strain to maintain homeostasis. This has led to the hypothesis that too much strain reduction conferred by a high degree of graft oversizing is detrimental to the aneurysm neck in the seal zone of abdominal aortic aneurysms after EVAR. We investigated this in a laboratory experiment by examining the effects that graft oversizing has on the pressure-normalized strain ( ε ρ + ¯ /pulse pressure [PP]) reduction using four different infrarenal EVAR endografts and our ultrasound elastography technique. Approximate graft oversizing percentages were 20% (30 mm phantom-graft combinations), 30% (28 mm phantom-graft combinations), and 50% (24 mm phantom-graft combinations). Methods: Axisymmetric, 10% by mass polyvinyl alcohol phantoms were connected to a flow simulator. Ultrasound elastography was performed before and after implantation with the four different endografts: (1) 36 mm polyester/stainless steel, (2) 36 mm polyester/electropolished nitinol, (3) 35 mm polytetrafluoroethylene (PTFE)/nitinol, and (4) 36 mm nitinol/polyester/platinum-iridium. Five ultrasound cine loops were taken of each phantom-graft combination. They were analyzed over two different cardiac cycles (end-diastole to end-diastole), yielding a total of 10 maximum mean principal strain ( ε ρ + ¯ ) values. ε ρ + ¯ was divided by pulse pressure to yield pressure-normalized strain ( ε ρ + ¯ /PP). An analysis of variance was performed for graft comparisons. We calculated the average percent ε ρ + ¯ /PP reduction by manufacturer and percent oversizing. These values were used for linear regression analysis. Results: Results from one-way analysis of variance showed a significant difference in ε ρ + ¯ /PP between the empty phantom condition and all oversizing conditions for all graft manufacturers (F(3, 56) = 106.7 [graft A], 132.7 [graft B], 106.5 [graft C], 105.7 [graft D], P < .0001 for grafts A-D). There was a significant difference when comparing the 50% condition with the 30% and 20% conditions across all manufacturers by post hoc analysis (P < .0001). No significant difference was found when comparing the 20% and 30% oversizing conditions for any of the manufacturers or when comparing ε ρ + ¯ /PP values across the manufacturers according to percent oversize. Linear regression demonstrated a significant positive correlation between the percent graft oversize and the all-graft average percent ε ρ + ¯ /PP reduction ( R 2  = 0.84, P < .0001). Conclusions: This brief report suggests that a 10% increase in graft oversizing leads to an approximate 5.9% reduction in ε ρ + ¯ /PP on average. Applied clinically, this increase may result in increased stiffness in axisymmetric vessels after EVAR. Further research is needed to determine if this is clinically significant.

Implementation of a Vascular Acute Care Surgery Model is Associated with Improved Surgeon Efficiency and Two-Year Mortality After Lower Extremity Intervention.

OBJECTIVE: Vascular surgeons work long, unpredictable hours with repeated exposure to high-stress situations. Inspired by general surgery acute care surgery models, we sought to organize the care of vascular emergencies with the implementation of a vascular acute care surgery (VACS) model. Within this model, a surgeon is in-house without elective cases and assigned for consultations and urgent operative cases on a weekly basis. This study examined the impact of a VACS model on postoperative mortality and surgeon efficiency. METHODS: This was a retrospective cohort analysis of institutional Vascular Quality Initiative data from July 2014 - July 2023. Patients undergoing lower extremity bypass, peripheral vascular intervention, or amputation were included. There was a washout period from January 2020 - January 2022 to account for COVID-19 pandemic practice abnormalities. Patients were separated into pre- or post-VACS groups. The primary clinical outcomes were 30-day and 2-year mortality. Secondary clinical outcomes included 30-day complications and 30-day and 1-year major adverse limb events (MALE). Separate analyses of operating room data from July 2017 - February 2024 and fiscal data from fiscal year 2019 - fiscal year 2024 were conducted. A washout period from January 2020 - January 2022 was applied. Efficiency outcomes included monthly relative value units (RVUs) per clinical fraction full-time equivalent (cFTE) and daytime (0730-1700, Monday-Friday) operating room minutes. Patient factors and operative efficiency were compared using appropriate statistical tests. Regression modeling was performed for the primary outcomes. RESULTS: There were 972 and 257 patients in the pre- and post-VACS groups, respectively. Pre-VACS patients were younger (66.8±12.0 vs 68.7±12.7 years, p=0.03) with higher rates of coronary artery disease (34.6% vs 14.8%, p<0.01), hypertension (88.4% vs 82.2%, p=0.01), and tobacco history (84.4% vs 78.2%, p=0.02). 30-day mortality (2.4% pre- vs 0.8% post-VACS, p=0.18) and Kaplan-Meier estimation of 2-year mortality remained stable after VACS (p=0.07). VACS implementation was not associated with 30-day mortality but was associated with lower 2-year mortality hazard on multivariable Cox regression (hazard ratio: 0.5, 95% confidence interval: 0.3-0.9, p=0.01). Operative efficiency improved post-VACS (850.0 [765.7, 916.3] vs 918.0 [881.0, 951.1] RVU/cFTE-month, median [inter-quartile range], p=0.03). Daytime operating minutes increased (469.1±287.5 vs 908.2±386.2 minutes, p<0.01), while non-daytime minutes (420.0 [266.0, 654.0] vs 469.5 [242.0, 738.3] minutes, p=0.40) and weekend minutes (129.0 [0.0, 298.0] vs 113.5 [0.0, 279.5] minutes, p=0.59) remained stable. CONCLUSIONS: A VACS model leads to improvement in surgeon operative efficiency while maintaining patient safety. The adoption of a vascular acute care model has a positive impact on the delivery of comprehensive vascular care.

A national census for the off-label treatment of complex aortic aneurysms.

OBJECTIVE: Despite regulatory challenges, device availability, and rapidly expanding techniques, off-label endovascular repair of complex aortic aneurysms (cAAs) has expanded in the past decade. Given the lack of United States Food and Drug Administration-approved endovascular technology to treat cAAs, we performed a national census to better understand volume and current practice patterns in the United States. METHODS: Targeted sampling identified vascular surgeons with experience in off-label endovascular repair of cAAs. An electronic survey was distributed with institutional review board approval from the University of Rochester to 261 individuals with a response rate of 38% (n = 98). RESULTS: A total of 93 respondents (95%) reported off-label endovascular repair of cAAs. Mean age was 45.7 ± 8.3 years, and 84% were male. Most respondents (59%) were within the first 10 years of practice, and 69% trained at institutions with a high-volume of off-label endovascular procedures for complex aortic aneurysms with or without a physician-sponsored investigational device exemption (PS-IDE). Twelve respondents from 11 institutions reported institutional PS-IDEs for physician-modified endografts (PMEGs), in-situ laser fenestration (ISLF), or parallel grafting technique (PGT), including sites with PS-IDEs for custom-manufactured devices. Eighty-nine unique institutions reported elective off-label endovascular repair with a mean of 20.2 ± 16.5 cases/year and ∼1757 total cases/year nationally. Eighty reported urgent/emergent off-label endovascular repair with a mean of 5.7 ± 5.4 cases/year and ∼499 total cases/year nationally. There was no correlation between high-volume endovascular institutions (>15 cases/year) and institutions with high volumes of open surgical repair for cAAs (>15 cases/year; odds ratio, 0.7; 95% confidence interval, 0.3-1.5; P = .34). Elective techniques included PMEG (70%), ISLF (30%), hybrid PMEG/ISLF (18%), and PGT (14%), with PMEG being the preferred technique for 63% of respondents. Techniques for emergent endovascular treatment of complex aortic disease included PMEG (52%), ISLF (40%), PGT (20%), and hybrid-PMEG/ISLF (14%), with PMEG being the preferred technique for 41% of respondents. Thirty-nine percent of respondents always or frequently offer referrals to institutions with PS-IDEs for custom-manufactured devices. The most common barrier for referral to PS-IDE centers included geographic distance (48%), longitudinal relationship with patient (45%), and costs associated with travel (33%). Only 61% of respondents participate in the Vascular Quality Initiative for complex endovascular aneurysm repair, and only 57% maintain a prospective institutional database. Eighty-six percent reported interest in a national collaborative database for off-label endovascular repair of cAA. CONCLUSIONS: Estimates of off-label endovascular repair of cAAs are likely underrepresented in the literature based on this national census. PMEG was the most common technique for elective and emergent procedures. Under-reported off-label endovascular repair of cAA outcomes data appears to be limited by non-standardized PS-IDE reporting to the United States Food and Drug Administration, and the lack of Vascular Quality Initiative participation and prospective institutional data collection. Most participants are interested in a national collaborative database for endovascular repair of cAAs.

Implementation of a vascular acute care surgery service model is associated with decreased surgeon burnout.

OBJECTIVE: Vascular surgeons have one of the highest rates of burnout among surgical specialties, often attributed to high patient acuity and clinical workload. Acute Care Surgery models are a potential solution used among general and trauma surgeons. METHODS: This is a retrospective analysis of prospectively collected Accreditation Council for Graduate Medical Education survey results from faculty and residents before and after implementation of a vascular Acute Care Surgery (VACS) model. The VACS model assigns a weekly rotation of an attending surgeon with no elective cases or clinic responsibilities and a monthly rotating resident team. Residents and attendings are in-house to cover all urgent and emergent vascular daytime consultations and procedures, whereas nights and weekend coverage remain a typical rotating schedule. Survey question results were binned into domains consistent with the Maslach Burnout Inventory. RESULTS: Both residents and faculty reported an increase in median scores in Maslach Burnout Inventory domains of emotional exhaustion (Faculty: 2.9 vs 3.4; P < .001; Residents: 3.1 vs 3.6; P < .001) and faculty reported higher personal accomplishment scores (Faculty: 3.3 vs 3.8; P = .005) after the VACS model implementation. CONCLUSIONS: A VACS model is a tangible practice change that can address a major problem for current vascular surgeons, as it is associated with decreased burnout for faculty and residents through improvement in both emotional exhaustion and personal accomplishment. Improved longitudinal assessment of resident and faculty burnout is needed and future work should identify specific practice patterns related to decreased burnout.

Stenting of a hepatic artery pseudoaneurysm rupture secondary to a celiac artery dissection.

Hepatic artery (HA) pseudoaneurysm rupture is a rare and potentially lethal pathology. We present the case of a celiac artery dissection complicated by an HA pseudoaneurysm rupture that was treated successfully with endovascular stenting. The patient's postoperative course was uncomplicated, and he was further evaluated for an underlying connective tissue disorder. There is no standard treatment for a ruptured HA pseudoaneurysm, although transarterial embolization is most frequently reported. This report demonstrates that self-expanding stent grafts are effective in the emergent repair of HA pseudoaneurysm rupture.

Validation of GCN5L1/BLOC1S1/BLOS1 antibodies using knockout cells and tissue.

GCN5L1, also known as BLOC1S1 and BLOS1, is a small intracellular protein involved in many key biological processes. Over the last decade, GCN5L1 has been implicated in the regulation of protein lysine acetylation, energy metabolism, endo-lysosomal function, and cellular immune pathways. An increasing number of published papers have used commercially-available reagents to interrogate GCN5L1 function. However, in many cases these reagents have not been rigorously validated, leading to potentially misleading results. In this report we tested several commercially-available antibodies for GCN5L1, and found that two-thirds of those available did not unambiguously detect the protein by western blot in cultured mouse cells or ex vivo liver tissue. These data suggest that previously published studies which used these unverified antibodies to measure GCN5L1 protein abundance, in the absence of other independent methods of corroboration, should be interpreted with appropriate caution.

Early Financial Outcomes of Physician Modified Endograft Programs Are Dictated by Device Cost.

INTRODUCTION: Physician-modified endografts (PMEGs) have been used for repair of thoracoabdominal aortic aneurysms (TAAAs) for 2 decades with good outcomes but limited financial data. This study compared the financial and clinical outcomes of PMEGs to the Cook Zenith-Fenestrated (ZFEN) graft and open surgical repair (OSR). METHODS: A retrospective review of financial and clinical data was performed for all patients who underwent endovascular or OSR of juxtarenal aortic aneurysms and TAAAs from January 2018 to December 2022 at an academic medical center. Clinical presentation, demographics, operative details, and outcomes were reviewed. Financial data was obtained through the institution's finance department. The primary end point was contribution margin (CM). RESULTS: Thirty patients met inclusion criteria, consisting of twelve PMEG, seven ZFEN, and eleven open repairs. PMEG repairs had a total CM of -$110,000 compared to $18,000 for ZFEN and $290,000 for OSR. Aortic and branch artery implants were major cost-drivers for endovascular procedures. Extent II TAAA repairs were the costliest PMEG procedure, with a total device cost of $59,000 per case. PMEG repairs had 30-d and 1-y mortality rates of 8.3% which was not significantly different from ZFEN (0.0%, P = 0.46; 0.0%, P = 0.46) or OSR (9.1%, P = 0.95; 18%, P = 0.51). Average intensive care unit and hospital stay after PMEG repairs were comparable to ZFEN and shorter than OSR. CONCLUSIONS: Our study suggests that PMEG repairs yield a negative CM. To make these cases financially viable for hospital systems, device costs will need to be reduced or reimbursement rates increased by approximately $8800.

Cardiomyocyte-specific deletion of GCN5L1 reduces lysine acetylation and attenuates diastolic dysfunction in aged mice by improving cardiac fatty acid oxidation.

Cardiac mitochondrial dysfunction is a critical contributor to the pathogenesis of aging and many age-related conditions. As such, complete control of mitochondrial function is critical to maintain cardiac efficiency in the aged heart. Lysine acetylation is a reversible post-translational modification shown to regulate several mitochondrial metabolic and biochemical processes. In the present study, we investigated how mitochondrial lysine acetylation regulates fatty acid oxidation (FAO) and cardiac function in the aged heart. We found a significant increase in mitochondrial protein acetylation in the aged heart which correlated with increased level of mitochondrial acetyltransferase-related protein GCN5L1. We showed that acetylation status of several fatty acid and glucose oxidation enzymes (long-chain acyl-coenzyme A dehydrogenase, hydroxyacyl-coA dehydrogenase, and pyruvate dehydrogenase) were significantly up-regulated in aged heart which correlated with decreased enzymatic activities. Using a cardiac-specific GCN5L1 knockout (KO) animal model, we showed that overall acetylation of mitochondrial proteins was decreased in aged KO animals, including FAO proteins which led to improved FAO activity and attenuated cardiac diastolic dysfunction observed in the aged heart. Together, these findings indicate that lysine acetylation regulates FAO in the aged heart which results in improved cardiac diastolic function and this is in part regulated by GCN5L1.

Preoperative Risk Factors Impacting Length of Stay After Transcarotid Artery Revascularization.

BACKGROUND: Transcarotid artery revascularization (TCAR), using interoperative flow reversal is a unique, hybrid operation utilized in treating critical carotid artery stenosis. Over the past decade, TCAR has been increasingly used to treat asymptomatic carotid artery disease and has a similar risk profile to traditional carotid endarterectomy. Postoperative length of stay (LOS) has a significant impact on cost-effectiveness and quality outcomes in this expanded setting. The objective of this study is to develop a multivariate regression model to identify key preoperative variables and their impact factor on LOS after TCAR for asymptomatic carotid artery stenosis. We hypothesized that high-risk preoperative patient factors historically identified in carotid endarterectomy would similarly impact LOS after TCAR. METHODS: A multi-institution, retrospective study of all adult patients undergoing TCAR with flow-reversal for intraoperative neuroprotection was performed using the Society for Vascular Surgery Vascular Quality Initiative (VQI) from January 2016 to August 2021. Patients with prolonged preoperative hospitalization (preoperative LOS ≥1 day) were excluded to enhance the capture of carotid artery stenosis as the index admission. Univariate analysis was done on preoperative factors against LOS using nonparametric statistical tests. A multivariate model was then constructed using a negative binomial regression. The study population was split into 80% "training" data for model formulation and 20% "test" data for model validation. RESULTS: Thirteen thousand four hundred eighty-three patients undergoing TCAR for asymptomatic carotid stenosis met the study's inclusion criteria with a median postoperative LOS of 1.82 days. Factors in VQI found to have a significant effect on LOS and retained in the multivariate model were lesion type (restenosis versus atherosclerotic), age, gender, chronic obstructive pulmonary disease, preoperative beta blocker, calcific lesion burden, hypertension status, and race (P < 0.05). The model accurately predicted LOS after TCAR within 1 day for 86.04% and within 2 days for 94.51% of patients in the test population. CONCLUSIONS: This large-scale analysis from 2016 to 2021 spans a considerable expansion in the practice of TCAR for asymptomatic carotid disease. All preoperative variables shown to significantly increase the postoperative LOS were derived from the VQI data set. As LOS is a measure of health-care efficiency and cost-effectiveness, this model can be used to identify patients at risk for increased postoperative LOS. It has the potential to be incorporated into a patient/physician decision support tool to optimize resource planning and patient selection for elective TCAR.

A registry-based study of paclitaxel drug-coated balloon angioplasty for the treatment of in-stent restenosis of the femoral-popliteal artery.

OBJECTIVE: The aim of this study was to report the results of a prospective, single-arm, registry-based study assessing the safety and performance of a paclitaxel drug-coated balloon (DCB) for the treatment of superficial femoral artery (SFA) or popliteal artery in-stent restenosis (ISR) in a United States population. METHODS: We conducted a prospective, non-randomized, multi-center, single-arm, post-market registry of the IN.PACT Admiral DCB for the treatment of ISR lesions in the SFA or popliteal artery at 43 sites within the Society for Vascular Surgery (SVS) Vascular Quality Initiative (VQI) Registry from December 2016 to January 2020. Clinical outcomes were assessed at 12, 24, and 36 months. The primary endpoint was target lesion revascularization at 12 months. Secondary endpoints included technical success, target vessel revascularization, major limb amputation, and all-cause mortality. Results are presented as survival probabilities based on Kaplan-Meier survival estimates. RESULTS: Patients (N = 300) were 58% male, with a mean age of 68 ± 10 years. Diabetes was present in 56%, 80% presented with claudication, and 20% with rest pain. Lesions included ISR of the SFA in 68%, SFA-popliteal in 26%, and popliteal arteries in 7%. The mean lesion length was 17.8 ± 11.8 cm. Lesions were categorized as occlusions in 43% (mean occluded length, 16 ± 10 cm). TASC type was A (17%), B (29%), C (38%), and D (15%). Technical success was 99%. Re-stenting was performed in 5% and thrombolysis in 0.6% of patients. Kaplan-Meier estimates for freedom from target lesion revascularization were 90%, 72%, and 62% at 12, 24, and 36 months. Freedom from target vessel revascularization was 88%, 68%, and 59% and freedom from major target limb amputation was 99.6%, 98.9%, and 98.9%, respectively, at 12, 24, and 36 months. Survival was 95%, 89%, and 85% at 12, 24, and 36 months. CONCLUSIONS: This post-market registry-based study shows promising results in treating femoral-popliteal ISR with paclitaxel DCB in comparison to the results of plain balloon angioplasty reported in the literature. These results demonstrate the ability of the SVS VQI to conduct post-market evaluation of peripheral devices in partnership with industry and federal regulators.

GCN5L1-mediated acetylation prevents Rictor degradation in cardiac cells after hypoxic stress.

Cardiomyocyte apoptosis and cardiac fibrosis are the leading causes of mortality in patients with ischemic heart disease. As such, these processes represent potential therapeutic targets to treat heart failure resulting from ischemic insult. We previously demonstrated that the mitochondrial acetyltransferase protein GCN5L1 regulates cardiomyocyte cytoprotective signaling in ischemia-reperfusion injury in vivo and hypoxia-reoxygenation injury in vitro. The current study investigated the mechanism underlying GCN5L1-mediated regulation of the Akt/mTORC2 cardioprotective signaling pathway. Rictor protein levels in cardiac tissues from human ischemic heart disease patients were significantly decreased relative to non-ischemic controls. Rictor protein levels were similarly decreased in cardiac AC16 cells following hypoxic stress, while mRNA levels remained unchanged. The reduction in Rictor protein levels after hypoxia was enhanced by the knockdown of GCN5L1, and was blocked by GCN5L1 overexpression. These findings correlated with changes in Rictor lysine acetylation, which were mediated by GCN5L1 acetyltransferase activity. Rictor degradation was regulated by proteasomal activity, which was antagonized by increased Rictor acetylation. Finally, we found that GCN5L1 knockdown restricted cytoprotective Akt signaling, in conjunction with decreased mTOR abundance and activity. In summary, these studies suggest that GCN5L1 promotes cardioprotective Akt/mTORC2 signaling by maintaining Rictor protein levels through enhanced lysine acetylation.

Locoregional Anesthesia's Association With Reduced Intensive Care Unit Stay After Elective Endovascular Aneurysm Repair: Impact of Temporal Changes in Practice Patterns.

BACKGROUND: Elective endovascular aneurysm repair (EVAR) can be performed via local anesthetics and/or regional (epidural or spinal) anesthesia (locoregional [LR]), versus general anesthesia (GA), conferring reduced intensive care unit (ICU) and hospital stays. Current analyses fail to account for temporal changes in vascular practice. Therefore, this study aimed to confirm reductions in ICU and hospital stays among LR patients while accounting for changes in practice patterns. MATERIALS AND METHODS: Using the Society for Vascular Surgery's Vascular Quality Initiative, elective EVARs from August 2003 to June 2021 were grouped into LR or GA. Outcomes included ICU admission and prolonged hospital stay (>2 d). Procedures were stratified into groups of 2 y periods, and outcomes were analyzed within each time period. Univariable and multivariate analyses were used to assess outcomes. RESULTS: LR was associated with reduced ICU admissions (22.3% versus 32.1%, P < 0.001) and prolonged hospital stays (14.3% versus 7.9%, P < 0.001) overall. When stratified by year, LR maintained its association with reduced ICU admissions in 2014-2015 (21.8% versus 34.0%, P < 0.001), 2016-2017 (23.6% versus 31.6%, P < 0.001), 2018-2019 (18.5% versus 30.2%, P < 0.001), and 2020-2021 (15.8% versus 28.8%, P < 0.001), although this was highly facility dependent. LR was associated with fewer prolonged hospital stays in 2014-2015 (15.6% versus 20.4%, P = 0.001) and 2016-2017 (13.3% versus 16.6%, P = 0.006) but not after 2017. CONCLUSIONS: GA and LR have similar rates of prolonged hospital stays after 2017, while LR anesthesia was associated with reduced rates of ICU admissions, although this is facility-dependent, providing a potential avenue for resource preservation in patients suitable for LR.

Long-term value in open and endovascular repair of chronic mesenteric ischemia.

OBJECTIVE: Guidelines recommend open revascularization (OR) over endovascular revascularization (ER) for the treatment of chronic mesenteric ischemia (CMI) for younger, healthier patients. However, little is known about the long-term costs of these recommendations with respect to patients' overall life expectancy. This study investigated whether 5-year value differs between these treatment modalities. METHODS: Patient data were extracted from the Statewide Planning and Research Cooperative System, the New York statewide all-payor database containing demographics, diagnoses, treatments, and charges. The database was queried for patients with an International Classification of Diseases, ninth revision, code for CMI, with the specific exclusion of acute ischemia cases. A propensity score match was performed using the Charlson Comorbidity Index, age, sex, race, renal status, and pulmonary disease for the final cohort of patients. Multiple linear regression and mixed effects linear regression were used to determine factors associated with 5-year value, calculated as life-years/$100k in charges. Charges were gathered from the index admission and subsequent admissions for acute or CMI, mesenteric angiography, or follow-up reintervention. Kaplan-Meier estimation was performed for survival and reintervention-free survival. RESULTS: From 2000 to 2014, 875 patients underwent intervention for CMI. Of those meeting inclusion criteria, 209 (28.1%) underwent OR and 535 (71.9%) ER. After propensity score matching (n = 209 in each group), the ER group showed higher value at 5 years after the procedure (8.04 ± 11.42 life-years/$100k charges vs 4.89 ± 5.28 life-years/$100k charges; P < .01). More patients underwent reintervention in the ER group (37 patients vs 17 patients; P < .01), with 55 reinterventions in the ER group and 19 in the OR group (P < .01). Multiple linear regression analysis showed that age, congestive heart failure, dysrhythmia, cancer, and days spent in the intensive care unit were negatively associated with value at 5 years, whereas ER was positively associated. Survival was 59.6 ± 3.76% vs 62.3% ± 3.49% at 5 years (P = .91), and reintervention-free survival was 43.7 ± 3.86% vs 58.1 ± 3.53% (P = .04), for ER and OR respectively. CONCLUSIONS: Despite increased reinterventions and lower reintervention-free survival, the value for patients with CMI was higher in those who underwent ER in the largest propensity score-matched cohort to date looking at long-term value. Factors negatively associated with value were OR, age, days in intensive care, congestive heart failure, dysrhythmia, and cancer. In patients with amenable anatomy, ER is validated as the first-choice treatment for CMI based on the superior procedural value.

Review of pediatric emergency care and the COVID-19 pandemic.

The coronavirus disease 2019 (COVID-19) pandemic posed new challenges in health care delivery for patients of all ages. These included inadequate personal protective equipment, workforce shortages, and unknowns related to a novel virus. Children have been uniquely impacted by COVID-19, both from the system of care and socially. In the initial surges of COVID-19, a decrease in pediatric emergency department (ED) volume and a concomitant increase in critically ill adult patients resulted in re-deployment of pediatric workforce to care for adult patients. Later in the pandemic, a surge in the number of critically ill children was attributed to multisystem inflammatory syndrome in children. This was an unexpected complication of COVID-19 and further challenged the health care system. This article reviews the impact of COVID-19 on the entire pediatric emergency care continuum, factors affecting ED care of children with COVID-19 infection, including availability of vaccines and therapeutics approved for children, and pediatric emergency medicine workforce innovations and/or strategies. Furthermore, it provides guidance to emergency preparedness for optimal delivery of care in future health-related crises.

GCN5L1-mediated acetylation prevents Rictor degradation in cardiac cells after hypoxic stress.

Cardiomyocyte apoptosis and cardiac fibrosis are the leading causes of mortality in patients with ischemic heart disease. As such, these processes represent potential therapeutic targets to treat heart failure resulting from ischemic insult. We previously demonstrated that the mitochondrial acetyltransferase protein GCN5L1 regulates cardiomyocyte cytoprotective signaling in ischemia-reperfusion injury in vivo and hypoxia-reoxygenation injury in vitro. The current study investigated the mechanism underlying GCN5L1-mediated regulation of the Akt/mTORC2 cardioprotective signaling pathway. Rictor protein levels in cardiac tissues from human ischemic heart disease patients were significantly decreased relative to non-ischemic controls. Rictor protein levels were similarly decreased in cardiac AC16 cells following hypoxic stress, while mRNA levels remained unchanged. The reduction in Rictor protein levels after hypoxia was enhanced by the knockdown of GCN5L1, and was blocked by GCN5L1 overexpression. These findings correlated with changes in Rictor lysine acetylation, which were mediated by GCN5L1 acetyltransferase activity. Rictor degradation was regulated by proteasomal activity, which was antagonized by increased Rictor acetylation. Finally, we found that GCN5L1 knockdown restricted cytoprotective Akt signaling, in conjunction with decreased mTOR abundance and activity. In summary, these studies suggest that GCN5L1 promotes cardioprotective Akt/mTORC2 signaling by maintaining Rictor protein levels through enhanced lysine acetylation.

Rehydration Rates and Outcomes in Overweight Children With Diabetic Ketoacidosis.

BACKGROUND AND OBJECTIVES: The Pediatric Emergency Care Applied Research Network Fluid Therapies Under Investigation in Diabetic Ketoacidosis (DKA) (FLUID) Trial found that rapid fluid infusion does not increase the risk of cerebral injury. Concern persists, however, whether fluid rates should be adjusted for overweight or obese patients. We used the FLUID Trial database to evaluate associations between fluid infusion rate and outcomes in these patients. METHODS: We compared children and youth who were overweight, obese, or normal weight, in regard to protocol adherence, mental status changes, time to DKA resolution, and electrolyte abnormalities. We investigated associations between outcomes and the amount of fluid received in these groups. RESULTS: Obese children and youth were more likely to receive fluids at rates slower than dictated by protocol. Overweight and obese children and youth in the fast fluid arms, who received fluids per the study protocol based on their measured weight, had similar rates of mental status changes or clinically apparent cerebral injury as those with normal weights. Risk of hypophosphatemia was increased in those receiving larger initial bolus volumes and reduced in those receiving higher rehydration rates. No other metabolic outcomes were associated with rehydration. CONCLUSIONS: Protocol adherence data in the FLUID Trial suggest that physicians are uncomfortable using weight-based fluid calculations for overweight or obese children. However, higher rates of fluid infusion were not associated with increased risk of mental status changes or cerebral injury, suggesting that physicians should not limit fluid resuscitation in obese children and youth with DKA.

Survival, Reintervention, and Value of Open and Endovascular Repair for Chronic Mesenteric Ischemia.

BACKGROUND: There are limited analyses of survival and postoperative outcomes in chronic mesenteric ischemia (CMI) using data from large cohorts. Current guidelines recommend open repair (OR) for younger, healthier patients when long-term benefits outweigh increased perioperative risks or for poor endovascular repair (ER) candidates. This study investigates whether long-term survival, reintervention, and value differ between these treatment modalities. METHODS: A retrospective cohort analysis was performed on data extracted from the Statewide Planning and Research Cooperative System, the New York statewide all-payer database containing demographics, diagnoses, treatments, and charges. Patients were selected for CMI and subsequent ER or OR using International Classification of Diseases, Ninth Revision codes. Patients with peripheral arterial disease were excluded to account for ambiguity in the International Classification of Diseases, Ninth Revision procedure code for angioplasty of noncoronary vessels, which includes angioplasty of upper and lower extremity vessels. Kaplan-Meier analysis was used to compare 1-year and 5-year survival and reintervention between treatment modalities using a propensity-matched cohort. Cox proportional hazards testing was performed to find factors associated with 1-year and 5-year survival and reintervention. Analysis of procedural value was performed using linear regression. RESULTS: From 2000 to 2014, 744 patients met inclusion criteria. Of these, 209 (28.1%) underwent OR and 535 (71.9%) ER. No difference between propensity-matched groups was found in 1-year (P = 0.46) or 5-year (P = 0.91) survival. Congestive heart failure (hazard ratio [HR]: 2.8, 95% confidence interval [CI]: 1.7-4.4; P < 0.01), cancer (HR: 2.8, 95% CI: 1.3-5.8; P < 0.01), and dysrhythmia (HR: 1.8, 95% CI: 1.1-2.8; P = 0.02) correlated with 1-year mortality. Cancer (HR: 2.9, 95% CI: 1.6-5.5; P < 0.01), congestive heart failure (HR: 2.2, 95% CI: 1.5-3.2; P < 0.01), chronic pulmonary disease (HR: 1.4, 95% CI: 1.0-2.0; P = 0.04), and age (HR: 1.03, 95% CI: 1.01-1.05; P < 0.01) correlated with 5-year mortality. Treatment modality was not associated with reintervention at 1 year on Kaplan-Meier analysis (P = 0.29). However, ER showed increased instances of reintervention at 5 years (P < 0.01). Additionally, ER was associated with an increased 5-year value (0.7 ± 0.9 vs. 0.5 ± 0.5 life years/charges at index admission [$10k], P < 0.01; b coefficient: 0.2, 95% CI: 0.1-0.4, P < 0.01). CONCLUSIONS: This is the largest retrospective propensity-matched single-study cohort to analyze long-term survival outcomes after intervention for CMI. Long-term mortality was independent of treatment modality and rather was associated with patient comorbidities. Therefore, treatment selection should depend on anatomic considerations and long-term value. ER should be considered over OR in patients with amenable anatomy based on the superior procedural value.

Limb shaking transient ischemic attack secondary to innominate artery stenosis.

Limb shaking transient ischemic attack is a rare disease manifestation typically caused by carotid stenosis but rarely caused by flow-limiting lesions involving more proximal vasculature. We demonstrate a case of limb shaking transient ischemic attack secondary to innominate stenosis in a 69-year-old woman who presented after a left leg shaking spell that caused her to fall and fracture her ipsilateral tibia. She did not experience changes in mentation and did not show any evidence of a postictal period. After receiving a comprehensive workup, she successfully underwent revascularization with innominate artery stenting. Continuous retrograde aspiration with the Enroute system (Silk Road Medical) and carotid clamping were used for embolic protection.

Substance use in adolescents: recognition and management in the emergency department.

Adolescent substance use continues to be a prevalent problem and is a cause of morbidity, mortality, and high rates of resource utilization. The variability in presentations of drug intoxication can make accurate identification of the ingested substance, and thus efficient treatment, challenging. This issue provides a review of typical presenting signs, symptoms, and physical examination findings of commonly used drugs. Evidence-based recommendations are offered for a general approach to managing adolescent patients who present with drug intoxication, with specific guidance, when indicated.

Intermediate pressure-normalized principal wall strain values are associated with increased abdominal aortic aneurysmal growth rates.

Introduction: Current abdominal aortic aneurysm (AAA) assessment relies on analysis of AAA diameter and growth rate. However, evidence demonstrates that AAA pathology varies among patients and morphometric analysis alone is insufficient to precisely predict individual rupture risk. Biomechanical parameters, such as pressure-normalized AAA principal wall strain (ερ+¯/PP, %/mmHg), can provide useful information for AAA assessment. Therefore, this study utilized a previously validated ultrasound elastography (USE) technique to correlate ερ+¯/PP with the current AAA assessment methods of maximal diameter and growth rate. Methods: Our USE algorithm utilizes a finite element mesh, overlaid a 2D cross-sectional view of the user-defined AAA wall, at the location of maximum diameter, to track two-dimensional, frame-to-frame displacements over a full cardiac cycle, using a custom image registration algorithm to produce ερ+¯/PP. This metric was compared between patients with healthy aortas and AAAs (≥3 cm) and compared between small and large AAAs (≥5 cm). AAAs were then separated into terciles based on ερ+¯/PP values to further assess differences in our metric across maximal diameter and prospective growth rate. Non-parametric tests of hypotheses were used to assess statistical significance as appropriate. Results: USE analysis was conducted on 129 patients, 16 healthy aortas and 113 AAAs, of which 86 were classified as small AAAs and 27 as large. Non-aneurysmal aortas showed higher ερ+¯/PP compared to AAAs (0.044 ± 0.015 vs. 0.034 ± 0.017%/mmHg, p = 0.01) indicating AAA walls to be stiffer. Small and large AAAs showed no difference in ερ+¯/PP. When divided into terciles based on ερ+¯/PP cutoffs of 0.0251 and 0.038%/mmHg, there was no difference in AAA diameter. There was a statistically significant difference in prospective growth rate between the intermediate tercile and the outer two terciles (1.46 ± 2.48 vs. 3.59 ± 3.83 vs. 1.78 ± 1.64 mm/yr, p = 0.014). Discussion: There was no correlation between AAA diameter and ερ+¯/PP, indicating biomechanical markers of AAA pathology are likely independent of diameter. AAAs in the intermediate tercile of ερ+¯/PP values were found to have nearly double the growth rates than the highest or lowest tercile, indicating an intermediate range of ερ+¯/PP values for which patients are at risk for increased AAA expansion, likely necessitating more frequent imaging follow-up.