Factors associated with successful median arcuate ligament release in an international, multi-institutional cohort.

OBJECTIVE: Prior research on median arcuate ligament syndrome has been limited to institutional case series, making the optimal approach to median arcuate ligament release (MALR) and resulting outcomes unclear. In the present study, we compared the outcomes of different approaches to MALR and determined the predictors of long-term treatment failure. METHODS: The Vascular Low Frequency Disease Consortium is an international, multi-institutional research consortium. Data on open, laparoscopic, and robotic MALR performed from 2000 to 2020 were gathered. The primary outcome was treatment failure, defined as no improvement in median arcuate ligament syndrome symptoms after MALR or symptom recurrence between MALR and the last clinical follow-up. RESULTS: For 516 patients treated at 24 institutions, open, laparoscopic, and robotic MALR had been performed in 227 (44.0%), 235 (45.5%), and 54 (10.5%) patients, respectively. Perioperative complications (ileus, cardiac, and wound complications; readmissions; unplanned procedures) occurred in 19.2% (open, 30.0%; laparoscopic, 8.9%; robotic, 18.5%; P < .001). The median follow-up was 1.59 years (interquartile range, 0.38-4.35 years). For the 488 patients with follow-up data available, 287 (58.8%) had had full relief, 119 (24.4%) had had partial relief, and 82 (16.8%) had derived no benefit from MALR. The 1- and 3-year freedom from treatment failure for the overall cohort was 63.8% (95% confidence interval [CI], 59.0%-68.3%) and 51.9% (95% CI, 46.1%-57.3%), respectively. The factors associated with an increased hazard of treatment failure on multivariable analysis included robotic MALR (hazard ratio [HR], 1.73; 95% CI, 1.16-2.59; P = .007), a history of gastroparesis (HR, 1.83; 95% CI, 1.09-3.09; P = .023), abdominal cancer (HR, 10.3; 95% CI, 3.06-34.6; P < .001), dysphagia and/or odynophagia (HR, 2.44; 95% CI, 1.27-4.69; P = .008), no relief from a celiac plexus block (HR, 2.18; 95% CI, 1.00-4.72; P = .049), and an increasing number of preoperative pain locations (HR, 1.12 per location; 95% CI, 1.00-1.25; P = .042). The factors associated with a lower hazard included increasing age (HR, 0.99 per increasing year; 95% CI, 0.98-1.0; P = .012) and an increasing number of preoperative diagnostic gastrointestinal studies (HR, 0.84 per study; 95% CI, 0.74-0.96; P = .012) Open and laparoscopic MALR resulted in similar long-term freedom from treatment failure. No radiographic parameters were associated with differences in treatment failure. CONCLUSIONS: No difference was found in long-term failure after open vs laparoscopic MALR; however, open release was associated with higher perioperative morbidity. These results support the use of a preoperative celiac plexus block to aid in patient selection. Operative candidates for MALR should be counseled regarding the factors associated with treatment failure and the relatively high overall rate of treatment failure.

Genomic deletion of malic enzyme 2 confers collateral lethality in pancreatic cancer.

The genome of pancreatic ductal adenocarcinoma (PDAC) frequently contains deletions of tumour suppressor gene loci, most notably SMAD4, which is homozygously deleted in nearly one-third of cases. As loss of neighbouring housekeeping genes can confer collateral lethality, we sought to determine whether loss of the metabolic gene malic enzyme 2 (ME2) in the SMAD4 locus would create cancer-specific metabolic vulnerability upon targeting of its paralogous isoform ME3. The mitochondrial malic enzymes (ME2 and ME3) are oxidative decarboxylases that catalyse the conversion of malate to pyruvate and are essential for NADPH regeneration and reactive oxygen species homeostasis. Here we show that ME3 depletion selectively kills ME2-null PDAC cells in a manner consistent with an essential function for ME3 in ME2-null cancer cells. Mechanistically, integrated metabolomic and molecular investigation of cells deficient in mitochondrial malic enzymes revealed diminished NADPH production and consequent high levels of reactive oxygen species. These changes activate AMP activated protein kinase (AMPK), which in turn directly suppresses sterol regulatory element-binding protein 1 (SREBP1)-directed transcription of its direct targets including the BCAT2 branched-chain amino acid transaminase 2) gene. BCAT2 catalyses the transfer of the amino group from branched-chain amino acids to α-ketoglutarate (α-KG) thereby regenerating glutamate, which functions in part to support de novo nucleotide synthesis. Thus, mitochondrial malic enzyme deficiency, which results in impaired NADPH production, provides a prime 'collateral lethality' therapeutic strategy for the treatment of a substantial fraction of patients diagnosed with this intractable disease.

Outcomes of Median Arcuate Ligament Release: A Single Institution Retrospective Review.

BACKGROUND: Median arcuate ligament syndrome (MALS) is an uncommon diagnosis that is often associated with variable clinical presentation and inconsistent response to treatment. Due to the nature of MALS, the optimal treatment modality and predictors of outcomes remain unclear. METHODS: A retrospective review was performed of all median arcuate ligament release (MALR) procedures at a single academic institution between 2000 and 2020. Variables examined included patient demographics, symptom characteristics, operative technique (open, robotic, laparoscopic), patient symptoms before release, symptom relief within 1 year, and recurrence of symptoms between release and last clinical follow-up. RESULTS: During the study period, 47 patients (75% female, mean age 42.1 years) underwent MALR with 19 (36%) robotic, 18 (34%) open, 14 (26%) laparoscopic, and 2 (4%) laparoscopic converted to open procedures. Abdominal pain, weight loss, and nausea and vomiting were the most common symptoms. Postoperatively, 19 (40%) had complete symptom relief within 1 year, 18 (38%) had partial relief, and 10 (21%) had no symptom improvement. 6 were excluded due to loss of follow-up. Laparoscopic and open procedures had the highest rate of complete symptom relief by year 1 with 7 (58%) and 8 (50%) respectively. Twenty-one (57%) patients had recurrence with the greatest rate of recurrence seen among laparoscopic (80%), compared to robotic (57%) and open (38%). Patients reporting a weight loss of 20 pounds or more before surgery were more likely to have partial or complete symptom relief after 1 year compared to those reporting less than 20-pound weight loss (92% vs. 64%). Furthermore, 84% of patients younger than 60 years old reported partial or complete symptom relief compared to only 56% of those older than 60. CONCLUSIONS: MALS continues to be a rare disorder with widely variable surgical outcomes, requiring further study. While our patients presented with several gastrointestinal symptoms, the most common was postprandial pain. Our center employed laparoscopic, open, and robotic operative techniques with varying success rates, in terms of symptom relief and recurrence. Consistent with current literature, our study found greater surgical success among patients younger than 60 years regardless of operative technique. This suggests the need for better predictors to determine which patients are the most likely to have complete or prolonged remission of symptoms following MALR.

Frailty Among Veterans Undergoing Abdominal Aortic Aneurysm Repair.

BACKGROUND: Frailty is a known risk factor for adverse outcomes following surgery and affects at least 3 of every 10 US Veterans aged 65 years and older. We designed a study to characterize the association between frailty and complications after endovascular aneurysm repair (EVAR) compared to open aneurysm repair (OAR) at our regional Veterans Affairs Medical Center. METHODS: Veterans who underwent either OAR or EVAR at our institution between January 1, 2000 and December 31, 2020 were identified. We examined medical history, procedure characteristics, perioperative complications, and frailty as measured by the 5-factor modified frailty index (mFI-5). Frailty was defined as an mFI-5 score ≥2. Primary endpoints were postoperative complications, duration of surgery, and length of hospital stay. Tests of association were performed with t-test and chi-squared analysis. RESULTS: Over the 21-year period, we identified 314 patients that underwent abdominal aortic aneurysm (AAA) repair with 115 (36.6%) OAR and 199 EVAR (63.4%) procedures. Patients undergoing EVAR were older on average (72.1 years vs. 70.2 years) and had a higher average mFI-5 compared to the open repair group (1.49 vs. 1.23, P = 0.036). When comparing EVAR and OAR cohorts, patients undergoing OAR had a larger AAA diameter (6.5 cm, standard deviation [SD]: 1.5) compared to EVAR (5.5 cm, SD: 1.1 P < 0.0001). Fewer frail patients underwent OAR (n = 40, 34.8%) compared to EVAR (n = 86, 43.2%), and frail EVAR patients had higher AAA diameter (5.8 cm, SD: 1.0) compared to nonfrail EVAR patients (5.3 cm, SD 1.2), P = 0.003. Among OAR procedures, frail patients had longer operative times (296 min vs. 253 min, P = 0.013) and higher incidence of pneumonia (17.5% vs. 5.3%, P = 0.035). Among frail EVAR patients, operative time and perioperative complications including wound dehiscence, surgical site infection, and pneumonia were not significantly different than their nonfrail counterparts. Overall, frail patients had more early complications (n = 55, 43.7%) as compared to nonfrail patients (n = 48, 25.5%, P = 0.001). OAR patients had higher rates of postoperative complications including wound dehiscence (7.0% vs. 0.5%, P = 0.001), surgical site infections (7.0% vs. 1.0%, P = 0.003), and pneumonia (9.6% vs. 0.5%, P=<0.0001). Open repair was also associated with overall longer average intensive care unit stays (11.0 days vs. 1.6 days, P < 0.0001) and longer average hospitalizations (13.5 days vs. 2.4 days, P < 0.0001). CONCLUSIONS: Our findings demonstrate that frailty is associated with higher rates of adverse outcomes in open repair compared to EVAR. Patients who underwent open repair had higher rates of wound dehiscence, surgical site infection, and pneumonia, compared to those undergoing endovascular repair. Frailty was associated with larger AAA diameter in the EVAR cohort and longer operative times, with higher frequency of postoperative pneumonia in the OAR cohort. Frailty is a strong risk factor that should be considered in the management of aortic aneurysms.

Impact of Housing Insecurity on Outcomes in Abdominal Aortic Aneurysm Repair Among Veterans.

BACKGROUND: Veterans are disproportionately affected by housing insecurity (HI), which can lead to adverse health outcomes and reduced life expectancy. We sought to examine the impact of HI on the outcomes of veterans who underwent abdominal aortic aneurysm (AAA) repair at our regional Veterans Affairs medical center. METHODS: Retrospective chart review was performed on patients who underwent AAA repair at our institution between January 1, 2000, and December 31, 2020. We examined medical history, procedure details, hospitalization course, and postoperative outcomes. Primary endpoints were a 30-day mortality and median survival. Secondary endpoints were hospital length of stay, readmission rate, and perioperative complications. Hypothesis testing was performed with t-test and chi-squared analysis. Survival analysis was conducted using Kaplan-Meier estimation. RESULTS: Of the 314 veterans that underwent AAA repair (mean age of 71.4 ± 7.8 years, 99.7% male) over the 21-year period, we identified 39 (12.4%) patients with a history of HI. The HI was associated with a positive smoking history (100% vs. 88.0%, P = 0.022), lower rate of hypertension diagnosis (69.2% vs. 84.0%, P = 0.024), and increased rate of surgical site infections (SSI) (10.3% vs. 1.8%, P = 0.016). The median postoperative survival was lower in the HI group (7.6 years [CI 6.0-11.2] vs. 8.9 [CI 6.9-10.3]). CONCLUSIONS: HI was associated with reduced median postoperative survival, greater readmission rate, and increased risk of SSI following AAA repair.

Lower Extremity Amputations Among Veterans: Have Ambulatory Outcomes and Survival Improved?

BACKGROUND: We hypothesize among patients undergoing lower extremity amputation, access to pre-, and post operative rehabilitation services; as well as improved medical care, have led to higher rates of postoperative ambulation, and improved survival. METHODS: Retrospective single center review of all major lower extremity amputations performed at the Greater Los Angeles Veterans Affairs Healthcare System from 2000-2020 stratified into multiyear cohorts. We abstracted demographics, operative indication, comorbidities, preoperative medical management, perioperative complications, discharge location, and pre and postoperative ambulatory status. Odds of ambulation after amputation were analyzed using multivariate logistic regression. Survival was analyzed using multivariate logistic regression and Kaplan-Meier survival analysis. Multivariate logistic predictors were selected based on prior literature and clinical experience. RESULTS: We identified 654 operations in our study, noting fewer amputations performed in the latest 3 cohort years as compared to the initial cohort (2000-2004). Patients undergoing below-knee amputations (BKA) had 2.7 times (P < 0.05) greater odds of postoperative ambulation and 86% (P < 0.05) increased odds of survival compared to above-knee amputations (AKA). The odds of ambulation increased by 8.8% (P < 0.05) for each consecutive study year. Ambulation post-amputation conferred 13.2 times (P < 0.05) greater odds of survival. The odds of survival in "emergent" operations decreased by 48% (P < 0.05) compared to an "elective" operation. For each additional comorbidity, the odds of survival decreased by 18% (P < 0.05). Patients with any perioperative complication had a 48% (P < 0.05) lower odds of survival. Kaplan-Meier survival estimates demonstrated significant survival difference between patients by amputation level and postoperative ambulatory status (P < 0.05). CONCLUSIONS: Ambulatory status following distal amputation has improved over time and is significantly associated with increased survival post-amputation. Patients undergoing a BKA or discharged home were most likely to ambulate postoperatively. Amputation level, preoperative comorbidities, and perioperative complications remain strong predictors of survival.

Mechanochemical Endovenous Ablation of the Saphenous Vein: A Look at Contemporary Outcomes.

BACKGROUND: Endovenous ablation techniques have replaced greater saphenous vein (GSV) ligation and stripping for treatment of venous insufficiency. Our objective was to investigate our initial procedural experience and clinical presentation of patients undergoing mechanochemical ablation (MOCA) at a single institution. We hypothesized that closure level and success rate improved over time and were comparable to other endovenous ablation techniques. METHODS: We retrospectively reviewed all MOCA procedures performed at the Greater Los Angeles Veterans Affairs Hospital from 2015 - 2020. Variables included CEAP and VCSS scores, patient symptoms, post procedure duplex ultrasound, closure level, and need for anticoagulation. Success was defined as GSV thrombosis on initial post procedure duplex ultrasound. Procedure associated extension of thrombus into the deep veins was defined using the American Venous Forum (AVF) endothermal heat induced thrombosis (EHIT) classification. RESULTS: 104 venous ablation procedures were performed on 86 patients. Eleven (12.8%) patients received bilateral interventions, and six (7%) patients had asynchronous interventions on the same leg. The average age was 58.4 years (SD 12) and 93% were male. Pre-procedural symptoms included pain (102, 98.1%), varicose veins (87, 83.7%), edema (58, 55.8%), and active ulcers (19, 18.3%). A CEAP category of C2 was the most common indication (34.6%), followed by C3 (22.1%) and C6 (21.2%). Forty-five (43.2%) patients had deep system reflux, and 53% had concomitant phlebectomies. Average VCSS score was 7.5 (SD 3.5).We observed a GSV ablation rate of 92.7% (n = 89) in the 96 procedures which had post-procedure follow up, with no temporal evidence of a learning curve. On post procedure duplex of the 89 technically successful ablations, 77 (86.5%) patients had AVF EHIT level 1 closure, three (3.4%) had level 2 closure, eight (8.9%) had level 3 closure, and one had a level 4 closure. Fourteen (15.7%) patients were newly started on anticoagulation for an average of 33.2 days (SD 34.1). Of the 19 legs treated for active venous ulcers, 13 (68.4%) had improvement or resolution of their venous ulcers. No pulmonary embolic complications were reported. CONCLUSIONS: We observed a successful GSV thrombosis rate of 92.7% using MOCA without evidence of a learning curve and comparable to that reported in the literature. The rate of thrombus extension into the deep veins was 14.6%, with no adverse effects associated with anticoagulation or clinically significant sequelae of AVF EHIT level 2 or greater. Comparisons with MOCA associated thrombus extension into deep veins in the literature are limited as post procedure screening duplex are not standard of care. However, we demonstrated that MOCA ablation of the GSV is a safe procedure that may be performed with good technical success.

Nanoconfining solution-processed organic semiconductors for emerging optoelectronics.

Solution-processable organic materials for emerging electronics can generally be divided into two classes of semiconductors, organic small molecules and polymers. The theoretical thermodynamic limits of device performance are largely determined by the molecular structure of these compounds, and advances in synthetic routes have led to significant progress in charge mobilities and light conversion and light emission efficiencies over the past several decades. Still, the uncontrolled formation of out-of-equilibrium film microstructures and unfavorable polymorphs during rapid solution processing remains a critical bottleneck facing the commercialization of these materials. This tutorial review provides an overview of the use of nanoconfining scaffolds to impose order onto solution-processed semiconducting films to overcome this limitation. For organic semiconducting small molecules and polymers, which typically exhibit strong crystal growth and charge transport anisotropy along different crystallographic directions, nanoconfining crystallization within nanopores and nanogrooves can preferentially orient the fast charge transport direction of crystals with the direction of current flow in devices. Nanoconfinement can also stabilize high-performance metastable polymorphs by shifting their relative Gibbs free energies via increasing the surface area-to-volume ratio. Promisingly, such nanoconfinement-induced improvements in film and crystal structures have been demonstrated to enhance the performance and stability of emerging optoelectronics that will enable large-scale manufacturing of flexible, lightweight displays and solar cells.

AMPK stimulation inhibits YAP/TAZ signaling to ameliorate hepatic fibrosis.

Hepatic fibrosis is driven by the activation of hepatic stellate cells (HSCs). The Hippo pathway and its effectors, YAP and TAZ, are key regulators of HSC activation and fibrosis. However, there is a lack of mechanistic understanding of YAP/TAZ regulation in HSCs. Here we show that AMPK activation leads to YAP/TAZ inhibition and HSC inactivation in vitro, while the expression of a kinase-inactive mutant reversed these effects compared to wild type AMPKɑ1. Notably, the depletion of LATS1/2, an upstream kinase of YAP/TAZ signaling, rescues YAP/TAZ activation, suggesting that AMPK may be mediating YAP/TAZ inhibition via LATS1/2. In the carbon tetrachloride mouse model of fibrosis, pharmacologic activation of AMPK in HSCs inhibits YAP/TAZ signaling and reduces fibrosis. The findings implicate AMPK as a critical regulator of YAP/TAZ signaling and HSC inactivation and highlight AMPK activation as a therapeutic target for the treatment of hepatic fibrosis.

First-principles investigation of possible room-temperature topological insulators in monolayers.

A Quantum Spin Hall (QSH) insulator with a large bulk band gap and tunable topological properties is crucial for both fundamental research and practical application. Chemical function-alization has been proposed as an effective route to realize the QSH effect. Using the ABINIT package, we have investigated the properties of (1) TlP, the functionalized monolayers TlPX2 (X = F, Cl, Br, I); (2) TlAs, the functionalized monolayers TlAsX2 (X = F, Cl, Br, I), and (3) GaGeTe, InGeTe, and InSnTe systems. The topological nature is verified by the calculation of the Z2 topo-logical invariant. We discovered TlPF2, TlPCl2, TlPBr2, TlPI2, TlAs, TlAsF2, TlAsCl2, TlAsBr2, and TlAsI2 were promising 2D TIs with bulk band gaps as large as 0.21 eV. Each monolayer was suitable for room-temperature application, and show great potential for their future applications in quantum computers, nanoelectronics, and spintronics.

Effect of teleconferencing variables on faculty impression of mock residency applicants.

Purpose: The objective of this study was to assess how teleconferencing variables influence faculty impressions of mock residency applicants. Methods: In October 2020, we conducted an online experiment studying five teleconferencing variables: background, lighting, eye contact, internet connectivity, and audio quality. We created interview videos of three mock residency applicants and systematically modified variables in control and intervention conditions. Faculty viewed the videos and rated their immediate impression on a 1-10 scale. The effect of each variable was measured as the mean difference between the intervention and control impression ratings. One-way analysis of variance (ANOVA) was performed to assess whether ratings varied across applicants. Paired-samples Wilcoxon signed-rank tests were conducted to assess the significance of the effect of each variable. Results: Of 711 faculty members who were emailed a link to the experiment, 97 participated (13.6%). The mean ratings for control videos were 8.1, 7.2, and 7.6 (P < .01). Videos with backlighting, off-center eye contact, choppy internet connectivity, or muffled audio quality had lower ratings when compared with control videos (P < .01). There was no rating difference between home and conference room backgrounds (P = .77). Many faculty participants reported that their immediate impressions were very much or extremely influenced by audio quality (60%), eye contact (57%), and internet connectivity (49%). Conclusions: Teleconferencing variables may serve as a source of assessment bias during residency interviews. Mock residency applicants received significantly lower ratings when they had off-center eye contact, muffled audio, or choppy internet connectivity, compared to optimal teleconferencing conditions. Supplementary Information: The online version contains supplementary material available at 10.1007/s44186-022-00053-w.

Telemedicine and Vascular Surgery: Expanding Access and Providing Care Through the COVID-19 Pandemic.

INTRODUCTION: Access to surgical service is limited by provider availability and geographic barriers. Telemedicine ensures that patients can access medical care. OBJECTIVE: The objective is to describe our use of telemedicine in delivering vascular surgery services to remote locations before and during the COVID-19 pandemic. METHODS: We conducted a retrospective chart review analyzing care delivered at six vascular surgery telemedicine clinics over a 22-month period. We examined vascular diagnoses, recommended interventions, referrals placed, and emergency department visits within 30 days of evaluation. We calculated travel distance saved for patients between their local clinic and our main hospital. RESULTS: We identified 94 patients and 144 telemedicine visits, with an average of 1.5 visits per patient (SD = 0.73). The most common referrals were for peripheral artery disease (20.2%) and abdominal aortic aneurysm (14.9%). Three patients were immediately referred to the emergency department due to concern for acute limb ischemia (2) or questionable symptomatic AAA (1). Telemedicine visit recommendations were distributed between no intervention (n = 30, 31.9%), medical management (n = 41, 43.6%), and surgical intervention (n = 23, 24.5%).The surgical intervention cohort was most commonly referred to arterial revascularization (n = 4), venous ablation (n = 4), and arteriovenous fistula procedures (n = 4). Fourteen patients came to our main hospital for surgery and four to local providers. Average travel distance saved per telemedicine visit was 104 miles (SD = 43.7). CONCLUSIONS: Telemedicine provided safe, efficient care during the COVID-19 pandemic and saved patients an average of 104 travel miles per visit.

Imaging tumor variation in response to photodynamic therapy in pancreatic cancer xenograft models.

PURPOSE: A treatment monitoring study investigated the differential effects of orthotopic pancreatic cancer models in response to interstitial photodynamic therapy (PDT), and the validity of using magnetic resonance imaging as a surrogate measure of response was assessed. METHODS AND MATERIALS: Different orthotopic pancreatic cancer xenograft models (AsPC-1 and Panc-1) were used to represent the range of pathophysiology observed in human beings. Identical dose escalation studies (10, 20, and 40J/cm) using interstitial verteporfin PDT were performed, and magnetic resonance imaging with T2-weighted and T1-weighted contrast were used to monitor the total tumor volume and the vascular perfusion volume, respectively. RESULTS: There was a significant amount of necrosis in the slower-growing Panc-1 tumor using high light dose, although complete necrosis was not observed. Lower doses were required for the same level of tumor kill in the faster-growing AsPC-1 cell line. CONCLUSIONS: The tumor growth rate and vascular pattern of the tumor affect the optimal PDT treatment regimen, with faster-growing tumors being relatively easier to treat. This highlights the fact that therapy in human beings shows a heterogeneous range of outcomes, and suggests a need for careful individualized treatment outcomes assessment in clinical work.