Does Preoperative Pharmacogenomic Testing of Patients Undergoing TKA Improve Postoperative Pain? A Randomized Trial.

BACKGROUND: Pharmacogenomics is an emerging and affordable tool that may improve postoperative pain control. One challenge to successful pain control is the large interindividual variability among analgesics in their efficacy and adverse drug events. Whether preoperative pharmacogenomic testing is worthwhile for patients undergoing TKA is unclear. QUESTIONS/PURPOSES: (1) Are the results of preoperative pharmacogenetic testing associated with lower postoperative pain scores as measured by the Overall Benefit of Analgesic Score (OBAS)? (2) Do the results of preoperative pharmacogenomic testing lead to less total opioids given? (3) Do the results of preoperative pharmacogenomic testing lead to changes in opioid prescribing patterns? METHODS: Participants of this randomized trial were enrolled from September 2018 through December 2021 if they were aged 18 to 80 years and were undergoing primary TKA under general anesthesia. Patients were excluded if they had chronic kidney disease, a history of chronic pain or narcotic use before surgery, or if they were undergoing robotic surgery. Preoperatively, patients completed pharmacogenomic testing (RightMed, OneOME) and a questionnaire and were randomly assigned to the experimental group or control group. Of 99 patients screened, 23 were excluded, one before randomization; 11 allocated patients in each group did not receive their allocated interventions for reasons such as surgery canceled, patients ultimately undergoing spinal anesthesia, and change in surgery plan. Another four patients in each group were excluded from the analysis because they were missing an OBAS report. This left 30 patients for analysis in the control group and 38 patients in the experimental group. The control and experimental groups were similar in age, gender, and race. Pharmacogenomic test results for patients in the experimental group were reviewed before surgery by a pharmacist, who recommended perioperative medications to the clinical team. A pharmacist also assessed for clinically relevant drug-gene interactions and recommended drug and dose selection according to guidelines from the Clinical Pharmacogenomics Implementation Consortium for each patient enrolled in the study. Patients were unaware of their pharmacogenomic results. Pharmacogenomic test results for patients in the control group were not reviewed before surgery; instead, standard perioperative medications were administered in adherence to our institutional care pathways. The OBAS (maximum 28 points) was the primary outcome measure, recorded 24 hours postoperatively. A two-sample t-test was used to compare the mean OBAS between groups. Secondary measures were the mean 24-hour pain score, total morphine milligram equivalent, and frequency of opioid use. Postoperatively, patients were assessed for pain with a VAS (range 0 to 10). Opioid use was recorded preoperatively, intraoperatively, in the postanesthesia care unit, and 24 hours after discharge from the postanesthesia care unit. Changes in perioperative opioid use based on pharmacogenomic testing were recorded, as were changes in prescription patterns for postoperative pain control. Preoperative characteristics were also compared between patients with and without various phenotypes ascertained from pharmacogenomic test results. RESULTS: The mean OBAS did not differ between groups (mean ± SD 4.7 ± 3.7 in the control group versus 4.2 ± 2.8 in the experimental group, mean difference 0.5 [95% CI -1.1 to 2.1]; p = 0.55). Total opioids given did not differ between groups or at any single perioperative timepoint (preoperative, intraoperative, or postoperative). We found no difference in opioid prescribing pattern. After adjusting for multiple comparisons, no difference was observed between the treatment and control groups in tramadol use (41% versus 71%, proportion difference 0.29 [95% CI 0.05 to 0.53]; nominal p = 0.02; adjusted p > 0.99). CONCLUSION: Routine use of pharmacogenomic testing for patients undergoing TKA did not lead to better pain control or decreased opioid consumption. Future studies might focus on at-risk populations, such as patients with chronic pain or those undergoing complex, painful surgical procedures, to test whether pharmacogenomic results might be beneficial in certain circumstances. LEVEL OF EVIDENCE: Level I, therapeutic study.

Exposure to IR Rotations in Osteopathic Medical Schools: Trends in Residency Applications and Matching.

Medical student exposure to interventional radiology (IR) through dedicated rotations represents a vital component for students to consider IR as a career and to ensure a successful match into the integrated residency pathway. Students from osteopathic medical schools have historically been underrepresented in integrated IR positions. During the 2022 match, 84.1% of successfully matched applicants overall were from U.S. allopathic medical schools, whereas 15.9% were from osteopathic medical schools. This brief report aims to categorize the landscape of IR rotation exposure at osteopathic medical schools and proposes a framework to increase student access to IR.

Survival and Toxicities after Yttrium-90 Transarterial Radioembolization of Cholangiocarcinoma in the RESiN Registry.

PURPOSE: To report outcomes in patients with intrahepatic cholangiocarcinoma treated with yttrium-90 resin microspheres (transarterial radioembolization [TARE]) from a multicenter, prospective observational registry. MATERIALS AND METHODS: Ninety-five patients (median age, 67 years [interquartile range {IQR}, 59-74]; 50 men) were treated in 27 centers between July 2015 and August 2020. Baseline demographic characteristics included imaging findings, performance status, and previous systemic or locoregional treatments. Dosimetry method was tracked. Overall survival (OS) and progression-free survival were calculated using the Kaplan-Meier method. The best imaging response was calculated using the Response Evaluation Criteria in Solid Tumors v1.1. Grade ≥3 toxicities were assessed using Common Terminology Criteria for Adverse Events v5. Cox regression analysis was performed. RESULTS: Fifty-two of 86 (60%) patients had multifocal tumors, and 24/89 (27%) had extrahepatic tumors. The median index tumor diameter was 7.0 cm (IQR, 4.9-10 cm). The activity calculation method was reported in 59/95 (62%) patients, with body surface area being the most frequently used method (45/59, 76%). Median OS for the cohort was 14 months (95% confidence interval, 12-22). OS at 3, 6, 12, and 24 months was 94%, 80%, 63%, and 34%, respectively. Median OS was longer in patients without cirrhosis (19.1 vs 12.2 months, P = .05). Cirrhosis, previous chemotherapy (OS, 19.1 vs 10.6 months for treatment-naïve; P = .07), and imaging response at 6 months (OS, 16.4 vs 9.5 months for no response; P = .06) underwent regression analysis. Imaging response predicted OS at regression (hazard ratio, 0.39; P = .008). Grade 3-4 bilirubin toxicities were noted in 5 of 72 (7%) patients. Grade 3 albumin toxicity was noted in 1 of 72 (1.4%) patients. CONCLUSIONS: Objective response at 6 months predicted longer OS after TARE for intrahepatic cholangiocarcinoma. The incidence of liver function toxicity was <10%.

Survival and Toxicities after 90Y Transarterial Radioembolization of Metastatic Colorectal Cancer in the RESIN Registry.

Background Patients with unresectable, chemorefractory hepatic metastases from colorectal cancer have considerable mortality. The role of transarterial radioembolization (TARE) with yttrium 90 (90Y) microspheres is not defined because most reports are from a single center with limited patient numbers. Purpose To report outcomes in participants with colorectal cancer metastases treated with resin 90Y microspheres from a prospective multicenter observational registry. Materials and Methods This study treated enrolled adult participants with TARE using resin microspheres for liver-dominant metastatic colorectal cancer at 42 centers, with enrollment from July 2015 through August 2020. TARE was used as the first-, second-, or third-line therapy or beyond. Overall survival (OS), progression-free survival (PFS), and toxicity outcomes were assessed by line of therapy by using Kaplan-Meier analysis for OS and PFS and Common Terminology Criteria for Adverse Events, version 5, for toxicities. Results A total of 498 participants (median age, 60 years [IQR, 52-69 years]; 298 men [60%]) were treated. TARE was used in first-line therapy in 74 of 442 participants (17%), second-line therapy in 180 participants (41%), and third-line therapy or beyond in 188 participants (43%). The median OS of the entire cohort was 15.0 months (95% CI: 13.3, 16.9). The median OS by line of therapy was 13.9 months for first-line therapy, 17.4 months for second-line therapy, and 12.5 months for third-line therapy (χ2 = 9.7; P = .002). Whole-group PFS was 7.4 months (95% CI: 6.4, 9.5). The median PFS by line of therapy was 7.9 months for first-line therapy, 10.0 months for second-line therapy, and 5.9 months for third-line therapy (χ2 = 8.3; P = .004). TARE-attributable grade 3 or 4 hepatic toxicities were 8.4% for bilirubin (29 of 347 participants) and 3.7% for albumin (13 of 347). Grade 3 and higher toxicities were greater with third-line therapy for bilirubin (P = .01) and albumin (P = .008). Conclusion Median overall survival (OS) after transarterial radioembolization (TARE) with yttrium 90 microspheres for liver-dominant metastatic colorectal cancer was 15.0 months. The longest OS was achieved when TARE was part of second-line therapy. Grade 3 or greater hepatic function toxicity rates were less than 10%. Clinical trial registration no. NCT02685631 Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Liddell in this issue.

Evaluation of the Benefit of Extended Catheter-Directed Thrombolysis with Serial Angiography for Acute Pulmonary Embolism.

PURPOSE: To evaluate whether extended catheter-directed thrombolysis (CDT) with repeat visits to the angiography suite provide added benefit in treatment of acute pulmonary embolism (PE). MATERIALS AND METHODS: This was a retrospective review of CDT procedures performed for acute PE in 156 patients (age 56.1 y ± 15.3, 46.2% women) between 2009 and 2019. All patients underwent at least 1 follow-up visit to the angiography suite for evaluation of pulmonary artery pressure (PAP) and thrombus burden (Miller score) before termination (111/156, 71.2%) or continuation of CDT (45/156, 28.8%). RESULTS: Patients who had CDT extended beyond the first follow-up visit required a higher total dose of tissue plasminogen activator (40.7 mg ± 14.3 vs 22.6 mg ± 9.9, P < .001) to achieve a similar final Miller score (6.4 ± 3.8 vs 7.6 ± 3.9, P = .1) and a similar reduction in systolic PAP (-14.4 mm Hg ± 10.2 vs -12.6 mm Hg ± 11.9, P = .6). The initial Miller scores were similar in both groups (19.7 ± 5.8 vs 19 ± 4, P = .4) but were significantly higher during the first follow-up visit (after 18 hours ± 5.5 vs 20 hours ± 4.8, P = .06) in patients requiring multiple follow-up visits (12.2 ± 5 vs 7.6 ± 3.9, P < .001). Multiple regression analyses identified heart rate > 100 beats/min and systolic PAP > 55 mm Hg as associated with the need for extended CDT. Extended CDT did not result in a higher hemorrhagic complication rate (1/45 vs 6/111, P = .7). CONCLUSIONS: Patients presenting with higher heart rates and systolic PAP may benefit from extended CDT to achieve similar reductions in PAP and thrombus burden, without clear added risk of hemorrhage.

Comparison of Contrast-Enhanced Ultrasound Versus Magnetic Resonance Imaging in the Detection and Characterization of Uterine Leiomyomas.

OBJECTIVES: Uterine fibroids are common findings in women with pelvic pain and abnormal uterine bleeding. The reference standard test in the pretreatment evaluation of fibroids is contrast-enhanced magnetic resonance (MR) imaging. This study compared the number, size, location, and enhancement of uterine fibroids identified by contrast-enhanced ultrasound (CEUS) and MR. The aim of this study was to demonstrate that CEUS performs similarly to MR and could be used as an alternative imaging modality. METHODS: In this prospective observational study, 26 women underwent transabdominal CEUS and MR examinations. Blinded to the original clinical MR interpretations, 2 readers reviewed the MR and CEUS studies for each patient. The number, size, location, and enhancement of each fibroid per patient were reported by MR and CEUS. A Pearson correlation coefficient was calculated for the number of fibroids identified by each modality. RESULTS: In total, 126 fibroids were imaged: 115 (91.3%) were observed on both examinations; 9 (7.1%) were observed by MR only; and 2 (1.6%) were observed by CEUS only. A high correlation was found between the modalities for the number of fibroids identified per patient (r = 0.97; P < .001). There was also no significant difference between the modalities for each patient in the fibroid number, size, location, or enhancement. CONCLUSIONS: These findings suggest that transabdominal CEUS may represent an alternative to MR in pretreatment evaluation of uterine fibroids and could serve as a test of choice in patients with a contraindication to MR.

Evaluation of Fibrinogen Levels during Catheter-Directed Thrombolysis for Acute Pulmonary Embolism.

PURPOSE: To evaluate the effect of catheter-directed thrombolysis (CDT) with tissue plasminogen activator (tPA) on plasma fibrinogen levels (PFLs) in the setting of acute pulmonary embolism (PE) and the relationship between PFL and hemorrhagic complications. MATERIALS AND METHODS: A retrospective review of CDT procedures between 2009 and 2019 identified 147 CDT procedures for massive or submassive PE (55.8% males; age, 56.5 ± 14.8 years; 90.5% submassive). All patients received therapeutic anticoagulation during CDT with unfractionated heparin (UFH) (69.4%) or low-molecular-weight heparin (LMWH, 30.6%) infusion. CDT was performed with ultrasound-accelerated thrombolysis (USAT) catheters (n = 98), conventional catheter-directed thrombolysis (CCDT) catheters (n = 34), or a combination of both (n = 15). RESULTS: There was a decrease (P = .007) of 15.1 ± 69.4 mg/dl from the initial PFL (376.1 ± 122.7 mg/dl) to the final PFL (361 ± 118.7 mg/dl), which was measured after a mean of 24.1 ± 11.7 hours with a mean tPA dose of 28.3 ± 14.2 mg. The fibrinogen nadir was 327.6 ± 107.1 mg/dl measured 13.4 ± 10.3 hours after initiation of thrombolysis. Of patients with hemorrhagic complications (n = 6), initial, final, and nadir PFL were not significantly lower (P = .053, P = .081, and P = .086, respectively) than the remainder of the cohort. No significant difference was noted in initial and final PFL between the LMWH and UFH groups (P = .2 and P = .1, respectively) or between the CCDT and USAT groups (P = .5 and P = .9, respectively). The UFH group had a lower nadir PFL than the LMWH group (P = .03). CONCLUSIONS: Despite a significant drop in PFL during CDT for acute PE, this was not associated with hemorrhagic complications. These findings were not affected by the choice of anticoagulant or catheter delivery system.

Evaluation of the Effect of Routine Antibiotic Administration after Uterine Artery Embolization on Infection Rates.

PURPOSE: To evaluate the effect of routine administration of post-procedural antibiotics following elective uterine artery embolization (UAE) on infectious complication rates. MATERIALS AND METHODS: The charts of patients who underwent UAE between January 2013 and September 2019 were retrospectively reviewed. Prior to January 15, 2016, all patients received post-procedural antibiotics with 500 mg of ciprofloxacin twice a day orally for 5 days. After January 15, 2016, none of the patients received post-procedural antibiotics. All patients in both groups received pre-procedural intravenous antibiotics. The post-procedural antibiotics group included 217 patients (age, 44.7 ± 6 years); the no-antibiotics group included 158 patients (age, 45.4 ± 5.6 years). Patients in the no-antibiotics group had a significantly higher rate of diabetes mellitus (P = .03) but fewer cases of adenomyosis (P = .048). Otherwise, demographic and fibroid characteristics were similar between the groups. RESULTS: Six infectious complications (6/375, 1.6%) were recorded. No statistically significant difference (P = .66) was observed in the number of infections between the post-procedural antibiotics group (4/217, 1.8%) and the no-antibiotics group (2/158, 1.3%). Three of the 6 infectious complications presented with malodorous vaginal discharge (3/375, 0.8%) and received nominal therapy. The 3 remaining complications (0.8%) were considered major and included 2 patients (0.5%) who underwent hysterectomy and 1 patient (0.3%) who underwent myomectomy. The major infection rate was 0.9% (2/217) in the post-procedural antibiotics group and 0.7% (1/158) in the no-antibiotics group (P = 1). There were no 90-day post-procedural mortalities. CONCLUSIONS: Discontinuation of routine post-procedural antibiotics with ciprofloxacin after elective UAE did not result in increased rates of infectious complications within the first 90 days post procedure.

Safety of Therapeutic Anticoagulation with Low-Molecular-Weight Heparin or Unfractionated Heparin Infusion during Catheter-Directed Thrombolysis for Acute Pulmonary Embolism.

PURPOSE: To examine the safety of therapeutic-dose anticoagulation during catheter-directed thrombolysis (CDT) for acute pulmonary embolism (PE). MATERIALS AND METHODS: A retrospective review of 156 consecutive cases (age, 56.6 ± 15.4 years; 85 males) of CDT with alteplase for acute PE (symptoms, <14 days) between 2009 and 2019 was performed. All patients received full-dose anticoagulation before, during, and after thrombolysis with low-molecular-weight heparin (LMWH) (n = 45) or unfractionated heparin (n = 111) infusion. Massive PE was diagnosed in 21 of 156 patients at presentation; submassive PE was diagnosed in 135 of 156 patients at presentation. The Simplified Pulmonary Embolism Severity Index was ≥1 in 69 of 156 patients. RESULTS: There were 4 mild (2.6%), 3 moderate (1.9%), and 3 severe (1.9%) hemorrhagic complications (Global Use of Strategies to Open Occluded Arteries), 1 of which (0.6%) was intracranial. No significant differences in hemorrhagic complication rates (P = .3, P = 1.0, and P = .6, respectively) or general complication rates (Society of Interventional Radiology [SIR] minor, P = .2; SIR major, P = .7) were noted between the LMWH and heparin groups. Mean pulmonary arterial pressure for the entire cohort improved from 28.9 ± 7.6 mmHg to 20.4 ± 6.5 mmHg (P < .001), whereas the Miller score improved from 19.3 ± 4.6 to 7.3 ± 3.9 (P < .001). The average infusion duration was 26 ± 11.9 hours over 2.3 ± 0.6 total visits to the angiography lab, during which a mean of 27.85 ± 14.2 mg of tissue plasminogen activator were infused. CONCLUSIONS: Therapeutic anticoagulation during CDT for PE appears to be safe. The current study did not find a significant difference between LMWH and heparin infusion with respect to hemorrhagic and general complication rates.

Large-Bore Aspiration Thrombectomy versus Catheter-Directed Thrombolysis for Acute Pulmonary Embolism: A Propensity Score-Matched Comparison.

PURPOSE: To compare effectiveness and safety of large-bore aspiration thrombectomy (LBAT) with catheter-directed thrombolysis (CDT) for treatment of acute massive and submassive pulmonary embolism (PE). MATERIALS AND METHODS: This retrospective review included patients with acute PE treated with LBAT or CDT using tissue plasminogen activator (tPA) between December 2009 and May 2020. A propensity score based on Pulmonary Embolism Severity Index class and PE severity (massive vs submassive) was calculated, and 26 LBAT cases (age 60.2 y ± 17.1, 14/26 women) were matched with 26 CDT cases (age 59.7 y ± 14.2, 14/26 women). RESULTS: The CDT group had 22.1 mg ± 8.1 tPA infused over 21.2 h ± 6.6. Both groups demonstrated similar initial and final systolic pulmonary artery pressure (PAP) (LBAT: 54.5 mm Hg ± 12.9 vs CDT: 54.5 mm Hg ± 16.3, P = .8, and LBAT: 42.5 mm Hg ± 14.1 vs CDT: 42.6 mm Hg ± 12.1, P = .8, respectively) and similar reductions in heart rate (LBAT: -5.4 beats/min ± 19.2 vs CDT: -9.6 beats/min ± 15.8, P = .4). CDT demonstrated a higher reduction in Miller score (-10.1 ± 3.9 vs -7.5 ± 3.8, P = .02). LBAT resulted in 1 minor hemorrhagic complication and 2 procedure-related mortalities, and CDT resulted in 1 minor and 1 major hemorrhagic complication. CONCLUSIONS: LBAT and CDT resulted in similar reductions of PAP and heart rate when used to treat acute PE. CDT reduced thrombus burden to a greater degree. Although hemorrhagic complications rates were not significantly different, the LBAT group demonstrated a higher rate of procedure-related mortality. Larger studies are needed to compare the safety of these techniques.

Clinical Review of the Pharmacogenomics of Direct Oral Anticoagulants.

PURPOSE: There is growing interest in the use of pharmacogenomics to optimize the safety and efficacy of anticoagulation therapy. While the pharmacogenomics of warfarin have been well-studied, the pharmacogenomics of direct oral anticoagulants (DOACs) continue to be a fledgling, but growing, field of interest. We present a pertinent clinical review of the present state of research on the pharmacogenomics of DOACs. METHODS AND RESULTS: The present article is a review of pertinent clinical and scientific research on the pharmacogenomics of DOACs between January 2008 and December 2017 using MEDLINE and the United States National Institutes of Health Clinical Trials Registry. Many studies have identified single-nucleotide polymorphisms (SNPs) in genes responsible for DOAC metabolism that impacted serum DOAC concentration but had uncertain clinical significance. CONCLUSIONS: As such, there is currently no strong evidence for the use of pharmacogenomic testing in optimizing the safety and efficacy of DOAC therapy. Nonetheless, genes of interest have been identified for each DOAC that may be of potential clinical utility. Further research is currently underway to elucidate the value of pharmacogenomics in this increasingly prescribed therapy.

Comparison of Ultrasound-Accelerated versus Pigtail Catheter-Directed Thrombolysis for the Treatment of Acute Massive and Submassive Pulmonary Embolism.

PURPOSE: To compare the technical and clinical effectiveness of ultrasound-accelerated endovascular thrombolysis (USAT) versus pigtail catheter-directed thrombolysis (PCDT) for the treatment of acute pulmonary embolism (PE). MATERIALS AND METHODS: A single-center retrospective study of patients treated with USAT or PCDT for acute massive or submassive PE between January 2010 and December 2016 was performed by reviewing electronic medical records. Sixty treatments were reviewed (mean patient age, 56.7 y ± 14.6), including 52 cases of submassive PE (21 treated with USAT, 31 with PCDT) and 8 cases of massive PE (3 treated with USAT, 5 with PCDT). Endpoints included pulmonary artery pressure (PAP), Miller PE severity index, tissue plasminogen activator (TPA) dose, infusion duration, procedural variables, and complications. RESULTS: Demographics, PE severity, and right:left ventricular diameter ratios were similar between groups. USAT and PCDT significantly reduced mean PAP (reductions of 7.4 mm Hg [P = .002] and 8.2 mm Hg [P < .001], respectively) and Miller index scores (reductions of 45.8% [P < .001] and 53% [P < .001], respectively) with similar effectiveness (P = .47 and P = .15, respectively). Procedure (P < .001) and fluoroscopy (P = .001) times were significantly longer in the USAT group. The USAT group underwent fewer sessions (2.2 ± 0.6 vs 2.4 ± 0.6; P = .17) with shorter infusion times (23.9 h ± 8.8 vs 30.4 h ± 12.6; P = .065) and a lower total dose of TPA (27.1 mg ± 11.3 vs 30.4 mg ± 12.6; P = .075) compared with the PCDT group, but the differences were not significant. Complications (P = .07) and 30-day mortality rates (P = .56) were not significantly different between groups. CONCLUSIONS: USAT and PCDT demonstrated comparable effectiveness and safety in the treatment of patients with acute PE.

Endovascular recanalization of native chronic total occlusions in patients with failed lower-extremity bypass grafts.

PURPOSE: To investigate the feasibility, safety, and outcome of endovascular recanalization of native chronic total occlusions (CTOs) in patients with failed lower-extremity bypass grafts. MATERIALS AND METHODS: Retrospective review of 19 limbs in 18 patients with failed lower-extremity bypass grafts that underwent recanalization of native arterial occlusions between February 2009 and April 2013 was performed. Nine of the limbs presented with acute ischemia and 10 presented with chronic ischemia, including eight with critical limb ischemia and two with disabling claudication. RESULTS: The mean patency of the failed bypass grafts (63% venous) was 27 months. All limbs had Transatlantic Inter-Society Consensus class D lesions involving the native circulation. Technical success of the endovascular recanalization procedure was achieved in all but one limb (95%). The mean ankle brachial indices before and after treatment were 0.34 and 0.73, respectively. There were no major complications or emergency amputations. Mean patient follow-up was 64 weeks, and two patients were lost to follow-up. Primary patency rates at 3, 6, and 12 months were 87%, 48%, and 16%, respectively. Successful secondary procedures were performed in seven patients, with secondary patency rates at 3, 6, and 12 months of 88%, 73%, and 44%, respectively. Limb salvage rates at 12 and 24 months were 94% and 65%, and amputation-free survival rates at 12 and 24 months were 87% and 60%, respectively. CONCLUSIONS: Endovascular recanalization of native CTOs in patients with failed lower-extremity bypass grafts is technically feasible and safe and results in acceptable limb salvage.

Recanalization of chronic total occlusions of the superior mesenteric artery in patients with chronic mesenteric ischemia: technical and clinical outcomes.

PURPOSE: To evaluate the safety and outcomes of endovascular recanalization of chronic total occlusions (CTOs) of the superior mesenteric artery (SMA) in patients with chronic mesenteric ischemia (CMI). MATERIALS AND METHODS: A single-institution retrospective review was performed of 47 consecutive patients (18 male, 29 female) who underwent endovascular stent placement for CTOs of the SMA between February 2006 and November 2012. All patients had symptoms of CMI. Procedural and follow-up data were collected for assessment of technical success, safety, and outcome. RESULTS: Technical success was achieved in 41 of 47 patients (87%). Forty-two of the 47 procedures were performed from a femoral approach. Fifteen patients underwent concurrent revascularization of the celiac artery. All patients who underwent successful recanalization reported symptomatic improvement. Kaplan-Meier analysis revealed primary freedom from symptomatic recurrence of 95% at 12 months and 78% at 24 months. Symptomatic recurrence was observed in seven patients, all of whom underwent successful assisted or secondary endovascular procedures. Secondary freedom from symptomatic recurrence rates were 100% at 12 months and 88% 24 months. There were three (7%) minor access-related complications and no major complications. CONCLUSIONS: Endovascular stent-assisted recanalization of chronic SMA occlusions is safe and effective, with an acceptable rate of technical success and excellent midterm clinical outcomes.

The Protégé Nitinol Self-Expanding Stent for the Treatment of Iliofemoral Veno-Occlusive Disease.

PURPOSE: To evaluate the safety and effectiveness of the Protégé nitinol self-expanding stent for the treatment of iliofemoral veno-occlusive disease. MATERIALS AND METHODS: A retrospective review was performed of 376 (284 left, 92 right) Protégé stents in 212 limbs of 183 patients (mean age: 53 ± 17 years, 52% female) treated for iliofemoral veno-occlusive disease between 2011 and 2018. Binary patency was assessed with duplex ultrasound and calculated by Kaplan Meier analysis. Clinical outcomes were evaluated by clinical-etiology-anatomy-pathophysiology (CEAP) classification and Villalta scores. Adverse events were recorded and categorized per Society of Interventional Radiology reporting standards. RESULTS: Of the 212 limbs, 125 presented with acute thrombosis and 28 with chronic thrombosis requiring thrombectomy (n = 44), catheter directed thrombolysis (n = 32), or both (n = 77). Fifty-nine limbs were non-thrombotic. Mean follow-up time was 11.44 ± 11.37 months. Kaplan Meier analysis revealed a primary limb-level patency of 92.3%, 88.6%, 86.9% and 86.9% at 6, 12, 24 and 36 months, respectively. CEAP and Villalta scores improved from a median of C3 (range: 0-6) to C1 (0-5) (p < 0.001) and from a mean of 13.4 ± 7.5 to 5.3 ± 4.9 (p < 0.001), respectively. Nine minor and 2 major adverse events were recorded. CONCLUSIONS: Endovascular treatment of iliofemoral veno-occlusive disease with the Protégé self-expanding stent appears to have good mid-term patency. LEVEL OF EVIDENCE: Level 4, Case Series.

Temporal Analysis of Tachycardia During Catheter Directed Thrombolysis for Acute Pulmonary Embolism.

PURPOSE: To evaluate the effect of catheter directed thrombolysis (CDT) on heart rate (HR) in patients with sinus tachycardia and acute pulmonary embolism (PE). METHODS: A retrospective chart review was performed for patients who underwent CDT with tPA for acute massive or submassive PE between 12/2009 and 2/2020. Included were patients who presented with tachycardia at the time of initiation of CDT. Patients with chronic PE, atrial fibrillation, beta blocker therapy, adjunctive endovascular therapy, systemic thrombolysis, or who expired before conclusion of CDT were excluded. HR was measured approximately every hour during CDT. Graphs were plotted of HR as a function of CDT duration. Two interventional radiologists identified the point of plateau (POP) on the graph where CDT had maximized its benefit in decreasing the patient's HR. Discrepancies were adjudicated by a third interventional radiologist and the median of the 3 measurements was selected. The primary endpoint was the duration of CDT from initiation until the POP. RESULTS: 48 patients were included (52.5 ± 14.7 years, 56.3% female). The POP occurred after 13.1 ± 6.1 hours, by which point HR had been reduced from 110 ± 9.2 bpm to 88 ± 10.6 bpm. Sinus tachycardia was not resolved in 10 patients even though they achieved maximal improvement in HR after 11.3 ± 6.7 hours. CONCLUSION: Patients presenting with sinus tachycardia related to acute PE achieved maximal, sustained reduction in heart rate from CDT, after approximately 13 hours of infusion. Patients who did not resolve their tachycardia by that point in time were unlikely to resolve it by the conclusion of CDT.

Mechanisms related to the cardioprotective effects of protein kinase C epsilon (PKC epsilon) peptide activator or inhibitor in rat ischemia/reperfusion injury.

The role of protein kinase C epsilon (PKC epsilon) in polymorphonuclear leukocyte (PMN)-induced myocardial ischemia/reperfusion (MI/R) injury and novel-related mechanisms, such as regulation of vascular endothelium nitric oxide (NO) and hydrogen peroxide (H2O2) release from blood vessels, have not been previously evaluated. A cell-permeable PKC epsilon peptide activator (1-10 microM) significantly increased endothelial NO release from non-ischemic rat aortic segments (p < 0.01). By contrast, PKC epsilon peptide inhibitor (1-10 microM) dose-dependently decreased NO release (p < 0.01). Then, these corresponding doses of PKC epsilon activator or inhibitor were examined in MI/R. The PKC epsilon inhibitor (5 microM given during reperfusion, n=6) significantly attenuated PMN-induced postreperfused cardiac contractile dysfunction and PMN adherence/infiltration (both p < 0.01), and expression of intracellular adhesion molecule-1 (ICAM-1; p < 0.05). By contrast, only PKC epsilon activator pretreated hearts (5 muM PKC epsilon activator given before ischemia (PT), n = 6), not PKC epsilon activator given during reperfusion (5 microM, n=6) exerted significant cardioprotection (p < 0.01). Moreover, the NO synthase inhibitor, N(G)-nitro-L: -arginine methyl ester, did not block the cardioprotection of PKC epsilon inhibitor, whereas it completely abolished the cardioprotective effects of PKC epsilon activator PT. In addition, PKC epsilon inhibitor (0.4 mg/kg) significantly decreased H(2)O(2) release during reperfusion in a femoral I/R model (p < 0.01). Therefore, the cardioprotection of PKC epsilon inhibitor maybe related to attenuating ICAM-1 expression and H2O2 release during reperfusion. By contrast, the cardioprotective effects of PKC epsilon activator PT may be mediated by enhancing vascular endothelial NO release before ischemia.