Constant Sub-second Cycling between Representations of Possible Futures in the Hippocampus.

Cognitive faculties such as imagination, planning, and decision-making entail the ability to represent hypothetical experience. Crucially, animal behavior in natural settings implies that the brain can represent hypothetical future experience not only quickly but also constantly over time, as external events continually unfold. To determine how this is possible, we recorded neural activity in the hippocampus of rats navigating a maze with multiple spatial paths. We found neural activity encoding two possible future scenarios (two upcoming maze paths) in constant alternation at 8 Hz: one scenario per ∼125-ms cycle. Further, we found that the underlying dynamics of cycling (both inter- and intra-cycle dynamics) generalized across qualitatively different representational correlates (location and direction). Notably, cycling occurred across moving behaviors, including during running. These findings identify a general dynamic process capable of quickly and continually representing hypothetical experience, including that of multiple possible futures.

Mechanical Thrombectomy vs. Pharmacomechanical Catheter Directed Thrombolysis for the Treatment of Iliofemoral Deep Vein Thrombosis: A Propensity Score Matched Exploratory Analysis of 12 Month Clinical Outcomes.

OBJECTIVE: To compare thrombus removal and residual venous symptoms and signs of disease following interventional treatment of iliofemoral deep vein thrombosis (DVT) with mechanical thrombectomy (MT) and pharmacomechanical catheter directed thrombolysis (PCDT). METHODS: Retrospective cohort analysis of propensity score matched subgroups from the multicentre prospective MT ClotTriever Outcomes registry and the PCDT arm of the randomised Acute Venous Thrombosis: Thrombus Removal with Adjunctive Catheter Directed Thrombolysis trial. Patients with bilateral DVT, symptom duration greater than four weeks, isolated femoral-popliteal disease, or incomplete case data were excluded. Patients with iliofemoral DVT were propensity score matched (1:1) on 10 baseline covariables, including race, sex, age, body mass index, leg treated, prior thromboembolism, Marder score, symptom duration, provoked deep vein thrombosis status, and Villalta score. Reduction in post-procedure thrombus burden (i.e., Marder scores), assessment of venous symptoms and signs (i.e., Villalta scores) at 12 months, and healthcare resource utilisation were compared between subgroups. RESULTS: Propensity score matching resulted in 130 patient pairs with no significant differences in baseline characteristics between the MT and PCDT groups. MT was associated with a greater reduction in Marder scores (91.0% vs. 67.7%, p < .001), and a greater proportion of patients at 12 months with no post-thrombotic syndrome (83.1% vs. 63.6%, p = .007) compared with matched patients receiving PCDT. No differences in rates of adjunctive stenting or venoplasty were identified (p = .27). Higher rates of single session treatment were seen with MT (97.7% vs. 26.9%, p < .001), which also showed shorter mean post-procedure hospital stays (1.81 vs. 3.46 overnights, p < .001), and less post-procedure intensive care unit utilisation (2.3% vs. 52.8%, p < .001). CONCLUSION: Compared with PCDT, MT was associated with greater peri-procedural thrombus reduction, more efficient post-procedure care, and improved symptoms and signs of iliofemoral vein disease at 12 months.

Six-Month Deep Vein Thrombosis Outcomes by Chronicity: Analysis of the Real-World ClotTriever Outcomes Registry.

PURPOSE: To analyze the first 250 patients from the prospective, multicenter, industry-sponsored ClotTriever Outcomes (CLOUT) registry, assessing the safety and effectiveness of mechanical thrombectomy for acute, subacute, and chronic deep vein thrombosis (DVT). MATERIALS AND METHODS: Real-world patients with lower extremity DVT were treated with the ClotTriever System (Inari Medical, Irvine, California). Adjuvant venoplasty, stent placement, or both were performed at the physician's discretion. Thrombus chronicity was determined by visual inspection of removed thrombus, categorizing patients into acute, subacute, and chronic subgroups. Serious adverse events (SAEs) were assessed through 30 days. Clinical and quality-of-life (QoL) outcomes are reported through 6 months. RESULTS: Thrombus chronicity was designated for 244 of the 250 patients (acute, 32.8%; subacute, 34.8%; chronic, 32.4%) encompassing 254 treated limbs. Complete or near-complete (≥75%) thrombus removal was achieved in 90.8%, 81.9%, and 83.8% of the limbs with acute, subacute, and chronic thrombus, respectively. No fibrinolytics were administered, and 243 (99.6%) procedures were single sessions. One (0.4%) patient in the subacute group experienced a device-related SAE, a fatal pulmonary embolism. On comparing baseline and 6-month data, improvements were demonstrated in median Villalta scores (acute, from 10 to 1; subacute, from 9 to 1; chronic, from 10 to 3; for all, P < .0001) and mean EuroQol group 5-dimension (EQ-5D) self-report questionnaire scores (acute, 0.58 to 0.89; subacute, 0.65 to 0.87; chronic, 0.58 to 0.88; for all, P < .0001). There were no significant differences in outcomes across the subgroups. CONCLUSIONS: Mechanical thrombectomy using the ClotTriever System with adjunctive venoplasty and stent placement is safe and similarly effective for acute, subacute, and chronic DVT.

Supra-Aortic Arterial Injuries Following Central Venous Catheterization Managed with Percutaneous Closure Devices: A Comprehensive Literature Review of Current Evidence.

BACKGROUND: Inadvertent supra-aortic arterial injuries during central venous catheterization can lead to devastating outcomes. These have been traditionally been managed with open repair or covered stent placement; only recently have percutaneous closure been incorporated into the management of these iatrogenic arterial injuries. METHODS: We performed a MEDLINE literature search in the English language, using the PubMed web-based search engine across years 2000 to 2020. This report reviews 34 published case reports and series reporting 71 iatrogenic supra-aortic arterial injuries managed with percutaneous vascular closure devices. RESULTS: In our review, the use of a closure device was successful in 87% of cases, even in some cases involving sheath sizes greater than 8F. The devices used in these situations caused minimal complications and offered a quick means to control bleeding. Thus, percutaneous closure devices are a helpful tool that offers an alternative to more invasive open surgical repair. CONCLUSIONS: Vascular closure devices offer a minimally invasive and effective approach to the treatment of inadvertent supra-aortic arterial injury following CVC.

Hemodynamic instability in the immediate postoperative setting after transcarotid artery revascularization.

OBJECTIVE: Transcarotid artery revascularization (TCAR) is a relatively recent development in the management of carotid artery occlusive disease, the utilization of which is becoming more prevalent. This study aims to evaluate the timing, prevalence, and types of hemodynamic instability after TCAR. METHODS: We performed a retrospective review of all TCAR procedures performed at two tertiary care academic medical centers within a single hospital system from 2017 through 2019. Demographics, comorbidities, preoperative patient factors, procedural details, and postoperative data were collected. Patients were assessed over 24 hours postoperatively for stroke, death, myocardial infarction (MI), and hemodynamic instability at 3, 6, 9, 12, and 24 hour intervals. Hemodynamic instability was defined as any vital sign abnormality which required pharmacological intervention with antihypertensive, vasopressor, and/or anti-arrhythmic agents. The incidence and timing of postoperative complications and hemodynamic instability were recorded. RESULTS: During the study period, 76 patients 80 TCAR procedures. Out of 80 procedures, 64 (80.0%) were receiving home antihypertensive medication and 28 (35.0%) were symptomatic lesions preoperatively. Intraoperatively, one patient (1.3%) received atropine, 26 (32.5%) received glycopyrrolate, 76 (95%) underwent predilatation, and 16 (20.0%) underwent postdilatation. Postoperatively, a total of 22 cases (27.5%) required medication for acute control of blood pressure or heart rate, which reached a peak of 19 patients (23.8%) within the first 3 hours, and tapered to nine patients (11.3%) by the 24 hour mark. A total of three patients (3.75%) required initiation of pharmacological management after the three-hour mark. Six patients (7.5%) underwent stroke code workup, 4 (5.0%) of whom were confirmed to have stroke on CT. Average time to neurologic event was 3.9 hours. No patients experienced MI or death. Median ICU and hospital days for unstable patients were two and three, respectively, compared to one and one for stable patients. CONCLUSIONS: Hemodynamic instability is common after TCAR and reliably presents at or before postoperative hour 3. Hypo- followed by hyper-tension were the most common manifestations of hemodynamic instability. Regardless, unstable patients and stroke patients were more likely to require longer periods of time in the ICU and in the hospital overall. This may have implications for postoperative ICU resource management when deciding to transfer patients out of a monitored setting. Further study is required to establish relationships between pre- and intra-operative risk factors and outcomes such as hemodynamic instability and/or stroke. At present, one should proceed with careful evaluation of preoperative medications, strict management of postoperative hemodynamics, and clear communication among team members should all be employed to optimize outcomes.

Endovascular Management of Bleeding Aortoenteric Fistula May be Feasible as a Definitive Repair.

Aorto-enteric fistula (AEF) is a complication with devastating sequelae and significant morbidity. Although open surgery remains primary treatment endovascular approach may be used as a temporary bridge but rarely as a definitive therapy. We present a case of a patient who presented with a secondary AEF, due to hemodynamic instability we chose to treat the fistula with an aortic endograft. The patient underwent bowel resection due to bowel obstruction with omental patch over the aortic rent, 6 weeks of antibiotics. Patient is now at 8-year follow-up without evidence of infection. Although there is scarce literature on this topic, endovascular treatment of bleeding AEF may be feasible as a definitive option. Due to high risk of graft infection we recommend close observation and suppressive antibiotics.

Objective Improvements in Peripheral Arterial Disease from Dorsal Root Ganglion Stimulation: A Case Series.

BACKGROUND: The sympathetic nervous system (SNS) is important in the regulation of perfusion. Dorsal root ganglion stimulation (DRG-S) modulates sympathetic tone and is approved to treat complex regional pain syndrome, a disorder related to SNS dysfunction. We herein present 3 cases of DRG-S therapy to improve blood flow and symptoms of ischemia in peripheral arterial disease (PAD). METHODS: Patient 1 is a 44-year-old female with dry gangrene of the third and fourth digits of her right hand due to Raynaud's syndrome who was scheduled for amputation of the affected digits. DRG-S leads were placed at the right C6, 7, and 8 DRG. Pulse volume recordings (PVR) were measured at baseline and after DRG-S. Patient 2 is a 55-year-old female with a non-healing ulcer of her left foot secondary to PAD scheduled for a below the knee amputation who underwent a DRG-S trial with leads placed at the left L4 and L5 DRG followed by a spinal cord stimulation trial with leads placed at the T9-T10 spinal levels for comparison. Transcutaneous oximetry (TcPO2) was measured at baseline and after 3 days of each therapy. Patient 3 is a 69-year-old female with persistent left foot pain at rest secondary to PAD with DRG-S leads placed at the left L4 and S1 levels. RESULTS: All 3 patients experienced a significant reduction in pain with DRG-S, along with improvements in blood flow of the involved extremities, avoiding or limiting amputation. PVR improved dramatically with DRG-S in patient 1. A greater improvement in TcPO2 was seen with the DRG-S trial compared to spinal cord stimulation trial in patient 2. Patient 3 experienced an increase in walking distance and demonstrated long term efficacy and limb salvage at 32 months postimplantation. CONCLUSIONS: Modulation of SNS output from DRG-S through orthodromic and antidromic autonomic pathways is likely responsible for improving blood flow. DRG-S may be a treatment option for PAD.

Acute Arterial Thromboembolism in Patients with COVID-19 in the New York City Area.

BACKGROUND: Coronavirus disease 2019 (COVID-19) predisposes to arterial and venous thromboembolic complications. We describe the clinical presentation, management, and outcomes of acute arterial ischemia and concomitant infection at the epicenter of cases in the United States. METHODS: Patients with confirmed COVID-19 infection between March 1, 2020 and May 15, 2020 with an acute arterial thromboembolic event were reviewed. Data collected included demographics, anatomical location of the thromboembolism, treatments, and outcomes. RESULTS: Over the 11-week period, the Northwell Health System cared for 12,630 hospitalized patients with COVID-19. A total of 49 patients with arterial thromboembolism and confirmed COVID-19 were identified. The median age was 67 years (58-75) and 37 (76%) were men. The most common preexisting conditions were hypertension (53%) and diabetes (35%). The median D-dimer level was 2,673 ng/mL (723-7,139). The distribution of thromboembolic events included upper 7 (14%) and lower 35 (71%) extremity ischemia, bowel ischemia 2 (4%), and cerebral ischemia 5 (10%). Six patients (12%) had thrombus in multiple locations. Concomitant deep vein thrombosis was found in 8 patients (16%). Twenty-two (45%) patients presented with signs of acute arterial ischemia and were subsequently diagnosed with COVID-19. The remaining 27 (55%) developed ischemia during hospitalization. Revascularization was performed in 13 (27%) patients, primary amputation in 5 (10%), administration of systemic tissue- plasminogen activator in 3 (6%), and 28 (57%) were treated with systemic anticoagulation only. The rate of limb loss was 18%. Twenty-one patients (46%) died in the hospital. Twenty-five (51%) were successfully discharged, and 3 patients are still in the hospital. CONCLUSIONS: While the mechanism of thromboembolic events in patients with COVID-19 remains unclear, the occurrence of such complication is associated with acute arterial ischemia which results in a high limb loss and mortality.

Contemporary outcomes of infrapopliteal atherectomy with angioplasty versus balloon angioplasty alone for critical limb ischemia.

OBJECTIVE: Limited data exist comparing atherectomy (At) with balloon angioplasty for infrapopliteal peripheral arterial disease. The objective of this study was to compare the outcomes of infrapopliteal At with angioplasty vs angioplasty alone in patients with critical limb ischemia. METHODS: This is a retrospective, single-center, longitudinal study comparing patients undergoing either infrapopliteal At with angioplasty or angioplasty alone for critical limb ischemia, between January 2014 and October 2017. The primary outcome was primary patency rates. Secondary outcomes were reintervention rates, assisted primary patency, secondary patency, major adverse cardiac events, major adverse limb events, amputation-free survival, overall survival, and wound healing rates. Data were analyzed in multivariate generalized linear models with log rank tests to determine survival in Kaplan-Meier curves. RESULTS: There were 342 infrapopliteal interventions, 183 percutaneous balloon angioplasty (PTA; 54%), and 159 atherectomies (At) with PTA (46%) performed on 290 patients, with a mean age of 67 ± 12 years; 61% of the patients were male. The PTA and At/PTA groups had similar demographics, tissue loss (79% vs 84%; P = .26), ischemic rest pain (21% vs 16%; P = .51), mean follow-up (19 ± 9 vs 20 ± 9 months; P = .32), mean number of vessels treated (1.7 ± 0.8 vs 1.9 ± 0.8; P = .08) and the mean lesion length treated (6.55 ± 5.00 cm vs 6.02 ± 4.00 cm; P = .08), respectively. Similar 3-month (96 ± 1% vs 94 ± 1%), 6-month (85 ± 2% vs 86 ± 3%), 12-month (68 ± 3% vs 69 ± 4%), and 18-month (57 ± 4% vs 62 ± 4%) primary patency rates were seen in the two groups (P = .87). At/PTA patients had significantly higher reintervention rates as compared with the PTA patients (28% vs 16%; P = .02). Similar assisted primary patency rates (67 ± 4% vs 69 ± 4%; P = .78) and secondary patency rates (61 ± 4% vs 66 ± 4%; P = .98) were seen in the PTA and At/PTA groups at 18 months. The 30-days major adverse cardiac event rates (3% vs 2%; P = .13) and 30-day major adverse limb event rates (5% vs 4%; P = .2) were similar in both groups. Wound healing rates (72 ± 3% vs 75 ± 2%; P = .12), 1-year amputation-free survival (68 ± 4.1% vs 70 ± 2%; P = .5), and 1-year overall survival (76 ± 4% vs 78 ± 4%; P = .39) rates did not differ in the PTA and At/PTA groups. THE At/PTA group had higher local complication rates (7 [4%] vs 1 [0.5%]; P = .03) CONCLUSIONS: At with angioplasty provides similar patency rates compared with angioplasty alone for infrapopliteal peripheral arterial disease, but associated with higher reintervention and local complication rates. Further appropriately designed studies are required to determine the exact role of At in this subset of patients.

Peripheral Vascular Complication of Transgender Reassignment Surgery.

BACKGROUND: Gender-reassignment surgeries are technically challenging and associated with detrimental vascular complications. METHODS: A 49 year-old female status-post phalloplasty presented with peripheral vascular complication resulting in disabling claudication. Initial anastomotic attempt was rendered nonviable to sustain the constructed phallus resulting in superficial femoral artery stenosis. Covered stent placement corrected the stenosis and alleviated the claudication. RESULTS: As gender-reassignment surgeries increase, greater understanding of potential vascular complications is needed. Involvement of multidisciplinary teams is necessary to optimize patient safety and outcomes. CONCLUSIONS: Vascular surgery should play a larger role in these complex revascularizations and vessel anastomoses to ensure quality blood flow to the reconstructed genitalia.

Relationships between the use of pharmacomechanical catheter-directed thrombolysis, sonographic findings, and clinical outcomes in patients with acute proximal DVT: Results from the ATTRACT Multicenter Randomized Trial.

Few studies have documented relationships between endovascular therapy, duplex ultrasonography (DUS), post-thrombotic syndrome (PTS), and quality of life (QOL). The Acute Venous Thrombosis: Thrombus Removal with Adjunctive Catheter-Directed Thrombolysis (ATTRACT) trial randomized 692 patients with acute proximal deep vein thrombosis (DVT) to receive anticoagulation or anticoagulation plus pharmacomechanical catheter-directed thrombolysis (PCDT). Compression DUS was obtained at baseline, 1 month and 12 months. Reflux DUS was obtained at 12 months in a subset of 126 patients. Clinical outcomes were collected over 24 months. At 1 month, patients who received PCDT had less residual thrombus compared to Control patients, evidenced by non-compressible common femoral vein (CFV) (21% vs 35%, p < 0.0001), femoral vein (51% vs 70%, p < 0.0001), and popliteal vein (61% vs 74%, p < 0.0001). At 12 months, in the ultrasound substudy, valvular reflux prevalence was similar between groups (85% vs 91%, p = 0.35). CFV non-compressibility at 1 month was associated with higher rates of any PTS (61% vs 46%, p < 0.001), a higher incidence of moderate-or-severe PTS (30% vs 19%, p = 0.003), and worse QOL (difference 8.2 VEINES-QOL (VEnous INsufficiency Epidemiological and Economic Study on Quality of Life) points; p = 0.004) at 24 months. Valvular reflux at 12 months was associated with moderate-or-severe PTS at 24 months (30% vs 0%, p = 0.01). In summary, PCDT results in less residual thrombus but does not reduce venous valvular reflux. CFV non-compressibility at 1 month is associated with more PTS, more severe PTS, and worse QOL at 24 months. Valvular reflux may predispose to moderate-or-severe PTS. ClinicalTrials.gov Identifier NCT00790335.

Routine Postoperative Cardiac Testing is Unnecessary after Carotid Endarterectomy.

BACKGROUND: Routine laboratory testing to rule out myocardial infarction (MI) after carotid endarterectomy (CEA) is common in many centers. Its use in this patient population has not been thoroughly investigated. We hypothesize that routine testing for MI in post-CEA patients is of low yield and not cost-effective. METHODS: A retrospective review of 291 consecutive CEAs from February 2011 to July 2015 was performed. Two patients were excluded: one for postoperative noncardiac death and one for preoperative MI. Patient demographics, medications, medical history, type of anesthesia, and postoperative laboratory results were reviewed. All patients had troponin-I and creatine kinase-MB levels taken postoperatively. A patient was judged to have an MI if troponin-I was greater than or equal to 0.6 ng/mL or CK-MB is >6.3 ng/mL. The incidence of postoperative MI was recorded, and a cost analysis was performed. RESULTS: The mean age was 70.2 years (range: 42-92). Of all, 59.5% were male, and 92.4% had a history of hypertension. Preoperatively, 57.4% were on beta-blocker therapy, 86.5% on aspirin, and 52.2% on both. Most (80.6%) were on preoperative statin therapy, 26.9% had a prior history of MI (37.2% within 5 years of surgery), and 56.4% of patients had a prior coronary intervention (27.6% percutaneous, 28.7% coronary artery bypass grafting, and 11% both). All patients received general anesthesia. The mean procedure time was 121.5 min (range: 62-258). The mean postoperative length of stay was 2.6 days. Eight patients (2.7%) were judged to have acute MI, one of which was symptomatic. Three of the 8 (38%) had a prior history of MI. In asymptomatic patients, the peak level of troponin-I ranges from 0.52 to 3.64 ng/mL and that of CK-MB from 11.8 to 24 ng/mL. The symptomatic patient had chest pain and bradycardia. The patient had a peak troponin-I level of 1.59 ng/mL, with a CK-MB level of 11.5 ng/mL. All patients were treated medically. The cost per troponin-I and CK-MB is $27.78 and $31.44, respectively, in our institution. We estimate that eliminating routine postoperative troponin-I and CK-MB testing in patients who underwent CEA would have saved an estimated $51,343 over the course of treatment of the studied population. CONCLUSIONS: Routine postoperative cardiac laboratory testing in asymptomatic patients after CEA increases the hospital cost. The low overall rate of postoperative MI suggests that cardiac testing is best reserved for symptomatic patients or those with clinical suspicion for MI.

Safety and Feasibility of Transradial Access for Noncoronary and Peripheral Vascular Interventions.

BACKGROUND: Transradial access (TRad) is becoming the preferred access for cardiac catheterization. The use and safety of TRad in noncoronary and peripheral vascular interventions remains ill-defined and serves as the basis for this study. METHODS: Patients undergoing noncoronary and peripheral endovascular procedures via TRad from August 2010 to February 2013 at our institution were reviewed retrospectively. Demographic data, indications, interventions performed, sheath size, procedural outcomes, and access-site complications were evaluated. Postprocedural radial artery patency and hand ischemic symptoms were evaluated clinically and by duplex ultrasound. RESULTS: Nineteen patients underwent 24 procedures via TRad for both diagnostic (11/24) and therapeutic (13/24) purposes. Twelve (63%) were women, and 75% (18/24) were from left radial artery. Indications included absent femoral pulses in 12 (50%), morbid obesity in 6 (25%), previous bypass originating or terminating in the groin in 4 (17%), and groin wound infection in 2 (8%) cases. A 5F sheath was used in 13 (54%) cases, 6F in 10 (42%) cases, and 7F in 1 (4%) case. Thirteen therapeutic interventions included 7 (29%) iliac angioplasties and/or stent, 3 (13%) femoral anastomosis angioplasties, 2 (8%) superficial femoral artery angioplasties, and 1 (4%) mesenteric angioplasty. No access-site hematoma or procedure-related deaths were reported. Postprocedural radial artery occlusion was observed in 6 (31%) patients. All occlusions were asymptomatic, except for 1 (4%) patient with self-limiting forearm pain lasting for 1 day. Sheath size strongly correlated with radial artery occlusion. CONCLUSIONS: TRad appears to be a safe and feasible alternative option for patients undergoing noncoronary and peripheral interventions. Radial artery occlusion, mostly asymptomatic, can occur and is directly related to the sheath size. Smaller sheath sizes, longer platform devices, better radial access kits, and better closure devices could potentially eliminate some of the challenges associated with TRad.

Catheter-Directed Therapy is Safe and Effective for the Management of Acute Inferior Vena Cava Thrombosis.

BACKGROUND: The management of acute thrombosis of inferior vena cava (AT-IVC) has evolved to catheter-based therapies, the results of which remain uncertain. We report our institution's experience treating AT-IVC using endovascular methods. METHODS: A 10-year retrospective review of patients presenting with symptomatic IVC thrombosis between the years 2005 and 2014 was performed. Demographic data, treatment modalities, and outcomes were reviewed. RESULTS: Twenty-five patients (44% men) underwent treatment for acute (<2 weeks) symptomatic IVC thrombosis. Presenting symptoms included pain and limb swelling in 23 (92%), motor dysfunction in 16 (64%), sensory loss in 14 (56%), and pulmonary embolism (PE) in 2 (8%) patients. Phlegmasia cerulea dolens was present in 5 patients, a history of malignancy was identified in 7 patients, and 21 patients had an IVC filter at presentation (Trapease 12, G2X 3, Option 2, Eclipse 2, Meridian 2). Four patients had a documented hypercoagulable state, 21 patients underwent venous angioplasty, and 7 (28%) patients underwent venous stenting of the IVC or iliofemoral veins. Significant (>50% luminal gain) angiographic resolution of venous thrombus was achieved in all 25 patients. Twenty-one (84%) patients reported moderate-to-complete symptomatic improvement immediately after completion of the procedures. Two patients had a clinically symptomatic PE and 1 patient underwent an above-knee amputation secondary to venous gangrene. Other complications included 6 minor bleeding complications (2 local hematoma, 4 hematuria) all of which resolved spontaneously. There were 2 major bleeding complications (1 disseminated intravascular coagulation, 1 retroperitoneal hematoma). CONCLUSIONS: Endovascular treatment of AT-IVC, regardless of etiology, is safe and effective with excellent short-term clinical results. An aggressive endovascular approach to treatment of AT-IVC is warranted even in the presence of a thrombosed vena cava filter.

Comparison of anticoagulation vs mechanical thrombectomy for the treatment of iliofemoral deep vein thrombosis.

OBJECTIVE: To compare the comparative effects of treatment with contemporary mechanical thrombectomy (MT) or anticoagulation (AC) on Villalta scores and post-thrombotic syndrome (PTS) incidence through 12 months in iliofemoral deep vein thrombosis (DVT). METHODS: Patients with DVT in the Acute Venous Thrombosis: Thrombus Removal with Adjunctive Catheter-Directed Thrombolysis (ATTRACT) randomized trial and the ClotTriever Outcomes (CLOUT) registry were included in this analysis. Both studies evaluated the effects of thrombus removal on the incidence of PTS. Patients with bilateral DVT, isolated femoral-popliteal DVT, symptom duration of >4 weeks, or incomplete case data for matching covariates were excluded. Propensity scores were used to match patients 1:1 who received AC (from ATTRACT) with those treated with mechanical thrombectomy (from CLOUT) using nearest neighbor matching on nine baseline covariates, including age, body mass index, leg treated, provoked DVT, prior venous thromboembolism, race, sex, Villalta score, and symptom duration. Clinical outcomes, including Villalta score and PTS, were assessed. Logistic regression was used to estimate the likelihood of developing PTS at 12 months. RESULTS: A total of 164 pairs were matched, with no significant differences in baseline characteristics after matching. There were fewer patients with any PTS at 6 months (19% vs 46%; P < .001) and 12 months (17% vs 38%; P < .001) in the MT treatment group. Modeling revealed that, after adjusting for baseline Villalta scores, patients treated with AC had significantly higher odds of developing any PTS (odds ratio, 3.1; 95% confidence interval, 1.5-6.2; P = .002) or moderate to severe PTS (odds ratio, 3.1; 95% confidence interval, 1.1-8.4; P = .027) at 12 months compared with those treated with MT. Mean Villalta scores were lower through 12 months among those receiving MT vs AC (3.3 vs 6.3 at 30 days, 2.5 vs 5.5 at 6 months, and 2.6 vs 4.9 at 12 months; P < .001 for all). CONCLUSIONS: MT treatment of iliofemoral DVT was associated with significantly lower Villalta scores and a lower incidence of PTS through 12 months compared with treatment using AC. Results from currently enrolling clinical trials will further clarify the role of these therapies in the prevention of PTS after an acute DVT event.

Six-Month Outcomes of Mechanical Thrombectomy for Treating Deep Vein Thrombosis: Analysis from the 500-Patient CLOUT Registry.

PURPOSE: Mechanical thrombectomy for the treatment of deep vein thrombosis (DVT) is being increasingly utilized to reduce symptoms and prevent postthrombotic syndrome (PTS), but more data on clinical outcomes are needed. Mechanical thrombectomy was studied in the ClotTriever Outcomes (CLOUT) registry with 6-month full analysis outcomes reported herein. MATERIALS AND METHODS: The CLOUT registry is a prospective, all-comer study that enrolled 500 lower extremity DVT patients across 43 US sites treated with mechanical thrombectomy using the ClotTriever System. Core-lab assessed Marder scores and physician-assessed venous patency by duplex ultrasound, PTS assessment using Villalta score, venous symptom severity, pain, and quality of life scores through 6 months were analyzed. Adverse events were identified and independently adjudicated. RESULTS: All-cause mortality at 30 days was 0.9%, and 8.6% of subjects experienced a serious adverse event (SAE) within the first 30 days, 1 of which (0.2%) was device related. SAE rethrombosis/residual thrombus incidence was 4.8% at 30 days and 8.0% at 6 months. Between baseline and 6 months, venous flow increased from 27.2% to 92.5% of limbs (P < 0.0001), and venous compressibility improved from 28.0% to 91.8% (P < 0.0001), while median Villalta scores improved from 9.0 at baseline to 1.0 at 6 months (P < 0.0001). Significant improvements in venous symptom severity, pain, and quality of life were also demonstrated. Outcomes from iliofemoral and isolated femoral-popliteal segments showed similar improvements. CONCLUSION: Outcomes from the CLOUT study, a large prospective registry for DVT, indicate that mechanical thrombectomy is safe and demonstrates significant improvement in symptoms and health status through 6 months. Level of Evidence 3: Non-randomized controlled cohort/follow-up study.

The transcription factor C/EBPß promotes vascular endothelial growth factor A expression and neural stem cell expansion.

The bZIP transcription factor CCAAT-enhancer-binding protein ß (C/EBPß) exhibits neurogenic, neuritogenic, and pro-survival effects in the central nervous system. Here, we show that C/EBPß regulates neural stem cell (NSC) expansion and vascular endothelial growth factor A (VEGF-A) level by acting on a C/EBPß-responsive element within the Vegf-a promoter. As predicted, C/EBPß depletion reduced VEGF-A production, NSC number, and average neurosphere size in proliferating cultures. Conversely, deletion of the C/EBPß repressor CHOP-10 induced C/EBPß and VEGF-A expression, while stimulating NSC expansion. These data highlight the role of C/EBPß in regulating VEGF-A production and the growth of NSCs and suggest CHOP-dependent antagonism of C/EBPß may function as a transcriptional rheostat linking stress-associated cues with stem cell quiescence among other pathological responses affecting the neurogenic niche.

Outcomes from the ClotTriever Outcomes Registry show symptom duration may underestimate deep vein thrombus chronicity.

OBJECTIVE: The all-comer ClotTriever Outcomes registry assessed indicators of thrombus chronicity in patients with acute, subacute, and chronic lower extremity deep vein thrombosis (DVT). The effectiveness of the ClotTriever System (Inari Medical, Irvine, CA) by chronicity subgroup was also assessed and reported here in this subanalysis. METHODS: All-comer patients with lower extremity DVT were enrolled, with no limitation based on the patients' symptom duration. Chronicity was assessed three times and compared: before the procedure based on symptom duration, during the procedure based on available pre-thrombectomy imaging, and visual inspection of the extracted thrombus morphology after thrombectomy. Patients were grouped into acute, subacute, and chronic subgroups according to their post-thrombectomy thrombus chronicity based on thrombus morphology. Analyses on baseline and procedural characteristics along with thrombus removal were performed across subgroups. The effectiveness of thrombus removal was determined by Marder scores adjudicated by an independent core laboratory, with a prespecified primary effectiveness end point of complete or near-complete (≥75%) thrombus removal. RESULTS: Of the 260 treated limbs from 250 patients, using symptom duration alone, 70.7% were considered acute, 20.9% subacute, and 8.4% chronic. Upon visual inspection, the extracted thrombus chronicity was approximately one-third in each subgroup: 32.7% had acute thrombus, 35.4% subacute thrombus, and 31.9% chronic thrombus. Chronicity assessed using symptom duration alone mismatched the post-thrombectomy chronicity in 55.1% of limbs (P < .0001) with 49.0% being more chronic than suggested by the patients' duration of symptoms. Chronicity assessed using pre-thrombectomy imaging mismatched the post-thrombectomy chronicity in 17.5% of limbs (P < .0001). No patients received thrombolytics and 99.6% were treated in a single session. Complete or near-complete thrombus removal was achieved in a high percentage of limbs regardless of thrombus chronicity: 90.8%, 81.9%, and 83.8% in limbs with acute, subacute, and chronic thrombus, respectively. CONCLUSIONS: This subanalysis from the all-comer ClotTriever Outcomes registry demonstrates that extracted thrombus in DVT may be more chronic than suggested by the patients' duration of symptoms. The addition of imaging is helpful to determine the ability of thrombus to respond to therapy. Irrespective of thrombus chronicity, the ClotTriever system can be effective at removing acute, subacute, and chronic thrombus in a single-session procedure without the need for thrombolytics.

Therapeutic deep brain stimulation disrupts movement-related subthalamic nucleus activity in parkinsonian mice.

Subthalamic nucleus deep brain stimulation (STN DBS) relieves many motor symptoms of Parkinson's disease (PD), but its underlying therapeutic mechanisms remain unclear. Since its advent, three major theories have been proposed: (1) DBS inhibits the STN and basal ganglia output; (2) DBS antidromically activates motor cortex; and (3) DBS disrupts firing dynamics within the STN. Previously, stimulation-related electrical artifacts limited mechanistic investigations using electrophysiology. We used electrical artifact-free GCaMP fiber photometry to investigate activity in basal ganglia nuclei during STN DBS in parkinsonian mice. To test whether the observed changes in activity were sufficient to relieve motor symptoms, we then combined electrophysiological recording with targeted optical DBS protocols. Our findings suggest that STN DBS exerts its therapeutic effect through the disruption of movement-related STN activity, rather than inhibition or antidromic activation. These results provide insight into optimizing PD treatments and establish an approach for investigating DBS in other neuropsychiatric conditions.

Interim outcomes of mechanical thrombectomy for deep vein thrombosis from the All-Comer CLOUT Registry.

OBJECTIVES: The multicenter, prospective, single arm CLOUT registry assesses the safety and effectiveness of the ClotTriever System (Inari Medical, Irvine, CA) for the treatment of acute and nonacute lower extremity deep vein thrombosis (DVT) in all-comer patients. Reported here are the outcomes of the first 250 patients. METHODS: All-comer patients with lower extremity DVT were enrolled, including those with bilateral DVT, those with previously failed DVT treatment, and regardless of symptom duration. The primary effectiveness end point is complete or near-complete (≥75%) thrombus removal determined by independent core laboratory-adjudicated Marder scores. Safety outcomes include serious adverse events through 30 days and clinical outcomes include post-thrombotic syndrome severity, symptoms, pain, and quality of life through 6 months. RESULTS: The median age was 62 years and 40% of patients had contraindications to thrombolytics. A range of thrombus chronicity (33% acute, 35% subacute, 32% chronic) was observed. No patients received thrombolytics and 99.6% were treated in a single session. The median thrombectomy time was 28 minutes. The primary effectiveness end point was achieved in 86% of limbs. Through 30 days, one device-related serious adverse event occurred. At 6 months, 24% of patients had post-thrombotic syndrome. Significant and sustained improvements were observed in all clinical outcomes, including the Revised Venous Clinical Severity Score, the numeric pain rating scale, and the EuroQol Group 5-Dimension Self-Report Questionnaire. CONCLUSIONS: The 6-month outcomes from the all-comer CLOUT registry with a range of thrombus chronicities demonstrate favorable effectiveness, safety, and sustained clinical improvements.