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.

Single-Session Treatment of Patients with Symptomatic Iliocaval and Iliofemoral Deep Vein Thrombosis: Technical Results of a Prospective Pilot Study.

PURPOSE: To investigate the short-term results of single-session treatment of iliocaval and iliofemoral DVT using a single thrombectomy device. MATERIALS AND METHODS: This prospective pilot study analyzed patients with acute iliocaval or iliofemoral DVT treated in a single session using the JETi thrombectomy system. All analyses were performed on an intention-to-treat basis. The cohort consisted of 53 limbs in 47 patients (27 women), with a mean age of 57 years (range, 16-88 years). The primary safety and efficacy endpoints were freedom from major adverse events (MAEs) and reestablishment of unobstructed flow in a single session, respectively. RESULTS: The mean duration of symptoms was 8.5 days ± SD 9.2, with 10 patients (11 limbs, 21.3%) presenting with a symptom duration of >14 days. Twelve (25.5%) patients had thrombosis of the inferior vena cava and the iliofemoral segments. During the index procedure, unobstructed flow was reestablished in 47 of 53 (88.6%) limbs in 41 of 47 (87.2%) patients (primary endpoint) with no MAEs through 30 days. Overall, unobstructed flow was restored in 50 of 53 (94.3%) limbs and in 44 of 47 (93.6%) patients. CONCLUSIONS: Successful single-session treatment of patients with acute iliocaval and iliofemoral DVT is feasible with a high rate of efficacy and a low rate of adverse events. Such patients may be treated on an outpatient basis.

Novel Utility of Amplatzer Septal Occlusion Device to Treat Persistent Aortocaval Fistula following Ruptured Endovascular Aortic Aneurysm Repair (rEVAR).

Aortocaval fistulas following endovascular repair of ruptured abdominal aortic aneurysms (rAAA) are rare. We herein describe repair using an Amplatzer Septal Occluder in a 68-year-old male who presented to the emergency department 6 months after ruptured endovascular aneurysm repair (rEVAR) with right heart failure. With the assistance of diagnostic angiography and intravascular ultrasound, the patient was found to have a 1.2 cm diameter aortocaval fistula and a type-II endoleak. His aortocaval fistula was successfully closed using an Amplatzer septal occluder device after failure of attempted closure with an Amplatzer plug and coiling of the aneurysm sac. His symptoms of heart failure improved, and he was discharged to an acute rehabilitation unit. Follow-up at 3 months demonstrated continued improvement in heart failure symptoms, and a small persistent type II endoleak. Aortocaval fistulae are a potentially fatal complication of rAAA. We discuss the sequelae and treatment strategies of aortocaval fistulas following rEVAR including the use of the Amplatzer Septal Occluder.

Evolution in the Treatment of Delayed Postpancreatectomy Hemorrhage: Surgery to Interventional Radiology.

OBJECTIVES: We summarized a single center's evolution in the management of postpancreatectomy hemorrhage (PPH) from surgical toward endovascular management. METHODS: Between 2003 and 2013, 337 patients underwent Whipple procedures. Using the International Study Group of Pancreatic Surgery (ISGPS) consensus definition, patients with PPH were identified and retrospectively analyzed for the presentation of hemorrhage, type of intervention, and 90-day mortality outcome measures. RESULTS: Management evolved from operative intervention alone, to combined operative and on-table angiographic intervention, to endovascular intervention alone. The prevalence of PPH was 3.0%. Delayed PPH occurred with a mean of 13.8 days. On angiography, visceral arteries affected were the gastroduodenal artery, hepatic artery, jejunal branches of the superior mesenteric artery, pancreaticoduodenal artery, and inferior phrenic artery. Ninety-day mortality for PPH was 20%. From early to recent experience, the mortality rate was 100% for operative intervention alone, 25% for combined operative and on-table angiographic intervention, and 0% for endovascular intervention alone. CONCLUSIONS: Our 10-year experience supports current algorithms in the management of PPH. Key considerations include the recognition of the sentinel bleed, the presence of a pancreatic fistula, and the initial operative role of a long gastroduodenal artery stump with radiopaque marker for safe and effective embolization should PPH occur.

40-year-old female with menorrhagia and abdominal pain: A case of metastatic gestational trophoblastic neoplasia.

Choriocarcinoma is part of a rare spectrum of placental abnormalities known as gestational trophoblastic disease (GTD). It is the most invasive form of GTD, with a mortality rate approaching 100% if left untreated. It spreads predominantly hematogenously to multiple target sites, most commonly the lungs. Due to its hypervascular nature, it is often complicated by bleeding. We describe a case of choriocarcinoma in a 40-year-old female with metastases to the lungs, brain, and bilateral kidneys resulting in large retroperitoneal hematomas.

63-year-old male with gastric outlet obstruction.

We describe a case of a 63-year-old male with complicated Bouveret's syndrome, both in its presentation and in its management. Bouveret's syndrome is a rare cause of gastric outlet obstruction resulting from mechanical obstruction from gallstones at the pyloroduodenal segment. As Bouveret's syndrome can be a diagnostic and therapeutic challenge for clinicians, we aim to identify clinical and radiologic pearls that can lower the threshold for the diagnosis of Bouveret's syndrome.

Planting the seeds of success: CT-guided gold seed fiducial marker placement to guide robotic radiosurgery.

Fiducial marker (FM)-guided stereotactic body radiation therapy (SBRT) allows for precise targeting and delivery of radiation to a tumor site. In this article, we briefly discuss SBRT, provide examples to describe CT-guided FM placement to guide SBRT, and discuss some of the associated risks and benefits. This article serves as a pictorial review for body imagers and interventional radiologists who perform CT-guided procedures and interpret diagnostic studies for oncology patients. CT-guided FMs were placed in patients who were appropriate candidates for SBRT. One week following placement, patients underwent diagnostic CT and/or MR examinations in order to include the FM data in the development of a treatment plan. From October 2007-November 2009, a total of 89 patients were implanted with FMs. Sites of implantation included lung, liver, bone, chest and abdominal wall, and peritoneum/retroperitoneum. Complications included pneumothorax and FM migration. Twenty-one patients (33%) with lung FM placement experienced at least a small pneumothorax and 6 patients (9%) required thoracostomy tubes. FM migration occurred in 5 patients (8%) with lung placement. SBRT provides a safer and more effective alternative to conventional radiotherapy, and CT-guided FM implantation of tumor sites increases the precision of SBRT. Technical improvements in FM placement can limit the complications associated with the procedure and further enable highly localized tumor therapy.

Early intervention to promote medical student interest in surgery and the surgical subspecialties.

OBJECTIVE: Concerns about projected workforce shortages are growing, and attrition rates among surgical residents remain high. Early exposure of medical students to the surgical profession may promote interest in surgery and allow students more time to make informed career decisions. The objective of this study was to evaluate the impact of a simple, easily reproducible intervention aimed at increasing first- and second-year medical student interest in surgery. DESIGN: Surgery Saturday (SS) is a student-organized half-day intervention of four faculty-led workshops that introduce suturing, knot tying, open instrument identification, operating room etiquette, and basic laparoscopic skills. Medical students who attended SS were administered pre-/post-surveys that gauged change in surgical interest levels and provided a self-assessment (1-5 Likert-type items) of knowledge and skills acquisition. PARTICIPANTS: First- and second-year medical students. OUTCOME MEASURES: Change in interest in the surgical field as well as perceived knowledge and skills acquisition. RESULTS: Thirty-three first- and second-year medical students attended SS and completed pre-/post-surveys. Before SS, 14 (42%) students planned to pursue a surgical residency, 4 (12%) did not plan to pursue a surgical residency, and 15 (46%) were undecided. At the conclusion, 29 (88%) students indicated an increased interested in surgery, including 87% (13/15) who were initially undecided. Additionally, attendees reported a significantly (p < 0.05) higher comfort level in the following: suturing, knot tying, open instrument identification, operating room etiquette, and laparoscopic instrument identification and manipulation. CONCLUSIONS: SS is a low resource, high impact half-day intervention that can significantly promote early medical student interest in surgery. As it is easily replicable, adoption by other medical schools is encouraged.

Oscillatory shear stress induces mitochondrial superoxide production: implication of NADPH oxidase and c-Jun NH2-terminal kinase signaling.

Fluid shear stress is intimately linked with vascular oxidative stress and atherosclerosis. We posited that atherogenic oscillatory shear stress (OSS) induced mitochondrial superoxide (mtO2•-) production via NADPH oxidase and c-Jun NH(2)-terminal kinase (JNK-1 and JNK-2) signaling. In bovine aortic endothelial cells, OSS (±3 dyn/cm2) induced JNK activation, which peaked at 1 h, accompanied by an increase in fluorescein isothiocyanate-conjugated JNK fluorescent and MitoSOX Red (specific for mtO2•- production) intensities. Pretreatment with apocynin (NADPH oxidase inhibitor) or N-acetyl cysteine (antioxidant) significantly attenuated OSS-induced JNK activation. Apocynin further reduced OSS-mediated dihydroethidium and MitoSOX Red intensities specific for cytosolic O2•- and mtO2•- production, respectively. As a corollary, transfecting bovine aortic endothelial cells with JNK siRNA (siJNK) and pretreating with SP600125 (JNK inhibitor) significantly attenuated OSS-mediated mtO2•- production. Immunohistochemistry on explants of human coronary arteries further revealed prominent phosphorylated JNK staining in OSS-exposed regions. These findings indicate that OSS induces mtO2•- production via NADPH oxidase and JNK activation relevant for vascular oxidative stress.

Nanoplatforms for constructing new approaches to cancer treatment, imaging, and drug delivery: what should be the policy?

Nanotechnology is the design and assembly of submicroscopic devices called nanoparticles, which are 1-100 nm in diameter. Nanomedicine is the application of nanotechnology for the diagnosis and treatment of human disease. Disease-specific receptors on the surface of cells provide useful targets for nanoparticles. Because nanoparticles can be engineered from components that (1) recognize disease at the cellular level, (2) are visible on imaging studies, and (3) deliver therapeutic compounds, nanotechnology is well suited for the diagnosis and treatment of a variety of diseases. Nanotechnology will enable earlier detection and treatment of diseases that are best treated in their initial stages, such as cancer. Advances in nanotechnology will also spur the discovery of new methods for delivery of therapeutic compounds, including genes and proteins, to diseased tissue. A myriad of nanostructured drugs with effective site-targeting can be developed by combining a diverse selection of targeting, diagnostic, and therapeutic components. Incorporating immune target specificity with nanostructures introduces a new type of treatment modality, nano-immunochemotherapy, for patients with cancer. In this review, we will discuss the development and potential applications of nanoscale platforms in medical diagnosis and treatment. To impact the care of patients with neurological diseases, advances in nanotechnology will require accelerated translation to the fields of brain mapping, CNS imaging, and nanoneurosurgery. Advances in nanoplatform, nano-imaging, and nano-drug delivery will drive the future development of nanomedicine, personalized medicine, and targeted therapy. We believe that the formation of a science, technology, medicine law-healthcare policy (STML) hub/center, which encourages collaboration among universities, medical centers, US government, industry, patient advocacy groups, charitable foundations, and philanthropists, could significantly facilitate such advancements and contribute to the translation of nanotechnology across medical disciplines.

Mid-term to long-term clinical and functional outcomes of minimally invasive correction and fusion for adults with scoliosis.

OBJECT: The goal of this study was to assess the operative outcomes of adult patients with scoliosis who were treated surgically with minimally invasive correction and fusion. METHODS: This was a retrospective study of 28 consecutive patients who underwent minimally invasive correction and fusion over 3 or more levels for adult scoliosis. Hospital and office charts were reviewed for clinical data. Functional outcome data were collected at each visit and at the last follow-up through self-administered questionnaires. All radiological measurements were obtained using standardized computer measuring tools. RESULTS: The mean age of the patients in the study was 67.7 years (range 22-81 years), with a mean follow-up time of 22 months (range 13-37 months). Estimated blood loss for anterior procedures (transpsoas discectomy and interbody fusions) was 241 ml (range 20-2000 ml). Estimated blood loss for posterior procedures, including L5-S1 transsacral interbody fusion (and in some cases L4-5 and L5-S1 transsacral interbody fusion) and percutaneous screw fixation, was 231 ml (range 50-400 ml). The mean operating time, which was recorded from incision time to closure, was 232 minutes (range 104-448 minutes) for the anterior procedures, and for posterior procedures it was 248 minutes (range 141-370 minutes). The mean length of hospital stay was 10 days (range 3-20 days). The preoperative Cobb angle was 22 degrees (range 15-62 degrees ), which corrected to 7 degrees (range 0-22 degrees ). All patients maintained correction of their deformity and were noted to have solid arthrodesis on plain radiographs. This was further confirmed on CT scans in 21 patients. The mean preoperative visual analog scale and treatment intensity scale scores were 7.05 and 53.5; postoperatively these were 3.03 and 25.88, respectively. The mean preoperative 36-Item Short Form Health Survey and Oswestry Disability Index scores were 55.73 and 39.13; postoperatively they were 61.50 and 7, respectively. In terms of major complications, 2 patients had quadriceps palsies from which they recovered within 6 months, 1 sustained a retrocapsular renal hematoma, and 1 patient had an unrelated cerebellar hemorrhage. CONCLUSIONS: Minimally invasive surgical correction of adult scoliosis results in mid- to long-term outcomes similar to traditional surgical approaches. Whereas operating times are comparable to those achieved with open approaches, blood loss and morbidity appear to be significantly lower in patients undergoing minimally invasive deformity correction. This approach may be particularly useful in the elderly.

Ultrafine particles from diesel engines induce vascular oxidative stress via JNK activation.

Exposure to particulate air pollution is linked to increased incidences of cardiovascular diseases. Ambient ultrafine particles (UFP) from diesel vehicle engines have been shown to be proatherogenic in ApoE knockout mice and may constitute a major cardiovascular risk in humans. We posited that circulating nano-sized particles from traffic pollution sources induce vascular oxidative stress via JNK activation in endothelial cells. Diesel UFP were collected from a 1998 Kenworth truck. Intracellular superoxide assay revealed that these UFP dose-dependently induced superoxide (O(2)(-)) production in human aortic endothelial cells (HAEC). Flow cytometry showed that UFP increased MitoSOX red intensity specific for mitochondrial superoxide. Protein carbonyl content was increased by UFP as an indication of vascular oxidative stress. UFP also up-regulated heme oxygenase-1 (HO-1) and tissue factor (TF) mRNA expression, and pretreatment with the antioxidant N-acetylcysteine significantly decreased their expression. Furthermore, UFP transiently activated JNK in HAEC. Treatment with the JNK inhibitor SP600125 and silencing of both JNK1 and JNK2 with siRNA inhibited UFP-stimulated O(2)(-) production and mRNA expression of HO-1 and TF. Our findings suggest that JNK activation plays an important role in UFP-induced oxidative stress and stress response gene expression.