Directional atherectomy before paclitaxel coated balloon angioplasty in complex femoropopliteal disease: The VIVA REALITY study.

BACKGROUND: Drug coated balloon (DCB) angioplasty significantly reduces reintervention rates in patients with symptomatic femoropopliteal peripheral artery disease (PAD). However, stand-alone DCB use in long, severely calcified lesions is frequently associated with vessel recoil and/or high-grade dissections necessitating provisional stent implantation. OBJECTIVES: Assess the safety and effectiveness of a vessel preparation strategy with directional atherectomy (DA) prior to DCB angioplasty in patients with symptomatic severely calcified femoropopliteal PAD. METHODS: REALITY (NCT02850107) prospectively enrolled subjects at 13 multinational centers with 8-36 cm femoropopliteal stenoses or occlusions with bilateral vessel wall calcification treated with DA prior to DCB angioplasty. The primary effectiveness endpoint was 12-month primary patency, and the primary safety endpoint was freedom from major adverse events through 30 days. Independent angiographic and duplex core laboratories assessed outcomes and a Clinical Events Committee adjudicated events. RESULTS: A total of 102 subjects were enrolled; one lesion was treated per subject. The mean lesion length was 17.9 ± 8.1 cm, 39.0% were chronic total occlusions (mean lesion length 22.6 ± 8.6 cm); 86.2% of lesions exhibited moderate to severe bilateral calcification. Provisional stents were implanted in 8.8% (9/102) of subjects. Twelve-month primary patency rate was 76.7% (66/86) and freedom from CD-TLR rate was 92.6% (87/94). No device or procedure related deaths and one index-limb major amputation were reported. CONCLUSIONS: Plaque excision with DA in patients with symptomatic severely calcified femoropopliteal arterial disease prior to DCB angioplasty is a safe and effective treatment strategy with a low provisional stent rate.

Biallelic loss of human CTNNA2, encoding αN-catenin, leads to ARP2/3 complex overactivity and disordered cortical neuronal migration.

Neuronal migration defects, including pachygyria, are among the most severe developmental brain defects in humans. Here, we identify biallelic truncating mutations in CTNNA2, encoding αN-catenin, in patients with a distinct recessive form of pachygyria. CTNNA2 was expressed in human cerebral cortex, and its loss in neurons led to defects in neurite stability and migration. The αN-catenin paralog, αE-catenin, acts as a switch regulating the balance between ß-catenin and Arp2/3 actin filament activities1. Loss of αN-catenin did not affect ß-catenin signaling, but recombinant αN-catenin interacted with purified actin and repressed ARP2/3 actin-branching activity. The actin-binding domain of αN-catenin or ARP2/3 inhibitors rescued the neuronal phenotype associated with CTNNA2 loss, suggesting ARP2/3 de-repression as a potential disease mechanism. Our findings identify CTNNA2 as the first catenin family member with biallelic mutations in humans, causing a new pachygyria syndrome linked to actin regulation, and uncover a key factor involved in ARP2/3 repression in neurons.

Biallelic Mutations in Citron Kinase Link Mitotic Cytokinesis to Human Primary Microcephaly.

Cell division terminates with cytokinesis and cellular separation. Autosomal-recessive primary microcephaly (MCPH) is a neurodevelopmental disorder characterized by a reduction in brain and head size at birth in addition to non-progressive intellectual disability. MCPH is genetically heterogeneous, and 16 loci are known to be associated with loss-of-function mutations predominantly affecting centrosomal-associated proteins, but the multiple roles of centrosomes in cellular function has left questions about etiology. Here, we identified three families affected by homozygous missense mutations in CIT, encoding citron rho-interacting kinase (CIT), which has established roles in cytokinesis. All mutations caused substitution of conserved amino acid residues in the kinase domain and impaired kinase activity. Neural progenitors that were differentiated from induced pluripotent stem cells (iPSCs) derived from individuals with these mutations exhibited abnormal cytokinesis with delayed mitosis, multipolar spindles, and increased apoptosis, rescued by CRISPR/Cas9 genome editing. Our results highlight the importance of cytokinesis in the pathology of primary microcephaly.

Outcomes of reinterventions after subintimal angioplasty.

OBJECTIVE: With increased use of subintimal angioplasty (SIA), the role of reintervention after recurrence is currently unknown. To more clearly define the technical feasibility, patency, and clinical outcomes of reinterventions after SIA, we reviewed our cumulative experience. METHODS: A retrospective review of patient information (including demographics, indications, procedures, noninvasive arterial studies, and postprocedural events) was performed on those patients undergoing reintervention after a primary subintimal angioplasty in the infrainguinal vessels. Continuous and noncontinuous data were compared using the Student t-test and the z test, respectively. Patency was calculated by Kaplan-Meier analysis. Survival curves were compared using log-rank and Wilcoxon testing for univariate analysis and Cox hazard-regression analysis for multivariate analysis. RESULTS: From December 2002, through July 2006, 495 SIAs were performed for infrainguinal disease in 482 patients. Of this cohort, 121 patients (25%) required 188 consecutive reinterventions. Each patient underwent an average of 1.5 +/- 0.8 (range, 1-7) reinterventions during this study. We analyzed only the outcomes of 124 consecutive, first reinterventions. Mean interval time between primary SIA and the first reintervention was 7.8 +/- 6.8 months (range, 1 day-31 months). Indications for reintervention were clinical only (recurrence of symptoms or worsening exam), diagnostics only (recurrence based on peripheral vascular lab studies), or both in 18%, 25%, and 52% of patients, respectively. Technical success was achieved in 94% (n = 117) of the procedures. Repeat SIA technique was utilized in 68% (n = 84) of reinterventions and other endovascular therapies (32%; n = 40), of which the majority were transluminal angioplasty, for the remaining reinterventions. Mean follow-up was 8.6 months (range, 0-34 months). The patency rate at 1 year for the first reintervention was 33%. One-year patency rates for reinterventions performed within 3 months of the primary SIA were worse than those performed after 3 months (22% vs 34%; P = .04). In addition, patients treated for claudication had better 1-year patency than those treated for critical limb ischemia (37% vs 27%; P = .03). Other demographic or procedural variables did not significantly affect patency. In patients with critical limb ischemia (CLI), limb salvage rate at 1 year was 71%. CONCLUSION: Endovascular reintervention after SIA is a safe and technically feasible procedure for recurrences and offers good limb salvage rate. Early reinterventions performed within 3 months of the original SIA portend a worse outcome. In addition, reinterventions are less durable in patients with CLI compared with claudication. Finally, by identifying a recurrent stenosis instead of an occlusion, close surveillance may contribute to improved overall outcome.

Successful repair of a ruptured Stanford type B aortic dissection during pregnancy.

We present our experience with an acute Stanford type B aortic dissection in a 25-year-old, 26-week gravid patient without a known connective tissue disorder and discuss a literature-based treatment strategy. After failed conservative treatment manifest by aneurysm rupture, emergency cesarean section delivery and immediate repair of her thoracic aorta was performed. Seven months later, she is fully caring for her healthy baby. During pregnancy, thoracic aortic dissection occurs from physiologic and hemodynamic changes. Emergency cesarean delivery, followed by immediate aortic repair, is the treatment choice if malperfusion syndrome, rupture, uncontrolled hypertension, or unremitting pain occurs.

Selective stenting in subintimal angioplasty: analysis of primary stent outcomes.

OBJECTIVE: Subintimal angioplasty (SIA) is being increasingly utilized to treat chronic arterial occlusions. The role of stents in SIA is currently unknown. We performed a retrospective review of selective stent use in SIA to assess outcomes and factors affecting these results. METHODS: A retrospective review of patient information--including demographics, indications, procedures, noninvasive studies, and post-procedural events--was performed on our database for patients undergoing SIA in the superficial femoral and popliteal arteries. Outcomes were calculated only on technically successful SIAs using Kaplan-Meier survival analysis. Continuous and non-continuous data were compared using the Student t test and the z test, respectively. Survival curves were compared using log-rank testing for univariate analysis and Cox hazard-regression analysis for multivariate analysis. RESULTS: Three-hundred-sixty-eight patients (382 limbs) underwent femoral and/or popliteal SIA for critical limb ischemia or disabling claudication from December 1, 2002 through July 31, 2006. Eighty-four limbs (22%) had a stent placed, while 298 (78%) did not receive a stent. Mean follow-up was 11.7 months (range, 0-45 months). One-year primary and secondary patency for stent vs no-stent group was 50% vs 45% (P = .73) and 70% vs 78% (P = .47), respectively. One-year limb salvage rate for the stent vs no-stent group was 85% vs 90% (P = .61). At 2 years, patients receiving a stent are more likely to undergo open bypass than those without a stent (P = .06). Eighty-three patients underwent 84 SIA with stent placement. The mean number of stents for each case was 1.4 +/- 0.7. Univariate analysis revealed that previous ipsilateral bypass surgery significantly decreased 1-year patency: 35% vs 56% (P = .05). SIA performed for disabling claudication had a trend toward improved 1-year patency 58% vs 39% for critical limb ischemia (P = .09). A stent diameter > or =7 mm displayed a trend toward better patency 53% vs 37% for diameter < or =6 mm (P = .08). None of these factors proved significant with multivariate analysis. CONCLUSION: Selective stents placed for suboptimal results after subintimal angioplasty produce similar patency rates to primary SIA without stents. Patients receiving stents with prior lower extremity bypass surgery will have worse outcomes than those without. Use of a stent diameter < or =6 mm and indication of critical limb ischemia will likely produce worse results. It appears that other stent variables (location, number, length, and overlap) do not alter patency. Finally, selective stent use after SIA provides excellent limb salvage.

Subintimal angioplasty: Our experience in the treatment of 506 infrainguinal arterial occlusions.

OBJECTIVE: The treatment of patients with chronic arterial occlusions involving the superficial femoral artery has changed significantly with the incorporation of subintimal angioplasty (SIA) into vascular surgery practice. To more clearly define technical feasibility, patency, and clinical outcomes of SIA, we reviewed our cumulative experience. METHODS: A retrospective review of all patients who underwent SIA of arterial occlusions originating in the superficial femoral artery was performed. Patient history, demographics, procedural details, and follow-up information were collected and analyzed. Patency, limb salvage, sustained improvement in claudication, freedom from surgical bypass, and survival were determined by Kaplan-Meier analysis. RESULTS: From December, 2002, through July, 2006, 506 infrainguinal SIA procedures were performed in 472 patients with chronic arterial occlusion involving the superficial femoral artery. The mean age of patients treated was 69.4 +/- 11.9 years and the indication for intervention was critical limb ischemia in 63% of limbs (n = 317) and disabling claudication in 37% (n = 189). Forty-seven percent of limbs (n = 237) had isolated SFA occlusions, 40% (n = 205) had femoropopliteal occlusions, and 13% of limbs had occlusions beginning in the SFA and extending into the tibial arteries (n = 64). Technical success was achieved in 87% of procedures. Following successful SIA, the mean ankle-brachial index increased by 54%, from 0.50 +/- 0.16 to 0.77 +/- 0.23 (P < .0001). Median follow-up was 12.4 months (0-48 months) and 30-day mortality was 0.8%. Primary patency at 12 and 36 months was 45% (SE 3.0%) and 25% (SE 3.6%) respectively. Secondary patency was 76% (SE 2.6%) and 50% (SE 4.8%) at 12 and 36 months. Factors associated with reduced primary patency included femorotibial occlusions (HR 1.57, CI 1.05-2.36) and the presence of critical limb ischemia (HR 1.39, CI 1.02-1.89). Limb salvage in patients with critical limb ischemia was 75% (SE 5.9%) at 36 months. Freedom from surgical bypass in patients with either critical limb ischemia or disabling claudication was 77% (SE 4.1%) at 36 months. CONCLUSION: SIA is an effective percutaneous technique for the revascularization of patients with lower extremity chronic arterial occlusions involving the superficial femoral artery. The procedure is successfully performed in all segments of the lower extremity with minimal morbidity or mortality. Rates of limb salvage and improvement in claudication are similar to those achieved by open surgical bypass, while modest reductions in limb salvage and primary patency are experienced in limbs with femorotibial occlusions.

The natural history of autologous fistulas as first-time dialysis access in the KDOQI era.

BACKGROUND: Patients on hemodialysis depend on durable, easily maintained vascular access. The autologous arteriovenous fistula (AVF) has been the gold standard since the introduction of the Brecia-Cimino fistula in 1966 and is echoed in the current Kidney Disease Outcomes and Quality Initiative (KDOQI) guidelines. The purpose of this study is to determine the natural history of AVF in patients requiring first-time permanent access in a large academic vascular surgery practice. METHODS: We performed a retrospective review of patients undergoing new access creation from January 1, 2005 to June 30, 2005. The study group consisted of patients with no prior permanent access that underwent AVF creation. Categorical data was compared using chi2 analysis, nominal data was compared using Student t-test, and patency was determined by Kaplan-Meier curves. RESULTS: During the 6-month period, there were 80 first time AVF creations. The majority of patients were male (69%), African American (55%), and a history of diabetes (55%) and hypertension (96%). Seventy-five percent of patients were already undergoing hemodialysis via catheter access. Seventy-six percent of patients underwent preoperative vein mapping with a mean vein diameter of 3.1 mm. Twenty-six radiocephalic AVF (RCAVF) and 54 brachiocephalic AVF (BCAVF) were created with a mean follow-up of 278 days. At the end of follow-up, 38 (48%) AVF were being used for hemodialysis and only nine (11%) matured without the need for additional intervention. Mean time for AVF maturation was 146 days. Thirty AVF (37%) were abandoned, 16 (20%) of which were primary failures. Mean time to abandonment was 162 days. Twelve (15%) AVF remained patent but were never cannulated. The intervention rate was 1.33 interventions/patient/year and 75% of interventions were percutaneous. Kaplan-Meier analysis determined primary, primary-assisted, and secondary patency was 36% +/- 8.3, 55% +/- 6.5, and 55% +/- 6.5 at 1 year, respectively. Cumulative functional patency was 63% at 1 year. CONCLUSIONS: In patients receiving a first time permanent access, we found that the majority were AVF and they resulted in low primary patency rates at 1 year and long maturation times. KDOQI encourages AVF creation in order to increase AVF use for dialysis, but the strategy of simply increasing the number being created may not lead to the desired result and potentially lead to an increase in catheter dependence.

Subintimal angioplasty for the treatment of claudication and critical limb ischemia: 3-year results.

OBJECTIVE: Subintimal angioplasty (SIA) is an increasingly used method of lower extremity revascularization for patients with chronic arterial occlusions. To assess the technical feasibility, safety, and 3-year outcomes of patients treated with SIA, we performed a retrospective review of our early experience. METHODS: Patient information-including demographics, indications, procedures, noninvasive arterial studies, and postprocedural events-was recorded in a database. Outcomes were determined on an intention-to-treat basis, as well as by technical success, by using Kaplan-Meier survival analysis. Continuous data were compared by using the Student t test, and survival curves were compared by log-rank testing. RESULTS: From December 2002 through December 2003, 104 patients (105 limbs) underwent SIA of 159 occlusive lesions involving the iliac (n = 10), superficial femoral (n = 85), popliteal (n = 48), or tibial (n = 16) arteries. Sixty-six (62.9%) patients were treated for critical limb ischemia, and 39 patients (37.1%) were treated for disabling claudication. Technical success was achieved in 91 procedures (86.7%) and resulted in a mean increase in ankle-brachial index of 0.36 +/- 0.16. The mean follow-up was 23.4 months (range, 0-46 months). During this period, 18 patients (17.0%) died, and 15 amputations (14.3%) were performed, 6 of which were performed for patients on whom SIA had been unsuccessful. In patients undergoing successful SIA, the primary patency was 55%, 43%, and 35% at 12, 24, and 36 months, respectively. Twenty-one patients underwent a total of 23 percutaneous procedures to maintain or restore patency of the SIA during the study period. This resulted in secondary patency rates of 71%, 63%, and 51% at 12, 24, and 36 months, respectively. Multivariate analysis revealed critical limb ischemia to be the only predictor of reduced primary patency. Fifteen patients with inoperable critical limb ischemia underwent successful SIA. Limb salvage in this group was 54% and 43% at 12 and 36 months, respectively. Limb salvage in operative candidates was 100% and 88% at the same intervals. In patients with disabling claudication, 94% experienced improvement in symptoms 3 months after the procedure, and 68% of patients reported sustained improvement at 36 months. In all operative candidates successfully treated with SIA, freedom from surgical bypass was 83% and 73% at 12 and 36 months, respectively. CONCLUSIONS: SIA for the treatment of lower extremity chronic arterial occlusions is technically feasible, results in minimal morbidity, and provides satisfactory revascularization without surgical bypass. Secondary patency is comparable to that of autologous vein bypass and is achieved with a low rate of reintervention. When used as first-line therapy, SIA provides most patients with limb salvage and freedom from surgical bypass at 3 years.

Conduits for hemodialysis access.

The role of prosthetic arteriovenous (AV) access is still important in the management and care of the renal dialysis patients. Multiple new modalities are available to the surgeon today and it is imperative that their role be understood so that optimum care can be delivered to this complex group of patients. This article describes significant changes in prosthetic management and newer configurations available to the surgeon.