Systemic single administration of anti-inflammatory microRNA 146a-5p loaded in polymeric nanomedicines with active targetability attenuates neointimal hyperplasia by controlling inflammation in injured arteries in a rat model.

Neointimal hyperplasia (NIH) after revascularization is a key unsolved clinical problem. Various studies have shown that attenuation of the acute inflammatory response on the vascular wall can prevent NIH. MicroRNA146a-5p (miR146a-5p) has been reported to show anti-inflammatory effects by inhibiting the NF-κB pathway, a well-known key player of inflammation of the vascular wall. Here, a nanomedicine, which can reach the vascular injury site, based on polymeric micelles was applied to deliver miR146a-5p in a rat carotid artery balloon injury model. In vitro studies using inflammation-induced vascular smooth muscle cell (VSMC) was performed. Results showed anti-inflammatory response as an inhibitor of the NF-κB pathway and VSMC migration, suppression of reactive oxygen species production, and proinflammatory cytokine gene expression in VSMCs. A single systemic administration of miR146a-5p attenuated NIH and vessel remodeling in a carotid artery balloon injury model in both male and female rats in vivo. MiR146a-5p reduced proinflammatory cytokine gene expression in injured arteries and monocyte/macrophage infiltration into the vascular wall. Therefore, miR146a-5p delivery to the injury site demonstrated therapeutic potential against NIH after revascularization.

Short interposition with a small-diameter prosthetic graft for flow reduction of a high-flow arteriovenous fistula.

OBJECTIVE: The objective of this study was to evaluate the outcome of a short interposition using a small-diameter prosthetic graft as a flow-limiting procedure to manage symptomatic high-flow arteriovenous fistula (AVF). METHODS: A retrospective review of medical records on a case series was conducted. From June 2004 to April 2017, there were 25 patients with clinical symptoms of high output cardiac failure and progressive dilation of aneurysmal fistula vein due to high-flow AVF (≥1.5 L/min) who underwent short interposition with a 5-mm prosthetic graft at Saitama Medical Center. The primary outcome was the relief of clinical symptoms; other outcome measures included technical success, surgical complications, patency of vascular access, and postoperative changes in local and systemic hemodynamics as assessed by Doppler ultrasound. RESULTS: Twenty-five patients underwent short interposition for cardiac indications (n = 16) and aneurysmal dilation (n = 9). The technical success rate was 100%. The clinical symptoms were relieved in 24 patients (96.0%). Mean reduction in access blood flow was 52.4%. Cumulative primary unassisted patency rates (± standard error) at 1 year, 2 years, and 3 years were 76.2% ± 9.3%, 70.4% ± 10.3%, and 58.1% ± 11.6%, respectively. Secondary patency rates (± standard error) at 1 year, 2 years, and 3 years were 81.8% ± 8.2%, 71.5% ± 9.9%, and 71.5% ± 9.9%, respectively. Complications included access occlusion due to late thrombosis (n = 5 [21.7%]) and graft infection (n = 1 [4.3%]) in the median follow-up period of 3.9 years. CONCLUSIONS: Short interposition with a prosthetic graft is a simple, effective, and durable treatment option for end-stage renal disease patients with cardiac symptoms and progressive dilation of the fistula vein due to high-flow AVF, offering clinical symptom resolution while preserving the autologous behavior of the initial access.

Proresolving Lipid Mediators Resolvin D1 and Protectin D1 Isomer Attenuate Neointimal Hyperplasia in the Rat Carotid Artery Balloon Injury Model.

BACKGROUND: Specialized proresolving mediators from ω-3 polyunsaturated fatty acid may control resolution of inflammation. We evaluated the influence of two specialized proresolving mediators, resolvin D1 (RvD1) and protectin D1 isomer (PD1 iso) on neointimal hyperplasia after balloon injury. MATERIALS AND METHODS: Sprague Dawley male rats at 12-14 wk of age were injured as a model of balloon angioplasty. Then, 1 µg/rat of RvD1 or PD1 iso was administered intravenously via the tail vein immediately and 2 d after angioplasty. The proliferation of injured artery and the infiltration of leukocytes, monocytes, and macrophages at 3 d after injury were evaluated by immunostaining. The activity of the inflammatory transcription factor nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) in the injured artery at 3 d after injury was evaluated using an enzyme-linked immuno sorbent assay kit. The proliferation of the neointima was evaluated by calculating the ratio of the neointimal and medial areas using specimens at 14 d after injury. RESULTS: RvD1 and PD1 iso attenuated proliferation of medial cells (P < 0.05) and infiltration of leukocytes (P < 0.05) and monocytes/macrophages (P < 0.01). Although both RvD1 and PD1 iso mitigated NFκB activity (P < 0.01), RvD1 attenuated this activity more strongly (P < 0.01). RvD1 decreased neointimal hyperplasia by 37.3% (P < 0.01), whereas PD1 iso decreased neointimal hyperplasia by 31.8% (P < 0.05) (RvD1 versus PD1 iso: P = 0.51). CONCLUSIONS: RvD1 and PD1 iso reduced the activity of inflammatory transcription factor NFκB within the injured artery and attenuated inflammatory cell infiltration, leading to a reduction in early inflammation and subsequent neointimal hyperplasia.

Increase in skin perfusion pressure predicts amputation-free survival after lower extremity bypass surgery for critical limb ischemia.

The objective of this study was to determine how postoperative skin perfusion pressure (SPP) as a measure of blood flow after revascularization affects limb prognosis in patients with critical limb ischemia (CLI). We retrospectively reviewed 223 consecutive bypass surgery cases performed in 192 patients with CLI during a 10-year period. SPP was measured 1-2 weeks before and after the procedure. An SPP of 40 mmHg was set as the cut-off value for revascularization. Patients were grouped according to their postoperative SPPs, and amputation-free survival (AFS) was analyzed. An SPP of ≥ 40 mmHg was recovered in 75% of the patients, but no significant difference was found between this group and the group that did not reach 40 mmHg. On the other hand, the values increased by ≥ 20 mmHg from the preoperative values in 70% of the patients. This group had a significantly better AFS than the group that did not increase by 20 mmHg. Logistic regression analysis revealed that (1) a preoperative SPP of < 20 mmHg and (2) a high serum albumin level (> 3.0 g/dL) were significant factors in increasing SPP by 20 mmHg. These results showed that an increase in SPP of ≥ 20 mmHg after bypass surgery was associated with better limb prognosis.

The relationship between medical expenses and the severity of peripheral arterial disease in Japan.

The main objective is to examine whether the severity of peripheral arterial disease (PAD) affects the expenses and hospital stay of the patients who undergo bypass surgery below the inguinal ligament for PAD. Eighty consecutive patients who underwent infrainguinal bypass surgery for PAD between January 2012 and December 2014 were included in the study. Patients were divided into groups according to their critical limb ischemia (CLI) symptoms and the Wound, Ischemia, and Foot Infection (WIfI) classification. As endpoints, we assessed the duration of postoperative hospital stay and expenses during hospitalization. CLI was a significant factor for longer hospital stay and increased medical expenses (p = 0.009 and p = 0.001). In the patients with CLI, significant factors for longer hospital stay and increased medical expenses were (1) history of distal bypass (p = 0.33 and p = 0.003, respectively) and stage 4 local lower limb status in WIfI classification (p = 0.0007 and p = 0.053). PAD severity was associated with prolonged postoperative hospital stay and increased medical expenses. The presence or absence of CLI and its severity according to the WIfI classification correlated with medical expenses and hospital stay duration between the milder and severe groups.

Lithocholic Acid Is a Vitamin D Receptor Ligand That Acts Preferentially in the Ileum.

The vitamin D receptor (VDR) is a nuclear receptor that mediates the biological action of the active form of vitamin D, 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3], and regulates calcium and bone metabolism. Lithocholic acid (LCA), which is a secondary bile acid produced by intestinal bacteria, acts as an additional physiological VDR ligand. Despite recent progress, however, the physiological function of the LCA−VDR axis remains unclear. In this study, in order to elucidate the differences in VDR action induced by 1,25(OH)2D3 and LCA, we compared their effect on the VDR target gene induction in the intestine of mice. While the oral administration of 1,25(OH)2D3 induced the Cyp24a1 expression effectively in the duodenum and jejunum, the LCA increased target gene expression in the ileum as effectively as 1,25(OH)2D3. 1,25(OH)2D3, but not LCA, increased the expression of the calcium transporter gene Trpv6 in the upper intestine, and increased the plasma calcium levels. Although LCA could induce an ileal Cyp24a1 expression as well as 1,25(OH)2D3, the oral LCA administration was not effective in the VDR target gene induction in the kidney. No effect of LCA on the ileal Cyp24a1 expression was observed in the VDR-null mice. Thus, the results indicate that LCA is a selective VDR ligand acting in the lower intestine, particularly the ileum. LCA may be a signaling molecule, which links intestinal bacteria and host VDR function.

Outcomes in Patients with Critical Limb Ischemia due to Arteriosclerosis Obliterans Who Did Not Undergo Arterial Reconstruction.

The prevalence of arteriosclerosis obliterans (ASO) and critical limb ischemia (CLI) is currently increasing, and arterial reconstruction is often attempted to salvage the limb. Some patients cannot undergo attempted revascularization because of contraindications, and they only receive conservative treatment. In this study, we investigate the comorbidities and survival rates of patients with CLI who receive conservative treatment. Thirty-five patients with CLI due to ASO, who had not undergone revascularization surgery (C group), were enrolled. As controls, 136 patients with CLI due to ASO who did undergo revascularization (R group), mainly via bypass surgery, were enrolled. Coronary artery disease, heart failure, and respiratory dysfunction were factors indicating conservative treatment. Limb salvage rates and survival rates were not significantly different between the two groups. Patients who had survived for less than two years after surgery had a higher prevalence of chronic heart failure, cardiovascular disease, and end-stage renal disease compared to patients who had survived for more than two years. The use of statins, dual antiplatelets, aspirin, or warfarin did not influence whether a patient survived for longer than two years. 77% of patients survived for more than two years after receiving only conservative therapies. Surgical revascularization did not improve the prognosis of patients with CLI as compared with the conservative therapy. Clinicians might start with conservative treatment while considering other treatment options for patients with CLI.

Favorable outcomes of very elderly patients with critical limb ischemia who undergo distal bypass surgery.

OBJECTIVE: To determine the midterm outcomes of distal bypass surgery for very elderly patients, and to determine the ideal candidates for this procedure. METHODS: Of 268 consecutive patients (328 limbs) with critical limb ischemia who were treated between 2006 and 2013, 106 (126 limbs) underwent distal bypass and were retrospectively reviewed. Nineteen patients (22 limbs) were aged ≥80 years (very elderly group) and 87 patients (104 limbs) were aged <80 years (control group). RESULTS: The baseline characteristics differed between the 2 groups in terms of regular hemodialysis rate (very elderly group, 4 [21%] vs control group, 60 [69%]; P = .0002) and the Charlson comorbidity index (very elderly group, 3.2 ± 1.7 vs control group, 5.0 ± 2.0; P = .0005). According to the Rutherford category of limb ischemia (4/5/6), the very elderly and control groups were classified as 5/17/0 and 11/87/6, respectively (P = .18). Before the surgery, 17 patients (77%) and 67 patients (64%) were ambulatory in the very elderly and control groups, respectively. At follow-up at 29 ± 22 months, the rates of primary (P = .33) and secondary patency (P = .14), limb salvage (P = .50), survival (P = .26), amputation-free survival (P = .42), major adverse limb event and also perioperative death (P = .11), and major adverse cardiovascular events (P = .36) did not significantly differ between the groups. In multivariate analysis, a history of coronary artery disease (hazard ratio [HR], 2.7; 95% confidence interval [CI], 1.3-5.9; P = .005), preoperative nonambulatory status (HR, 4.2; 95% CI, 2.1-8.1; P < .0001), and serum albumin levels <3 g/dL (HR, 2.7; 95% CI, 1.3-5.4; P = .01) were significantly related to poor amputation-free survival. Thirteen patients (59%) remained ambulatory at the latest follow-up. In 91 patients (110 limbs) with tissue loss, the Society for Vascular Surgery lower extremity threatened limb classification system: risk stratification based on Wound, Ischemia, and foot Infection classification stages 3 and 4 negatively affected complete wound healing, according to multivariate analysis (HR, 0.34; 95% CI, 0.20-0.61; P = .0005). CONCLUSIONS: A very elderly age should not preclude a patient from undergoing distal bypass surgery. A history of coronary artery disease, a nonambulatory status, and hypoalbuminemia, along with the Wound, Ischemia, and foot Infection classification for patients with tissue loss, should be carefully considered to obtain the most benefit from distal bypass surgery.

Systemic delivery of proresolving lipid mediators resolvin D2 and maresin 1 attenuates intimal hyperplasia in mice.

Vascular injury induces a potent inflammatory response that influences vessel remodeling and patency, limiting long-term benefits of cardiovascular interventions such as angioplasty. Specialized proresolving lipid mediators (SPMs) derived from ω-3 polyunsaturated fatty acids [eicosapentaenoic acid and docosahexaenoic acid (DHA)] orchestrate resolution in diverse settings of acute inflammation. We hypothesized that systemic administration of DHA-derived SPMs [resolvin D2 (RvD2) and maresin 1 (MaR1)] would influence vessel remodeling in a mouse model of arterial neointima formation (carotid ligation). In vitro, SPM treatment inhibited mouse aortic smooth muscle cell migration (IC50 ≅ 1 nM) to a PDGF gradient and reduced TNF-α-stimulated p65 translocation, superoxide production, and proinflammatory gene expression (MCP-1). In vivo, adult FVB mice underwent unilateral carotid artery ligation with administration of RvD2, MaR1, or vehicle (100 ng by intraperitoneal injection at 0, 1, 3, 5, and 7 d after ligation). In ligated carotid arteries at 4 d, SPM treatment was associated with reduced cell proliferation and neutrophil and macrophage recruitment and increased polarization of M2 macrophages in the arterial wall. Neointimal hyperplasia (at 14 d) was notably attenuated in RvD2 (62%)- and MaR1 (67%)-treated mice, respectively. Modulation of resolution pathways may offer new opportunities to regulate the vascular injury response and promote vascular homeostasis.

Endovascular Stent Graft Placement and Coil Embolization for Splenic Artery Aneurysm with an Anatomical Variant.

A 62-year-old woman with abdominal pain was diagnosed with a splenic artery aneurysm (SAA) and an anatomical variant in the splenic artery (SA) arising from the superior mesenteric artery (SMA) as its first branch. To treat the SAA, the draining artery and a small branch of the SAA were embolized, and then small-diameter stent grafts were deployed from SMA orifice, covering the aberrant origin of the SA and preserving the second branch of SMA. Intraoperative angiography confirmed successful exclusion of the SAA without endoleak or arterial dissection. The stent graft was patent and the aneurysm had shrunk 3.5 years after the operation.

Vitamin D receptor activation enhances benzo[a]pyrene metabolism via CYP1A1 expression in macrophages.

Benzo[a]pyrene (BaP) activates the aryl hydrocarbon (AHR) and induces the expression of genes involved in xenobiotic metabolism, including CYP1A1. CYP1A1 is involved not only in BaP detoxification but also in metabolic activation, which results in DNA adduct formation. Vitamin D receptor (VDR) belongs to the NR1I subfamily of the nuclear receptor superfamily, which also regulates expression of xenobiotic metabolism genes. We investigated the cross-talk between AHR and VDR signaling pathways and found that 1α,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)], a potent physiological VDR agonist, enhanced BaP-induced transcription of CYP1A1 in human monocytic U937 cells and THP-1 cells, breast cancer cells, and kidney epithelium-derived cells. 1,25(OH)(2)D(3) alone did not induce CYP1A1, and 1,25(OH)(2)D(3) plus BaP did not increase CYP1A2 or CYP1B1 mRNA expression in U937 cells. The combination of 1,25(OH)(2)D(3) and BaP increased CYP1A1 protein levels, BaP hydroxylation activity, and BaP-DNA adduct formation in U937 cells and THP-1 cells more effectively than BaP alone. The combined effect of 1,25(OH)(2)D(3) and BaP on CYP1A1 mRNA expression in U937 cells and/or THP-1 cells was inhibited by VDR knockdown, VDR antagonists, and α-naphthoflavone, an AHR antagonist. Electrophoretic mobility shift assays and chromatin immunoprecipitation assays showed that VDR directly bound to an everted repeat (ER) 8 motif in the human CYP1A1 promoter. Thus, CYP1A1 is a novel VDR target gene involved in xenobiotic metabolism. Induction of CYP1A1 by the activation of VDR and AHR may contribute to BaP-mediated toxicity and the physiological function of this enzyme.

Successful endovascular repair of iliac artery aneurysms with unsuitable anatomy by combining unibody bifurcated endograft and iliac branch systems to preserve hypogastric artery blood flow: a report of two cases.

BACKGROUND: To overcome the anatomical limitation of a narrow aorta and short length from the renal artery to the terminal aorta, unibody endograft AFX2 and iliac branch endoprosthesis (IBE) can be combined. CASE PRESENTATION: Case 1: The first patient was an 89-year-old woman who had a right saccular common iliac artery (CIA) aneurysm (38 mm); the abdominal aorta was not aneurysmal (diameter, 19 mm). The right CIA's origin was 10 mm in diameter. A bifurcated AFX2 was placed in an ordinary manner. Then, IBE was inserted in the right leg of the AFX2. Case 2: The second patient was an 87-year-old man diagnosed with an abdominal aortic aneurysm (55 mm), right dissecting CIA aneurysm (20 mm), and right hypogastric artery aneurysm (22 mm) extending to the bifurcation of the superior and inferior gluteal arteries. The length between the renal artery and terminal aorta was 107 mm. The beginning of the right CIA was segmentally stenotic (13 mm). A bifurcated AFX2 was placed in the infrarenal aorta; IBE was advanced to the origin of the right limb of the AFX2. To control the type 1b endoleak, the right superior gluteal artery was embolized with coils and internal iliac components were deployed toward the inferior gluteal artery. Satisfactory results were obtained in both cases. CONCLUSION: The AFX2 main body and IBE could be combined to preserve hypogastric blood flow and overcome anatomical limitations.

Clinical Impact of Stent Graft Thrombosis in Femoropopliteal Arterial Lesions.

OBJECTIVES: This study sought to elucidate the clinical impact and prognosis of stent graft (SG) thrombosis. BACKGROUND: The VIABAHN SG offers a favorable outcome in long peripheral artery occlusive disease (PAOD) lesions in the femoropopliteal artery. One concern after SG deployment is the incidence of stent thrombosis and consequent acute limb ischemia (ALI). METHODS: In this retrospective multicenter study, we collected the clinical data of PAOD patients treated with VIABAHN SG who subsequently experienced SG thrombosis. The clinical symptoms of SG thrombosis, patency after reintervention, and predictors of loss of patency after reintervention were examined. RESULTS: VIABAHN SGs were used for 1,215 patients; SG thrombosis occurred in 159 (13%) patients at a median of 6.4 months (interquartile range: 2.8 to 13.5 months) after SG implantation; 21 (13%) patients presented with ALI. A total of 131 (82%) patients underwent reintervention for SG thrombosis, whereas 2 (1%) underwent primary major amputation and the remaining 26 (16%) were treated conservatively. The patency rate 1 year after reintervention, freedom from major adverse limb events, and limb salvage after reintervention were 54.9%, 73.6%, and 92.5%, respectively. Critical limb-threatening ischemia at SG implantation and ALI presentation at SG thrombosis were positively associated with an increased risk of rethrombosis, whereas distal stent diameter was negatively associated with the risk of rethrombosis. CONCLUSIONS: SG thrombosis is associated with a considerable risk of ALI, but the risk of primary major amputation was not high. Clinical outcomes after reinterventions for thrombosed SGs were suboptimal.

Wound healing after revascularization for critical limb ischemia.

BACKGROUND: Wound healing is one of the most important endpoints after revascularization for critical limb ischemia. The purpose of this study was to evaluate the risk factors for wound healing after revascularization for critical limb ischemia (CLI). METHODS: A retrospective study was conducted at a single university hospital, and data were collected retrospectively between January 2005 and September 2016. All admitted patients who were diagnosed with CLI and underwent revascularization for the first time were enrolled. The risk factors for wound healing were analyzed. RESULTS: The risk factors for wound healing were analyzed in 153 patients. The cumulative rate of wound healing at 12 months after revascularization was 79%. The independent risk factors for wound healing were non-ambulatory status (hazard ratio, 1.95; 95% CI [1.22-3.21], P=0.004), and wound, ischemia and foot infection (WIfI) stage 4 (hazard ratio, 1.89; 95% CI [1.25-2.91], P=0.002). CONCLUSIONS: In our study, non-ambulatory status and WIfI stage 4 were independent risk factors for wound healing after revascularization. WIfI criteria well reflected the prognosis of patients with CLI in wound healing, as well as limb salvage.

Drug Therapy for Abdominal Aortic Aneurysms Utilizing Omega-3 Unsaturated Fatty Acids and Their Derivatives.

BACKGROUND: Abdominal aortic aneurysms (AAA) are life-threatening because of the potential for rupture, resulting in death. The current standard treatment for AAA is surgery, comprising laparotomic graft replacement and endovascular repair. However, because surgery carries the risk of major complications and re-intervention, drug therapies are desirable because they may reduce the occurrence of enlargement and rupture. OBJECTIVE: Recent research shows that the progression of AAA is related to inflammatory reactions, especially those in the NF-κB pathway. Omega-3 polyunsaturated fatty acids (PUFA) show antiinflammatory effects. Some derivatives of omega-3 PUFA are known as specialized pro-resolving lipid mediators (SPM) such as resolvins. They play an important role in resolving inflammation. CONCLUSION: Omega-3 PUFA and SPM may show promised effects for drug treatment of AAA.

Targeting ability of self-assembled nanomedicines in rat acute limb ischemia model is affected by size.

Peripheral artery disease (PAD) is one of the most spreading diseases all over the world. The treatment strategies are limited to surgical or endovascular procedures for final stage chronic PAD or acute limb ischemia, and no pharmacological approaches have been achieved to prevent the worsening of chronic PAD or to regenerate the tissues of acute limb ischemia. Therefore, the improvement of therapeutic strategy is strongly demanded in clinics. Here, we adopted an acute hindlimb ischemia model in rats, which provides concomitant inflammatory response, to evaluate the application of drug delivery system against PAD. Through comparative experiments by using different-sized nanomedicine analogues, polyion complex (PIC) micelles with 30 nm diameter and PIC vesicles with 100- and 200-nm diameter (PICs-30, -100, -200 respectively), we found the size-dependent accumulation and retention in the collateral arteries. In contrast to PICs-30 and -200, histological analysis showed that PICs-100 were around the arterioles and co-localized with macrophages, which indicates that the PICs-100 can achieve moderate interaction with phagocytes. Our data suggests that controlling the size of nanomedicines has promise for developing novel angiogenic treatments toward the effective management of collateral arteries.

1α,25-Dihydroxyvitamin D3 enhances TRPV6 transcription through p38 MAPK activation and GADD45 expression.

The active form of vitamin D, 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3], acts as a ligand for the vitamin D receptor (VDR), and regulates various physiological processes, including calcium and bone metabolism, cellular growth and differentiation, immunity and cardiovascular function. A number of vitamin D derivatives have been synthesized for the treatment of cancer and inflammatory disease, but the adverse effect of hypercalcemic activity due to intestinal calcium absorption has limited wide clinical application. The VDR target gene product TRPV6 is essential for intestinal calcium absorption. Our prior study has demonstrated that 1,25(OH)2D3 induces TRPV6 mRNA expression at lower concentrations than for induction of CYP24A1, a VDR target gene involved in vitamin D inactivation, in intestinal SW480 cells, suggesting an additional mechanism for vitamin D signaling on TRPV6 induction. By searching for a signal transduction pathway involved in 1,25(OH)2D3-induced expression of TRPV6, we found that a p38 mitogen-activated protein kinase (MAPK) inhibitor reduces the expression of TRPV6 but not CYP24A1 in 1,25(OH)2D3-treated SW480 cells. Knockdown experiments showed that p38α is involved in 1,25(OH)2D3-induced expression of TRPV6 but not CYP24A1. Treatment with a de novo protein synthesis inhibitor suppressed 1,25(OH)2D3-induced TRPV6 expression. Finally, we found that 1,25(OH)2D3 treatment induced expression of GADD45A, which encodes the GADD45α MAPK kinase kinase activator, earlier than TRPV6 expression and that GADD45A knockdown reduced TRPV6 induction by 1,25(OH)2D3. These findings indicate that p38α and GADD45α are involved in an enhanced vitamin D signaling on TRPV6 expression.

Results of surgical interventions for critical limb ischemia due to vasculitis or collagen-tissue related disease.

BACKGROUND: In this study, we aimed to clarify both systemic and local prognosis after surgical interventions for critical limb ischemia (CLI) due to vasculitis or connective tissue related disease, and to search for any risk factors that can worsen the prognosis. METHODS: One hundred and ninety three patients that underwent surgical interventions for CLI between 2005 and 2014 were followed up for a median of 2.7 years. The patients were grouped into a group with vasculitis or connective tissue related disease (V) or with atherosclerosis (control: C). Two groups were retrospectively reviewed and compared. RESULTS: Thirty-one patients were grouped into the V group. At three years after intervention, V group showed significantly higher survival rate compared to C group (89% vs. 73%). On the other hand, limb survival rate after bypass surgery was significantly lower (74% vs. 94%), due to lower patency of the bypassed graft. Within V group, preoperative skin perfusion pressure of lower than 20 mmHg showed significantly worse prognosis of the limb. (HR 1.8; P=0.01) Regarding specific diseases, systemic scleroderma, rheumatoid arthritis and systemic lupus erythematosus tended to show worse prognosis. CONCLUSIONS: Patients with CLI due to vasculitis or connective tissue related disease have a longer life expectancy with lower limb salvage rate that can lead to low quality of the remaining life.

Stenotic lesion level did not affect outcomes of carotid endarterectomy.

Background Carotid endarterectomy is the established treatment for carotid artery stenosis, and remains the primary surgical option due to its superior outcomes compared to carotid arterial stenting. However, Japanese patients are known to have unfavorable anatomical conditions for carotid endarterectomy, with a relatively higher level of the carotid artery bifurcation than in the Western population. We investigated the outcomes of carotid endarterectomy in our institute and evaluated the procedural quality by comparing patients based on higher or lower lesion levels. Methods The clinical data of 65 patients who underwent carotid endarterectomy were collected retrospectively. The outcomes reviewed included stroke-free survival and stroke-free rate. The patients were divided into a higher group ( n = 25) and a lower group ( n = 40), based on lesion location in respect of the 2nd cervical vertebral level. Results There was no perioperative death and only one case of stroke in the higher group within 30 days after carotid endarterectomy. At 5 years after carotid endarterectomy, the stroke-free survival rates were 83.4% in the higher group and 87.8% in the lower group, while the stroke-free rates were 96.0% and 94.0%, respectively; there were no significant differences between groups. Conclusions Stenotic lesion level did not affect the outcome or procedural quality of carotid endarterectomy.

Pulse volume recordings to identify falsely elevated ankle brachial index.

BACKGROUND: Ankle brachial index can be falsely elevated in cases of medial arterial calcification, and its clinical use should be limited, especially in patients with diabetes. The aim of this study was to evaluate the potential role of pulse volume recording in detecting falsely elevated ankle brachial index. METHODS: Two parameters of the pulse waveform were automatically calculated: upstroke time and percentage mean artery pressure. Pulse volume recordings were retrospectively evaluated in 171 consecutive patients (342 limbs); 73 (43%) had a diagnosis of diabetes. RESULTS: On multivariate analysis, diabetes (hazard ratio = 1.7), ankle brachial index ≤ 0.90 (hazard ratio = 4.4), upstroke time ≥ 180 ms (hazard ratio = 2.1), and percentage mean artery pressure ≥ 45% (hazard ratio = 2.8) were significantly related to toe brachial index < 0.60. Further analysis for falsely elevated ankle brachial index was performed in 196 limbs (146 patients) with ankle brachial index > 0.90. The difference between ankle brachial index and toe brachial index differentiated the limbs of diabetic patients, with percentage mean artery pressure ≥ 45%, from controls (0.45 ± 0.17 vs. 0.35 ± 0.16, p = 0.03); upstroke time was not found to be a discriminating factor. CONCLUSIONS: Although measurement of ankle brachial index remains the gold standard for diagnosing peripheral arterial disease, percentage mean artery pressure, automatically obtained in ankle brachial index measurement, may be useful to detect falsely elevated ankle brachial index, especially in patients with diabetes.