Real-world outcomes of ponatinib treatment in 724 patients with CML and Ph+ ALL: a post-marketing surveillance study with a special interest in arterial occlusive events in Japan.

BACKGROUND: In September 2016, ponatinib was approved in Japan for the treatment of patients with chronic myeloid leukemia with resistance/intolerance to prior tyrosine kinase inhibitors and patients with relapsed or refractory Philadelphia chromosome-positive acute lymphoblastic leukemia. METHODS: We conducted a post-marketing all-case surveillance to study the safety and efficacy of ponatinib in clinical practice, focusing on arterial occlusive events. RESULTS: Data from 724 patients were collected for 2 years from the initiation of ponatinib. The arterial occlusive events were reported in 6.49% (47/724) with an exposure-adjusted incidence rate of 6.8/100 person-years. The risks associated with arterial occlusive events were age and comorbidities including hypertension and diabetes. At 104 weeks, the cumulative major molecular response rate in patients with chronic-phase chronic myeloid leukemia was 67.2% and the complete cytogenetic response in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia was 80.0%. Furthermore, the estimated 1-year overall survival rate was 98.5% for chronic-phase chronic myeloid leukemia and 68.6% for Philadelphia chromosome-positive acute lymphoblastic leukemia. CONCLUSIONS: This surveillance demonstrated that ponatinib has a favorable safety and efficacy profile in Japanese patients and also showed the necessity of closely monitoring arterial occlusive events in older adults and patients with predisposing factors for atherosclerosis.

Incidence and Outcomes of Visceral Ischemia in Acute Aortic Occlusion.

BACKGROUND: Acute aortic occlusion (AAO) is a morbid diagnosis in which mortality correlates with severity of ischemia on presentation. Visceral ischemia (VI) is challenging to diagnose and its presentation as a consequence of AAO is not well-studied. We aim to identify characteristics associated with VI in AAO to facilitate diagnosis. METHODS: Patients diagnosed with AAO who underwent revascularization were identified retrospectively from institutional records (2006-2020). The primary outcome was the development of VI (intra-abdominal ischemia). Univariate analysis was used to compare demographic, exam, imaging, and intraoperative variables between patients with and without VI in the setting of AAO. RESULTS: Ninety-one patients were included. The prevalence of VI was 20.9%. Preoperative comorbidities, time to revascularization, and operative approach did not differ between patients with and without VI. Patients with VI more frequently were transferred from outside institutions (100% vs. 53%, P = 0.02), presented with advanced acute limb ischemia (Rutherford III 36.9% vs. 7.5%, P < 0.01), and had elevated preoperative serum lactate (4.31 vs. 2.41 mmol/L, P < 0.01). VI patients had an increased occurrence of bilateral internal iliac artery (IIA) occlusion (47.4% vs. 18.1%, P = 0.01). Unilateral IIA occlusion, level of aortic occlusion, and patency of inferior mesenteric arteries were not associated with VI. Patients with VI had worse postoperative outcomes. In particular, VI conferred significant risk of mortality (odds ratio 5.45, P < 0.01). CONCLUSIONS: Visceral ischemia is a common consequence of AAO. Elevated lactate, bilateral IIA occlusion, and advanced acute limb ischemia (ALI) should increase clinical suspicion for concomitant VI with AAO and may facilitate earlier diagnosis to improve outcomes.

Distal Radiation Access as an Alternative to Conventional Radial Access for Coronary Angiography and Percutaneous Coronary Interventions (According to TENDERA Trial).

The aim of this study was to assess the immediate and medium-term (3 months) results of the safety and efficacy of distal radial access (DRA) in coronary interventions compared with conventional transradial radial access (TRA). TRA is the recommended access for coronary procedures because of increased safety: fewer local complications, large and small bleeding. Recently, DRA has emerged as a promising alternative access to minimize radial artery occlusion (RAO) risk, as well as other complications. A large-scale, international, randomized trial comparing medium-term results with TRA and DRA is lacking. An analysis of 776 patients of the prospective randomized TENDERA trial was carried out: the distal artery access group (DRA) - 391, the transradial access group (TRA) - 385. Statistically more often the crossover access was in the DRA group (5.1% and 0.8%, P < 0.001). The primary endpoint was early or late thrombosis/occlusion of the radial artery (RA). Secondary endpoints: (1) composite complications from access vessels; (2) access parameters. Statistically significant differences were obtained for the primary endpoint: DRA 2.7% (n = 10), TRA 6.8% (n = 26), P = 0.008. Occlusion of the distal radial artery (DRAt), with patent RA: DRA 1.3% (n = 5), TRA 0 (0), P = 0.023. At the secondary composite endpoint, statistically significant differences were obtained for the following groups of complications: BARC type I bleeding (DRA: 3.8% (n = 14), TRA: 21.7% (n = 83), P < 0.001); hematoma larger than 5 cm on day 1 (DRA: 10% [n = 37], TRA: 25.9% [n = 98], P < 0.001); hematoma larger than 5 cm on day 7 (DRA: 12.4% [n = 45], TRA: 34.6% [n = 132], P < 0.001). Of the access parameters, the following statistically significantly differed: puncture time DRA 19.0 (8.0; 50), TRA 13.5 (5.0; 29), P < 0.001; insertion of introducer DRA 42.0 (26.0; 84.0), TRA 35.0 (23.0; 55.0), P < 0.001, access artery hemostasis duration (min.) DRA 180.0 (120.0; 480.0), TRA 155.0 (115.0; 195.0), P < 0.001. The duration of the procedure and fluoroscopy, radiation dose, RA spasm in both groups had no statistically significant differences. In the TENDERA trail, DRA demonstrated efficacy and safety in interventional coronary interventions compared with TRA in the medium-term follow-up period: a statistically significant lower incidence of RA occlusion and local complications.

Incidence and predictors of radial artery occlusion following transradial coronary angiography: the proRadial trial.

OBJECTIVES: This study investigated the contemporary incidence and predictors of radial artery occlusion as well as the effectiveness of antithrombotic treatment for radial artery occlusion following transradial coronary angiography. BACKGROUND: The radial artery is the standard access for coronary angiography and even complex interventions. Postprocedural radial artery occlusion is still a common and significant complication. METHODS: This prospective study enrolled 2004 patients following transradial coronary angiography. After sheath removal, hemostasis was obtained in a standardized fashion. Radial artery patency was evaluated by duplex ultrasonography in all patients. In case of occlusion, oral anticoagulation was recommended and patients were scheduled for a 30-day follow-up including Doppler ultrasonography. RESULTS: A new-diagnosed radial occlusion was found in 4.6% of patients. The strongest independent predictors of radial occlusion were female sex and active smoking status. In the subgroup of patients with percutaneous coronary interventions, female sex followed by sheath size > 6 French were the strongest predictors of radial occlusion. 76 of 93 patients with radial occlusion received an oral anticoagulation for 30 days. However, reperfusion at 30 days was found in 32% of patients on oral anticoagulation. CONCLUSION: The incidence of radial artery occlusion following coronary angiography in contemporary practice appears with 4.6% to be lower as compared to previous cohorts. Female sex and smoking status are the strongest independent predictors of radial occlusion followed by procedural variables. The limited effectiveness of oral anticoagulation for treatment of radial artery occlusion suggests a primarily traumatic than thrombotic mechanism of this complication.

COVID-19-related Peripheral Arterial Thrombosis Treated in a Large Health Maintenance Organization.

BACKGROUND: COVID-19 was initially identified as an acute respiratory disease, but it was quickly recognized that multiple organ systems could be affected. Venous thrombosis and pulmonary embolism have been well reported. However, there is a paucity of data on COVID-19-related arterial thrombosis. We examined the incidence, characteristics, treatment, and outcome in patients with acute COVID-19-related arterial thrombosis in a large health maintenance organization (HMO). METHODS: A retrospective multicenter case review was performed from March 2020 to March 2021. Cases were identified through a questionnaire sent to vascular surgeons. Patient characteristics, imaging, treatment, and outcome were reviewed. Successful revascularization was defined as restoration of blood flow with viability of the end organ and absence of death within 30 days. Limb salvage was defined as prevention of major amputation (transtibial or transfemoral) and absence of death in 30 days. RESULTS: There were 37,845 patients admitted with COVID-19 complications during this time. Among this group, 26 patients (0.07%) had COVID-19-related arterial thrombosis. The mean age was 61.7 years (range, 33-82 years) with 20 men (77%) and 6 women (23%). Ethnic minorities comprised 25 of 26 cases (96%). Peripheral arterial disease (PAD) was present in 4 of 26 (15%), active smoking in 1 of 26 (3.8%), and diabetes in 19 of 26 (73%) cases. Most patients developed acute arterial ischemia in the outpatient setting, 20 of 26 (77%). Of the outpatients, 6 of 20 (30%) had asymptomatic COVID-19 and 14 of 20 (70%) had only mild upper respiratory symptoms. Distribution of ischemia was as follows: 23 patients had at least one lower extremity ischemia, one patient had cerebral and lower extremity, one had mesenteric and lower extremity, and one had upper extremity ischemia. Revascularization was attempted in 21 patients, of which 12 of 21 (57%) were successful. Limb salvage was successful in 13 of 26 (50%) patients. The overall mortality was 31% (8/26). CONCLUSIONS: Our experience in a large HMO revealed that the incidence of COVID-19-related arterial thrombosis was low. The actual incidence is likely to be higher since our method of case collection was incomplete. The majority of arterial thrombosis occurred in the outpatient setting in patients with asymptomatic or mild/moderate COVID-19 respiratory disease. Acute ischemia was the inciting factor for hospitalization in these cases. Acute lower extremity ischemia was the most common presentation, and limb salvage rate was lower than that expected when compared to ischemia related to PAD. Arterial thrombosis associated with COVID-19 portends a significantly higher mortality. Education of primary care providers is paramount to prevent delayed diagnosis as most patients initially developed ischemia in the outpatient setting and did not have a high cardiovascular risk profile.

Treating Peripheral Arterial Occlusive Disease and Acute Limb Ischemia During a COVID-19 Pandemic in 2020.

BACKGROUND: For many surgeons the outbreak of SARS-CoV-2 meant a downscaling of surgical interventions. The aim of this study was to investigate the impact of the measures taken on the care for patients with peripheral arterial disease (PAOD) and acute limb ischemia (ALI). METHODS: A retrospective analysis of the vascular practices of 2 major teaching hospitals in the Netherlands was performed. All interventions and outpatient visits for PAOD or ALI in 2020 were included. Patients treated in 2018 and 2019 were to serve as a control group. Data were analysed using descriptive statistics. RESULTS: In 2020, a total of 1513 procedures were performed for PAOD or ALI. This did not differ significantly from previous years. Overall, Fontaine 2 and 4 were the most frequent indications for intervention. A significant increase in the number of major amputations was observed in 2020 compared to 2018 (P< 0.01). This was mainly due to patients suffering from PAOD Fontaine 4. Inversely, a reduction in the number of femoro-popliteal bypasses was observed between 2020 and 2018. The number of outpatient visit due to Fontaine 2 was significantly lower in 2020 compared to 2018. CONCLUSIONS: The vascular practices of our hospitals were minimally influenced by the measures taken due to the outbreak of SARS-CoV-2. There was an increase in the number of amputation but an enormous surge in patients presenting with critical limb ischemia was not observed.

Negative-pressure wound therapy combined with artificial dermis (Terudermis) followed by split-thickness skin graft might be an effective treatment option for wounds exposing tendon and bone: A retrospective observation study.

ABSTRACT: Skin grafts are not suitable for closing tendon- or bone-exposing wounds, which require flap surgery. Dermal regeneration templates have value for closing such wounds, but the disadvantages of the technique include implantation failures because of infection, hematoma formation, or inappropriate immobilization. Negative-pressure wound therapy was reported to increase graft acceptance in difficult wounds.This retrospective case series of 65 patients evaluated negative-pressure therapy combined with artificial dermis for the treatment of acute or chronic tendon- or bone-exposing wounds. The artificial dermis was placed after adequate wound-bed preparation, with simultaneous application of a vacuum-assisted closure system. Split-thickness skin grafting was performed after the implanted artificial dermis had become established.The overall success rate was 88.1% (59/67): 88.6% (39/44) in the chronic wounds group and 87% (20/23) in the acute-trauma group separately. The overall mean survival time of artificial dermis in success cases was 13.24 ±â€Š7.14 days. In separately, the survival time of artificial dermis had no statistically difference in chronic wound group (13.64 ±â€Š7.53 vs 12.60 ±â€Š5.86. P = .943), but had significant statistical difference in acute trauma group (12.45 ±â€Š6.44 days vs 23.33 ±â€Š4.04 days, P = .018). Also, comorbidity of PAOD was found a strong risk factor of failure in chronic wound group (100% vs 23.1%, P < 0.001).We concluded that artificial dermis combined with negative-pressure therapy followed by split-thickness skin grafting might be a reliable and effective option for surgical reconstruction of tendon- or bone-exposing wounds, and could decreasing waiting periods of autologous skin graft.

Splanchnic occlusive disease predicts for spinal cord injury after open descending thoracic and thoracoabdominal aneurysm repair.

OBJECTIVE: In the present study, we sought to discern the effects of splanchnic occlusive disease (SOD; renal, superior mesenteric, and/or celiac axis arteries) on spinal cord injury (SCI; paraparesis or paraplegia) and major adverse events (MAE) after descending thoracic aneurysm (DTA) and thoracoabdominal aortic aneurysm (TAAA) open repair. METHODS: Patients who had undergone DTA/TAAA repair at our institution were dichotomized according to the presence of SOD, which was investigated as a predictive factor of our primary (SCI) and secondary (operative mortality, myocardial infarction, stroke, tracheostomy, de novo dialysis, MAE, survival) endpoints. Risk adjustment used both propensity score matching and multivariable logistic regression. RESULTS: From July 1997 to October 2019, 888 patients had undergone DTA/TAAA repair, of whom 19 were excluded from our analysis for missing data. SOD was absent in 712 patients and present in 157 patients. The patients with SOD had presented with a greater incidence of preoperative renal impairment (61 [38.9%] vs 175 [24.6%]; P < .01) and peripheral arterial disease (60 [38.2%] vs 162 [22.8%]; P < .01] and decreased left ventricular ejection fraction (45%; interquartile range, 10%; vs 50%; interquartile range, 4%; P < .01). The etiology of aortic disease was more frequently dissection in the SOD group (56.1% vs 43.7%) and more frequently nondissecting aneurysm in the non-SOD group (56.3% vs 43.9%; P < .01). Patients without SOD had presented with aneurysms more cranially located (DTA, 34.0% vs 7.6%; extent I TAAA, 44.0% vs 7.6%). In contrast, patients with SOD had presented with aneurysms more caudally located (extent II TAAA, 36.9% vs 8.6%; extent III TAAA, 30.6% vs 11.0%; extent IV TAAA, 17.2% vs 2.5%; P < .01). Propensity score matching led to 144 pairs, with SOD significantly associated with SCI (10 [6.9%] vs 2 [1.4%]; P = .03) and MAE (47 [32.6%] vs 26 [15%]; P < .01). Ten-year survival was reduced in those with SOD (31.5% vs 45.2%; P < .01). Conditional multivariable regression confirmed SOD to be a predictor of SCI in the matched sample (odds ratio, 6.60; P = .02). CONCLUSIONS: Our results have shown that SOD is a significant predictor of SCI in patients undergoing open DTA/TAAA repair. The investigation of measures to prolong neuronal ischemia tolerance (eg, hypothermia) is warranted for such patients.

Incidence, diagnosis and treatment of popliteal artery entrapment syndrome in current vascular practice in Japan.

Few data regarding popliteal artery entrapment syndrome (PAES) is available in Japan. In this study, we investigated incidence, diagnosis and treatment of PAES in current vascular practice. A retrospective analysis of all patients with PAES visiting 31 participating institutes between 2003 and 2015 was conducted. Thirty-five limbs (28 patients) were identified during the 13-year study period, and the incidence of PAES was 0.12% of all peripheral artery disease cases revascularized. Mean age was 32.0 ± 16.9 years old, and 60 and more years old was 10.7%. Also, 92.9% were male and 39.3% were athletes. Most frequent initial symptoms were intermittent claudication in 23 limbs (65.7%); 4 limbs (11.4%) had chronic limb-threatening ischemia. CT scan was most frequently (94.3%) used for the diagnostic imaging followed by MRI (45.7%) and duplex ultrasound (45.7%). Stress test such as dorsal flexion during duplex ultrasound was used only in 28.6%. Thirty-two limbs (91.4%) received surgical treatment, including 23 arterial reconstructions (71.9%); there were no major perioperative complications. All patients achieved improvement of their symptoms, and the average ankle brachial index increased from 0.69 ± 0.22 to 1.00 ± 0.14 post-surgery. The average postoperative follow-up period was 26.0 months with only one reintervention during the follow-up. In conclusion, PAES was a rare condition and traditional surgical treatment was solid. However, given a broad spectrum of clinical feature of PAES and less usage of diagnostic duplex ultrasound with stress test, there might be a miss- or delayed diagnosis of PAES even in the current vascular practice.

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.

IVUS-Guided Wiring Improves the Clinical Outcomes of Angioplasty for Long Femoropopliteal CTO Compared with the Conventional Intraluminal Approach.

AIMS: This study aimed to assess the clinical efficacy of intravascular ultrasound (IVUS)-guided intraplaque wiring for femoropopliteal (FP) chronic total occlusion (CTO). METHODS: This single-center, retrospective, observational study was performed at the Japanese Red Cross Kyoto Daini Hospital. From March 2013 to June 2017, a total of 75 consecutive patients (mean age: 75.4±8.5 years; 59 males), who underwent endovascular treatment (EVT), having 82 de novo FP-CTO lesions, were enrolled in this study. Eleven of the lesions that met the exclusion criteria were excluded, and the remaining 71 lesions were divided into the IVUS-guided wiring group (n=34) and non-IVUS-guided wiring group (n=37). Primary patency, defined as a peak systolic velocity ratio of ＜2.4 on duplex ultrasonography, and freedom from clinically driven target lesion revascularization (CD-TLR) at 12 months were the primary outcomes. RESULTS: The mean lesion length was 21.6±8.9 cm. The frequencies of primary patency and freedom from CD-TLR were significantly higher in the IVUS-guided wiring group than in the non-IVUS-guided wiring group (70.0% vs. 52.2%, p=0.045; 83.9% vs. 62.8%, p=0.036, respectively). The complete clinically true lumen angioplasty rate was also higher in the IVUS-guided wiring group than in the non-IVUS-guided wiring group (91.1% vs. 51.3%, p＜0.001, respectively). The clinically true and false wire passage rates were respectively 97.3% and 2.7% in the IVUS-guided wiring group. CONCLUSION: IVUS-guided wiring improves the clinical outcomes of EVT for FP-CTO by achieving a high clinically true lumen wire passage rate.

Philadelphia-negative myeloproliferative neoplasms among Kuwaiti Nationals.

The epidemiology, genetics, and thrombosis risk of MPNs among Arabs are largely unknown. This may be attributed to scarce epidemiological data, particularly from our region. Our study included 381 Kuwaiti nationals with Ph-negative MPNs and a confirmed driver mutation involving JAK2 (exon 12 14), CALR, or MPL. This first regional study examines the demographics, clinical parameters, and thrombosis-related attributes of the participants. This study reported a median age of 58 years, with females and males representing 54.9% and 45.1%, respectively. ET was the most frequent subtype of Ph-negative MPNs in our population, accounting for 52.0% of the cases, followed by PV, found in 34.6% of the participants, and PMF, found in 8.4% of participants. The crude annual cumulative incidence of Ph-negative MPNs in Kuwait ranged from 0.674 to 3.177 per 100,000 population across the study period. The most common driver mutation was JAK2V617F, with a frequency of 89.5%. At diagnosis, 19.2% of the patients presented with unexplained thrombosis, and almost half were of arterial origins. Males were more likely to present with arterial thrombosis than females (61.5% vs. 35.3%), whereas venous thrombotic events were more common in females than in males (47.1% vs. 17.9%; p-value = 0.025). Ph-negative MPNs in Kuwait are rare; however, thrombosis is a frequent complication, being documented in up to 19.2% of cases at presentation, more commonly at arterial sites. These findings call for thorough evaluation of patients with unexplained derangements in their hematological parameters during follow-ups.

Incidence of Major Arterial Abnormality in Patients with Wound Dehiscence after Lower Extremity Orthopedic Procedures.

BACKGROUND: Surgical dehiscence can occur after lower extremity orthopedic procedures. Underlying vascular aberrancy and localized ischemia contribute to chronic wound development requiring advanced techniques such as free tissue transfer. Localized vascular abnormality is an underrecognized contributing factor to such dehiscence. The authors reviewed their lower extremity free tissue transfer experience in this population to analyze the incidence of arterial abnormality and outcomes. METHODS: The authors conducted a retrospective review of 64 lower extremity free tissue transfers performed for chronic wounds after orthopedic procedures from 2011 to 2018. The primary outcome was major arterial abnormality as identified on angiography. Secondary outcomes were flap success, limb salvage, and ambulation status. RESULTS: The median age was 58 years, and 44 were men (69 percent). Comorbidities included osteomyelitis (77 percent), diabetes (39 percent), and peripheral vascular disease (17 percent). The incidence of arterial abnormality on angiography was 47 percent. Defect location correlated with angiosome of arterial abnormality in 53 percent. The flap success rate was 92 percent. Limb salvage and ambulation rates were 89 and 89 percent, respectively, at an average follow-up of 17.6 months. Men demonstrated an increased rate of limb salvage (p = 0.026). Diabetes (p = 0.012), arterial abnormality (p = 0.044), and arterial flap complication (p = 0.010) correlated with amputation. CONCLUSIONS: The high incidence of arterial abnormality in this population highlights the importance of expedient multidisciplinary care, including vascular and plastic surgery. Diagnostic angiography is important for identifying major arterial abnormality and the need for free tissue transfer for definitive coverage.

The frequency of radial artery occlusion following cardiac catheterization with the use of transradial pneumatic compression band.

OBJECTIVES: Radial artery occlusion is a silent complication of a transradial approach to cardiac catheterization that may complicate subsequent transradial procedures in patients undergoing cardiac catheterization. A transradial band reduces vascular complications and provides brisk, powerful and effective haemostasis. The purpose of this study was to assess the frequency of radial artery occlusion in 180 patients undergoing transradial coronary catheterization. RESULTS: The median age of the study cohort was 58 years. Radial artery occlusion was found in 14 (7.8%) patients. When stratifying by age group and sex, there was no significant difference in radial artery occlusion between age groups and sex. It was likewise found that comorbidities such as diabetes mellitus, hypertension and smoking, increased the risk of radial artery occlusion however this was observed to be significant only for diabetes mellitus. We therefore conclude that a transradial pneumatic pressure band is an extremely helpful and safe strategy to prevent radial artery occlusion.

Prospective Screening of Extracranial Systemic Arteriopathy in Young Adults with Moyamoya Disease.

Background RNF213 is a major susceptibility gene for moyamoya disease (MMD), characterized by chronic progressive steno-occlusion of the intracranial arteries. However, coincidental extracranial arteriopathy is sporadically described in a few cases and in children with MMD. Methods and Results This study prospectively enrolled 63 young adults (aged 20-49 years) without a known history of systemic vascular diseases who were confirmed to have definite (bilateral, n=54) or probable (unilateral, n=9) MMD, as per typical angiographic findings. Coronary and aorta computed tomography angiography was performed to characterize extracranial arteriopathy and investigate its correlation with clinical characteristics and MMD status, including the RNF213 p.Arg4810Lys variation (c.14429G>A, rs112735431). Altogether, 11 of 63 patients (17%) had significant (>50%) stenosis in the coronary (n=6), superior mesenteric (n=2), celiac (n=2), renal (n=1), and/or internal iliac artery (n=1). One patient showed both mesenteric and iliac artery stenosis. Patients with extracranial arteriopathy were more likely to have diabetes mellitus and posterior cerebral artery involvement. Moreover, a higher prevalence of extracranial arteriopathy was observed in the presence of the RNF213 p.Arg4810Lys variant (67% in homozygotes). After controlling for diabetes mellitus and posterior cerebral artery involvement, the p.Arg4810Lys variant was independently associated with extracranial arteriopathy (additive model; P=0.035; adjusted odds ratio, 4.57; 95% CI, 1.11-27.20). Conclusions Young adults with MMD may have concomitant extracranial arteriopathy in various locations. Patients with RNF213 variants, especially the p.Arg4810Lys homozygous variant, should be screened for systemic arteriopathy.

Current Trends in Epidemiology and Clinical Features of Thromboangiitis Obliterans in Japan　- A Nationwide Survey Using the Medical Support System Database.

BACKGROUND: The epidemiology and clinical features of thromboangiitis obliterans (TAO) in Japan have not been updated extensively.Methods and Results:This retrospective study used the Japanese Ministry of Health, Labour and Welfare (JMHLW) medical support system database and associated health insurance data. The number of medical financial support recipients registered as TAO patients and estimated prevalence of TAO decreased from fiscal year (FY) 2000 (10,089 and 7.95 [95% confidence interval, CI: 7.79-8.10] per 100,000 population) to FY 2010 (7,147 and 5.58 [95% Cl: 5.45-5.71] per 100,000) and leveled off until 2014. The prevalence of TAO among patients with peripheral arterial occlusive diseases declined from 7.15% (95% Cl: 7.00-7.31) in FY 2008 to 6.12% (95% Cl: 5.98-6.26) in FY 2014. Clinicodemographic features were obtained from 89 new recipients in FY 2013 and 2014: 12 (13%) women, 36 (40%) aged ≥50 years, 26 (29%) had probable onset age ≥50 years, 7 (8%) were non-smokers, and 12 (13%) had arteriosclerosis-related comorbidities. The symptoms were similar regardless of registration age, smoking history, or sex. Although 40 (45%) had digit ulcers, only 12 (13%) fulfilled Shionoya's criteria. They rarely had infrapopliteal lesions combined with upper extremity involvement or phlebitis. CONCLUSIONS: The prevalence of TAO has decreased in Japan. In the current diagnosis of TAO, various clinical characteristics including late onset, arteriosclerotic factors, non-smoking, or mild symptoms should be considered.

Do Surgical Site Infections in Open Aortoiliac Surgery Differ Between Occlusive and Aneurysmal Arterial Disease?

BACKGROUND: Surgical site infections (SSI) are frequently seen after aortoiliac vascular surgery (2%-14%). Deep SSIs are associated with graft infection, sepsis, and mortality. This study evaluates the difference in incidence and nature of SSI following open aortoiliac surgery for aneurysmal disease compared to occlusive arterial disease. METHODS: A retrospective cohort study was conducted, including all consecutive patients who underwent open aortoiliac vascular surgery between January 2005 and December 2016 in the Amphia Hospital, Breda, the Netherlands. Patients were grouped by disease type, either aneurysmal or occlusive arterial disease. Data were gathered, including patient characteristics, potential risk factors, and development of SSI. Surgical site infections were defined in accordance with the criteria of the Centers for Disease Control. RESULTS: Between January 2005 and December 2016, a total of 756 patients underwent open aortoiliac surgery of which 517 had aortoiliac aneurysms and 225 had aortoiliac occlusive disease. The group with occlusive disease was younger, predominantly male, and had more smokers. After exclusion of 228 patients undergoing acute surgery, the SSI rate after elective surgery was 6.2%, with 10 of 301 SSIs in the aneurysmal group (3.0%) and 22 of 213 SSIs in the group with occlusive disease (10.3%, P < .001). Also, infection-related readmission and reintervention were higher after occlusive surgery, 6.6% versus 0.9% (P < .001) and 4.2% versus 0.9% (P = .003), respectively. Staphylococcus aureus was found as the most common pathogen, causing 64% of SSI in occlusive disease versus 10% in aneurysmal disease (P = .005). Logistic regression showed occlusive arterial disease and chronic renal disease were associated with SSI. CONCLUSION: Our study presents evidence for a higher rate of SSI in patients with aortoiliac occlusive disease compared to aortoiliac aneurysmal disease, in part due to inherent use of inguinal incision in patients with occlusive disease. All precautions to prevent SSI should be taken in patients undergoing vascular surgery for arterial occlusive disease.

Relation between serum cotinine levels and trophic lesions in patients with critical limb ischemia: a pilot study.

Aim: To evaluate if smoking, quantified by the serum cotinine levels, is related to the evolution of patients with critical limb ischemia (CLI).Method: A pilot study was conducted on CLI patients who addressed at the Second Surgery Clinic of the Emergency County Hospital, Cluj-Napoca, Romania between November 2015 and December 2016. The sample of patients was split into two groups using the threshold of 15 ng/mL for the serum level of cotinine (low cotinine level - LCL vs. high cotinine level - HCL). Furthermore, the ROC analysis was conducted to identify the threshold of cotinine level able to discriminate between CLI patients with and without trophic lesions.Results: The mean age of patients was 60.7 ± 10.5 years with a significantly higher percentage of male patients (84%). A significant association was identified between urban origin and serum cotinine level, which is related to the increased number of cigarettes smoked per day among urban participants. Excepting necrectomy and toe disarticulation, no differences were found between LCL and HCL group regarding symptoms, signs or comorbidities. In smokers with CLI (38/43), a serum cotinine cut-off of 9.765 ng/mL was observed on eight out of 10 CLI patients with necrectomy and five out of 28 patients without necrectomy.Conclusion: Our study showed higher serum cotinine levels associated with a higher number of smoked cigarettes and necrectomy in patients with CLI. The serum cotinine could be a fair screening test for necrectomy in smokers CLI patients.

Impact of hepatitis virus infection on arterial calcification among incident hemodialysis patients.

BACKGROUND: The impact of hepatitis virus infection on arterial calcification (AC) was not studied. OBJECTIVE: To study the prevalence, severity and distribution of AC in incident hemodialysis patients with hepatitis B and C viral infection. CASES AND METHODS: 172 stage 5 CKD adults (98 male and 74 female) were included; 58 of them were seronegative for both hepatitis B and C (SN group), 48 were positive for hepatitis B virus infection (HBV group) and 66 were hepatitis C virus positive (HCV group). Beside histopathology of the obtained arterial samples, all these cases were examined for body mass index (BMI), serum calcium (Ca), phosphorus (P), alkaline phosphatase (AP), serum albumin, uric acid (UA), alanine transaminase (ALT), parathormone (PTH), fibroblast growth factor 23(FGF23), interleukin 6 (IL6), and 25 hydroxy vitamin D (25 (OH) vit D), hemoglobin concentration, and serum ferritin. RESULTS: 86 (50%) of the cases had AC; 11 of them were in SN group (19%), 9 in HBV group (18.8%) and all the 66 HCV group (100%). In SN group, 4 had intimal calcification, 5 had medial calcification, and 2 had both intimal and medial calcification. In HBV group, 9 had intimal calcification, while no cases were encountered with either medial or both site calcifications. In HCV group, 16 had intimal calcification, 31 had medial calcification, and 19 had both intimal and medial calcification. Calcification was in the form of spots in one case in SN group, and 6 cases in HBV group, a single plaque of calcification in 5 cases of SN group, 3 cases of HBV group, and 16 cases of HCV group, multiple plaques were detected in 4 cases in SN group, and 31 cases in HCV group, and diffuse calcification in one case in SN group, and 19 cases in HCV group. In HBV group, calcification was only detected in patients with high viremia, while all patients with low or moderate viremia were devoid of calcification. In HCV group, all patients with low viremia had intimal solitary plaque of calcification, all patients with moderate viremia had multiple plaques of medial calcification, while all patients with high viremia had diffuse intimal and medial calcification. Both groups of viral hepatitis were significantly different in comparison to SN group in either distribution or calcification score (P<0.001 in all). HBV group had significantly lower serum P, CaxP and PTH in comparison to SN group (4.6±0.66 vs. 5.45±0.77mg/dL, 36.4±7.2 vs. 44.1±8.69, and 348±65.4 vs. 405.9±83.2pg/mL, P<0.001, <0.001, and 0.035 respectively). On the other hand, HCV group did not show any significant difference in any of the studied parameters compared to SN group. CONCLUSION: HCV positive patients are more prone to develop AC that is more extensive. HBV positive patients were less likely to have arterial medial calcification, probably related to lower serum phosphorus, CaxP product and PTH. HCV infection should be added as risk factor for AC among CKD patients. Further studies are needed to confirm these findings.

Impact of Stent Graft Design on External Iliac Artery Limb Occlusion Rates After Endovascular Aneurysm Repair: Post-hoc Analysis of a Japanese Multicentre Database.

OBJECTIVE/BACKGROUND: It was hypothesised that a helical stent with expanded polytetrafluoroethylene (ePTFE) grafts could provide a preventive effect for external iliac artery (EIA) limb occlusion following endovascular aortic aneurysm repair (EVAR). Therefore, a post-hoc analysis of a Japanese multicentre database was conducted to assess the impact of the stent graft design on EIA limb occlusion rates. METHODS: Patients who underwent EVAR with EIA limb deployment between 2008 and 2016 were evaluated. The stent graft limbs were divided into two groups: group A comprised stent graft limbs made of a helical stent with ePTFE grafts (Excluder; n = 255), and group B comprised stent graft limbs made of a Z stent with polyester grafts (Zenith, Flex and Endurant; n = 173). The main outcome was the incidence of limb occlusion and severe limb stenosis (EIA related limb complications). The risk factors for EIA related limb complications were analysed and the midterm results between groups A and B compared. Fine-Gray generalisation of the proportional hazards model was used after propensity score matching to calculate the hazard ratio (HR). RESULTS: One complication occurred in group A and 10 complications occurred in group B. The risk factors for EIA related limb complications for the entire group were a stent graft limb size ≤10 mm (HR 5.41; p = .01) and inclusion in group B (HR 14.9; p = .009). After propensity matching, group A (n = 159) was matched with group B (n = 159). The cumulative incidence function of EIA related limb complications at five years was 0.66% in group A and 7.8% in group B (HR 8.67; p = .039). CONCLUSION: Stent graft design can affect limb patency in EIA limb deployment. When EIA limb deployment is necessary for patients with a small EIA, such as Japanese patients, stent graft limbs made of a helical stent with ePTFE should be used to reduce the risk of limb occlusion.