Severe Peripheral Arterial Occlusive Disease Research Articles

Topicality of the fundamental and determining importance of chronic critical ischemia of the extremities and its restorative treatment using crural/pedal bypasses in Germany and in Saxony-Anhalt

Currently, there is an increase in severe stages of peripheral arterial occlusive disease (PAOD) with critical ischemia. This seems to correspond to the general demographic change as well as aconsequence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic of the last 3years. The now established and accepted interventional/endovascular approach for severe lower leg PAOD in experienced hands is still considered the first-line treatment but from the authors' perspective crural/pedal venous bypass is experiencing arenaissance. Compact narrative review of the current state of crural/pedal bypass surgery in Germany and Saxony-Anhalt (SA) combined with selective references from the current scientific medical literature and own clinical experiences. The current statistics of case-related diagnosis-related groups (DRG) data show that, especially with the occurrence of the corona pandemic, adecrease in inpatient case numbers of patients with PAOD stage IIB can be observed nationwide and also in SA. The severe PAOD stages have remained approximately the same in case numbers but increased in SA. The risk stratification based on the wound, ischemia and foot infection (WIFI) classification offers the possibility to be able to make statements about the risk of amputation, benefits and type of revascularization measures. The length of the occlusion, occlusion site of the affected vessels and degree of calcification are taken into account in the global limb anatomic staging system (GLASS) to assess the prognosis. The evaluation of the case-based hospital statistics from 2015 to 2020 showed aconstant use of femorocrural/femoropedal bypass surgery in Germany as well as aslight increase in reconstruction using femorocrural bypasses in SA, which seems to correlate with the tendency for an increase in the number of cases of severe PAOD. Parameter-based objectification of the severity of critical limb ischemia should be included in the indications for placement of a crural/pedal bypass. The WIFI classification and GLASS are suitable for this purpose as arelative prognosis of success is also possible. The treatment of critical limb ischemia by crural/pedal bypass surgery continues to find aconstant application in Germany and SA.

Factors affecting the outcome of lower extremity osteomyelitis treated with microvascular free flaps: an analysis of 65 patients

BackgroundFree flaps have been a useful modality in the management of lower extremity osteomyelitis particularly in limb salvage. This study aimed to determine the factors affecting the outcome of free flap reconstruction in the treatment of osteomyelitis.MethodsThis retrospective study assessed 65 osteomyelitis patients treated with free flap transfer from 2015 to 2020. The treatment outcomes were evaluated in terms of the flap survival rate, recurrence rate of osteomyelitis, and amputation rate. The correlation between outcomes and comorbidities, causes of osteomyelitis, and treatment modalities was analyzed. The following factors were considered: smoking, peripheral artery occlusive disease, renal disease, diabetic foot ulcer, flap types, using antibiotic beads, and negative pressure wound therapy.ResultAmong the 65 patients, 21 had a severe peripheral arterial occlusive disease. Osteomyelitis developed from diabetic foot ulcers in 28 patients. Total flap failure was noted in six patients, and osteomyelitis recurrence was noted in eight patients, for which two patients underwent amputation surgery during the follow-up period. Only end-stage renal disease had a significant correlation with the recurrence rate (odds ratio = 16.5, p = 0.011). There was no significant relationship between outcomes and the other factors.ConclusionThis study showed that free flaps could be safely used for the treatment of osteomyelitis in patients with comorbidities and those who had osteomyelitis developing from diabetic foot ulcers. However, care should be taken in patients diagnosed with end-stage renal disease.

Percutaneous Deep Vein Arterialization for a Chronic Limb-Threatening Ischemia Patient in Taiwan.

Patients with a severe peripheral arterial occlusive disease, defined as chronic limb-threatening ischemia (CLTI),1 with an increase of 1-year mortality and amputation rates.2 Deep venous arterialization (DVA) creates a shunting blood flow from the artery to the deep vein. The DVA provides an alternative treatment for CLTI, and the safety and successful revascularization by percutaneous DVA (pDVA) was reported in Europe.3 There was also a successful pilot study in Singapore for pDVA by using the LimFlow device.4 Here, we report a case in Taiwan with CLTI, which failed in the prior endovascular procedure. We used total pDVA to create an arterial-venous bypass for ischemic limb salvage and with a perfect long-term outcome without using LimFlow device.

The Role of Oxidative Stress Markers in Predicting Acute Thrombotic Occlusion of Haemodialysis Vascular Access and Progressive Stenotic Dysfunction Demanding Angioplasty.

Haemodialysis vascular access (VA) dysfunction is a major cause of morbidity in haemodialysis (HD) patients. Primary venous outflow occlusion and restenosis after percutaneous transluminal angioplasty (PTA) are two major obstacles for the long-term use of dialysis VA. It remains unclear whether oxidative stress markers can be used as predictors for thrombotic occlusion of VA and progressive stenosis dysfunction demanding PTA. All routine HD patients at one teaching hospital participated in this study including ankle-brachial index (ABI) examinations and serum oxidative stress markers. The serum oxidative stress markers (high-sensitivity C-reactive protein (hs-CRP), matrix metalloproteinase-2 (MMP-2), MMP-9, homocysteine, asymmetrical dimethylarginine (ADMA), nitrate oxidase (NO), tumour necrosis factor-α (TNF-α), monocyte chemotactic protein 1 (MCP-1), interleukin-1β (IL-1β), and transforming growth factor-β (TGF-β)) were measured using immunosorbent assays in 159 HD patients (83 men and 76 women; mean age: 65 ± 12 years). The participants met the following criteria: (1) received regular HD treatment for at least 6 months, without clinical evidence of acute or chronic inflammation, recent myocardial infarction, unstable angina or circulatory congestion; and (2) received an arteriovenous fistula (AVF)/arteriovenous graft (AVG: polytetrafluoroethylene, PTFE) as the current VA for more than 6 months, without interventions within the last 6 months. All the participants were followed up clinically for up to 12 months to estimate the amount of primary thrombotic occlusion and VA dysfunction demanding PTA. During the 12-month observation, 24 patients (15.1%) had primary thrombotic occlusion of VAs. Another 24 patients (15.1%) required PTA because of clinical dysfunction of access. Additionally, during the follow-up period, restenosis occurred in 12 patients (50% of 24 patients). The access types of arteriovenous grafts (AVGs) and a diagnosis of peripheral arterial occlusive disease (PAOD) were two strong predictors for acute thrombotic events of VA (hazard ratio (HR): 16.93 vs. 2.35; p < 0.001 vs. 0.047). Comparing dysfunctional with non-dysfunctional VAs, up to 27.7% of patients with high levels of ADMA (>0.6207 μM, N = 65) received required PTA compared with 4.4% of those with low levels (≤0.6207 μM; N = 90; p < 0.001). In multivariate analysis, the plasma baseline levels of ADMA independently conferred nearly 4.55 times the risk of primary stenotic dysfunction of HD VA (HR: 4.55; 95% confidence interval: 1.20 to 17.26; p = 0.026). In conclusion, our findings suggest the role of ADMA in the development of symptomatic VA dysfunction. Additionally, PAOD severity can be used in clinical practice to predict whether acute thrombotic occlusion of VA will easily occur in HD patients.

Multidimensional Vascular Evaluation in Patients Treated with Tyrosine Kinase Inhibitors (TKIs): From Plaque Formation to Evolution and Follow up on 150 Patients

Background Among the unresolved issues concerning management of chronic myeloid leukemia (CML) patients, the most feared are long-term adverse events due to TKI treatment. Although TKIs have revolutionized CML outcomes, their use has also been associated with severe side effects including cardiovascular events, of which peripheral arterial occlusive disease (PAOD) is the most frequently reported. In 2010 we began a long-term collaboration with local angiologists and vascular surgeons to investigate, screen and follow patients on TKI therapy. Placque formation, evolution and follow up of 150 patients were studied and are presented here. Methods We analyzed 143 CML and 7 Ph+ Acute Lymphoid leukemia (ALL) patients, all of whom were treated with TKIs. Careful assessment of cardiovascular risk factors (i.e., age, smoking, obesity, diabetes, high blood pressure, high LDL or low HDL cholesterol levels, family history of heart disease or other cardiovascular disease) were done according to the European Society of Cardiology Systematic Coronary Risk Evaluation (SCORE) risk charts. A complete vascular screening, including physical examination, and a series of instrumental tests were performed for all patients. Tests included doppler echocardiography (US) of supra-aortic arteries with measurement of pre-bulbar IMT, abdominal arteries and inferior limbs arteries and veins (IL), ABI of the posterior tibial artery and digital photoplethysmography (FPG). Patients needing surgical intervention were referred to a surgeon. The team of hematologists, angiologists and surgeons met periodically to discuss results and intervention approaches. Results Patients included 76 males and 74 females with a median age of 53.7 yo (range 18-85). All patients were treated with a TKI at diagnosis, 87 (58%) with imatinib, 63 (42%) with other TKIs, including ponatinib (2 LLA), and all received TKI therapy for a minimum of 12 months since 2010. For analyses purposes, patients were divided in 7 different age groups at diagnosis (18-30, 31-40, 41-50, 51-60, 61-70, 71-80 and 81-85 years; patients incidence per group was 6%, 18%, 18.6%, 27.4%, 13.3%, 12.7% and 4%, respectively). Each patient in the study received yearly screening, and this increased to every 3-6 mo if abnormalities occurred. Of the 150 patients in the study, 10 (7%) developed severe PAOD (grade 3-4) requiring revascularization. Districts involved were: carotid (5), renal (2) and extremities (14 IL, 1 subclavian). Three patients were polyvascular requiring intervention in multiple regions. 18 patients with no malignancies requiring surgery were used as a control group and matched for sex, age, diabetes, smoking, district and intervention to compare patency rates, morbidity and mortality. At event, these 10 patients were taking imatinib (1), bosutinib (1), nilotinib (5) and ponatinib (3). None of them had a previous PAOD, but all had cardiovascular risk factors (100% were hypertensive). Median age was 66.8 yo (range 46-82) and the median number of PAOD risk factors (age &amp;gt;60, hypertension, diabetes, male gender, nicotine abuse and coronary heart disease) was 2 (range 1-5). Plaque was deemed significant when stenosis was &amp;gt;30%; at this point it developed very rapidly, with signs of arterial thrombosis within a year, requiring intervention. IMT scores (measuring thickness of carotid artery wall) and ABI followed by FPG and their variation over time proved predictive for plaque evolution. No patient died due to complications relating directly to surgical intervention or within 30 days post-surgery. One patient required a major limb amputation at 12 months. Patency rates were similar in the TKI and control group at 12 months (88.2% vs 80%), however the frequency of reintervention (endo or open) was 50% in TKI patients (n=5) and 11% in the control group (n=2; P&amp;lt;0.01). Discussion Multidisciplinary evaluation, comorbidity analysis and cardiovascular risk assessment in CML patients are highly recommended, at diagnosis if possible, to implement a tailored treatment strategy and to identify patients who require strict monitoring of risk factors during treatment. Extensive and detailed information on the 150 patients in this study will be presented with a focus on the onset and characteristics of thrombotic arterial events, medical/surgical interventions, analysis of instrumental parameters (ABI, IMT, FPG) and correlation with clinical data. Disclosures Abruzzese: Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bms: Honoraria.

Red Blood Cell Distribution Width Predicts 1-month Complications after Percutaneous Transluminal Angioplasty.

SummaryBackgroundThe identification of patients at higher risk of developing percutaneous transluminal angioplasty (PTA)-related complications is pivotal for achieving better clinical outcomes. We carried out a single-center, observational, retrospective study to explore whether in-hospital changes of red blood cell distribution width (RDW) may help predicting early development of PTA-related complications.MethodsThe study population consisted of all consecutive patients who underwent PTA for severe peripheral artery occlusive disease (PAOD) during a 2-year period. RDW was measured at hospital admission and discharge, and the delta was calculated. Patient follow-up was routinely performed 1-month after hospital discharge, and was based on thoughtful medical assessment and arterial ultrasonography. The control population consisted of 352 ostensibly healthy subjects.ResultsThe final PTA group consisted of 224 patients. Hemoglobin was lower, whilst mean corpuscular volume (MCV) and RDW were higher in PAOD cases than in controls. Overall, 11 PAOD patients (4.9%) developed clinically significant PTA-related complications 1-month after hospital discharge. Patients who developed 1-month PTA-related complications had lower hemoglobin concentration, but higher RDW and delta RDW than those who did not. Patients with delta RDW >1 had 60% higher risk of developing 1-month PTA-related complications and 88% higher risk of developing early reocclusion. Overall, RDW exhibited an area under the curve (AUC) of 0.68 and 0.74 for predicting 1-month PTA-related complications and early reocclusion, respectively.ConclusionsThe results of this study suggest that RDW may play a role for guiding the clinical decision making of PTA patients immediately after hospital discharge.

Efficacy of Stent Implantation Combined with Balloon Dilatation in the Treatment of Severe Peripheral Arterial Occlusive Disease of Lower Extremity in Macao—A Single Center Experience

Efficacy of Stent Implantation Combined with Balloon Dilatation in the Treatment of Severe Peripheral Arterial Occlusive Disease of Lower Extremity in Macao—A Single Center Experience

Systemic vasculitis is associated with a higher risk of lower extremity amputation in patients with severe peripheral arterial occlusive disease: a secondary analysis of a nationwide, population-based health claims database.

Previous research has shown that diabetes mellitus increases the risk of lower extremity amputation in patients with peripheral arterial occlusive disease. However, to our knowledge, no studies have investigated whether systemic autoimmune disease, in particular systemic vasculitis is associated with a higher risk of lower extremity amputation in these patients. To investigate the association between systemic autoimmune disease and lower extremity amputation in patients with severe peripheral arterial occlusive disease based on a secondary analysis of a nationwide, population-based health claims database. Using the inpatient datafile of the Taiwan's National Health Insurance Research Database (NHIRD), we identified 432 patients with severe peripheral arterial occlusive disease that required hospitalization between 2000 and 2012. We also identified patients who had undergone lower extremity amputation and their comorbidities using the same datafile. The risk of lower extremity amputation was assessed using multiple logistic regression analysis, adjusting for age, sex, insured amount, the urbanization level of residence, and the presence of comorbidities. Among patients with severe peripheral arterial occlusive disease, those with systemic vasculitis exhibited a significant higher risk of lower extremity amputation (adjusted odds ratio [aOR]=6.82, p<0.001). Diabetes mellitus (aOR=4.90, p<0.001) and chronic obstructive pulmonary disease (aOR=2.87, p=0.007) were also significantly associated with a higher risk of lower extremity amputation. Among patients with severe peripheral arterial occlusive disease, a significantly higher risk of lower extremity amputation was observed in those with systemic vasculitis.

The role of Visfatin in atherosclerotic peripheral arterial obstructive disease

Visfatin is an adipokine molecule acting as an essential coenzyme in multiple cellular redox reactions. The increased serum levels of Visfatin have been correlated with metabolic syndrome and endothelial homeostasis. In this study we investigate the possible relationship of Visfatin serum levels with the severity and location of atherosclerotic peripheral arterial occlusive disease (PAOD).Study protocol included 45 consecutive PAOD and 20 Control patients with age >55years old. Definition of PAOD was based in Rutherord’s classification (RC). End-stage PAOD patients (RC-V & -VI) were excluded from study. Data were collected prospectively and included age, gender, atherosclerotic risk factors and the body mass index (BMI). In PAOD patients recorded the PAOD’s clinical stage and the presence of carotid stenosis >50%. PAOD patients divided in two subgroups, those with mild (RC-I & -II) and moderate disease (RC-III & -IV). In all serum samples Visfatin was measured, blindly, twice by anosoenzymatic technique. Statistical analysis was performed by non-parametric Mann-Whitney U test, Pearson’s chi-square, One Way Anova and Kruskall-Wallis tests, as appropriate.The mean Visfatin value in PAOD and Control groups were 38.5±16.0 and 13.9±3.8ng/ml respectively (p<0.0005). In-PAOD subgroup of patients the visfatin values were not affected by demographics, BMI and atherosclerotic risk factors (p>0.05). Univariate analysis showed that severity of PAOD (mild vs severe), presence of carotid stenosis >50% and multilevel disease significantly affected outcomes (p=0.018, p=0.010 and p=0.006 respectively). In multivariate regression analysis severity of PAOD was the solely factor with strong correlation with high visfatin values (p=0.001).High Visfatin levels seem to be strongly correlated with the presence and severity of PAOD. Further and in depth investigation is needed to define the possible role of Visfatin in atherosclerosis and it’s value as a potential prognostic biomarker of PAOD.

Partial Calcanectomy Facilitates Wound Closure of Heel Defects in High-Risk Patients

Heel ulcers in patients with severe peripheral artery occlusive disease represent a challenge to the treating physician. They become more difficult to treat with underlying medical comorbidities. The purpose of this report is to document evidence that partial calcanectomy is simple to perform and clears infected bone, tissue, and ulceration. Between July 2011 and August 2013, 30 consecutive patients presented to our department with heel wounds caused by diabetes mellitus and pressure. After evaluation by a vascular surgeon, 12 patients diagnosed with near total occlusive peripheral vascular disease were included in this report. Of the 12 patients, 7 were women. Their ages ranged from 65 to 79 years (mean, 73.3 years). After admission, surgical debridement was performed emergently with subsequent partial calcanectomy and wound closure. Eight heel wounds (75%) healed completely with no further surgery to achieve defect coverage. Wound dehiscence developed in 4 patients (25%). The mean number of debridements was 1.75 (range, 1-3) with a total operation time of 71.5 minutes (range, 45-114 min). One patient died of acute myocardial infarction 2 weeks after discharge. The mean length of hospital stay was 8.3 days (range, 5-16 days). In this study, we demonstrate that partial calcanectomy is practical for the treatment of plantar heel ulcers in patients with severe comorbidities. With proper surgical planning and postoperative care, partial calcanectomy is a viable alternative to below-the-knee amputation and may better serve the patient who would otherwise be restricted to a sedentary lifestyle.

Urinary cysteinyl leukotrienes in one-year follow-up of percutaneous transluminal angioplasty for peripheral arterial occlusive disease

Background and aimsTreatment of severe peripheral arterial occlusive disease requires percutaneous revascularization. However, little is known about risk factors or predictors for reocclusion/restenosis. Cysteinyl leukotrienes are highly bioactive lipid mediators of inflammation. Their intravascular production may take place in the atheromatous plaque or result from interaction within activated leukocyte-platelet aggregates. MethodsWe prospectively measured urinary leukotriene E4, the main end-metabolite of cysteinyl leukotrienes in a group of 179 subjects with peripheral artery occlusive disease of the lower extremities. At the enrollment to the study, 22.9% had angioplasty and the remaining had angioplasty with stent implantation. During 12-month follow-up, 29.6% developed reocclusion/restenosis despite a standard pharmacotherapy. We evaluated treatment outcomes at 1, 3, 6 and 12-month follow-up visits, along with urinary leukotriene E4 excretion. ResultsDuring the study period, we observed a linear increase of urinary leukotriene E4 excretion only in subjects whose lower limb ischemia worsened. Moreover, elevated leukotriene E4 in urine was found only in subjects who developed reocclusion/restenosis. This was significant not only as a coincidence at the time of the follow-up visit, but leukotriene E4 elevation preceded clinical manifestation of reocclusion/restenosis. ConclusionsOur results demonstrated that serial measurements of urinary leukotriene E4 allowed to predict failure of angioplasty with/or without stent implantation for peripheral artery occlusive disease. However, to prove causality between cysteinyl leukotrienes overproduction and occlusive lower limb ischemia, a clinical trial with leukotrienes modifying drugs would be required.

Cardiovascular risk profile of patients with peripheral arterial occlusive disease during nilotinib therapy.

Over the past few years, data have suggested that severe peripheral arterial occlusive disease (PAOD) is associated with nilotinib exposure. However, the characteristics of this adverse drug reaction are poorly described since its frequency is low. As far as we know, no study using a spontaneous adverse drug reactions reporting system was performed to describe the characteristics of cases of PAOD related to nilotinib. We performed a study to describe the cardiovascular risk profile of cases of PAOD in patients treated with nilotinib spontaneously reported to the French Pharmacovigilance Database (FPVD). We selected all cases of "vascular disorders," as the System Organ Class in MedDRA®, in which nilotinib was "suspected" and recorded in the French Pharmacovigilance Database between 2007 and 21 October 2014. We then identified cases of PAOD with a Low Level Term and through a detailed summary of the clinical description. We identified 25 cases of POAD. Most of the patients were older than 60years (84%) or had another cardiovascular risk factor such as hypercholesterolemia, arterial hypertension, overweight/obesity, smoking, or diabetes mellitus (72%). Females (13 cases) and males (12 cases) were equally represented, but the presence of cardiovascular risk factors was more frequent in females than in males. The mean time from initiation of nilotinib to PAOD onset was 24months and was significantly longer in patients aged less than 60years compared with those aged over 60 years (33.8 ± 24.6months vs. 22.6 ± 17.5months, p = 0.002). Pre-existing cardiovascular risk factors, especially diabetes mellitus, also seem to accelerate its occurrence. The FPVD is a useful tool in describing the cardiovascular risk profile of patients with PAOD during nilotinib exposure. Physicians have to be particularly vigilant in patients older than 60years of age; in patients younger than 60years of age, long-term surveillance has to be maintained.

MAGnesium-oral supplementation to reduce PAin in patients with severe PERipheral arterial occlusive disease: the MAG-PAPER randomised clinical trial protocol

IntroductionMagnesium exerts analgaesic effects in several animal pain models, as well as in patients affected by acute postoperative pain and neuropathic chronic pain. There is no evidence that magnesium can...

Preserve the lower limb in a patient with calcaneal osteomyelitis and severe occlusive peripheral vascular disease by partial calcanectomy

Heel ulcers in patients with severe peripheral artery occlusive disease represent a challenge to the treating physician. They become more difficult to treat with underlying medical comorbidities. We report a case of 76-year-old man with hypertension, diabetes mellitus, and end-stage renal disease in uremia status presented to our hospital with a 3-month history of a diabetic foot ulcer on his right heel. He was diagnosed with near total artery occlusion below the knee at the local hospital, and vascular reconstruction failed. After admission, surgical debridement was performed with subsequent partial calcanectomy facilitating wound closure without tension. After surgery, the foot was immobilized with a short-leg splint for 2 weeks. Thereafter, ankle immobilization was accomplished using a thermal protective plastic splint and cast shoes with a posterior window for wound care. The wound healed well with no recurrence during the 12-month follow-up period, and the patient may return to an ambulatory status, including a normal gait pattern. In this case, we demonstrate that the partial calcanectomy is practical for the treatment of plantar heel ulcers in a patient with severe comorbidities. With proper surgical planning and postoperative care, partial calcanectomy is a viable alternative to below-the-knee amputation and may better serve the patient who would otherwise be restricted to a sedentary lifestyle.

The Role of the Newer Tyrosine Kinase Inhibitors As First Line Treatment in Chronic Phase Chronic Myeloid Leukemia – an Updated Meta-Analysis

▪Background: Imatinib, nilotinib and dasatinib are all considered first line treatment in chronic phase (CP) chronic myeloid leukemia (CML) patients. The choice of the most suitable tyrosine kinase inhibitor (TKI) for an individual patient is influenced by multiple factors including disease characteristics, patient comorbidities and preferences, as well as each TKI’s unique profile of adverse events. A meta-analysis of second generation TKIs as first line treatment for patients with CML was published by our group in 2011. In view of the recently published long term results of three of the trials included in the previous meta-analysis and data from two new trials, we decided to update our data.Objectives: To evaluate the efficacy and toxicity of different TKIs as first line treatment for patients with CML.Methods: Systematic review and meta-analysis of randomized controlled trials comparing first line treatment with the newer TKIs (nilotinib, dasatinib, bosutinib and ponatinib) to imatinib in patients with CP-CML. The MEDLINE, conference proceedings and references were searched until August 2014. Two reviewers appraised the quality of trials and extracted data. The following outcomes were assessed: complete cytogenetic response (CCyR); major molecular response (MMR); complete molecular response (CMR), defined as a 4.5 log reduction in BCR-ABL transcripts; early molecular response, defined as BCR-ABL transcript levels of 10% or less at 3 months; progression to accelerated phase (AP) / blastic crisis (BC); all-cause mortality (ACM) and toxicity. Relative risks (RR) were estimated and pooled. Random-effect model was used in all analysis.Results: Our search yielded six trials including 2,426 patients. These trials compared the effects of nilotinib, dasatinib, bosutinib or ponatinib to imatinib. Data from the six trials were available for analysis of MMR. Treatment with the newer TKIs significantly improved MMR at all-time points (3, 12, 18, 24 and 48 months) compared to imatinib (Table 1). Of note, the newer TKIs significantly increased the rate of CMR compared to imatinib at 12 months (RR 2.68, 95% CI 1.64-4.36, 5 trials, figure 1) and at 24 months (RR 2.04, 95% CI 1.62-2.57, 3 trials). Moreover, there was a statistically significant advantage in favor of the newer TKIs as compared to imatinib in terms of early molecular response at 3 months (RR 1.34, 95% CI 1.27-1.41, 5 trials). Importantly, progression rate to AP/BC at 24 months was significantly lower with the newer TKIs in comparison with imatinib (RR 0.35, 95% CI 0.20-0.61, 4 trials). However there was no difference in ACM (RR 0.73, 95% CI 0.46-1.15, 4 trials). We conducted a meta-analysis for specific adverse events according to the distinct toxicity profile of the different TKIs. Severe peripheral arterial occlusive disease occurs more frequently in the newer TKIs arm (i.e. nilotinib and ponatinib) (RR 8.13, 95% CI 1.51-43.83, 2 trials) than in the imatinib arm. In addition, pleural effusion requiring discontinuation occurs at a higher rate in the newer TKIs arm (RR 4.61, 95% CI 1.31-16.23, 4 trials; dasatinib and bosutinib vs. imatinib). Regarding hematologic toxicity including grade 3-4 anemia and neutropenia, there was no difference between the two arms (all newer TKIs vs. imatinib). However, regarding thrombocytopenia grade 3-4, there were more events with thrombocytopenia in the newer TKIs arm compared to imatinib (RR 1.41, 95% CI 1.01-1.97).Conclusions: With a longer follow-up of 4 years, the newer TKIs remain more potent than imatinib in terms of MMR, CMR and early molecular response. Yet, an effect on overall survival cannot be shown. Since CMR is a prerequisite for treatment discontinuation, the newer TKIs can potentially facilitate cessation of treatment more frequently than imatinib. These data should be taken into consideration in choosing treatment for a newly diagnosed CML patient.Table 1 –MMR at different time pointsTime pointRelative risk95% Confidence of intervalNo. of trials3 months6.632.31-19.01512 months1.681.48-1.89618 months1.371.18-1.59424 months1.281.06-1.54448 months1.201.05-1.383 [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Biomarkers of inflammation may be of use for identification of more severe peripheral arterial occlusive disease

Background:Atherosclerosis is a multifactorial disease with an inflammatory pathophysiological basis. Cytokines released during the atherosclerotic process induce production of C-reactive protein (CRP) in the liver, which is an important marker of inflammation.Objective:We tested whether inflammatory biomarkers were associated with deterioration of peripheral arterial occlusive disease (PAOD) in a population at high cardiovascular risk.Methods:1,330 subjects ≥30 years of age underwent clinical and laboratory examinations as part of a population-based study of the prevalence of diabetes. PAOD was defined as an ankle-brachial index (ABI) ≤0.90. After application of exclusion criteria, the sample comprised 1,038 subjects. Traditional risk factors, CRP and interleukin 6 (IL-6) were also compared across three ABI categories (≤0.70; 0.71-0.90; ≥0.90). Mean values for these variables were compared by presence/absence of DAOP (Student's t test) and by ABI categories (ANOVA). Poisson regression and logistic regression models were used to test for associations between risk factors and DAOP and between risk factors and the ABI categories. Pearson's linear correlation coefficients were calculated for the relationship between CRP and IL-6 levels.Results:Mean age was 56.8±12.9 years, 54% of the sample were women and the prevalence of DAOP was 21.0% (95%CI 18.4-24.1). Individuals with ABI ≤0.70 had higher concentrations of CRP-us (2.1 vs. 1.8) and of IL-6 (1.25 vs. 1.17). Concentrations of CRP and IL-6 were only correlated in patients with DAOP, (p=0.004).Conclusions:The finding that CRP and IL-6 levels were only elevated among people with advanced DAOP may suggest that these biomarkers have a role to play as indicators of more severe disease. Prospective studies are needed to test this hypothesis.

Rapid clinical improvement of peripheral artery occlusive disease symptoms after nilotinib discontinuation despite persisting vascular occlusion

Rapid clinical improvement of peripheral artery occlusive disease symptoms after nilotinib discontinuation despite persisting vascular occlusion

Non-Contrast-Enhanced MR Angiography at 3 Tesla in Patients with Advanced Peripheral Arterial Occlusive Disease

PurposeThe aim of this study was to assess the diagnostic performance of ECG-gated non-contrast-enhanced quiescent interval single-shot (QISS) magnetic resonance angiography at a magnetic field strength of 3 Tesla in patients with advanced peripheral arterial occlusive disease (PAOD).Method and MaterialsA total of 21 consecutive patients with advanced PAOD (Fontaine stage IIb and higher) referred for peripheral magnetic resonance angiography (MRA) were included. Imaging was performed on a 3 T whole body MR. Image quality and stenosis diameter were evaluated in comparison to contrast-enhanced continuous table and TWIST MRA (CE-MRA) as standard of reference. QISS images were acquired with a thickness of 1.5 mm each (high-resolution QISS, HR-QISS). Two blinded readers rated the image quality and the degree of stenosis for both HR-QISS and CE-MRA in 26 predefined arterial vessel segments on 5-point Likert scales.ResultsWith CE-MRA as the reference standard, HR-QISS showed high sensitivity (94.1%), specificity (97.8%), positive (95.1%), and negative predictive value (97.2%) for the detection of significant (≥50%) stenosis. Interreader agreement for stenosis assessment of both HR-QISS and CE-MRA was excellent (κ-values of 0.951 and 0.962, respectively). As compared to CR-MRA, image quality of HR-QISS was significantly lower for the distal aorta, the femoral and iliac arteries (each with p<0.01), while no significant difference was found in the popliteal (p = 0.09) and lower leg arteries (p = 0.78).ConclusionNon-enhanced ECG-gated HR-QISS performs very well in subjects with severe PAOD and is a good alternative for patients with a high risk of nephrogenic systemic fibrosis.

Laterale Supramalleolarlappenplastiken zur Defektdeckung im Sprunggelenks- und Fußbereich

Defect reconstruction by transposition of well-vascularized thin and pliable skin. Defect coverage involving the antero- and dorsolateral distal one third of the lower leg, the dorsolateral and dorsomedial hindfoot and dorsal midfoot. Severe peripheral arterial occlusive disease (PAOD), previous trauma at the anterolateral aspect of the lower leg and foot. Lateral fasciocutaneous supramalleolar flap with orthograde blood flow, fasciocutaneous lateral supramalleolar perforator flap with orthograde blood flow, adipofascial lateral supramalleolar flap with orthograde blood flow, lateral fasciocutaneous supramalleolar flap based on the lateral tarsal artery with retrograde blood flow, lateral fasciocutaneous supramalleolar flap based on the anterolateral malleolar artery with retrograde blood flow according to Oberlin. "Tie over" dressing for grafting site for 5 days (healing of split/full-thickness skin graft), complete immobilization of the lower leg for 7 days in a dorsal plaster splint (ensure that there is no pressure on the flap), progressive increase of range of motion after 1 week, postoperative standardized compression therapy, combined with scar therapy (silicone sheet). Reliable, excellent functional and aesthetic results with thin skin in small to midsize defects. Increasing morbidity of grafting site in larger flaps and risk of neuroma when the superficial peroneal nerve was exposed.

A new COL3A1 mutation in Ehlers–Danlos syndrome type IV

The vascular type of the Ehlers-Danlos syndrome (Ehlers-Danlos syndrome type IV, EDS IV; OMIM #130050) is a rare connective tissue disorder with autosomal dominant transmission caused by mutations in the COL3A1 gene resulting in increased fragility of connective tissue with arterial, intestinal, and uterine ruptures and premature death. We present a 28-year-old female who in addition to typical EDS IV symptoms had severe peripheral artery occlusive disease (PAOD) and subtotal stenosis of the abdominal aorta. COL3A1 sequencing resulted in detection of an as yet undescribed mutation in exon 36 at position 2465 leading to a nucleotide replacement (c.2465G>C; p.G822A). Ultrastructural analysis of a skin biopsy revealed abnormal morphology and distribution of dermal collagen fibres. We conclude that PAOD is a possible manifestation of EDS IV and that further research is required to define its true prevalence among patients with EDS IV and its molecular pathology including genotype-phenotype correlation.