Occurrence of Major Local Lower Limb Events in Type 2 Diabetic Patients with Lower Extremity Arterial Disease: Impact of Metformin.

BACKGROUNDS: Patients with type 2 diabetes mellitus (T2DM) are particularly at risk of developing major adverse cardiovascular events (MACE) and peripheral artery disease (PAD) due to an acceleration of the atherosclerotic process linked to hyperglycemia and inflammation with a greater risk of local complications. We aimed to identify the predictive factors for major adverse limb events (MALE) in T2DM patients with PAD to manage modifiable factors at an early stage. METHODS: This is a prospective study in which T2DM patients with PAD were included from November 2017 to May 2018 and followed over 12 months. The predictive factors for the onset of MALE, MACE, and death from all causes have been identified. RESULTS: A total of 100 patients were included; 37% of the patients developed a MALE. After multivariate analysis, metformin was associated with a decrease of MALE (odds ratio (OR) = 0.26; 95% confidence interval (CI) [0.10; 0.68]; P = 0.007), and a history of the treatment of intravenous iloprost was associated with an increased risk of MALE (OR = 5.70; 95% CI [1.31; 31.93]; P = 0.029). Regular physical activity was associated with a decreased risk of MACE (OR = 0.07; 95% CI [0; 0.44]; P = 0.021). A history of stroke and a history of venous thromboembolism were associated with an increased all-cause mortality risk with OR = 3.68; 95% CI [1.17; 11.5]; P = 0.025 and OR = 3.78; 95% CI [1.16; 12.3]; P = 0.027. CONCLUSIONS: Metformin is protective against local complications in people with diabetes with PAD and should be prescribed to diabetic patients with PAD at an early stage.

Peripheral arterial disease and systematic detection of circulating tumor cells: rationale and design of the DETECTOR prospective cohort study.

BACKGROUND: Smoking is a strong risk factor for cancer and atherosclerosis. Cancer mortality, especially from lung cancer, overtakes cardiovascular (CV) death rate in patients with peripheral arterial disease (PAD). Only a few patients with lung cancer after PAD management may benefit from surgical excision. Circulating tumor cells (CTC) associated with low-dose chest CT (LDCT) may improve early cancer detection. This study focuses on a screening strategy that can address not only lung cancer but all tobacco-related cancers in this high-risk population. METHODS: DETECTOR Project is a prospective cohort study in two French University hospitals. Participants are smokers or former smokers (≥30 pack-years, quitted ≤15 years), aged ≥55 to 80 years, with atherosclerotic PAD or abdominal aortic aneurysm. After the first screening round combining LDCT and CTC search on a blood sample, two other screening rounds will be performed at one-year interval. Incidental lung nodule volume, volume doubling time and presence of CTC will be taken into consideration for adapted diagnostic management. In case of negative LDCT and presence of CTC, a contrast enhanced whole-body PET/CT will be performed for extra-pulmonary malignancy screening. Psychological impact of this screening strategy will be evaluated in population study using a qualitative methodology. Assuming 10% prevalence of smoking-associated cancer in the studied population, a total of at least 300 participants will be enrolled. DISCUSSION: Epidemiological data underline an increase incidence in cancer and related death in the follow-up of patients with PAD, compared with the general population, particularly for tobacco-related cancers. The clinical benefit of a special workup for neoplasms in patients with PAD and a history of cigarette smoking has never been investigated. By considering CTCs detection in this very high-risk selected PAD population for tobacco-induced cancer, we expect to detect earlier pulmonary and extra-pulmonary malignancies, at a potentially curable stage. TRIAL REGISTRATION: The study was registered in the French National Agency for Medicines and Health Products Safety (No N° EUDRACT_ID RCB: 2016-A00657-44) and was approved by the ethics Committee for Persons Protection (IRB number 1072 and n° initial agreement 2016-08-02; ClinicalTrials.gov identifier NCT02849041).

Hyposplenism revealed by Plasmodium malariae infection.

BACKGROUND: Hyposplenism, due to splenectomy, inherited red blood cell disorders or acquired conditions such as celiac disease, has an important impact on the severity of malaria, especially in non-immune patients. Conversely, that malaria may reveal functional hyposplenism has not been described previously. METHODS: A 31-year old gardener was diagnosed with an uncomplicated attack of Plasmodium malariae 11 years after leaving the endemic area. In addition to trophozoites and schizonts, thick and thin smears also showed Howell-Jolly bodies, pointing to functional hyposplenism. This was later confirmed by the presence of a calcified spleen in the context of S/ß + sickle-cell syndrome in a patient previously unaware of this condition. CONCLUSION: Malaria may reveal hyposplenism. Although Howell-Jolly bodies are morphologically similar to nuclei of young Plasmodium trophozoite, distinction on smears is based on the absence of cytoplasm and irregular size of Howell-Jolly bodies. In the patient reported here, hyposplenism was revealed by the occurrence of P. malariae infection relatively late in life. Timely diagnosis of hyposplenism resulted in the implementation of appropriate measures to prevent overwhelming infection with capsulated bacteria. This observation highlights the importance of diagnosing hyposplenism in patients with malaria despite the morphological similarities between ring nuclei and Howell-Jolly bodies on thick smears.

Fluoroquinolone Use Preceding Visceral Artery Dissection: A Case Series.

Fluoroquinolones (FQ), commonly prescribed antibiotics, may trigger aortic and carotid dissections. We report three successive cases of visceral artery dissection: one patient with celiac trunk dissection and two with dissection of the superior mesenteric artery. These events occurred up to 4 months after 7 to 14 days of FQ treatment (2 cases of ofloxacin, 1 of norfloxacin). There was no other apparent cause of dissection. These dissections were isolated, apart from a minimal aortic dissection separate from the visceral arterial dissection in one case. A case series cannot certify the relationship between dissection and FQ, but it can be hypothesized. The association between fluoroquinolone use and higher occurrence of aneurysm and dissection remains discussed in aortic syndrome. The potential link between FQ and visceral artery dissection is even less described but should be reported in the absence of previous cases in the literature. The pathophysiological theory is the induction of overexpression of some matrix metalloproteinases and a decrease of their inhibitors, provoking a dysregulation in collagen synthesis and degradation of the extracellular matrix.

Women Specific Characteristics and 1-Year Outcome Among Patients Hospitalized for Peripheral Artery Disease: A Monocentric Cohort Analysis in a Tertiary Center.

Although women have lower age-standardized cardiovascular disease incidence, prevalence, and death-related rates than men, there are also reports indicating that women with cardiovascular disease receive less care, fewer investigations, and have poorer outcomes after a coronary event. The aims of this study were to compare the characteristics of men and women hospitalized for peripheral artery disease (PAD), their cardiovascular and limb outcomes, and their 1-year mortality. The study is a prospective registry collecting data about all consecutive patients hospitalized for PAD within the vascular department of the tertiary center Georges-Pompidou European Hospital (Paris, France). Patients were required to have one of three inclusion criteria: previous revascularization of the lower limb or any lower limb artery occlusion due to an atherosclerotic vascular disease or hemodynamic evidence of PAD. Exclusion criteria were patients with lower extremity arterial occlusion due to another cause. All patients were followed-up for at least 12 months after the initial hospitalization. Among the 235 patients included, there were 61 women (26%), older than men with a median age of 75.6 and 68.3 years, respectively. Main cardiovascular risk factors and comorbidities were similar for men and women except more former or current smokers [145 (83.4%) vs. 33 (54.1%)] and more history of coronary heart disease [42 (24.1%) vs. 7 (11.5%)] in men. Most patients [138 (58.8%)] had critical limb ischemia and 97 (41.3%) had claudication, with no difference for sex. After discharge, 218 patients received an antithrombotic therapy (93.2%), 195 a lipid-lowering drug (83.3%), 185 an angiotensin converting enzyme inhibitor or angiotensin-receptor blocker (78.9%), similarly between sex. At 1-year, overall mortality, major adverse cardiovascular events, major adverse limb events did not differ with 23 (13.2%), 11 (6.3%) and 32 (18.4%) in men, and 8 (13.1%), 3 (4.9%), 15 (24.6%) in women, respectively, despite the difference in age. Overall mortality, cardiovascular outcomes, limb revascularization or amputation did not differ between men and women, 1-year after hospitalization for PAD although the latter were older, less smoker and had less coronary artery disease. Due to the small size of this cohort, larger studies and future research are needed to better understand sex-specific mechanisms in the pathophysiology and natural history of PAD.

"Ranger BTK" a Prospective Single-Centre Cohort Study on a New Drug-Coated Balloon for Below the Knee Lesions in Patients with Critical Limb Ischemia.

PURPOSE: Restenosis remains a limitation of endovascular angioplasty with a patency of 30% in BTK at 12 months. Several studies on drug-coated balloons have not demonstrated any improvements in terms of patency and target lesions revascularization in BTK lesions. This prospective single-centre cohort study evaluates the safety and efficacy of a new generation low-dose drug-coated balloon (DCB) with a reduced crystalline structure to treat below the knee (BTK) lesions in patients with critical limb ischemia (CLI). MATERIALS AND METHODS: Between November 2016 and November 2017, 30 consecutive patients (mean 68.8 ± 12.7 years, 6 female) with BTK lesions and CLI were included in this single-centre, prospective non-randomized cohort study. All patients with rest pain and/or ischemic wound associated with BTK lesions were included in the study. Mean lesion length was 133.6 ± 94.5 mm and 18(60%) were chronic total occlusions. The primary safety outcome parameter was a composite of all-cause mortality and major amputation at 6 months. The primary efficacy outcome parameter was the primary angiographic patency at 6 months (defined as freedom from clinically driven target lesion revascularization and the absence of significant restenosis (> 50%) as determined by core laboratory angiography assessment. Immediate technical success, late lumen loss (LLL), clinical target lesion revascularization (TLR) and ulcer healing rates at 12 months were also evaluated. RESULTS: Immediate technical success was 97%(29/30): one patient had an acute thrombosis at the completion of index procedure. Primary safety outcome parameter was 94%(28/30): one patient underwent major amputation and one patient died of other comorbidities at 2 months. Another patient had a major amputation at 7.5 months. Angiographic follow-up was available in 20 patients. Primary angiographic patency was 57%(12/21 lesions), and LLL was 0.99 ± 0.68 mm at 6 months. Freedom from TLR was 89% at 12 months. The rate of ulcer healing was 76% at 12 months. CONCLUSION: Ranger DCB balloons to treat CLI patients demonstrated a positive trend with good safety outcomes parameters. Further randomized studies are needed to understand the usefulness compared to POBA.

Acute Digital Ischemia After Arterial Injection of Crushed Zolpidem Tablets: Role of Microcrystalline Cellulose? A Case Report.

Literature is scarce on acute ischemia after intra-arterial injection of crushed tablets and no effective medical treatment against the progression of lesions is reported. The only factor able to modify the outcome is the delay between injection and management by a specialized vascular team. Moreover the risk of necrosis seems higher after benzodiazepine intra-arterial injection than with other drugs. We tried to find out mechanistic explanations. We report on the case of a 31-year-old drug addict woman who self-injected into her left brachial artery crushed tablets of zolpidem. She developed an acute ischemia of the left hand, with necrosis of the intermediate and distal phalanges of fingers II, III, and IV. Angiogram of the left upper arm confirmed the distal arterial occlusions with no run-off after the palmar arch in the necrotic fingers. Once she was admitted into our vascular unit, intravenous vasodilator therapy by iloprost, heparin and local protective care were rapidly introduced. After delineation between living and necrotic tissues, she required distal amputations of the affected fingers. The clinical severity of arterial injections of benzodiazepine tablets is linked to the association of several pathophysiological mechanisms. Rather than related benzodiazepine pharmacologic effects with tissue ischemia, by the inhibition of phosphodiesterase, a vasodilator intermediate, or through the peripheral benzodiazepine-type receptor, the predominant mechanism is more likely in relation with microcrystalline cellulose, one component of zolpidem tablets, known as potential embolic agents. They are insoluble and resistant to degradation in water. These properties are probably prominent in the case we described here. Through this case report we want to drag attention of physicians in charge of a patient with acute ischemia after crushed tablet accidental intra-arterial injection, not only to look at the drug injected but also the other components of the tablet and especially to microcrystalline cellulose.

Non-invasive recanalization of deep venous thrombosis by high frequency ultrasound in a swine model with follow-up.

AIMS: Pulsed cavitational ultrasound therapy (thombotripsy) allows the accurate fractionation of a distant thrombus. We aimed to evaluate the efficacy and safety of non-invasive thrombotripsy using a robotic assisted and high frequency ultrasound approach to recanalize proximal deep venous thrombosis (DVT) in a swine model. METHODS: Occlusive thrombosis was obtained with a dual jugular and femoral endoveinous approach. The therapeutic device was composed of a 2.25 MHz focused transducer centered by a linear ultrasound probe, and a robotic arm. The feasibility, security, and efficacy (venous channel patency) assessment after thrombotripsy was performed on 13 pigs with acute occluded DVT. To assess the mid-term efficacy of this technique, 8 pigs were followed up for 14 days after thrombotripsy and compared with 8 control pigs. The primary efficacy endpoint was the venous patency. Safety was assessed by the search for local vessel wall injury and pulmonary embolism. RESULTS: We succeeded in treating all pigs except two with no accessible femoral vein. After median treatment duration of 23 minutes of cavitation, all treated DVT were fully recanalized acutely. At 14 days, in the treated group, six of the eight pigs had a persistent patent vein and two pigs had a venous reocclusion. In the control group all pigs had a persistent venous occlusion. At sacrifice, no local vein nor arterial wall damage were observed as well as no evidence of pulmonary embolism in all pigs. CONCLUSION: High frequency thrombotripsy seems to be effective and safe for non-invasive venous recanalization of DVT.

Impact of betablockers on general and local outcome in patients hospitalized for lower extremity peripheral artery disease: The COPART Registry.

Lower extremity peripheral artery disease (PAD) is one manifestation of atherosclerosis. Patients with PAD have an increased rate of mortality due to concurrent coronary artery disease and hypertension. Betablockers (BB) may, therefore, be prescribed, especially in case of heart failure. However, BB safety in PAD is controversial, because of presumed peripheral hemodynamic consequences of BB that could lead to worsening of symptoms in patients with PAD. In this context, we aimed to determine the impact of BB on all-cause and cardiovascular mortality and amputation rate at 1 year after hospitalization for PAD from the COPART Registry population. This is a prospective multicenter observational study collecting data from consecutive patients hospitalized for PAD in vascular medicine departments of 4 academic hospitals in France. Patients with, either claudication, critical limb ischemia or acute lower limb ischemia related to a documented PAD were included. We compared the outcomes of patients with BB versus those without BB in their prescription list at hospital discharge. The mean age of the study population was 70.9 years, predominantly composed of males (71%). Among the 1267 patients at admission, 28% were treated by BB for hypertension, prior myocardial infarction or heart failure. During their hospital stay, 40% underwent revascularization (including bypass surgery 29% and angioplasty 74%), 17% required an amputation, and 5% died. In a multivariate analysis, only prior myocardial infarction was found associated with BB prescription with an odds ratio (OR) of 3.11, P < 0.001. Conversely, chronic obstructive pulmonary disease or PAD with ulcer impeded BB prescription (OR: 0.57 and 0.64, P = 0.007; P = 0.001, respectively). One-year overall mortality of patients with BB did not differ from those without (23% vs. 23%, P = 0.95). The 1-year amputation rate did not differ either (4% vs. 6%, P = 0.14). Patients hospitalized for PAD with a BB in their prescription did not worsen their outcome at 1 year compared to patients without BB. Based on these safety data, prospective study could be conducted to assess the effect of BB on long-term mortality and amputation rate in patients with mild, moderate, and severe PAD.