Challenges and opportunities in the management of type 2 diabetes in patients with lower extremity peripheral artery disease: a tailored diagnosis and treatment review.

Lower extremity peripheral artery disease (PAD) often results from atherosclerosis, and is highly prevalent in patients with type 2 diabetes mellitus (T2DM). Individuals with T2DM exhibit a more severe manifestation and a more distal distribution of PAD compared to those without diabetes, adding complexity to the therapeutic management of PAD in this particular patient population. Indeed, the management of PAD in patients with T2DM requires a multidisciplinary and individualized approach that addresses both the systemic effects of diabetes and the specific vascular complications of PAD. Hence, cardiovascular prevention is of the utmost importance in patients with T2DM and PAD, and encompasses smoking cessation, a healthy diet, structured exercise, careful foot monitoring, and adherence to routine preventive treatments such as statins, antiplatelet agents, and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. It is also recommended to incorporate glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) in the medical management of patients with T2DM and PAD, due to their demonstrated cardiovascular benefits. However, the specific impact of these novel glucose-lowering agents for individuals with PAD remains obscured within the background of cardiovascular outcome trials (CVOTs). In this review article, we distil evidence, through a comprehensive literature search of CVOTs and clinical guidelines, to offer key directions for the optimal medical management of individuals with T2DM and lower extremity PAD in the era of GLP-1RA and SGLT2i.

Late Post-Dissection Dynamic Intermittent Malperfusion of the Aortic Arch in Association with a Rare Heterogenous LOX Gene Variation.

Late ischaemic consequences of type A aortic dissection are rare. We present a 6-year late complication of type A aortic dissection treated by Bentall surgery in a 41-year-old patient. The patient presented with several episodes of lipothymia associated with hypertensive attacks with anisotension, cervicalgia, hemicranial headache, abdominal pain and lower limb slipping initially on exertion and later at rest. On dynamic examination, we diagnosed an intermittent dynamic occlusion of the aortic arch and rare LOX gene variation, which is considered to be associated with aneurysm or dissection of the ascending aorta in young patients. Surgical treatment by replacement of the ascending aorta and the aortic arch with reimplantation of the brachiocephalic trunk (BcTr) allowed the symptoms to resolve.

Symptomatic Carotid Free-Floating Thrombus: About Management of 50 Cases in a Referral Neurovascular Center.

BACKGROUND: Carotid free-floating thrombus (CFFT) is an uncommon disorder. The aim of this study was to describe a French cohort of CFFT patients. METHODS: We conducted a retrospective monocentric study from a Stroke Center among patients admitted for stroke with CFFT. RESULTS: Between January 2017 to December 2019, 2038 ischemic strokes were recorded. A total of 50 patients with CFFT were consecutively included (32 men/18 women). The mean age was 58.2 years (±11.7). Their etiologies were atheroma (46%), carotid dissection and web (20%), hypercoagulability disorders (16%) and arrhythmia (10%). Exclusive medical management was performed in 38 patients (76%): 29 (59.2%) were anticoagulated and 9 (18.4%) received antiplatelets alone in the first week. Surgical intervention was performed in the first 30 days for 11 patients (22%). The main surgical indication was a residual carotid stenosis over 70%. Only three patients had a recurrent stroke in the medical group with anticoagulants. No patients in the antiplatelet group or the surgical group had a recurrent stroke. CONCLUSIONS: Our study summarized a large cohort of 50 patients with CFFT. This diagnosis implies the need to search for a local arterial disease and to screen for hypercoagulability states. An initial medical strategy followed by a delayed carotid surgery if the follow-up imaging shows a residual stenosis appears to be safe.

Identifying patients with prostate cancer at increased risk for haematuria during anticoagulation for venous thromboembolism.

BACKGROUND: Haematuria is a common complication in prostate cancer patients receiving anticoagulation for venous thromboembolism (VTE). Early identification of at-risk patients might help to reduce its incidence and severity. METHODS: We used data from the RIETE registry to develop a prognostic score for haematuria during the first year of anticoagulation for VTE. The prognostic score was built using regression coefficients. RESULTS: From March 2001 through March 2021, 1934 patients with prostate cancer and acute VTE were enrolled. Of these, 1034 (53 %) initially presented as pulmonary embolism and 900 (47 %) as isolated deep vein thrombosis (DVT). During anticoagulation (median 181 days; inter-quartile range: 97-354), 99 patients (5.1 %) developed haematuria (fatal 1, major 27, non-major 72). The incidence rate was: 8 events per 100 patient-years (95%CI 6.5-9.7). Median time to haematuria was 53 days (IQR 4-134). On multivariable analysis, recent haematuria, initial presentation as DVT, comorbidity, metastases, haemoglobin levels <11 g/dL, creatinine >1.2 mg/dL, and radiotherapy independently predicted the risk for haematuria. C-statistics was 0.71 (95%CI: 0.65-0.77). A cut-off of ≥1.5 points classified 312 patients (20 %) at high-risk and had the highest sensitivity (51 %; 95%CI: 39-62) and specificity (82 %; 95%CI: 79-83). Our score improved the performance and non-event net reclassification index (NRI) of the RIETE score (c-statistics: 0.61; 95%CI: 0.54-0.68; NRI: 0.09) or VTE-BLEED score (c-statistics: 0.64; 95%CI: 0.58-0.71; NRI: 0.76). CONCLUSIONS: A prognostic score for haematuria during anticoagulation for VTE performed well in patients with prostate cancer, and improved identification compared to other validated scores.

Major gastrointestinal bleeding in patients receiving anticoagulant therapy for venous thromboembolism.

INTRODUCTION: The gastrointestinal (GI) tract is a frequent site of bleeding in patients receiving anticoagulant therapy for venous thromboembolism (VTE). At-risk patients have not been consistently identified yet. METHODS: We used the RIETE registry to assess the clinical characteristics of patients developing major GI bleeding during the course of anticoagulation. Then, we built a predictive score based on multivariable analysis, aiming to identify patients at increased risk for major GI bleeding. RESULTS: We included 87,431 patients with acute VTE. During the course of anticoagulation, 778 (0.89%) suffered major GI bleeding, 815 (0.93%) non-major GI bleeding and 1462 (1.67%) had major bleeding outside the GI tract. During the first 30 days after major GI bleeding, 7.6% of patients re-bled, 3.9% had VTE recurrences and 33% died. On multivariable analysis, male sex, age ≥70 years, initial VTE presentation as pulmonary embolism, active cancer, prior VTE, recent major bleeding in the GI tract, esophageal varicosities, anemia, abnormal prothrombin time, renal insufficiency and use of corticosteroids were associated to an increased risk for major GI bleeding. Using the predictive score, 39,591 patients (45%) were at low risk; 36,602 (42%) at intermediate-risk; 9315 (11%) at high-risk; and 1923 (2.2%) at very high risk. Their rates of major GI bleeding were: 0.21%, 0.96%, 2.41% and 6.08%, respectively. The c-statistics was 0.771 (95%CI. 0.755-0.786). CONCLUSIONS: We have developed a score which has the potential to identify patients at increased risk for GI bleeding, but needs to be externally validated."

STABILISE Technique for a Non-A Non-B Acute Aortic Dissection in Marfan Syndrome.

A 35-year-old man, with a deep pectus excavatum due to a Marfan syndrome treated 9 years before for an acute type A dissection involving only the aortic arch, by a Bentall surgery, was admitted for acute chest pain. Computed tomography (CT) scan showed an acute type non-A non-B dissection extending to the iliac. After 5 days with strict arterial blood pressure management, the patient had recurrent refractory chest pain and a hybrid technique associating full supra-aortic vessels debranching and STABILISE technique during the same procedure was performed. The patient had an uneventful recovery with CT scan showing complete aortic arch aneurysm exclusion.

Fenestrated endovascular aneurysm repair and open surgical repair for the treatment of juxtarenal aortic aneurysms.

OBJECTIVE: The objective of this study was to compare surgical risk and early and late mortality of patients treated for anatomically classified juxtarenal aortic aneurysms (JRAs) by fenestrated endovascular aneurysm repair (F-EVAR) or open surgical repair (OSR) during a period when the two treatments were available and to validate an institutional algorithm for JRA repair. METHODS: We retrospectively included all patients treated electively in our center between January 2005 and December 2015 for JRAs classified into three anatomic categories, excluding suprarenal aneurysms. Lee score and American Society of Anesthesiologists (ASA) class evaluated preoperative surgical risk. We compared clinical and radiologic parameters between the patients treated by F-EVAR and those treated by OSR. The primary study end point was 30-day mortality. We also compared 5-year survival. RESULTS: From 2005 to 2015, there were 191 patients separated into two groups, one treated by OSR (n = 134; mean age, 69 years) and the other treated by F-EVAR (n = 57; mean age, 74 years). Patients of the F-EVAR group were significantly older (P = .001). Intensive care unit length of stay was significantly higher in the OSR group (3.4 days vs 1.5 days; P = .01). Surgical risk was significantly higher in the F-EVAR group as measured by Lee score ≥2 (OSR, 8.9 %; F-EVAR, 21%; P = .02) and ASA class 3 and class 4 (OSR, 32.8%; F-EVAR, 73.6%; P = .001), whereas 30-day postoperative mortality was not significantly different (OSR, 1.5%; F-EVAR, 0%; P = .394). The 5-year survival was not significantly different in the two groups (OSR, 82.1%; F-EVAR, 69.2%). CONCLUSIONS: In this study, despite a higher surgical risk by Lee score and higher ASA class in the group of patients treated by F-EVAR, postoperative mortality was not significantly different between these groups. In our opinion, F-EVAR and OSR of JRA are complementary.

Total Endovascular Treatment of Acute Non-A-non-B Dissection Complicated by Visceral Malperfusion without Primary Entry Tear Coverage.

Management of visceral ischemia due to non-A, non-B dissection is extremely challenging due to the position of the primary entry tear at the level of the brachiocephalic vessels. We report on a patient who was admitted for a complicated non-A, non-B-type dissection with visceral and leg ischemia. A covered stent graft was implanted below the primary entry tear to redirect the flow in the true lumen, associated with stents implantation in the visceral arteries, to treat the dissection's static component. The patient did well, without need for bowel resection visceral or late stent restenosis. Stent-graft implantation below the primary entry tear in cases of visceral ischemia due to non-A, non-B dissection seems feasible.

[Arterial dissection: Different entities for the same name]. / Dissection artérielle : un même nom, plusieurs entités.

Spontaneous arterial dissection is a disease whose prevalence is difficult to know and which varies according to the affected artery territory. It can affect the aorta and all medium caliber peripheral arteries including cerebrovascular arteries, coronary arteries and renal arteries. The pathophysiology is common, it is a bleeding in the media. The causes are diverse and vary by territory. Affected patients have few cardiovascular risk factors. Fibromuscular dysplasia is the condition to look for in these few presentations. The vital and functional prognosis may be engaged. Treatment varies depending on territory, severity, and etiology. Conservative treatment is the first-line treatment.

Young Women with a Long Past of Resistant Hypertension Cured after Surgery of Severe Bilateral Ostial Renal Artery Stenosis.

Fibromuscular dysplasia (FMD) is an underdiagnosed disease which can affect young people and with poor prognosis such as dissection or aneurysm rupture if unknown. This case illustrates a multi-vessel FMD with symptomatic severe bilateral ostial renal artery stenosis and intracranial aneurysms. One of the original features is a very late delay to diagnosis with 23 years between onset of hypertension and renal stenosis diagnosis, particularly due to lower quality of initial CT scan with milder and uncommon abnormalities. The experiment neuroradiologist had suspected the diagnosis of renal FMD because she developed intracranial aneurysms and he confirmed this diagnosis with an artery renal contrast injection during an intracranial angiogram Because of very tight and short stenosis, surgery was chosen for treatment and permitted the cure of hypertension, with normal home blood pressure after 6 months. Several particularities of FMD were presented in this case: important delay diagnosis due to rare lesion and lower sensitivity of CT in this form, the possibility to perform an angiography in high suspicion of FMD, poor prognosis risk with intracranial aneurisms and premature birth child, and the choice for surgery with cure of hypertension. We thought that hypertension etiologic evaluation must be repeated in case of resistant hypertension in young patients, particularly when they developed intracranial aneurysms.

Emergency Embolization of a Ruptured Aneurysm of the Internal Iliac Artery by Direct Ultrasound-Guided Puncture: Report of a Case.

We report the emergency embolization of a ruptured aneurysm of the internal iliac artery in a patient at high surgical risk. Admission computed tomography scan showed that the ostium of the aneurysmal internal iliac artery was covered by a covered stent. In this patient, we chose to carry out an embolization of the aneurysm and its efferent arteries by direct puncture of the aneurysmal sac using an antero-external abdominal approach under ultrasound guidance. Short-term results were favorable and we consider that this technique is one of the therapeutic options to discuss in such situation.

Aneurysm sac shrinkage after endovascular repair: predictive factors and long-term follow-up.

BACKGROUND: The aim of this study was to determine the predictive factors of reduction in diameter ≥10 mm of the aneurysm sac after endovascular treatment and analyze evolution in these patients. METHODS: Between December 1997 and December 2008, all patients electively treated at our center for an infrarenal abdominal aortic aneurysm (AAA) were included in a prospective registry. We did a retrospective study between patients whose aneurysm was reduced by at least 10 mm in diameter on computed tomography scan during follow-up (Group 1) and the other patients who did not (Group 2). A univariate and multivariate statistical analysis was performed. RESULTS: The files of 197 patients (mean age 74.8 years) with a mean follow-up of 54.8 months were reviewed. One hundred two patients (51.8%) had a reduction of ≥10 mm of AAA diameter (Group 1); this reduction was achieved after an average follow-up of 23.6 months. The delay to obtain at least a 10-mm diameter reduction was not influenced by any preoperative characteristics of patients or characteristics of the AAA. Patients in Group 1 were younger (74 vs. 76 years, P = 0.039), with a longer (31 vs. 27.7 mm, P = 0.038) and narrower upper neck (23.1 vs. 24.0 mm, P = 0.02) compared with Group 2. After multivariate analysis, these 3 variables were independently predictive of reduction in AAA diameter. In Group 1, secondary procedures were performed in 13 patients after a diameter reduction of ≥10 mm, including 3 type 1 endoleaks treated after 36 months (1 case) and after 123 months (2 cases) and 1 type 3 endoleak treated after 78 months. In Group 2, secondary procedures were performed in 28 patients, including 9 type 1 endoleaks treated after a median time of 26 months and no type 3 endoleak. Secondary procedures were significantly more frequent in Group 2 than in Group 1 (29.4% vs. 12.7%, respectively; P = 0.005). Freedom from secondary procedure at 5 years was 87.9% in Group 1 and 65.4% in Group 2 (P = 0.003). Freedom from AAA rupture at 8 years was significantly superior in Group 1 than in Group 2 (100% vs. 83.5%, P = 0.008). CONCLUSIONS: Sac shrinkage after endovascular aortic aneurysm repair is more likely observed in younger patients with long and small proximal neck anatomy and is associated with better long-term outcomes. However, late failures do occur even in those with significant sac shrinkage; therefore, follow-up should continue lifelong.

Intranuclear expression of progesterone receptors in smooth muscle cells of renovascular fibromuscular dysplasia: a pilot study.

BACKGROUND: The pathogenesis of fibromuscular dysplasia (FMD) remains poorly understood. Yet, understanding this mechanism has taken on new urgency after recent evidence indicating that FMD is not as rare as previously thought. We speculated that hormonal receptors in the walls of dysplastic renal arteries were implicated in the pathogenesis of FMD. METHODS: We undertook a pilot prospective case-control study comparing histologic findings from renal arteries that were surgically removed in 2 patient groups. The case group included 6 samples from FMD patients who underwent surgery for stenosis or aneurysm caused by FMD. The control group included 3 FMD-free patients who underwent nephrectomy for nonvascular causes. Surgical specimens were sent to the histology laboratory. FMD was defined preoperatively using conventional radiologic criteria and was confirmed by histologic examination. RESULTS: Immunohistochemical staining detected intense progesterone receptor expression in the nuclei of smooth muscle cells in FMD patients. No progesterone receptor expression was found in the FMD-free patients. Estrogen receptor expression was not noted in the 2 groups. CONCLUSIONS: This preliminary finding may suggest that progesterone plays a key role in the pathogenesis of FMD and opens the fields of genetic and therapeutic approaches.

Severe symptomatic stenosis of visceral and renal arteries leading primary antiphospholipid syndrome diagnosis.

Antiphospholipid syndrome (APS) is an autoimmune disorder with combination of at least 1 clinical and 1 laboratory criterion as defined by the SAPPORO statement. Clinical criteria result from vascular thrombosis that can affect artery, venous, or small vessel in any tissue or organ. Arterial stenosis is a rare lesion involved in APS, affecting mainly renal or intracranial arteries. We reported a case of a 33-year-old woman with abdominal angina and high blood pressure (BP). Imaging showed tight, not calcified, and hypodense stenosis of mesenteric superior artery and left renal artery, and a thrombosis of the celiac trunk. Treatment was digestive rest followed by angioplasty and stenting of mesenteric and renal artery, anticoagulation, antiplatelet, and statin therapy. Normal BP and digestive function were obtained postoperatively. Biological tests showed a positive lupus anticoagulant at diagnosis and at 12 weeks, which allowed us to make the diagnosis of APS. Physiopathology of stenosis in APS remains unclear but suggests arterial wall partial thrombosis, accelerated atherosclerosis, and/or proliferation of smooth muscle cells. We recommend screening of arterial stenosis in patients with APS and arterial symptoms, and inversely, searching for APS in young patients with atypical arterial stenosis to allow optimal therapy.

Sphingosine kinase 1 expressed by endothelial colony-forming cells has a critical role in their revascularization activity.

AIMS: Cell therapy based on endothelial colony-forming cells (ECFCs) is a promising option for ischaemic cardiovascular diseases. A better understanding of the mechanisms by which these cells promote revascularization remains a critical challenge to improving their therapeutic potential. We aimed to identify the critical mechanisms involved in the revascularization activity of ECFCs by using the paracrine properties of mesenchymal stem cells (MSC). METHODS AND RESULTS: Conditioned medium from human bone marrow-derived MSCs (MSC-CM) increased the angiogenic activity of cord blood ECFCs in vitro (proliferation, migration, and pseudo-tube formation), the survival of ECFCs in mice (Matrigel Plug assay), and the capacity of ECFCs to promote the recovery of blood perfusion in mice with hindlimb ischaemia. Furthermore, the capillary density in ischaemic gastrocnemius muscle was significantly increased in mice transplanted with the ECFCs pre-treated with the MSC-CM. The enhancement of ECFCs activity involved the up-regulation of sphingosine kinase 1 (SphK1) expression and activity. The inhibition of SphK1 in ECFCs by using an inhibitor or a siRNA knockdown of SphK1 prevented the stimulation of the ECFCs induced by the MSC-CM. The improvement of ECFC activity by MSC-CM also involved the up-regulation of sphingosine-1-phosphate receptor 1 (S1P1) and a S1P/S1P1/3-dependent mechanism. Finally, we showed that the stimulation of ECFCs with exogenous S1P increased angiogenesis and promoted blood perfusion in hindlimb ischaemia. CONCLUSION: The up-regulation of SphK1 and S1P-dependent pathways is critical for the angiogenic/vasculogenic activity of ECFCs. The identification of this pathway provides attractive targets to optimize cell-based therapy for revascularization in ischaemic diseases.

Plasmatic level of leukocyte-derived microparticles is associated with unstable plaque in asymptomatic patients with high-grade carotid stenosis.

OBJECTIVES: This study sought to analyze whether the plasmatic level of leukocyte-derived microparticles (LMP) is associated with unstable plaques in patients with high-grade carotid stenosis. BACKGROUND: Preventive carotid surgery in asymptomatic patients is currently debated given the improvement of medical therapy. Therefore, noninvasive biomarkers that can predict plaque instability are needed. The LMPs, originating from activated or apoptotic leukocytes, are the major microparticle (MP) subset in human carotid plaque extracts. METHODS: Forty-two patients with >70% carotid stenosis were enrolled. Using a new standardized high-sensitivity flow cytometry assay, LMPs were measured before thromboendarterectomy. The removed plaques were characterized as stable or unstable using histological analysis according to the American Heart Association criteria. The LMP levels were analyzed according to the plaque morphology. RESULTS: The median LMP levels were significantly higher in patients with unstable plaque (n = 28; CD11bCD66b+ MP/µl 240 [25th to 75th percentile: 147 to 394], and CD15+ MP/µl 147 [60 to 335]) compared to patients with stable plaque (16 [0 to 234] and 55 [36 to 157]; p < 0.001 and p < 0.01, respectively). The increase in LMP levels was also significant when considering only the group of asymptomatic patients with unstable plaque (n = 10; CD11bCD66b+ MP/µl 199 [153 to 410] and CD15+ MP/µl 78 [56 to 258] compared with patients with stable plaque (n = 14; 20 [0 to 251] and 55 [34 to 102]; p < 0.05 and p < 0.05, respectively). After logistic regression, the neurologic symptoms (odds ratio: 48.7, 95% confidence interval: 3.0 to 788, p < 0.01) and the level of CD11bCD66b+ MPs (odds ratio: 24.4, 95% confidence interval: 2.4 to 245, p < 0.01) independently predicted plaque instability. CONCLUSIONS: LMP constitute a promising biomarker associated with plaque vulnerability in patients with high-grade carotid stenosis. These data provide clues for identifying asymptomatic subjects that are most at risk of neurologic events.