Clinical Implications of Diabetic Peripheral Neuropathy in Primary Infrapopliteal Angioplasty Approach for Neuro-Ischemic Foot Wounds.

BACKGROUND: To assess the clinical effects of diabetic peripheral neuropathy (DPN) in patients with chronic limb-threatening ischemia (CLTI) treated by primary infrapopliteal angioplasty for neuro-ischemic Rutherford 5, foot wounds. MATERIALS AND METHODS: Over a 10-year period (2009-2019), a series of 304 diabetic ischemic limbs adding or not evincible neuropathic affectation were treated by primary infrapopliteal angioplasty and their files were retrospectively reviewed. Mean length of treated arterial lesions was 6.1 cm (range 1-22 cm). Inferior limb vibration perception threshold diagnostic was performed for comparing and scoring detectable DPN in all studied diabetic patients (classed from 0 to 10 points). There were 19% limbs with normal (0-1 points) perception (group 1), 55% others with "mild" and "moderate" (2-6 points) neuropathic impairment (group 2), and 26% limbs showing "severe" (7-10 points) DPN (group 3). RESULTS: Primary infrapopliteal angioplasty succeeded in 89% cases in group 1, in 82% in group 2, and in 68% of limbs in group 3. This latest group assembled the heaviest neuropathic affectation and arterial calcifications and proved the lowest clinical benefit at 36 months: 35% (95% confidence interval [CI]=22% to 48%) of primary patency, 36% (95% CI=22% to 50%) wound healing, and 54% (95% CI=39% to 69%) limb preservation rates. A comparison between groups 1 vs 3 and 2 vs 3 of primary patency (p=0.014 and p=0.043), tissue healing (p=0.049 and p=0.01), and limb salvage (p=0.006 and p=0.023) proved significant, yet without statistical weight for group 1 vs 2 (p>0.05). Overall survival was not significantly affected between groups (p=0.34). CONCLUSION: The presence of severe DPN may jeopardize the results of infrapopliteal angioplasty in terms of patency, tissue cicatrization, and limb preservation, yet without significance on survival of these patients. When present, DPN requires appropriate stratification as specific indicator in CLTI treatment.

Positron Emission Tomography/Computed Tomography Predicts and Detects Complications After Endovascular Repair of Abdominal Aortic Aneurysms.

Purpose: To assess if aortic 18F-fluorodeoxyglucose (FDG) uptake on positron emission tomography/computed tomography (PET/CT) could play a role in predicting complications after endovascular aneurysm repair (EVAR). Materials and Methods: This study involved 2 cohorts of men with abdominal aortic aneurysm treated by EVAR: those who underwent a PET/CT scan before EVAR (n=17) and those who had a PET/CT during follow-up (n=34). Uptake of FDG was measured as the standardized uptake value (SUV). D-dimer, a marker of fibrinolysis, was measured in blood drawn concomitantly with the PET/CT. Results: A significant uptake of FDG in the aneurysm wall was detected by PET/CT before EVAR in 6 of 17 patients. During the first year after EVAR, type II endoleaks developed in 5 of these FDG+ patients vs 3 of 11 FDG- patients (p=0.04). Two of the FDG+ patients had continued sac growth and required conversion to open repair. A significant association between sac growth rate, SUV, and the presence of endoleak was found in the 34 patients who underwent PET/CT after EVAR. Finally, D-dimer was significantly increased in patients with both endoleak and positive PET/CT in the post-EVAR group. Conclusion: This study suggests that the presence of FDG uptake in the aortic wall might be a useful tool to predict patients at high risk of developing post-EVAR complications.

Risk Factor Assessment in a Greek Cohort of Patients With Large Abdominal Aortic Aneurysms.

Environmental and genetic risk factors contribute to the etiology of abdominal aortic aneurysms (AAAs). Matrix metalloproteinases (MMPs) have been associated with the pathophysiology of AAAs. A prospective, nonrandomized case-control study was undertaken to investigate the risk factors for large AAAs (≥5.5 cm) among 175 male Greek AAA patients and to compare the results with a cohort of 166 male controls free from any aortic dilatation, as confirmed by ultrasonography from an existing AAA screening program in the same region. We also assessed the potential association between 2 functional single nucleotide polymorphisms in the genes MMP9 (-1561C/T; rs3918242) and MMP13 (-77A/G; rs2252070), and the presence of large AAAs. Multiple logistic regression analysis revealed AAA family history ( P = .028), hypercholesterolemia ( P < .001), and current smoking ( P < .001) as AAA risk factors. Statistical difference was reached in genotype ( P = .047) and allele ( P = .037) frequencies for rs2252070, but the results did not remain significant after correction for multiple testing. No significant differences in genotype or allele frequencies for rs3918242 were detected. In summary, AAA family history, hypercholesterolemia, and current smoking were found to be risk factors for large AAAs.

Therapeutic Applications of Prostaglandins and Thromboxane A2 Inhibitors in Abdominal Aortic Aneurysms.

BACKGROUND: Abdominal aortic aneurysm (AAA) is one of the leading causes of death in western countries. Surgery is still, at the present time, the sole treatment that has however a significant mortality and cost rate. Many pharmacological agents are under investigation aiming to reduce growth and prevent AAA rupture. These drugs target different pathological pathways and, notably, the excessive production of prostanoids by cyclooxygenases (COX). Intra-aneurysmal thrombus plays an adverse key role in the progression of AAA, platelets being a primary source of prostanoids as thromboxane A2. OBJECTIVE: In this review, we summarize studies targeting prostanoids production and down-stream pathways in cardiovascular diseases, and more specifically in AAA. RESULTS AND CONCLUSION: Various inhibitors of COX or antagonists of prostanoids receptors have been investigated in AAA animal models with conflicting results. In human AAA, only a few number of studies focused on anti-platelet therapy mostly using acetylsalicylic acid (aspirin, ASA), a COX1 inhibitor. Finally, we report preliminary promising results of a model of AAA in rats receiving a thromboxane A2 inhibitor, BM-573 that induced a reduction of aneurysmal growth.

Bilateral central serous retinopathy in a patient with paroxysmal nocturnal hemoglobinuria treated with deferoxamine.

PURPOSE: To report a case of acute bilateral central serous retinopathy associated with deferoxamine therapy in the context of paroxysmal nocturnal hemoglobinuria. METHODS: Spectral-domain optical coherence tomography and fundus autofluorescence were used to investigate posterior segment changes. RESULTS: A 76-year-old man with paroxysmal nocturnal hemoglobinuria and hereditary spherocytosis was started on deferoxamine for iron overload secondary to previous blood transfusions. Four days after initiation of treatment, he developed bilateral reduced vision and metamorphopsia. He was noted to have bilateral central serous retinopathy. Symptoms and serous retinal detachment resolved rapidly following discontinuation of treatment. CONCLUSIONS: This case represents the first report of acute bilateral central serous retinopathy associated with deferoxamine therapy. Cessation of deferoxamine resulted in rapid visual recovery.

Extending Abdominal Aortic Aneurysm Detection to Older Age Groups: Preliminary Results from the Liège Screening Programme.

BACKGROUND: There is evident benefit in terms of reduced aneurysm-related mortality from screening programs of abdominal aortic aneurysm (AAA) in men aged 65 years and more. Recent studies in the United Kingdom and Sweden have shown a decline of the prevalence of AAA in the general population. Current screening policies (e.g., men aged 65-74 years), however, do not account for aging and increased life expectancy of Western populations. This study investigated AAA detection by extending the target population to older age groups (75-85 years). METHODS: AAA screening was conducted in the County of Chaudfontaine (Liège, Belgium) on the population of elderly (n = 3,054). The participation rate was 36%. The 1,101 participants (722 men aged 65-85 years and 379 women aged 74-85 years) were examined by ultrasound scan. AAA was defined as an infrarenal aortic outer-outer diameter of at least 3 cm. Demographics, clinical parameters, and risk factors were also recorded. AAA prevalence was estimated, and patients with and without AAA were compared by logistic regression. RESULTS: The overall AAA prevalence was 3.6% (n = 40). In female participants, AAA prevalence was low (1.3%). In men, it amounted 2.7% in the 65-74 age group but rose to 7.3% in the age-extended group (75-85 years). Further in addition to age, height, current smoking, history of coronary artery disease, hypercholesterolemia, peripheral artery disease of the lower limbs, and varicose veins were significantly associated with the presence of AAA. CONCLUSIONS: These preliminary findings, based on a representative sample of the elderly population of the Liège region, support the idea that current AAA screening policies should be updated to cover an increasingly aging population. The presence of varicose veins as a potential risk factor for AAA should also be considered during screening.

Cervical artery dissections and type A aortic dissection in a family with a novel missense COL3A1 mutation of vascular type Ehlers-Danlos syndrome.

Cervical artery dissection (CeAD) is a rare condition. One of the causes is the vascular type of Ehlers-Danlos syndrome (vEDS). A novel missense mutation in COL3A1 was found in a young patient with CeAD as the single manifestation of vEDS. This is a heterozygous c.953G > A mutation in exon 14, disrupting the normal Gly-X-Y repeats of type III procollagen, by converting glycine to aspartic acid.

Sex differences in abdominal aortic aneurysm: the role of sex hormones.

Abdominal aortic aneurysm (AAA) is a complex multifactorial disease with genetic and environmental components. AAA is more common in men, whereas women have a greater risk of rupture and more frequently have concomitant thoracic aortic aneurysms. Moreover, women are diagnosed with AAA about 10 years later and seem to be protected by female sex hormones. In this MEDLINE-based review of literature, we examined human and animal in vivo and in vitro studies to further deepen our understanding of the sexual dimorphism of AAA. We focus on the role of sex hormones during the formation and growth of AAA. Endogenous estrogens and exogenous 17ß-estradiol were found to exert favorable actions protecting from AAA in animal models, whereas exogenous hormone replacement therapy in humans had inconclusive results. Androgens, known to have detrimental effects in the vasculature, in sufficient levels maintain the integrity of the aortic wall through their anabolic actions and act differentially in men and women, whereas lower levels of testosterone have been associated with AAA in humans. In conclusion, sex differences remain an important area of AAA research, but further studies especially in humans are needed. Furthermore, differential molecular mechanisms of sex hormones constitute a potential therapeutic target for AAA.

Serum levels of IGF-I, IGFBP-3 and colorectal cancer risk: results from the EPIC cohort, plus a meta-analysis of prospective studies.

Several prospective studies have shown a moderate positive association between increasing circulating insulin-like growth factor-I (IGF-I) levels and colorectal cancer risk. However, the associations were often statistically nonsignificant, and the relationship of cancer risk with IGF-I's major binding protein, IGFBP-3, showed major discrepancies between studies. We investigated the association of colorectal cancer risk with serum IGF-I, total and intact IGFBP-3, in a case-control study nested within the EPIC cohort (1,121 cases of colorectal cancer and 1,121 matched controls). Conditional logistic regression was used to adjust for possible confounders. Our present study results were combined in a meta-analysis with those from 9 previous prospective studies to examine the overall evidence for a relationship of prediagnostic serum IGF-I with colorectal cancer risk. In the EPIC study, serum concentrations of IGF-I and IGFBP-3 showed no associations with risk of colorectal cancer overall. Only in subgroup analyses did our study show moderate positive associations of IGF-I levels with risk, either among younger participants only (and only for colon cancer) or among participants whose milk intakes were in the lowest tertile of the population distribution (RR for an increase of 100 ng/ml = 1.43 [95% CI = 1.13-1.93]). Nevertheless, in the meta-analysis a modest positive association remained between serum IGF-I and colorectal cancer risk overall (RR = 1.07 [1.01-1.14] for 1 standard deviation increase in IGF-I). Overall, data from our present study and previous prospective studies combined indicate a relatively modest association of colorectal cancer risk with serum IGF-I.

Lifestyle factors and serum androgens among 636 middle aged men from seven countries in the European Prospective Investigation into Cancer and Nutrition (EPIC).

OBJECTIVE: To evaluate the association between lifestyle and dietary factors and serum concentrations of androgens in middle-aged healthy men. METHODS: We conducted a cross-sectional analysis of the association of lifestyle factors with circulating concentrations of androstenedione (A-dione), 3-alpha-androstanediol glucuronide (A-diol-g), testosterone (T), SHBG (sex hormone-binding globulin), and free testosterone (FT) among 636 men in the European Prospective Investigation into Cancer and Nutrition. RESULTS: Compared with the youngest age group (40-49 years), the oldest (70-79 years) had a higher mean concentration of SHBG (by 44%) and lower mean concentrations of A-diol-g (by 29%) FT (19%). Men in the highest BMI group (> or =29.83 kg/m(2)) had a higher mean A-diol-g concentration (by 38%) and lower mean concentration of T (by 20%) SHBG (29%) compared with the lowest (<24.16 kg/m(2)). Current smokers had higher mean concentrations of T (by 13%), SHBG (14%), and A-dione (15%) compared with never smokers. Physical activity and dietary factors were not associated with androgen concentrations, although men in the highest fifth of alcohol intake had higher mean concentrations of A-dione (by 9%), FT (11%) compared with the lowest. CONCLUSION: Our results suggest that age, body weight, smoking, and alcohol intake are associated with circulating androgen concentrations in men.