Severe early-onset manifestations of pseudoxanthoma elasticum resulting from the cumulative effects of several deleterious mutations in ENPP1, ABCC6 and HBB: transient improvement in ectopic calcification with sodium thiosulfate.

Pseudoxanthoma elasticum (PXE) is a rare disorder characterized by fragmentation and progressive calcification of elastic fibres in connective tissues. Overlap has been reported between the inherited PXE phenotype associated with ENPP1, ABCC6 or NT5E mutations and acquired PXE clinical manifestations associated with haemoglobinopathies induced by HBB mutations. No treatment is currently available for PXE. A young boy presented with severe early-onset systemic calcifications occurring in the skin as elastosis perforans serpiginosa (EPS) and in the arteries, causing mesenteric and limb ischaemia. Analyses revealed deleterious ABCC6, ENPP1 and HBB mutations. The diagnosis of severe PXE was retained and we have coined the term 'PXE+ syndrome' to describe the cumulative effects of the various mutations in this uncommon phenotype. Given the severity, rapid progression and a potentially fatal prognosis, intravenous sodium thiosulfate (STS) was initiated at 25 g three times weekly for 6 months. Numerous side-effects prompted dosage adjustment to 10 g intravenously daily. Treatment efficacy was evaluated at 6 months. Asthaenia, anorexia and pre-/postprandial pain had subsided, entailing weight gain. Abdominal EPS had diminished. Calcific stenosis of the coeliac and mesenteric arteries was no longer detectable on arterial ultrasonography. Follow-up revealed only transient efficacy of STS. Discontinuation of treatment to evaluate the persistence of effects resulted in relapse of the initial symptomatology after 4 months. STS efficacy is conceivably due to strong antioxidant properties and chelation of calcium to form soluble calcium thiosulfate complexes. This case is suggestive of PXE+ syndrome for which STS may represent potential treatment in severe cases. What's already known about this topic? Generalized arterial calcification of infancy may occur in association with ABCC6 mutations and pseudoxanthoma elasticum (PXE) can be linked to ENPP1 mutations. A PXE-like phenotype has also been reported in a subset of patients with inherited haemoglobinopathies, namely sickle cell disease or ß-thalassaemia, related to HBB mutations. To date, there is still no cure for PXE. What does this study add? We report a severe case of PXE resulting from the cumulative effects of several deleterious mutations in ENPP1, ABCC6 and HBB. We suggest the term 'PXE+ syndrome' to describe such patients. Sodium thiosulfate therapy could represent a potential option in severe cases of PXE+ syndrome.

[Impact of sickle cell trait on arterial stiffness in African subjects]. / Impact du trait drépanocytaire sur la rigidité artérielle des sujets africains.

Sickle cell trait (SCT) is the benign condition of sickle cell disease. Often asymptomatic, the carriers of the sickle cell trait have hemorheological disturbances with increased oxidative stress compared to healthy subjects. These disturbances can lead to structural and functional changes in large vessels. The aim of the study was to measure arterial stiffness, an independent marker of subclinical atherosclerosis, SCT carriers compared to sickle cell anemia (SCA) subjects. Nine SCT carriers aged 32±9 years (7 men) were compared to 14 SCA subjects aged 29±9 years (2 men) and 22 control subjects aged 34±9 years (11 men) recruited by the National blood transfusion center (CNTS) in Dakar (Senegal). Arterial stiffness was assessed by measurement of the finger-toe pulse wave velocity (PWVft) using pOpmètre® (Axelife SAS-France). The cardiovascular risk (CVR) was assessed according to the Framingham Laurier score. The SCT carriers had a higher PWVft (m/s) than SCA subjects (8.2±2.2 vs 6.1±0.9m/s, P=0.004) but not different from that of healthy controls (8.2±2.2 vs 7.4±1.8m/s, P=0.33). Linear regression showed a positive relationship between PWVft and the pulse pressure (PP) (P˂0.001; r2=0.39; F=13.20). The results show that the SCT carriers have stiffer arteries than SCA subjects. Linear regressions adjusted for age, mean arterial pressure (MAP) and PP, showed that only age and PP were independently correlated with arterial stiffness in the entire population.

Osteoprotegerin levels are associated with liver fat and liver markers in dysmetabolic adults.

AIM: This study aimed to determine the association between visceral adipose tissue (VAT), liver fat (LF) content, and other markers of the metabolic syndrome (MetS) and osteoprotegerin (OPG) in dysmetabolic adults. METHODS: Subjects from the NUMEVOX cohort were included if they fulfilled at least one MetS criterion. They then underwent a thorough metabolic and cardiovascular evaluation, including arterial stiffness, atherosclerotic plaques, homoeostasis model assessment for insulin resistance (HOMA-IR) indices and OPG. VAT and LF content were measured by magnetic resonance imaging (MRI). Ultrasound examination of arteries and arterial stiffness were recorded, and age- and gender-adjusted paired correlations calculated. RESULTS: Body mass index, waist circumference and MRI-derived VAT correlated with OPG, whereas abdominal subcutaneous fat did not. OPG levels were strongly correlated with LF content (r=0.25, P=0.003), liver markers such as alanine aminotransferase (r=0.39, P<0.001) and HOMA-IR index (r=0.39, P<0.0001). Plasma OPG also correlated with arterial stiffness and the number of atherosclerotic sites. CONCLUSION: Plasma OPG levels are positively associated with both liver markers and increased LF content, but not with subcutaneous fat in dysmetabolic men. These findings suggest that elevated OPG levels may play a role in the link between fatty liver disease and enhanced cardiovascular risk.

Evidence for a vasomotor cyclo-oxygenase dependent mechanism of sensitization at the cutaneous level.

AIMS: Current-induced vasodilation (CIV) is an axon-reflex response observed during monopolar current application such as iontophoresis. Cyclo-oxygenase derivates (COD) participate in CIV and act as sensitizing agents at the anodal level. Mechanisms involved during cathodal current application (CCA) are partially unknown. In a randomized double-blind crossover trial, we tested in 16 healthy subjects (i) the influence of the inter-stimulation interval (I-I) by comparing CIV following all-at-once 10 s CCA against 2 × 5 s CCA with intervals ranging from15 s-16 min and (ii) the participation of COD in CIV using 1 g aspirin or placebo intake. METHODS: Measurements were repeated 2 h and 14 days after treatment. Laser Doppler flowmetry assessed cutaneous blood flow, reported in multiples of baseline. RESULTS: Before treatment, peak vasodilation 10 min after the last current application (CVCstim2 ) increased compared with baseline whatever the I-I. Increase in CVCstim2 from baseline was greater for the 4 min (9.4 (5.3, 10.9) times; median (1(st) percentile, 3(rd) percentile)) and higher I-Is compared with all-at-once delivery (3.0 (2.1, 4.3) times, P < 0.05). The response was similar after placebo but aspirin abolished this vasodilation (increase by 1.2 (1.1, 1.3) times for all-at-once delivery and by 1.5 (1.3, 1.7) ± 0.3 times for 4 min interval, 2 h after aspirin intake) that recovered after 14 days. CONCLUSIONS: This confirms the participation of COD in CIV with CCA and their sensitizing action. This model can represent an attractive way to study the axon-reflex and sensitizing function of COD in humans.

Can we identify response markers to antihypertensive drugs? First results from the IDEAL Trial.

Current antihypertensive strategies do not take into account that individual characteristics may influence the magnitude of blood pressure (BP) reduction. Guidelines promote trial-and-error approaches with many different drugs. We conducted the Identification of the Determinants of the Efficacy of Arterial blood pressure Lowering drugs (IDEAL) Trial to identify factors associated with BP responses to perindopril and indapamide. IDEAL was a cross-over, double-blind, placebo-controlled trial, involving four 4-week periods: indapamide, perindopril and two placebo. Eligible patients were untreated, hypertensive and aged 25-70 years. The main outcome was systolic BP (SBP) response to drugs. The 112 participants with good compliance had a mean age of 52. One in every three participants was a woman. In middle-aged women, the SBP reduction from drugs was -11.5 mm Hg (indapamide) and -8.3 mm Hg (perindopril). In men, the response was significantly smaller: -4.8 mm Hg (indapamide) and -4.3 (perindopril) (P for sex differences 0.001 and 0.015, respectively). SBP response to perindopril decreased by 2 mm Hg every 10 years of age in both sexes (P=0.01). The response to indapamide increased by 3 mm Hg every 10 years of age gradient in women (P=0.02). Age and sex were important determinants of BP response for antihypertensive drugs in the IDEAL population. This should be taken into account when choosing drugs a priori.

Comparison of reported symptoms to those produced by treadmill testing in patients with claudication suspected of arterial origin.

AIM: We aimed at comparing lower limb symptoms reported by history to those observed during a standard treadmill test. METHODS: We retrospectively studied symptomatic patients referred over a three years period for suspected arterial claudication and used the Edinburgh claudication questionnaire before exercise and symptoms observed on a treadmill. We confronted, right and left, proximal (lower-back thigh or buttocks) and distal (leg or foot) lower-limb symptoms before and during treadmill exercise. Results are reported as mean ± standard deviation for percentage and 95% confidence interval and Kappa statistics are performed. RESULTS: Of 795 patients with claudication, aged 63 ± 12 years, treadmill test resulted in 715 reporting lower-limb symptoms on treadmill. Cohen's Kappa for the site-specific analysis of symptoms by history vs. symptoms on treadmill was 0.509 ± 0.21 (P < 0.01), showing a moderate agreement. Nevertheless, symptoms on treadmill reproduced, at least partly, symptoms by history in 675 (84.9% 95CI: 82.3-87.2) of patients, although symptoms on treadmill were strictly of the same localizations as symptoms by history in only 378 (47.6% 95CI: 44.1-51.0) of all studied patients. Last, 279 patients (35.1% of all patients) reported non limb symptoms on treadmill. CONCLUSION: Although on a site by site basis the concordance of symptoms by history to symptoms by treadmill is moderate, most patients reproduced their usual symptoms on treadmill. Age does not seem to impair the concordance. Last, beyond the sole measurement of maximal walking capacity, treadmill frequently unmasks non-limb limiting symptoms that may require clinical attention.

Disseminated arterial calcification and enhanced myogenic response are associated with abcc6 deficiency in a mouse model of pseudoxanthoma elasticum.

OBJECTIVE: Pseudoxanthoma elasticum is an inherited metabolic disorder resulting from ABCC6 gene mutations. It is characterized by progressive calcification and fragmentation of elastic fibers in the skin, retina, and the arterial wall. Despite calcium accumulation in the arteries of patients with pseudoxanthoma elasticum, functional consequences remain unknown. In the present study, we investigated arterial structure and function in Abcc6(-/-) mice, a model of the human disease. APPROACH AND RESULTS: Arterial calcium accumulation was evaluated using alizarin red stain and atomic absorption spectrometry. Expression of genes involved in osteochondrogenic differentiation was measured by polymerase chain reaction. Elastic arterial properties were evaluated by carotid echotracking. Vascular reactivity was evaluated using wire and pressure myography and remodeling using histomorphometry. Arterial calcium accumulation was 1.5- to 2-fold higher in Abcc6(-/-) than in wild-type mice. Calcium accumulated locally leading to punctuate pattern. Old Abcc6(-/-) arteries expressed markers of both osteogenic (Runx2, osteopontin) and chondrogenic lineage (Sox9, type II collagen). Abcc6(-/-) arteries displayed slight increase in arterial stiffness and vasoconstrictor tone in vitro tended to be higher in response to phenylephrine and thromboxane A2. Pressure-induced (myogenic) tone was significantly higher in Abcc6(-/-) arteries than in wild type. Arterial blood pressure was not significantly changed in Abcc6(-/-), despite higher variability. CONCLUSIONS: Scattered arterial calcium depositions are probably a result of osteochondrogenic transdifferentiation of vascular cells. Lower elasticity and increased myogenic tone without major changes in agonist-dependent contraction evidenced in aged Abcc6(-/-) mice suggest a reduced control of local blood flow, which in turn may alter vascular homeostasis in the long term.

External validation of the "walking estimated limitation calculated by history" (WELCH) questionnaire in patients with claudication.

OBJECTIVE: To externally validate the recently proposed "Walking Estimated Limitation Calculated by History" (WELCH) questionnaire. METHODS: A prospective study was performed on 450 new patients referred to our laboratory for treadmill testing (constant load 3.2 km/h and 10% slope for 15 minutes and then incremental increases). Results are presented as mean ± SD or median [25th-75th percentiles] or number (percentage). An ankle brachial index <0.90 defined the presence of peripheral artery disease (PAD). Typical "vascular-type claudication" is a lower-limb pain or discomfort that is absent at rest, appears at exercise, forces stopping, and disappears within 10 minutes of exercise stopping. The Spearman r coefficient of correlation between maximal walking time (MWT) on treadmill and WELCH scores was calculated for patients with (PAD+) or without (PAD-) PAD, and reporting typical vascular-type claudication (VTC+) or not (VTC-). RESULTS: The WELCH score was obtained in all included patients. The number (%) of patients with a WELCH score <25 was 37 (54%), 198 (65%), 14 (44%), and 18 (38%), and the Spearman correlation coefficient between WELCH score and treadmill MWT was 0.588, 0.609, 0.581, and 0.591 in the VTC-/PAD+, VTC+/PAD+, VTC-/PAD-, and VTC+/PAD- groups respectively (all p < .001). In PAD+/VTC+ patients, the WELCH positive predictive value for the inability to walk for 5 minutes on the treadmill was 79%. CONCLUSION: The WELCH score correlates moderately with treadmill-walking capacity in patients with or without PAD, and with or without typical VTC. It appears to be a simple to complete and easily scored instrument to help clinicians standardise the subjective estimation of walking capacity in their patients.

High-frequency (20-50 MHz) ultrasonography of pseudoxanthoma elasticum skin lesions.

BACKGROUND: In most patients pseudoxanthoma elasticum (PXE) manifests with yellowish cutaneous papules and dermal elastorrhexis on skin biopsy. In a small number of cases there are no skin manifestations on clinical examination, and establishing a diagnosis of PXE in such patients is challenging. High-frequency ultrasonography (HFUS) may be of use in predicting skin areas that would yield a biopsy specimen positive for elastorrhexis. OBJECTIVES: To describe characteristics of clinically visible PXE skin using HFUS, and to evaluate its relevance for diagnosis. METHODS: HFUS was performed in a cohort of patients with PXE and in controls at a referral centre. HFUS images of PXE skin were compared with those of other conditions. Five operators blind-scored multiple HFUS images of photoprotected or photoexposed skin from patients with PXE and controls. The diagnostic indices (sensitivity, specificity, likelihood ratios, interobserver agreement) were calculated. RESULTS: The HFUS changes considered as diagnostic for PXE were primarily oval homogeneous hypoechogenic areas in the mid-dermis. The size of these areas closely matched the extent of the histological changes. The sensitivity and specificity of the diagnostic items and interobserver agreement were high, particularly in photoprotected skin. Dermal hypoechogenicity in PXE could be related to high hydration of connective tissue due to the presence of glycosaminoglycans despite elastic fibre mineralization. CONCLUSIONS: HFUS provides suggestive images of PXE skin lesions. HFUS should now be studied to determine whether it is a potentially valuable technique for the noninvasive identification of elastorrhexis in patients with PXE in whom skin involvement is clinically minimal or absent.

[Regional and peripheral arterial stiffness measured by pOpmetre® in patients with Cvx risk factor, link with carotid plaques]. / Rigidité artérielle mesurée par pOpmètre® chez les patients à risque cardiovasculaire, lien aux plaques d'athérome carotidien.

PURPOSE: Aortic stiffness is a functional and structural consequence of ageing and arteriosclerosis. Regional arterial stiffness can be easily evaluated using pOpmetre(®) (Axelife SAS, France). This new technique assesses the pulse wave transit time (TT) between the finger (TTf) and the toe (TTt). Based on height chart, regional pulse wave velocity (PWV) between the toe and the finger can be estimated (PWVtf). pOpscore(®) index is also calculated as the ratio between PWVtoe and PWVfinger and can be considered as a peripheral vascular stiffness index. The aim of the study was to evaluate the relationship between pOpmetre(®) indices and the presence of carotid plaques in a population with cardiovascular risk factors. METHODS: In 77 consecutive patients recruited for a vascular screening for atherosclerosis (46 men aged 54 ± 2 years; 31 women aged 49 ± 3 years; ns), the difference between TTt and TTf (called Dt-f), the regional pulse wave velocity between the toe and the finger (PWVtf = constant × height/Dt-fm/s) and pOpscore(®) were measured by pOpmetre(®). Presence of carotid plaques was assessed using ultrasound imaging. The local aortic stiffness (AoStiff) was evaluated by the Physioflow(®) system. RESULTS: No difference was found between patients with or without carotid plaques (n=25 versus 52) for Ankle-Brachial Pressure Index (ABPI: 1.15 ± 0.04 versus 1.12 ± 0.03), nor for diastolic or systolic blood pressure (87 ± 3 versus 82 ± 2; 137 ± 3 versus 132 ± 2 mmHg). The first group was older than the second (59 ± 2 versus 49 ± 2 years, P<0.002) with a larger intimae media thickness (0.69 ± 0.02 versus 0.63 ± 0.01 mm, P<0.004), a higher AoStiff (10.4 ± 0.7 versus 8.2 ± 0.5m/s, P<0.02), and PWVtf (14.3 ± 1.0 versus 10.7 ± 0.7 m/s, P<0.004) and a shorter Dt-f (57.9 ± 5.1 versus 73.5 ± 3.5 ms, P<0.01). PWVtf (r(2)=0.49, P<0.0001) and Dt-f (r(2)=0.54, P<0.0001) correlated with age. A significant difference in pOpscore(®) index was observed between both groups (1.51 ± 0.3 versus 1.41 ± 0.2, P<0.006). CONCLUSION: Our results show a significant arterial stiffness indices measured by pOpmetre(®) in patients with and without carotid plaques.

MRI measurement of liver fat content predicts the metabolic syndrome.

BACKGROUND AND AIMS: The prevalence of non-alcoholic fatty liver disease among cardiometabolic patients is not completely known because liver biopsy cannot be routinely performed. However, as magnetic resonance imaging (MRI) allows accurate and safe measurement of the hepatic fat fraction (HFF), the aim of this study was to quantify liver fat content in a dysmetabolic adult population. METHODS: A total of 156 adults were included in this cross-sectional study. Liver and visceral fat were assessed by MRI in these subjects, who presented with zero to five metabolic components of the metabolic syndrome (MetS). Arterial stiffness was recorded by ultrasonography, and the maximum Youden index was used to set the optimal HFF cutoff value predictive of the presence of the MetS. RESULTS: Overall, 72% of participants displayed three or more MetS components. HFF ranged from 0.3% to 52% (mean 13.4%). Age- and gender-adjusted HFF was positively correlated with BMI (r=0.44), blood pressure (r=0.19), triglyceridaemia (r=0.22) and glycaemia (r=0.31). MRI-measured visceral adipose tissue did not influence the relationship of steatosis with glycaemia, HOMA-IR and carotid stiffness, but there was a dose-response relationship between the number of MetS components and mean HFF. The optimal HFF for predicting the MetS was found to be 5.2% according to the maximum Youden index point. CONCLUSION: This study highlighted the impact of liver steatosis on cardiometabolic abnormalities with an optimal cutoff value of 5.2% for defining increased metabolic risk.

[Myopia in pseudoxanthoma elasticum]. / Le pseudoxanthome élastique et la myopie.

INTRODUCTION: Refraction in patients with pseudoxanthoma elasticum (PXE) has not yet been studied in the literature. The purpose of our study was to determine if PXE may be associated with myopia, similarly to Marfan syndrome, another collagen-vascular disease. PATIENTS AND METHODS: This cross-sectional study evaluated 53 consecutive patients (32 women and 21 men, mean age 50 ± 16) from September 2009 to June 2011, with 53 age- and sex-matched controls. For each patient, we measured spherical equivalent, visual acuity, keratometry, axial length and crystalline lens power of each eye. Results were compared with Student's t-test. RESULTS: There was a significant difference between the mean values of myopia in the PXE population (-0.98) compared to the group of healthy controls (-0.33, P<0.0093). There was no significant difference between the two groups for the axial length (23.9 mm versus 23.69 mm; P=0.236), keratometry (43.53 versus 43.44; P=0.68), lens power (22.03 versus 21.71; P=0.225). DISCUSSION: PXE induces calcification of elastic fibers in various human tissues (skin, retina, vascular walls). Since there are no elastic fibers in the cornea or lens, we assume that the elastic zonular fibers may be pathologic in PXE patients. This could result in an anterior displacement of the lens in PXE, which could explain the moderate myopia. CONCLUSION: PXE may be associated with mild myopia compared to healthy controls. Additional studies, including more patients and evaluating anterior chamber depth and zonular histology are necessary to confirm these preliminary findings.

Estimation of running capacity can likely be removed from questionnaires estimating walking impairment in patients with claudication.

OBJECTIVE: The Estimating Ambulation Capacity by History-Questionnaire (EACH-Q) and the Walking Impairment Questionnaire (WIQ) are used to estimate maximal walking distance (MWD). The EACH-Q and WIQ included 4 and 14 items respectively, among which one item dealing with running capacity. We hypothesised that this item was of little interest in patients with claudication. DESIGN: The WIQ and EACH-Q were self-completed and corrected before a constant load (3.2 km h(-1); 10% slope) treadmill tests, maximised to 15 min. PATIENTS: 371 patients (298 males/73 females, 62.9 ± 11.2 years). METHODS: The number of errors (duplicate, absent or paradoxical answers to one item) and correlation of questionnaire scores with MWD on treadmill were calculated, before and after skipping the answer to the running item. RESULTS: The proportion of questionnaires with errors was 27% with the EACH-Q and 48% with the WIQ. Two-hundred and twenty-one (59.6%) and 245 (66%) out of 371 patients reported to be unable to run, for the EACH-Q and WIQ, respectively. The rate of errors was reduced by 15% for the EACH-Q (p < 0.05) when skipping the running item for scoring. The correlation coefficients between the MWD and the questionnaire scores were 0.449 and 0.485 for the EACH-Q and were 0.571 and 0.572 for the WIQ, before and after skipping the running item, respectively. CONCLUSION: Most of our patients reported to be unable to run and skipping the running item reduce the rate of errors in self-completing the questionnaires without impairing the correlation of questionnaire scores with treadmill results. It is likely that the running item could be removed from the WIQ and EACH-Q questionnaires.

Carotid rete mirabile and pseudoxanthoma elasticum: an accidental association?

We report the case of a young female patient with a transient amaurosis due to a carotid rete mirabile (CRM), a rare congenital carotid malformation, and pseudoxanthoma elasticum (PXE), an inherited autosomal recessive systemic metabolic disorder characterised by fragmentation and mineralisation of elastic fibres in connective tissues (skin, eyes) and the vascular system. CRM is a rare form of intracranial carotid malformation whose association with PXE (6 cases at present) would appear not to be accidental. This observation suggests a new link between congenital arterial remodelling and the PXE.

Exercise treadmill testing in patients with claudication, with and without diabetes.

AIM: To compare symptoms and walking capacities of patients with and without diabetes reporting vascular-type claudication. METHODS: We recorded self-reported maximal walking distance, maximal walking distance on treadmill test (3.2 km h(-1) , 10% slope), exercise transcutaneous oxygen pressure DROP index [limb transcutaneous oxygen pressure (TcpO2) changes from rest minus chest TcpO2 changes from rest] and symptoms on treadmill in 230 patients with diabetes and 982 patients without diabetes. Exercise-induced proximal and distal symptoms were analysed in the perspective of underlying proximal and distal ischaemia (DROP value < negative 15 mmHg). RESULTS: Self-reported maximal walking distance did not differ between groups, whereas maximal walking distance on treadmill test was lower in patients with diabetes vs. patients without diabetes (261 ± 257 and 339 ± 326 m, respectively; P < 0.05 when adjusted for potential confounders). In patients with ischaemia, the number of ischaemic areas (proximal and/or distal on right and/or left) was comparable between the two groups. Patients with diabetes had more distal ischaemia than patients without diabetes (38 vs. 29%, respectively; P < 0.01), whereas proximal ischaemia was similar between groups. The prevalence of lower-limb exercise-related symptoms without ischaemia was comparable between groups. There were more symptoms other than lower-limb pain in patients with diabetes than patients without diabetes (29.6 vs. 18.3%, respectively; P < 0.01). CONCLUSIONS: Patients with diabetes show more severe limitation on the treadmill and more non-limb symptoms than patients without diabetes, although self-reported walking capacity is comparable between the two groups. Using TcpO2, we confirm that patients with diabetes reporting claudication show more distal ischaemia than patients without diabetes, with no difference at the buttock level. Treadmill testing is of interest in patients with peripheral artery disease and diabetes.

Chest tcpO2 changes during constant-load treadmill walking tests in patients with claudication.

Changes in chest transcutaneous-pO(2) at rest (ΔtcpO(2)) mimic absolute changes in arterial-pO(2) during moderate exercise, although the absolute starting values may dramatically differ. We retrospectively studied 485 patients (group 1), prospectively studied 292 new patients (group 2) and estimated the intra-test and the test-retest reproducibility of ΔtcpO(2) during constant-load treadmill tests: 3.2 km h(-1), 10% grade, using the cross correlation technique. Patients were classified into groups according to their best fit to nine pre-defined mathematic models. Respectively, 71% and 76% of patients of groups 1 and 2 fitted with a model showing a ΔtcpO(2) increase during and a decrease following exercise. Another 18% and 12% of the patients of groups 1 and 2 respectively fitted with a model that showed an abrupt decrease at exercise onset, a slow increase during walking and an overshoot in the recovery period, referred here as a walking-induced transcutaneous hack (WITH) profile. The mean r(max) value for the cross-correlation analysis was 0.919 ± 0.091 and 0.800 ± 0.129 for intra-test and test-retest reproducibility. Most profiles show the expected ΔtcpO(2) exercise-induced increase. Future studies are needed to confirm and explain the WITH profiles that we found, and screen for potential-associated diseases.

Limitations of self-reported estimates of functional capacity using the Walking Impairment Questionnaire.

OBJECTIVE: A potential issue with the Walking Impairment Questionnaire (WIQ) is that it is relatively complex. We estimated the number of errors made by patients when self-completing the WIQ, and assessed the benefit of correcting missing, duplicate or paradoxical (i.e., reported lower difficulty for a higher-intensity task) answers. DESIGN: Prospective non-interventional study. MATERIALS: All consecutive new patients with claudication over a 3-month period. METHODS: The WIQ was self-completed before patients performed a constant-load treadmill walking test (maximised to 750 m). MAIN OUTCOME MEASURE: We analysed the coefficient of determination of the linear relationship between overall WIQ score (mean of the available subscales when at least two subscales are available) and treadmill maximal walking distance (MWD), before and after correction of errors. RESULTS: We studied 73 patients. Thirty-seven questionnaires had to be corrected for one or more errors. The coefficient of determination between the overall WIQ score and MWD was R(2) = 0.391 (n = 56) and R(2) = 0.426 (n = 73) before and after correction, respectively. CONCLUSION: Supervision of self-completed WIQs detects errors in almost half of the questionnaires, resulting in a missing overall WIQ score in 23% of cases among uncorrected questionnaires. The overall WIQ score correlates only moderately with MWD, even after correction. CLINICAL TRIAL REGISTRATION: NIH database: NCT01114178.

Functional outcome of hypogastric revascularisation for prevention of buttock claudication in patients with peripheral artery occlusive disease.

We have defined proximal lower limb ischaemia as a decrease in Exercise-transcutaneous oxygen pressure (TcPO(2)) lower than minus 15mmHg at the buttock level in patients with peripheral artery occlusive disease. The purpose of this study was to objectively evaluate the benefits of direct versus indirect revascularisation of internal iliac arteries (IIAs) for prevention of buttock claudication in this population. We retrospectively reviewed the charts of proximal ischaemia patients who underwent revascularisation and both preoperative and postoperative stress TcPO(2) testing. Revascularisation procedures were classified as either direct revascularisation, including percutaneous transluminal angioplasty and internal iliac artery bypass, resulting in a direct inflow in a patent IIA (group 1) or indirect revascularisation, including aortobifemoral bypass and recanalisation of the femoral junction on the ischaemic side, resulting in indirect inflow from collateral arteries in the hypogastric territory (group 2). Patency was checked 3 months after revascularisation in all cases. Treadmill exercise stress tests were performed before and after revascularisation using the same protocol designed to assess pain, determine maximum walking distance (MWD) and measure TcPO(2) during exercise. In addition, ankle-brachial indices (ABIs) were calculated. Between May 2001 and March 2008, a total of 93 patients with objectively documented proximal ischaemia underwent 145 proximal revascularisation procedures using conventional open techniques in 109 cases and endovascular techniques in 36. Direct revascularisation was performed on 50 limbs (35%) (group 1) and indirect revascularisation on 95 limbs (65%) (group 2). The mean interval between revascularisation and stress testing was 60+/-74 days preoperatively and 149+/-142 days postoperatively. No postoperative thrombosis was observed. Buttock claudication following revascularisation was more common in group 2 (p<0.001). No difference was observed between the two groups with regard to improvement in MWD (365 / 294 m) and ABI (0.20/0.22). Disappearance of proximal ischaemia was more common after direct revascularisation (p<0.01). The extent of lesions graded according to the TASC II classification appeared not to be predictive of improvement in assessment criteria following revascularisation. Conversely, patency of the superficial femoral artery was correlated with improvement (p<0.01). This study indicates that direct revascularisation, if feasible, provides the best functional outcome for prevention of buttock claudication.

Transcutaneous oxygen pressure measurements in diabetic and non-diabetic patients clinically suspected of severe limb ischemia: a matched paired retrospective analysis.

AIM: It was recently suggested that a 6 mmHg difference exists in both chest and foot transcutaneous oxygen pressure (TcPo2) between diabetic and non-diabetic volunteers apparently free from vascular disease. If a difference can also be found in diabetic and non-diabetic patients with clinically suspected critical limb ischemia (CLI), this may question the use of the same 30 mmHg threshold proposed by the "TASC" in the definition of CLI. We analyse whether a difference can be found for chest and foot TcPo2 respectively between diabetic and non-diabetic patients referred for clinically suspected CLI. METHODS: A retrospective matched paired study was performed among 60 diabetic and 60 non-diabetic subjects with peripheral artery disease and suspected critical limb ischemia. Results are presented as median [25-75 centiles]. RESULTS: Groups were comparable in terms of gender, age, height, systolic blood pressure and treatments (except for renin-angiotensin inhibitors). Chest-TcPo2 was 53 [43-57] mmHg in diabetic and 60[49-65] mmHg in non-diabetic patients (P<0.01). Foot-TcPo2 was 12[3-34] mmHg in diabetic and 15[3-36] mmHg in non-diabetic patients (Non significant). A multi-parametric step by step regression analysis showed that chest-TcPo2 was inversely associated with weight, then with diabetes and gender. CONCLUSIONS: TcPo2 is lower at the chest but not at the foot level in diabetic than in non-diabetic patients with suspected CLI. Then, the "30 mmHg threshold" proposed in the definition of lower-limb CLI is likely applicable in both diabetic and non-diabetic patients.