Acute venous thromboembolism in patients with brain cancer: clinical course.

Background: Patients with brain cancer have been excluded or were underrepresented in studies on the treatment of venous thromboembolism (VTE), mainly due to the fear of intracranial hemorrhage (ICH). Objectives: The aim of this study was to provide data on the risk of ICH, recurrent VTE, and major bleeding in patients with active brain cancer. Methods: This was a multicenter, international cohort study at participating sites of the Registro Informatizado Enfermedad Tromboembólica Registry. Patients included in this study were classified as having known active brain cancer, active nonbrain cancer, or without active cancer. ICH at 3 months was the primary study outcome. Results: Overall, 98,377 patients with VTE were included: 616 with active brain cancer, 16,807 with active nonbrain cancer, and 80,954 without active cancer. At 3 months follow-up, ICH occurred in 2.8%, 0.3%, and 0.2% of the patients, respectively, and was fatal in 1.3%, 0.2%, and 0.1%, respectively. Both rates of major bleeding (3.7% vs 3.2% vs 1.5%, respectively) and recurrent VTE (3.9% vs 3.4% vs 1.1%, respectively) were higher in patients with brain or nonbrain cancer than in patients without cancer. Glioblastomas were associated with a numerically higher risk of ICH, fatal ICH, and recurrent VTE than other brain tumors. Conclusion: In patients with VTE, active brain cancer was associated with a higher risk of ICH or fatal ICH than nonbrain or no active cancer. Further studies are needed to assess the value of different treatment approaches in patients with brain cancer and VTE.

Anti-coagulant Treatment of Cancer-Associated Thrombosis in Frail Patients: Impact of Frailties on the Management of Drug-Drug Interactions.

Low molecular weight heparins (LMWH) and anti-Xa direct oral anti-coagulants (DOACs) are recommended for the long-term treatment of cancer-associated thrombosis (CAT) based on well-documented randomised controlled trials. Anti-Xa DOACs are viewed as a first choice for the treatment of patients with CAT. A large number of drug-drug interactions have been reported between DOACs and chemotherapy drugs, modifying circulating levels of DOAC leading to fears of increased bleeding risks or thrombotic recurrence. Progresses in anti-neoplastic therapies have improved the prognosis and the survival, thus increasing the prevalence of frail patients with cancer. However, since frailties tend to be excluded from large trials due to multiple co-morbidities, current guidelines are not fully applicable to this population. The management of these frail patients with CAT is particularly complex and requires a risk assessment on a case-by-case basis with specific focus on cancer, patient-related risk factors and drug-drug interactions. In this brief review we have identified age, co-morbidities and co-medications as key factors of frailty that require careful attention and we have developed a therapeutic decision algorithm to help clinicians optimising the use of anti-coagulants in patients with cancer with CAT, especially in case of anti-Xa DOACs concomitant medications. With the evaluation of the bleeding risk according to the type of cancer, and anticipating drug-drug interactions intensity, taking into account patient frailties allows the optimisation of the anti-coagulant choice. A systematic collaboration between oncologists, vascular pathology specialists and pharmacists is warranted to ensure an optimal patient management. Clinical studies are needed to determine the real impact of these interactions.

Mouth opening in systemic sclerosis: A longitudinal analysis from the French National Cohort Study.

BACKGROUND: Few studies have evaluated mouth opening (MO) in systemic sclerosis (SSc). None have studied MO trajectories. OBJECTIVE: To study MO trajectories in SSc. METHODS: This multicentre study included patients enrolled in the French national SSc cohort with at least one MO assessment, described patients based on MO baseline measure, modeled MO trajectories, and associated MO measures with SSc prognosis. RESULTS: We included 1101 patients. Baseline MO was associated with disease severity. On Kaplan-Meier analysis, MO < 30 mm was associated with worse 30-year-survival (p<0.01) and risk of pulmonary arterial hypertension (p<0.05). Individual MO trajectories were heterogenous among patients. The best model of MO trajectories according to latent-process mixed modeling showed that 88.8% patients had a stable MO trajectory and clustered patients into 3 groups that predicted SSc survival (p<0.05) and interstitial lung disease (ILD) occurrence (p<0.05). The model highlighted a cluster of 9.5% patients with diffuse cutaneous SSc (dcSSc) (p<0.05) and high but decreasing MO over 1 year (p<0.0001) who were at increased risk of poor survival and ILD. CONCLUSION: MO, which is a simple and reliable measure, could be used to predict disease severity and survival in SSc. Although MO remained stable in most SSc patients, dcSSc patients with high but decreasing MO were at risk of poor survival and ILD. This article is protected by copyright. All rights reserved.

25 mm Hg versus 35 mm Hg elastic compression stockings to prevent post-thrombotic syndrome after deep vein thrombosis (CELEST): a randomised, double-blind, non-inferiority trial.

BACKGROUND: The optimal strength of compression needed to prevent post-thrombotic syndrome (PTS) after a proximal deep vein thrombosis (DVT) is debated. We aimed to assess whether 25 mm Hg elastic compression stockings (ECS) are non-inferior to 35 mm Hg ECS in preventing PTS after a DVT. METHODS: In this multicentre, double-blind, non-inferiority, randomised controlled trial, we enrolled adults (≥18 years) with a first ipsilateral proximal DVT attending 46 French vascular medicine hospital departments or private practices. Participants were randomly allocated (1:1, stratified by centre, age, and sex; with varying block sizes of two and four) to wear 25 mm Hg or 35 mm Hg ECS for 2 years. The primary outcome was the cumulative rate of PTS 2 years after inclusion, defined by a Villalta scale (≥5). Efficacy was assessed by intention-to-treat and in eligible participants who had complete primary outcome data. A per-protocol analysis was also conducted among compliant patients as a secondary outcome measure. Safety was assessed in all participants who used ECS at least once, and for which we have at least some tolerance information during follow-up. The margin for non-inferiority was 12·5%. This study is registered with ClinicalTrials.gov, NCT01578122, and has been completed. FINDINGS: Between June 28, 2012, and July 21, 2017, we enrolled 341 eligible participants who consented to randomisation. 233 (68%) were men and median age was 59 years (IQR 45-70). Collection of ethnicity and race as a routine research variable is not authorised in France. Median follow-up was 735 days (IQR 721-760). 249 (73%) had complete data at 2 years. For the primary analysis, 40 (31%) of 129 participants with complete data in the 25 mm Hg ECS group and 40 (33%) of 120 in the 35 mm Hg group had PTS (absolute difference -2·3% [90% CI -12·1 to 7·4], pnon-inferiority=0·0062; relative risk 0·93, 95% CI 0·65 to 1·33). Results remained similar after imputation of missing data in patients we were authorised to do so: the cumulative proportion of PTS was 45 (29%) of 154 in the 25 mm Hg ECS group versus 52 (35%) of 148 in the 35 mm Hg ECS group (relative risk 0·83, 95% CI 0·60 to 1·16). Absolute difference was -5·9%, (90% CI -14·7 to 2·9), p=0·0003 for non-inferiority. Adherence was optimal (>80% and modified GIRERD score of 0-2) for 75 (51%) of 146 patients assigned to 25 mm Hg ECS and for 56 (42%) of 134 patients assigned to 35 mm Hg ECS (p=0·11). Regarding major adverse events related to ECS, there were no between-group differences in rates of deep vein thrombosis (0 vs 1 [0·6%]), ipsilateral leg ulcer (0 vs 1 [0·6%]), infection (0 vs 0), or death (0 vs 0) between the 169 patients evaluated in the 25 mm Hg ECS group and the 159 patients in the 35 mm Hg ECS group. Two (1%) of 328 patients who ever wore ESC developed ECS-related serious adverse events, one distal DVT and one leg ulcer (both in the 35 mm Hg ECS group). In the 25 mm Hg group, 6 patients died, 14 had a venous thromboembolic recurrence (proximal DVT or pulmonary embolism), and 7 had a major bleed. In the 35 mm Hg group, 5 patients died, 10 had a venous thromboembolic recurrence (proximal DVT or pulmonary embolism), and 6 had a major bleed. INTERPRETATION: Although we did not reach the prespecified sample size, our results suggest that 25 mm Hg ECS are non-inferior to 35 mm Hg ECS in preventing PTS. Larger more powerful studies are needed. FUNDING: Laboratoires Innothera, France.

Rivaroxaban vs Dalteparin in Cancer-Associated Thromboembolism: A Randomized Trial.

BACKGROUND: Direct oral anticoagulants (DOACs) are an alternative to low-molecular-weight heparin for treating cancer-associated VTE. RESEARCH QUESTION: Is rivaroxaban as efficient and safe as dalteparin to treat patients with cancer-associated VTE? STUDY DESIGN AND METHODS: In a randomized open-label noninferiority trial, patients with active cancer who had proximal DVT, pulmonary embolism (PE), or both were assigned randomly to therapeutic doses of rivaroxaban or dalteparin for 3 months. The primary outcome was the cumulative incidence of recurrent VTE, a composite of symptomatic or incidental DVT or PE, and worsening of pulmonary vascular or venous obstruction at 3 months. RESULTS: Of 158 randomized patients, 74 and 84 patients were assigned to receive rivaroxaban and dalteparin, respectively. Mean age was 69.4 years, and 115 patients (76.2%) had metastatic disease. The primary outcome occurred in 4 and 6 patients in the rivaroxaban and dalteparin groups, respectively (both the intention-to-treat and per-protocol populations: cumulative incidence, 6.4% vs 10.1%; subdistribution hazard ratio [SHR], 0.75; 95% CI, 0.21-2.66). Major bleeding occurred in 1 and 3 patients in the rivaroxaban and dalteparin groups, respectively (cumulative incidence, 1.4% vs 3.7%; SHR, 0.36; 95% CI, 0.04-3.43). Major or clinically relevant nonmajor bleeding occurred in 9 and 8 patients in the rivaroxaban and dalteparin groups, respectively (cumulative incidence, 12.2% vs 9.8%; SHR, 1.27; 95% CI, 0.49-3.26). Overall, 19 patients (25.7%) and 20 patients (23.8%) died in the rivaroxaban and dalteparin groups, respectively (hazard ratio, 1.05; 95% CI, 0.56-1.97). INTERPRETATION: In this trial comparing rivaroxaban and dalteparin in the treatment of cancer-associated VTE, the number of patients was insufficient to reach the predefined criteria for noninferiority, but efficacy and safety results were consistent with those previously reported with DOACs. An updated meta-analysis of randomized trials comparing DOACs with low-molecular-weight heparin in patients with cancer-associated VTE is provided. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT02746185; URL: www. CLINICALTRIALS: gov.

Arterial and venous thromboembolism in COVID-19: a study-level meta-analysis.

BACKGROUND: The prevalence of venous thromboembolic event (VTE) and arterial thromboembolic event (ATE) thromboembolic events in patients with COVID-19 remains largely unknown. METHODS: In this meta-analysis, we systematically searched for observational studies describing the prevalence of VTE and ATE in COVID-19 up to 30 September 2020. RESULTS: We analysed findings from 102 studies (64 503 patients). The frequency of COVID-19-related VTE was 14.7% (95% CI 12.1% to 17.6%, I2=94%; 56 studies; 16 507 patients). The overall prevalence rates of pulmonary embolism (PE) and leg deep vein thrombosis were 7.8% (95% CI 6.2% to 9.4%, I2=94%; 66 studies; 23 117 patients) and 11.2% (95% CI 8.4% to 14.3%, I2=95%; 48 studies; 13 824 patients), respectively. Few were isolated subsegmental PE. The VTE prevalence was significantly higher in intensive care unit (ICU) (23.2%, 95% CI 17.5% to 29.6%, I2=92%, vs 9.0%, 95% CI 6.9% to 11.4%, I2=95%; pinteraction<0.0001) and in series systematically screening patients compared with series testing symptomatic patients (25.2% vs 12.7%, pinteraction=0.04). The frequency rates of overall ATE, acute coronary syndrome, stroke and other ATE were 3.9% (95% CI 2.0% to to 3.0%, I2=96%; 16 studies; 7939 patients), 1.6% (95% CI 1.0% to 2.2%, I2=93%; 27 studies; 40 597 patients) and 0.9% (95% CI 0.5% to 1.5%, I2=84%; 17 studies; 20 139 patients), respectively. Metaregression and subgroup analyses failed to explain heterogeneity of overall ATE. High heterogeneity limited the value of estimates. CONCLUSIONS: Patients admitted in the ICU for severe COVID-19 had a high risk of VTE. Conversely, further studies are needed to determine the specific effects of COVID-19 on the risk of ATE or VTE in less severe forms of the disease.

Reversal of rivaroxaban anticoagulant effect by prothrombin complex concentrates: which dose is sufficient to restore normal thrombin generation?

Rivaroxaban has the most available data to support the use of prothrombin complex concentrates (PCC) as a reversal agent. However, PCC might increase the incidence of thrombotic events by shifting the haemostatic balance towards hypercoagulability. We assessed the in vitro efficacy and safety of three 4-factor PCCs for reversing rivaroxaban anticoagulant effect. Our in vitro finding indicates that 4-factor PCCs at the dose of 25 U.kg- 1 may be sufficient to reverse rivaroxaban anticoagulant effect.

Extended anticoagulation for the secondary prevention of venous thromboembolic events: An updated network meta-analysis.

BACKGROUND: Extended treatment is preconized in a significant proportion of patients with unprovoked venous thromboembolism (VTE). However, limited direct/indirect comparisons are available to appropriately weight the benefit/risk ratio of the diverse treatments available. We aimed to compare the rate of symptomatic recurrent VTE and major bleeding (MB), the net clinical benefit (VTE+MB) and death on vitamin-K antagonist (VKA), direct oral anticoagulants (DOAC) and antiplatelet drugs for extended anticoagulation. METHODS: A systematic literature search through September 2018 identified randomized trials studying these pharmacologic therapies for extended anticoagulation following VTE. Treatment effects were calculated using network meta-analysis with frequentist fixed-effects model. RESULTS: 18 trials (18,221 patients) were included in the analysis. All treatments reduced the risk of recurrence compared to placebo/observation. Nonetheless, VKA (RR 0.22; 95%CI 0.13-0.39) and DOAC (RRs ranging from 0.25-0.32; 95%CI ranging from 0.13-0.52) were more effective than aspirin, whereas low-dose VKA was less effective than standard-dose VKA (RR 2.47; 95%CI 1.34-4.55). The efficacy of DOAC was globally comparable to standard-adjusted dose VKA. Low- (RR 3.13; 95%CI 1.37-7.16) and standard-dose (RR 3.23; 95%CI 1.16-8.99) VKA also increased the risk of MB, which was not the case for any DOAC. Low-dose VKA and low-dose DOAC had similar effects on MB compared to standard-doses. Although there was a trend for reduced MB and enhanced net clinical benefit for DOAC compared to VKA, this was not statistically significant. The specific anticoagulant therapies had no significant effects on deaths. CONCLUSION: Standard-dose VKA and low/standard-dose DOAC share similar effects on VTE recurrence and MB, whereas aspirin and low-dose VKA were associated with lower benefit/risk ratio.

Vascular Events and Carotid Atherosclerosis: A 5-Year Prospective Cohort Study in Patients with Type 2 Diabetes and a Contemporary Cardiovascular Prevention Treatment.

BACKGROUND AND AIMS: European recommendations on cardiovascular prevention suggest that carotid atherosclerosis assessment by duplex ultrasonography could help in some cases to better assess CV risk. We investigated whether the presence of carotid atherosclerosis determined by duplex ultrasonography is associated with cardiovascular events in patients with type 2 diabetes and could therefore help to reclassify cardiovascular risk. METHODS: Among 624 consecutive patients with type 2 diabetes and carotid atherosclerosis assessment by duplex ultrasonography between January and December 2012, 583 (93%) were included and followed up prospectively. The primary endpoint was the occurrence of cardiovascular events. The rate of new cardiovascular events was compared between patients with (n = 104) and those without (n = 479) prior cardiovascular events. RESULTS: A total of new 104 cardiovascular events occurred in 72 patients (12.5%) during a mean ± SD follow-up period of 5.1 ± 1.6 years. At baseline, for 202 patients (34.6%), carotid evaluation was normal; 381 (65.4%) had a carotid atherosclerosis lesion. The presence of carotid atherosclerosis at baseline was not significantly associated with an increased risk of new cardiovascular events in both groups. The rate of new cardiovascular events was more than twice as high in patients with prior cardiovascular event than those without. CONCLUSION: Systematic carotid atherosclerosis assessment by duplex ultrasonography in patients with type 2 diabetes and a contemporary cardiovascular prevention treatment does not offer additional information as to the risk of cardiovascular events. This trial is registered with ClinicalTrials.gov (ID: NCT02929355).

Scaling up quality improvement intervention for perinatal care in Nepal (NePeriQIP); study protocol of a cluster randomised trial.

INTRODUCTION: Nepal Perinatal Quality Improvement Project (NePeriQIP) intends to scale up a quality improvement (QI) intervention for perinatal care according to WHO/National guidelines in hospitals of Nepal using the existing health system structures. The intervention builds on previous research on the implementation of Helping Babies Breathe-quality improvement cycle in a tertiary healthcare setting in Nepal. The objective of this study is to evaluate the effect of this scaled-up intervention on perinatal health outcomes. METHODS/DESIGN: Cluster-randomised controlled trial using a stepped wedged design with 3 months delay between wedges will be conducted in 12 public hospitals with a total annual delivery rate of 60 000. Each wedge will consist of 3 hospitals. Impact will be evaluated on intrapartum-related mortality (primary outcome), overall neonatal mortality and morbidity and health worker's performance on neonatal care (secondary outcomes). A process evaluation and a cost-effectiveness analysis will be performed to understand the functionality of the intervention and to further guide health system investments will also be performed. DISCUSSION: In contexts where resources are limited, there is a need to find scalable and sustainable implementation strategies for improved care delivery. The proposed study will add to the scarce evidence base on how to scale up interventions within existing health systems. If successful, the NePeriQIP model can provide a replicable solution in similar settings where support and investment from the health system is poor, and national governments have made a global pledge to reduce perinatal mortality. TRIAL REGISTRATION NUMBER: ISRCTN30829654.

Usefulness of a systematic screening of carotid atherosclerosis in asymptomatic people with type 2 diabetes for cardiovascular risk reclassification.

AIMS: Routine screening of carotid atherosclerosis lesions is frequently suggested for people with type 2 diabetes, the presence of a carotid lesion being associated with a significant increase risk for vascular events. However, the impact of this strategy on medical management is not validated. We herein question the usefulness of such screening. METHODS: We assessed the prevalence and severity of carotid lesions in 337 consecutive people with type 2 diabetes without known cardiovascular disease who underwent a systematic carotid duplex ultrasonography. We analyzed whether the results of duplex ultrasonography allowed reclassification of cardiovascular risk level relative to the most recent international recommendations on diabetes and modified therapy. RESULTS: We found that 35.9% of people had no atherosclerotic lesion. Prevalence of carotid stenosis<20%, between 20 and 50% and ≥50% were 32.9%, 28.4% and 2.7% respectively. Regarding the use of statins and LDL-C target, the result of carotid duplex ultrasonography allowed to reclassify respectively 11.8% to 55.2% of the cohort in a higher cardiovascular risk level. For the indication of antiplatelet agent, reclassification in a higher risk level concerned 6.8% of the patients. No subject had an indication of carotid revascularization. CONCLUSIONS: Carotid atherosclerosis is frequent in asymptomatic people with type 2 diabetes in primary cardiovascular prevention. Screening for carotid atherosclerosis by duplex ultrasonography seems useful to redefine the level of cardiovascular risk.

Carotid atherosclerosis progression and cerebrovascular events in patients with diabetes.

AIM: Carotid atherosclerosis progression is associated with a higher risk of cerebrovascular events but there is no specific data for diabetes. We assessed in a cohort of patients with diabetes the rate of atherosclerosis progression by Doppler ultrasonography and the association with cerebrovascular events. METHODS: We analyzed a retrospective cohort of 342 patients with a mean duration of diabetes of 13.6 ± 10.6 years. The mean delay between the first and last Doppler ultrasonography was 6.4 ± 4.6 years, with a mean of 3.4 examinations per person. Cerebrovascular events were noted. RESULTS: A progression of carotid atherosclerosis was observed in 20.1% of cases. No factor was significantly associated with progression. A prophylactic carotid endarterectomy was performed on 6 of the 27 patients with a stenosis ≥50%. A cerebrovascular event occurred in 1.2% of patients; none of them had carotid atherosclerosis progression. CONCLUSIONS: Carotid atherosclerosis progression in patients with diabetes is frequent but surgical treatment and cerebrovascular events are low. The benefit of a systematic follow-up of carotid atherosclerosis seems limited.

2008 French national guidelines for the treatment of venous thromboembolism in patients with cancer: report from the working group.

Venous thromboembolism (VTE) is a major therapeutic issue in cancer patients. Advances in this field and heterogeneities in clinical practices prompted us to establish guidelines in the management of VTE in cancer patients according to the SOR (Standards, Options and Recommendations) methodology. A literature review of the studies published on this topic between 1999 and 2007 was performed. The guidelines were developed from the analysis of 38 out of 418 publications selected. They were peer-reviewed by 65 independent experts. The treatment of VTE in patients with cancer, including those with intracranial malignancies, should be based on low-molecular-weight heparins administered at therapeutic doses for at least 3 months. In the event of recurrent VTE, pulmonary embolism with hemodynamic failure or contra-indication to anticoagulant treatment, the indications and usages of vena cava filters and thrombolytic drugs should be the same as in non-cancer patients.

[Recommendations for venous thromboembolic events treatment and central venous catheter thrombosis management in cancer patients]. / Traitement curatif de la maladie thromboembolique veineuse et prise en charge des thromboses veineuses sur cathéter chez les patients atteints de cancer Méthode SOR.

The "Standards, Options: Recommendations" (SOR) project has been undertaken by the French National Federation of Cancer Centers (FNCLCC) and is now part of the French National Cancer Institute. The project involves the development and updating of evidence-based Clinical Practice Guidelines (CPG) in oncology. In order to answer questions related to venous thromboembolic events (VTE) treatment and to central venous catheter thrombosis (CVCT) management in cancer patients, the SOR elaborated national guidelines, here presented in a short report. It results of a collaborative work with members from three learned societies (<< Société nationale française de médecine interne >> : SNFMI, << Société française de médecine vasculaire >> : SFMV and << Société française d'anesthésie-réanimation >> : SFAR).

[2008 Standards, Options: Recommendations for venous thromboembolic events(VTE)treatment and central venous catheter thrombosis(CVCT) management in cancer patients]. / Standards, Options : Recommandations 2008. Traitement curatif de la maladie thromboembolique veineuse, prevention et traitement des thromboses veineuses sur catheter chez les patients atteints de cancer.

The Standards, Options: Recommendations (SOR) project has been undertaken by the French National Federation of Cancer Centers (FNCLCC) is now part of the French National Cancer Institute. The project involves the development and updating of evidence-based Clinical Practice Guidelines (CPG) in oncology. In order to answer questions related to venous thromboembolic events(VTE) treatment and to central venous catheter thrombosis (CVCT) management in cancer patients, the SOR elaborated national guidelines, here presented in a short report. It results of a collaborative work with members from three learned societies("société nationale française de médicine interne": SNFMI, "société française de médicine vasculaire": SFMV and "société française dEanesthésie-réanimation:SFAR).

[2008 Standards, Options: recommendations for venous thromboembolic events (VTE) treatment and central venous catheter thrombosis (CVCT) management in cancer patients]. / Standards, Options : Recommandations 2008. Traitement curatif de la maladie thromboembolique veineuse, prévention et traitement des thromboses veineuses sur cathéter chez les patients atteints de cancer.

The <> (SOR) project has been undertaken by the French National Federation of Cancer Centers (FNCLCC) is now part of the French National Cancer Institute. The project involves the development and updating of evidence-based Clinical Practice Guidelines (CPG) in oncology. In order to answer questions related to venous thromboembolic events (VTE) treatment and to central venous catheter thrombosis (CVCT) management in cancer patients, the SOR elaborated national guidelines, here presented in a short report. It results of a collaborative work with members from three learned societies ("société nationale française de médicine interne": SNFMI, "société française de médicine vasculaire": SFMV and "société française d'anesthésie-réanimation": SFAR).

Mesenteric ischemia in giant cell arteritis: 6 cases and a systematic review.

OBJECTIVE: To report the main features of mesenteric ischemia related to giant cell arteritis (GCA). METHODS: We screened 13 French internal medicine tertiary care centers for their cases of patients exhibiting GCA-associated mesenteric ischemia during a 16-year period (1990-2006). Patients were included if they reported newly developed abdominal symptoms associated with histological proof of GCA-associated mesenteric vasculitis and/or radiological abnormalities consistent with GCA-associated mesenteric vasculitis. We performed a Medline search to identify previously reported cases of GCA-associated mesenteric ischemia. RESULTS: We included 6 original cases and 22 cases identified in the literature (mean age of the 28 patients: 72.4 +/- 7.1 yrs; women: 79%). GCA was histologically proven for all patients. In 12 patients GCA diagnosis preceded mesenteric inflammatory arteritis. Mesenteric ischemia occurred either soon after initiation of steroid therapy (n = 6, mean time to onset after starting steroid 12 +/- 11 days) or with a low-dose steroid regimen (n = 6, dosage 0-10 mg/day). In 16 other patients, the mesenteric involvement was the first manifestation of GCA. Only 6 patients (21%) reported cardiovascular risk factors. Clinical manifestations of GCA-associated mesenteric ischemia, as well as biological markers (mean C-reactive protein level 91 +/- 50 mg/l), were very nonspecific. Imaging explorations were performed for 14 patients and showed specific signs of vasculitis on the mesenteric artery in 10 (71%). Nineteen patients (68%) required laparotomy and 9 patients (33%) died. CONCLUSION: Early diagnosis and medical management of mesenteric GCA may ameliorate the severe prognosis of this possibly underdiagnosed complication.

IL13RA2 gene polymorphisms are associated with systemic sclerosis.

OBJECTIVE: To investigate the influence of genetic variability on the phenotypic expression of systemic sclerosis (SSc), by testing possible associations between single nucleotide polymorphisms (SNP) in IL13RA1 and IL13RA2 genes and SSc in a Caucasian population. METHODS: As IL13RA1 and IL13RA2 are located on the X chromosome and SSc occurs far more frequently in women than in men, only women were genotyped. The study group comprised 97 women with SSc, 36 with diffuse (dcSSc) and 61 with limited (lcSSc) cutaneous forms of disease, and 109 healthy controls. Patients and controls were Caucasian. We investigated 4 SNP in IL13RA1 and 3 in IL13RA2 by polymerase chain reaction amplifications and enzymatic digestion or primer extension reactions and denaturing high-performance liquid chromatography. RESULTS: We detected an association between IL13RA2 rs638376 and patients with SSc [p = 0.004, odds ratio (OR) = 1.85, confidence interval (CI) 1.22-2.74, p corr = 0.02], as well as with dcSSc in that subgroup of patients (p = 0.01, OR 2.22, 95% CI 1.27-3.89, p corr = 0.05). The IL13RA2 rs638376G allele frequency was higher in patients with SSc (51.6%) than in controls (36.4%, p = 0.003, OR 1.86, 95% CI 1.24-2.79, p corr = 0.015) and in the subgroup with dcSSc (57.6%) than in controls (36.4%, p = 0.003, OR 2.37, 95% CI 1.35-4.15, p corr = 0.015). One other IL13RA2 SNP was only associated with the dcSSc subgroup: the IL13RA2 rs5946040G allele was more common in patients with dcSSc (33.8%) than in controls (17%, p = 0.004, OR 2.5, 95% CI 1.36-4.60, p corr = 0.02). CONCLUSION: Our data suggest that IL13RA2 gene polymorphisms may be involved in susceptibility to SSc. Further studies are under way to show that they contribute to disease.