Tenecteplase in acute ischemic stroke: Review of the literature and expert consensus from the French Neurovascular Society.

BACKGROUND: Intravenous alteplase is the only thrombolytic treatment approved for patients with acute ischemic stroke (AIS). Although no randomized controlled trial (RCT) has shown the superiority of tenecteplase over alteplase in AIS, tenecteplase is increasingly used off-label in Stroke Units. The purpose of the present work was to provide an up-to-date set of expert consensus statements on the use of tenecteplase in AIS. METHODS: Members of the working group were selected by the French Neurovascular Society. RCTs comparing tenecteplase and alteplase in the treatment of AIS were reviewed. Recent meta-analysis and real-life experience data on tenecteplase published until 30th October 2021 were also analyzed. After a description of the available data, we tried to answer the subsequent questions about the use of tenecteplase in AIS: What dosage of tenecteplase should be preferred? How effective is tenecteplase for cerebral artery recanalization? What is the clinical effectiveness of tenecteplase? What is the therapeutic safety of tenecteplase? What are the benefits associated with tenecteplase ease of use? Then expert consensus statements for tenecteplase use were submitted. In October 2021 the working group was asked to review and revise the manuscript. In November 2021, the current version of the manuscript was approved. EXPERT CONSENSUS: A set of three expert consensus statements for the use of tenecteplase within 4.5hours of symptom onset in AIS patients were issued: (1) It is reasonable to use tenecteplase 0.25mg/kg when mechanical thrombectomy (MT) is planned. (2) Tenecteplase 0.25mg/kg can be used as an alternative to alteplase 0.9mg/kg in patients with medium- or small-vessel occlusion not retrievable with MT. (3) Tenecteplase 0.25mg/kg could be considered as an alternative to alteplase 0.9mg/kg in patients without vessel occlusion. CONCLUSIONS: These expert consensus statements could provide a framework to guide the clinical decision-making process for the use of tenecteplase according to admission characteristics of AIS patients. However, existing data are limited, requiring inclusions in ongoing RCTs or real-life registries.

Safety and outcome of mechanical thrombectomy in ischaemic stroke related to carotid artery dissection.

BACKGROUND: The net clinical benefit of mechanical thrombectomy (MT) in patients with anterior circulation ischaemic stroke associated with large vessel occlusion (AIS-LVO) related to carotid artery dissection (CAD) is uncertain. The aim of the study was to investigate the safety and clinical outcomes of patients treated by MT for a CAD-related stroke. METHODS: We included consecutive patients with AIS-LVO treated by MT between 1st 2015 and January 1st 2020 at Lille University Hospital. We compared the safety and clinical outcomes, including successful recanalisation, defined as a modified thrombolysis in cerebral infarction (mTICI) ≥ 2b and favourable functional outcome at 3 months (defined as a modified Rankin Scale (mRS) ≤ 2 or equal to pre-stroke), in patients with CAD-related stroke versus patients with other aetiologies. RESULTS: We included 1422 patients, among them, 43 patients with CAD-related AIS-LVO were matched to 86 patients with other aetiologies. Procedural complications, sICH (ECASS-3 criteria) and mortality rates were similar in the two groups (OR 0.85, 95% CI 0.21-3.49, p = 0.82; OR 1.54 95% CI 0.33-2.79, p = 0.58; OR 0.18 95% CI 0.02-1.46, p = 0.11, respectively), as well as the rates of intracranial angiographic successful recanalisation and favourable functional outcome (OR 0.67 (95% CI 0.26-1.73, p = 0.41; OR 1.26 (95% CI 0.61-2.64, p = 0.53). In patients with CAD-related stroke, intracranial angiographic success after MT was significantly associated with favourable functional outcome. CONCLUSIONS: In patients with AIS-LVO related to CAD, safety profiles and clinical outcomes after MT are similar compared to matched patients with other stroke aetiologies.

Career aspirations among specialty residents in France: a cross-sectional gender-based comparison.

BACKGROUND: Most studies evaluating career aspirations among gender are performed in Anglo-Saxon countries. Two recent French studies looked at the career choice of residents in obstetrics & gynecology. It seemed useful to us to broaden this questioning to other specialties, by proposing a study to all residents in the same Faculty. The objective of our study was to describe residents' career aspirations and possible barriers according to gender. METHODS: Declarative cross-sectional survey, using questionnaires sent by email to the specialty residents of the Faculty of Medicine of Lille (France). An analysis by specialty group (i.e., medicine, surgery, obstetrics & gynecology, and anesthesia & resuscitation) and a comparison of the results according to gender were performed. RESULTS: Of the 1384 specialty residents currently in training, 462 answered the questionnaire (33.38%), among whom 289 women and 173 men (average age = 27.08 ± 0.091 years). Seventeen women (5.9%) were currently considering a university hospital career versus 37 men (21.4%) (p = 0.001). Gender analysis made it possible to identify obstacles to engaging in a university career: lacking a female model, more frequent doubting the ability to undertake this type of career among women (61.6%) than men (35.3%) (p < 0.001), and gender discrimination felt in the workplace for 51.6% of women (versus 7.5% of men, p < 0.001). Subgroup analysis showed specificities related to each specialty. CONCLUSIONS: Few residents plan to embark upon a university hospital career, let alone female residents. There are considerations specific to each specialty and marked gender differences regarding career aspirations. Many features have been identified as obstacles to access to university hospital positions for women. It is important to develop strategies to remove these barriers and enable women to pursue such university careers. TRIAL REGISTRATION: Not applicable (no intervention).

Impact of recanalisation by mechanical thrombectomy in mild acute ischemic stroke with large anterior vessel occlusion.

BACKGROUND: The net clinical benefit of mechanical thrombectomy (MT) in patients presenting acute anterior circulation ischemic stroke with large-vessel occlusion (AIS-LVO) and mild neurological deficit is uncertain. AIMS: To investigate efficacy and safety of MT in patients with acute AIS-LVO and mild neurological deficit by evaluating i) the influence of recanalisation on three-month outcome and ii) mortality, symptomatic intracerebral hemorrhage (sICH) and procedural complications. METHODS: We included consecutive patients with acute AIS-LVO and National Institute of Stroke Scale (NIHSS) score<8, treated by MT at Lille University Hospital. Recanalisation was graded according to modified thrombolysis in cerebral infarction (mTICI) score, mTICI 2b/2c/3 being considered successful. We recorded procedural complications and classified intra-cerebral hemorrhages (ICH) and sICH according with European Cooperative Acute Stroke Study (ECASS) and ECASS2 criteria. Three-month outcome was evaluated by modified Rankin scale (mRS). Excellent and favourable outcomes were respectively defined as mRS 0-1 and 0-2 (or similar to pre-stroke). RESULTS: We included 95 patients. At three months, 56 patients (59. 0%) achieved an excellent outcome and 69 (72, 6%) a favourable outcome, both being more frequent in patients with successful recanalisation than in patients without (excellent outcome 71, 1% versus 10, 5%, P<0.001 and favourable outcome 82.9% versus 31.6%, P<0.001). The difference remained unchanged after adjustment for age and pre-MT infarct volume. Similar results were observed in patients with pre-MT NIHSS ≤5. Death occurred in five patients (5.3%), procedural complications in 12 (12.6%), any ICH in 38 (40.0%), including 3 (3.2%) sICH. CONCLUSIONS: Achieving successful recanalisation appears beneficial and safe in acute AIS-LVO patients with NIHSS<8 before MT.

The impact of anti-mould prophylaxis on Aspergillus PCR blood testing for the diagnosis of invasive aspergillosis.

BACKGROUND: The performance of the galactomannan enzyme immunoassay (GM-EIA) is impaired in patients receiving mould-active antifungal therapy. The impact of mould-active antifungal therapy on Aspergillus PCR testing needs to be determined. OBJECTIVES: To determine the influence of anti-mould prophylaxis (AMP) on the performance of PCR blood testing to aid the diagnosis of proven/probable invasive aspergillosis (IA). METHODS: As part of the systematic review and meta-analysis of 22 cohort studies investigating Aspergillus PCR blood testing in 2912 patients at risk of IA, subgroup analysis was performed to determine the impact of AMP on the accuracy of Aspergillus PCR. The incidence of IA was calculated in patients receiving and not receiving AMP. The impact of two different positivity thresholds (requiring either a single PCR positive test result or ≥2 consecutive PCR positive test results) on accuracy was evaluated. Meta-analytical pooling of sensitivity and specificity was performed by logistic mixed-model regression. RESULTS: In total, 1661 (57%) patients received prophylaxis. The incidence of IA was 14.2%, significantly lower in the prophylaxis group (11%-12%) compared with the non-prophylaxis group (18%-19%) (P < 0.001). The use of AMP did not affect sensitivity, but significantly decreased specificity [single PCR positive result threshold: 26% reduction (P = 0.005); ≥2 consecutive PCR positive results threshold: 12% reduction (P = 0.019)]. CONCLUSIONS: Contrary to its influence on GM-EIA, AMP significantly decreases Aspergillus PCR specificity, without affecting sensitivity, possibly as a consequence of AMP limiting the clinical progression of IA and/or leading to false-negative GM-EIA results, preventing the classification of probable IA using the EORTC/MSGERC definitions.

Benefit of first-pass complete reperfusion in thrombectomy is mediated by limited infarct growth.

BACKGROUND AND PURPOSE: The number of clot retrieval attempts required to achieve complete reperfusion by mechanical thrombectomy impacts functional outcome in acute ischaemic stroke (AIS). Complete reperfusion [expanded Treatment In Cerebral Infarction (eTICI) score = 3] at first pass (FP), is associated with the highest rates of favorable outcome compared to complete reperfusion by multiple passes. The aim of the present study was to investigate the relationship between FP complete reperfusion and infarct growth (IG). METHODS: Anterior AIS patients with baseline and 24-h diffusion-weighted magnetic resonance imaging were included from two prospective registries. IG was measured by voxel-based segmentation of initial and 24-h diffusion-weighted imaging lesions. IG and favorable 3-month modified Rankin Scale (mRS) score (≤ 2) were compared between patients in whom complete reperfusion (eTICI 3) was achieved with a single pass (FP group) and those for whom multiple passes were required (MP group), after matching for confounding factors. Mediation analysis was performed to examine the association between FP and 3-month mRS score, with IG as mediating variable. RESULTS: A total of 200 patients were included, of whom 118 (28.9%) had FP complete reperfusion. In case-control analysis, the FP group had lower IG than the MP group [8.7 (5.4-12.9) ml vs. 15.2 (11-22.6) ml, respectively; P = 0.03). Favorable outcome was higher in the FP population compared to a matched MP population (70.9% vs. 53.2%, respectively; P = 0.04). FP compete reperfusion (eTICI 3) was independently associated with favorable outcome in multivariable regression analysis [odds ratio 1.86, 95% confidence interval (CI) 1.01-4.39; P = 0.04]. The effect of complete reperfusion at FP on functional outcome was explained by limited IG in mediation analysis [indirect effect: -0.32 (95% CI -0.47 to -0.09)]. CONCLUSION: Complete reperfusion at FP is independently associated with significant decrease in IG compared to complete reperfusion by multiple attempts, explaining better functional outcomes.

Intracerebral haemorrhage, microbleeds and antithrombotic drugs.

Antithrombotic therapy is a cornerstone for secondary prevention of ischaemic events, cerebral and extra-cerebral. A number of clinical questions remain unanswered concerning the impact of antithrombotic drugs on the risk of first-ever and recurrent macro or micro cerebral haemorrhages, raising the clinical dilemma on the risk/benefit balance of giving antiplatelets and anticoagulants in patients with potential high risk of brain bleeds. High field magnetic resonance imaging (MRI) blood-weighted sequences, including susceptibility weighted imaging (SWI), have expanded the spectrum of these clinical questions, because of their increasing sensitivity in detecting radiological markers of small vessel disease. This review will summarise the literature, focusing on four main clinical questions: how do cerebral microbleeds impact the risk of cerebrovascular events in healthy patients, in patients with previous ischaemic stroke or transient ischaemic attack, and in patients with intracerebral haemorrhage? Is the risk/benefit balance of oral anticoagulants shifted by the presence of microbleeds in patients with atrial fibrillation after recent ischaemic stroke or transient ischaemic attack? Should we restart antiplatelet drugs after symptomatic intracerebral haemorrhage or not? Are oral anticoagulants allowed in patients with a history of atrial fibrillation and previous intracerebral haemorrhage?

Cerebral ischaemia with unknown onset: Outcome after recanalization procedure.

BACKGROUND: Stroke of unknown time of onset (UTOS) accounts for one-third of contra-indications for revascularization procedures. With modern neuroimaging techniques it is possible to differentiate the core infarcts and the presence of penumbra. OBJECTIVE: To evaluate outcomes in patients with UTOS, treated with intravenous (i.v.) recombinant tissue-plasminogen activator (rt-PA), mechanical thrombectomy (MT), or both. METHOD: We conducted this observational study in patients treated by i.v. rt-PA, MT, or both, selected by a diffusion-weighted image/fluid-attenuated inversion recovery mismatch. We evaluated outcomes with the modified Rankin scale (mRS) at 3 months. RESULTS: Of 992 consecutive patients (522 women, 52.6%; median age 76 years; median baseline national institutes of health stroke scale [NIHSS] 10), 153 (15.4%) had UTOS, including 101 with wake-up strokes. Compared to other patients, they were more likely to have pre-existing mRS scores >2 (P=0.022), multiple infarcts (P<0.001), middle cerebral artery occlusions (P=0.023), and to undergo MT (P=0.003), and less likely to receive i.v. rt-PA (P<0.001). They had higher NIHSS scores (P<0.001) and longer discovery to treatment initiation times (P<0.001). They were more likely to develop pulmonary (P=0.001) and urinary (P=0.006) infections, and pulmonary embolism (P=0.019), and tended to have a higher mortality rate (P=0.052) within 7 days. After adjustment, there was no association of UTOS with any of these outcome measures anymore. CONCLUSION: Patients with UTOS have more severe strokes and more comorbidities, but after adjustment, their outcomes did not differ from those of other patients.

Access to mechanical thrombectomy for cerebral ischaemia: A population-based study in the North-of-France.

BACKGROUND AND PURPOSE: Hospitals admitting acute strokes should offer access to mechanical thrombectomy (MT), but local organisations are still based on facilities available before MT was proven effective. MT rates and outcomes at population levels are needed to adapt organisations. We evaluated rates of MT and outcomes in inhabitants from the North-of-France (NoF) area. METHOD: We prospectively evaluated rates of MT and outcomes of patients at 3 months, good outcomes being defined as a modified Rankin scale (mRS) 0 to 2 or like the pre-stroke mRS. RESULTS: During the study period (2016-2017), 666 patients underwent MT (454, 68.1% associated with intravenous thrombolysis [IVT]). Besides, 1595 other patients received IVT alone. The rate of MT was 81 (95% confidence interval [CI] 72-90) per million inhabitants-year, ranging from 36 to 108 between districts. The rate of IVT was 249 (95% CI 234-264) per million inhabitants-year, ranging from 155 to 268. After 3 months, 279 (41.9%) patients who underwent MT had good outcomes, and 167 (25.1%) had died. Patients living outside the district of Lille where the only MT centre is, were less likely to have good outcomes at 3 months, after adjustment on age, sex, baseline severity, and delay. CONCLUSION: The rate of MT is one of the highest reported up to now, even in low-rate districts, but outcomes were significantly worse in patients living outside the district of Lille, and this is not only explained by the delay.

Hippocampal Deformations and Entorhinal Cortex Atrophy as an Anatomical Signature of Long-Term Cognitive Impairment: from the MCAO Rat Model to the Stroke Patient.

Stroke patients have an elevated risk of developing long-term cognitive disorders or dementia. The latter is often associated with atrophy of the medial temporal lobe. However, it is not clear whether hippocampal and entorhinal cortex atrophy is the sole predictor of long-term post-stroke dementia. We hypothesized that hippocampal deformation (rather than atrophy) is a predictive marker of long-term post-stroke dementia on a rat model and tested this hypothesis in a prospective cohort of stroke patients.Male Wistar rats were subjected to transient middle cerebral artery occlusion and assessed 6 months later. Ninety initially dementia-free patients having suffered a first-ever ischemic stroke were prospectively included in a clinical study. In the rat model, significant impairments in hippocampus-dependent memories were observed. MRI studies did not reveal significant atrophy of the hippocampus volume, but significant deformations were indeed observed-particularly on the ipsilateral side. There, the neuronal surface area was significantly lower in ischemic rats and was associated with a lower tissue density and a markedly thinner entorhinal cortex. At 6 months post-stroke, 49 of the 90 patients displayed cognitive impairment (males 55.10%). Shape analysis revealed marked deformations of their left hippocampus, a significantly lower entorhinal cortex surface area, and a wider rhinal sulcus but no hippocampal atrophy. Hence, hippocampal deformations and entorhinal cortex atrophy were associated with long-term impaired cognitive abilities in a stroke rat model and in stroke patients. When combined with existing biomarkers, these markers might constitute sensitive new tools for the early prediction of post-stroke dementia.

MRI for in vivo diagnosis of cerebral amyloid angiopathy: Tailoring artifacts to image hemorrhagic biomarkers.

Cerebral amyloid angiopathy (CAA) is a frequent age-related small vessel disease (SVD) with cardinal magnetic resonance imaging (MRI) signatures that are hemorrhagic in nature, and include the presence of strictly lobar (superficial) cerebral microbleeds and intracerebral hemorrhages as well as cortical superficial siderosis. When investigating a patient with suspected CAA in the context of intracranial hemorrhage (parenchymal or subarachnoid) or cognitive dysfunction, various MRI parameters influence the optimal detection and characterization (and prognostication) of this frequent SVD. The present report describes the influence of imaging techniques on the detection of the key hemorrhagic CAA imaging signatures in clinical practice, in research studies, and the imaging parameters that must be understood when encountering a CAA patient, as well as reviewing CAA literature.

Are the results of intravenous thrombolysis trials reproduced in clinical practice? Comparison of observed and expected outcomes with the stroke-thrombolytic predictive instrument (STPI).

AIM: In patients with cerebral ischemia, intravenous (i.v.) recombinant tissue plasminogen activator (rt-PA) increases survival without handicap or dependency despite an increased risk of bleeding. This study evaluated whether the results of randomized controlled trials are reproduced in clinical practice. METHOD: Data from a registry of consecutive patients treated by rt-PA at Lille University Hospital were retrospectively analyzed for outcomes, using modified Rankin Scale (mRS) scores, at 3 months. The observed outcomes were then compared with the probability of good (mRS 0-1) and of catastrophic (mRS 5-6) outcomes, as predicted by the stroke-thrombolytic predictive instrument (STPI). RESULTS: Of the 1000 consecutive patients (469 male, median age 74 years, median baseline National Institutes of Health Stroke Scale 11, median onset-to-needle time 143min), 438 (43.8%) had a good outcome, 565 (56.5%) had an mRS score 0-2 or similar to their pre-stroke mRS, 155 (15.5%) died within 3 months and 74 (7.4%) developed symptomatic intracerebral hemorrhage according to ECASS-II (Second European-Australasian Acute Stroke Study) criteria. Of the 613 patients (61.3%) eligible for evaluation by the s-TPI, the observed rate of good outcomes was 41.3% (95% CI: 37.5-45.3%), while expected rates with and without rt-PA were 48.8% (95% CI: 44.8-52.7%) and 32.5% (95% CI: 28.8-36.2%), respectively; the observed rate of catastrophic outcomes was 17.0% (95% CI: 14.0-19.9%), while the expected rate was 19.2% (95% CI: 16.1-22.4%) with or without rt-PA. CONCLUSION: In clinical practice, the rate of good outcomes is slightly lower than expected, according to the s-TPI, except for the most severe cases, whereas the rate of catastrophic outcomes is roughly similar. However, the rate of good outcomes is higher than predicted without treatment. This finding suggests that rt-PA is effective for improving outcomes in clinical practice.

[Long-term blood pressure outcome after unilateral adrenalectomy for primary hyperaldosteronism]. / Contrôle à long terme de la pression artérielle après surrénalectomie pour hyperaldostéronisme primaire.

OBJECTIVES: To evaluate long-term results of adrenalectomy for primary aldosteronism (PA) and to identify prognostic factors associated. METHODS: Exhaustive retrospective review of all consecutive patients undergoing adrenalectomy for PA between 2002 and 2013 in our department. All patients underwent preoperative: clinical evaluation (age, sex, height, weight, systolic and diastolic BP under treatment, identification of anti-hypertension treatment), biological evaluation (potassium, renin, aldosterone) and radiological evaluation (CT and/or MRI). Blood pressure was assessed postoperatively at 1 month, 1 year, then at the date of the latest news. The patients were classified into three categories: cured (no antihypertensive therapy in postoperative associated with strictly lower blood pressures of 140/90mmHg), improved (decreased number of drugs or number unchanged but with better blood pressure control), and refractory (no change in the number of drug and blood pressure, or deterioration of one or other of these two parameters). RESULTS: We evaluated 43 patients, 23 men and 20 women, with a median follow-up of 74.4 months [16.8 to 141]. Pathological analysis described 34 adenomas (79%), 7 hyperplasias (16%) (5 micro-nodular and 2 macro-nodular) and 2 adrenocortical carcinoma (5%). The postoperative long-term assessment found 20% of cured patients (n=8), 65% of improved (n=26) and 15% of refractory (n=6). Prognostic factors associated with favorable long-term blood pressure outcome were those typically associated with ARS score [preoperative number of anti-hypertension drugs (P=0.005), BMI<25kg/m2 (P=0.009), and duration of hypertension (P=0.007)]. CONCLUSION: Adrenalectomy for PA is a long-term effective treatment for blood pressure control. Prognostic factors associated with long-term success are those conventionally described in ARS score. LEVEL OF EVIDENCE: 4.

The topography of cortical microbleeds in frontotemporal lobar degeneration: a post-mortem 7.0-tesla magnetic resonance study.

INTRODUCTION: Cerebrovascular lesions are rare in frontotemporal lobar degeneration (FTLD), in contrast to other neurodegenerative diseases. Cortical microbleeds (CoMBs) are frequent in Alzheimer's disease, in particular in cases associated with cerebral amyloid angiopathy. The present study investigates the gyral topographic distribution of CoMBs in post-mortem FTLD brains with 7.0-tesla magnetic resonance imaging. MATERIAL AND METHODS: The distribution of CoMBs in 11 post-mortem FTLD brains and in 12 control brains was compared on T2*-GRE MRI of six coronal sections of a cerebral hemisphere. The mean values of CoMBs were determined in twenty-two different gyri. The findings were correlated to those separately observed on neuropathological examination. RESULTS: As a whole there was a trend of more CoMBs in the prefrontal section of FTLD as well as of the control brains. CoMBs were significantly increased in the superior frontal gyrus and the insular cortex (p ≤ 0.001) and also in the inferior frontal gyrus and the superior temporal gyrus (p ≤ 0.01). CONCLUSIONS: CoMBs in FTLD are only increased in the regions mainly affected by the neurodegenerative lesions. They probably do not reflect additional cerebrovascular disease.

[Complete resolution of inflammatory myofibroblastic tumor of the bladder after antibiotic therapy]. / Régression complète d'une tumeur myofibroblastique inflammatoire de vessie après antibiothérapie.

Inflammatory myofibroblastic tumors (IMT) are rare benign tumors, most commonly arising in the lungs and urinary bladder. Many etiologic factors are suspected in their development, but none have been formally demonstrated. Conventional treatment for bladder IMT is complete surgical resection by partial cystectomy or transurethral resection. We report the case of an 8-year-old girl with documented bladder IMT that resolved completely after antibiotic therapy.

Blood biomarkers in the early stage of cerebral ischemia.

In ischemic stroke patients, blood-based biomarkers may be applied for the diagnosis of ischemic origin and subtype, prediction of outcomes and targeted treatment in selected patients. Knowledge of the pathophysiology of cerebral ischemia has led to the evaluation of proteins, neurotransmitters, nucleic acids and lipids as potential biomarkers. The present report focuses on the role of blood-based biomarkers in the early stage of ischemic stroke-within 72h of its onset-as gleaned from studies published in English in such patients. Despite growing interest in their potential role in clinical practice, the application of biomarkers for the management of cerebral ischemia is not currently recommended by guidelines. However, there are some promising clinical biomarkers, as well as the N-methyl-d-aspartate (NMDA) peptide and NMDA-receptor (R) autoantibodies that appear to identify the ischemic nature of stroke, and the glial fibrillary acidic protein (GFAP) that might be able to discriminate between acute ischemic and hemorrhagic strokes. Moreover, genomics and proteomics allow the characterization of differences in gene expression, and protein and metabolite production, in ischemic stroke patients compared with controls and, thus, may help to identify novel markers with sufficient sensitivity and specificity. Additional studies to validate promising biomarkers and to identify novel biomarkers are needed.

Vascular expression of annexin A2 in lupus nephritis.

AIMS: To evaluate vascular expression of annexin A2 (ANXA2) and its subunit S100A10 in lupus nephritis (LN). METHODS: The present histological study included 14 patients with LN and 11 controls (patients with non-lupus kidney diseases). Kidney biopsies from patients with lupus were scored for lupus glomerulonephritis (according to the International Society of Nephrology/Renal Pathology Society 2003 classification) and vascular lesions (such as microthrombi and antiphospholipid syndrome nephropathy (APSN)). ANXA2 and S100A10 expression in glomerular and peritubular capillaries was evaluated by immunohistochemistry on tissue sections. The staining intensity score ranged from 0 (no expression) to 4 (intense expression). RESULTS: In patients with LN, the median age (range) at first kidney biopsy was 36 (18-49). Vascular lesions were observed in six patients (including two with APSN). We observed intense expression of ANXA2 in glomerular and peritubular capillaries while expression of S100A10 was weaker. However, one of the patients with APSN showed strong S100A10 expression. Patients with LN and controls differed significantly in terms of S100A10 expression in peritubular capillaries. We also observed a statistical difference between patients who had LN with renal vascular lesions and those without renal vascular lesions in terms of ANXA2 expression in peritubular capillaries. CONCLUSIONS: The presence of vascular lesions in LN appears to be associated with significant differences in the vascular expression of ANXA2. Vascular expression of ANXA2 was somewhat higher in LN. Vascular expression of S100A10 was somewhat lower in LN (except one of the two patients with APSN). Further studies of ANXA2's putative value as a biomarker of active LN or of vascular lesions in LN are required.