Search

Macrophagic myofasciitis (MMF) syndrome is a subtype of autoimmune/inflammatory syndrome induced by adjuvants (ASIA) or Shoenfeld's syndrome, characterized by the presence of stereotyped inflammatory lesions at muscle biopsy attesting the long-term persistence of aluminum hydroxide particles at the site of previous immunization. Most frequently reported symptoms are chronic arthromyalgias and fatigue and cognitive complaint. MMF-associated cognitive disorder (MACD) is characterized by the dysfunctioning of attention, executive functions, short-term term and long-term memory, and, in some instances, left ear extinction. MACD is expressed in a chronic, nonevolving, well-defined syndromic framework within which the expression in terms of severity differs from one patient to another. While brain MRI is usually noncontributive, functional imaging using SPECT and PET has revealed the existence of a suggestive pathological pattern with involvement of posterior associative areas, temporal lobes, limbic system, and cerebellum. Put together, neuropsychological and functional neuroimaging investigations support the view that MACD relates to organic central nervous system involvement.

Introduction: Mechanical thrombectomy (MT) for large vessels occlusion of anterior circulation acute ischemic stroke (AIS) improves functional outcome at 3-month. However, elderly patients (≥80 years old) are a growing and fragile population for whom data are scarce. Hypothesis: To determine the factors associated with a favorable functional outcome after endovascular treatment for anterior circulation AIS in elderly patients. Methods: All patients aged≥ 80 years old with anterior circulation AIS and a primary functional independence (mRS Results: A total of 82 patients were treated for anterior circulation AIS with a recanalization rate of 87%. The NIHSS score was improved from 16.7 ± 6 [range: 3-27], to 12.2 ± 8.2 [range: 0-32] at 24h, (p=0.0001) and 9.3 ± 7.77 [range: 0-32] at discharge (p=6 x 10-7). We found a SIH rate of 1% while 40% of patients had intracranial hemorrhage, mortality was 27%, and at 3 months 29% of patients were functionally independent (mRS ≤ 2) and 16% had moderate disability (mRS=3). DWI-ASPECTS (p=0.007), low initial NIHSS (p=0.013), age (p=0.02) and IV thrombolysis (p=0.03), were associated with a favorable functional outcome. Use of general anesthesia (p=0.09), diabetes (p=0.05) and hyperglycemia (p=0.05) were associated with a poorer outcome at a lesser degree. Conclusions: MT of anterior circulation AIS in elderly patients is safe and effective.

Introduction: Ischemic strokes with tandem occlusions are associated with a poor prognosis. Recent studies demonstrating the effectiveness of endovascular treatment for large vessel occlusions have shown less impressive results in patients with tandem occlusions than in those with isolated intracranial occlusions. Besides, the indications and effects of ICA stenting remain unclear. Hypothesis: To determine the factors associated with favorable outcome at 3-month in this subtype of AIS. Methods: From a prospectively gathered registry, we analyzed the data of 70 consecutive patients who underwent mechanical endovascular treatment for acute stroke with tandem occlusions from November 2011 to August 2014. Clinical (including demographics, NIHSS, and stroke etiology), imaging (including DWI-ASPECTS), and endovascular treatment data were assessed and reviewed in consensus by two observers. Good clinical outcome was defined as a modified Rankin Scale (mRS) of ≤2 at 3-month follow-up. The mRS at 3 months follow-up was available in 67 patients. Results: At 3-month follow-up, 33 of 67 (49.3%) patients had a good clinical outcome and 34 (50.8%) had a poor clinical outcome, including 9 deaths (13.4%). Lower NIHSS (initial, at day 1, and at discharge) and successful recanalization (TICI 2b-3) were associated with a good clinical outcome (P Conclusions: Despite the recent randomized control trials demonstrating the effectiveness of thrombectomy, there is still a research gap about tandem occlusions. This subtype of stroke, which usually responds poorly to intravenous thrombolysis, is also difficult to treat by endovascular means.

Introduction: The ADAPT (a direct aspiration first pass technique for acute stroke thrombectomy), using large bore aspiration catheters, has been reported to be a fast, safe, simple and effective method of mechanical thrombectomy (MT) that has facilitated the treatment of acute ischemic strokes. Hypothesis: An attempt to determinate the favorable factors leading to a satisfactory reperfusion (TICI 2b/3) with ADAPT in anterior circulation ischemic stroke patients with confirmed large vessel occlusions. Methods: Based on our prospectively gathered database we extracted patients who were admitted for MT in anterior circulation ischemic strokes since August 2013 and for whom ADAPT was used as the first MT option. Patient demographics, initial NIHSS, localization and lateralization of the occlusion, DWI-ASPECTS, IV thrombolysis prior to MT, time from stroke onset to femoral puncture, final TICI score and 3-month mRS were analyzed. Results: ADAPT was effective in achieving a TICI2b/3 in 54.7% of 309 patients. Two factors influenced positively the success of reperfusion with ADAPT as a stand alone procedure: an isolated MCA occlusion (p Conclusions: ADAPT is very effective in case of isolated MCA occlusion ischemic strokes. The relevance of ADAPT over stent retrievers in other anterior circulation localizations (carotid siphon and tandem occlusions) has to be evaluated with a randomized study.

Background and purposeThe angiography based Capillary Index Score (CIS) has recently emerged as a potential surrogate marker of cerebral perfusion before intra-arterial thrombolysis. We assessed the prevalence of a favorable CIS (f-CIS) and its relationship with clinical outcome in patients treated by mechanical thrombectomy (MT).MethodsData from consecutive patients treated by MT from acute middle cerebral artery (MCA) occlusion were retrospectively analyzed. CIS was calculated from a pre-intervention cerebral angiogram. Association with favorable clinical outcome (modified Rankin Scale score ≤2) at 3 months was assessed in multivariate analysis.Results146 patients were included in the study. f-CIS was observed in 106/146 (72%) patients with an acceptable inter-rater agreement (κ=0.73, p4 (p=0.004). In binary regression, a favorable outcome was independently associated with f-CIS (OR (−95% CI, +95% CI)=3.8 (1.3 to 10.9), p=0.013), as well as NIHSS (p=0.007), ASPECTS (p=0.005), isolated M1/M2 occlusion (p=0.013), and age (p=0.032). The positive predictive value of f-CIS for a favorable outcome was 67%.Conclusionsf-CIS was strongly associated with a favorable outcome after MT of acute MCA occlusion. As an easy surrogate marker of cerebral perfusion, it may be a useful—albeit not sufficient—diagnostic test to select patients just before an MT or to manage them after recanalization.

Purpose: The angiography-based capillary index Score (CIS) has recently emerged as a potential tool for assessing viable tissue. Our study aimed at correlating the CIS with patient outcomes. Materials and Methods: Based on our prospective gathered (December 2011 to April 2014) database, we analyzed the charts of patients who presented with anterior circulation acute ischemic stroke and elected for mechanical thrombectomy (MT). Patient age, NIHSS at admission, DWI-ASPECTS, pre-MT TICI score, CIS, post-MT TICI score, time from onset to reperfusion, 3-month mRS were analyzed. Patients were dichotomized into two groups: favorable (mRS≤2) and poor (mRS≥3) outcomes at 3-month follow-up. Univariate statistical analysis was carried out to determine which factors were the most determinant for patient outcome using the 3-month outcome. Then logistic regression analysis was performed to refine the results. Results: A total of 287 consecutive patients were elected for anterior circulation MT, 160 patients had a CIS and 138 of them had a complete follow-up including a 3-month mRS. They were (72 males, 67 females; mean age: 64). Sixty-nine out of the 138 patients (50.0 %) had a favorable outcome at 3-month. The 3-month mortality was 18.1%. Good reperfusion (TICI ≥ 2b) was obtained in 77.1% of the patients. The mean time from stroke onset to reperfusion was 5.9 hours. Univariate analysis showed that the statistically significant factors for a favorable 3-month outcome were the CIS and the NIHSS at admission (p Conclusions: High initial CIS are associated with better outcomes in acute ischemic stroke patients who undergo MT arguing that, along with the infarct volume, the assessment of arterial collateral supply is a striking determinant of patient outcome.

Intravenous thrombolysis (IVT) followed by mechanical thrombectomy (MT) is recommended to treat acute ischemic stroke (AIS) with a large vessel occlusion (LVO). Most hospitals do not have on-site MT facilities, and most patients need to be transferred secondarily after IVT (drip and ship), which may have an effect on the neurologic outcome.To compare the functional independence at 3 months between patients treated under the drip-and-ship paradigm and those treated on site (mothership).This study used a prospectively gathered registry of patients with AIS to select patients admitted through the Saint-Antoine and Tenon (drip and ship) or the Fondation Rothschild (mothership) hospitals from January 1, 2013, through April 30, 2016. The study included patients older than 18 years treated with bridging therapy for AIS with LVO of the anterior circulation. Among the 159 patients who received MT at the mothership, 100 had been transferred after IVT from the drip-and-ship hospitals and 59 had received IVT on site.The main outcome was 3-month functional independence (modified Rankin scale score ≤2). Both groups were compared using a multivariate linear model, including variables that were significantly different in the 2 groups.During the study period, 497 patients were hospitalized at the drip-and-ship and mothership hospitals for an AIS eligible to reperfusion therapy; 11 patients had a basilar artery occlusion and were excluded, leaving 100 patients in the drip-and-ship group (mean age, 73 years; age range, 60-81 years; 57 men [57.0%]) and 59 in the mothership group (mean age, 70 years; age range, 58-82 years; 29 men [49.2%]). The proportion of patients with a favorable neurologic outcome at 3 months was similar in both groups (drip and ship, 61 [61.0%]; mothership, 30 [50.8%]; P = .26), even after adjusting the analysis for the baseline National Institutes of Health Stroke Scale score, diffusion-weighted imaging Alberta Stroke Program Early Computed Tomography Score, and general anesthesia (P = .82). Patients had less severe conditions in the drip-and-ship group (median baseline National Institutes of Health Stroke Scale score, 15 vs 17 [P = .03]; median diffusion-weighted imaging Alberta Stroke Program Early Computed Tomography Score, 7.5 vs 7 [P = .05]). Process times were longer in the drip-and-ship group (onset-to-needle time, 150 vs 135 minutes; onset-to-puncture time, 248 vs 189 minutes; and onset-to-recanalization time, 297 vs 240 minutes; P .001). Both groups were similar in terms of substantial recanalization (Thrombolysis in Cerebral Ischemia scores 2B to 3; drip and ship, 84 [84.0%]; mothership, 47 [79.7%]; P = .49) and symptomatic hemorrhagic transformation (drip and ship, 2 [2.0%]; mothership, 2 [3.4%]; P = .63).This study found that patients treated under the drip-and-ship paradigm also benefit from bridging therapy, with no statistically significant difference compared with those treated directly in a comprehensive stroke center.

Cancer cells have an increased ability to squeeze through extracellular matrix gaps that they create by promoting proteolysis of its components. Major sites of degradation are specialized micro-domains in the plasma membrane collectively named invadosomes where the Arp2/3 complex and formin proteins cooperate to spatio-temporally control actin nucleation and the folding of a dynamic F-actin core. At invadosomes, proper coupling of exo-endocytosis allows polarized delivery of proteases that facilitate degradation of ECM and disruption of the cellular barrier. We investigated the contribution of the actin nucleator Spire-1 to invadosome structure and function, using Src-activated cells and cancer cells. We found that Spire-1 is specifically recruited at invadosomes and is part of a multi-molecular complex containing Src kinase, the formin mDia1 and actin. Spire-1 interacts with the Rab3A GTPase, a key player in the regulation of exocytosis that is present at invadosomes. Finally, over- and under-expression of Spire-1 resulted in cells with an increased or decreased potential for matrix degradation, respectively, therefore suggesting a functional interplay of Spire-1 with both actin nucleation and vesicular trafficking that might impact on cell invasive and metastatic behavior.

Summary Toxoplasma gondii , a human pathogen and a model apicomplexan parasite, actively and rapidly invades host cells. To initiate invasion, the parasite induces the formation of a parasite–cell junction, and progressively propels itself through the junction, inside a newly formed vacuole that encloses the entering parasite. Little is known about how a parasite that is a few microns in diameter overcomes the host cell cortical actin barrier to achieve the remarkably rapid process of internalization (less than a few seconds). Using correlative light and electron microscopy in conjunction with electron tomography and three-dimensional image analysis we identified that toxofilin, an actin-binding protein, secreted by invading parasites correlates with localized sites of disassembly of the host cell actin meshwork. Moreover, quantitative fluorescence speckle microscopy of cells expressing toxofilin showed that toxofilin regulates actin filament disassembly and turnover. Furthermore, Toxoplasma tachyzoites lacking toxofilin, were found to be impaired in cortical actin disassembly and exhibited delayed invasion kinetics. We propose that toxofilin locally upregulates actin turnover thus increasing depolymerization events at the site of entry that in turn loosens the local host cell actin meshwork, facilitating parasite internalization and vacuole folding.

International audience; Toxoplasma gondii is a human protozoan parasite that belongs to the phylum of Apicomplexa and causes toxoplasmosis. As the other members of this phylum, T. gondii obligatory multiplies within a host cell by a peculiar type of mitosis that leads to daughter cell assembly within a mother cell. Although parasite growth and virulence have been linked for years, few molecules controlling mitosis have been yet identified and they include a couple of kinases but not the counteracting phosphatases. Here, we report that in contrast to other animal cells, type 2C is by far the major type of serine threonine phosphatase activity both in extracellular and in intracellular dividing parasites. Using wild type and transgenic parasites, we characterized the 37kDa TgPP2C molecule as an abundant cytoplasmic and nuclear enzyme with activity being under tight regulation. In addition, we showed that the increase in TgPP2C activity significantly affected parasite growth by impairing cytokinesis while nuclear division still occurred. This study supports for the first time that type 2C protein phosphatase is an important regulator of cell growth in T. gondii.

A correction has been published:The Journal of Infectious Diseases, Volume 218, Issue 8, 15 October 2018, Page 1350, https://doi.org/10.1093/infdis/jiy315; International audience; Background:We assessed prevalence and risk factors for anal human papillomavirus (HPV) in human immunodeficiency virus (HIV)-positive men who have sex with men (MSM), who are at high-risk of HPV-related anal cancer.Methods:APACHES is a multicentric, prospective study of anal HPV infection and lesions in HIV-positive MSM aged ≥35 years. At baseline, participants underwent anal swabs for HPV and cytology, plus high-resolution anoscopy. High-risk HPV (HR-HPV) was tested by Cobas4800, with genotyping of HR-HPV positives by PapilloCheck.Results:Among 490 participants, prevalence of HPV16 and HR-HPV was 29% and 70%, respectively, and did not differ significantly by age, sexual behavior, or markers of HIV or immune deficiency. Smoking was the only, albeit weak (odds ratio, 1.8; 95% confidence interval, 1.2-2.7), predictor of HR-HPV. High-risk HPV and HPV16 prevalence increased strongly with anal diagnosis severity, both by worse cytological/histological (composite) diagnosis at APACHES baseline and worse historical diagnosis. HPV16 rose from 19% among participants who were negative for lesions to 63% among participants with high-grade lesions. In contrast, non-HPV16 HR-HPVs were less prevalent in high-grade (37%) than negative (64%) composite diagnosis, and their causal attribution was further challenged by multiple HPV infections.Conclusions:Human papillomavirus 16 is ubiquitously frequent among human immunodeficiency virus -positive men having sex with men, and more strongly associated with high-grade anal lesions than other high-risk types, confirming it as a target for anal cancer prevention.