Results of watchful waiting of unruptured intracranial aneurysms in a Western patient population: a single-center cohort.

BACKGROUND: The natural history of unruptured intracranial aneurysms (UIAs) in Western populations is still debated, especially for those <7 mm. Reporting data of a large single-center cohort managed with watchful waiting is therefore interesting. METHODS: From January 2011 to June 2019, 662 UIAs were followed up by yearly MR angiography. Morphologically stable UIAs were managed conservatively while unstable UIAs were offered treatment. The patients' clinical and radiological data were analyzed retrospectively. RESULTS: UIAs were ≤4 mm in 60%, 4.1-7.0 mm in 33%, and >7 mm in 7%. They were located on the anterior circulation in 90% of cases. The mean follow-up duration was 51.32 months for a total of 2831 aneurysm-years. During follow-up, 37 UIAs (5.5%) were treated because of an increase in size, and 8 UIAs were treated because of patient decision. Three aneurysms ruptured during follow-up for an annual risk of rupture of 0.1% (95% CI 0% to 0.24%). No risk factors for rupture were identified. The three ruptured cases made an excellent recovery. During follow-up, annual mortality from unrelated causes was 0.8% (95% CI 0.51% to 1.18%). CONCLUSIONS: This single-center cohort evaluated our watchful waiting policy applied in two-thirds of all incidental UIAs. Morphological change of UIAs during follow-up led to treatment in 5.5% of cases. With such a management paradigm, we found a low rupture rate in these selected UIAs and the mortality was unrelated to aneurysms.

Results of transvenous embolization of intracranial dural arteriovenous fistula: a consecutive series of 136 patients with 142 fistulas.

OBJECTIVE: Intracranial dural arteriovenous fistula (DAVF) is mainly treated with an endovascular approach. Two major treatment advances include transvenous embolization (TVE) with coils in 1989 and, more recently, transarterial embolization with Onyx. The aim of this study was to present a large monocentric series of patients with DAVF treated with TVE. This series reports more than 20 years of experience and describes the evolution of the medical management of these patients, as well as current indications for this treatment at the authors' center. METHODS: Consecutive patients treated for intracranial DAVFs with TVE from 1995 to 2018 were included. Clinical and imaging data were systematically collected. Univariate and multivariate analyses were performed to identify factors that were significantly associated with adverse clinical course or complications. RESULTS: In this study of 136 patients with 142 DAVFs treated with TVE, the occlusion rate was 90%. The median length of follow-up was 11 months. The rate of permanent complications was 5.1%, and the procedure-related mortality rate was 1.5%. Procedure-related mortality was associated with extension of thrombosis that was observed early in our experience. The introduction of a postoperative anticoagulation regimen has drastically decreased the occurrence of this complication. Other minor complications included cochleovestibular syndrome after embolization of lateral sinus DAVF and oculomotor nerve damage after embolization of cavernous sinus DAVF. CONCLUSIONS: TVE allows efficient occlusion of DAVF. It remains a valid option for DAVF located on a sinus that does not participate in normal venous drainage of the brain.

Predictive score for complete occlusion of intracranial aneurysms treated by flow-diverter stents using machine learning.

BACKGROUND: Complete occlusion of an intracranial aneurysm (IA) after the deployment of a flow-diverter stent is currently unpredictable. The aim of this study was to develop a predictive occlusion score based on pretreatment clinical and angiographic criteria. METHODS: Consecutive patients with ≥6 months follow-up were included from 2008 to 2019 and retrospectively analyzed. Each IA was evaluated using the Raymond-Roy occlusion classification (RROC) and dichotomized as occluded (A) or residual (B/C); 80% of patients were randomly assigned to the training sample. Feature selection and binary outcome prediction relied on logistic regression and threshold maximizing class separation selected by a CART tree algorithm. The feature selection was addressed by a genetic algorithm selected from the 30 pretreatment available variables. RESULTS: The study included 146 patients with 154 IAs. Feature selection yielded a combination of six variables with a good cross-validated accuracy on the test sample, a combination we labeled DIANES score (IA diameter, indication, parent artery diameter ratio, neck ratio, side-branch artery, and sex). A score of more than -6 maximized the ability to predict RROC=A with sensitivity of 87% (95% CI 79% to 95%) and specificity of 82% (95% CI 64% to 96%) in the training sample. Accuracy was 86% (95% CI 79% to 94%). In the test sample, sensitivity and specificity were 89% (95% CI 77% to 98%) and 60% (95% CI 33% to 86%), respectively. Accuracy was 81% (95% CI 69% to 91%). CONCLUSION: A score was developed as a grading scale for prediction of the final occlusion status of IAs treated with a flow-diverter stent.

Effect of Mesenchymal Stromal Cells on T Cells in a Septic Context: Immunosuppression or Immunostimulation?

Sepsis is a complex process, including a first wave of damage partially due to the body's response to pathogens, followed by a phase of immune cell dysfunction. The efficacy of a pharmacological approach facing a rapidly evolving system implies a perfect timing of administration-this difficulty could explain the recent failure of clinical trials. Mesenchymal stromal cells (MSCs) are usually defined as immunosuppressive and their beneficial effects in preclinical models of acute sepsis have been shown to rely partly on such ability. If nonregulated, this phenotype could be harmful in the immunosuppressed context arising hours after sepsis onset. However, MSCs being environment sensitive, we hypothesized that they could reverse their immunosuppressive properties when confronted with suffering immune cells. Our objective was to evaluate the effect of human MSCs on activated human lymphocytes in an in vitro endotoxemia model. Peripheral blood mononuclear cells (PBMCs) underwent a 24-h lipopolysaccharide (LPS) intoxication and were stimulated with phytohemagglutinin (PHA) in contact with MSCs. MSCs induced a differential effect on lymphocytes depending on PBMC intoxication with LPS. Unintoxicated lymphocytes were highly proliferative with PHA and were inhibited by MSCs, whereas LPS-intoxicated lymphocytes showed a low proliferation rate, but were supported by MSCs, even when monocytes were depleted. These data, highlighting MSC plasticity in their immunomodulatory activity, pave the way for further studies investigating the mechanisms of mutual interactions between MSCs and immune cells in sepsis. Thus, MSCs might be able to fight against both early sepsis-induced hyperinflammatory response and later time points of immune dysfunction.

Comparative Study of Injury Models for Studying Muscle Regeneration in Mice.

BACKGROUND: A longstanding goal in regenerative medicine is to reconstitute functional tissues or organs after injury or disease. Attention has focused on the identification and relative contribution of tissue specific stem cells to the regeneration process. Relatively little is known about how the physiological process is regulated by other tissue constituents. Numerous injury models are used to investigate tissue regeneration, however, these models are often poorly understood. Specifically, for skeletal muscle regeneration several models are reported in the literature, yet the relative impact on muscle physiology and the distinct cells types have not been extensively characterised. METHODS: We have used transgenic Tg:Pax7nGFP and Flk1GFP/+ mouse models to respectively count the number of muscle stem (satellite) cells (SC) and number/shape of vessels by confocal microscopy. We performed histological and immunostainings to assess the differences in the key regeneration steps. Infiltration of immune cells, chemokines and cytokines production was assessed in vivo by Luminex®. RESULTS: We compared the 4 most commonly used injury models i.e. freeze injury (FI), barium chloride (BaCl2), notexin (NTX) and cardiotoxin (CTX). The FI was the most damaging. In this model, up to 96% of the SCs are destroyed with their surrounding environment (basal lamina and vasculature) leaving a "dead zone" devoid of viable cells. The regeneration process itself is fulfilled in all 4 models with virtually no fibrosis 28 days post-injury, except in the FI model. Inflammatory cells return to basal levels in the CTX, BaCl2 but still significantly high 1-month post-injury in the FI and NTX models. Interestingly the number of SC returned to normal only in the FI, 1-month post-injury, with SCs that are still cycling up to 3-months after the induction of the injury in the other models. CONCLUSIONS: Our studies show that the nature of the injury model should be chosen carefully depending on the experimental design and desired outcome. Although in all models the muscle regenerates completely, the trajectories of the regenerative process vary considerably. Furthermore, we show that histological parameters are not wholly sufficient to declare that regeneration is complete as molecular alterations (e.g. cycling SCs, cytokines) could have a major persistent impact.

Heterogeneous functions of perinatal mesenchymal stromal cells require a preselection before their banking for clinical use.

Perinatal sources of mesenchymal stromal cells (MSCs) have raised growing interest because they are readily and widely available with minimal ethical/legal issues and can easily be stored for allogeneic settings. In addition, perinatal tissues are known to be important in mediating the fetomaternal tolerance of pregnancy, which confer upon perinatal-MSCs (P-MSCs) a particular interest in immunomodulation. It has been recently shown that it is possible to deeply modify the secreted factor profiles of MSCs with different cytokine stimuli such as interferon gamma or tumor necrosis factor alpha to license MSCs for a better immunosuppresive potential. Therefore, we aimed to compare adult bone marrow-MSCs with MSCs from perinatal tissues (cord blood, umbilical cord, amnion, and chorion) on their in vitro immunological and stromacytic efficiencies under different priming conditions. Our results showed that P-MSCs had a potential to modulate the in vitro immune response and be useful for hematopoietic progenitor cell ex vivo expansion. However, we showed contrasted effects of cytokine priming embedded in an important between-donor variability. In conclusion, our study highlights the importance to elaborate predicitive in vitro tests to screen between-donor variability of perinatal tissues for banking allogeneic standardized MSCs.