Association of intravenous thrombolysis and pre-interventional reperfusion: a post hoc analysis of the SWIFT DIRECT trial.

BACKGROUND A potential benefit of intravenous thrombolysis (IVT) before mechanical thrombectomy (MT) is pre-interventional reperfusion. Currently, there are few data on the occurrence of pre-interventional reperfusion in patients randomized to IVT or no IVT before MT. METHODS SWIFT DIRECT (Solitaire With the Intention For Thrombectomy Plus Intravenous t-PA vs DIRECT Solitaire Stent-retriever Thrombectomy in Acute Anterior Circulation Stroke) was a randomized controlled trial including acute ischemic stroke IVT eligible patients being directly admitted to a comprehensive stroke center, with allocation to IVT with MT versus MT alone. The primary endpoint of this analysis was the occurrence of pre-interventional reperfusion, defined as a pre-interventional expanded Thrombolysis in Cerebral Infarction score of ≥2a. The effect of IVT and potential treatment effect heterogeneity were analyzed using logistic regression analyses. RESULTS Of 396 patients, pre-interventional reperfusion occurred in 20 (10.0%) patients randomized to IVT with MT, and in 7 (3.6%) patients randomized to MT alone. Receiving IVT favored the occurrence of pre-interventional reperfusion (adjusted OR 2.91, 95% CI 1.23 to 6.87). There was no IVT treatment effect heterogeneity on the occurrence of pre-interventional reperfusion with different strata of Randomization-to-Groin-Puncture time (p for interaction=0.33), although the effect tended to be stronger in patients with a Randomization-to-Groin-Puncture time >28 min (adjusted OR 4.65, 95% CI 1.16 to 18.68). There were no significant differences in rates of functional outcomes between patients with and without pre-interventional reperfusion. CONCLUSION Even for patients with proximal large vessel occlusions and direct access to MT, IVT resulted in an absolute increase of 6% in rates of pre-interventional reperfusion. The influence of time strata on the occurrence of pre-interventional reperfusion should be studied further in an individual patient data meta-analysis of comparable trials. TRIAL REGISTRATION NUMBER clinicaltrials.gov NCT03192332

Mononeuritis multiplex following immune checkpoint inhibitors in malignant pleural mesothelioma

IntroductionMononeuritis multiplex is frequently related to vasculitic neuropathy and has been reported only sporadically as an adverse event of immune checkpoint inhibitors.MethodsCase series of three patients with mononeuritis multiplex—all with mesothelioma—identified in the databases of two French clinical networks (French Reference Center for Paraneoplastic Neurological Syndromes, Lyon; OncoNeuroTox, Paris; January 2015–October 2022) set up to collect and investigate n-irAEs on a nationwide level.ResultsThree patients (male; median age 86 years; range 72–88 years) had pleural mesothelioma and received 10, 4, and 6 cycles, respectively, of first-line nivolumab plus ipilimumab combined therapy. In patient 1, the neurological symptoms involved the median nerves, and in the other two patients, there was a more diffuse distribution; the symptoms were severe (common terminology criteria for adverse events, CTCAE grade 3) in all patients. Nerve conduction studies indicated mononeuritis multiplex in all patients. Peripheral nerve biopsy demonstrated necrotizing vasculitis in patients 1 and 3 and marked IgA deposition without inflammatory lesions in patient 2. Immune checkpoint inhibitors were permanently withdrawn, and corticosteroids were administered to all patients, leading to complete symptom regression (CTCAE grade 0, patient 2) or partial improvement (CTCAE grade 2, patients 1 and 3). During steroid tapering, patient 1 experienced symptom recurrence and spreading to other nerve territories (CTCAE grade 3); he improved 3 months after rituximab and cyclophosphamide administration.DiscussionWe report the occurrence of mononeuritis multiplex, a very rare adverse event of immune checkpoint inhibitors, in the three patients with mesothelioma. Clinicians must be aware of this severe, yet treatable adverse event

Abstract Number ‐ 240: Association of intravenous thrombolysis and pre‐interventional reperfusion: a post‐hoc analysis of the SWIFT DIRECT trial

Introduction One potential benefit of intravenous thrombolysis (IVT) before mechanical thrombectomy (MT) is pre‐interventional reperfusion. Currently, there is a paucity of data regarding the occurrence of pre‐interventional reperfusion in patients randomized to IVT or no‐IVT before MT. Methods SWIFT DIRECT was a randomized controlled trial including acute ischemic stroke IVT‐eligible patients being directly admitted to a comprehensive stroke center, with allocation to either MT alone or IVT + MT. Primary endpoint of this analysis was the occurrence of pre‐interventional reperfusion defined as pre‐interventional expanded Thrombolysis in Cerebral Infarction score ≥ 2a. The effect of IVT and potential treatment effect heterogeneity were analyzed using logistic regression analyses. Results Out of the 396 patients analyzed, pre‐interventional reperfusion occurred in 20 (10.0%) of patients randomized to IVT+MT, and 7 (3.6%) of patients randomized to MT alone. Receiving IVT favored the occurrence of pre‐interventional reperfusion (aOR 2.91 [95% CI 1.23 – 6.87]). There was no IVT treatment effect heterogeneity on the occurrence of pre‐interventional reperfusion with different strata of Randomization‐to‐Groin‐Puncture (p for interaction = 0.33), although the effect tended to be stronger in patients with Randomization‐to‐Groin‐Puncture >28 minutes (aOR 4.65 [95% CI 1.16 – 18.68]). There were no significant difference in rates of functional outcomes between patients with and without pre‐interventional reperfusion. Conclusions Even for patients with proximal large vessel occlusions and direct access to MT, IVT leads towards an absolute increase of 6.9% (95% CI 1.7‐12.2%) in the rates of pre‐interventional reperfusion. The effect of IVT tended to be more pronounced when Randomization‐to‐Groin‐Puncture intervals were longer, but this heterogeneity did not reach statistical significance

Impact of Number of Passes Before Rescue Therapy in Thrombectomy for Basilar Artery Strokes

Background When standard endovascular thrombectomy techniques fail to achieve a successful recanalization, it is often necessary to use rescue therapies (RTs). RTs are more commonly used in basilar artery occlusions and conventionally thought to represent “a last resort option.” We sought to study the outcomes of basilar artery occlusion patients who received RT, and further hypothesize that the number of instrumental passes before initiation of RT may be associated with increased risk for poor clinical outcomes. Methods We performed a retrospective analysis of the ETIS (“Endovascular Treatment in Ischemic Stroke”) registry. Our primary analysis included 277 patients who underwent thrombectomy for basilar artery occlusion, of whom 74 patients (26.7%) who received RT, defined as the use of intra‐arterial drugs, angioplasty, or stenting. Primary outcome measures included successful or complete reperfusion (final modified thrombolysis in cerebral infarction ≥2b or 3), functional independence (modified Rankin scale of 0–2), and mortality at 3 months. Results RT patients were more likely to have an atherosclerotic cause than non‐RT patients (46/74 [62.2%] versus 38/203 [18.7%]), were more likely to die (42/74 [56.8%] versus 73/203 [36.0%]), and were less likely to achieve functional independence (12/74 [16.2%] versus 84/203 [41.4%]). In the RT cohort, 17 of 74 patients (23.0%) had 1 pass before RT initiation, and 8 of 17 (47.1%) achieved a modified Rankin scale score of 0 to 2 at 3 months, with a mortality rate of 23.5% (4/17). The chance of achieving good clinical outcome decreased with each additional pass, whereas mortality increased. The odds of mortality at 3 months were highest in the >3 passes group, with an odds ratio of 10.29 (95% CI, 2.42–43.81) compared with 1 pass. None of the 25 patients with >3 passes before RT achieved 3‐month functional independence. Conclusions There is a significant correlation between the number of passes before initiation of RT and 3‐month clinical outcomes in basilar artery occlusion patients

Effect of Operator's Experience on Proficiency in Mechanical Thrombectomy: A Multicenter Study

International audienceBackground and Purpose:We aimed to evaluate among trained interventional neuroradiologist, whether increasing individual experience was associated with an improvement in mechanical thrombectomy (MT) procedural performance metrics.Methods:Individual MT procedural data from 5 centers of the Endovascular Treatment in Ischemic Stroke registry and 2 additional high-volume stroke centers were pooled. Operator experience was defined for each operator as a continuous variable, cumulating the number of MT procedures performed since January 2015, as MT became standard of care or, if later than this date, since the operator started performing mechanical thrombectomies in autonomy. We tested the associations between operator’s experience and procedural metrics.Results:A total of 4516 procedures were included, performed by 36 operators at 7 distinct centers, with a median of 97.5 endovascular treatment procedures per operator (interquartile range, 57–170.2) over the study period. Higher operator’s experience, analyzed as a continuous variable, was associated with a significantly shorter procedural duration (β estimate, −3.98 [95% CI, −5.1 to −2.8]; P<0.001), along with local anesthesia and M1 occlusion location in multivariable models. Increasing experience was associated with better Thrombolysis in Cerebral Infarction scores (estimate, 1.02 [1–1.04]; P=0.013).Conclusions:In trained interventional neuroradiologists, increasing experience in MT is associated with significantly shorter procedural duration and better reperfusion rates, with a theoretical ceiling effect observed after around 100 procedures. These results may inform future training and practice guidelines to set minimal experience standards before autonomization, and to set-up operators’ recertification processes tailored to individual case volume and prior experience

Table_1_Mononeuritis multiplex following immune checkpoint inhibitors in malignant pleural mesothelioma.DOCX

IntroductionMononeuritis multiplex is frequently related to vasculitic neuropathy and has been reported only sporadically as an adverse event of immune checkpoint inhibitors.MethodsCase series of three patients with mononeuritis multiplex—all with mesothelioma—identified in the databases of two French clinical networks (French Reference Center for Paraneoplastic Neurological Syndromes, Lyon; OncoNeuroTox, Paris; January 2015–October 2022) set up to collect and investigate n-irAEs on a nationwide level.ResultsThree patients (male; median age 86 years; range 72–88 years) had pleural mesothelioma and received 10, 4, and 6 cycles, respectively, of first-line nivolumab plus ipilimumab combined therapy. In patient 1, the neurological symptoms involved the median nerves, and in the other two patients, there was a more diffuse distribution; the symptoms were severe (common terminology criteria for adverse events, CTCAE grade 3) in all patients. Nerve conduction studies indicated mononeuritis multiplex in all patients. Peripheral nerve biopsy demonstrated necrotizing vasculitis in patients 1 and 3 and marked IgA deposition without inflammatory lesions in patient 2. Immune checkpoint inhibitors were permanently withdrawn, and corticosteroids were administered to all patients, leading to complete symptom regression (CTCAE grade 0, patient 2) or partial improvement (CTCAE grade 2, patients 1 and 3). During steroid tapering, patient 1 experienced symptom recurrence and spreading to other nerve territories (CTCAE grade 3); he improved 3 months after rituximab and cyclophosphamide administration.DiscussionWe report the occurrence of mononeuritis multiplex, a very rare adverse event of immune checkpoint inhibitors, in the three patients with mesothelioma. Clinicians must be aware of this severe, yet treatable adverse event.</p

Should Patients With Acute Minor Ischemic Stroke With Isolated Internal Carotid Artery Occlusion Be Thrombolysed?

International audienceBACKGROUND: We recently reported a worrying 30% rate of early neurological deterioration (END) occurring within 24 hours following intravenous thrombolysis (IVT) in minor stroke with isolated internal carotid artery occlusion (ie, without additional intracranial occlusion), mainly due to artery-to-artery embolism. Here, we hypothesize that in this setting IVT-as compared to no-IVT-may foster END, in particular by favoring artery-to-artery embolism from thrombus fragmentation. METHODS: From a large multicenter retrospective database, we compared minor stroke (National Institutes of Health Stroke Scale score <6) isolated internal carotid artery occlusion patients treated within 4.5 hours of symptoms onset with either IVT or antithrombotic therapy between 2006 and 2020 (inclusion date varied among centers). Primary outcome was END within 24 hours (≥q4 National Institutes of Health Stroke Scale points increase within 24 hours), and secondary outcomes were END within 7 days (END(7d)) and 3-month modified Rankin Scale score 0 to 1. RESULTS: Overall, 189 patients were included (IVT=95; antithrombotics=94 [antiplatelets, n=58, anticoagulants, n=36]) from 34 centers. END within 24 hours and END(7d) occurred in 46 (24%) and 60 (32%) patients, respectively. Baseline clinical and radiological variables were similar between the 2 groups, except significantly higher National Institutes of Health Stroke Scale (median 3 versus 2) and shorter onset-to-imaging (124 versus 149min) in the IVT group. END within 24 hours was more frequent following IVT (33% versus 16%, adjusted hazard ratio, 2.01 [95% CI, 1.07-3.92]; P=0.03), driven by higher odds of artery-to-artery embolism (20% versus 9%, P=0.09). However, END(7d) and 3-month modified Rankin Scale score of 0 to 1 did not significantly differ between the 2 groups (END(7d): adjusted hazard ratio, 1.29 [95% CI, 0.75-2.23]; P=0.37; modified Rankin Scale score of 0-1: adjusted odds ratio, 1.1 [95% CI, 0.6-2.2]; P=0.71). END(7d) occurred earlier in the IVT group: median imaging-to-END 2.6 hours (interquartile range, 1.9-10.1) versus 20.4 hours (interquartile range, 7.8-34.4), respectively, P<0.01. CONCLUSION: In our population of minor strokes with iICAO, although END rate at 7 days and 3-month outcome were similar between the 2 groups, END-particularly END due to artery-to-artery embolism-occurred earlier following IVT. Prospective studies are warranted to further clarify the benefit/risk profile of IVT in this population

Successful thrombectomy is beneficial in patients with pre-stroke disability: Results from an international multicenter cohort study

International audienceAbstract Excessive alcohol consumption is the leading cause of liver diseases in Western countries, especially in France. Alcohol‐related liver disease (ARLD) is an extremely broad context and there remains much to accomplish in terms of identifying patients, improving prognosis and treatment, and standardising practices. The French Association for the Study of the Liver wished to organise guidelines together with the French Alcohol Society in order to summarise the best evidence available about several key clinical points in ARLD. These guidelines have been elaborated based on the level of evidence available in the literature and each recommendation has been analysed, discussed and voted by the panel of experts. They describe how patients with ARLD should be managed nowadays and discuss the main unsettled issues in the field

Mechanical Thrombectomy for Acute Ischemic Stroke Amid the COVID-19 Outbreak

International audienceBackground and Purpose: The efficiency of prehospital care chain response and the adequacy of hospital resources are challenged amid the coronavirus disease 2019 (COVID-19) outbreak, with suspected consequences for patients with ischemic stroke eligible for mechanical thrombectomy (MT). Methods: We conducted a prospective national-level data collection of patients treated with MT, ranging 45 days across epidemic containment measures instatement, and of patients treated during the same calendar period in 2019. The primary end point was the variation of patients receiving MT during the epidemic period. Secondary end points included care delays between onset, imaging, and groin puncture. To analyze the primary end point, we used a Poisson regression model. We then analyzed the correlation between the number of MTs and the number of COVID-19 cases hospitalizations, using the Pearson correlation coefficient (compared with the null value). Results: A total of 1513 patients were included at 32 centers, in all French administrative regions. There was a 21% significant decrease (0.79; [95%CI, 0.76–0.82]; P <0.001) in MT case volumes during the epidemic period, and a significant increase in delays between imaging and groin puncture, overall (mean 144.9±SD 86.8 minutes versus 126.2±70.9; P <0.001 in 2019) and in transferred patients (mean 182.6±SD 82.0 minutes versus 153.25±67; P <0.001). After the instatement of strict epidemic mitigation measures, there was a significant negative correlation between the number of hospitalizations for COVID and the number of MT cases ( R 2 −0.51; P =0.04). Patients treated during the COVID outbreak were less likely to receive intravenous thrombolysis and to have unwitnessed strokes (both P <0.05). Conclusions: Our study showed a significant decrease in patients treated with MTs during the first stages of the COVID epidemic in France and alarming indicators of lengthened care delays. These findings prompt immediate consideration of local and regional stroke networks preparedness in the varying contexts of COVID-19 pandemic evolution