Advancements in diagnostic and interventional radiology for stroke treatment: the path from trial to bedside through the pre-MR CLEAN, MR CLEAN, and MR CLEAN II eras.

The stroke field is inevitably connected with imaging in which radiologists fulfill a central role. Our landmark MR CLEAN trial led to the implementation of baseline computed tomography angiography or magnetic resonance angiography in the acute stroke workup and subsequent endovascular treatment (EVT) for ischemic stroke patients with a large vessel occlusion in the anterior circulation, resulting in numerous patients worldwide currently being treated often successfully. A reversal of the pathophysiologic process behind an acute cerebrovascular event was made possible. Subsequently, in the MR CLEAN II trials, the clinical impact of both diagnostic and interventional radiologists remained a cornerstone of our research, which means value-based radiology. Within these MR CLEAN II trials, we proved that aspirin and heparin during EVT should be avoided due to increased symptomatic intracranial hemorrhage risk (MR CLEAN-MED). We concluded there is additional benefit of EVT in the 6-to-24-h window after stroke in the presence of good collaterals on baseline CTA (MR CLEAN-LATE). The impactful success of our stroke trials that changed many guidelines was mainly attributable to (1) the societal burden of the disease, with two thirds of patients dying or being independent at 3 months; (2) the fact that stroke is a common disease, (3) the relatively simple and pragmatic approach of the trials resembling real-world setting; (4) the acceleration of implementation in clinical practice facilitated by a structured approach to guideline development and conditional funding; and foremost (5) the excellent collaboration on a professional level between-disciplines, i.e., diagnostic radiologists, interventionalists, and neurologists.Critical relevance statement The MR CLEAN and MR CLEAN II trials have had tremendous impact on clinical practice, directly by more patients being treated with an effective intervention and indirectly through adoption of evidence-based guidelines. It is in this setting of stroke treatment that diagnostic and interventional radiologists have played a crucial role and created clinical impact.

Admission systolic blood pressure and effect of endovascular treatment in patients with ischaemic stroke: an individual patient data meta-analysis.

BACKGROUND: Current guidelines for ischaemic stroke treatment recommend a strict, but arbitrary, upper threshold of 185/110 mm Hg for blood pressure before endovascular thrombectomy. Nevertheless, whether admission blood pressure influences the effect of endovascular thrombectomy on outcome remains unknown. Our aim was to study the influence of admission systolic blood pressure (SBP) on functional outcome and on the effect of endovascular thrombectomy. METHODS: We used individual patient data from seven randomised controlled trials (MR CLEAN, ESCAPE, EXTEND-IA, SWIFT PRIME, REVASCAT, PISTE, and THRACE) that randomly assigned patients with anterior circulation ischaemic stroke to endovascular thrombectomy (predominantly using stent retrievers) or standard medical therapy (control) between June 1, 2010, and April 30, 2015. We included all patients for whom SBP data were available at hospital admission. The primary outcome was functional outcome (modified Rankin Scale) at 90 days. We assessed the association of SBP with outcome in both the endovascular thrombectomy group and the control group using multilevel regression analysis and tested for non-linearity and for interaction between SBP and effect of endovascular thrombectomy, taking into account treatment with intravenous thrombolysis. FINDINGS: We included 1753 patients (867 assigned to endovascular thrombectomy, 886 assigned to control) after excluding 11 patients for whom SBP data were missing. We found a non-linear association between SBP and functional outcome with an inflection point at 140 mm Hg (732 [42%] of 1753 patients had SBP <140 mm Hg and 1021 [58%] had SBP ≥140 mm Hg). Among patients with SBP of 140 mm Hg or higher, admission SBP was associated with worse functional outcome (adjusted common odds ratio [acOR] 0·86 per 10 mm Hg SBP increase; 95% CI 0·81-0·91). We found no association between SBP and functional outcome in patients with SBP less than 140 mm Hg (acOR 0·97 per 10 mm Hg SBP decrease, 95% CI 0·88-1·05). There was no significant interaction between SBP and effect of endovascular thrombectomy on functional outcome (p=0·96). INTERPRETATION: In our meta-analysis, high admission SBP was associated with worse functional outcome after stroke, but SBP did not seem to negate the effect of endovascular thrombectomy. This finding suggests that admission SBP should not form the basis for decisions to withhold or delay endovascular thrombectomy for ischaemic stroke, but randomised trials are needed to further investigate this possibility. FUNDING: Medtronic.

Safety and efficacy of periprocedural antithrombotics in patients with successful reperfusion after endovascular stroke treatment.

OBJECTIVES: We aimed to evaluate whether the overall harmful effect of periprocedural treatment with aspirin or heparin during endovascular stroke treatment is different in patients with a successful reperfusion after the procedure. MATERIALS AND METHODS: We performed a post-hoc analysis of the MR CLEAN-MED trial, including adult patients with a large vessel occlusion in the anterior circulation eligible for endovascular treatment (EVT). In this trial, patients were randomized for periprocedural intravenous treatment with aspirin or no aspirin (1:1 ratio), and for moderate-dose unfractionated heparin, low-dose unfractionated heparin or no unfractionated heparin (1:1:1 ratio). We tested for interaction between the post-EVT extended thrombolysis in cerebral infarction (eTICI) score and treatment with periprocedural medication with multivariable regression analyses. The primary outcome was the modified Rankin Scale score at 90 days. Secondary outcomes were final infarct volume, intracranial hemorrhage, and symptomatic intracranial hemorrhage. RESULTS: Of 534 included patients, 93 (17%) had a post-EVT eTICI score of 0-2a, 115 (22%) a score of 2b, 73 (14%) a score of 2c, and 253 (47%) a score of 3. For both aspirin and heparin, we found no interaction between post-EVT eTICI score and treatment on the modified Rankin Scale score (p=0.76 and p=0.47, respectively). We found an interaction between post-EVT eTICI score and treatment with heparin on the final infarct volume (p=0.01). Of note, this interaction showed a biologically implausible distribution over the subgroups. CONCLUSIONS: The overall harmful effect of periprocedural aspirin and unfractionated heparin is not different in patients with a successful reperfusion after EVT.

Safety and efficacy of aspirin, unfractionated heparin, both, or neither during endovascular stroke treatment (MR CLEAN-MED): an open-label, multicentre, randomised controlled trial.

BACKGROUND: Aspirin and unfractionated heparin are often used during endovascular stroke treatment to improve reperfusion and outcomes. However, the effects and risks of anti-thrombotics for this indication are unknown. We therefore aimed to assess the safety and efficacy of intravenous aspirin, unfractionated heparin, both, or neither started during endovascular treatment in patients with ischaemic stroke. METHODS: We did an open-label, multicentre, randomised controlled trial with a 2 × 3 factorial design in 15 centres in the Netherlands. We enrolled adult patients (ie, ≥18 years) with ischaemic stroke due to an intracranial large-vessel occlusion in the anterior circulation in whom endovascular treatment could be initiated within 6 h of symptom onset. Eligible patients had a score of 2 or more on the National Institutes of Health Stroke Scale, and a CT or MRI ruling out intracranial haemorrhage. Randomisation was done using a web-based procedure with permuted blocks and stratified by centre. Patients were randomly assigned (1:1) to receive either periprocedural intravenous aspirin (300 mg bolus) or no aspirin, and randomly assigned (1:1:1) to receive moderate-dose unfractionated heparin (5000 IU bolus followed by 1250 IU/h for 6 h), low-dose unfractionated heparin (5000 IU bolus followed by 500 IU/h for 6 h), or no unfractionated heparin. The primary outcome was the score on the modified Rankin Scale at 90 days. Symptomatic intracranial haemorrhage was the main safety outcome. Analyses were based on intention to treat, and treatment effects were expressed as odds ratios (ORs) or common ORs, with adjustment for baseline prognostic factors. This trial is registered with the International Standard Randomised Controlled Trial Number, ISRCTN76741621. FINDINGS: Between Jan 22, 2018, and Jan 27, 2021, we randomly assigned 663 patients; of whom, 628 (95%) provided deferred consent or died before consent could be asked and were included in the modified intention-to-treat population. On Feb 4, 2021, after unblinding and analysis of the data, the trial steering committee permanently stopped patient recruitment and the trial was stopped for safety concerns. The risk of symptomatic intracranial haemorrhage was higher in patients allocated to receive aspirin than in those not receiving aspirin (43 [14%] of 310 vs 23 [7%] of 318; adjusted OR 1·95 [95% CI 1·13-3·35]) as well as in patients allocated to receive unfractionated heparin than in those not receiving unfractionated heparin (44 [13%] of 332 vs 22 [7%] of 296; 1·98 [1·14-3·46]). Both aspirin (adjusted common OR 0·91 [95% CI 0·69-1·21]) and unfractionated heparin (0·81 [0·61-1·08]) led to a non-significant shift towards worse modified Rankin Scale scores. INTERPRETATION: Periprocedural intravenous aspirin and unfractionated heparin during endovascular stroke treatment are both associated with an increased risk of symptomatic intracranial haemorrhage without evidence for a beneficial effect on functional outcome. FUNDING: The Collaboration for New Treatments of Acute Stroke consortium, the Brain Foundation Netherlands, the Ministry of Economic Affairs, Stryker, Medtronic, Cerenovus, and the Dutch Heart Foundation.

Predictors of poor outcome despite successful endovascular treatment for ischemic stroke: results from the MR CLEAN Registry.

BACKGROUND: Approximately one-third of patients with ischemic stroke treated with endovascular treatment do not recover to functional independence despite rapid and successful recanalization. We aimed to quantify the importance of predictors of poor functional outcome despite successful reperfusion. METHODS: We analyzed patients from the MR CLEAN Registry between March 2014 and November 2017 with successful reperfusion (extended Thrombolysis In Cerebral Infarction ≥2B). First, predictors were selected based on expert opinion and were clustered according to acquisition over time (ie, baseline patient factors, imaging factors, treatment factors, and postprocedural factors). Second, several models were constructed to predict 90-day functional outcome (modified Rankin Scale (mRS)). The relative importance of individual predictors in the most extensive model was expressed by the proportion of unique added χ2 to the model of that individual predictor. RESULTS: Of 3180 patients, 1913 (60%) had successful reperfusion. Of these 1913 patients, 1046 (55%) were functionally dependent at 90 days (mRS >2). The most important predictors for mRS were baseline patient factors (ie, pre-stroke mRS, added χ2 0.16; National Institutes of Health Stroke Scale score at baseline, added χ2 0.12; age, added χ2 0.10), and postprocedural factors (ie, symptomatic intracranial hemorrhage (sICH), added χ2 0.12; pneumonia, added χ2 0.09). The probability of functional independence for a typical stroke patient with sICH was 54% (95% CI 36% to 72%) lower compared with no sICH, and 21% (95% CI 4% to 38%) for pneumonia compared with no pneumonia. CONCLUSION: Baseline patient factors and postprocedural adverse events are important predictors of poor functional outcome in successfully reperfused patients with ischemic stroke. This implies that prevention of postprocedural adverse events has the greatest potential to further improve outcomes in these patients.

Blood Pressure in the First 6 Hours Following Endovascular Treatment for Ischemic Stroke Is Associated With Outcome.

Background and Purpose: Optimal blood pressure (BP) management in the acute phase of ischemic stroke remains an unresolved issue. It is uncertain whether guidelines for BP management during and after intravenous alteplase can be extrapolated to endovascular treatment (EVT) for stroke due to large artery occlusion in the anterior circulation. We evaluated the associations between systolic BP (SBP) in the first 6 hours following EVT and functional outcome as well as symptomatic intracranial hemorrhage. Methods: Patients of 8 MR CLEAN (Multicenter Randomized Controlled Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) Registry centers, with available data on SBP in the 6 hours following EVT, were analyzed. We evaluated maximum, minimum, and mean SBP. Study outcomes were functional outcome (modified Rankin Scale) at 90 days and symptomatic intracranial hemorrhage. We used multivariable ordinal and binary regression analysis to adjust for important prognostic factors and studied possible effect modification by successful reperfusion. Results: Post-EVT SBP data were available for 1161/1796 patients. Higher maximum SBP (per 10 mm Hg increments) was associated with worse functional outcome (adjusted common odds ratio, 0.93 [95% CI, 0.88­0.98]) and a higher rate of symptomatic intracranial hemorrhage (adjusted odds ratio, 1.17 [95% CI, 1.02­1.36]). The association between minimum SBP and functional outcome was nonlinear with an inflection point at 124 mm Hg. Minimum SBP lower and higher than the inflection point were associated with worse functional outcomes (adjusted common odds ratio, 0.85 per 10 mm Hg decrements [95% CI, 0.76­0.95] and adjusted common odds ratio, 0.81 per 10 mm Hg increments [95% CI, 0.71­0.92]). No association between mean SBP and functional outcome was observed. Successful reperfusion did not modify the relation of SBP with any of the outcomes. Conclusions: Maximum SBP in the first 6 hours following EVT is positively associated with worse functional outcome and an increased risk of symptomatic intracranial hemorrhage. Both lower and higher minimum SBP are associated with worse outcomes. A randomized trial to evaluate whether modifying post-intervention SBP results in better outcomes after EVT for ischemic stroke seems justified.

Effect of Heparinized Flush Concentration on Safety and Efficacy During Endovascular Thrombectomy for Acute Ischemic Stroke: Results from the MR CLEAN Registry.

BACKGROUND: Currently, there are no recommendations regarding the use of heparinized flush during endovascular thrombectomy (EVT) for acute ischemic stroke. Periprocedural heparin could, however, affect functional outcome and symptomatic intracranial hemorrhage (sICH). We surveyed protocols on heparin flush concentrations in Dutch EVT centers and assessed its effect on safety and efficacy outcomes. METHODS: Patients registered in the MR CLEAN Registry, from 2014 up to 2017 were included. We collected data on center protocols regarding heparin flush concentrations (IU/L) and grouped patients by their per protocol administered heparin flush concentration. We used a random effects model with random intercepts by EVT center and analyzed endpoints using regression models. Endpoints were sICH, mRS at 90 days, mortality and reperfusion rates. RESULTS: A total of 3157 patients were included of which 45% (6 centers) received no heparin in the flush fluids, 1.8% (1 center) received flush fluids containing 2000 IU/L heparin, 26% (4 centers) received 5000 IU/L, 22% (4 centers) received 10.000 IU/L and 5.6% (1 center) received 25.000 IU/L. Higher heparin concentration was associated with increased sICH (aOR 1.15; 95% CI 1.02-1.29), but not with functional outcome, mortality or reperfusion rates. CONCLUSION: Effect of heparin in flush fluids should not be ignored by clinicians or researchers as higher concentrations may be associated with higher rates of ICH. The observed variation in protocols regarding heparin concentrations between EVT centers should encourage further studies, ideally in a controlled way, resulting in recommendations on heparin use in flush fluids in future guidelines.

Blood Pressure During Endovascular Treatment Under Conscious Sedation or Local Anesthesia.

OBJECTIVE: To evaluate the role of blood pressure (BP) as mediator of the effect of conscious sedation (CS) compared to local anesthesia (LA) on functional outcome after endovascular treatment (EVT). METHODS: Patients treated in the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN) Registry centers with CS or LA as preferred anesthetic approach during EVT for ischemic stroke were analyzed. First, we evaluated the effect of CS on area under the threshold (AUT), relative difference between baseline and lowest procedural mean arterial pressure (∆LMAP), and procedural BP trend, compared to LA. Second, we assessed the association between BP and functional outcome (modified Rankin Scale [mRS]) with multivariable regression. Lastly, we evaluated whether BP explained the effect of CS on mRS. RESULTS: In 440 patients with available BP data, patients treated under CS (n = 262) had larger AUTs (median 228 vs 23 mm Hg*min), larger ∆LMAP (median 16% vs 6%), and a more negative BP trend (-0.22 vs -0.08 mm Hg/min) compared to LA (n = 178). Larger ∆LMAP and AUTs were associated with worse mRS (adjusted common odds ratio [acOR] per 10% drop 0.87, 95% confidence interval [CI] 0.78-0.97, and acOR per 300 mm Hg*min 0.89, 95% CI 0.82-0.97). Patients treated under CS had worse mRS compared to LA (acOR 0.59, 95% CI 0.40-0.87) and this association remained when adjusting for ∆LMAP and AUT (acOR 0.62, 95% CI 0.42-0.92). CONCLUSIONS: Large BP drops are associated with worse functional outcome. However, BP drops do not explain the worse outcomes in the CS group.

Prior antiplatelet therapy in patients undergoing endovascular treatment for acute ischemic stroke: Results from the MR CLEAN Registry.

BACKGROUND: Antiplatelet therapy may increase the risk of symptomatic intracranial hemorrhage after endovascular treatment for ischemic stroke but may also have a beneficial effect on functional outcome. The aim of this study is to compare safety and efficacy outcomes after endovascular treatment in patients with and without prior antiplatelet therapy. METHODS: We analyzed patients registered in the MR CLEAN Registry between March 2014 and November 2017, for whom data on antiplatelet therapy were available. We used propensity score nearest-neighbor matching with replacement to balance the probability of receiving prior antiplatelet therapy between the prior antiplatelet therapy and no prior antiplatelet therapy group and adjusted for baseline prognostic factors to compare these groups. Primary outcome was symptomatic intracranial hemorrhage. Secondary outcomes were 90-day functional outcome (modified Rankin Scale), successful reperfusion (extended thrombolysis in cerebral infarction score ≥2B) and 90-day mortality. RESULTS: Thirty percent (n = 937) of the 3154 patients were on prior antiplatelet therapy, who were matched to 477 patients not on prior antiplatelet therapy. Symptomatic intracranial hemorrhage occurred in 74/937 (7.9%) patients on prior antiplatelet therapy and in 27/477 (5.6%) patients without prior antiplatelet therapy adjusted odds ratio 1.47, 95% confidence interval 0.86-2.49. No associations were found between prior antiplatelet therapy and functional outcome (adjusted common odds ratio 0.87, 95% confidence interval 0.65-1.16), successful reperfusion (adjusted odds ratio 1.23, 95% confidence interval 0.77-1.97), or 90-day mortality (adjusted odds ratio 1.15, 95% confidence interval 0.86-1.54). CONCLUSION: We found no evidence of an association of prior antiplatelet therapy with the risk of symptomatic intracranial hemorrhage after endovascular treatment, nor on functional outcome, reperfusion, or mortality. A substantial beneficial or detrimental effect of antiplatelet therapy on clinical outcome cannot be excluded. A randomized clinical trial comparing antiplatelet therapy versus no antiplatelet therapy is needed.

Endovascular treatment in older adults with acute ischemic stroke in the MR CLEAN Registry.

OBJECTIVE: To explore clinical outcomes in older adults with acute ischemic stroke treated with endovascular thrombectomy (EVT). METHODS: We included consecutive patients (2014-2016) with an anterior circulation occlusion undergoing EVT from the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN) Registry. We assessed the effect of age (dichotomized at ≥80 years and as continuous variable) on the modified Rankin Scale (mRS) score at 90 days, symptomatic intracranial hemorrhage (sICH), and reperfusion rate. The association between age and mRS was assessed with multivariable ordinal logistic regression, and a multiplicative interaction term was added to the model to assess modification of reperfusion by age on outcome. RESULTS: Of the 1,526 patients, 380 (25%) were ≥80 years of age (referred to here as older adults). Older adults had a worse functional outcome than younger patients (adjusted common odds ratio [acOR] for an mRS score shift toward better outcome 0.31, 95% confidence interval [CI] 0.24-0.39). Mortality was also higher in older adults (51% vs 22%, adjusted odds ratio 3.12, 95% CI 2.33-4.19). There were no differences in proportion of patients with mRS scores of 4 to 5, sICH, or reperfusion rates. Successful reperfusion was more strongly associated with a shift toward good functional outcome in older adults than in younger patients (acOR 3.22, 95% CI 2.04-5.10 vs 2.00, 95% CI 1.56-2.57, p interaction = 0.026). CONCLUSION: Older age is associated with an increased absolute risk of poor clinical outcome, while the relative benefit of successful reperfusion seems to be higher in these patients. These results should be taken into consideration in the selection of older adults for EVT.

Endovascular Treatment for Acute Ischemic Stroke in Patients on Oral Anticoagulants: Results From the MR CLEAN Registry.

Background and Purpose- The use of oral anticoagulants (OAC) is considered a contra-indication for intravenous thrombolytics as acute treatment of ischemic stroke. However, little is known about the risks and benefits of endovascular treatment in patients on prior OAC. We aim to compare outcomes after endovascular treatment between patients with and without prior use of OAC. Methods- Data of patients with acute ischemic stroke caused by an intracranial anterior circulation occlusion, included in the nationwide, prospective, MR CLEAN Registry between March 2014 and November 2017, were analyzed. Outcomes of interest included symptomatic intracranial hemorrhage and functional outcome at 90 days (modified Rankin Scale score). Outcomes between groups were compared with (ordinal) logistic regression analyses, adjusted for prognostic factors. Results- Three thousand one hundred sixty-two patients were included in this study, of whom 502 (16%) used OAC. There was no significant difference in the occurrence of symptomatic intracranial hemorrhage between patients with and without prior OACs (5% versus 6%; adjusted odds ratio, 0.63 [95% CI, 0.38-1.06]). Patients on OACs had worse functional outcomes than patients without OACs (common odds ratio, 0.57 [95% CI, 0.47-0.66]). However, this observed difference in functional outcome disappeared after adjustment for prognostic factors (adjusted common odds ratio, 0.91 [95% CI, 0.74-1.13]). Conclusions- Prior OAC use in patients treated with endovascular treatment for ischemic stroke is not associated with an increased risk of symptomatic intracranial hemorrhage or worse functional outcome compared with no prior OAC use. Therefore, prior OAC use should not be a contra-indication for endovascular treatment.

Periprocedural Intravenous Heparin During Endovascular Treatment for Ischemic Stroke: Results From the MR CLEAN Registry.

Background and Purpose- Intravenous administration of heparin during endovascular treatment for ischemic stroke may improve outcomes. However, risks and benefits of this adjunctive therapy remain uncertain. We aimed to evaluate periprocedural intravenous heparin use in Dutch stroke intervention centers and to assess its efficacy and safety. Methods- Patients registered between March 2014 and June 2016 in the MR CLEAN Registry (Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke), including all patients treated with endovascular treatment in the Netherlands, were analyzed. The primary outcome was functional outcome (modified Rankin Scale) at 90 days. Secondary outcomes were successful recanalization (extended Thrombolysis in Cerebral Infarction ≥2B), symptomatic intracranial hemorrhage, and mortality at 90 days. We used multilevel regression analysis to evaluate the association of periprocedural intravenous heparin on outcomes, adjusted for center effects and prognostic factors. To account for possible unobserved confounding by indication, we analyzed the effect of center preference to administer intravenous heparin, defined as percentage of patients treated with intravenous heparin in a center, on functional outcome. Results- One thousand four hundred eighty-eight patients from 16 centers were analyzed, of whom 398 (27%) received intravenous heparin (median dose 5000 international units). There was substantial between-center variability in the proportion of patients treated with intravenous heparin (range, 0%-94%). There was no significant difference in functional outcome between patients treated with intravenous heparin and those without (adjusted common odds ratio, 1.17; 95% CI, 0.87-1.56), successful recanalization (adjusted odds ratio, 1.24; 95% CI, 0.89-1.71), symptomatic intracranial hemorrhage (adjusted odds ratio, 1.13; 95% CI, 0.65-1.99), or mortality (adjusted odds ratio, 0.95; 95% CI, 0.66-1.38). Analysis at center level showed that functional outcomes were better in centers with higher percentages of heparin administration (adjusted common odds ratio, 1.07 per 10% more heparin, 95% CI, 1.01-1.13). Conclusions- Substantial between-center variability exists in periprocedural intravenous heparin use during endovascular treatment, but the treatment is safe. Centers using heparin more often had better outcomes. A randomized trial is needed to further study these effects.

Conscious sedation or local anesthesia during endovascular treatment for acute ischemic stroke.

OBJECTIVE: To investigate the effect of conscious sedation (CS) on functional outcome and complication rates after intra-arterial treatment (IAT) for acute ischemic stroke (AIS) compared to the use of local anesthesia (LA) at the puncture site only. METHODS: Patients undergoing IAT for AIS with CS or LA in the Erasmus University Medical Center from March 2014 to June 2016 were included for analysis. The primary outcome was the score on the ordinal modified Rankin Scale (mRS). We compared CS to LA by ordinal logistic regression with covariate adjustment using propensity scoring. RESULTS: In 146 AIS patients treated with IAT, use of CS was associated with a shift towards worse mRS scores (odds ratio [OR] 0.4 [95% confidence interval (CI) 0.2-0.7]) compared to LA. Mortality after 90 days was higher in the CS group compared to the LA group (OR 2.3 [95% CI 1.0-5.2]). No differences between groups were noted with regard to procedure duration (8 minutes, ß = 6.3 [95% CI -7.4 to 20.0]) or occurrence of procedure-related complications (OR 1.3 [95% CI 0.6-2.7]). CONCLUSION: CS was associated with poor functional outcome and increased mortality rates compared to LA. Furthermore, CS did not reduce duration of intervention or interventional complications. CS during IAT for AIS is of no benefit if LA is considered safe. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence, because of nonrandom allocation, that for patients with AIS undergoing IAT, LA rather than CS improves functional outcome.

Periprocedural Antithrombotic Treatment During Acute Mechanical Thrombectomy for Ischemic Stroke: A Systematic Review.

BACKGROUND: More than one-third of the patients with ischemic stroke caused by an intracranial large vessel occlusion do not recover to functional independence despite fast and successful recanalization by acute mechanical thrombectomy (MT). This may partially be explained by incomplete microvascular reperfusion. Some antithrombotics, e.g., antiplatelet agents and heparin, may be able to restore microvascular reperfusion. However, antithrombotics may also increase the risk of symptomatic intracranial hemorrhage (sICH). The aim of this review was to assess the potential safety and functional outcome of periprocedural antiplatelet or heparin use during acute MT for ischemic stroke. METHODS: We systematically searched PubMed, Embase, Medline, Web of Science, and Cochrane for studies investigating the safety and functional outcome of periprocedural antiplatelet or heparin treatment during acute MT for ischemic stroke. The primary outcome was the risk for sICH. Secondary outcomes were functional independence after 3-6 months (modified Rankin Scale 0-2) and mortality within 6 months. RESULTS: 837 studies were identified through the search, of which 19 studies were included. The sICH risks of the periprocedural use of antiplatelets ranged from 6 to 17%, and for heparin from 5 to 12%. Two of four studies reporting relative effects of the use of antithrombotics are pointing toward an increased risk of sICH. Among patients treated with antiplatelet agents, functional independence varied from 23 to 60% and mortality from 18 to 33%. For heparin, this was, respectively, 19-54% and 19-33%. The three studies presenting relative effects of antiplatelets on functional independence showed neutral effects. Both studies reporting relative effects of heparin on functional independence found it to increase this chance. CONCLUSION: Randomized controlled trials investigating the effect of periprocedural antithrombotic treatment in MT are lacking. Some observational studies report a slight increase in sICH risk, which may be acceptable because they also suggest a beneficial effect on functional outcome. Therefore, randomized controlled trials are warranted to address the question whether the potentially higher risk of sICH could be outweighed by improved functional outcome.

Risk factors for necrotizing enterocolitis in neonates: a systematic review of prognostic studies.

BACKGROUND: Necrotizing enterocolitis (NEC) is a severe multifactorial disease in preterm neonates associated with high morbidity and mortality. Better insight into prognostic values of the many reported factors associated with NEC is needed to enable identification of neonates at risk for NEC. The aim was to systematically review the literature to identify independent risk factors for NEC from the literature. METHODS: Medline, Cochrane, Embase, Pubmed and Google Scholar were searched systematically for cohort studies reporting prognostic factors for NEC in neonates using multivariable analysis. Studies were scored with the Quality In Prognosis Studies tool (QUIPS). RESULTS: From 5154 initial hits, 14 prognostic studies were included, with various designs. Study quality was rated high in three studies, moderate or low in the 11 others. Significant prognostic factors for NEC reported in at least two studies were: low birth weight, small for gestational age, low gestational age, assisted ventilation, premature rupture of membranes, black ethnicity, sepsis, outborn, hypotension (all increased risk), surfactant therapy (conflicting results) and cesarean section (lower risk). Meta-analysis was considered not feasible. CONCLUSION: High quality studies on prognostic factors for NEC are rare. Several prognostic factors, that are not necessarily causal, are associated with NEC. High quality prognostic research is necessary to establish the predictive values of these factors.

One-Year Follow-Up After Hybrid Thoracoabdominal Aortic Repair.

BACKGROUND: Compared to open thoracoabdominal aortic aneurysm (TAAA) repair, hybrid repair is thought to be less invasive with better perioperative outcomes. Due to the extent of the operation and long recovery period, studying perioperative results may not be sufficient for evaluation of the true treatment effect. The aim of this study is to evaluate 1-year mortality and morbidity in patients with TAAA undergoing hybrid repair. METHODS: In a retrospective cohort study, all medical records of patients undergoing hybrid repair for TAAA at the Erasmus University Medical Center between January 2007 and January 2015 were studied. Primary outcome measures were 30-day and 1-year mortality. Secondary outcome measures included major in-hospital postoperative complications. RESULTS: A total of 15 patients were included. All-cause mortality was 33% (5 of the 15) at 30 days and 60% (9 of the 15) at 1 year. Aneurysm-related mortality was 33% (5 of the 15) and 53% (8 of the 15) at 30-day and 1-year follow-up, respectively, with colon ischemia being the most common cause of death. Major complication rate was high: myocardial infarction in 2 (13%) cases, acute kidney failure in 5 (33%) cases, bowel ischemia in 3 (20%) cases, and spinal cord ischemia in 1 (7%) case. CONCLUSION: The presumed less invasive nature of hybrid TAAA repair does not seem to result in lower complication rates. The high mortality rate at 30 days continues to rise dramatically thereafter, suggesting that 1-year mortality is a more useful clinical parameter to use in preoperative decision-making for this kind of repair.