The best management of patients with persistent distal occlusion after mechanical thrombectomy with or without IV thrombolysis remains unknown. We sought to evaluate the variability and agreement in decision-making for persistent distal occlusions.
MATERIALS AND METHODS:
A portfolio of 60 cases was sent to clinicians with varying backgrounds and experience. Responders were asked whether they considered conservative management or rescue therapy (stent retriever, aspiration, or intra-arterial thrombolytics) a treatment option as well as their willingness to enroll patients in a randomized trial. Agreement was assessed using κ statistics.
RESULTS:
The electronic survey was answered by 31 physicians (8 vascular neurologists and 23 interventional neuroradiologists). Decisions for rescue therapies were more frequent (n = 1116/1860, 60%) than for conservative management (n = 744/1860, 40%; P < .001). Interrater agreement regarding the final management decision was "slight" (κ = 0.12; 95% CI, 0.09–0.14) and did not improve when subgroups of clinicians were studied according to background, experience, and specialty or when cases were grouped according to the level of occlusion. On delayed re-questioning, 23 of 29 respondents (79.3%) disagreed with themselves on at least 20% of cases. Respondents were willing to offer trial participation in 1295 of 1860 (69.6%) cases.
CONCLUSIONS:
Individuals did not agree regarding the best management of patients with persistent distal occlusion after mechanical thrombectomy and IV thrombolysis. There is sufficient uncertainty to justify a dedicated randomized trial.
With the advent of new cellular and targeted therapies, treatment options for relapsed and refractory (r/R) lymphomas have multiplied, and the optimal approach offering the best outcomes remains a matter of passionate debate. High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is still considered a treatment option for patients with chemosensitive lymphoma when cure is the expected goal. The myeloablative conditioning regimen preceding the stem cell infusion is considered the effective component of this approach. Carmustine (BCNU)-based preparative regimens, such as BEAM and BEAC, are considered the standard of care and have shown efficacy and low nonrelapse mortality (NRM). Comparative studies between conditioning regimens have failed to identify a better option. After a BCNU drug shortage in Canada followed by a steep increase in price, we elected to substitute BCNU for bendamustine (benda) in the preparative regimen. The purpose of this substitution was to improve response while preserving safety and controlling costs. From May 2015 to May 2018, a total of 131 consecutive lymphoma patients received benda-EAM conditioning. These patients were compared with 96 consecutive patients who received BCNU-based conditioning from January 2012 to May 2015. Apart from conditioning, supportive care measures were the same in the 2 groups. Patients receiving benda were older (55.7 years versus 51.1 years; P = .002). The development of grade ≥3 mucositis was more frequent with benda conditioning (39.5% versus 7.8%; P < .001) leading to a greater requirement for parenteral nutrition (48.9% versus 21.9%; P < .001). A transient creatinine increase >1.5 times the upper limit of normal (15.3% versus 4.2%; P < .008) and intensive care unit admission (6.9% versus 1.1%; P < .029) were more frequent with benda; however, there were no between-group differences in cardiac, pulmonary, or liver toxicity and NRM. With a median follow-up of 48 months for the benda group and 60 months for the BCNU group, benda was associated with significantly better progression-free survival (71% versus 61%; P = .040; hazard ratio [HR], 1.6; 95% confidence interval [CI], 1.0 to 2.7) and overall survival (86% vs 71%; P = .0066; HR, 2.6; 95% CI, 1.3 to 5.4) compared with BCNU-based conditioning regimens. While novel therapies emerge, our study demonstrates that benda-EAM is safe and effective and should be considered a valid alternative to BCNU conditioning to improve outcomes of patients with chemosensitive r/R lymphomas undergoing ASCT.
Purpose: Prior studies have described complications of radiofrequency ablation (RFA) of liver tumours. The aim of this study was to identify risk factors for hospitalization duration longer than 24 hours following RFA of liver tumours. Methods: This retrospective, single-centre study included patients with liver tumours undergoing RFA between October 2017 and July 2020. Medical records were reviewed to collect patient, tumours, and procedure characteristics for each RFA session. The association between potential risk factors and duration of hospitalization (less than or more than 24 hours) was analyzed using univariate and multivariate logistic regressions. Results: Our study included 291 patients (mean age: 65.2 ± 11.2 [standard deviation]; 201 men) undergoing 324 RFA sessions. Sixty-eight sessions (21.0%) resulted in hospitalization of more than 24 hours. Multivariate analysis identified each additional needle insertion per session (OR 1.4; 95% CI [1.1-1.9]; P = .02), RFA performed in segment V (OR 2.8; 95% CI [1.4-5.7]; P = .004), and use of artificial pneumothorax (OR 14.5; 95% CI [1.4-146.0]; P = .02) as potential risk factors. A history of hepatic encephalopathy (OR 2.6; 95% CI [1.1-6.0]; P = .03) was only significant in univariate analysis. Post-hoc, subgroup analysis of patients with hepatocellular carcinoma (69.8%) did not identify other risk factors. Conclusion: Risk factors for a hospitalization duration longer than 24 hours include a higher number of needle insertions per session, radiofrequency ablation in segment V, and use of an artificial pneumothorax.
BACKGROUND AND PURPOSE: Flow diversion is a recent endovascular treatment for intracranial aneurysms. We compared the safety and efficacy of flow diversion with the alternative standard management options. MATERIALS AND METHODS: A parallel group, prerandomized, controlled, open-label pragmatic trial was conducted in 3 Canadian centers. The trial included all patients considered for flow diversion. A Web-based platform 1:1 randomly allocated patients to flow diversion or 1 of 4 alternative standard management options (coiling with/without stent placement, parent vessel occlusion, surgical clipping, or observation) as prespecified by clinical judgment. Patients ineligible for alternative standard management options were treated with flow diversion in a registry. The primary safety outcome was death or dependency (mRS > 2) at 3 months. The composite primary efficacy outcome included the core lab–determined angiographic presence of a residual aneurysm, aneurysm rupture, progressive mass effect during follow-up, or death or dependency (mRS > 2) at 3–12 months. RESULTS: Between May 2011 and November 2020, three hundred twenty-three patients were recruited: Two hundred seventy-eight patients (86%) had treatment randomly allocated (139 to flow diversion and 139 to alternative standard management options), and 45 (14%) received flow diversion in the registry. Patients in the randomized trial frequently had unruptured (83%), large (52% ≥10 mm) carotid (64%) aneurysms. Death or dependency at 3 months occurred in 16/138 patients who underwent flow diversion and 12/137 patients receiving alternative standard management options (relative risk, 1.33; 95% CI, 0.65–2.69; P = .439). A poor primary efficacy outcome was found in 30.9% (43/139) with flow diversion and 45.6% (62/136) of patients receiving alternative standard management options, with an absolute risk difference of 14.7% (95% CI, 3.3%–26.0%; relative risk, 0.68; 95% CI, 0.50–0.92; P = .014). CONCLUSIONS: For patients with mostly unruptured, large, anterior circulation (carotid) aneurysms, flow diversion was more effective than the alternative standard management option in terms of angiographic outcome. ASMO : alternative standard management option DSMC : Data Safety and Monitoring Committee FD : flow diversion FIAT : Flow Diversion in Intracranial Aneurysm Treatment PVO : parent vessel occlusion RCT : randomized controlled trial
Surgical clipping and endovascular treatment are commonly used in patients with unruptured intracranial aneurysms. We compared the safety and efficacy of the 2 treatments in a randomized trial.
MATERIALS AND METHODS:
Clipping or endovascular treatments were randomly allocated to patients with one or more 3- to 25-mm unruptured intracranial aneurysms judged treatable both ways by participating physicians. The study hypothesized that clipping would decrease the incidence of treatment failure from 13% to 4%, a composite primary outcome defined as failure of aneurysm occlusion, intracranial hemorrhage during follow-up, or residual aneurysms at 1 year, as adjudicated by a core lab. Safety outcomes included new neurologic deficits following treatment, hospitalization of >5 days, and overall morbidity and mortality (mRS > 2) at 1 year. There was no blinding.
RESULTS:
Two hundred ninety-one patients were enrolled from 2010 to 2020 in 7 centers. The 1-year primary outcome, ascertainable in 290/291 (99%) patients, was reached in 13/142 (9%; 95% CI, 5%–15%) patients allocated to surgery and in 28/148 (19%; 95% CI, 13%–26%) patients allocated to endovascular treatments (relative risk: 2.07; 95% CI, 1.12–3.83; P = .021). Morbidity and mortality (mRS >2) at 1 year occurred in 3/143 and 3/148 (2%; 95% CI, 1%–6%) patients allocated to surgery and endovascular treatments, respectively. Neurologic deficits (32/143, 22%; 95% CI, 16%–30% versus 19/148, 12%; 95% CI, 8%–19%; relative risk: 1.74; 95% CI, 1.04–2.92; P = .04) and hospitalizations beyond 5 days (69/143, 48%; 95% CI, 40%–56% versus 12/148, 8%; 95% CI, 5%–14%; relative risk: 0.18; 95% CI, 0.11–0.31; P < .001) were more frequent after surgery.
CONCLUSIONS:
Surgical clipping is more effective than endovascular treatment of unruptured intracranial aneurysms in terms of the frequency of the primary outcome of treatment failure. Results were mainly driven by angiographic results at 1 year.
Conventional angiography is the benchmark examination to diagnose cerebral vasospasm, but there is limited evidence regarding its reliability. Our goals were the following: 1) to systematically review the literature on the reliability of the diagnosis of cerebral vasospasm using conventional angiography, and 2) to perform an agreement study among clinicians who perform endovascular treatment.
MATERIALS AND METHODS:
Articles reporting a classification system on the degree of cerebral vasospasm on conventional angiography were systematically searched, and agreement studies were identified. We assembled a portfolio of 221 cases of patients with subarachnoid hemorrhage and asked 17 raters with different backgrounds (radiology, neurosurgery, or neurology) and experience (junior ≤10 and senior >10 years) to independently evaluate cerebral vasospasm in 7 vessel segments using a 3-point scale and to evaluate, for each case, whether findings would justify endovascular treatment. Nine raters took part in the intraobserver reliability study.
RESULTS:
The systematic review showed a very heterogeneous literature, with 140 studies using 60 different nomenclatures and 21 different thresholds to define cerebral vasospasm, and 5 interobserver studies reporting a wide range of reliability (κ = 0.14–0.87). In our study, only senior raters reached substantial agreement (κ ≥ 0.6) on vasospasm of the supraclinoid ICA, M1, and basilar segments and only when assessments were dichotomized (presence or absence of ≥50% narrowing). Agreement on whether to proceed with endovascular management of vasospasm was only fair (κ ≤ 0.4).
CONCLUSIONS:
Research on cerebral vasospasm would benefit from standardization of definitions and thresholds. Dichotomized decisions by experienced readers are required for the reliable angiographic diagnosis of cerebral vasospasm.
Background: Flow diversion (FD) is a recent endovascular treatment for intracranial aneurysms. We undertook a pragmatic randomized trial to compare the safety and efficacy of FD with alternative standard management options (ASMO). Methods: A parallel group pre-randomised controlled open label trial was conducted in 3 Canadian centers. The trial included all patients considered for FD. A web-based platform 1:1 randomly allocated FD or one of 4 ASMOs (coiling with/without stenting, parent vessel occlusion, surgical clipping, or observation) pre-specified by clinical judgement. Patients ineligible for ASMO were treated within a registry. The primary safety outcome was death or dependency (mRS > 2) at 3 months. The primary efficacy outcome was a composite including core-lab determined angiographic occlusion/near-occlusion at 3–12 months and an independent clinical outcome (mRS < 3). Findings: Between May 2011 and November 2020, 323 patients were recruited: 278 patients (86%) had treatment randomly allocated (139 FD and 139 ASMO), and 45 (14%) received FD in the registry. Patients in the randomized trial frequently had unruptured (83%) large (52% ≥10mm) carotid (64%) aneurysms. Death or dependency at 3 months occurred in 16/139 FD patients and 12/139 ASMO patients (OR: 1·4; 95%CI[0·6-3·0]; P=0·44). A good primary efficacy outcome was found in 96 FD and 74 ASMO patients (OR: 0·5; 95%CI[0·3-0·9]; P=0·013). Interpretation: FD was more effective than ASMO, particularly for unruptured, large, carotid aneurysms. Medical devices can be assessed using pragmatic trials. More randomized data is needed to determine the role of FD for other intracranial aneurysms.Trial Registration Details: Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01349582 Funding Information: There was no funding for this study. Declaration of Interests: Authors declare no competing interests.Ethics Approval Statement: All sites received Institutional Review Board approval. All patients or designates signed an informed consent form.
Stent-assisted coiling may improve angiographic results of endovascular treatment of unruptured intracranial aneurysms compared with coiling alone, but this has never been shown in a randomized trial.
MATERIALS AND METHODS:
The Stenting in the Treatment of Aneurysm Trial was an investigator-led, parallel, randomized (1:1) trial conducted in 4 university hospitals. Patients with intracranial aneurysms at risk of recurrence, defined as large aneurysms (≥10 mm), postcoiling recurrent aneurysms, or small aneurysms with a wide neck (≥4 mm), were randomly allocated to stent-assisted coiling or coiling alone. The composite primary efficacy outcome was "treatment failure," defined as initial failure to treat the aneurysm; aneurysm rupture or retreatment during follow-up; death or dependency (mRS > 2); or an angiographic residual aneurysm adjudicated by an independent core laboratory at 12 months. The primary hypothesis (revised for slow accrual) was that stent-assisted coiling would decrease treatment failures from 33% to 15%, requiring 200 patients. Primary analyses were intent to treat.
RESULTS:
Of 205 patients recruited between 2011 and 2021, ninety-four were allocated to stent-assisted coiling and 111 to coiling alone. The primary outcome, ascertainable in 203 patients, was reached in 28/93 patients allocated to stent-assisted coiling (30.1%; 95% CI, 21.2%–40.6%) compared with 30/110 (27.3%; 95% CI, 19.4%–36.7%) allocated to coiling alone (relative risk = 1.10; 95% CI, 0.7–1.7; P = .66). Poor clinical outcomes (mRS >2) occurred in 8/94 patients allocated to stent-assisted coiling (8.5%; 95% CI, 4.0%–16.6%) compared with 6/111 (5.4%; 95% CI, 2.2%–11.9%) allocated to coiling alone (relative risk = 1.6; 95% CI, 0.6%–4.4%; P = .38).
CONCLUSIONS:
The STAT trial did not show stent-assisted coiling to be superior to coiling alone for wide-neck, large, or recurrent unruptured aneurysms.
After aneurysmal SAH, transcranial Doppler is commonly used to monitor cerebral vasospasm. The diagnostic accuracy of transcranial Doppler flow velocity values in detecting angiographic vasospasm in patients requiring urgent endovascular intervention has not been established.We performed a retrospective analysis of a consecutive series of patients with aneurysmal SAH who underwent transcranial Doppler (index test) within 24 hours of conventional angiography (reference test). The judgment of 33%, 50%, and 66% degree of vessel narrowing on angiography was independently established by multiple neuroendovascular clinicians. Vessel-specific per-segment and per-patient transcranial Doppler velocities were studied using receiver operating characteristic curves, the Youden index, and minimal acceptable sensitivity models. Optimal mean flow-velocity thresholds were explored to calculate sensitivity and specificity using a per-patient judgment of vasospasm of at least 50% angiographic narrowing in any large arterial segment except A1.In 221 patients, vasospasm was found in 15%, 8%, and 4% of arteries when the degree of reference angiographic luminal narrowing was 33%, 50%, and 66%, respectively. Mean flow velocities were significantly higher in vasospastic segments (P = . 001), but per-segment exploratory analyses yielded unsound mean flow velocity thresholds. The Youden and minimal acceptable sensitivity models proposed mean flow velocity thresholds of approximately 160 cm/s for the anterior circulation and 80 cm/s for the posterior circulation in the per-patient diagnosis of angiographic vasospasm (≥50%), yielding a sensitivity of 80%-90% (95% CI, 0.77-0.96), but with a corresponding specificity of 50% (95% CI, 0.40-0.56).In this study, a threshold transcranial Doppler mean flow-velocity value that would accurately diagnose ≥50% angiographic vasospasm remained elusive.
