Effect of Occlusion Site on the Safety and Efficacy of Intravenous Alteplase Before Endovascular Thrombectomy: A Prespecified Subgroup Analysis of DIRECT-MT

Background and Purpose: Recent trials showed thrombectomy alone was comparable to bridging therapy in patients with anterior circulation large vessel occlusion eligible for both intravenous alteplase and endovascular thrombectomy. We performed this study to examine whether occlusion site modifies the effect of intravenous alteplase before thrombectomy. Methods: This is a prespecified subgroup analysis of a randomized trial evaluating risk and benefit of intravenous alteplase before thrombectomy (DIRECT-MT [Direct Intra-Arterial Thrombectomy in Order to Revascularize AIS Patients With Large Vessel Occlusion Efficiently in Chinese Tertiary Hospitals]). Among 658 randomized patients, 640 with baseline occlusion site information were included. The primary outcome was the score on the modified Rankin Scale at 90 days. Multivariable ordinal logistic regression analysis with an interaction term was used to estimate treatment effect modification by occlusion location (internal carotid artery versus M1 versus M2). We report the adjusted common odds ratio for a shift toward better outcome on the modified Rankin Scale after thrombectomy alone compared with combination treatment adjusted for age, the National Institutes of Health Stroke Scale score at baseline, the time from stroke onset to randomization, the modified Rankin Scale score before stroke onset, and collateral score per the DIRECT-MT statistical analysis plan. Results: The overall adjusted common odds ratio was 1.08 (95% CI, 0.82–1.43) with thrombectomy alone compared with combination treatment, and there was no significant treatment-by-occlusion site interaction ( P =0.47). In subgroups based on occlusion location, we found the following adjusted common odds ratios: 0.99 (95% CI, 0.62–1.59) for internal carotid artery occlusions, 1.12 (95% CI, 0.77–1.64) for M1 occlusions, and 1.22 (95% CI, 0.53–2.79) for M2 occlusions. No treatment-by-occlusion site interactions were observed for dichotomized modified Rankin Scale distributions and successful reperfusion (extended thrombolysis in Cerebral Infarction score ≥2b) before thrombectomy. Differences in symptomatic hemorrhage rate were not significant between occlusion locations (internal carotid artery occlusion: 7.02% in bridging therapy versus 7.14% for thrombectomy alone, P =0.97; M1 occlusion: 5.06% versus 2.48%, P =0.22; M2 occlusion: 9.09% versus 4.76%; P =0.78). Conclusions: In this prespecified subgroup of a randomized trial, we found no evidence that occlusion location can inform intravenous alteplase decisions in endovascular treatment eligible patients directly presenting at endovascular treatment capable centers. Future studies are needed to confirm our findings. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03469206.

Liver Transplantation for Hepatocellular Carcinoma after Downstaging or Bridging Therapy with Immune Checkpoint Inhibitors

Liver transplantation offers excellent outcomes for patients with HCC. For those who initially present within the Milan criteria, bridging therapy is essential to control disease while awaiting liver transplant. For those who present beyond the Milan criteria, a liver transplant may still be considered following successful downstaging. Since the introduction of atezolizumab as part of the first-line treatment for HCC in 2020, there has been increasing interest in the use of ICIs as bridging or downstaging therapies prior to liver transplant. A total of six case reports/series have been published on this topic, with mixed outcomes. Overall, liver transplantation can be performed safely following prolonged ICI use, though ICIs may increase the risk of fulminant acute rejection early in the post-operative period. A minimal washout period between the last dose of ICI and liver transplantation has been identified as an important factor predicting transplant outcomes; however, further research is needed.

A novel nomogram for predicting prognosis after mechanical thrombectomy in patients with acute ischemic stroke

Background: Mounting evidence has shown that mechanical thrombectomy [MT] improves clinical outcomes for large vessel occlusions [LVOs] in patients with acute ischemic stroke [AIS] of the anterior circulation. The present study aimed to provide a comprehensive analysis of risk factors associated with clinical outcomes in AIS patients receiving MT. Methods: A total of 212 consecutive patients who underwent MT for AIS were enrolled in the present study. Clinical characteristics were recorded at admission. Two endpoints were defined according to the 3-month modified Rankin scale [mRS] score after AIS [good outcome, mRS 0-2; and death, mRS 6]. Additionally, we compared the clinical outcomes and safety of MT alone and bridging therapy in AIS patients. Results: Of the 212 patients treated with MT, 114 [53.77%] patients had a good outcome and 31 [14.62%] died. The incidence of a worse outcome after MT was significantly elevated in males and patients with high WBC counts, high admission blood glucose levels, high baseline NIHSS scores and a long interval time from groin puncture to reperfusion in AIS patients treated with MT after adjustment for covariates [P<0.05]; these risk factors were further confirmed by our constructed nomograms. In addition, we observed no significant benefit of bridging therapy compared to MT alone in AIS patients. Conclusion: Our constructed nomogram based on male sex, admission WBC, admission blood glucose, NIHSS, and the interval time from groin puncture to reperfusion predicts prognosis after mechanical thrombectomy in patients with acute ischemic stroke.

Utilization of apixaban anti-Xa levels in transition from apixaban to warfarin in a patient with chronic renal dysfunction

Disclaimer In an effort to expedite the publication of articles related to the COVID-19 pandemic, AJHP is posting these manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Purpose The effect of apixaban on anti–factor Xa (anti-Xa) assays and international normalized ratio (INR) complicates transitions between anticoagulant agents. When switching from apixaban to warfarin, the recommendation is to begin both a parenteral anticoagulant and warfarin at the time of the next apixaban dose and to discontinue the parenteral agent when INR is in an acceptable range. This proves challenging in renal dysfunction, as continued presence of apixaban contributes to both a prolonged effect on the INR and continued therapeutic levels of anticoagulation. Summary This case describes the transition of apixaban to warfarin in a patient with acute on chronic kidney disease and recent deep vein thrombosis, utilizing chromogenic apixaban anti-Xa assays to assess the level of anticoagulation and avoid unnecessary parenteral anticoagulation. Conclusion Utilization of apixaban anti-Xa levels aided in the transition from apixaban to warfarin in a patient with chronic renal failure and avoided need for parenteral bridging therapy.

Long- and short-term clinical impact of awake extracorporeal membrane oxygenation as bridging therapy for lung transplantation

Background As lung transplantation (LTx) is becoming a standard treatment for end-stage lung disease, the use of bridging with extracorporeal membrane oxygenation (ECMO) is increasing. We examined the clinical impact of being awake during ECMO as bridging therapy in patients awaiting LTx. Methods In this single-center study, we retrospectively reviewed 241 consecutive LTx patients between October 2012 and March 2019; 64 patients received ECMO support while awaiting LTx. We divided into awake and non-awake groups and compared. Results Twenty-five patients (39.1%) were awake, and 39 (61.0%) were non-awake. The median age of awake patients was 59.0 (interquartile range, 52.5–63.0) years, and 80% of the group was men. The awake group had better post-operative outcomes than the non-awake group: statistically shorter post-operative intensive care unit length of stay [awake vs. non-awake, 6 (4–8.5) vs. 18 (11–36), p < 0.001], longer ventilator free days [awake vs. non-awake, 24 (17–26) vs. 0 (0–15), p < 0.001], and higher gait ability after LTx (awake vs. non-awake, 92% vs. 59%, p = 0.004), leading to higher 6-month and 1-year lung function (forced expiratory volume in 1 s: awake vs. non-awake, 6-month, 77.5% vs. 61%, p = 0.004, 1-year, 75% vs. 57%, p = 0.013). Furthermore, the awake group had significantly lower 6-month and 1-year mortality rates than the non-awake group (6-month 12% vs. 38.5%, p = 0.022, 1-year 24% vs. 53.8%, p = 0.018). Conclusions In patients with end-stage lung disease, considering the long-term and short-term impacts, the awake ECMO strategy could be useful compared with the non-awake ECMO strategy.

Bridging thrombolysis in atrial fibrillation stroke is associated with increased hemorrhagic complications without improved outcomes

BackgroundAtrial fibrillation (AF) associated ischemic stroke is associated with worse functional outcomes, less effective recanalization, and increased rates of hemorrhagic complications after intravenous thrombolysis (IVT). Conversely, AF is not associated with hemorrhagic complications or functional outcomes in patients undergoing mechanical thrombectomy (MT). This differential effect of MT and IVT in AF associated stroke raises the question of whether bridging thrombolysis increases hemorrhagic complications in AF patients undergoing MT.MethodsThis international cohort study of 22 comprehensive stroke centers analyzed patients with large vessel occlusion (LVO) undergoing MT between June 1, 2015 and December 31, 2020. Patients were divided into four groups based on comorbid AF and IVT exposure. Baseline patient characteristics, complications, and outcomes were reported and compared.Results6461 patients underwent MT for LVO. 2311 (35.8%) patients had comorbid AF. In non-AF patients, bridging therapy improved the odds of good 90 day functional outcomes (adjusted OR (aOR) 1.29, 95% CI 1.03 to 1.60, p=0.025) and did not increase hemorrhagic complications. In AF patients, bridging therapy led to significant increases in symptomatic intracranial hemorrhage and parenchymal hematoma type 2 (aOR 1.66, 1.07 to 2.57, p=0.024) without any benefit in 90 day functional outcomes. Similar findings were noted in a separate propensity score analysis.ConclusionIn this large thrombectomy registry, AF patients exposed to IVT before MT had increased hemorrhagic complications without improved functional outcomes, in contrast with non-AF patients. Prospective trials are warranted to assess whether AF patients represent a subgroup of LVO patients who may benefit from a direct to thrombectomy approach at thrombectomy capable centers.