Journals
2019 EN
Osama O. Zaidat · Diogo C Haussen · Ameer E Hassan
+5 more
Background and Purpose- The safety and efficacy of mechanical thrombectomy in patients with acute ischemic stroke has been demonstrated. However, the impact of stent retriever size on clinical and angiographic outcomes is not well established. Methods- This was a retrospective ad hoc analysis of data from the STRATIS (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke) registry-a prospective, multicenter study of patients with large vessel occlusion treated with the Solitaire stent retriever. An independent core laboratory, blinded to clinical outcomes, reviewed all procedures and angiographic data to classify stent retriever size, targeted clot location, recanalization after each pass, and the number of stent retriever passes. The primary angiographic end point was first-pass effect (FPE) as determined by a core laboratory and defined as achieving near-complete revascularization (modified Thrombolysis in Cerebral Infarction ≥2c) after the first pass without the use of rescue therapy. Rates of modified FPE were also assessed, defined as meeting all criteria for FPE but achieving modified Thrombolysis in Cerebral Infarction ≥2b after first pass. The primary clinical end point was functional independence (modified Rankin Scale, 0-2) at 3 months as determined on-site. Outcome comparisons were made across the stent retriever size groups and adjusted for baseline characteristics. Results- Of 715 patients, a 4×20 stent retriever was used in 201 (28%) patients, 4×40 was used in 270 (38%) patients, and 6×30 was used in 244 (34%) patients. The 4×40 group had the highest rate of FPE ( P=0.003 versus 6×30) and modified FPE ( P=0.038 versus 4×20; P=0.0001 versus 6×30). Final revascularization was not significantly different across the groups, and there were no significant differences in functional dependence or mortality at 90 days post-procedure. Use of the longer stent retriever (4×40) was an independent predictor of achieving modified FPE ( P=0.037 versus 6×30; P=0.037 versus 4×20). Conclusions- The longer stent retriever (4×40) demonstrated the highest rate FPE and modified FPE compared with larger diameter or shorter stent retrievers, suggesting that their routine use may improve early revascularization success. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT02239640.
Lippincott Williams & Wilkins
Journals
2019 EN
Michael J. Alexander · Alois Zauner · John C. Chaloupka
+24 more
Background and Purpose- The WEAVE trial (Wingspan Stent System Post Market Surveillance) is a postmarket surveillance trial mandated by the Food and Drug Administration to assess the periprocedural safety of the Wingspan Stent system in the treatment of symptomatic intracranial atherosclerotic disease. Methods- A total of 152 consecutive patients who met the Food and Drug Administration on-label usage criteria were enrolled at 24 hospitals and underwent angioplasty and stenting with the Wingspan stent. On-label criteria included age 22 to 80 years, symptomatic intracranial atherosclerotic stenosis of 70% to 99%, baseline modified Rankin Scale score ≤3, ≥2 strokes in the vascular territory of the stenotic lesion with at least 1 stroke while on medical therapy, and stenting of the lesion ≥8 days after the last stroke. The primary analysis assessed the periprocedural stroke, bleed, and death rate within 72 hours of the procedure with adjudication by a core study Stroke Neurologist. Results- The trial was stopped early after interim analysis of 152 consecutive patients demonstrated a lower than expected 2.6% (4/152 patients) periprocedural stroke, bleed, and death rate. This was lower than the 4% periprocedural primary event safety benchmark set for the interim analysis in the study. A total of 97.4% (148/152) patients were event-free at 72 hours, 1.3% (2/152) had nonfatal strokes, and 1.3% (2/152) of patients died. Conclusions- With experienced interventionalists, and proper patient selection following the on-label usage guidelines, the use of the Wingspan stent for intracranial atherosclerotic disease demonstrated a low periprocedural complication rate and excellent safety profile. This is the largest on-label, multicenter, prospective trial of the Wingspan stent system to date with the lowest reported complication rate. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT02034058.
Lippincott Williams & Wilkins
Journals
2019 EN
Parita Bhuva · Albert J. Yoo · Ashutosh P. Jadhav
+17 more
Background and Purpose— It is unknown whether noncontrast computed tomography (NCCT) can identify patients who will benefit from intra-arterial treatment (IAT) in the extended time window. We sought to characterize baseline Alberta Stroke Program Early CT Score (ASPECTS) in DAWN (DWI or CTP Assessment With Clinical Mismatch in the Triage of Wake-Up and Late Presenting Strokes Undergoing Neurointervention With Trevo) and to assess whether ASPECTS modified IAT effect. Methods— Core lab adjudicated ASPECTS scores were analyzed. The trial cohort was divided into 2 groups by qualifying imaging (computed tomography versus magnetic resonance imaging). ASPECTS-by-treatment interaction was tested for the trial coprimary end points (90-day utility-weighted modified Rankin Scale (mRS) score and mRS, 0–2), mRS 0 to 3, and ordinal mRS. ASPECTS was evaluated separately as an ordinal and a dichotomized (0–6 versus 7–10) variable. Results— Of 205 DAWN subjects, 123 (60%) had NCCT ASPECTS, and 82 (40%) had diffusion weighted imaging ASPECTS. There was a significant ordinal NCCT ASPECTS-by-treatment interaction for 90-day utility-weighted mRS (interactionP =0.04) and mRS 0 to 2 (interactionP =0.02). For both end points, IAT effect was more pronounced at higher NCCT ASPECTS. The dichotomized NCCT ASPECTS-by-treatment interaction was significant only for mRS 0 to 2 (interactionP =0.04), where greater treatment benefit was seen in the ASPECTS 7 to 10 group (odds ratio, 7.50 [2.71–20.77] versus odds ratio, 0.48 [0.04–5.40]). A bidirectional treatment effect was observed in the NCCT ASPECTS 0 to 6 group, with treatment associated with not only more mRS 0 to 3 outcomes (50% versus 25%) but also more mRS 5 to 6 outcomes (40% versus 25%). There was no significant modification of IAT effect by diffusion weighted imaging ASPECTS.Conclusions— Baseline NCCT ASPECTS appears to modify IAT effect in DAWN. Higher NCCT ASPECTS was associated with greater benefit from IAT. No treatment interaction was observed for diffusion weighted imaging ASPECTS.
Lippincott Williams & Wilkins
Journals
2019 EN
Amin Aghaebrahim · Ashutosh P. Jadhav · Ricardó A. Hanel
+17 more
Background and Purpose- The impact of transfer status on clinical outcomes in the DAWN (DWI or CTP Assessment With Clinical Mismatch in the Triage of Wake-Up and Late Presenting Strokes Undergoing Neurointervention With Trevo) population is unknown. We analyzed workflow and clinical outcome differences between direct versus transfer patients in the DAWN population. Methods- The following time metrics were analyzed for each group: (1) last known well to hospital arrival, (2) hospital arrival to eligibility imaging, (3) hospital arrival to arterial puncture, (4) qualifying imaging to arterial puncture, (5) last known well to arterial puncture, (6) last known well to reperfusion. The primary end point was the rate of functional independence (90-day modified Rankin Scale [mRS] score, 0-2). Using univariate unconditional logistic regression, we calculated odds ratios and 95% CIs for the association between clinically relevant time metrics, transfer status, and functional independence (mRS 0-2). Results- A total of 206 patients were enrolled. Among these, 121 (59%) patients were transferred, and 85 (41%) patients presented directly to a thrombectomy capable center. Median time last seen well to hospital arrival time was similar between the 2 groups (678 versus 696 minutes). The time from hospital arrival to groin puncture was significantly longer in direct patients compared with transferred patients 140 minutes (interquartile range, 105.5-177.5 minutes) and 88 minutes (interquartile range, 55-125 minutes), respectively (P<0.001). Differences in treatment effect or differences in rates of mRS 0-2 in the thrombectomy treated patients were not statistically significant in direct versus transfer patients (odds ratios for mRS 0-2, thrombectomy versus control, were 5.62 in direct and 6.63 in transfer patients, respectively, Breslow-Day P=0.817). Conclusions- Although transfer patients had a faster door to puncture time, benefits of thrombectomy, and rates of mRS 0 to 2 in the treatment group were similar between direct and transferred patients in the DAWN population. These results may inform prehospital and primary stroke centers triage protocols in patients presenting in the late time window. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT02142283.
Lippincott Williams & Wilkins
Journals
2019 EN
Ashutosh P. Jadhav · Amin Aghaebrahim · Brian T. Jankowitz
+16 more
Background and Purpose— It is unknown whether the benefit of thrombectomy in late presenting acute stroke patients with imaging evidence of clinical-infarct mismatch is different in patients presenting with wake-up stroke compared with those presenting with witnessed onset or unwitnessed onset. Methods— Prespecified secondary analysis was performed from DAWN (Diffusion Weighted Imaging [DWI] or Computerized Tomography Perfusion [CTP] Assessment With Clinical Mismatch in the Triage of Wake Up and Late Presenting Strokes Undergoing Neurointervention), a multicenter, prospective, randomized clinical trial with blinded end point assessment comparing thrombectomy with the Trevo device against standard medical therapy in patients with acute stroke and clinical-infarct mismatch presenting 6 to 24 hour after the time last seen well. For the purposes of this study, the primary outcome was the proportion of modified Rankin Scale score 0 to 2 at 90 days. Univariable analysis and multivariable logistic regression was used to assess the relationship between outcome and mode of onset. Results— All 206 enrolled patients were included in the study. Mode of onset was: wake-up stroke (55.3%, n=114), witnessed onset (12.1%, n=25), and unwitnessed onset (32.5%, n=67) with median time last seen well to randomization (13.4±3.7, 10.0±3.7, 14.1±4.9 hours) respectively. Rates of 90-day modified Rankin Scale score of 0 to 2 and symptomatic intracerebral hemorrhage in the thrombectomy arm were not statistically different across patient onset subtypes (P =0.79 andP =0.40, respectively). The benefit of thrombectomy compared with best medical therapy was maintained across all 3 onset modes (rates of 90-day modified Rankin Scale score of 0 to 2 in patients allocated to thrombectomy versus control: wake-up stroke—49.3% versus 10.6%, witnessed onset—63.6% versus 21.4%, UW—41.4% versus 13.2%;P ×interaction=0.79). In univariable and multivariable analyses, mode of onset was not identified as a significant predictor of modified Rankin Scale score 0 to 2 at 90 days.Conclusions— In patients with acute ischemic stroke presenting between 6 and 24 hours from time last seen well and harboring clinical-infarct mismatch, the benefit of thrombectomy was similar regardless of the wake-up, unwitnessed, or witnessed mode of onset.
Lippincott Williams & Wilkins
Journals
2019 EN
Wondwossen Tekle · Ameer E Hassan · Ashutosh P. Jadhav
+15 more
Background and Purpose- Because of unique attributes of mechanical thrombectomy performed between 6 and 24 hours after symptom onset in acute ischemic stroke patients, it is not known if predictors of angiographic recanalization and favorable outcome in patients treated with thrombectomy in the late (6-24 hour) time window are similar to those treated in the early time window. Methods- We analyzed data from the DAWN trial (DWI or CTP Assessment With Clinical Mismatch in the Triage of Wake-Up and Late Presenting Strokes Undergoing Neurointervention With Trevo) which enrolled patients with symptom onset 6 to 24hours after last known well and occlusion of the intracranial internal carotid artery or proximal middle cerebral artery with a mismatch between severity of clinical deficit and infarct core volume as identified by computed tomography-perfusion or diffusion magnetic resonance imaging. We evaluated the effect of tandem occlusions, periprocedural heparin use, procedural speed (from puncture to procedure completion), general anesthesia, balloon-guide catheters, thrombectomy device size, and number of passes on substantial reperfusion (modified Thrombolysis in Cerebral Infarction 2b/3) and on likelihood of obtaining a modified Rankin Scale at 3 months indicating functional independence. Results- Of 107 patients who underwent MT in the interventional arm of DAWN, substantial reperfusion and modified Rankin Scale score 0 to 2 at 3 months was seen in 90 (84%) and 52 (49%), respectively. In univariate analysis, general anesthesia (odds ratio [OR] 0.27; P =0.042) and ≥3 passes with stent retriever (OR, 0.17; P =0.002) were inversely associated with substantial reperfusion. In multivariate analyses, only ≥3 passes were associated with lack of revascularization (OR, 0.17; P =0.002). in univariate analysis ≥3 passes (OR, 0.24; P =0.003) and baseline National Institutes of Health Stroke Scale score >17 (OR, 0.19; P <0.001) were inversely associated with functional independence at 3 months. In multivariate analyses, ≥3 passes (OR, 0.24; P =0.003) and National Institutes of Health Stroke Scale score >17 (OR, 0.19; P <0.001) remained inversely associated with favorable outcome at 3 months. Conclusions- Patients requiring ≥3 thrombectomy passes had reduced substantial reperfusion and favorable outcome at 3 months in DAWN. Whether or not additional thrombectomy techniques beyond ≥3 thrombectomy passes with the Trevo stent retriever are beneficial for patient outcomes in this patient population remains to be clarified by future studies. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT02142283.
Lippincott Williams & Wilkins
Journals
2019 EN
Ameer M. Elbuluk · Francesca R. Coxe · Peter D. Fabricant
+3 more
Background: Double-row transosseous-equivalent (TOE) rotator cuff repair techniques have been widely accepted because of their superior biomechanical properties when compared with arthroscopic single-row repair. Concerns regarding repair overtensioning with medial-row knot tying have led to increased interest in knotless repair techniques; however, there is a paucity of clinical data to guide the choice of technique. Hypothesis: Arthroscopic TOE repair techniques using knotless medial-row fixation will demonstrate lower retear rates and greater improvements in the Constant score relative to conventional knot-tying TOE techniques. Study Design: Systematic review; Level of evidence, 4. Methods: A systematic review of 3 databases (PubMed, Cochrane, and Embase) was performed using PRISMA (Preferred Reporting Items for Systematic Meta-Analyses) guidelines. Inclusion criteria were English-language studies that examined repair integrity or Constant scores after arthroscopic rotator cuff repair with TOE techniques. Two investigators independently screened results for relevant articles. Data regarding the study design, surgical technique, retear rate, and Constant shoulder score were extracted from eligible studies. A quality assessment of all articles was performed using the Methodological Index for Non-Randomized Studies (MINORS) criteria. Results: The systematic review identified a total of 32 studies (level of evidence, 1-4) that met inclusion and exclusion criteria. Of the 32 studies, 5 reported on knotless TOE techniques, 25 reported on knot-tying TOE techniques, and 2 reported on both. In the knotless group, retear rates ranged from 6% to 36%, and Constant scores ranged from 38-65 (preoperative) to 73-83 (postoperative). In the knot-tying group, retear rates ranged from 0% to 48%, and Constant scores ranged from 42-64 (preoperative) to 55-96 (postoperative). Conclusion: Despite several theoretical advantages of knotless TOE repair, both knotless and knot-tying techniques reported considerable improvement in functional outcomes after rotator cuff repair. Although tendon failure rates showed a downward trend in knotless studies, additional prospective studies are warranted to better understand the role of medial-row fixation on tendon repair integrity and postoperative clinical outcomes.
Journals
2019 EN
Tabrez A. Mohammad · Yun S. Tsai · Safwa Ameer
+3 more
Background Cell lines form the cornerstone of cell-based experimentation studies into understanding the underlying mechanisms of normal and disease biology including cancer. However, it is commonly acknowledged that contamination of cell lines is a prevalent problem affecting biomedical science and available methods for cell line authentication suffer from limited access as well as being too daunting and time-consuming for many researchers. Therefore, a new and cost effective approach for authentication and quality control of cell lines is needed. Results We have developed a new RNA-seq based approach named CeL-ID for cell line authentication. CeL-ID uses RNA-seq data to identify variants and compare with variant profiles of other cell lines. RNA-seq data for 934 CCLE cell lines downloaded from NCI GDC were used to generate cell line specific variant profiles and pair-wise correlations were calculated using frequencies and depth of coverage values of all the variants. Comparative analysis of variant profiles revealed that variant profiles differ significantly from cell line to cell line whereas identical, synonymous and derivative cell lines share high variant identity and are highly correlated ( ρ > 0.9). Our benchmarking studies revealed that CeL-ID method can identify a cell line with high accuracy and can be a valuable tool of cell line authentication in biomedical science. Finally, CeL-ID estimates the possible cross contamination using linear mixture model if no perfect match was detected. Conclusions In this study, we show the utility of an RNA-seq based approach for cell line authentication. Our comparative analysis of variant profiles derived from RNA-seq data revealed that variant profiles of each cell line are distinct and overall share low variant identity with other cell lines whereas identical or synonymous cell lines show significantly high variant identity and hence variant profiles can be used as a discriminatory/identifying feature in cell authentication model. Electronic supplementary material The online version of this article (10.1186/s12864-018-5371-9) contains supplementary material, which is available to authorized users.
Journals
2019 EN
Chinthana Dematapitiya · Chiara Perera · Wajira Chinthaka
+7 more
Background Infectious mononucleosis is one of the main manifestations of Epstein – Barr virus, which is characterized by fever, tonsillar-pharyngitis, lymphadenopathy and atypical lymphocytes. Although 60% of patients with IMN develop cold type antibodies, clinically significant hemolytic anemia with a high ferritin level is very rare and validity of serum ferritin as an important biomarker has not been used frequently. Case presentation 18-year-old girl presented with fever, malaise and sore throat with asymptomatic anemia, generalized lymphadenopathy, splenomegaly and mild hepatitis. Investigations revealed that she had cold type autoimmune hemolysis, significantly elevated serum ferritin, elevated serum lactate dehydrogenase level with serological evidence of recent Epstein Barr infection. She was managed conservatively and her hemoglobin and serum ferritin levels normalized without any intervention following two weeks of the acute infection. Conclusion Cold type autoimmune hemolytic anemia is a rare manifestation of infectious mononucleosis and serum ferritin is used very rarely as an important biomarker. Management of cold type anemia is mainly supportive and elevated serum ferritin indicates severe viral disease.
Journals
2019 EN
Rashid Nadeem · Zainab Ameer Obeida · Sahish Kamat
+1 more
To the Editor: We read with great interest the article published in a recent issue of Critical Care by Grahl et al. [1]. The authors illustrated that there is no association between delirium and cefepime, penicillin, carbapenems, fluoroquinolones, or macrolides. We would like to point out following concerns about this study. We believe sample was not representative of general population and sample size was not powered enough to draw these conclusions. Study sample does not include all consecutive subjects from a time frame; a large portion of subjects 96 records (18%) were excluded because medication data was not available. Intention to include analysis might change results significantly. Authors did not mention if excluded patients’ profile was similar to included patients’ profile. Delirium was documented in 318 (76%), which is significantly more than expected from a typical ICU which suggests that sample may not be representative of general population. Sample predominantly comprises of Caucasian population (88%) so results may not be applicable to African American population. This study found no association between delirium and cefipime. Although the analysis is performed for cefipime as individual drug, actual number of patients treated with cefipime was not provided; the key