Thrombectomy With the pRESET vs Solitaire Stent Retrievers as First-Line Large Vessel Occlusion Stroke Treatment: A Randomized Clinical Trial.

Importance: Stent retriever-based thrombectomy is highly beneficial in large vessel occlusion (LVO) strokes. Many stent retriever designs are currently available, but comparison of these technologies in well-conducted studies is lacking. Objective: To determine whether thrombectomy for LVO stroke with the pRESET stent retriever is noninferior to treatment with the Solitaire stent retriever. Design, Setting, and Participants: This study was a multicenter, prospective, randomized, controlled, open-label, adaptive, noninferiority trial with blinded primary end point evaluation. Between October 2019 and February 2022, multicenter participation occurred across 19 research hospitals and/or universities in the US and 5 in Germany. Patients with LVO stroke were enrolled and included up to 8 hours after symptom onset. Interventions: Patients underwent 1:1 randomization to thrombectomy with the pRESET or Solitaire stent retriever. Main Outcomes and Measures: The primary outcome was the difference in the rate of 90-day functional independence across the 2 devices, using a -12.5% noninferiority margin for the lower bound of the 1-sided 95% CI of the difference between pRESET and Solitaire retrievers. Results: Of 340 randomized patients, 170 (50.0%) were female, and the median (IQR) age was 73.0 (64.0-82.0) years. The study procedure was completed in 322 of the 340 randomized patients. The primary end point of 90-day functional independence was achieved by 95 patients (54.9%; 95% CI, 48.7-61.1) in the pRESET group and in 96 (57.5%; 95% CI, 51.2-63.8) in the Solitaire group (absolute difference, -2.57%; 95% CI, -11.42 to 6.28). As the lower bound of the 95% CI was greater than -12.5%, the pRESET retriever was deemed noninferior to the Solitaire retriever. The noninferiority of pRESET over Solitaire was also observed in the secondary clinical end point (90-day shift in modified Rankin Scale score) and in both angiographic end points (Expanded Treatment in Cerebral Infarction [eTICI] score of 2b50 or greater within 3 passes: 146 of 173 [84.4%] vs 149 of 167 [89.2%]; absolute difference, -4.83%; 95% CI, -10.84 to 1.19; eTICI of 2c or greater following the first pass: 76 of 173 [43.7%] vs 74 of 167 [44.3%]; absolute difference, -0.63%; 95% CI, -9.48 to 8.21). Symptomatic intracranial hemorrhage occurred in 0 patients in the pRESET group and 2 (1.2%) in the Solitaire group. Mortality occurred in 25 (14.5%) in the pRESET group and in 24 (14.4%) in the Solitaire group at 90 days. Findings of the per-protocol and as-treated analyses were in concordance with findings of the intention-to-treat analysis. Conclusions and Relevance: In this study, among patients with LVO stroke, thrombectomy with the pRESET stent retriever was noninferior to thrombectomy with the Solitaire stent retriever. Findings suggest that pRESET offers a safe and effective option for flow restoration and disability reduction in patients with LVO stroke.

Low body mass index patients have worse outcomes after mechanical thrombectomy.

BACKGROUND: There is evidence that frailty is an independent predictor of worse outcomes after stroke. Similarly, although obesity is associated with a higher risk for stroke, there are multiple reports describing improved mortality and functional outcomes in higher body mass index (BMI) patients in a phenomenon known as the obesity paradox. We investigated the effect of low BMI on outcomes after mechanical thrombectomy (MT). METHODS: We conducted a retrospective analysis of 231 stroke patients who underwent MT at an academic medical center between 2020-2022. The patients' BMI data were collected from admission records and coded based on the Centers for Disease Control and Prevention (CDC) obesity guidelines. Recursive partitioning analysis (RPA) in R software was employed to automatically detect a BMI threshold associated with a significant survival benefit. Frailty was quantified using the Modified Frailty Index 5 and 11. RESULTS: In our dataset, by CDC classification, 2.6% of patients were underweight, 27.3% were normal BMI, 30.7% were overweight, 19.9% were class I obese, 9.5% were class II obese, and 10% were class III obese. There were no significant differences between these groups. RPA identified a clinically significant BMI threshold of 23.62 kg/m2. Independent of frailty, patients with a BMI ≤23.62 kg/m2 had significantly worse overall survival (P<0.001) and 90-day modified Rankin Scale (P=0.027) than patients above the threshold. CONCLUSIONS: Underweight patients had worse survival and functional outcomes after MT. Further research should focus on the pathophysiology underlying poor prognosis in underweight MT patients, and whether optimizing nutritional status confers any neuroprotective benefit.

Venous Sinus Stenting: Safety and Health Care Resource Evaluation for Optimal Recovery in an Evolving Health Care Environment.

BACKGROUND: Increasing evidence supports the effectiveness of venous sinus stenting (VSS) with favorable outcomes, safety, and expenses compared with shunting for idiopathic intracranial hypertension. Yet, no evidence is available regarding optimal postoperative recovery, which has increasing importance with the burdens on health care imposed by the coronavirus disease 2019 pandemic. We examined adverse events and costs after VSS and propose an optimal recovery pathway to maximize patient safety and reduce stress on health care resources. METHODS: A retrospective review was undertaken of elective VSS operations performed from May 2008 to August 2021 at a single institution. Primary data included hospital length of stay, intensive care unit (ICU) length of stay, adverse events, need for ICU interventions, and hospital costs. RESULTS: Fifty-three patients (98.1% female) met the inclusion criteria. Of these patients, 51 (96.2%) were discharged on postoperative day (POD) 1 and 2 patients were discharged on POD 2. Both patients discharged on POD 2 remained because of groin hematomas from femoral artery access. There were no major complications or care that required an ICU. Eight patients (15.1%) were lateralized to other ICUs or remained in a postanesthesia care unit because the neurosciences ICU was above capacity. Total estimated cost for initial recovery day in a neurosciences ICU room was $2361 versus $882 for a neurosurgery/neurology ward room. In our cohort, ward convalescence would save an estimated $79,866 for bed placement alone and increase ICU bed availability. CONCLUSIONS: Our findings reaffirm the safety of VSS. These patients should recover on a neurosurgery/neurology ward, which would save health care costs and increase ICU bed availability.

Prospective study on embolization of intracranial aneurysms with the pipeline device (PREMIER study): 3-year results with the application of a flow diverter specific occlusion classification.

BACKGROUND: The pipeline embolization device (PED; Medtronic) has presented as a safe and efficacious treatment for small- and medium-sized intracranial aneurysms. Independently adjudicated long-term results of the device in treating these lesions are still indeterminate. We present 3-year results, with additional application of a flow diverter specific occlusion scale. METHODS: PREMIER (prospective study on embolization of intracranial aneurysms with pipeline embolization device) is a prospective, single-arm trial. Inclusion criteria were patients with unruptured wide-necked intracranial aneurysms ≤12 mm. Primary effectiveness (complete aneurysm occlusion) and safety (major neurologic event) endpoints were independently monitored and adjudicated. RESULTS: As per the protocol, of 141 patients treated with a PED, 25 (17.7%) required angiographic follow-up after the first year due to incomplete aneurysm occlusion. According to the Core Radiology Laboratory review, three (12%) of these patients progressed to complete occlusion, with an overall rate of complete aneurysm occlusion at 3 years of 83.3% (115/138). Further angiographic evaluation using the modified Cekirge-Saatci classification demonstrated that complete occlusion, neck residual, or aneurysm size reduction occurred in 97.1%. The overall combined safety endpoint at 3 years was 2.8% (4/141), with only one non-debilitating major event occurring after the first year. There was one case of aneurysm recurrence but no cases of delayed rupture in this series. CONCLUSIONS: The PED device presents as a safe and effective modality in treating small- and medium-sized intracranial aneurysms. The application of a flow diverter specific occlusion classification attested the long-term durability with higher rate of successful aneurysm occlusion and no documented aneurysm rupture. TRIAL REGISTRATION: NCT02186561.

Safety of intra-arterial chemotherapy with or without osmotic blood-brain barrier disruption for the treatment of patients with brain tumors.

Background: Intra-arterial administration of chemotherapy with or without osmotic blood-brain barrier disruption enhances delivery of therapeutic agents to brain tumors. The aim of this study is to evaluate the safety of these procedures. Methods: Retrospectively collected data from a prospective database of consecutive patients with primary and metastatic brain tumors who received intra-arterial chemotherapy without osmotic blood-brain barrier disruption (IA) or intra-arterial chemotherapy with osmotic blood-brain barrier disruption (IA/OBBBD) at Oregon Health and Science University (OHSU) between December 1997 and November 2018 is reported. Chemotherapy-related complications are detailed per Common Terminology Criteria for Adverse Events (CTCAE) guidelines. Procedure-related complications are grouped as major and minor. Results: 4939 procedures (1102 IA; 3837 IA/OBBBD) were performed on 436 patients with various pathologies (primary central nervous system lymphoma [26.4%], glioblastoma [18.1%], and oligodendroglioma [14.7%]). Major procedure-related complications (IA: 12, 1%; IA/OBBBD: 27, 0.7%; P = .292) occurred in 39 procedures including 3 arterial dissections requiring intervention, 21 symptomatic strokes, 3 myocardial infarctions, 6 cervical cord injuries, and 6 deaths within 3 days. Minor procedure-related complications occurred in 330 procedures (IA: 41, 3.7%; IA/OBBBD: 289, 7.5%; P = .001). Chemotherapy-related complications with a CTCAE attribution and grade higher than 3 was seen in 359 (82.3%) patients. Conclusions: We provide safety and tolerability data from the largest cohort of consecutive patients who received IA or IA/OBBBD. Our data demonstrate that IA or IA/OBBBD safely enhance drug delivery to brain tumors and brain around the tumor.

New Class of Radially Adjustable Stentrievers for Acute Ischemic Stroke: Primary Results of the Multicenter TIGER Trial.

[Figure: see text].

Carotid Revascularization: Current Practice and Future Directions.

Carotid stenosis is responsible for approximately 15% of ischemic strokes. Carotid revascularization significantly decreases patients' stroke risk. Carotid endarterectomy has first-line therapy for moderate-to-severe carotid stenosis after a series of pivotal randomized controlled trials were published almost 30 years ago. Revascularization with carotid stenting has become a popular and effective alternative in a select subpopulation of patients. We review the current state of the literature regarding revascularization indications, patient selection, advantages of each revascularization approach, timing of intervention, and emerging interventional techniques, such as transcarotid artery revascularization.

Embolization of Basilar Tip Aneurysm via Ascending Cervical Artery.

BACKGROUND: Unusual vascular anatomy can present treatment challenges as traditional approaches may be unfeasible. CASE DESCRIPTION: In this case we describe a patient who presented with subarachnoid hemorrhage due to a ruptured basilar apex aneurysm, with an occluded left vertebral artery and severely stenotic right vertebral artery. Coil embolization was performed via catheterization of an ascending cervical artery, with a successful clinical and radiographic outcome. CONCLUSIONS: This demonstrates novel use of an endovascular technique in the setting of multiple vascular pathologies.

Prospective study on embolization of intracranial aneurysms with the pipeline device: the PREMIER study 1 year results.

BACKGROUND: Preliminary clinical studies on the safety and efficacy of the pipeline embolization device (PED) for the treatment of small/medium aneurysms have demonstrated high occlusion rates with low complications. OBJECTIVE: To evaluate the safety and effectiveness of the PED for treatment of wide necked small and medium intracranial aneurysms. METHODS: PREMIER is a prospective, multicenter, single arm trial. Patients were treated with the PED for unruptured wide necked aneurysms, measuring ≤12 mm along the internal carotid artery or vertebral artery, between July 2014 and November 2015. At 1 year post-procedure, the primary effectiveness endpoint was complete occlusion (Raymond grade 1) without major parent vessel stenosis (≤50%) or retreatment, and the primary safety endpoint was major stroke in the territory supplied by the treated artery or neurologic death. RESULTS: A total of 141 patients were treated with PEDs (mean age 54.6±11.3 years, 87.9% (124/141) women). Mean aneurysm size was 5.0±1.92 mm, and 84.4% (119/141) measured <7 mm. PED placement was successful in 99.3% (140/141) of patients. Mean number of PEDs implanted per patient was 1.1±0.26; a single PED was used in 92.9% (131/141) of patients. At 1 year, 97.9% (138/141) of patients underwent follow-up angiography with 76.8% (106/138) of patients having met the study's primary effectiveness endpoint. The combined major morbidity and mortality rate was 2.1% (3/140). CONCLUSIONS: Treatment of wide necked small/medium aneurysms with the PED results in high rates of complete occlusion without significant parent vessel stenosis and low rates of permanent neurologic complications. TRIAL REGISTRATION: NCT02186561.

Indentation properties and glycosaminoglycan content of human menisci in the deep zone.

Menisci are two crescent shaped fibrocartilaginous structures that provide fundamental load distribution and support within the knee joint. Their unique shape transmits axial stresses (i.e. "body force") into hoop or radial stresses. The menisci are primarily an inhomogeneous aggregate of glycosaminoglycans (GAGs) supporting bulk compression and type I collagen fibrils sustaining tension. It has been shown that the superficial meniscal layers are functionally homogeneous throughout the three distinct regions (anterior, central and posterior) using a 300 µm diameter spherical indenter tip, but the deep zone of the meniscus has yet to be mechanically characterized at this scale. Furthermore, the distribution and content of GAG throughout the human meniscal cross-section have not been examined. This study investigated the mechanical properties, via indentation, of the human deep zone meniscus among three regions of the lateral and medial menisci. The distribution of GAGs through the cross-section was also documented. Results for the deep zone of the meniscus showed the medial posterior region to have a significantly greater instantaneous elastic modulus than the central region. No significant differences in the equilibrium modulus were seen when comparing regions or the hemijoint. Histological results revealed that GAGs are not present until at least ~600 µm from the meniscal surface. Understanding the role and distribution of GAG within the human meniscus in conjunction with the material properties of the meniscus will aid in the design of tissue engineered meniscal replacements.

Feasibility of shutter-speed DCE-MRI for improved prostate cancer detection.

The feasibility of shutter-speed model dynamic-contrast-enhanced MRI pharmacokinetic analyses for prostate cancer detection was investigated in a prebiopsy patient cohort. Differences of results from the fast-exchange-regime-allowed (FXR-a) shutter-speed model version and the fast-exchange-limit-constrained (FXL-c) standard model are demonstrated. Although the spatial information is more limited, postdynamic-contrast-enhanced MRI biopsy specimens were also examined. The MRI results were correlated with the biopsy pathology findings. Of all the model parameters, region-of-interest-averaged K(trans) difference [ΔK(trans) ≡ K(trans)(FXR-a) - K(trans)(FXL-c)] or two-dimensional K(trans)(FXR-a) vs. k(ep)(FXR-a) values were found to provide the most useful biomarkers for malignant/benign prostate tissue discrimination (at 100% sensitivity for a population of 13, the specificity is 88%) and disease burden determination. (The best specificity for the fast-exchange-limit-constrained analysis is 63%, with the two-dimensional plot.) K(trans) and k(ep) are each measures of passive transcapillary contrast reagent transfer rate constants. Parameter value increases with shutter-speed model (relative to standard model) analysis are larger in malignant foci than in normal-appearing glandular tissue. Pathology analyses verify the shutter-speed model (FXR-a) promise for prostate cancer detection. Parametric mapping may further improve pharmacokinetic biomarker performance.

Benign prostatic hyperplasia: a brief overview of pathogenesis, diagnosis, and therapy.

Benign prostatic hyperplasia is a common condition, causing symptoms in 75% of men over the age of 70. To understand the role of a novel treatment for this condition, an understanding of the pathology, approach to diagnosis, and range of existing therapies are important. This article provides a general overview of benign prostatic hyperplasia evaluation and management.

Cell membrane water exchange effects in prostate DCE-MRI.

Prostate Dynamic-Contrast-Enhanced (DCE) MRI often exhibits fast and extensive global contrast reagent (CR) extravasation - measured by K(trans), a pharmacokinetic parameter proportional to its rate. This implies that the CR concentration [CR] is high in the extracellular, extravascular space (EES) during a large portion of the DCE-MRI study. Since CR is detected indirectly, through water proton signal change, the effects of equilibrium transcytolemmal water exchange may be significant in the data and thus should be admitted in DCE-MRI pharmacokinetic modeling. The implications for parameter values were investigated through simulations, and analyses of actual prostate data, with different models. Model parameter correlation and precision were also explored. A near-optimal version of the exchange-sensitized model was found. Our results indicate that ΔK(trans) (the K(trans) difference returned by this version and a model assuming exchange to be effectively infinitely fast) may be a very useful biomarker for discriminating malignant from benign prostate tissue. Using an exchange-sensitized model, we find that the mean intracellular water lifetime (τ(i)) - an exchange measure - can be meaningfully mapped for the prostate. Our results show prostate glandular zone differences in τ(i) values.

The evaluation of esophageal adenocarcinoma using dynamic contrast-enhanced magnetic resonance imaging.

Although neoadjuvant chemoradiation eradicates esophageal adenocarcinoma in a substantial proportion of patients, conventional imaging techniques cannot accurately detect this response. Dynamic contrast-enhanced magnetic resonance imaging is an emerging approach that may be well suited to fill this role. This pilot study evaluates the ability of this method to discriminate adenocarcinoma from normal esophageal tissue. Patients with esophageal adenocarcinoma and control subjects underwent scanning. Patients treated with neoadjuvant therapy underwent pre- and postchemoradiation scans. Parameters were extracted for each pixel were Ktrans (equilibrium rate for transfer of contrast reagent across the vascular wall), ve (volume fraction of interstitial space), and taui (mean intracellular water lifetime). Five esophageal adenocarcinoma patients and two tumor-free control subjects underwent scanning. The mean Ktrans value was 5.7 times greater in esophageal adenocarcinoma, and taui is 2.0 times smaller, than in the control subjects. Ktrans decreased by 11.4-fold after chemoradiation. Parametric maps qualitatively demonstrate a difference in Ktrans. DCE MRI of the esophagus is feasible. Ktrans, a parameter that has demonstrated discriminative ability in other malignancies, also shows promise in differentiating esophageal adenocarcinoma from benign tissue. The determination of Ktrans represents an in vivo assay for endothelial permeability and thus may serve as a quantitative measure of response to induction chemoradiation.

Assessment of prostate-specific antigen doubling time in prediction of prostate cancer on needle biopsy.

OBJECTIVES: Prostate-specific antigen (PSA) kinetics have failed to predict for the presence of prostate cancer in screening populations in which many patients harbor subclinical disease. We hypothesized that the prebiopsy PSA doubling time (PSADT) and PSA velocity (PSAV) could predict for cancer detection in a referral population with a suspicion of prostate cancer. METHODS: Data were collected from 1699 consecutive veterans with a PSA level of 10 ng/mL or less who underwent prostate biopsy. Logistic regression analysis was performed on the following: age, race, family history, digital rectal examination findings, PSA, PSA density, PSADT, PSAV, prostate volume, and ultrasound lesions. Model building was accomplished with 70% of the data, and validation was done using the remaining 30%. These data were also analyzed using classification and regression tree analysis. RESULTS: Using logistic regression analysis (P <0.05) on the model building set, prostate cancer was associated with age (older than 70 years), PSA level (greater than 2.9 ng/mL), PSA density (more than 0.12 ng/mL/cm3), digital rectal examination findings, and the presence of a lesion on ultrasonography. A PSADT of 2 to 5 years was marginally associated with prostate cancer detection (odds ratio 1.6, 95% confidence interval 1.1 to 2.3), and a PSADT of less than 2 years or longer than 5 years and PSAV were not predictive. On classification and regression tree analysis, PSADT was not selected as a predictive factor. Furthermore, neither PSADT nor PSAV was predictive of Gleason score 7 or worse cancer. CONCLUSIONS: In contrast to its prognostic value after the diagnosis of prostate cancer has been established, PSA kinetics offer little to clinical decision making as predictors of cancer or high-grade cancer in men with a PSA level of 10 ng/mL or less.