Abstract Due to the lack of patient-specific inlet flow waveform measurements, most computational fluid dynamics (CFD) simulations of intracranial aneurysms usually employ waveforms that are not ...patient-specific as inlet boundary conditions for the computational model. The current study examined how this assumption affects the predicted hemodynamics in patient-specific aneurysm geometries. We examined wall shear stress (WSS) and oscillatory shear index (OSI), the two most widely studied hemodynamic quantities that have been shown to predict aneurysm rupture, as well as maximal WSS (MWSS), energy loss (EL) and pressure loss coefficient (PLc). Sixteen pulsatile CFD simulations were carried out on four typical saccular aneurysms using 4 different waveforms and an identical inflow rate as inlet boundary conditions. Our results demonstrated that under the same mean inflow rate, different waveforms produced almost identical WSS distributions and WSS magnitudes, similar OSI distributions but drastically different OSI magnitudes. The OSI magnitude is correlated with the pulsatility index of the waveform. Furthermore, there is a linear relationship between aneurysm-averaged OSI values calculated from one waveform and those calculated from another waveform. In addition, different waveforms produced similar MWSS, EL and PLc in each aneurysm. In conclusion, inlet waveform has minimal effects on WSS, OSI distribution, MWSS, EL and PLc and a strong effect on OSI magnitude, but aneurysm-averaged OSI from different waveforms has a strong linear correlation with each other across different aneurysms, indicating that for the same aneurysm cohort, different waveforms can consistently stratify (rank) OSI of aneurysms.
Locally compacting the mesh of a flow diverter by a dynamic push-pull technique can accelerate intracranial aneurysm healing. We asked how this deployment strategy compares with overlapping 2 flow ...diverters for aneurysmal flow reduction.
Using a high-fidelity virtual stent placement method, we simulated 3 flow-diverter strategies (single noncompacted, 2 overlapped, and single compacted) in 3 aneurysms (fusiform, large saccular, and medium saccular). Computational fluid dynamics analysis provided posttreatment hemodynamic parameters, including time-averaged inflow rate, aneurysm-averaged velocity, wall shear stress, total absolute circulation, and turnover time. We examined the relationship between the achieved degree of compaction and aneurysm orifice area.
Flow-diverter compaction resulted in a compaction coverage of 57%, 47%, and 22% over the orifice of the fusiform, large, and medium saccular aneurysm, respectively. Compaction coverage increased linearly with orifice area. In the fusiform aneurysm, the single compacted flow diverter accomplished more aneurysmal flow reduction than the other 2 strategies, as indicated by all 5 hemodynamic parameters. In the 2 saccular aneurysms, the overlapped flow diverters achieved the most flow reduction, followed by the single compacted and the noncompacted flow diverter.
Compacting a single flow diverter can outperform overlapping 2 flow diverters in aneurysmal flow reduction, provided that the compaction produces a mesh denser than 2 overlapped flow diverters and this denser mesh covers a sufficient portion of the aneurysm orifice area, for which we suggest a minimum of 50%. This strategy is most effective for aneurysms with large orifices, especially fusiform aneurysms.
Risk factors for acute ischemic stroke following flow-diverter treatment of intracranial aneurysms are poorly understood. Using the International Retrospective Study of Pipeline Embolization Device ...(IntrePED) registry, we studied demographic, aneurysm, and procedural characteristics associated with postoperative acute ischemic stroke following Pipeline Embolization Device (PED) treatment.
We identified patients in the IntrePED registry with post-PED-treatment acute ischemic stroke. The rate of postoperative acute ischemic stroke was determined by demographics, comorbidities, aneurysm characteristics, and procedure characteristics (including anticoagulation use, platelet testing, number of devices used, sheaths, and so forth). Categoric variables were compared with χ(2) testing, and continuous variables were compared with the Student t test. Odds ratios and 95% confidence intervals were obtained by using univariate logistic regression. Multivariate logistic regression analysis was used to determine which factors were independently associated with postoperative stroke.
Of 793 patients with 906 aneurysms, 36 (4.5%) patients had acute ischemic stroke. Twenty-six (72.2%) strokes occurred within 30 days of treatment (median, 3.5 days; range, 0-397 days). Ten patients died, and the remaining 26 had major neurologic morbidity. Variables associated with higher odds of acute ischemic stroke on univariate analysis included male sex, hypertension, treatment of MCA aneurysms, treatment of fusiform aneurysms, treatment of giant aneurysms, and use of multiple PEDs. However, on multivariate analysis, the only one of these variables independently associated with stroke was treatment of fusiform aneurysms (OR, 2.74; 95% CI, 1.11-6.75; P = .03). Fusiform aneurysms that were associated with stroke were significantly larger than those not associated with stroke (mean, 24.5 ± 12.5 mm versus 13.6 ± 6.8 mm; P < .001).
Ischemic stroke following PED treatment is an uncommon-but-devastating complication. Fusiform aneurysms were the only variable independently associated with postoperative stroke.
A new in vitro cerebrovascular occlusion model of the intracranial circulation was developed recently for testing thrombectomy devices. Using this model, we compared recanalization success associated ...with different modern endovascular thrombectomy approaches.
Model experiments were performed in 4 thrombectomy test groups: 1) primary or direct Stentriever thrombectomy with a conventional guide catheter (control group), 2) primary Stentriever thrombectomy with a balloon-guide catheter, 3) combined Stentriever-continuous aspiration approach, and 4) direct aspiration alone. Successful recanalization was defined as a TICI score of 2b or 3.
Seventy-one thrombectomy experiments were conducted. Similar rates of TICI 2b-3 scores were achieved with balloon-guide and conventional guide catheters (P = .34). The combined Stentriever plus aspiration approach and the primary aspiration thrombectomy resulted in significantly higher rates of TICI 2b or 3 than the conventional guide-catheter approach in the control group (P = .008 and P = .0001, respectively). The primary Stentriever thrombectomy with the conventional guide catheter showed the highest rate of embolization to new territories (53%).
Data from our in vitro model experiments show that the Stentriever thrombectomy under continuous aspiration and primary aspiration thrombectomy approaches led to the highest degree of recanalization.
Spontaneous intraparenchymal hemorrhage is a dreaded complication of unknown etiology following flow-diversion treatment. Using the International Retrospective Study of the Pipeline Embolization ...Device registry, we studied demographic, aneurysm, and procedural characteristics associated with intraparenchymal hemorrhage following Pipeline Embolization Device treatment.
We identified patients in the International Retrospective Study of the Pipeline Embolization Device registry with intraparenchymal hemorrhage unrelated to index aneurysm rupture post-Pipeline Embolization Device treatment. The rate of intraparenchymal hemorrhage was determined by baseline demographics, comorbidities, aneurysm characteristics, and procedural characteristics (including anticoagulation use, platelet testing, number of devices used, sheaths, catheters, and guidewires). Categoric variables were compared with χ(2) testing, and continuous variables were compared with the Student t test.
Of 793 patients with 906 aneurysms, 20 (2.5%) had intraparenchymal hemorrhage. Fifteen intraparenchymal hemorrhages (75.0%) occurred within 30 days of treatment (median, 5 days; range, 0-150 days). Nine patients with intraparenchymal hemorrhage (45.0%) died, 10 (50.0%) had major neurologic morbidity, and 1 had minor neurologic morbidity (5.0%). Intraparenchymal hemorrhage was ipsilateral to the Pipeline Embolization Device in 16 patients (80%) and contralateral in 3 patients (15.0%). Variables associated with higher odds of intraparenchymal hemorrhage included treatment of ruptured aneurysms (OR, 4.44; 95% CI, 1.65-11.94; P = .005) and the use of ≥ 3 Pipeline Embolization Devices (OR, 4.10; 95% CI, 1.34-12.58; P = .04). The Shuttle sheath was not associated with intraparenchymal hemorrhage (OR, 0.97; 95% CI, 0.38-2.45; P = .95).
Spontaneous intraparenchymal hemorrhage following Pipeline Embolization Device treatment is a rare-but-devastating complication, with nearly all patients having morbidity or mortality. Variables associated with intraparenchymal hemorrhage included the use of multiple Pipeline Embolization Devices and treatment of ruptured aneurysms. The Shuttle, a device that was previously thought to be associated with intraparenchymal hemorrhage, was not associated with it.
Neurovascular flow diverters are flexible, braided stent-meshes for intracranial aneurysm treatment. We applied the dynamic push-pull technique to manipulate the flow-diverter mesh density at the ...aneurysm orifice to maximize flow diversion. This study investigated the hemodynamic impact of the dynamic push-pull technique on patient-specific aneurysms by using the developed high-fidelity virtual-stenting computational modeling technique combined with computational fluid dynamics.
We deployed 2 Pipeline Embolization Devices into 2 identical sidewall anterior cerebral artery aneurysm phantoms by using the dynamic push-pull technique with different delivery-wire advancements. We then numerically simulated these deployment processes and validated the simulated mesh geometry. Computational fluid dynamics analysis was performed to evaluate detailed hemodynamic changes by deployed flow diverters in the sidewall aneurysm and a fusiform basilar trunk aneurysm (deployments implemented previously). Images of manipulated flow diverter mesh from sample clinical cases were also evaluated.
The flow diverters deployed in silico accurately replicated in vitro geometries. Increased delivery wire advancement (21 versus 11 mm) by using a dynamic push-pull technique produced a higher mesh compaction at the aneurysm orifice (50% metal coverage versus 36%), which led to more effective aneurysmal inflow reduction (62% versus 50% in the sidewall aneurysm; 57% versus 36% in the fusiform aneurysm). The dynamic push-pull technique also caused relatively lower metal coverage along the parent vessel due to elongation of the flow diverter. High and low mesh compactions were also achieved for 2 real patients by using the dynamic push-pull technique.
The described dynamic push-pull technique increases metal coverage of pure braided flow diverters over the aneurysm orifice, thereby enhancing the intended flow diversion, while reducing metal coverage along the parent vessel to prevent flow reduction in nearby perforators.
Psychosis treatment guidelines recommend cognitive behaviour therapy (CBT) and family intervention (FI), for all patients with first episode psychosis (FEP), though guidance borrows heavily from ...literature in adults from high income countries. To our knowledge, there are few randomized controlled trials (RCTs) examining the comparative effect of these commonly endorsed psychosocial interventions in individuals with early psychosis from high-income countries and no such trials from low and middle-income countries (LMICs). The present study aims to confirm the clinical-efficacy and cost-effectiveness of delivering culturally adapted CBT (CaCBT) and culturally adapted FI (CulFI) to individuals with FEP in Pakistan.
A multi-centre, three-arm RCT of CaCBT, CulFI, and treatment as usual (TAU) for individuals with FEP (n = 390), recruited from major centres across Pakistan. Reducing overall symptoms of FEP will be the primary outcome. Additional aims will include improving patient and carer outcomes and estimating the economic impact of delivering culturally appropriate psychosocial interventions in low-resource settings. This trial will assess the clinical-efficacy and cost-effectiveness of CaCBT and CulFI compared with TAU in improving patient (positive and negative symptoms of psychosis, general psychopathology, depressive symptoms, quality of life, cognition, general functioning, and insight) and carer related outcomes (carer experience, wellbeing, illness attitudes and symptoms of depression and anxiety).
A successful trial may inform the rapid scale up of these interventions not only in Pakistan but other low-resource settings, to improve clinical outcomes, social and occupational functioning, and quality of life in South Asian and other minority groups with FEP.
NCT05814913.
Flow diversion with the Pipeline Embolization Device (PED) for the treatment of intracranial aneurysms is associated with a high rate of aneurysm occlusion. However, clinical and radiographic ...predictors of incomplete aneurysm occlusion are poorly defined. In this study, predictors of incomplete occlusion at last angiographic follow-up after PED treatment were assessed.
A retrospective analysis of consecutive aneurysms treated with the PED between 2009 and 2016, at 3 academic institutions in the United States, was performed. Cases with angiographic follow-up were selected to evaluate factors predictive of incomplete aneurysm occlusion at last follow-up.
We identified 465 aneurysms treated with the PED; 380 (81.7%) aneurysms (329 procedures; median age, 58 years; female/male ratio, 4.8:1) had angiographic follow-up, and were included. Complete occlusion (100%) was achieved in 78.2% of aneurysms. Near-complete (90%-99%) and partial (<90%) occlusion were collectively achieved in 21.8% of aneurysms and defined as incomplete occlusion. Of aneurysms followed for at least 12 months (211 of 380), complete occlusion was achieved in 83.9%. Older age (older than 70 years), nonsmoking status, aneurysm location within the posterior communicating artery or posterior circulation, greater aneurysm maximal diameter (≥21 mm), and shorter follow-up time (<12 months) were significantly associated with incomplete aneurysm occlusion at last angiographic follow-up on univariable analysis. However, on multivariable logistic regression, only age, smoking status, and duration of follow-up were independently associated with occlusion status.
Complete occlusion following PED treatment of intracranial aneurysms can be influenced by several factors related to the patient, aneurysm, and treatment. Of these factors, older age (older than 70 years) and nonsmoking status were independent predictors of incomplete occlusion. While the physiologic explanation for these findings remains unknown, identification of factors predictive of incomplete aneurysm occlusion following PED placement can assist in patient selection and counseling and might provide insight into the biologic factors affecting endothelialization.
Abstract
Human Papillomavirus (HPV) is the most common cause of sexually transmitted diseases and causes a wide range of pathologies including cervical carcinoma. Integration of the HR-HPV DNA into ...the host genome plays a crucial role in cervical carcinoma. An alteration of the pRb pathways by the E7 proteins is one of the mechanisms that’s account for the transforming capacity of high-risk papillomavirus. For the proper understanding of the underline mechanism of the progression of the disease, the present study investigate the correlation of concentration of host pRb protein, viral E7 oncoprotein and viral load in early and advanced stages of cervical carcinoma. It was found that the viral load in early stages (stage I and II) was less (log
10
transformed mean value 2.6 and 3.0) compared to advanced stages (stage III and IV) (Log
10
transformed value 5.0 and 5.8) having high expression of HPV E7 onco-protein and reduced level of pRb protein, signifying the role of viral load and expression level of E7 oncoprotein in the progression of cervical cancer.
The necessity for platelet-inhibition testing before aneurysm treatment in patients premedicated with antiplatelet agents is controversial. Using the International Retrospective Study of Pipeline ...Embolization Device registry, we studied complication rates in groups of patients who underwent platelet testing and those who did not undergo platelet testing to determine if these test results were associated with improved outcomes.
Patients in the International Retrospective Study of Pipeline Embolization Device registry with an unruptured aneurysm were categorized as those who underwent platelet testing before Pipeline embolization device treatment or those who did not. Complication rates were compared by using the Fisher exact or Pearson χ(2) test. Multivariate analysis was performed to determine if platelet function testing was independently associated with poor outcomes after adjusting for age, number of devices and aneurysms, aneurysm location and size, and practitioner and center volume.
Compared with the patients who received a Pipeline embolization device without platelet testing, those who underwent platelet testing and Pipeline embolization device placement experienced higher rates of intracranial hemorrhage (0 of 187 0.0% vs 12 of 511 2.3%, respectively; P = .04), neurologic morbidity (4 of 187 2.1% vs 42 of 511 8.2%, respectively; P < .01), and combined neurologic morbidity and mortality (6 of 187 3.2% vs 45 of 511 8.8%, respectively; P = .01). More patients in the platelet testing and Pipeline embolization device group were treated with multiple devices (227 38.0% vs 56 27.8 patients, respectively; P = .01). On multivariate analysis, the group of patients who underwent platelet testing and Pipeline embolization device placement had higher odds of neurologic morbidity (OR, 3.25 95% CI, 1.10-9.61; P = .03).
Platelet testing in patients who undergo Pipeline embolization device placement is associated with higher rates of morbidity. Additional prospective studies are needed to determine if and when platelet testing in these patients is appropriate.
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