In this study involving 2103 men with elevated PSA levels, the use of both MRI-targeted and 12-core systematic biopsies was more effective at detecting clinically significant prostate cancers than ...either biopsy method alone.
Multiple studies demonstrate magnetic resonance imaging (MRI)-targeted biopsy detects more clinically significant cancer than systematic biopsy; however, some clinically significant cancers are ...detected by systematic biopsy only. While these events are rare, we sought to perform a retrospective analysis of these cases to ascertain the reasons that MRI-targeted biopsy missed clinically significant cancer which was subsequently detected on systematic prostate biopsy.
Patients were enrolled in a prospective study comparing cancer detection rates by transrectal MRI-targeted fusion biopsy and systematic 12-core biopsy. Patients with an elevated prostate specific antigen (PSA), abnormal digital rectal examination, or imaging findings concerning for prostate cancer underwent prostate MRI and subsequent MRI-targeted and systematic biopsy in the same setting. The subset of patients with grade group (GG) ≥3 cancer found on systematic biopsy and GG ≤2 cancer (or no cancer) on MRI-targeted biopsy was classified as MRI-targeted biopsy misses. A retrospective analysis of the MRI and MRI-targeted biopsy real-time screen captures determined the cause of MRI-targeted biopsy miss. Multivariable logistic regression analysis compared baseline characteristics of patients with MRI-targeted biopsy misses to GG-matched patients whose clinically significant cancer was detected by MRI-targeted biopsy.
Over the study period of 2007 to 2019, 2,103 patients met study inclusion criteria and underwent combined MRI-targeted and systematic prostate biopsies. A total of 41 (1.9%) men were classified as MRI-targeted biopsy misses. Most MRI-targeted biopsy misses were due to errors in lesion targeting (21, 51.2%), followed by MRI-invisible lesions (17, 40.5%) and MRI lesions missed by the radiologist (3, 7.1%). On logistic regression analysis, lower Prostate Imaging-Reporting and Data System (PI-RADS
) score was associated with having clinically significant cancer missed on MRI-targeted biopsy.
While uncommon, most MRI-targeted biopsy misses are due to errors in lesion targeting, which highlights the importance of accurate co-registration and targeting when using software-based fusion platforms. Additionally, some patients will harbor MRI-invisible lesions which are untargetable by MRI-targeted platforms. The presence of a low PI-RADS score despite a high PSA is suggestive of harboring an MRI-invisible lesion.
While magnetic resonance imaging (MRI)-targeted biopsy (TBx) results in better prostate cancer (PCa) detection relative to systematic biopsy (SBx), the combination of both methods increases ...clinically significant PCa detection relative to either Bx method alone. However, combined Bx subjects patients to higher number of Bx cores and greater detection of clinically insignificant PCa.
To determine if prebiopsy prostate MRI can identify men who could forgo combined Bx without a substantial risk of missing clinically significant PCa (csPC).
Men with MRI-visible prostate lesions underwent combined TBx plus SBx.
The primary outcomes were detection rates for grade group (GG) ≥2 and GG ≥3 PCa by TBx and SBx, stratified by Prostate Imaging-Reporting and Data System (PI-RADS) score.
Among PI-RADS 5 cases, nearly all csPCs were detected by TBx, as adding SBx resulted in detection of only 2.5% more GG ≥2 cancers. Among PI-RADS 3–4 cases, however, SBx addition resulted in detection of substantially more csPCs than TBx alone (8% vs 7.5%). Conversely, TBx added little to detection of csPC among men with PI-RADS 2 lesions (2%) relative to SBx (7.8%).
While combined Bx increases the detection of csPC among men with MRI-visible prostate lesions, this benefit was largely restricted to PI-RADS 3–4 lesions. Using a strategy of TBx only for PI-RADS 5 and combined Bx only for PI-RADS 3–4 would avoid excess biopsies for men with PI-RADS 5 lesions while resulting in a low risk of missing csPC (1%).
Our study investigated an optimized strategy to diagnose aggressive prostate cancer in men with an abnormal prostate MRI (magnetic resonance imaging) scan while minimizing the risk of excess biopsies. We used a scoring system for MRI scan images called PI-RADS. The results show that MRI-targeted biopsies alone could be used for men with a PI-RADS score of 5, while men with a PI-RADS score of 3 or 4 would benefit from a combination of MRI-targeted biopsy and systematic biopsy.
This trial is registered at ClinicalTrials.gov as NCT00102544.
For men found to have Prostate Imaging-Reporting and Data System (PI-RADS) 5 lesions on prostate magnetic resonance imaging (MRI) it is reasonable to perform MRI-targeted biopsy only, as very few clinically significant cancers will be missed. However, for men with PI-RADS 3–4 lesions on MRI, a combined MRI-targeted and systematic biopsy should be used, as each biopsy method contributes substantially to detection of clinically significant cancer.
This paper presents the design and optimisation of an aerofoil with active continuous trailing-edge flap (CTEF) investigated as a potential rotorcraft active control device. Several structural ...cross-section models are developed: high-fidelity NASA STRucture ANalysis (NASTRAN) and University of Michigan/Variational Asymptotic Beam Section Code (UM/VABS) models and a reduced-order analysis model. The validation of the reduced-order model is established by comparing its predictions of CTEF deformations with those of NASTRAN and UM/VABS analyses, which both show good agreement. The 2D aerodynamic characteristics of the CTEF aerofoil are evaluated using XFOIL and Computational Fluid Dynamics (CFD) analyses: FUN3D and Overset Transonic Unsteady Rotor Navier-Stokes (OVERTURNS). XFOIL, coupled with the reduced-order structure model, is adopted for optimisation study. The accuracy of XFOIL in predicting the aerodynamic pressure of the CTEF aerofoil is verified using CFD simulations, which shows sufficient fidelity. The predicted variations of aerodynamic coefficients with a CTEF angle are compared among the aerodynamic analyses. The optimisation process is developed and applied to two bimorph bender configurations: a Macro-Fibre Composite (MFC) solid bender and an MFC stack bender. The solid bender is used to confirm the functioning of the optimisation procedure and to use its optimal layout as a reference to the stack design, the primary design object. A linear tapered shape is found to be the optimum for a MFC solid bender, which generates an average of 63% more CTEF angles than those of an optimal rectangular bender. An optimised MFC stack bender is shown to resemble the shape of the solid bender. A four-ply bimorph is considered the best choice among the stack layouts because of its large output of CTEF angles and relatively less plies required. The CTEF angle produced by the four-ply optimal layout ranges from 7.6° to 5.3° with speeds from 0 to 200m/s at an angle of attack (AoA) of 6°. The reduction in the CTEF angle with AoA is less steep than that with speed, ranging from 6.5° to 5.8° with AoA from 0 to 8° at speed of 166m/s. An average of 14% increase in CTEF angles is achieved through optimisation for the four-ply bimorph.
Reply by Authors Williams, Cheyenne; Ahdoot, Michael; Daneshvar, Michael A. ...
The Journal of urology,
01/2022, Letnik:
207, Številka:
1
Journal Article
Reply by Authors Williams, Cheyenne; Ahdoot, Michael; Daneshvar, Michael A ...
The Journal of urology,
01/2022, Letnik:
207, Številka:
1
Journal Article
Reply by Authors Williams, Cheyenne; Ahdoot, Michael; Daneshvar, Michael A ...
The Journal of urology,
01/2022, Letnik:
207, Številka:
1
Journal Article
The pathogenesis of multi-organ dysfunction associated with severe acute SARS-CoV-2 infection remains poorly understood. Endothelial damage and microvascular thrombosis have been identified as ...drivers of COVID-19 severity, yet the mechanisms underlying these processes remain elusive. Here we show alterations in fluid shear stress-responsive pathways in critically ill COVID-19 adults as compared to non-COVID critically ill adults using a multiomics approach. Mechanistic in-vitro studies, using microvasculature-on-chip devices, reveal that plasma from critically ill COVID-19 adults induces fibrinogen-dependent red blood cell aggregation that mechanically damages the microvascular glycocalyx. This mechanism appears unique to COVID-19, as plasma from non-COVID sepsis patients demonstrates greater red blood cell membrane stiffness but induces less significant alterations in overall blood rheology. Multiomics analyses in pediatric patients with acute COVID-19 or the post-infectious multi-inflammatory syndrome in children (MIS-C) demonstrate little overlap in plasma cytokine and metabolite changes compared to adult COVID-19 patients. Instead, pediatric acute COVID-19 and MIS-C patients show alterations strongly associated with cytokine upregulation. These findings link high fibrinogen and red blood cell aggregation with endotheliopathy in adult COVID-19 patients and highlight differences in the key mediators of pathogenesis between adult and pediatric populations.
We report a cell-mediated, targeted drug delivery system utilizing polyelectrolyte multilayer capsules that hybridize with the patient’s own platelets upon intravenous administration. The hybridized ...platelets function as the sensor and actuator for targeted drug delivery and controlled release in our system. These capsules are biochemically and mechanically tuned to enable platelet adhesion and capsule rupture upon platelet activation and contraction, enabling the targeted and controlled “burst” release of an encapsulated biotherapeutic. As platelets are the “first responders” in the blood clot formation process, this platelet-hybridized system is ideal for the targeted delivery of clot-augmenting biotherapeutics wherein immediate therapeutic efficacy is required. As proof-of-concept, we tailored this system to deliver the pro-clotting biotherapeutic factor VIII for hemophilia A patients that have developed inhibitory antifactor VIII antibodies. The polyelectrolyte multilayer capsules physically shield the encapsulated factor VIII from the patient’s inhibitors during circulation, preserving its bioactivity until it is delivered at the target site via platelet contractile force. Using an in vitro microfluidic vascular injury model with factor VIII-inhibited blood, we demonstrate a 3.8× increase in induced fibrin formation using capsules loaded with factor VIII at a concentration an order of magnitude lower than that used in systemic delivery. We further demonstrate that clot formation occurs 18 min faster when factor VIII loaded capsules are used compared to systemic delivery at the same concentration. Because platelets are integral in the pathophysiology of thrombotic disorders, cancer, and innate immunity, this paradigm-shifting smart drug delivery system can be similarly applied to these diseases.
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