Prostate cancer treatment with Irreversible Electroporation (IRE): Safety, efficacy and clinical experience in 471 treatments.

BackgroundIrreversible Electroporation (IRE) is a novel image-guided tissue ablation technology that induces cell death via very short but strong pulsed electric fields. IRE has been shown to have preserving properties towards vessels and nerves and the extracellular matrix. This makes IRE an ideal candidate to treat prostate cancer (PCa) where other treatment modalities frequently unselectively destroy surrounding structures inducing severe side effects like incontinence or impotence. We report the retrospective assessment of 471 IRE treatments in 429 patients of all grades and stages of PCa with 6-year maximum follow-up time.Material and findingsThe patient cohort consisted of low (25), intermediate (88) and high-risk cancers (312). All had multi-parametric magnetic resonance imaging, and 199 men had additional 3D-mapping biopsy for diagnostic work-up prior to IRE. Patients were treated either focally (123), sub-whole-gland (154), whole-gland (134) or for recurrent disease (63) after previous radical prostatectomy, radiation therapy, etc. Adverse effects were mild (19.7%), moderate (3.7%) and severe (1.4%), never life-threatening. Urinary continence was preserved in all cases. IRE-induced erectile dysfunction persisted in 3% of the evaluated cases 12 months post treatment. Mean transient IIEF-5-Score reduction was 33% within 12-month post IRE follow-up and 15% after 12 months. Recurrences within the follow-up period occurred in 10% of the treated men, 23 in or adjacent to the treatment field and 18 outside the treatment field (residuals). Including residuals for worst case analysis, Kaplan Maier estimation on recurrence rate at 5 years resulted in 5.6% (CI95: 1.8-16.93) for Gleason 6, 14.6% (CI95: 8.8-23.7) for Gleason 7 and 39.5% (CI95: 23.5-61.4) for Gleason 8-10.ConclusionThe results indicate comparable efficacy of IRE to standard radical prostatectomy in terms of 5-year recurrence rates and better preservation of urogenital function, proving the safety and suitability of IRE for PCa treatment. The data also shows that IRE, besides focal therapy of early PCa, can also be used for whole-gland ablations, in patients with recurrent PCa, and as a problem-solver for local tumor control in T4-cancers not amenable to surgery and radiation therapy anymore

Overcoming synecdoche: why practice development and quality improvement approaches should be better integrated

Commentary on: Lavery, G. (2016) Quality improvement – rival or ally of practice development? International Practice Development Journal. Vol. 6. No. 1. Article 1

Hochauflösende MRI gegen Mehrschicht-CT, welche Technik stellt den trabekulären Knochen am Besten dar?

Das Ziel dieser Studie war es, Strukturparameter des trabek. Knochens von HR-MR und MS-CT Bildern zu akquirieren und mit den kontaktradiograph. Aufnahmen von korresp. Probeschnitten zu vergleichen.Es wurden signif. Korrelationen zwischen MR- und CT-ermittelten Strukturparam. sowie den in der kontaktradiograph. Aufnahme ermittelten Strukturparam. nachgewiesen. R-Werte bis zu 0,75 wurden für die HR-MR-Bilder ermittelt und bis zu 0,7 für die MS-CT. Im Durchschnitt zeigen sich höhere Korrelationen für die im MR als für die im CT ermittelten Daten. Für die MR-Daten war der Einfluss des so genannten "Threshold" Algorithmus beträchtlich.Die im HR-MR und MS-CT des distalen Radius ermittelten trabekulären Knochenstrukturparam. korrelierten signifikant mit den in den korrespondierten Makroschnitten bestimmten Parameter. Bei der Prädiktion der Knochenstruktur ist die HR-MR der MS-CT tendenziell überlegen

Tensegrity modelling and the high toughness of spider dragline silk

This work establishes a tensegrity model of spider dragline silk. Tensegrity systems are ubiquitous in nature, being able to capture the mechanics of biological shapes through simple and effective modes of deformation via extension and contraction. Guided by quantitative microstructural characterization via air plasma etching and low voltage scanning electron microscopy, we report that this model is able to capture experimentally observed phenomena such as the Poisson effect, tensile stress-strain response, and fibre toughness. This is achieved by accounting for spider silks’ hierarchical organization into microfibrils with radially variable properties. Each fibril is described as a chain of polypeptide tensegrity units formed by crystalline granules operating under compression, which are connected to each other by amorphous links acting under tension. Our results demonstrate, for the first time, that a radial variability in the ductility of tensegrity chains is responsible for high fibre toughness, a defining and desirable feature of spider silk. Based on this model, a discussion about the use of graded tensegrity structures for the optimal design of next-generation biomimetic fibres is presented

Characterizing cross‐linking within polymeric biomaterials in the SEM by secondary electron hyperspectral imaging

A novel capability built upon secondary electron (SE) spectroscopy provides an enhanced cross‐linking characterization toolset for polymeric biomaterials, with cross‐linking density and variation captured at a multiscale level. The potential of SE spectroscopy for material characterization has been investigated since 1947. The absence of suitable instrumentation and signal processing proved insurmountable barriers to applying SE spectroscopy to biomaterials, and consequently, capturing SE spectra containing cross‐linking information is a new concept. To date, cross‐linking extent is inferred from analytical techniques such as nuclear magnetic resonance (NMR), differential scanning calorimetry, and Raman spectroscopy (RS). NMR provides extremely localized information on the atomic scale and molecular scale, while RS information volume is on the microscale. Other methods for the indirect study of cross‐linking are bulk mechanical averaging methods, such as tensile and compression modulus testing. However, these established averaging methods for the estimation of polymer cross‐linking density are incomplete because they fail to provide information of spatial distributions within the biomaterial morphology across all relevant length scales. The efficacy of the SE spectroscopy capability is demonstrated in this paper by the analysis of poly(glycerol sebacate)‐methacrylate (PGS‐M) at different degrees of methacrylation delivering new insights into PGS‐M morphology

Revealing spider silk’s 3D nanostructure through low temperature plasma etching and advanced low-voltage SEM

The excellent mechanical properties of spider dragline silk are closely linked to its multiscale hierarchical structuring which develops as it is spun. If this is to be understood and mimicked, multiscale models must emerge which effectively bridge the length scales. This study aims to contribute to this goal by exposing structures within Nephila dragline silk using low-temperature plasma etching and advanced Low Voltage Scanning Electron Microscopy (LV-SEM). It is shown that Secondary Electron Hyperspectral Imaging (SEHI) is sensitive to compositional differences on both the micro and nano scale. On larger scales it can distinguish the lipids outermost layer from the protein core, while at smaller scales SEHI is effective in better resolving nanostructures present in the matrix. Key results suggest that the silks spun at lower reeling speeds tend to have a greater proportion of smaller nanostructures in closer proximity to one-another in the fiber, which we associate with the fiber's higher toughness but lower stiffness. The bimodal size distribution of ordered domains, their radial distribution, nanoscale spacings, and crucially their interactions may be key in bridging the length scale gaps which remain in current spider silk structure-property models. Ultimately this will allow successful biomimetic implementation of new models

Spinning beta silks requires both pH activation and extensional stress

Synthetic silk production has undergone significant technological and commercial advances over the past 5 years, with fibers from most labs and companies now regularly matching the properties of natural silk by one metric or another. Yet the fundamental links between silk protein processing and performance remain largely unresolved and fiber optimization is commonly achieved through non-natural methods. In an effort to address this challenge, data that closes this loop of processing and performance is presented by spinning a native silk feedstock ex vivo into a near-native fiber using just two naturally occurring parameters; pH activation and extensional flow (i.e., spinning rate). This allows us to link previous experimental and modelling hypothesis surrounding silk's pH responsiveness directly to multiscale hierarchical structure development during spinning. Finally, fibers that match, and then exceed, natural silk's mechanical properties are spun and understood by rate of work input. This approach not only provides energetic insights into natural silk spinning and controlled protein denaturation, but is believed will help interpret and improve synthetic silk processing. Ultimately, it is hoped that these results will contribute towards novel bioinspired energy-efficient processing strategies that are driven by work input optimization and where excellent mechanical properties are self-emergent

Vastus lateralis/vastus medialis cross-sectional area ratio impacts presence and degree of knee joint abnormalities and cartilage T2 determined with 3T MRI – an analysis from the incidence cohort of the Osteoarthritis Initiative

SummaryObjectiveTo study the role of vastus lateralis/vastus medialis cross-sectional area CSA ratio (VL/VM CSA ratio) in preclinical knee osteoarthritis (OA) using magnetic resonance imaging (MRI)-based cartilage T2 mapping technique and morphological analysis at 3.0T in non-symptomatic, middle-aged subjects.Material and methods174 non-symptomatic individuals aged 45–55 years with OA risk factors were selected from the Osteoarthritis Initiative (OAI) incidence cohort. OA-related knee abnormalities were analyzed using the whole-organ magnetic resonance imaging score (WORMS). Knee cartilage T2 maps were generated using sagittal 2D multi-echo spin-echo images of the right knee. CSA of thigh muscles was measured using axial T1W images of the right mid thigh. Spline-based segmentation of cartilage and muscles was performed on a SUN/SPARC workstation. Muscle measurements were normalized to body size using body surface area (BSA). Statistical significance was determined using Student’s t-test, Pearson correlation test, and multiple regression models. To correct for multiple testing, Bonferroni adjustments were applied across all tests within each of the primary results tables (Tables III–VII).ResultsHigher T2 values were associated with increased prevalence and severity of cartilage degeneration. In our study, male and female subjects with higher VL/VM CSA ratio demonstrated significantly lower mean cartilage T2 values (all compartments combined) (mean 44.10 vs 45.17, P=0.0017), and significantly lower WORMS scores (mean 14.12 vs 18.68, P=0.0316). Regression analyses of combined mean cartilage T2 using VL/VM CSA ratio as a continuous predictor showed a significant curvilinear relationship between these two variables (P=0.0082).ConclusionOur results suggested that higher VL/VM CSA ratio is associated with lower T2 values and decreased presence and severity of OA-related morphological changes. Additional studies will be needed to determine causality