Suture button versus syndesmotic screw in ankle fractures - evaluation with 3D imaging-based measurements

Background Inadequate reduction of syndesmotic injuries can result in disabling clinical outcomes. The aim of the study was to compare syndesmosis congruity after fixation by syndesmotic screws (SYS) or a suture button system (SBS) using three-dimensional (3D) computed imaging techniques. Methods In a retrospective single-center study, patients with unilateral stabilization of an ankle fracture with a syndesmotic injury and post-operative bilateral CT scans were analyzed using a recently established 3D method. The side-to-side differences were compared for tibio-fibular clear space (∆CS), translation angle (∆α), and vertical offset (∆z) among patients stabilized with syndesmotic screws or suture button system. Syndesmotic malreduction was defined for ∆CS > 2 mm and for |∆α| > 5°. ∆CS and ∆α were correlated with two-dimensional (2D) measurements. Results Eighteen patients stabilized with a syndesmosis screw and 29 stabilized with a suture button system were analyzed. After stabilization, both groups revealed mild diastasis (SYS: mean ∆CS 0.3 mm, SD 1.1 mm vs SBS: mean ∆CS 0.2 mm, SD 1.2 mm, p = 0.710). In addition, both stabilization methods showed slight dorsalization of the fibula (SYS: mean ∆α 0.5°, SD 4.6° vs SBS: mean ∆α 2.1°, SD 3.7°, p = 0.192). Also, restoration of the fibula-to-tibia length ratio also did not differ between the two groups (SYS: mean Δz of 0.5 mm, SD 2.4 mm vs SBS: mean Δz of 0 mm, SD 1.2 mm; p = 0.477). Malreduction according to high ∆α was most common (26% of cases), with equal distribution between the groups (p = 0.234). ∆CS and ∆α showed good correlation with 2D measurements (ρ = 0.567; ρ = 0.671). Conclusion This in vivo analysis of post-operative 3D models showed no differences in immediate post-operative alignment after syndesmotic screws or suture button system. Special attention should be paid to syndesmotic malreduction in the sagittal orientation of the fibula in relation to the tibia in radiological control of the syndesmotic congruity as well as intra-operatively.

Dual Energy Computed Tomography (DECT) for Determination of Renal Calculi Composition - In-Vivo Analysis and In-Vitro Comparison with Qualitative Chemical Analysis - A Prospective Comparative Study at a Single Centre at SDM Medical College and Hospital – Dharwad, Karnataka

BACKGROUND Dual energy computed tomography (DECT) is a new method of computed tomography (CT) imaging which allows to determine stone composition in addition to assessing stone morphology. The purpose of this study was to evaluate the role of dual energy CT (DECT) preoperatively to assess the composition of urinary stones and to compare it with post-operative in vitro qualitative chemical analysis as reference standard. METHODS Forty patients (18 male and 22 female) who presented with symptoms of renal stones in the department of urology were included in the study. All 40 patients who were diagnosed to have renal stones clinically and by ultrasonography (USG) kidney, ureter and bladder (KUB) region were subjected to dual energy CT. The stone composition assessed in vivo using DECT preoperatively and in vitro by chemical analysis post operatively after stone extraction by surgical procedure. The results were compared by statistical analysis. Sensitivity, specificity and positive predictive value (PPV) were calculated and descriptive study done using Statistical Package for Social Sciences (SPSS) 20.00 version. Data was analysed by comparing it with correlative qualitative chemical analysis. RESULTS In our study, in vivo analysis using DECT showed most common type of stone was calcium oxalate seen in 20 cases compromising 50 % of total cases. Next common stone type was uric acid stone (22.5 %) followed by cysteine (17.5 %) and calcium hydroxyapatite (10 %) respectively. When the same stones were subjected to ex vivo chemical analysis, one of the calcium oxalate stone came out to be calcium phosphate and one of the cysteine stone came out to be mixed stone. Thus, out of 40 stones, 38 stones were found to have the same result in ex vivo chemical analysis as that of in vivo analysis by dual energy CT. Hence, accuracy of dual energy CT in diagnosis of renal stones was found to be 100 % with CI 91.19 % - 100 %. CONCLUSIONS With dual energy CT, it is possible to determine the composition of renal calculi in vivo non-invasively (with specificity of 100 % in our present study). Therefore, this helps in deciding the modality of treatment pre-operatively whether the stone is amenable to medical management (e.g., Uric acid stones) or requires extracorporeal shock wave lithotripsy (ESWL) or surgical intervention can be determined preoperatively. This helps to reduce the unnecessary financial burden and is found to be time saving. KEYWORDS Renal Calculus, Dual Energy CT, Stone Composition, Uric Acid Stones, Non-Uric Acid Stones, Attenuation, Hounsfield Units HU, Chemical Analysis of Stones.

Targeted Fluorogenic Cyanine Carbamates Enable In Vivo Analysis of Antibody-Drug Conjugate Linker Chemistry

Antibody-drug conjugates (ADCs) are a rapidly emerging therapeutic platform. The chemical linker between the antibody and the drug payload plays an essential role in the efficacy and tolerability of these agents. New methods that quantitively assess cleavage efficiency in complex tissue settings could provide valuable insights into the ADC design process. Here we report the development of a near-infrared (NIR) optical imaging approach that measures the site and extent of linker cleavage in mouse models. This approach is enabled by a superior variant of our recently devised cyanine carbamate (CyBam) platform. We identify a novel tertiary amine-containing norcyanine, the product of CyBam cleavage, that exhibits dramatically in-creased cellular signal due to improved cellular permeability and lysosomal accumulation. The resulting cyanine lysosome-targeting carbamates (CyLBams) are ~50X brighter in cells, and we find this strategy is essential for high-contrast in vivo targeted imaging. Finally, we compare a panel of several common ADC linkers across two antibodies and tumor models. These studies indicate that cathepsin-cleavable linkers provide dramatically higher tumor activation relative to hindered or non-hindered disulfides – an observation that is only apparent with in vivo imaging. This strategy enables quantitative comparisons of cleavable linker chemistries in complex tissue settings with implications across the drug delivery landscape.

Targeted Fluorogenic Cyanine Carbamates Enable In Vivo Analysis of Antibody-Drug Conjugate Linker Chemistry

Antibody-drug conjugates (ADCs) are a rapidly emerging therapeutic platform. The chemical linker between the antibody and the drug payload plays an essential role in the efficacy and tolerability of these agents. New methods that quantitively assess cleavage efficiency in complex tissue settings could provide valuable insights into the ADC design process. Here we report the development of a near-infrared (NIR) optical imaging approach that measures the site and extent of linker cleavage in mouse models. This approach is enabled by a superior variant of our recently devised cyanine carbamate (CyBam) platform. We identify a novel tertiary amine-containing norcyanine, the product of CyBam cleavage, that exhibits dramatically in-creased cellular signal due to improved cellular permeability and lysosomal accumulation. The resulting cyanine lysosome-targeting carbamates (CyLBams) are ~50X brighter in cells, and we find this strategy is essential for high-contrast in vivo targeted imaging. Finally, we compare a panel of several common ADC linkers across two antibodies and tumor models. These studies indicate that cathepsin-cleavable linkers provide dramatically higher tumor activation relative to hindered or non-hindered disulfides – an observation that is only apparent with in vivo imaging. This strategy enables quantitative com-parisons of cleavable linker chemistries in complex tissue settings with implications across the drug delivery landscape.