The "BioHumi" Humeral Head Osteochondral Allograft Transplantation for Reverse Hill-Sachs Lesion of the Shoulder.

Osteochondral defects of the shoulder due to posterior instability are less frequent than those caused by anterior instability. Although uncommon, locked posterior dislocations can create sizable osteochondral lesions of the anterior humeral head known as reverse Hill-Sachs lesions. Treatment of these defects to restore the congruent contour of the glenohumeral joint is essential to reduce recurrence of instability and prevent long-term sequelae of arthritis. Historically, nonanatomic options, such as transposition of the subscapularis tendon or lesser tuberosity into the defect and humeral rotational osteotomy, have been endorsed to treat reverse Hill-Sachs lesions. More contemporary techniques have focused on restoring not only the bony architecture but also the chondral surface using fresh osteochondral allografts. The evolution of this approach has been challenging because of the large impacted wedge-shaped defect typically encountered with a locked posterior dislocation. Many surgeons employ techniques using multiple circular grafts or customizing a nonanatomic graft to fill these defects. Given the unstable nature of these grafts, metallic screws are often placed through the chondral surface for fixation. The evolution of the "BioHumi" technique has made treatment of large reverse Hill-Sachs lesions technically simpler and more reproducible using innovative instrumentation to transplant an elliptical osteochondral allograft.

Tuning the performance of CAR T cell immunotherapies.

BACKGROUND: Simultaneous advances in gene editing, T cell engineering and biotechnology currently provide an opportunity for rapid progress in medicine. The approval of chimeric antigen receptor (CAR) T cell therapies by the US Food and Drug Administration (FDA) and the European Commission have generated substantial momentum for these first-in-class therapies to be used in patients with B cell malignancies. MAIN BODY: Considerable efforts focus on improved outcomes and reduced side effects of the newly approved therapies. Using innovative strategies, researchers aim to extend CAR T cell use to tackle difficulties inherent in solid tumors. Efforts are underway to broaden the applications of CAR T cells, and the strategy has been successful in chronic viral infections and preclinical models of autoimmunity. Research is in progress to generate "off-the-shelf" CAR T cells, an advance, which would greatly increase patient availability and reduce treatment cost. CONCLUSIONS: In this thematic review, we highlight advances that may help develop genetically engineered cells into a new category of medical therapies.

Complications in a Young Adult Attributable to a Retained Pediatric Dynamic Hip Screw.

INTRODUCTION: Orthopedic implants are used for many different conditions in the pediatric population. The literature on hardware removal is controversial and vague. CASE REPORT: We highlight a young adult male who underwent a dynamic hip screw (DHS) due to a motor vehicle accident at 11 years old. He healed the fracture and did well for years. He was lost to follow-up and the hardware was never removed. The patient presented to our facility with a periprosthetic subtrochanteric proximal femur fracture just distal to the retained hardware. The DHS was removed and the fracture fixed with an intramedullary nail. The patient healed the fracture and did well. DISCUSSION: A literature review was performed to highlight the benefits and complications of hardware removal vs. retention. We hope to equip the orthopedic surgeon with the reasons for or against hardware removal to optimize treatment to each patient. In this instance, we recommend hardware removal due to the serious consequences of retained hardware in the adolescent/young adult population.

Registration of clinical volumes to beams-eye-view images for real-time tracking.

PURPOSE: The authors combine the registration of 2D beam's eye view (BEV) images and 3D planning computed tomography (CT) images, with relative, markerless tumor tracking to provide automatic absolute tracking of physician defined volumes such as the gross tumor volume (GTV). METHODS: During treatment of lung SBRT cases, BEV images were continuously acquired with an electronic portal imaging device (EPID) operating in cine mode. For absolute registration of physician-defined volumes, an intensity based 2D/3D registration to the planning CT was performed using the end-of-exhale (EoE) phase of the four dimensional computed tomography (4DCT). The volume was converted from Hounsfield units into electron density by a calibration curve and digitally reconstructed radiographs (DRRs) were generated for each beam geometry. Using normalized cross correlation between the DRR and an EoE BEV image, the best in-plane rigid transformation was found. The transformation was applied to physician-defined contours in the planning CT, mapping them into the EPID image domain. A robust multiregion method of relative markerless lung tumor tracking quantified deviations from the EoE position. RESULTS: The success of 2D/3D registration was demonstrated at the EoE breathing phase. By registering at this phase and then employing a separate technique for relative tracking, the authors are able to successfully track target volumes in the BEV images throughout the entire treatment delivery. CONCLUSIONS: Through the combination of EPID/4DCT registration and relative tracking, a necessary step toward the clinical implementation of BEV tracking has been completed. The knowledge of tumor volumes relative to the treatment field is important for future applications like real-time motion management, adaptive radiotherapy, and delivered dose calculations.

An initial study on the estimation of time-varying volumetric treatment images and 3D tumor localization from single MV cine EPID images.

PURPOSE: In this work the authors develop and investigate the feasibility of a method to estimate time-varying volumetric images from individual MV cine electronic portal image device (EPID) images. METHODS: The authors adopt a two-step approach to time-varying volumetric image estimation from a single cine EPID image. In the first step, a patient-specific motion model is constructed from 4DCT. In the second step, parameters in the motion model are tuned according to the information in the EPID image. The patient-specific motion model is based on a compact representation of lung motion represented in displacement vector fields (DVFs). DVFs are calculated through deformable image registration (DIR) of a reference 4DCT phase image (typically peak-exhale) to a set of 4DCT images corresponding to different phases of a breathing cycle. The salient characteristics in the DVFs are captured in a compact representation through principal component analysis (PCA). PCA decouples the spatial and temporal components of the DVFs. Spatial information is represented in eigenvectors and the temporal information is represented by eigen-coefficients. To generate a new volumetric image, the eigen-coefficients are updated via cost function optimization based on digitally reconstructed radiographs and projection images. The updated eigen-coefficients are then multiplied with the eigenvectors to obtain updated DVFs that, in turn, give the volumetric image corresponding to the cine EPID image. RESULTS: The algorithm was tested on (1) Eight digital eXtended CArdiac-Torso phantom datasets based on different irregular patient breathing patterns and (2) patient cine EPID images acquired during SBRT treatments. The root-mean-squared tumor localization error is (0.73 ± 0.63 mm) for the XCAT data and (0.90 ± 0.65 mm) for the patient data. CONCLUSIONS: The authors introduced a novel method of estimating volumetric time-varying images from single cine EPID images and a PCA-based lung motion model. This is the first method to estimate volumetric time-varying images from single MV cine EPID images, and has the potential to provide volumetric information with no additional imaging dose to the patient.

Antimicrobial activity of water-soluble triazole phenazine clickamers against E. coli.

The antimicrobial potency of phenazine derivatives is attenuated by their inherently hydrophobic nature, complicating their use as antibiotic drugs. We have analyzed the cytotoxicity and mode of action of water-soluble bis-triazolyl phenazines against E. coli and a human epithelial (HaCat) cell line. We observed complete inhibition of bacterial growth over concentration ranges that do not affect the viability of human epithelial cells. Confocal fluorescence microscopy revealed a high degree of interaction between the phenazine compounds and E. coli, as well as evidence of membrane damage in phenazine-treated E. coli. Additional data suggests that the potency of these particular water-soluble phenazine compounds does not result from the production of reactive oxygen species, but rather from cytotoxic interference with metabolic electron-transfer cascades.

Click to bind: metal sensors.

The copper-catalyzed azide-alkyne "click" cycloaddition reaction is an efficient coupling reaction that results in the formation of a triazole ring. The wide range of applicable substrates for this reaction allows the construction of a variety of conjugated systems. The additional function of triazoles as metal-ion ligands has led to the click reaction being used for the construction of optical sensors for metal ions. The triazoles are integral binding elements, which are formed in an efficient modular synthesis. Herein, we review recent examples of triazoles as a metal-binding element in conjugated metal-ion sensors.

Water-soluble bis-triazolyl benzochalcogendiazole cycloadducts as tunable metal ion sensors.

A series of bis-triazolyl benzochalcogendiazoles was synthesized to investigate their metal-binding capabilities. These fluorophores were formed through the cycloaddition of an ethynylated benzochalcogendiazole and a water-soluble azide. Variation of the chalcogen heteroatom was seen to affect the photophysical properties as well as the metal-binding activity. These cycloadducts exhibited a distinct response to Cu(2+), Ni(2+), and Ag(+) in water. The binding affinity for the copper and nickel ions increased moving the chalcogen atom from O to Se. Statistical analysis of the spectral data enabled differentiation of Ag(+), Cu(2+), and Ni(2+) ions.

Alkynylated phenazines: synthesis, characterization, and metal-binding properties of their bis-triazolyl cycloadducts.

We have synthesized a series of ethynylated phenazines and their bis-triazolyl cycloadducts to serve as metal ion sensors. Binding of metal ions is achieved through coordination to the phenazine nitrogen atom and the triazole ring. To allow metal sensing in aqueous solution, the triazole units are substituted with water-soluble ethylene glycol chains. These phenazine cycloadducts exhibit a selective affinity for binding silver ions. Examination of the halogenated analogues reveals a lowering of the band gap and the corresponding bathochromic shifts in the absorption and emission spectra. The electron-withdrawing properties of these halogens also result in significantly decreased metal-binding activity of the phenazine cycloadducts.

Water-soluble distyrylbenzenes: one core with two sensory responses--turn-on and ratiometric.

The synthesis of four water-soluble distyrylbenzenes (compounds 1-4) is reported. Their acidochromicity in aqueous media was investigated. Blue shifts and increases in the quantum yields were observed as a general response. The pH-dependent photophysics of 1b-3b in water reveal unexpected protonation sequences upon titration: compound 1b is green-yellow fluorescent at high pH (10) but becomes very weakly fluorescent between pH 5 and pH 3, whereas below pH 2 strong blue fluorescence is observed. This behavior can be explained in terms of the interplay in the protonation of aniline and of the carboxylate groups. In compound 4, a higher basicity of the amino group is observed and ratiometric fluorescence change takes place upon protonation or on reaction with zinc salts in water. Compound 4 can therefore act as a weak ratiometric zinc ligand in water, even though it has only a dimethylamino unit as a binding motif.