Interleukin-7-dependent nonclassical monocytes and CD40 expression are affected in children with type 1 diabetes

The important role of IL-7 in the generation of self-reactive T-cells in autoimmune diseases is well established. Recent studies on autoimmunity-associated genetic polymorphisms indicated that differential IL-7 receptor (IL-7R) expression of monocytes may play a role in the underlying pathogenesis. The relevance of IL-7-mediated monocyte functions in type 1 diabetes remains elusive. In the present study, we characterized monocyte phenotype and IL-7-mediated effects in children with type 1 diabetes and healthy controls with multicolor flow cytometry and t-distributed Stochastic Neighbor-Embedded (t-SNE)-analyses. IL-7R expression of monocytes rapidly increased in vitro and was boosted through LPS. In the presence of IL-7, we detected lower monocyte IL-7R expression in type 1 diabetes patients as compared to healthy controls. This difference was most evident for the subset of nonclassical monocytes, which increased after IL-7 stimulation. t-SNE analyses revealed IL-7-dependent differences in monocyte subset distribution and expression of activation and maturation markers (i.e., HLA-DR, CD80, CD86, CD40). Notably, monocyte CD40 expression increased considerably by IL-7 and CD40/IL-7R co-expression differed between patients and controls. This study shows the unique effects of IL-7 on monocyte phenotype and functions. Lower IL-7R expression on IL-7-induced CD40_high monocytes and impaired IL-7 response characterize monocytes from patients with type 1 diabetes.     

Development of an Off-the-Shelf Tissue-Engineered Sinus Valve for Transcatheter Pulmonary Valve Replacement: a Proof-of-Concept Study

Tissue-engineered heart valves with self-repair and regeneration properties may overcome the problem of long-term degeneration of currently used artificial prostheses. The aim of this study was the development and in vivo proof-of-concept of next-generation off-the-shelf tissue-engineered sinus valve (TESV) for transcatheter pulmonary valve replacement (TPVR). Transcatheter implantation of off-the-shelf TESVs was performed in a translational sheep model for up to 16 weeks. Transapical delivery of TESVs was successful and showed good acute and short-term performance (up to 8 weeks), which then worsened over time most likely due to a non-optimized in vitro valve design. Post-mortem analyses confirmed the remodelling potential of the TESVs, with host cell infiltration, polymer degradation, and collagen and elastin deposition. TESVs proved to be suitable as TPVR in a preclinical model, with encouraging short-term performance and remodelling potential. Future studies will enhance the clinical translation of such approach by improving the valve design to ensure long-term functionality.     

Development of a Transcatheter Tricuspid Valve Prosthesis Through Steps of Iterative Optimization and Finite Element Analysis

The development of a transcatheter tricuspid valve prosthesis for the treatment of tricuspid regurgitation (TR) is presented. The design process involves an iterative development method based on computed tomography data and different steps of finite element analysis (FEA). The enhanced design consists of two self‐expandable stents, one is placed inside the superior vena cava (SVC) for primary device anchoring, the second lies inside the tricuspid valve annulus (TVA). Both stents are connected by flexible connecting struts (CS) to anchor the TVA‐stent in the orthotopic position. The iterative development method includes the expansion and crimping of the stents and CS with FEA. Leaflet performance and leaflet–stent interaction were studied by applying the physiologic pressure cycle of the right heart onto the leaflet surfaces. A previously implemented nitinol material model and a new porcine pericardium material model derived from uniaxial tensile tests were used. Maximum strains/stresses were approx. 6.8% for the nitinol parts and 2.9 MPa for the leaflets. Stent displacement because of leaflet movement was ≤1.8 mm at the commissures and the coaptation height was 1.6–3 mm. This led to an overall good performance of the prosthesis. An anatomic study showed a good anatomic fit of the device inside the human right heart.     

3D Image Registration Marginally Improves the Precision of HR-pQCT Measurements Compared to Cross-Sectional-Area Registration in Adults With Osteogenesis Imperfecta

Repositioning error in longitudinal high-resolution peripheral-quantitative computed tomography (HR-pQCT) imaging can lead to different bone volumes being assessed over time. To identify the same bone volumes at each time point, image registration is used. While cross-sectional area image registration corrects axial misalignment, 3D registration additionally corrects rotations. Other registration methods involving matched angle analysis (MA) or boundary transformations (3D-TB) can be used to limit interpolation error in 3D-registering micro-finite-element data. We investigated the effect of different image registration methods on short-term in vivo precision in adults with osteogenesis imperfecta, a collagen-related genetic disorder resulting in low bone mass, impaired quality, and increased fragility. The radii and tibiae of 29 participants were imaged twice on the same day with full repositioning. We compared the precision error of different image registration methods for density, microstructural, and micro-finite-element outcomes with data stratified based on anatomical site, motion status, and scanner generation. Regardless of the stratification, we found that image registration improved precision for total and trabecular bone mineral densities, trabecular and cortical bone mineral contents, area measurements, trabecular bone volume fraction, separation, and heterogeneity, as well as cortical thickness and perimeter. 3D registration marginally outperformed cross-sectional area registration for some outcomes, such as trabecular bone volume fraction and separation. Similarly, precision of micro-finite-element outcomes was improved after image registration, with 3D-TB and MA methods providing greatest improvements. Our regression model confirmed the beneficial effect of image registration on HR-pQCT precision errors, whereas motion had a detrimental effect on precision even after image registration. Collectively, our results indicate that 3D registration is recommended for longitudinal HR-pQCT imaging in adults with osteogenesis imperfecta. Since our precision errors are similar to those of healthy adults, these results can likely be extended to other populations, although future studies are needed to confirm this. © 2022 American Society for Bone and Mineral Research (ASBMR).     

Adherence with Use of Oral Agents in the Treatment of Chronic Hepatitis B

Oral nucleos(t)ide agents are used to prevent major complications of chronic hepatitis B infection, such as the development of cirrhosis, hepatic decompensation, hepatocellular carcinoma, and death. To achieve benefit, long-term, and potentially, life-long, antiviral therapy is needed to maintain adequately suppressed hepatitis B viral loads, and therefore, medication adherence is essential. However, long-term therapy may also be complicated by virological breakthrough and the development of antiviral resistance. This will be a brief review of the several recent studies that have examined how patient adherence affects virological outcomes, as well as the potential factors that can affect adherence to antiviral therapy for hepatitis B. infection.     

Optical nerve identification in head and neck surgery after Er:YAG laser ablation

Facial nerve function may be hampered by iatrogenic damage during head and neck laser surgery procedures. Optical techniques can serve as a basis for feedback-controlled tissue-specific laser surgery on the jaw bone and the parotid gland. In order to preserve nerve tissue during laser surgery, the alteration of optical tissue properties through laser-tissue interactions have to be taken into account. It was the aim of this study to evaluate the viability of optical tissue differentiation through diffuse reflectance spectroscopy after exposure to laser light as a basis for a feedback system for tissue-specific laser surgery. Spectra of diffuse reflectance (wavelength, 350–650 nm) of nerves, salivary glands, and cortical and cancellous bone of the midfacial region (ex vivo domestic pig heads) were acquired before/after Er:YAG laser (wavelength, 2.94 μm) ablation (each 16,800 spectra). Principal component analysis was computed followed by quadratic discriminant analysis. The tissue classification performance as well as area under the curve (AUC) sensitivity and specificity for tissue differentiation was assessed before and after laser-tissue exposure. A high classification performance was observed before laser ablation (total error, 7.74 %). Nerve tissue was differentiated from bone and salivary glands with results greater than 0.96 in AUC, sensitivity and specificity. After laser exposure, a total classification error of 18.61 % was observed. The differentiation of nerve tissue was reduced with an AUC of >0.94, sensitivity of >0.95, and specificity >0.87. Er:YAG laser ablation only slightly reduces the differentiation performance through diffuse reflectance in the investigated tissue types. The results show the general viability of diffuse reflectance spectroscopy in identifying neural structures in the vicinity of salivary glands and bone as a basis for nerve preservation during feedback-controlled laser surgery.