Surface Modification of Porous Polyethylene Implants with an Albumin-Based Nanocarrier-Release System

Background: Porous polyethylene (PPE) implants are used for the reconstruction of tissue defects but have a risk of rejection in case of insufficient ingrowth into the host tissue. Various growth factors can promote implant ingrowth, yet a long-term gradient is a prerequisite for the mediation of these effects. As modification of the implant surface with nanocarriers may facilitate a long-term gradient by sustained factor release, implants modified with crosslinked albumin nanocarriers were evaluated in vivo. Methods: Nanocarriers from murine serum albumin (MSA) were prepared by an inverse miniemulsion technique encapsulating either a low-or high-molar mass fluorescent cargo. PPE implants were subsequently coated with these nanocarriers. In control cohorts, the implant was coated with the homologue non-encapsulated cargo substance by dip coating. Implants were consequently analyzed in vivo using repetitive fluorescence microscopy utilizing the dorsal skinfold chamber in mice for ten days post implantation. Results: Implant-modification with MSA nanocarri-ers significantly prolonged the presence of the encapsulated small molecules while macromolecules were detectable during the investigated timeframe regardless of the form of application. Conclusions: Surface modification of PPE implants with MSA nanocarriers results in the alternation of release kinetics especially when small molecular substances are used and therefore allows a prolonged factor release for the promotion of implant integration.</p

The role of structured reporting and structured operation planning in functional endoscopic sinus surgery

Computed tomography (CT) scans represent the gold standard in the planning of functional endoscopic sinus surgeries (FESS). Yet, radiologists and otolaryngologists have different perspectives on these scans. In general, residents often struggle with aspects involved in both reporting and operation planning. The aim of this study was to compare the completeness of structured reports (SR) of preoperative CT images and structured operation planning (SOP) to conventional reports (CR) and conventional operation planning (COP) to potentially improve future treatment decisions on an individual level. In total, 30 preoperative CT scans obtained for surgical planning of patients scheduled for FESS were evaluated using SR and CR by radiology residents. Subsequently, otolaryngology residents performed a COP using free texts and a SOP using a specific template. All radiology reports and operation plannings were evaluated by two experienced FESS surgeons regarding their completeness for surgical planning. User satisfaction of otolaryngology residents was assessed by using visual analogue scales. Overall radiology report completeness was significantly higher using SRs regarding surgically important structures compared to CRs (84.4 vs. 22.0%, p<0.001). SOPs produced significantly higher completeness ratings (97% vs. 39.4%, p<0.001) regarding pathologies and anatomical variances. Moreover, time efficiency was not significantly impaired by implementation of SR (148 s vs. 160 s, p = 0.61) and user satisfaction was significantly higher for SOP (VAS 8.1 vs. 4.1, p<0.001). Implementation of SR and SOP results in a significantly increased completeness of radiology reports and operation planning for FESS. Consequently, the combination of both facilitates surgical planning and may decrease potential risks during FESS

Photocleavable core cross-linked polymeric micelles of polypept(o)ides and ruthenium(II) complexes

Core cross-linking of polymeric micelles has been demonstrated to contribute to enhanced stability that can improve the therapeutic efficacy. Photochemistry has the potential to provide spatial resolution and on-demand drug release. In this study, light-sensitive polypyridyl-ruthenium(II) complexes were combined with polypept(o)ides for photocleavable core cross-linked polymeric micelles. Block copolymers of polysarcosine-block-poly(glutamic acid) were synthesized by ring-opening N-carboxyanhydride polymerization and modified with aromatic nitrile-groups on the glutamic acid side chain. The modified copolymers self-assembled into micelles and were cross-linked by cis-diaquabis(2,2'-bipyridine)-ruthenium(II) ([Ru(bpy)2(H2O)2]2+) or cis-diaquabis(2,2'-biquinoline)-ruthenium(II) ([Ru(biq)2(H2O)2]2+). Depending on the flexibility and hydrophobicity of the nitrile linker, either small spherical structures (Dh 45 nm, PDI 0.11) or worm-like micelles were obtained. The cross-linking reaction did not affect the overall size distribution but induced a change in the metal-to-ligand charge transfer peak from 482 to 420 nm and 592 to 548 nm. The cross-linked micelles displayed colloidal stability after incubation with human blood plasma and during gel permeation chromatography in hexafluoroisopropanol. Light-induced cleavage of [Ru(bpy)2(H2O)2]2+ was accomplished within 300 s, while [Ru(biq)2(H2O)2]2+ could not be completely released. Analysis in HuH-7 cells revealed increased cytotoxicity via micellar delivery of [Ru(bpy)2(H2O)2]2+ but mostly irradiation damage for [Ru(biq)2(H2O)2]2+. Further evaluation in ovo confirmed stable circulation pointing towards the future development of quick-release complexes.Drug Delivery Technolog

Impact of structured reporting on developing head and neck ultrasound skills

Background: Reports of head and neck ultrasound examinations are frequently written by hand as free texts. This is a serious obstacle to the learning process of the modality due to a missing report structure and terminology. Therefore, there is a great inter-observer variability in overall report quality. Aim of the present study was to evaluate the impact of structured reporting on the learning process as indicated by the overall report quality of head and neck ultrasound examinations within medical school education. Methods: Following an immersion course on head and neck ultrasound, previously documented images of three common pathologies were handed out to 58 medical students who asked to create both standard free text reports (FTR) and structured reports (SR). A template for structured reporting of head and neck ultrasound examinations was created using a web-based approach. FTRs and SRs were evaluated with regard to overall quality, completeness, required time to completion and readability by two independent raters (Paired Wilcoxon test, 95% CI). Ratings were assessed for inter-rater reliability (Fleiss’ kappa). Additionally, a questionnaire was utilized to evaluate user satisfaction. Results: SRs received significantly better ratings in terms of report completeness (97.7% vs. 53.5%, p &lt; 0.001) regarding all items. In addition, pathologies were described in more detail using SRs (70% vs. 51.1%, p &lt; 0.001). Readability was significantly higher in all SRs when compared to FTRs (100% vs. 54.4%, p &lt; 0.001). Mean time to complete was significantly lower (79.6 vs. 205.4 s, p &lt; 0.001) and user satisfaction was significantly higher when using SRs (8.5 vs. 4.1, p &lt; 0.001). Also, inter-rater reliability was very high (Fleiss’ kappa 0.93). Conclusions: SRs of head and neck ultrasound examinations provide more detailed information with a better readability in a time-saving manner within medical education. Also, medical students may benefit from SRs in their learning process due to the structured approach and standardized terminology

Dominant Glint Based Prey Localization in Horseshoe Bats: A Possible Strategy for Noise Rejection

Rhinolophidae or Horseshoe bats emit long and narrowband calls. Fluttering insect prey generates echoes in which amplitude and frequency shifts are present, i.e. glints. These glints are reliable cues about the presence of prey and also encode certain properties of the prey. In this paper, we propose that these glints, i.e. the dominant glints, are also reliable signals upon which to base prey localization. In contrast to the spectral cues used by many other bats, the localization cues in Rhinolophidae are most likely provided by self-induced amplitude modulations generated by pinnae movement. Amplitude variations in the echo not introduced by the moving pinnae can be considered as noise interfering with the localization process. The amplitude of the dominant glints is very stable. Therefore, these parts of the echoes contain very little noise. However, using only the dominant glints potentially comes at a cost. Depending on the flutter rate of the insect, a limited number of dominant glints will be present in each echo giving the bat a limited number of sample points on which to base localization. We evaluate the feasibility of a strategy under which Rhinolophidae use only dominant glints. We use a computational model of the echolocation task faced by Rhinolophidae. Our model includes the spatial filtering of the echoes by the morphology of the sonar apparatus of Rhinolophus rouxii as well as the amplitude modulations introduced by pinnae movements. Using this model, we evaluate whether the dominant glints provide Rhinolophidae with enough information to perform localization. Our simulations show that Rhinolophidae can use dominant glints in the echoes as carriers for self-induced amplitude modulations serving as localization cues. In particular, it is shown that the reduction in noise achieved by using only the dominant glints outweighs the information loss that occurs by sampling the echo

Impact of primary kidney disease on the effects of empagliflozin in patients with chronic kidney disease: secondary analyses of the EMPA-KIDNEY trial

Background: The EMPA KIDNEY trial showed that empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death in patients with chronic kidney disease mainly through slowing progression. We aimed to assess how effects of empagliflozin might differ by primary kidney disease across its broad population. Methods: EMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA). Patients were eligible if their estimated glomerular filtration rate (eGFR) was 20 to less than 45 mL/min per 1·73 m2, or 45 to less than 90 mL/min per 1·73 m2 with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher at screening. They were randomly assigned (1:1) to 10 mg oral empagliflozin once daily or matching placebo. Effects on kidney disease progression (defined as a sustained ≥40% eGFR decline from randomisation, end-stage kidney disease, a sustained eGFR below 10 mL/min per 1·73 m2, or death from kidney failure) were assessed using prespecified Cox models, and eGFR slope analyses used shared parameter models. Subgroup comparisons were performed by including relevant interaction terms in models. EMPA-KIDNEY is registered with ClinicalTrials.gov, NCT03594110. Findings: Between May 15, 2019, and April 16, 2021, 6609 participants were randomly assigned and followed up for a median of 2·0 years (IQR 1·5–2·4). Prespecified subgroupings by primary kidney disease included 2057 (31·1%) participants with diabetic kidney disease, 1669 (25·3%) with glomerular disease, 1445 (21·9%) with hypertensive or renovascular disease, and 1438 (21·8%) with other or unknown causes. Kidney disease progression occurred in 384 (11·6%) of 3304 patients in the empagliflozin group and 504 (15·2%) of 3305 patients in the placebo group (hazard ratio 0·71 [95% CI 0·62–0·81]), with no evidence that the relative effect size varied significantly by primary kidney disease (pheterogeneity=0·62). The between-group difference in chronic eGFR slopes (ie, from 2 months to final follow-up) was 1·37 mL/min per 1·73 m2 per year (95% CI 1·16–1·59), representing a 50% (42–58) reduction in the rate of chronic eGFR decline. This relative effect of empagliflozin on chronic eGFR slope was similar in analyses by different primary kidney diseases, including in explorations by type of glomerular disease and diabetes (p values for heterogeneity all &gt;0·1). Interpretation: In a broad range of patients with chronic kidney disease at risk of progression, including a wide range of non-diabetic causes of chronic kidney disease, empagliflozin reduced risk of kidney disease progression. Relative effect sizes were broadly similar irrespective of the cause of primary kidney disease, suggesting that SGLT2 inhibitors should be part of a standard of care to minimise risk of kidney failure in chronic kidney disease. Funding: Boehringer Ingelheim, Eli Lilly, and UK Medical Research Council