Development of a Novel Valve-Controlled Drug-Elutable Microstent for Microinvasive Glaucoma Surgery: In Vitro and Preclinical In Vivo Studies

Purpose: Microinvasive glaucoma surgery (MIGS) has become an important treatment approach for primary open-angle glaucoma, although the safe and long-term effective lowering of intraocular pressure with currently available implants for MIGS is not yet achieved to a satisfactory extent. The study focusses on the development and in vitro and in vivo testing of a novel microstent for MIGS. Methods: A silicone elastomer-based microstent was developed. Implants were manufactured using dip coating, fs-laser cutting, and spray coating. Within the current study no antifibrotic drug was loaded into the device. Sterilized microstents were analyzed in vitro regarding pressure–flow characteristics and biocompatibility. Six New Zealand white rabbits were implanted with a microstent draining the aqueous humor from the anterior chamber into the subconjunctival space. Drainage efficacy was evaluated using oculopressure tonometry as a transient glaucoma model. Noninvasive imaging was performed. Results: Microstents were manufactured successfully and characterized in vitro. Implantation in vivo was successful for four animals with additional device fixation. Without additional fixation, dislocation of microstents was found in two animals. Safe and effective intraocular pressure reduction was observed for the four eyes with correctly implanted microstent during the 6-month trial period. Conclusions: The described microstent represents an innovative treatment approach for MIGS. The incorporation of a selectively antifibrotic drug into the microstent drugelutable coating will be addressed in future investigations. Translational Relevance: The current preclinical study successfully provided proof of concept for our microstent for MIGS which is suitable for safe and effective intraocular pressure reduction and offers promising perspectives for the clinical management of glaucoma

Hypohidrotic Ectodermal Dysplasia and Immunodeficiency with Coincident NEMO and EDA Mutations

Ectodermal dysplasias (ED) are uncommon genetic disorders resulting in abnormalities in ectodermally derived structures. Many ED-associated genes have been described, of which ectodysplasin-A (EDA) is one of the more common. The NF-κB essential modulator (NEMO encoded by the IKBKG gene) is unique in that mutations result in severe humoral and cellular immunologic defects in addition to ED. We describe three unrelated kindreds with defects in both EDA and IKBKG resulting from X-chromosome crossover. This demonstrates the importance of thorough immunologic consideration of patients with ED even when an EDA etiology is confirmed, and raises the possibility of a specific phenotype arising from coincident mutations in EDA and IKBKG

Development of a biodegradable microstent for minimally invasive treatment of Fallopian tube occlusions

Obstructions of the Fallopian tube represent one of the most common reasons for an unfulfilled desire to have children. Microstent technology opens up new therapeutic possibilities to restore the natural lumen of the Fallopian tube within a single treatment. Within the current work we developed a self-expandable biodegradable microstent for gynecological applications. Based on a novel microstent design, prototypes were manufactured from poly-L-lactide tubing by means of fs-laser cutting. Microstent prototypes were characterized morphologically by means of scanning electron microscopy and biaxial laser scanning. As manufactured, a microstents outside diameter of about 2.3 mm and a strut thickness/width of about 114 µm/103 µm was measured. Mechanical characterization of microstents included bending as well as crimping and release behavior. After crimping to a minimum diameter of 0.8 mm and consecutive release, a microstent recovery to a diameter of 1.8 mm was found. Therefore, proof-of-concept for the self-expandable microstent could be successfully provided. © 2020 by Walter de Gruyter Berlin/Boston 2020

Efficacy and Safety of Hizentra®, a New 20% Immunoglobulin Preparation for Subcutaneous Administration, in Pediatric Patients with Primary Immunodeficiency

Subcutaneous IgG treatment for primary immunodeficiencies (PI) is particularly well suited for children because it does not require venous access and is mostly free of systemic adverse events (AEs). In a prospective, open-label, multicenter, single-arm, Phase III study, 18 children and five adolescents with PI were switched from previous intravenous (IVIG) or subcutaneous (SCIG) IgG treatment to receive dose-equivalent, weekly subcutaneous infusions of Hizentra® for 40 weeks. Mean IgG trough levels were maintained in patients previously on SCIG, or increased in those previously on IVIG, regardless of age. No serious bacterial infections were reported during the efficacy period of the study. The rates of non-serious infections were 4.77 (children) and 5.18 (adolescents) infections per patient per year. Related AEs were observed in seven children (38.9%) and two adolescents (40%). Three serious AEs and two AEs leading to discontinuation (all unrelated) were reported in children. Hizentra® is an effective and well-tolerated treatment for pediatric patients

Preventing and Reducing Coercive Measures—An Evaluation of the Implementation of the Safewards Model in Two Locked Wards in Germany

IntroductionAggression and violence are highly complex problems in acute psychiatry that often lead to the coercive interventions. The Safewards Model is an evidence-informed conflict-reduction strategy to prevent and reduce such incidents. The aim of this study was to evaluate the implementation of this model with regard to coercive interventions in inpatient care.Materials and MethodsWe evaluated outcomes of the implementation of the Safewards Model in two locked psychiatric wards in Germany. Frequency and duration of coercive interventions applied during a period of 11 weeks before and 11 weeks after the implementation period were assessed through routine data. Fidelity to the Safewards Model was assessed by the Organization Fidelity Checklist.ResultsFidelity to the Safewards Model was high in both wards. The overall use of coercive measures differed significantly between wards [case-wise: χ2 (1, n = 250) = 35.34, p ≤ 0.001; patient-wise: χ2 (1, n = 103) = 21.45, p ≤ 0.001] and decreased post-implementation. In one ward, the number of patients exposed to coercive interventions in relation to the overall number of Patients decreased significantly [χ2 (1, 281) = 6.40, p = 0.01]. Furthermore, the mean duration of coercive interventions overall declined significantly [U(55,21) = −2.142, p = 0.032] with an effect size of Cohen’s d = −0.282 (95% CI: −0.787, 0.222) in that ward. Both aspects declined as well in the other ward, but not significantly.DiscussionResults indicate that the implementation of the Safewards interventions according to the model in acute psychiatric care can reduce coercive measures. They also show the role of enabling factors as well as of obstacles for the implementation process

Risk and safety requirements for diagnostic and therapeutic procedures in allergology : World Allergy Organization Statement

Peer reviewe

Transient Euler-Lagrange/DEM simulation of stent thrombosis

Stent implantation is the treatment of choice for cardiovascular diseases. By introduction of biodegradable thick strut stents investigations of thrombosis formation is one focus of research. This study deals with a transient Euler-Lagrange/DEM approach to simulate the flow field, platelet movement and clotting. The recirculation zones prolong particle residence time. As a result, the vicinity of stent struts shown a particularly higher risk for stent thrombosis

Testing of dynamic wrist joint external fixator mobility and reaction moment

For the investigation of reaction moments of wrist joint with external fixator, a test device was developed that allows a well-defined investigation of the joint loads during hand flexion movements. The reaction moments are considered as a measure for the joint loads due to the constraint forces, which occur with differences of the rotation axis of the fixator device from the physiological rotation axis of the wrist joint. The developed test device allows a dynamic momentum load application into the wrist by a servohydraulic testing machine. This testing device converts the force to a moment by a constant lever arm and allows thereby the measurement of the reaction moments by the force load cell of the testing machine. Measurements on cadaveric wrist joints with external fixator can be thereby performed under reproducible conditions. The cadaveric wrist joints can be integrally casted into bone cement and thereby clamped to the testing device. Preliminary experiments with artificial bones showed that forces within the measuring range of the load cell of the testing machine can be measured. The design of the test device is presented. Hence, the requirements for measurements of the reaction moments with wrists with external fixator for distal radius fractures under dynamic loads are created