Novel, standardized sample collection from the brain-nose interface.

Background: Diagnostics for neurodegenerative diseases lack non-invasive approaches suitable for early-stage biochemical screening and routine examination of neuropathology. Biomarkers of neurodegenerative diseases pass through the brain-nose interface (BNI) and accumulate in nasal secretion. Sample collection from the brain-nose interface presents a compelling prospect as basis for a non-invasive molecular diagnosis of neuropathologies.

Treatment regimens for laryngeal and hypopharyngeal squamous cell carcinoma: a "real life" multicenter study of 2307 patients.

Objective: This retrospective multicenter study aimed to evaluate surgical versus conservative treatment in patients with hypopharyngeal and laryngeal cancer under real world conditions.

Methods: This study included 2307 patients diagnosed with hypopharyngeal or laryngeal squamous cell carcinoma (SCC) in five German tertiary head and neck centers between 01/2004 and 12/2014. Overall, 783 patients with advanced SCC consecutively underwent laryng(opharyng)ectomy (L(P)E).

In-line monitoring of solid dispersion preparation in small scale extrusion based on UV-vis spectroscopy.

The poor solubility of a large number of active pharmaceutical ingredients (APIs) is a major challenge in pharmaceutical research. Therefore, the extrusion of amorphous solid dispersions (ASDs) is one promising approach to enhance the dissolution rate by molecularly dissolving the API in an amorphous carrier polymer. During ASD extrusion, crucial parameters as the dissolution of the API in the carrier polymer need to be monitored.

UV-VIS spectra as potential process analytical technology (PAT) for measuring the density of compressed materials: Evaluation of the CIELAB color space.

Measurement methods for determining the density of compressed materials, being a critical quality attribute, provide an important parameter for successful processing. In this study, a novel approach was developed for determining the density of compacts using ultraviolet-visible spectrophotometry. The assumption within this context was that a change in density affects the corresponding color information of the compact.

Novel Cleaning-in-Place Strategies for Pharmaceutical Hot Melt Extrusion.

To avoid any type of cross-contamination, residue-free production equipment is of utmost importance in the pharmaceutical industry. The equipment cleaning for continuous processes such as hot melt extrusion (HME), which has recently gained popularity in pharmaceutical applications, necessitates extensive manual labour and costs. The present work tackles the HME cleaning issue by investigating two cleaning strategies following the extrusion of polymeric formulations of a hormonal drug and for a sustained release formulation of a poorly soluble drug.

Development and Validation of an In-Line API Quantification Method Using AQbD Principles Based on UV-Vis Spectroscopy to Monitor and Optimise Continuous Hot Melt Extrusion Process.

A key principle of developing a new medicine is that quality should be built in, with a thorough understanding of the product and the manufacturing process supported by appropriate process controls. Quality by design principles that have been established for the development of drug products/substances can equally be applied to the development of analytical procedures. This paper presents the development and validation of a quantitative method to predict the concentration of piroxicam in Kollidon VA 64 during hot melt extrusion using analytical quality by design principles.

The nasal valve: new insights on the static and dynamic NV with MR-imaging.

Purpose: We assessed the static nasal valve angle with MR imaging in healthy subjects and evaluated the complex mechanism of nasal valve dynamics during physiologic and forced inspiration.

Methods: In 17 healthy subjects, measurements of the static nasal valve angle were conducted on MR scans, using a TSE Axial T2-weighted sequence and a 3 mm slice thickness. The dynamic changes of nasal valve movement were detected using MR Cine-imaging techniques.

[Advantages of piezoelectric technology in rhinoplasty].

Background: Facial plastic and reconstructive surgery requires delicate, atraumatic handling of cartilage, bone and the surrounding soft tissue. Piezoelectric instrumentation (PEI) has previously been shown to be a precise and safe surgical instrument in rhinoplasty. It offers good preservation of surrounding soft tissue and high cutting precision and thus a good surgical applicability in rhinoplasty.

Investigations Concerning the Residence Time Distribution of Twin-Screw-Extrusion Processes as Indicator for Inherent Mixing.

Over recent years Twin-Screw-Extrusion (TSE) has been established as a platform technology for pharmaceutical manufacturing. Compared to other continuous operation, one of the major benefits of this method is the combination of several unit operations within one apparatus. Several of these are linked to the Residence Time Distribution (RTD), which is typically expressed by the residence time density function.

Vitronectin promotes the vascularization of porous polyethylene biomaterials.

Rapid implant vascularization is a prerequisite for successful biomaterial engraftment. Vitronectin (VN) is a matricellular glycoprotein well known for its capability to interact with growth factors, proteases, and protease inhibitors/receptors. Since such proteins are highly relevant for angiogenic processes, we hypothesized that VN contributes to the tissue integration of biomaterials.

Scale-Up and In-line Monitoring During Continuous Melt Extrusion of an Amorphous Solid Dispersion.

Chemical degradation of drug substances remains a major drawback of extrusion. Larger-scale extrusion equipment has advantages over smaller equipment due to deeper flight elements and added flexibility in terms of screw design, unit operations, and residence time. In a previous study, we extruded a meloxicam-copovidone amorphous solid dispersion (ASD) on a Nano-16 extruder and achieved 96.

In-Line UV-Vis Spectroscopy as a Fast-Working Process Analytical Technology (PAT) during Early Phase Product Development Using Hot Melt Extrusion (HME).

This paper displays the potential of an in-line PAT system for early phase product development during pharmaceutical continuous manufacturing following a Quality by Design (QbD) framework. Hot melt extrusion (HME) is used as continuous manufacturing process and UV⁻Vis spectroscopy as an in-line monitoring system. A sequential design of experiments (DoE) (screening, optimisation and verification) was used to gain process understanding for the manufacture of piroxicam (PRX)/Kollidon VA64 amorphous solid dispersions.

A 2-Year Follow-up Study of an Absorbable Implant to Treat Nasal Valve Collapse.

The safety and effectiveness of an absorbable implant for lateral cartilage support have been recently demonstrated in subjects with nasal valve collapse (NVC) at 12 months postprocedure. This follow-up study aimed to assess whether the safety and effectiveness of the implant persist in these patients for 24 months after the procedure. Thirty subjects with Nasal Obstruction Symptom Evaluation (NOSE) score ≥ 55 and isolated NVC were treated; 14 cases were performed in an operating suite under general anesthesia and 16 cases were performed in a clinic-based setting under local anesthesia.

Inline Determination of Residence Time Distribution in Hot-Melt-Extrusion.

In the framework of Quality-by-Design (QbD), the inline determination of process parameters or quality attributes of a product using sufficient process analytical technology (PAT) is a center piece for the establishment of continuous processes as a standard pharmaceutical technology. In this context, Twin-Screw-Extrusion (TSE) processes, such as Hot-Melt-Extrusion (HME), are one key aspect of current research. The main benefit of this process technology is the combination of different unit operations.

Inline UV/Vis spectroscopy as PAT tool for hot-melt extrusion.

Hot-melt extrusion on co-rotating twin screw extruders is a focused technology for the production of pharmaceuticals in the context of Quality by Design. Since it is a continuous process, the potential for minimizing product quality fluctuation is enhanced. A typical application of hot-melt extrusion is the production of solid dispersions, where an active pharmaceutical ingredient (API) is distributed within a polymer matrix carrier.

Use of a fibrinogen-thrombin sponge in rhinoplasty.

Background: Although several methods have been described to address nasal dorsum augmentation and smoothing of irregularities in rhinoplasty, establishing the ideal method has proven controversial.

Objective: Here, we introduce a novel technique of cartilage grafting for nasal dorsum augmentation by wrapping cartilage in a fibrinogen- and thrombin-coated collagen patch called TachoSil®.

Material And Methods: In a pilot study comprising ten cases, the use of the collagen patch was examined in various indications in rhinoplasty.

The Clinical Impact of Bet v 6 in Birch Pollen-Sensitized Patients.

Background: Bet v 6, a minor birch pollen allergen, is commercially available for allergen-specific IgE antibody testing. However, there is hardly any literature on the clinical impact of Bet v 6. The aim of the present study was to analyze if testing specific IgE against Bet v 6 can add valuable benefit to the standard diagnostics of birch pollen-sensitized patients, especially in patients with unknown sensitization-eliciting allergens.

Absorbable Implant to Treat Nasal Valve Collapse.

 To evaluate the safety and effectiveness of an absorbable implant for lateral cartilage support in subjects with nasal valve collapse (NVC) with 12 months follow-up.  Thirty subjects with Nasal Obstruction Symptom Evaluation (NOSE) score ≥ 55 and isolated NVC were treated; 14 cases were performed in an operating suite under general anesthesia and 16 cases were performed in a clinic-based setting under local anesthesia. The implant, a polylactic acid copolymer, was placed with a delivery tool within the nasal wall to provide lateral cartilage support.

Patient benefit from Cochlear implantation in single-sided deafness: a 1-year follow-up.

The objective of the study was to evaluate the quality of life and benefit in patients with single-side deafness before and 1 year after cochlear implantation. In a prospective observational study design, ten adult patients with single-sided deafness undergoing cochlear implantation were included. All patients had on the implantation side no speech discrimination with normal hearing aids.

Usefulness of component resolved analysis of cat allergy in routine clinical practice.

Background: Cat allergy is of great importance, and its prevalence is increasing worldwide. Cat allergens and house dust mite allergens represent the major indoor allergens; however, they are ubiquitous. Cat sensitization and allergy are known risk factors for rhinitis, bronchial hyperreactivity and asthma.