[Assessment of Flexible Single-Use Rhinolaryngoscopes with Working Channel in the Upper Airways].

Flexible rhinolaryngoscopy is a frequently used ENT examination method. It is usually performed with reusable endoscopy systems. Since 2019, flexible single-use rhinolaryngoscopes from various manufacturers with and without a working channel are available on the German market.

Pharmacometrics-Enhanced Bayesian Borrowing for Pediatric Extrapolation - A Case Study of the DINAMO Trial.

Bayesian borrowing analyses have an important role in the design and analysis of pediatric trials. This paper describes use of a prespecified Pharmacometrics Enhanced Bayesian Borrowing (PEBB) analysis that was conducted to overcome an expectation for reduced statistical power in the pediatric DINAMO trial due to a greater than expected variability in the primary endpoint. The DINAMO trial assessed the efficacy and safety of an empagliflozin dosing regimen versus placebo and linagliptin versus placebo on glycemic control (change in HbA1c over 26 weeks) in young people with type 2 diabetes (T2D).

Duration of and time to response in oncology clinical trials from the perspective of the estimand framework.

Duration of response (DOR) and time to response (TTR) are typically evaluated as secondary endpoints in early-stage clinical studies in oncology when efficacy is assessed by the best overall response and presented as the overall response rate. Despite common use of DOR and TTR in particular in single-arm studies, the definition of these endpoints and the questions they are intended to answer remain unclear. Motivated by the estimand framework, we present relevant scientific questions of interest for DOR and TTR and propose corresponding estimand definitions.

Pharmacometrics enhanced Bayesian borrowing approach to improve clinical trial efficiency: Case of empagliflozin in type 2 diabetes.

We report use of a pharmacometrics enhanced Bayesian borrowing (PEBB) approach to leverage historical clinical trial data on a drug product to build models, project the outcome of future clinical trials, and borrow information from these projections to improve the efficiency of future target trials. This design takes a two-stage approach. First, a design phase is performed before target trial data are available to determine the operating characteristics and an appropriate tuning parameter that will be used in the subsequent analysis phase of a chosen target trial.

Real-world evidence for the effectiveness and safety of dupilumab in patients with CRSwNP after 1 year of therapy.

Objectives: For nearly 3 years, the monoclonal antibody dupilumab has been approved in Germany for the treatment of patients with chronic rhinosinusitis with nasal polyps (CRSwNP). Although efficacy has been demonstrated in large double-blind, placebo-controlled clinical trials, few reports of real-world data on this therapy have been published to date.

Methods: Patients with an indication for treatment with dupilumab for CRSwNP were included in the study and followed up every 3 months for a period of 1 year.

Propensity score stratified MAP prior and posterior inference for incorporating information across multiple potentially heterogeneous data sources.

Incorporation of external information is becoming increasingly common when designing clinical trials. Availability of multiple sources of information has inspired the development of methodologies that account for potential heterogeneity not only between the prospective trial and the pooled external data sources but also between the different external data sources themselves. Our approach proposes an intuitive way of handling such a scenario for the continuous outcomes setting by using propensity score-based stratification and then utilizing robust meta-analytic predictive priors for each stratum to incorporate the prior data to distinguish among different external data sources in each stratum.

Nasal residence time and rheological properties of a new bentonite-based thixotropic gel emulsion nasal spray - AM-301.

Objective: The present work provides characterization of rheological properties of a new bentonite-based thixotropic gel emulsion nasal spray (AM-301), its nasal residence time, distribution, safety and tolerability.

Significance: The nasal epithelium is a portal of entry for allergens and primary infection by airborne pathogens. Non-pharmacological interventions, which enhance physical and biological barriers, protect against allergens and pathogens without drug-related side effects.

A transfacet approach to the lumbar nerve root canal: technical note.

Background: Intraforaminal and extraforaminal nerve root compressions caused by disk herniation or stenosis are relatively common causes of lumbar radiculopathy. Currently, the two available surgical treatment methods are decompression from the spinal canal or lateral decompression via the Wiltse approach.

Objective: To describe a novel transosseous approach to the lumbar nerve root canal.

Xenon-Enhanced Dynamic Dual-Energy CT Is Able to Quantify Sinus Ventilation Using Laminar and Pulsating Air-/Gas Flow Before and After Surgery: A Pilot Study in a Cadaver Model.

Background: Chronic rhinosinusitis is a common disease with a significant impact on the quality of life. Topical drug delivery to the paranasal sinuses is not efficient to prevent sinus surgery or expensive biologic treatment in a lot of cases as the affected mucosa is not reached. More efficient approaches for topical drug delivery are, therefore, necessary.

ENT Residents Benefit from a Structured Operation Planning Approach in the Training of Functional Endoscopic Sinus Surgery.

: Preoperative planning utilizing computed tomographies (CT) is of utmost importance in functional endoscopic sinus surgery (FESS). Frequently, no uniform documentation and planning structures are available to residents in training. Consequently, overall completeness and quality of operation planning may vary greatly.

Incidence and Outcome of Aneurysmal Subarachnoid Hemorrhage: The Swiss Study on Subarachnoid Hemorrhage (Swiss SOS).

Background And Purpose: The purpose of this study was to assess nationwide incidence and outcomes of aneurysmal subarachnoid hemorrhage (aSAH). The Swiss SOS (Swiss Study on Subarachnoid Hemorrhage) was established in 2008 and offers the unique opportunity to provide this data from the point of care on a nationwide level.

Methods: All patients with confirmed aneurysmal subarachnoid hemorrhage admitted between January 1, 2009 and December 31, 2014, within Switzerland were recorded in a prospective registry.

Long-Term Reduction of Sacroiliac Joint Pain With Peripheral Nerve Stimulation.

Background: We recently demonstrated that 86% of the patients treated with peripheral nerve stimulation (PNS) for therapy-refractory sacroiliac joint (SIJ) pain were satisfied with the result after 1 year of treatment.

Objective: To investigate the long-term (up to 4 years) response rate of this novel treatment.

Methods: Sixteen consecutive patients with therapy-refractory SIJ pain were treated with PNS and followed for 4 years in 3 patients, 3 years in 6 patients, and 2 years in 1 patient.

Neonatal hypoxia-ischemia in rat increases doublecortin concentration in the cerebrospinal fluid.

Doublecortin (DCX) is a microtubule-associated protein widely used as an indicator of neurogenesis in immunohistochemical analyses of the postmortem adult brain. A recent study reported that DCX can be quantified in the cerebrospinal fluid (CSF) from healthy rats between postnatal day 0 (P0) and P30. However, it is currently unclear whether the concentration of DCX in the CSF (CSF-DCX) may represent a measure of endogenous neurogenesis.

Simulation-based adjustment after exploratory biomarker subgroup selection in phase II.

As part of the evaluation of phase II trials, it is common practice to perform exploratory subgroup analyses with the aim of identifying patient populations with a beneficial treatment effect. When investigating targeted therapies, these subgroups are typically defined by biomarkers. Promising results may lead to the decision to select the respective subgroup as the target population for a subsequent phase III trial.

Probability of success for phase III after exploratory biomarker analysis in phase II.

The probability of success or average power describes the potential of a future trial by weighting the power with a probability distribution of the treatment effect. The treatment effect estimate from a previous trial can be used to define such a distribution. During the development of targeted therapies, it is common practice to look for predictive biomarkers.

Reverse phase protein arrays enable glioblastoma molecular subtyping.

In the present study we investigated the phosphorylation status of the 12 most important signaling cascades in glioblastomas. More than 60 tumor and control biopsies from tumor center and periphery (based on neuronavigation) were subjected to selective protein expression analysis using reverse-phase protein arrays (RPPA) incubated with antibodies against posttranslationally modified cancer pathway proteins. The ratio between phosphorylated (or modified) and non-phosphorylated protein was assessed.

An Enzyme- and Serum-free Neural Stem Cell Culture Model for EMT Investigation Suited for Drug Discovery.

Epithelial to mesenchymal transition (EMT) describes the process of epithelium transdifferentiating into mesenchyme. EMT is a fundamental process during embryonic development that also commonly occurs in glioblastoma, the most frequent malignant brain tumor. EMT has also been observed in multiple carcinomas outside the brain including breast cancer, lung cancer, colon cancer, gastric cancer.

On confidence intervals for the hazard ratio in randomized clinical trials.

The log-rank test is widely used to compare two survival distributions in a randomized clinical trial, while partial likelihood (Cox, 1975) is the method of choice for making inference about the hazard ratio under the Cox (1972) proportional hazards model. The Wald 95% confidence interval of the hazard ratio may include the null value of 1 when the p-value of the log-rank test is less than 0.05.

Standard first-line chemotherapy with or without nintedanib for advanced ovarian cancer (AGO-OVAR 12): a randomised, double-blind, placebo-controlled phase 3 trial.

Background: Angiogenesis is a target in the treatment of ovarian cancer. Nintedanib, an oral triple angiokinase inhibitor of VEGF receptor, platelet-derived growth factor receptor, and fibroblast growth factor receptor, has shown activity in phase 2 trials in this setting. We investigated the combination of nintedanib with standard carboplatin and paclitaxel chemotherapy in patients with newly diagnosed advanced ovarian cancer.

Risk factors for postoperative CSF leakage after elective craniotomy and the efficacy of fleece-bound tissue sealing against dural suturing alone: a randomized controlled trial.

Object: Cerebrospinal fluid leakage is an immanent risk of cranial surgery with dural opening. Recognizing the risk factors for this complication and improving the technique of dural closure may reduce the associated morbidity and its surgical burden. The aim of this paper was to investigate whether the addition of TachoSil on top of the dural suture reduces postoperative CSF leakage compared with dural suturing alone and to assess the frequency and risk factors for dural leakage and potentially related complications after elective craniotomy.

Current practice in neuropsychological outcome reporting after aneurysmal subarachnoid haemorrhage.

Background: Neuropsychological deficits (NPD) are common in patients with aneurysmal subarachnoid haemorrhage (aSAH). NPD are one of the major limiting factors for patients with an otherwise acceptable prognosis for sustained quality of life. There are only a few studies reporting outcome after aSAH, which used a standardized neuropsychological test battery as a primary or secondary outcome measure.

Non-invasive neural stem cells become invasive in vitro by combined FGF2 and BMP4 signaling.

Neural stem cells (NSCs) typically show efficient self-renewal and selective differentiation. Their invasion potential, however, is not well studied. In this study, Sox2-positive NSCs from the E14.

Comparison of different autografts for aural cartilage in aesthetic rhinoplasty: is the tragal cartilage graft a viable alternative?

Auricular cartilage is an important source of grafts for various reconstructive procedures such as aesthetic rhinoplasty. The purpose of this investigation was to compare tragal cartilage with auricular cartilage harvested from the concha and scapha, and describe its clinical viability, indications, and morbidity in rhinoplasty. A total of 150 augmentation rhinoplasties with a total of 170 grafts were included.

Introducing a nationwide registry: the Swiss study on aneurysmal subarachnoid haemorrhage (Swiss SOS).

Background: Aneurysmal subarachnoid haemorrhage (aSAH) is a haemorrhagic form of stroke and occurs in a younger population compared with ischaemic stroke or intracerebral haemorrhage. It accounts for a large proportion of productive life-years lost to stroke. Its surgical and medical treatment represents a multidisciplinary effort.