[Position Paper: Perioperative Management of Adult Patients with Obstructive Sleep Apnea in ENT Surgery]. / Positionspapier zum perioperativen Management von erwachsenen Patienten mit obstruktiver Schlafapnoe bei HNO-ärztlichen Eingriffen.

Obstructive sleep apnea (OSA) is a common sleep-related breathing disorder with an increasing prevalence. Affected individuals suffer from a repetitive partial or complete occlusion of the pharyngeal airway despite continued respiratory efforts leading to sleep fragmentation, abnormal gas exchange and significant cardiovascular and metabolic morbidity. Surgical patients with OSA, which in the majority of cases has not been diagnosed prior to surgery, have an increased risk of developing a variety of pulmonary, cardiovascular and other complications throughout the perioperative period. Certain actions may contribute to increase the safety of patients with OSA during this time. Among them are preoperatively, a timely recognition and assessment of OSA and potentially co-existing diseases, intraoperatively, the selection of an appropriate anaesthesia and monitoring technique, and postoperatively, the continuation of monitoring for an adequate period of time with the option of intensive care treatment. The actual clinical approach should follow the risk profile of the individual patient which is determined by OSA severity, invasiveness of the surgical procedure and requirement for postoperative opioids as well as the incidence of critical events in the early postoperative period. Initiated and mandated by the German Society of Oto-Rhino-Laryngology, Head and Neck Surgery, and conceived on the basis of the available literature and existing guidelines, the following paper provides recommendations for the perioperative management of adult patients with OSA in ENT surgery.

Asymmetric-flow field-flow fractionation for measuring particle size, drug loading and (in)stability of nanopharmaceuticals. The joint view of European Union Nanomedicine Characterization Laboratory and National Cancer Institute - Nanotechnology Characterization Laboratory.

Asymmetric-flow field-flow fractionation (AF4) has been recognized as an invaluable tool for the characterisation of particle size, polydispersity, drug loading and stability of nanopharmaceuticals. However, the application of robust and high quality standard operating procedures (SOPs) is critical for accurate measurements, especially as these complex drug nanoformulations are most often inherently polydisperse. In this review we describe a unique international collaboration that lead to the development of a robust SOP for the measurement of physical-chemical properties of nanopharmaceuticals by multi-detector AF4 (MD-AF4) involving two state of the art infrastructures in the field of nanomedicine, the European Union Nanomedicine Characterization Laboratory (EUNCL) and the National Cancer Institute-Nanotechnology Characterisation Laboratory (NCI-NCL). We present examples of how MD-AF4 has been used for the analysis of key quality attributes, such as particle size, shape, drug loading and stability of complex nanomedicine formulations. The results highlight that MD-AF4 is a very versatile analytical technique to obtain critical information on a material particle size distribution, polydispersity and qualitative information on drug loading. The ability to conduct analysis in complex physiological matrices is an additional very important advantage of MD-AF4 over many other analytical techniques used in the field for stability studies. Overall, the joint NCI-NCL/EUNCL experience demonstrates the ability to implement a powerful and highly complex analytical technique such as MD-AF4 to the demanding quality standards set by the regulatory authorities for the pre-clinical safety characterization of nanomedicines.

Measuring particle size distribution of nanoparticle enabled medicinal products, the joint view of EUNCL and NCI-NCL. A step by step approach combining orthogonal measurements with increasing complexity.

The particle size distribution (PSD) and the stability of nanoparticles enabled medicinal products (NEP) in complex biological environments are key attributes to assess their quality, safety and efficacy. Despite its low resolution, dynamic light scattering (DLS) is the most common sizing technique since the onset of NEP in pharmaceutical technologies. Considering the limitations of the existing sizing measurements and the challenges posed by complex NEPs both scientists and regulators encourage the combination of multiple orthogonal high-resolution approaches to shed light in the NEP sizing space (e.g. dynamic light scattering, electron microscopy, field flow fractionation coupled to online sizing detectors, centrifugal techniques, particle tracking analysis and tunable resistive pulse sensing). The pharmaceutical and biotechnology developers are now challenged to find their own pragmatic characterisation approaches, which should be fit for purpose and minimize costs at the same time, in a complicated landscape where only a few standards exist. In order to support the community, the European Nanomedicine Characterisation Laboratory (EUNCL) and the US National Cancer Institute Nanotechnology Characterization Laboratory (NCI-NCL) have jointly developed multiple standard operating procedures (SOPs) for NEP assessment, including the measurements of particle size distribution, and are offering wide access to their 'state of the art' characterisation platforms, in addition to making SOPs publicly available. This joint perspective article would like to present the NCI-NCL and EUNCL multi-step approach of incremental complexity to measure particle size distribution and size stability of NEPs, consisting of a quick preliminary step to assess sample integrity and stability by low resolution techniques (pre-screening), followed by the combination of complementary high resolution sizing measurements performed both in simple buffers and in complex biological media. Test cases are presented to demonstrate: i) the need for employing at least one high-resolution sizing technique, ii) the importance of selecting the correct sizing techniques for the purpose, and iii) the robustness of utilizing orthogonal sizing techniques to study the physical properties of complex NEP samples.