COVID-VU - ENT-UK national survey of flexible nasendoscopy in the upper aerodigestive tract amidst the COVID-19 pandemic.

BACKGROUND: Flexible nasendoscopy (FNE) is an invaluable multi-disciplinary tool for upper aerodigestive tract (UADT) examination. During the COVID-19 pandemic concerns were raised that FNE had the potential of generating aerosols resulting in human cross-contamination when performed on SARS-COV2 carriers. In the UK, and other European countries, national guidelines were issued restricting FNE to essential cases. We surveyed ENT-UK members and Royal College of Speech and Language Therapists (RCSLT) members to determine the impact of the COVID-19 pandemic (first peak) on FNE practice in the UK. METHODS: An observational internet-based survey constructed in accordance to the CHERRIES checklist and setup in SurveyMonkey of FNE practice amongst UK-based ENT surgeons and speech and language therapists in community clinics, the outpatient department, inpatient wards, ICU, emergency department and operating theatres (through the NHS and private sector) prior to, during and following the first COVID-19 wave in the UK. RESULTS: 314 responses collected (24% response rate), 82% from ENT clinicians, 17% from SLTs and 1% from other allied healthcare professionals. Overall, there has been a large reduction in the volume and indications for FNE during the first peak of the COVID-19 pandemic with limited recovery by mid-August 2020. Cancer and airway assessments were impacted less. A wide range of FNE protocols influenced by local factors are reported, varying in endoscope preference, Personal Protective Equipment (PPE) and sterilization methods. Where dedicated Aerosol Generating Procedure (AGP) rooms were unavailable, clinicians resorted to window opening and variable room "down-time" between patients. Endoscope preference reflected availability and user familiarity, ENT trainees favoring the use of single-use video endoscopes. CONCLUSION: Despite national guidance, local practice of FNE remains interrupted and highly variable in the UK. A collaborative inter-disciplinary approach is required to re-introduce FNE safely in volume across healthcare settings, re-establishing timely endoscopic diagnosis and pre-pandemic levels of patient care.

Is Small Cell Lung Cancer a Surgical Disease at the Present Time?

Small cell lung cancer is an aggressive form of cancer. Previously, surgery was rarely considered because most patients present at the advanced stages of the disease. New research and the advances in medical imaging has challenged this notion proving that, as part of a multimodal treatment pathway, surgery has a key role to play in the management of patients with early small cell lung cancer. In this chapter, we present the most pertinent research that has shaped clinical practice and outline the current treatment algorithm for small cell lung cancer.

Pamidronate "zebra lines": A treatment timeline.

Osteogenesis imperfecta is a hereditary bone dysplasia characterized by bone fragility, deformity, and short stature. Treatment focuses on preventing bone fractures and symptom relief. Pamidronate, a second-generation bisphosphonate drug that minimizes bone loss, is the chosen treatment in osteogenesis imperfecta. Radiologically, each cycle of pamidronate treatment is depicted as a line of sclerosed nondecalcified cartilage at the metaphysis, termed a pamidronate line. In this case report, we demonstrate that a treatment timeline can be visualized on plain radiographs as the number and spacing of pamidronate lines reflects the number and timing of treatment cycles. The educational value of this is to reassure physicians of the benign nature of "zebra lines," to demonstrate that the pamidronate lines migrate and fade with bone growth, and alert physicians that the lack of expected pamidronate lines during treatment may reflect a change in the patient's condition that reduces the effectiveness of bisphosphonate infusions.

CFTR potentiators partially restore channel function to A561E-CFTR, a cystic fibrosis mutant with a similar mechanism of dysfunction as F508del-CFTR.

BACKGROUND AND PURPOSE: Dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel causes the genetic disease cystic fibrosis (CF). Towards the development of transformational drug therapies for CF, we investigated the channel function and action of CFTR potentiators on A561E, a CF mutation found frequently in Portugal. Like the most common CF mutation F508del, A561E causes a temperature-sensitive folding defect that prevents CFTR delivery to the cell membrane and is associated with severe disease. EXPERIMENTAL APPROACH: Using baby hamster kidney cells expressing recombinant CFTR, we investigated CFTR expression by cell surface biotinylation, and function and pharmacology with the iodide efflux and patch-clamp techniques. KEY RESULTS: Low temperature incubation delivered a small proportion of A561E-CFTR protein to the cell surface. Like F508del-CFTR, low temperature-rescued A561E-CFTR exhibited a severe gating defect characterized by brief channel openings separated by prolonged channel closures. A561E-CFTR also exhibited thermoinstability, losing function more quickly than F508del-CFTR in cell-free membrane patches and intact cells. Using the iodide efflux assay, CFTR potentiators, including genistein and the clinically approved small-molecule ivacaftor, partially restored function to A561E-CFTR. Interestingly, ivacaftor restored wild-type levels of channel activity (as measured by open probability) to single A561E- and F508del-CFTR Cl(-) channels. However, it accentuated the thermoinstability of both mutants in cell-free membrane patches. CONCLUSIONS AND IMPLICATIONS: Like F508del-CFTR, A561E-CFTR perturbs protein processing, thermostability and channel gating. CFTR potentiators partially restore channel function to low temperature-rescued A561E-CFTR. Transformational drug therapy for A561E-CFTR is likely to require CFTR correctors, CFTR potentiators and special attention to thermostability.