Individualized approach to elexacaftor/tezacaftor/ivacaftor dosing in cystic fibrosis, in response to self-reported anxiety and neurocognitive adverse events: A case series.

The prevalence of mental health disorders is high among people with Cystic Fibrosis. The psychological symptoms in CF are associated with poor adherence, worse treatment outcomes, and greater health utilization/cost. Mental health and neurocognitive Adverse Events (AEs) have been reported with all available Cystic Fibrosis Transmembrane conductance Regulator (CFTR) modulators in small groups of patients. We report our experience with a dose reduction strategy in 10 of our patients on elexacaftor/tezacaftor/ivacaftor (7.9% of total number of patients) who self-reported developing intense anxiety, irritability, sleep disturbance and/or mental slowness after initiation of full dose treatment. Standard dose elexacaftor/tezacaftor/ivacaftor resulted in 14.3 points improvement in mean Percent Predicted Forced Expiratory Volume in 1 s (ppFEV1), and a mean difference in sweat chloride of -39.3 mmol/L. We initially discontinued and/or reduced therapy according to the AEs severity, with a subsequent planned dose escalation every 4-6 weeks guided by sustainability of clinical effectiveness, absence of AEs recurrence, and patients' preferences. Clinical parameters including lung function and sweat chloride were monitored for up to 12 weeks to assess ongoing clinical response to the reduced dose regimen. Dose reduction resulted in resolution of self-reported mental/psychological AEs, without loss of clinical effectiveness (ppFEV1 was 80.7% on standard dose, and 83.4% at 12 weeks on reduced dose; sweat chloride was 33.4 and 34 mmol/L on standard and reduced dose, respectively). Furthermore, in a subgroup of patients who completed 24 weeks of the reduced dose regimen, repeat low dose Computed Tomography imaging showed a significant response when compared to pre-initiation of elexacaftor/tezacaftor/ivacaftor.

Single Use or Disposable Flexible Bronchoscopes: Bench Top and Preclinical Comparison of Currently Available Devices.

BACKGROUND: Data regarding the risk of infection related to reusable bronchoscopes, the global drive toward disposable technology and the COVID-19 pandemic have led to an increase in the use and production of single use or disposable bronchoscopes. An in-depth comparison of all available devices has not been published. METHODS: A benchtop comparison of the Ambu®aScopeTM, Boston Scientific® EXALTTM Model B, the Surgical Company Broncoflex© Vortex, Pentax® Medical ONE Pulmo™, and Vathin® H-SteriscopeTM (all 2.8 mm inner dimension other than the Pentax single-use flexible bronchoscope (3 mm)) was undertaken including measurement of maximal flexion and extension angles, thumb force required and suction with and without biopsy forceps. Thereafter, preclinical assessment was performed with data collected including experience, gender, hand size, and scope preference. RESULTS: The Vathin single-use flexible bronchoscope had the biggest range of tip movement from flexion to extension with and without forceps. The Boston single-use flexible bronchoscope required the maximal thumb force but had the least reduction of tip movement with forceps. The Boston single-use flexible bronchoscope significantly outperformed all other scopes including the standard Pentax scope and was the only scope capable of suctioning pseudo-mucus around the forceps. Although there was no significant difference in preference in the overall group, females and those with smaller hand size preferred the Pentax and males the Broncoflex single-use flexible bronchoscope. CONCLUSIONS: Currently available single-use flexible bronchoscopes differ in several factors other than scope sizes and monitor including suction, turning envelope, and handle size. Performance in the clinical setting will be key to their success.

A Malignant Connection: Bronchoesophageal-Pleural Fistula in an Elderly Farmer.

Bronchoesophageal-pleural fistula (BEPF) is a very rare entity that can present as a late manifestation of oesophageal malignancy. Here, we describe the case of an elderly farmer with no past medical history of note who presented with acute respiratory failure associated with a five-month history of dysphagia and weight loss. Computerised tomography of the thorax showed a connection between the oesophagus, bronchus and pleural space: a bronchoesophageal-pleural fistula. Ultrasound-guided thoracentesis was followed by chest drain insertion into an empyema containing food debris. Histopathological analysis of endoscopic biopsies confirmed an eroding squamous cell carcinoma (SCC) of the oesophagus. An oesophageal stent was inserted to seal off the fistula and broad-spectrum antibiotics were maximised. Ultimately, after four weeks in hospital, palliative therapy was initiated. BEPF remains a very rare and devastating complication of oesophageal malignancy. Endoscopic stenting may provide symptomatic relief.

Single-Use or Disposable Flexible Bronchoscopy in Advanced Bronchoscopy Procedures: Experience in a Quaternary Referral Centre.

BACKGROUND: The development of single-use flexible or disposable bronchoscopes (SUFBs) has accelerated in recent years, with the reduced risk of infectious transmission and reduced need for endoscopy staffing particularly advantageous in the COVID-19 pandemic era. OBJECTIVE: The objective of this study was to assess the performance of a novel single-use bronchoscope in an academic quaternary referral centre with on-site interventional pulmonology programme. METHODS: With ethical approval in a quaternary referral centre, we prospectively collected data on sequential bronchoscopy procedures using The Surgical Company Broncoflex© range of SUFBs. Data collected included demographic, procedural, scope performance, user satisfaction, and complication parameters in a tertiary bronchoscopy service. RESULTS: 139 procedures were performed by five pulmonology faculty from January to July 2021. The majority were carried out for infection (45%) and malignancy (32%). Most were performed in the endoscopy suite and 8% were COVID positive or suspected. Most procedures reported the highest score in satisfaction (85%) with technical limitations reported in 15% (predominately related to scope suction or inadequate image quality) reverting to a reusable scope in 2.8 %. CONCLUSION: In our subset of patients in a bronchoscopy unit, SUFBs are safe, and both routine and advanced bronchoscopy procedures can be performed with high satisfaction reported.