Treatment With Avacopan in Patients With Respiratory Tract Manifestations of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

Objective: The ADVOCATE trial demonstrated that treatment of active granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) with avacopan was noninferior in achieving remission at week 26 and superior for sustained remission at week 52 compared with a prednisone taper. This analysis of ADVOCATE evaluated the efficacy and safety of avacopan in patients with ear, nose, throat (ENT), or lung manifestations.

Methods: This post hoc analysis included patients enrolled in ADVOCATE with ENT or lung manifestations at baseline.

Identifying Molecular Pathophysiology and Potential Therapeutic Options in Iatrogenic Tracheal Stenosis.

Introduction: While most patients with iatrogenic tracheal stenosis (ITS) respond to endoscopic ablative procedures, approximately 15% experience a recalcitrant, recurring disease course that is resistant to conventional management. We aimed to explore genetic profiles of patients with recalcitrant ITS to understand underlying pathophysiology and identify novel therapeutic options.

Methods: We collected 11 samples of granulation tissue from patients with ITS and performed RNA sequencing.

Gene expression profiles in COVID-19-associated tracheal stenosis indicate persistent anti-viral response and dysregulated retinol metabolism.

Introduction: Coronavirus disease 2019 (COVID-19)-associated tracheal stenosis (COATS) may occur as a result of prolonged intubation during COVID-19 infection. We aimed to investigate patterns of gene expression in the tracheal granulation tissue of patients with COATS, leverage gene expression data to identify dysregulated cellular pathways and processes, and discuss potential therapeutic options based on the identified gene expression profiles.

Methods: Adult patients (age ≥ 18 years) presenting to clinics for management of severe, recalcitrant COATS were included in this study.

Novel composite trachea grafts using 3-dimensional printing.

Objective: Porcine-derived small intestine submucosa (SIS) extracellular matrix (ECM) surgical patches claim to have greater regenerative properties compared with dermal extracellular matrices. We hypothesized that using SIS-ECM in a bioengineered composite tracheal graft would allow better incorporation into the native tissue.

Methods: Two types of size-matched polycaprolactone support scaffolds were designed: rigid and flexible.

The relapsing polychondritis damage index (RPDAM): Development of a disease-specific damage score for relapsing polychondritis.

Objectives: Relapsing polychondritis is a rare, multi-systemic and inflammatory condition of unknown origin. We currently lack a core set of measures to assess and follow damage in patients suffering from this condition. Our primary aim was to derive a disease-specific damage measuring tool for relapsing polychondritis, the Relapsing Polychondritis Damage Index (RPDAM).

Circumferential Three-Dimensional-Printed Tracheal Grafts: Research Model Feasibility and Early Results.

Background: Methods for tracheal graft research have presented persistent challenges to investigators, and three-dimensional (3D)-printed biosynthetic grafts offer one potential development platform. We aimed to develop an efficient research platform for customizable circumferential 3D-printed tracheal grafts and evaluate feasibility and early structural integrity with a large-animal model.

Methods: Virtual 3D models of porcine subject tracheas were generated using preoperative computed tomography scans.

Three-Dimensional-Printed Bioengineered Tracheal Grafts: Preclinical Results and Potential for Human Use.

Background: We aimed to develop a process using three-dimensional (3D) printing to create bioengineered tracheal grafts (BETGs) for reconstruction of anterior tracheal defects in a large-animal model (porcine) that would have translational relevance for potential human use.

Methods: Preoperative computed tomographic scans were used to create virtual 3D models of the animal airways. Anatomically scaled tracheal grafts were subsequently developed using 3D-printed polycaprolactone and extracellular matrix.

Reconstruction of Anterior Tracheal Defects Using a Bioengineered Graft in a Porcine Model.

Background: Reconstruction of long-segment tracheal defects can be challenging and a suitable tracheal substitute remains lacking. We sought to create a bioengineered tracheal graft to repair such lesions using acellullar bovine dermis extracellular matrix (ECM) and male human mesenchymal stem cells (hMSCs) and implant it in a porcine model.

Methods: hMSCs were seeded on the ECM and incubated for 1 week with chondrogenic factors.

Treatment of Benign Tracheal Stenosis Using Endoluminal Spray Cryotherapy.

Importance: Tracheal stenosis is a debilitating disorder with heterogeneity in terms of disease characteristics and management. Repeated recurrences substantially alter patients' quality of life. There is limited evidence for the use of spray cryotherapy (SCT) in the management of benign airway disease.

Multilevel airway stenosis in patients with granulomatosis with polyangiitis (Wegener's).

Objectives: To describe the presentation and clinical course of subglottic stenosis (SGS), in particular the development of concurrent airway lesions, in patients with Granulomatosis with Polyangiitis (Wegener's) (GPA).

Materials And Methods: Retrospective review of clinical data from all patients presenting to our institution from 2000 to 2012 with SGS and GPA.

Results: Thirty-five patients were identified.

Effectiveness of rituximab for the otolaryngologic manifestations of granulomatosis with polyangiitis (Wegener's).

Objective: Ear, nose, and throat (ENT) involvement is the most prevalent manifestation of granulomatosis with polyangiitis (Wegener's) (GPA) and correlates with permanent damage and decreased quality of life. Although prior studies have evaluated the efficacy of rituximab (RTX) for granulomatous features of GPA, none have evaluated its efficacy solely for ENT manifestations. We compared the effectiveness of RTX to other therapies for the ENT manifestations of GPA in a large, well-characterized cohort.

The Relapsing Polychondritis Disease Activity Index: development of a disease activity score for relapsing polychondritis.

Objective: The rarity of relapsing polychondritis (RP) has hindered the development of standardized tools for clinical assessment. Here, we describe the development of a preliminary score for disease assessing activity in RP, the Relapsing Polychondritis Disease Activity Index (RPDAI).

Methods: Twenty-seven RP experts participated in an international collaboration.

Laryngeal manifestations of relapsing polychondritis and a novel treatment option.

Objectives: Laryngotracheal involvement in relapsing polychondritis (RP) is rare. However, it is one of the most common causes of death in this patient population. We present three patients who primarily presented with laryngeal manifestations of RP and a novel treatment option for bamboo nodules.

Timely airway stenting improves survival in patients with malignant central airway obstruction.

Background: The survival of patients with malignant central airway obstruction is very limited. Although airway stenting results in significant palliation of symptoms, data regarding improved survival after stenting for advanced thoracic cancer with central airway obstruction are lacking.

Methods: Fifty patients received a total of 72 airway stents for malignant central airway obstruction over a two-year period at a single institution.

Endoscopic tracheoplasty: segmental tracheal ring resection in a porcine model.

Endoscopic tracheoplasty is used for the relief of airway obstruction because of several benign conditions such as postintubation stenosis, inflammatory disorders such as Wegener granulomatosis, and benign neoplastic processes. Several endoscopic treatment modalities exist for these conditions, all with good initial results. However, recurrence is common and often requires frequent reintervention.

Intravenous delivery of 5'-iododeoxyuridine during hyperfractionated radiotherapy for locally advanced head and neck cancers: results of a pilot study.

Objectives: Locally advanced cancers of the head and neck require aggressive treatment, often with limited effectiveness and significant toxicity and morbidity. This pilot study was designed to assess tolerance using combined hyperfractionated radiotherapy and the halogenated pyrimidine radiosensitizer 5'-iododeoxyuridine (IdUrd).

Study Design: This was a prospective single-arm study open to patients with advanced head and neck cancers that had a poor chance of control with conventional radiation therapy.

Endolymphatic sac tumors. A source of morbid hearing loss in von Hippel-Lindau disease.

Objectives: Isolated reports suggest a possible association of endolymphatic sac tumors (ELSTs), which are extremely rare in the general population, with von Hippel-Lindau disease (VHL). To determine if hearing loss and ELSTs are a component of VHL, we examined prevalence, clinical presentation, and natural history of hearing loss and ELSTs in VHL.

Design: Brain magnetic resonance images (MRIs) from 374 patients screened for VHL were reviewed for evidence of ELSTs.

Human olfactory neuroepithelial cells: tyrosine phosphorylation and process extension are increased by the combination of IL-1beta, IL-6, NGF, and bFGF.

Olfactory neuroepithelial cells (ONC) grown from biopsies of human donors are a novel cell culture system that may facilitate studies into normal and disease-related human neurobiology. We further characterized the expression of cell surface markers and intermediate filaments, and responses to neurotrophic factors by ONC. ONC are positive for cell surface markers N-CAM, PSA-N-CAM, neutral endopeptidase, N-aminopeptidase, NGF low-affinity receptor homologue (CD40), and transferrin receptor by flow cytometry for the intermediate filament proteins peripherin, vimentin, and NF-H by immunocytochemistry.

Clinical features and therapeutic management of subglottic stenosis in patients with Wegener's granulomatosis.

Objective: To determine the clinical features and optimal treatment of subglottic stenosis (SGS) in patients with-Wegener's granulomatosis (WG).

Methods: Review of 43 patients with SGS and treatment of 20 patients with intratracheal dilation-glucocorticoid injection therapy.

Results: SGS developed in 43 of 189 patients with WG who were followed up at the National Institutes of Health Clinical Center.

Nasal mucosal cells in human immunodeficiency virus type 1-seropositive patients with sinusitis.

Recently, sinusitis has been recognized as a frequent clinical problem in human immunodeficiency virus (HIV-1)-infected individuals. We hypothesized that quantitative defects in immune cells in the nasal mucosa of HIV-positive subjects might mirror those in the peripheral blood and explain a predisposition to sinus disease in this population. Nasal mucosa biopsies were obtained from three different groups of patients-HIV-1 seropositive with sinusitis, HIV-1 seronegative with sinusitis, and HIV-1 seronegative without sinusitis (normal volunteer)-and phenotyped for cluster of differentiation antigen (CD) markers.