Katrin Hasselbacher

Outcome after one year of upper airway stimulation for obstructive sleep apnea in a multicenter German post‐market study

Upper airway stimulation (UAS) of the hypoglossal nerve has been implemented in the routine clinical practice for patients with moderate‐to‐severe obstructive sleep apnea (OSA) who could not adhere to continuous positive airway pressure. This study reports objective and patient‐reported outcome after 12 months of implantation.

Adherence to Upper-Airway Stimulation in the Treatment of OSA

AFFILIATIONS: From the Intermountain Heart Institute (Ms Van De Graaff; Messrs Benuzillo and Cable; and Drs Poll and Lappé), and the Pulmonary and Critical Care Division (Drs Beesley, Oniki, Hopkins, and Brown; and Ms Francis), Intermountain Medical Center; the Geriatric Research Education and Clinical Center (Dr Butler), George E. Wahlen Department of Veterans Affairs Medical Center; the Department of Medicine (Drs Beesley and Brown), University of Utah, Salt Lake City, UT; and the Psychology Department and Neuroscience Center (Dr Hopkins), Brigham Young University, Provo, UT. FINANCIAL/NONFINANCIAL DISCLOSURES: None declared. CORRESPONDENCE TO: Samuel M. Brown, MD, Shock Trauma ICU, Intermountain Medical Center, 5121 S Cottonwood St, Murray, UT 84107; e-mail: samuel.brown@imail.org Copyright 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved. DOI: https://doi.org/10.1016/j.chest.2017.09.046

Selective upper airway stimulation in older patients

OBJECTIVE Selective stimulation of the hypoglossal nerve has proven to be an effective therapy for patients with obstructive sleep apnea (OSA). The aim of the study is to investigate the efficacy of selective upper airway stimulation (sUAS) in older adults. METHODS All consecutive patients older than 64 years and who received an implant for sUAS were enrolled. As a control group, an equal number of patients younger than 65 years with matched apnea hypopnea index (AHI) and body-mass-index (BMI) were selected. Treatment outcome data were collected including daytime sleepiness as well as demographics with co-morbidities, BMI, adverse events and adherence to therapy. RESULTS 62 patients were included. Both the control and study group did not differ significantly for AHI, BMI, and Epworth Sleepiness Scale (ESS) (28.7-28.4/h; 30.1 to 28.4 kg/m2; 14.6 to 12.0 points); but co-morbidities were significantly higher in the study group. Our data showed no significant difference between the outcomes of study and control group for AHI, Oxygen desaturation index (ODI) and ESS (6.0-6.0/h; 7.9 to 5.5/h; 5.0 to 7.0 points). Serious adverse events did not occur in both groups and surgical implantation time did not differ. CONCLUSION sUAS leads to significant reductions of AHI, ODI and ESS in older patients. Despite higher age and more co-morbidities, surgical implantation time was not affected. Older patients showed higher usage of sUAS. Advanced age seems not to be a limiting factor for treatment outcomes of sUAS, thus indication for this treatment can also be applied to older people.

Nuclear expression of p65 (RelA) in patients receiving post-operative radiotherapy for locally advanced squamous cell carcinoma of the head and neck

BackgroundThis study investigated the prognostic role of nuclear expression of p65 in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) receiving post-operative radio(chemo)therapy.MethodsNuclear p65-expression (H-score ≤50 versus >50) plus twelve characteristics were analyzed in 151 patients for overall survival (OS), metastases-free survival (MFS) and loco-regional control (LRC). Additional characteristics included age, gender, Karnofsky performance score (KPS), pre-radiotherapy hemoglobin levels, tumor site, histological grading, human papilloma virus (HPV)-status, T-classification, N-classification, American Joint Committee on Cancer (AJCC)-stage, extent of resection and concurrent chemotherapy. Univariate analyses were performed with Kaplan-Meier method and log-rank test, multivariate analyses with Cox proportional hazards model.ResultsOn univariate analyses, p65-expression had a significant impact on OS (p < 0.001) and LRC (p < 0.001) but not on MFS (p = 0.29). On multivariate analysis, KPS ≥80 (risk ratio [RR] 2.23; p = 0.012), HPV-positivity (RR 5.83; p = 0.020), T1-T2 (RR 1.38; p = 0.048), N0-N2a (RR 2.72; p = 0.005) and complete resection (RR 2.02; p = 0.049) were positively associated with OS; p65-negativity achieved borderline significance (RR 3.02; p = 0.052). Better MFS was associated with KPS ≥80 (RR 2.49; p = 0.015), T1-T2 (RR: 1.74; p = 0.005), N0-N2a (RR: 6.22; p < 0.001) and complete resection (RR 3.43; p = 0.003). Positive associations with LRC were found for p65-negativity (RR 5.06; p = 0.008), T1-T2 (RR: 1.49; p = 0.022), N0-N2a (RR: 2.97; p = 0.004) and favorable tumor site (RR 1.28; p = 0.025).ConclusionsP65-negativity was significantly associated with improved LRC and achieved borderline significance with respect to improved OS. Thus, p65-expression may be an additional target for novel agents in the treatment of locally advanced SCCHN.

Upper-Airway Stimulation Before, After, or Without Uvulopalatopharyngoplasty: A Two-Year Perspective: UPPP in Upper Airway Stimulation

Upper airway stimulation (UAS) is an effective second‐line treatment for obstructive sleep apnea (OSA). In certain patients, there is a considerable need for advanced programming, notably with inadequate palatal response to therapy. The aim of the study was to investigate the impact of uvulopalatopharyngoplasty and tonsillectomy (UPPP‐TE) on UAS therapy outcomes from a 2‐year perspective after implantation.

In situ detection of PR3-ANCA+ B cells and alterations in the variable region of immunoglobulin genes support a role of inflamed tissue in the emergence of auto-reactivity in granulomatosis with polyangiitis

Circulating anti-neutrophilic cytoplasmic autoantibodies targeting proteinase 3 (PR3-ANCA) are a diagnostic and pathogenic hallmark of granulomatosis with polyangiitis (GPA). It is, however, incompletely understood if inflamed tissue supports presence or emergence of PR3-ANCA+ B cells. In search of such cells in inflamed tissue of GPA, immunofluorescence staining for IgG and a common PR3-ANCA idiotype (5/7 Id) was undertaken. Few 5/7 Id+/IgG+ B cells were detected in respiratory and kidney tissue of GPA. To gain more insight into surrogate markers possibly indicative of an anti-PR3-response, a meta-analysis comprising IGVH and IGVL genes derived from respiratory tract tissue of GPA (231 clones) was performed. Next generation sequencing-based IGHV genes derived from peripheral blood of healthy donors (244.353 clones) and previously published IGLV genes (148 clones) served as controls. Additionally, Ig genes of three murine and five known human monoclonal anti-PR3 antibodies were analyzed. Primary and probably secondary rearrangements led to altered VDJ usage and an extended complementarity determining region 3 (CDR3) of IGHV clones from GPA tissue. Selection against amino acid exchanges was prominent in the framework region of IGHV clones from GPA tissue. The comparison of V(D)J rearrangements and deduced amino acid sequences of the CDR3 yielded no identities and few similarities between clones derived from respiratory tissue of GPA and anti-PR3 antibodies, arguing against a presence of B cells that carry PR3-ANCA-prone Ig genes among the clones. In line with the scarcity of 5/7 Id+ B lymphocytes in GPA tissue, the results suggest that with respect to a local anti-PR3 response, methods detecting rare clones are required.

Pathogenetic and Clinical Aspects of Anti-Neutrophil Cytoplasmic Autoantibody-Associated Vasculitides

Anti-neutrophil cytoplasmic autoantibodies (ANCA) targeting proteinase 3 (PR3) and myeloperoxidase expressed by innate immune cells (neutrophils and monocytes) are salient diagnostic and pathogenic features of small vessel vasculitis, comprising granulomatosis with polyangiitis (GPA), microscopic polyangiitis, and eosinophilic GPA. Genetic studies suggest that ANCA-associated vasculitides (AAV) constitute separate diseases, which share common immunological and pathological features, but are otherwise heterogeneous. The successful therapeutic use of anti-CD20 antibodies emphasizes the prominent role of ANCA and possibly other autoantibodies in the pathogenesis of AAV. However, to elucidate causal effects in AAV, a better understanding of the complex interplay leading to the emergence of B lymphocytes that produce pathogenic ANCA remains a challenge. Different scenarios seem possible; e.g., the break of tolerance induced by a shift from non-pathogenic toward pathogenic autoantigen epitopes in inflamed tissue. This review gives a brief overview on current knowledge about genetic and epigenetic factors, barrier dysfunction and chronic non-resolving inflammation, necro-inflammatory auto-amplification of cellular death and inflammation, altered autoantigen presentation, alternative complement pathway activation, alterations within peripheral and inflamed tissue-residing T- and B-cell populations, ectopic lymphoid tissue neoformation, the characterization of PR3-specific T-cells, properties of ANCA, links between autoimmune disease and infection-triggered pathology, and animal models in AAV.

Primäres Plattenepithelkarzinom der Schilddrüse beim 90-Jährigen

Einleitung: Die notfallmasige Versorgung alter Patienten mit malignen Stenosen der oberen Atemwege stellt nach wie vor keine Standardsituation, sondern eine interdisziplinare Herausforderung dar. Methoden: Fallvorstellung eines 90-Jahrigen Patienten mit primar inoperablem Plattenepithelkarzinom der Schilddruse, linksseitigem medianen Stimmbandstillstand infolge Lahmung des N. recurrens, zirkularer Infiltration der Trachea, des Osophagus und des Mediastinums, der sich mit inspiratorischem Stridor und Dyspnoe in unserer Notfallambulanz vorstellte. Ergebnis: Nach linksseitiger definitiver Laterofixation nach Lichtenberger, Trachealstent-Einlage und PEG-Anlage konnte die ambulante definitive Strahlentherapie des Patienten in einem stabilen Allgemeinzustand, freier endolaryngealer Atmung und sehr guter Sprache mit anschliesender Erhaltungstherapie mit Cetuximab ohne Komplikationen durchgefuhrt werden. Diskussion: Anhand des Fallbeispiels wird die erfolgreiche palliative Therapie einer malignen Tracheal- und Larynxstenose unter Vermeidung einer Tracheostomie funf Monate nach Erstvorstellung diskutiert. Schlussfolgerung: Neue Kriterien zur Einschatzung der individuellen Durchfuhrbarkeit von Standardtherapien bei uber 80-Jahrigen Patienten mit malignen Erkrankungen der oberen Atemwege sind notwendig. Der Erstautor gibt keinen Interessenkonflikt an.