Drug-Induced Sleep Endoscopy Upper Airway Collapse Patterns and Maxillomandibular Advancement.

OBJECTIVES/HYPOTHESIS: To evaluate upper airway (UA) collapse patterns during drug-induced sleep endoscopy (DISE) and maxillomandibular advancement (MMA) surgery outcome, paying particular attention to the DISE phenotype complete concentric collapse at the level of the palate (CCCp). STUDY DESIGN: Prospective case series. METHODS: Nineteen patients diagnosed with obstructive sleep apnea (OSA) prospectively underwent mandibular advancement device (MAD) treatment followed by MMA surgery. UA collapse patterns were evaluated before and after MMA surgery. Baseline apnea-hypopnea index (AHI) was compared with AHI during MAD treatment and after MMA surgery. UA collapse patterns and the presence of baseline CCCp were assessed. AHI differences between patients with and without CCCp after MMA surgery were compared. RESULTS: In 14 patients, a full dataset was obtained: 8/6 (male/female), mean age = 51 ± 7 years, body mass index (BMI) = 25.6 ± 3.7 kg/m2 , and baseline AHI = 40.2 ± 25.6 per hour of sleep. MMA surgery reduced AHI to 9.9 ± 7.2 per hour of sleep (P = .0001). Eight patients benefited from additional AHI reduction compared to MAD treatment (P = .0113). Six out of 14 (43%) patients showed baseline CCCp. Baseline patient characteristics (age, BMI, and AHI) did not significantly differ between patients with and without CCCp. AHI was equally reduced after MMA, whether (P = .0145) or not (P = .0075) CCCp was present at baseline. All patients showed resolution of CCCp (P = .0159) during postoperative DISE. CONCLUSIONS: CCCp seems not to be a negative predictor for MMA surgery outcome measured by AHI reduction. Furthermore, MMA is likely to eliminate CCCp. Therefore, MMA might be a solution for OSA patients showing CCCp and broadens the perspective for personalized medicine and combination therapy. However, a large sample is required for definitive results. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:E268-E274, 2020.

Accelerated cellular senescence as underlying mechanism for functionally impaired bone marrow-derived progenitor cells in ischemic heart disease.

BACKGROUND AND AIMS: Bone marrow (BM)-derived progenitor cells are functionally impaired in patients with ischemic heart disease (IHD), thereby hampering the outcome of autologous stem cell therapy. In search for underlying mechanisms for this BM dysfunction, accelerated cellular senescence was explored. METHODS: We analysed telomere length of BM-derived mononuclear cells (MNC) by MMqPCR in patients with coronary artery disease (n = 12), ischemic heart failure (HF; n = 9), non-ischemic HF (n = 7) and controls (n = 10), and related it to their myeloid differentiation capacity. Expressions of senescence-associated genes p53, p21Cip1 and p16lnk4A; and telomere maintenance genes TERT, TRF1/2, Sirt1 in BM-MNC were evaluated using qPCR. Pro-inflammatory cytokine levels (TNFα, IFNy, IL-6) in BM were measured by MSD. RESULTS: BM-MNC telomere length was shortened in patients with IHD, irrespective of associated cardiomyopathy, and shortened further with increasing angiographic lesions. This telomere shortening was associated with reduced myeloid differentiation capacity of BM-MNC, suggesting accelerated senescence as underlying cause for progenitor cell dysfunction in IHD. Both p16lnk4A and p21Cip1 were activated in IHD and inversely related to myeloid differentiation capacity of BM-MNC; hence, the BM-MNC functional impairment worsens with increasing senescence. While BM-MNC telomere attrition was not related with alterations in TERT, TRF1/2 and Sirt1 expression, IFNy levels were associated with p21Cip1/p16lnk4A upregulation, suggesting a link between inflammation and cellular senescence. Still, the trigger for telomere shortening in IHD needs to be elucidated. CONCLUSIONS: Accelerated replicative senescence is associated with a functional impairment of BM-derived progenitor cells in IHD and could be targeted to improve efficacy of stem cell therapy.

Bone Marrow-Derived Progenitor Cells Are Functionally Impaired in Ischemic Heart Disease.

To determine whether the presence of ischemic heart disease (IHD) per se, or rather the co-presence of heart failure (HF), is the primum movens for less effective stem cell products in autologous stem cell therapy, we assessed numbers and function of bone marrow (BM)-derived progenitor cells in patients with coronary artery disease (n = 17), HF due to ischemic cardiomyopathy (n = 8), non-ischemic HF (n = 7), and control subjects (n = 11). Myeloid and erythroid differentiation capacity of BM-derived mononuclear cells was impaired in patients with underlying IHD but not with non-ischemic HF. Migration capacity decreased with increasing IHD severity. Hence, IHD, with or without associated cardiomyopathy, is an important determinant of progenitor cell function. No depletion of hematopoietic and endothelial progenitor cells (EPC) within the BM was observed, while circulating EPC numbers were increased in the presence of IHD, suggesting active recruitment. The observed myelosuppression was not driven by inflammation and thus other mechanisms are at play.

Health related quality of life after mandibular resection for oral and oropharyngeal squamous cell carcinoma.

The impact of several clinical parameters on health related quality of life (HrQOL) was evaluated in patients with squamous cell carcinoma adjacent or fixed to the mandible with special emphasis on postoperative radiotherapy and type of mandibular resection. One-hundred and five returned EORTC-questionnaires were available for this study. Correlation analyses were used to determine the relationship between clinical parameters and HrQOL. Postoperative radiotherapy was the clinical parameter that affected HrQOL most. The type of mandibular resection had no influence on HrQOL. The affected QOL-items were all associated with eating problems, i.e. use of a feeding tube, use of nutritional supplements, swallowing, social eating, mouth opening and dry mouth. Postoperative radiotherapy should only be applied if strictly indicated. This implies that the application of postoperative radiotherapy may need reconsideration in cases without strict criteria for postoperative radiotherapy.