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BackgroundObstructive sleep apnea (OSA) is an independent risk factor for cardiovascular (CV) morbidity and mortality, but the benefit of continuous positive airway pressure (CPAP) therapy is uncertain. However, most randomized-controlled trials have focused on the role of CPAP in secondary prevention although there is growing evidence of a potential benefit on early CV disease. Weight loss in combination with CPAP may be superior but is difficult to achieve and maintain with conventional measures alone. The aim of this study was to gain insights into the effect of CPAP on early atherosclerotic processes and to compare it to a glucagon-like-peptide (GLP)-1-mediated weight loss regimen in OSA.MethodsWe performed a randomized proof-of-concept study (clinicaltrials.gov:NCT04186494) comparing CPAP, a liraglutide-based weight loss regimen (Lir) alone or both in combination for 24 weeks in 30 non-diabetic patients with moderate to severe OSA (50±7 years, 80% males, apnea-hypopnea index [AHI] 50±19/hr, body mass index [BMI] 35.0 ±3 kg/m2). Baseline characteristics were similar between groups. Beside extensive evaluation for CV risk factors and endothelial function at baseline and end of study, subjects underwent 18F-fluorodeoxyglucose (FDG)-PET-CT for measurement of aortic wall inflammation (target-to-background ratio [TBR]) and coronary CT angiography (CCTA) for semi- automated coronary plaque analysis.ResultsCPAP alone and combination resulted in greater reduction in AHI than Lir alone at 24 weeks (mean difference -45/hr and -43/hr, respectively, vs -12/hr, pLow-attenuation coronary artery plaque volume as marker of unstable plaque also decreased with CPAP (from 571±490 to 334±185mm3) and with combination therapy (from 401±145 to 278±126mm3) but not with Lir.ConclusionThese data suggest that CPAP therapy, but not GLP-1 mediated weight loss, improves vascular inflammation and reduces low-attenuation coronary artery plaque volume in OSA patients. These novel findings support the benefit of CPAP therapy in modifying early CV disease.Clinical PerspectiveWhat is new?This is the first study comparing standard CPAP therapy to a GLP-1 mediated weight loss regimen in obstructive sleep apnea (OSA).The study utilized 18F-FDG PET CT and artificial intelligence-enabled coronary CT quantification of coronary artery plaque subtypes to determine treatment effects on early atherosclerotic disease processes.What are the clinical implications?CPAP in contrast to GLP-1-mediated weight loss may improve early atherosclerotic and potentially modifiable disease processes in obstructive sleep apnea (OSA).These data support the benefit of CPAP in the primary prevention of cardiovascular diseases in OSA.

Obstructive sleep apnea (OSA) is an increasingly prevalent health concern characterized by repeated episodes of pharyngeal collapse during sleep. It is frequently associated with daytime sleepiness and impaired functional capacity, but it is also linked to cardiovascular disease by a growing body of epidemiological, clinical, and translational research. The severity of OSA is traditionally evaluated by the apnea‑hypopnea index (AHI), but the value of this marker as a predictor of cardiovascular outcomes is limited. Thus, there is an increasing focus on alternative classification methods such as the hypoxic burden, other polysomnographic traits, and phenotypic subgroups based on clinical symptoms. There is a need to identify subgroups of patients with OSA who will benefit most from treatment, as recent large randomized controlled trials in selected populations have failed to show benefit in reducing overall cardiovascular mortality. Obstructive sleep apnea adversely affects cardiovascular structure and function by several distinct mechanisms such as intermittent hypoxia, sleep fragmentation, and intrathoracic pressure swings. These mechanisms lead to sympathetic activation, inflammation, and oxidative stress, which may result in the clinical consequences of OSA such as hypertension, coronary artery disease, heart failure, and cerebrovascular disease. This review focuses on the epidemiology and potential mechanisms of cardiovascular diseases in OSA. Furthermore, we will briefly discuss the role of personalized medicine, alternative treatment options, and precise phenotyping to optimize treatment of this complex condition and its associated cardiovascular risk.

Intermittent hypoxia (IH) plays a key role in the pathogenesis of insulin resistance (IR) in obstructive sleep apnoea (OSA). IH induces a pro-inflammatory phenotype of the adipose tissue with M1 macrophage polarisation, subsequently impeding adipocyte insulin signalling, and these changes are in striking similarity to those seen in obesity. However, the detailed molecular mechanisms of IH-induced macrophage polarisation are unknown and identification of same should lead to the identification of novel therapeutic targets. In the present study, we tested the hypothesis that IH acts through similar mechanisms as obesity, activating Toll-like-receptor (TLR)4/nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) and nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) signalling pathways leading to the upregulation and secretion of the key cytokines interleukin (IL)-1β and IL-6. Bone-marrow derived macrophages (BMDMs) from lean and obese C57BL/6 male mice were exposed to a state-of-the-art in vitro model of IH. Independent of obesity, IH led to a pro-inflammatory M1 phenotype characterised by increased inducible nitric oxide synthase and IL-6 mRNA expression, robust increase in NF-κB DNA-binding activity and IL-6 secretion. Furthermore, IH significantly increased pro-IL-1β mRNA and protein expression and mature IL-1β secretion compared to control treatment. Providing mechanistic insight, pre-treatment with the TLR4 specific inhibitor, TAK-242, prevented IH-induced M1 polarisation and upregulation of IL-1β mRNA and pro-IL-1β protein expression. Moreover, IH-induced increase in IL-1β secretion was prevented in BMDMs isolated from NLRP3 knockout mice. Thus, targeting TLR4/NF-κB and NLRP3 signalling pathways may provide novel therapeutic options for metabolic complications in OSA.

Sleep medicine is a rapidly developing field of medicine that is well-suited to initiatives such as Telehealth to provide safe, effective clinical care to an expanding group of patients. The increasing prevalence of sleep disorders has resulted in long waiting lists and lack of specialist availability. Telemedicine has potential to facilitate a move toward an integrated care model, which involves professionals from different disciplines and different organizations working together in a team-oriented way toward a shared goal of delivering all of a person's care requirements. Issues around consumer health technology and nonphysician sleep providers are discussed further in the article.

Background: The diagnostic work-up for suspected interstitial lung disease often includes surgical lung biopsy or VATs (Video-Assisted-Thoracoscopy) biopsy. VATs is recommended where the underlying diagnosis is in question and has been shown in the past to have relatively high mortality and morbidity rates. Aims: To evaluate the mortality, morbidity, diagnostic efficacy and outcomes associated with surgical lung biopsy via VATs. Methods: We carried out a retrospective review of 144 patients with suspected interstitial lung disease who underwent VATs lung biopsy between 2010 and 2016. Biopsies were carried out in three Irish centres. Our main outcome measures were mortality at 30 and 90 days, morbidity, histological diagnoses and correlation with suspected radiological diagnoses. Results: 30 day mortality following VATs biopsy was 4.4%. All 6 patients who died within 30 days were in the Intensive Care Unit (ICU) at time of biopsy. 90 day mortality was 7.9%. 24% of patients had some morbidity at 30 days, primarily pain and pneumothorax. The most commonly diagnosed condition on biopsy was Hypersensitivity Pneumonitis in 25% of cases, followed by Usual Intersitial Pneumonia (UIP) in 16% of cases. There was no mortality in UIP cases. A definitive diagnosis was made at VATs biopsy in all cases, in 82% of cases it provided a new diagnosis or altered clinical treatment. Conclusion: This large review finds that mortality following VATs biopsy was low and in line with international findings. The 30 day mortality rate was 0% in patients not in ICU at the time of biopsy. We found that VATs biopsy is safe and effective and should be considered where the diagnosis is in question.

e14683 Background: Colorectal cancer remains a significant cause of cancer related mortality worldwide. KRAS status has been used as a negative predictive marker. Its effect on the natural history ...

e15549 Background: Clinical stage one testicular seminoma has a survival rate over 99%. Current guidelines recommend Active Surveillance as the mainstay of treatment. The present analysis aims to i...