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Introduction Exercise is one of several factors known to lower the risk of developing cancer, as well as improve outcomes in patients already diagnosed. People who exercise after cancer have lower rates of cancer complications, treatment toxicities, relapse and improved survival. This review highlights the supportive data and biochemical processes, which explain these potential benefits. Sources of data PubMed, Embase, Medline and Cochrane libraries were searched for papers which addressed the effects of exercise and physical activity on cancer for this review. The search terms used were physical activity, exercise and cancer up to February 2021. We also referred to the background research required for international exercise intervention study involving men with prostate cancer (INTERVAL-GAP4) and scrutinized references within the robust papers published on this subject to ensure we did not miss any clinically studies. One hundred and eighty eight papers were included. Areas of agreement Exercise programmes mitigate many of the complications and risks associated with cancer, particularly thromboembolism, fatigue, weight gain, arthralgia, cognitive impairment and depression. Areas of controversy Molecular and biomarker changes, resulting from exercise, suggest that exercise elicits beneficial changes in insulin-related pathways, down-regulates inflammation and serum oestrogen levels, and enhances oxidative, immune and cellular repair pathways. Nonetheless, the evidence remains preliminary. Growing points The timing, intensity and challenges of prehabilitation, adjunct and rehabilitation exercise programmes are being increasingly understood but their implementation remains sporadic. Areas for developing research More robust clinical trial data are needed to substantiate a causal effect of exercise on overall and cancer-specific survival. These studies are ongoing. Research evaluating the most cost-efficient ways of incorporating prehabilitation, adjunct and rehabilitation programmes into routine practice would be helpful to funding bodies and health care strategists.

Background Assess if changes in sleep quality (Sleep Quality Index, SQI) based on cardiopulmonary coupling-analysis (CPC) impacts serum adiponectin-levels in patients with cardiovascular disease (CVD). Methods Secondary analysis of electrocardiogram (ECG) data from the Heart Biomarker Evaluation in Apnea Treatment study (HeartBEAT), a multicenter, controlled trial in patients with CVD and moderate-severe sleep apnea, randomly assigned to intervention of Continuous Positive Airway Pressure (CPAP), Nocturnal Supplemental Oxygen (NSO) or Healthy Lifestyle and Sleep Hygiene Education (HLSE; control group). Participants with good-quality ECG-signal (n = 241) were included. Results Improving CPC-sleep quality was associated with net average improvements in serum adiponectin-levels 2.69 μg/ml (p = 0.005) irrespective of therapy initiated. After controlling for confounders, a unit increase in SQI was associated with increase in serum adiponectin-levels 0.071 μg/ml (p = 0.012) and decrease in insulin-levels 0.197 μIU/ml (p = 0.0018). Similarly, a percentage point increase in sleep apnea indicator (SAI) was associated with decrease in serum adiponectin-levels of 0.071 μg/ml (p = 0.017) and increase in insulin-levels of 0.218 μIU/ml (p = 0.020). A percentage point increase in CPC-sleep fragmentation (eLFCBB) had a predicted increase in glucose-levels 0.371 mg/dl (p = 0.009) and insulin-levels 0.284 μIU/ml (p = 0.010). In patients receiving CPAP-therapy, a difference in serum adiponictin levels of 3.82 μg/ml (p = 0.025) is observed comparing patients in which SQI-improved to patients that SQI-declined during the study period. The difference is mostly due to a decrease in serum adiponectin levels in patients that decline in SQI (−3.20 μg/ml). Conclusion Improvements in sleep quality were associated with higher serum adiponectin-levels, and improved measures of glycemic metabolism which may have beneficial effects on metabolic syndrome and cardiovascular health. Clinical trial registration name and number The Heart Biomarker Evaluation in Apnea Treatment (HeartBEAT) study is registered at https://clinicaltrials.gov/ct2/show/NCT01086800 .

STUDY OBJECTIVES: The recognition of specific endotypes as drivers of sleep apnea suggests the need of therapies targeting individual mechanisms. Acetazolamide is known to stabilize respiration at high altitude but benefits at sea level are less well understood. METHODS: All controlled studies of acetazolamide in obstructive sleep apnea and/or central sleep apnea (CSA) were evaluated. The primary outcome was the apnea-hypopnea index. RESULTS: Fifteen trials with a total of 256 patients were pooled in our systematic review. Acetazolamide reduced the overall apnea-hypopnea index (mean difference [MD] −15.82, 95% CI: −21.91 to −9.74, P < .00001) in central sleep apnea (MD −22.60, 95% CI: −29.11 to −16.09, P < .00001), but not in obstructive sleep apnea (MD −10.29, 95% CI: −33.34 to 12.77, P = .38). Acetazolamide reduced the respiratory related arousal index (MD −0.82, 95% CI: −1.56 to −0.08, P = .03), improved partial arterial of oxygen (MD 11.62, 95% CI: 9.13–14.11, P < .00001), mean oxygen saturation (MD 1.78, 95% CI: 0.53–3.04, P = .005), total sleep time (MD 25.74, 95% CI: 4.10–47.38, P = .02), N2 sleep (MD 3.34, 95% CI: 0.12–6.56, P = .04) and sleep efficiency (MD 4.83, 95% CI: 0.53–9.13, P = .03). CONCLUSIONS: Acetazolamide improves the apnea-hypopnea index and several sleep metrics in central sleep apnea. The drug may be of clinical benefit in patients with high loop gain apnea of various etiologies and patterns. The existence of high heterogeneity is an important limitation in applicability of our analysis. SYSTEMATIC REVIEW REGISTRATION: Registry: PROSPERO; Name: The effect of acetazolamide in patients with sleep apnea at sea level: a systematic review and meta analysis; URL: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020163316; Identifier: CRD42020163316. CITATION: Ni Y-N, Yang H, Thomas RJ. The role of acetazolamide in sleep apnea at sea level: a systematic review and meta-analysis. J Clin Sleep Med. 2021;17(6):1295–1304.

Background While obesity is linked with brain atrophy and dementia incidence, associations with regional adiposity are uncertain. Our goal was to determine whether cerebral gray matter volume is related to neck circumference (NC), a measure of regional adiposity having unique relationships with metabolic disorders and cardiovascular disease. Methods Magnetic resonance imaging and NC were cross-sectionally assessed from 2011 to 2014 in a population-based sample of 2916 men and women in the Korean Genome and Epidemiology Study. Results For men, NC was inversely associated with total and regional gray matter in the frontal, temporal, and occipital lobes after adjusting for age and intracranial brain volume. Associations were especially strong in the presence of diabetes. With further adjustment for indices of body composition and other characteristics, total and frontal gray matter in diabetic men were lowered by 6.1 mL (95% confidence interval: 2.5-9.7, P=0.004) and 2.9 mL (95% confidence interval: 1.0-4.9, P=0.017), respectively, per SD increase in NC (2.3 cm). For men without diabetes, and in all women, associations were less apparent. Conclusions In men with diabetes, NC was inversely associated with cerebral gray matter volume. The link between neck anthropometry and brain aging in diabetic men warrants further consideration.

Background Complete heart block (CHB) is a frequent cause for acute admission in older patients with significant cardiac conduction disease. Common presenting symptoms are syncope and dyspnoea. Some patients may exhibit clinical and radiological signs of left ventricular (LV) decompensation, despite preserved LV ejection fraction on transthoracic echocardiography (TTE) and absent pre-existing LV dysfunction. Case summary In this clinical report, we present a case of CHB associated with transient but severe elevation in pulmonary artery systolic pressure, measured as the equivalent right ventricular systolic pressure (RVSP = 99 mmHg) by TTE in the absence of right ventricular outflow tract obstruction, that subsequently ‘normalized’ after implantation of a permanent pacemaker. After searching our echocardiogram database, we did find other cases with similar findings. Discussion There is limited literature describing transient acute elevation in estimated pulmonary pressures in the setting of new CHB that is subsequently reversed by permanent pacing. The true prevalence and mechanism of transient estimated pulmonary pressure as a result of CHB remains unknown. Based on our limited assessment, we postulate that the acute elevation in estimated pulmonary pressures is predominantly related to a compensatory augmentation of RV stroke volume and is caused by the underlying bradycardia and need to maintain forward cardiac output. This phenomenon may require further investigation and validation in future studies.

Tea contains polyphenols such as flavonoids, anthocyanidins, flavanols and phenolic acids which in laboratory studies have reported to promote antioxidant enzyme formation, reduces excess inflammation, slow cancer cell proliferation and promote apoptosis. Evidence from epidemiological studies on the effect of tea consumption on prostate cancer (CaP) incidence has been conflicting. We analysed data from 25 097 men within the intervention arm of the 155 000 participant Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Histologically confirmed cases of prostate cancer were reported in 3088 men (12·3 %) during the median 11·5 year follow-up. Tea consumption was assessed with a FFQ. Baseline characteristics were compared between groups using χ2 and Kruskal–Wallis tests. Cox regression models were used to assess associations between tea intake and CaP incidence. There was no statistical difference between the risk of CaP between men who never drank tea to those who drank tea at any quantity. Amongst tea drinkers, those in the highest third of consumption group had a small but significantly lower risk compared with those in the lowest third (11·2 % v. 13·2 % hazard ratio 1·16; (95 % CI 1·05, 1·29), P = 0·004). This pattern persisted with adjustments for demographics and lifestyle. In conclusion, among tea drinkers, there was a small positive association between drinking tea and a reduced risk of prostate cancer. It does not support starting to drink tea, if men previously did not, to reduce the risk. Further research is needed to establish whether tea is justified for future prospective nutritional intervention studies investigating CaP prevention.

International audience; Background: Ofatumumab, a subcutaneous anti-CD20 monoclonal antibody, selectively depletes B cells. Teriflunomide, an oral inhibitor of pyrimidine synthesis, reduces T-cell and B-cell activation. The relative effects of these two drugs in patients with multiple sclerosis are not known.Methods: In two double-blind, double-dummy, phase 3 trials, we randomly assigned patients with relapsing multiple sclerosis to receive subcutaneous ofatumumab (20 mg every 4 weeks after 20-mg loading doses at days 1, 7, and 14) or oral teriflunomide (14 mg daily) for up to 30 months. The primary end point was the annualized relapse rate. Secondary end points included disability worsening confirmed at 3 months or 6 months, disability improvement confirmed at 6 months, the number of gadolinium-enhancing lesions per T1-weighted magnetic resonance imaging (MRI) scan, the annualized rate of new or enlarging lesions on T2-weighted MRI, serum neurofilament light chain levels at month 3, and change in brain volume.Results: Overall, 946 patients were assigned to receive ofatumumab and 936 to receive teriflunomide; the median follow-up was 1.6 years. The annualized relapse rates in the ofatumumab and teriflunomide groups were 0.11 and 0.22, respectively, in trial 1 (difference, -0.11; 95% confidence interval [CI], -0.16 to -0.06; P

International audience; High dose methotrexate (HD-MTX) based chemoimmunotherapy is a central part of the standard approach to treatment of primary central nervous system lymphoma (PCNSL). Renal dysfunction leads to delayed MTX complete elimination and critical MTX concentration. Despite the recommendations, hemodialysis status should not exclude HD-MTX. We report the case of a 64 years old woman on chronic hemodialysis with PCNSL successfully treated with HD-MTX-based chemoimmunotherapy with an adjusted dose of 100 mg/m(2), instead of the usual dose of 3500 mg/m(2), and daily hemodialysis started 24 h later. The patient had no significant toxicity and was in complete remission at 1 year after the end of the treatment. We argue that ESRD is not an absolute pitfall to the use of HD-MTX for hematological malignancies. Experts should consider the use of adjusted dose at 100 mg/m(2) as a viable therapeutic modality in ESRD patients. (C) 2021 Sociedad Espanola de Nefrologia. Published by Elsevier Espana, S.L.U.

Background and Purpose— Commonly used tools to determine functional outcome after aneurysmal subarachnoid hemorrhage (aSAH) have limitations. Time spent at the patient’s home has previously been proposed as a robust outcome measure after ischemic stroke. Here, we set out to validate home-time as an outcome measure after aSAH. Methods— We examined prospectively collected data from a nationwide multicenter registry of aSAH patients admitted to a tertiary neurosurgical department in Switzerland (Swiss SOS [Swiss Study on Aneurysmal Subarachnoid Hemorrhage]; 2009–2015). We calculated mean home-time (defined as days spent at home for the first 90 days after aSAH) and 95% CIs for each category of modified Rankin Scale at discharge and 1-year follow-up, using linear regression models to analyze home-time differences per modified Rankin Scale category. Results— We had home-time data from 1076 of 1866 patients (57.7%), and multiple imputation was used to fill-in missing data from the remaining 790 patients. Increasing home-time was associated with improved modified Rankin Scale scores at time of hospital discharge ( P P Conclusions— Home-time for the first 90 days after aSAH offers a robust and easily ascertainable outcome measure, discriminating particularly well across better recovery levels at time of hospital discharge and at 1-year follow-up. This measure complies with the modern trend of patient-centered healthcare and research, representing an outcome that is particularly relevant to the patient. Clinical Trial Registration— URL: https://clinicaltrials.gov . Unique identifier: NCT03245866.

Background Excessive daytime sleepiness (EDS), a primary symptom of obstructive sleep apnea (OSA), negatively affects functioning and quality of life (QoL). EDS can persist despite primary airway therapy, and often remains unmanaged, potentially due to inadequate provider-patient communication. Ethnographic research was conducted to assess provider-patient communication about EDS. Methods Participating physicians (primary care n = 5; pulmonologists n = 5; sleep specialists n = 3) identified adult patients (n = 33) diagnosed with OSA who were prescribed positive airway pressure (PAP) therapy ≥6 months prior and previously reported EDS. Visits and post-visit interviews were video-recorded and analyzed using standardized, validated sociolinguistic techniques. Results Despite 55% of patients (18/33) reporting QoL impacts post-visit, this was discussed during 28% (5/18) of visits. Epworth Sleepiness Scale was administered during 27% (9/33) of visits. Many patients (58% [19/33]) attributed EDS to factors other than OSA. Physicians provided EDS education during 24% of visits (8/33). Prior to the visit, 30% (10/33) of patients were prescribed EDS medication, of which 70% (7/10) reported currently experiencing EDS symptoms. Conclusions EDS was minimally discussed and rarely reassessed or treated after PAP therapy initiation in this study. Patients often attributed EDS to factors other than OSA. The findings suggest physicians and patients may benefit from dialogue tools, routine use of screening tools, and patient education.

Objective: Sleep related respiratory abnormalities are typically detected using polysomnography. There is a need in general medicine and critical care for a more convenient method to automatically detect sleep apnea from a simple, easy-to-wear device. The objective is to automatically detect abnormal respiration and estimate the Apnea-Hypopnea-Index (AHI) with a wearable respiratory device, compared to an SpO2 signal or polysomnography using a large (n = 412) dataset serving as ground truth. Methods: Simultaneously recorded polysomnographic (PSG) and wearable respiratory effort data were used to train and evaluate models in a cross-validation fashion. Time domain and complexity features were extracted, important features were identified, and a random forest model employed to detect events and predict AHI. Four models were trained: one each using the respiratory features only, a feature from the SpO2 (%)-signal only, and two additional models that use the respiratory features and the SpO2 (%)-feature, one allowing a time lag of 30 seconds between the two signals. Results: Event-based classification resulted in areas under the receiver operating characteristic curves of 0.94, 0.86, 0.82, and areas under the precision-recall curves of 0.48, 0.32, 0.51 for the models using respiration and SpO2, respiration-only, and SpO2-only respectively. Correlation between expert-labelled and predicted AHI was 0.96, 0.78, and 0.93, respectively. Conclusions: A wearable respiratory effort signal with or without SpO2 predicted AHI accurately. Given the large dataset and rigorous testing design, we expect our models are generalizable to evaluating respiration in a variety of environments, such as at home and in critical care., Co-First Authors: Wolfgang Ganglberger, Abigail A. Bucklin Co-Senior Authors: Robert J. Thomas, M. Brandon Westover

A new concept of non-rapid eye movement (NREM) and rapid eye movement (REM) sleep is proposed, that of multi-component integrative states that define stable and unstable sleep, respectively, NREMS, NREMUS REMS, and REMUS. Three complementary data sets are used: obstructive sleep apnea (20), healthy subjects (11), and high loop gain sleep apnea (50). We use polysomnography (PSG) with beat-to-beat blood pressure monitoring, and electrocardiogram (ECG)-derived cardiopulmonary coupling (CPC) analysis to demonstrate a bimodal, rather than graded, characteristic of NREM sleep. Stable NREM (NREMS) is characterized by high probability of occurrence of the US) has the opposite features: a fragmented and discontinuous integrated multicomponent network model of NREM sleep which captures sleep onset (e.g., ventrolateral preoptic area-based sleep switch) processes, synaptic homeostatic delta power kinetics, and the interaction of global and local sleep processes as reflected in the spatiotemporal evolution of cortical “UP” and “DOWN” states, while incorporating the complex dynamics of autonomic-respiratory-hemodynamic systems during sleep. Bimodality of REM sleep is harder to discern in health. However, individuals with combined obstructive and central sleep apnea allows ready recognition of REMS and REMUS (stable and unstable REM sleep, respectively), especially when there is a discordance of respiratory patterns in relation to conventional stage of sleep.

Background After liver resection (LR), patients with hepatocellular cancer (HCC) are at high risk of recurrence. There are no approved anti-cancer therapies known to affect such risk, highlighting the acute need for novel systemic therapies to control the probability of disease relapse. Immunotherapy is expanding as a novel treatment option for HCC. Emerging data from cohort 4 of the CA209–040 study, which investigated the safety and preliminary efficacy of nivolumab/ipilimumab co-administration in advanced HCC, suggest that the combination can be delivered safely with an acceptable proportion of reversible grade 3–4 toxicities (27.1%) and a low discontinuation rate (2%) in patients with HCC. Here, we describe the design and rationale of PRIME-HCC, a two-part, multi-centre, phase Ib study to assess safety and bioactivity of the nivolumab/ipilimumab combination prior to LR in early-stage HCC. Methods The study involves an initial safety run-in phase (Part 1) to allow for preliminary safety characterisation within the first 6 patients enrolled and a subsequent expansion (Part 2). Ipilimumab will be administered once only on Day 1. Nivolumab will be administered on Day 1 and Day 22 (± 3 days) for a total of two 21-day cycles (i.e. 6 weeks of treatment). The primary objective of the study is to determine the safety and tolerability of the nivolumab/ipilimumab combination prior to LR. The secondary objective is to preliminarily characterize the efficacy of the combination prior to LR, including objective response rate (ORR) and pathologic response rates. Additional exploratory objectives include preliminary evidence of long-term disease control and to identify predictive correlates of response to the nivolumab/ipilimumab combination in HCC. Discussion The results of this study will help define the positioning of neoadjuvant nivolumab/ipilimumab combination in the perioperative management of HCC, with potential to improve survival outcomes in this patient population. Trial registration EudraCT Number: 2018–000987-27 Clinical trial registry & ID: ClinicalTrials.gov: NCT03682276.

Background Antibodies to the aquaporin-4 (AQP4) water channel in neuromyelitis optica spectrum disorder (NMOSD) are reported to trigger the complement cascade, which is implicated in astrocyte damage and subsequent neuronal injury. The PREVENT study demonstrated that the terminal complement inhibitor eculizumab reduces adjudicated relapse risk in patients with anti-AQP4 immunoglobulin G-positive (AQP4+) NMOSD. The objective of this analysis was to evaluate the efficacy of eculizumab in reducing relapse risk and its safety in AQP4+ NMOSD across clinically relevant subgroups in PREVENT. Methods In the randomized, double-blind, time-to-event, phase 3 PREVENT trial, 143 adults received eculizumab (maintenance dose, 1200 mg/2 weeks) or placebo (2:1), with stable-dose concomitant immunosuppressive therapy (IST) permitted (except rituximab and mitoxantrone). Post hoc analyses of relapses and adverse events were performed for prespecified and post hoc subgroups based on concomitant IST and prior rituximab use, demographic and disease characteristics, and autoimmune comorbidity. Results The significant reduction in relapse risk observed for eculizumab versus placebo in the overall PREVENT population was consistently maintained across subgroups based on concomitant IST and previous rituximab use, age, sex, region, race, time since clinical onset of NMOSD, historical annualized relapse rate, baseline Expanded Disability Status Scale score, and history of another autoimmune disorder. The serious infection rate was lower with eculizumab than placebo regardless of rituximab use in the previous year, concomitant IST use, or history of another autoimmune disorder. Conclusion Across a wide range of clinically relevant AQP4+ NMOSD patient subgroups in PREVENT, eculizumab therapy was consistently effective versus placebo in reducing relapse risk, with no apparent increase in serious infection rate. Trial registration NCT01892345 (ClinicalTrials.gov).

STUDY OBJECTIVES: To describe sex, age, and body mass index (BMI) differences in comorbidities and polysomnography measures, categorized using 3 different apnea-hypopnea index (AHI) criteria in sleep clinic patients with mild obstructive sleep-disordered breathing. METHODS: A retrospective cohort of 305 (64% female) adult sleep clinic patients who underwent full-night in-laboratory polysomnography having been diagnosed with mild sleep-disordered breathing and prescribed positive airway pressure. Effects of sex, age, and BMI on comorbidities and polysomnography measures, including rates of AHI defined by ≥ 3% desaturations (AHI(3%)), with arousals (AHI(3%A)), by ≥ 4% desaturations (AHI(4%)), and by respiratory disturbance index, were evaluated. RESULTS: Sixty-nine (23%), 116 (38%), 258 (85%), and 267 (88%) patients had AHI(4%), AHI(3%), AHI(3%A), and respiratory disturbance index ≥ 5 events/h, respectively. Ninety-day positive airway pressure adherence rates were 45.9% overall and higher in women > 50-years-old (51.2%, P = 0.013) and men (54.5%, P = 0.024) with no difference whether AHI(4%) or AHI(3%A) was < 5 or ≥ 5 events/h. Men and women had similar rates of daytime sleepiness (43.3%), anxiety (44.9%), and hypertension (44.9%). Women were more likely to have obesity, anemia, asthma, depression, diabetes, fibromyalgia, hypothyroidism, migraine, and lower rates of coronary artery disease. More patients with AHI(4%) < 5 events/h had depression, migraines, and anemia, and more patients with AHI(4%) ≥ 5 events/h had congestive heart failure. Women were more likely to have higher sleep maintenance and efficiency, shorter average obstructive apnea and hypopnea durations, and less supine-dominant pattern. Average obstructive apnea and hypopnea duration decreased with increasing BMI, and average hypopnea duration increased with age. Obstructive apnea duration and obstructive hypopnea with arousal duration decreased with increasing BMI. More women had AHI(4%) < 5 (81.5% vs 69.1%), AHI(3%) < 5 (68.7% vs 49.1%), and AHI(3%A) < 5 events/h (18.5% vs 10.0%). Greater age and higher BMI were associated with higher AHI. CONCLUSIONS: Current AHI criteria do not predict comorbidities or adherence in mild sleep-disordered breathing patients. In this hypothesis-generating descriptive analysis, sex, BMI, and age may all be factors that should be accounted for in future research of mild sleep-disordered breathing patients. Different sleep study measures may weigh differently in calculations of risk for cardiovascular versus somatic comorbidities. CITATION: Johnson KG, Johnson DC, Thomas RJ, Rastegar V, Visintainer P. Cardiovascular and somatic comorbidities and sleep measures using three hypopnea criteria in mild obstructive sleep-disordered breathing: sex, age, and body mass index differences in a retrospective sleep clinic cohort. J Clin Sleep Med. 2020;16(10):1683–1691.

Objectives This study sought to evaluate the proportion of patients with atrial fibrillation (AF) who also have undiagnosed sleep apnea and examine the impact of its diagnosis on adherence to sleep apnea therapies. Background Sleep apnea is a modifiable risk factor for AF. However, the proportion of patients with AF who also have undiagnosed sleep apnea and the impact of its diagnosis on therapy have not been well studied. Methods This prospective study included 188 consecutive patients with AF without a prior diagnosis of sleep apnea who were scheduled to undergo AF ablation. Participants underwent home sleep apnea testing, completed a sleep apnea screening questionnaire (STOP-BANG [Snoring; Tiredness, Fatigue, or Sleepiness During the Daytime; Observation of Apnea and/or Choking During Sleep; Hypertension; Body Mass Index >35 kg/m2; Age >50 Years; Neck Circumference >40 cm; and Male Sex]) and were followed for ≥2 years to evaluate the impact of diagnosis on therapy. Results Home sleep apnea testing was positive in 155 of 188 patients (82.4%); among those 155, 127 (82%) had a predominant obstructive component and 28 (18%) had mixed sleep apnea with a 15.2 ± 7.4% central component. Sleep apnea severity was mild in 43.8%, moderate in 32.9%, and severe in 23.2%. The sensitivity and specificity of a STOP-BANG questionnaire were 81.2% and 42.4%, respectively. In a multivariate analysis, STOP-BANG was not predictive for sleep apnea (odds ratio: 0.54; 95% confidence interval: 0.17 to 1.76; p = 0.31). Therapy with continuous positive airway pressure ventilators was initiated in 73 of 85 patients (85.9%) with moderate or severe sleep apnea, and 68 of the 73 patients (93.1%) remained complaint after a mean follow-up period of 21 ± 6.2 months. Conclusions Sleep apnea is exceedingly prevalent in patients with AF who are referred for ablation, with a large proportion being undiagnosed due the limited predictive value of sleep apnea symptoms in this AF population. Screening for sleep apnea resulted in high rate of long-term continuous positive airway pressure adherence.

We investigated both independent and interconnected effects of 3 lifestyle factors on brain volume, measuring yearly changes using large-scale longitudinal magnetic resonance imaging, in middle-aged to older adults. We measured brain volumes in a cohort (n = 984, 49-79 years) from the Korean Genome and Epidemiology Study group, using baseline and follow-up estimates after 4 years. In our analysis, the accelerated brain atrophy in normal aging was observed across regions (e.g., brain tissue: -0.098 ± 0.01 mL/y, p0.001). An independent lifestyle-specific trend of brain atrophy across time was also evident in men, where smoking (p = 0.012) and physical activity (p = 0.014) showed the strongest association with the atrophy rate. Linear regression analysis of the interconnected effect revealed that brain atrophy is mitigated by intense physical activity in smoking males. Lifestyle factors did not show any significant effect on brain volume in women. These results provide important information regarding lifestyle factors that affect brain aging in mid-to-late adulthood. Our findings may aid in the identification of preventive measures against dementia.

BACKGROUND There are limited data on the association between obstructive sleep apnea (OSA), which is characterized by intermittent hypoxia, and male-pattern baldness (MPB). Low blood iron levels are reportedly associated with hypoxia and hair loss. This study explored a possible link among OSA, iron status, and MPB. METHODS Polysomnography (PSG) and hair assessments were conducted in a cross-sectional study including 932 men aged 46-76 years. OSA was defined as an apnea-hypopnea index ≥5 by PSG evaluation and MPB as scales from IV to VII according to the Norwood-Hamilton scale classification. Serum transferrin saturation (TSA) levels were assessed. RESULTS A total of 224 men (24%) were identified as MPB cases and 495 men (53%) as having OSA. After considering potential risk factors, OSA and other sleep-related variables were not associated with MPB. In joint analysis of OSA and family history of hair loss, men with these two factors showed a sevenfold higher multivariate odds ratio (95% confidence interval: 3.70, 12.56) for MPB than those without both of them (P

Sleep, a vital process of human being, is carefully orchestrated by the brain and consists of cyclic transitions between rapid eye movement (REM) and non-REM (NREM) sleep. Autonomic tranquility during NREM sleep is characterized by vagal dominance and stable breathing, providing an opportunity for the cardiovascular-neural axis to restore homeostasis, in response to use, distress or fatigue inflicted during wakefulness. Abrupt irregular swings in sympathovagal balance during REM sleep act as phasic loads on the resting cardiovascular system. Any causes of sleep curtailment or fragmentation such as sleep restriction, sleep apnea, insomnia, periodic limb movements during sleep, and shift work, not only impair cardiovascular restoration but also impose a stress on the cardiovascular system. Sleep disturbances have been reported to play a role in the development of stroke and other cardiovascular disorders. This review aims to provide updated information on the role of abnormal sleep in the development of stroke, to discuss the implications of recent research findings, and to help both stroke clinicians and researchers understand the importance of identification and management of sleep pathology for stroke prevention and care.

Bradykinin (BK) promotes insulin sensitivity and glucose uptake in adipocytes and other cell types. We demonstrated that in rat adipocytes BK enhances insulin-stimulated glucose transport via endothelial nitric oxide synthase, nitric oxide (NO) generation, and decreased activity of the mitogen-activated protein kinase (MAPK) JNK (c-Jun NH2-terminal kinase). In endothelial cells, NO increases soluble guanylate cyclase (sGC) activity, which, in turn, activates protein kinase G (PKG) by increasing cGMP levels. In this study, we investigated whether BK acts via the sGC-cGMP-PKG pathway to inhibit the negative effects of JNK on insulin signaling and glucose uptake in rat adipocytes. BK augmented cGMP concentrations. The BK-induced enhancement of insulin-stimulated glucose uptake was mimicked by the sGC activator YC-1 and a cell-permeable cGMP analog, CPT-cGMP, and inhibited by the sGC inhibitor ODQ and the PKG inhibitor KT 5823. Transfection of dominant-negative PKG reduced the BK augmentation of insulin-induced Akt phosphorylation. The activation of JNK and ERK1/2 by insulin was attenuated by BK, which was mediated by the sGC-cGMP-PKG pathway. Whereas insulin-stimulated phosphorylation of upstream activators of JNK and ERK, i.e., MKK4 and MEK1/2, was unaffected, BK augmented insulin-mediated induction of MKP-5 mRNA and protein levels. Furthermore, zaprinast, a phosphodiesterase inhibitor, enhanced cGMP and MKP-5 and prolonged the action of BK. These data indicate that BK enhances insulin action by inhibition of negative feedback by JNK and ERK via upregulation of MKP-5, mediated by the sGC-cGMP-PKG signaling pathway.

Background:While normative data on neuropsychological performance provide baseline metrics for the assessment and diagnosis of mild cognitive impairment and dementia, a lack of comparative normative data in non-Caucasian populations makes it difficult to conduct similar evaluations and studies in individuals from diverse backgrounds. The current paper aims to provide normative data on a range of cognitive measures in a Korean general population sample and investigate various demographic and health variables associated with cognitive performance in this representative population.Method(s):The study population was 1,528 stroke and dementia-free individuals who participated in the Korean Genome and Epidemiology study (KoGES) (mean age 60.43 ± 7.30, 52.42% female). All participants underwent a comprehensive neuropsychological test battery that included verbal and visual memory, language, attention, and executive function measures. A health examination and a questionnaire-based interview were also administered.Results:The majority of cognitive test results were associated with age, education, and gender. In general, higher education and younger age was associated with better cognitive performance. Explained variance increased modestly in models that included measures of general health and depressive symptoms.Conclusion:Normative data of cognitive performance in a community based Korean population are presented. These norms provide reference values in a non-Caucasian middle to older aged sample.

Current cell therapy product limitations include the need for in-depth product understanding to ensure product potency, safety and purity. New technologies require development and validation to address issues of production scale-up to meet clinical need; assays are required for process control, validation and release. Prior to clinical realization, an understanding of production processes is required to implement process changes that are essential for process control. Identification of key parameters forms the basis of process tolerances, allowing for validated, adaptive manufacturing processes. This enables greater process control and yield while withstanding regulatory scrutiny. This report summaries key milestones in specifically for ventral midbrain dopaminergic neuroprogenitor differentiation and key translational considerations and recommendations to enable successful, robust and reproducible current cell therapy product-manufacturing.

New trials, PARTNER 3 and Evolut Low Risk, showed promising results for transcatheter aortic valve replacement for low-risk surgical patients with severe aortic stenosis. However, there remain caveats to its use in this population in clinical practice. Aortic stenosis (AS) is the most common valve disease in developed countries.1 In the absence of valve replacement, severe AS has a 2-year mortality rate of more than 50%.2 Historically, surgery was the predominant treatment option for severe AS. However, two recent randomised controlled trials have further examined the use of a minimally invasive approach: transcatheter aortic valve replacement (TAVR). PARTNER 33 and Evolut Low Risk4 examined the safety and efficacy of TAVR in patients with severe AS at low risk for surgical AVR (SAVR). Patients having open operations can be categorised into low, intermediate and high risk for perioperative mortality using a validated risk-prediction model called the Society of Thoracic Surgery (STS) score.5 PARTNER 3 randomised …

Each night millions of patients use continuous positive airway pressure (CPAP) to treat obstructive sleep apnea (OSA). To facilitate monitoring of treatment success, modern CPAP machines routinely record and analyze the respiratory signal in near real-time and submit some of these data to the manufacturer's centralized cloud server. Some of the conditions frequently associated with OSA such as heart failure or chronic obstructive pulmonary disease result in characteristic changes of the respiratory signal (“signatures”), especially during exacerbations. Thus, this infrastructure could be leveraged to detect changes in patients' health status facilitating early interventions. To illustrate this concept, we present and discuss the case of a patient with OSA who showed abrupt changes in his breathing pattern (increase in periodic breathing and machine-detected obstructive apneas) from 10 days prior until 8 days after a hospitalization for acute heart failure exacerbation. CITATION: Schmickl CN, Heckman E, Owens RL, Thomas RJ. The respiratory signature: a novel concept to leverage continuous positive airway pressure therapy as an early warning system for exacerbations of common diseases such as heart failure. J Clin Sleep Med. 2019;15(6):923–927.

Introduction Boerhaave syndrome is associated with high morbidity and mortality rates. Outcomes are dependent on early recognition and intervention. Until recently, surgery has been the mainstay of management. However, with recent advances in therapeutic endoscopy, there has been increasing interest in endoscopic options, including endoluminal vacuum therapy (EVT). EVT is a minimally invasive technique, allowing wound debridement and drainage; promoting granulation tissue formation to enable wound healing. EVT has been associated with excellent clinical outcomes, including lower mortality rates when compared to both surgery and oesophageal stenting. EVT has been adopted into practice across Europe for the management of oesophageal perforations. However, in the UK there have only been two cases reported. We report a case of a 66 year old female with Boerhaave syndrome, successfully managed with EVT. Methods EVT for oesophageal perforation involves the placement of a polyurethane sponge into the wound cavity. The cavity is initially assessed with an endoscope before an overtube is introduced under visual control. The sponge is pushed into the cavity through the overtube. Once the sponge is in place, the overtube is removed; allowing the sponge to unfold. Sponge position is confirmed endoscopically and adjusted if necessary. The sponge is connected via a trans-nasal drain to continuous negative pressure. Sponge exchange is performed every 3–5 days. Results Having been deemed unfit for surgical intervention, due to difficulties with ventilation and haemodynamic instability, our patient was initially stabilised on the Intensive Care Unit (ICU) with the aid of radiologically placed chest drains and intravenous antibiotics. She was subsequently referred for EVT, using the EsoSPONGE ® (B.Braun, Medical Ltd, Sheffield, UK). Her first therapeutic endoscopy took place on Day 10 of admission; revealing a 5 cm defect in the oesophageal wall and an adjacent cavity; major vessels and the chest drains could be visualised endoscopically. The EsoSPONGE was placed into the cavity and connected to suction. She remained on ICU for 3 months and during this period her EsoSPONGE was exchanged 16 times; resulting in resolution of sepsis and healing of the defect. She was successfully stepped down from ICU and has now been discharged. Conclusions EVT was an effective management strategy for our patient with Boerhaave syndrome. Use of the EsoSPONGE aided drainage of the septic focus and closure of the defect; with this our patient made an excellent recovery. Mortality for this case would otherwise have been extremely high as she was too unstable for surgery. This case supports the evidence that EVT provides a promising approach for the management of Boerhaave syndrome.

Background The apnea-hypopnea index (AHI) (or one of its derivatives) is the primary clinical metric for characterizing sleep disordered breathing—the value of which with respect to a threshold determines severity of diagnosis and eligibility for treatment reimbursement. The index value, however, is taken as a perfect point estimate, with no measure of statistical uncertainty. Thus, current practice does not robustly account for variability in diagnosis/eligibility due to chance. In this paper, we quantify the statistical uncertainty associated with respiratory event indices for sleep disordered breathing and the effect of uncertainty on treatment eligibility. Methods We develop an empirical estimate of uncertainty using a non-parametric bootstrap on the interevent times, as well as a theoretical Poisson estimate reflecting the current formulation of the AHI. We then apply these methods to estimate AHI uncertainty for 2049 subjects (954/1095 M/F, age: mean 69 ± 9.1) from the Multi-Ethnic Study of Atherosclerosis (MESA). Results and Conclusions The mean 95% empirical confidence interval width was 11.500 ± 6.208 events per hour and the mean 95% theoretical Poisson confidence interval width was 5.998 ± 2.897 events per hour, suggesting that uncertainty is likely a major confounding factor within the current diagnostic framework. Of the 278 subjects in the symptomatic population (ESS>10), 27% (76/278) had uncertain diagnoses given the 95% empirical confidence interval. Of the 2049 subjects in the full population, 43% (880/2049) had uncertain diagnoses given the 95% empirical confidence interval. The inclusion of subjects with uncertain diagnoses increases the number of eligible patients by 21.3% for the symptomatic population and by 84.8% for the full population. The exclusion of subjects with uncertain diagnoses given the 95% empirical confidence interval decreases the number of eligible patients by 12.4% for the symptomatic population and by 34.8% for full population. Additional analyses suggest that it is practically infeasible to gain diagnostic statistical significance through additional testing for a broad range of borderline cases. Overall, these results suggest that AHI uncertainty is a vital additional piece of information that would greatly benefit clinical practice, and that the inclusion of uncertainty in epidemiological analysis might help improve the ability for researchers to robustly link AHI with co-morbidities and long-term outcomes.

When the fungus Candida albicans proliferates in the oropharyngeal cavity during experimental oropharyngeal candidiasis (OPC), it undergoes large-scale genome changes at a much higher frequency than when it grows in vitro. Previously, we identified a specific whole chromosome amplification, trisomy of Chr6 (Chr6x3), that was highly overrepresented among strains recovered from the tongues of mice with OPC. To determine the functional significance of this trisomy, we assessed the virulence of two Chr6 trisomic strains and a Chr5 trisomic strain in the mouse model of OPC. We also analyzed the expression of virulence-associated traits in vitro. All three trisomic strains exhibited characteristics of a commensal during OPC in mice. They achieved the same oral fungal burden as the diploid progenitor strain but caused significantly less weight loss and elicited a significantly lower inflammatory host response. In vitro, all three trisomic strains had reduced capacity to adhere to and invade oral epithelial cells and increased susceptibility to neutrophil killing. Whole genome sequencing of pre- and post-infection isolates found that the trisomies were usually maintained. Most post-infection isolates also contained de novo point mutations, but these were not conserved. While in vitro growth assays did not reveal phenotypes specific to de novo point mutations, they did reveal novel phenotypes specific to each lineage. These data reveal that during OPC, clones that are trisomic for Chr5 or Chr6 are selected and they facilitate a commensal-like phenotype., Author summary Opportunistic fungal pathogens commonly acquire extra copies of chromosomes that can provide a fitness benefit under acute stress such as exposure to antifungal agents but how these extra copies affect fungal life-style and interactions with their hosts is poorly understood. Here we show that in C. albicans the acquisition of specific whole chromosome trisomies during oropharyngeal infection in mice results in a commensal-like phenotype. Our data indicate that trisomies of chromosomes 5 and 6 alter several related virulence-associated traits that affect how the host recognizes and responds to C. albicans during oropharyngeal infection, thereby inducing this commensal-like phenotype. Whole genome sequencing revealed that trisomies were mostly maintained in subsequent oral infections and that de novo mutations that arose were not shared among strains. We hypothesize that both in vivo and in vitro phenotypes are likely the result of allelic imbalance of specific genes on the trisomic chromosomes, rather than due to whole chromosome trisomy.

The human electroencephalogram (EEG) of sleep undergoes profound changes with age. These changes can be conceptualized as “brain age”, which can be compared to chronological age to reflect the degree of deviation from normal aging. Here, we develop an interpretable machine learning model to predict brain age based on two large sleep EEG datasets: the Massachusetts General Hospital sleep lab dataset (MGH, N = 2,532; ages 18 to 80); and the Sleep Hearth Health Study (SHHS, N = 1,974; ages 40 to 80). The model obtains a mean absolute deviation of 7.6 years between brain age (BA) and chronological age (CA) in healthy participants in the MGH dataset. As validation, a subset of SHHS containing longitudinal EEGs 5.2 years apart shows an average of 5.4 years increase in BA. Participants with significant neurological or psychiatric disease exhibit a mean excess brain age, or “brain age index” (BAI = BA - CA) of 4 years relative to healthy controls. Participants with hypertension and diabetes have a mean excess brain age of 3.5 years. The findings raise the prospect of using the sleep EEG as a potential biomarker for healthy brain aging.

Rationale: Primary treatment of obstructive sleep apnea can be accompanied by a persistence of excessive sleepiness despite adherence. Furthermore, effectiveness of sleep apnea treatment is limited by poor adherence. Currently available pharmacologic options for the treatment of sleepiness in this population are limited. Objectives: To evaluate the efficacy and safety of solriamfetol (JZP-110), a selective dopamine and norepinephrine reuptake inhibitor with robust wake-promoting effects, for the treatment of excessive sleepiness in participants with obstructive sleep apnea with current or prior sleep apnea treatment. Methods: This was a double-blind, randomized, placebo-controlled, parallel-group, 12-week trial comparing solriamfetol, 37.5, 75, 150, and 300 mg, with placebo. Measurements and Main Results: Of 476 randomized participants, 459 were included in the prespecified efficacy analyses. Coprimary endpoints (Maintenance of Wakefulness Test sleep latency and Epworth Sleepiness Scale score) were met at all solriamfetol doses (P

Study objectives Age-related brain white matter changes (WMC) have been associated separately with obstructive sleep apnea (OSA) and short telomere length (TL). No studies have examined their interaction effect on WMC. Methods This is a cross-sectional study with a community-based sample of 420 participants (mean age, 61.3 ± 7.2) from the Korean Genome and Epidemiology Study during 2011-2012. An overnight fasted blood sample was taken to determine glucose and blood lipid levels at the sleep laboratory of Korea University Ansan Hospital. The status of brain WMC was determined using structural magnetic resonance imaging at 1.5 Tesla. Overnight polysomnography was performed, and leukocyte TL was measured. OSA was determined based on apnea-hypopnea index, and short TL was defined as the lowest quartile of the study participants. Results Adjusting for age, sex, BMI, smoking, drinking, snoring, and hypertension, odds ratio (OR) of brain WMC was estimated using multivariate logistic regression. The odds ratio was significant for cardiovascular disease (OR, 4.5; 95% CI, 1.2-16.3) and OSA (OR, 4.0; 95% CI, 1.0-15.2) among those with short TL; and for diabetes (OR, 3.0; 95% CI, 1.3-13.0) and age (OR, 1.1; 95% CI, 1.0-1.1) among those with longer TL. Interaction effect of OSA and short TL (OR, 4.3; 95% CI, 1.4-13.8) was significant, compared to those with neither OSA nor short TL. Conclusions This study provides a first evidence of mediated interaction of short TL with OSA on brain WMC in a community-based sample. The results generate new hypotheses regarding mechanisms of impaired brain health in sleep apnea.

Key Points Question Can an electroencephalography-based brain age index, calculated as the difference between chronological and estimated brain age through sleep electroencephalography, serve as a potential biomarker associated with dementia? Findings This cross-sectional study of 9834 polysomnograms using machine learning found that brain age index increased monotonically from nondementia to dementia subpopulations. Meaning These findings suggest that brain age index may be a useful biomarker associated with dementia and could have utility as a screening tool for the presence of underlying neurodegenerative disease and monitoring of disease progression., This cross-sectional study examines a sleep electroencephalography-based brain age index as a potential biomarker associated with dementia., Importance Dementia is an increasing cause of disability and loss of independence in the elderly population yet remains largely underdiagnosed. A biomarker for dementia that can identify individuals with or at risk for developing dementia may help close this diagnostic gap. Objective To investigate the association between a sleep electroencephalography-based brain age index (BAI), the difference between chronological age and brain age estimated using the sleep electroencephalogram, and dementia. Design, Setting, and Participants In this retrospective cross-sectional study of 9834 polysomnograms, BAI was computed among individuals with previously determined dementia, mild cognitive impairment (MCI), or cognitive symptoms but no diagnosis of MCI or dementia, and among healthy individuals without dementia from August 22, 2008, to June 4, 2018. Data were analyzed from November 15, 2018, to June 24, 2020. Exposure Dementia, MCI, and dementia-related symptoms, such as cognitive change and memory impairment. Main Outcomes and Measures The outcome measures were the trend in BAI when moving from groups ranging from healthy, to symptomatic, to MCI, to dementia and pairwise comparisons of BAI among these groups. Findings A total of 5144 sleep studies were included in BAI examinations. Patients in these studies had a median (interquartile range) age of 54 (43-65) years, and 3026 (59%) were men. The patients included 88 with dementia, 44 with MCI, 1075 who were symptomatic, and 2336 without dementia. There was a monotonic increase in mean (SE) BAI from the nondementia group to the dementia group (nondementia: 0.20 [0.42]; symptomatic: 0.58 [0.41]; MCI: 1.65 [1.20]; dementia: 4.18 [1.02]; P

Study Objectives To assess, using fractional anisotropy (FA) analysis, alterations of brain network connectivity in adults with obstructive sleep apnea (OSA). Abnormal networks could mediate clinical functional deficits and reflect brain tissue injury. Methods Structural brain networks were constructed using diffusion tensor imaging (DTI) from 165 healthy (age 57.99 ± 6.02 years, male 27.9%) and 135 OSA participants (age 59.01 ± 5.91 years, male 28.9%) and global network properties (strength, global efficiency, and local efficiency) and regional efficiency were compared between groups. We examined MRI biomarkers of brain tissue injury using FA analysis and its effect on the network properties. Results Differences between groups of interest were noted in global network properties (p-value < 0.05, corrected), and regional efficiency (p-value < 0.05, corrected) in the left middle cingulate and paracingulate gyri, right posterior cingulate gyrus, and amygdala. In FA analysis, OSA participants showed lower FA values in white matter (WM) of the right transverse temporal, anterior cingulate and paracingulate gyri, and left postcentral, middle frontal and medial frontal gyri, and the putamen. After culling fiber tracts through WM which showed significant differences in FA, we observed no group difference in network properties. Conclusions Changes in WM integrity and structural connectivity are present in OSA participants. We found that the integrity of WM affected brain network properties. Brain network analysis may improve understanding of neurocognitive deficits in OSA, enable longitudinal tracking, and provides explanations for specific symptoms and recovery kinetics.

Apnea/hypopnea index (AHI), especially without arousal criteria, does not adequately risk stratify patients with mild obstructive sleep apnea (OSA). We describe and test scoring reliability of an event, Flow Limitation/Obstruction With recovery breath (FLOW), representing obstructive airflow disruptions using only pressure transducer and snore signals available without electroencephalography.The following process was used (i) Development of FLOW event definition, (ii) Training period and definition refinement, and (iii) Reliability testing on 10 100-epoch polysomnography (PSG) samples and two 100-sample tests. Twenty full-night in-laboratory baseline PSGs in OSA patients with AHI with ≥4% desaturations15 were rescored for FLOW events, traditional hypopneas with desaturations, respiratory-related arousal (RRA) events (hypopneas with arousals and respiratory-effort related arousals) and non-respiratory arousals (NRA).Scoring of FLOW events in 100-epoch samples had good reliability with intraclass correlation (ICC) of 0.91. The overall kappa for presence of events on two sets of 100 sample events was 0.84 and 0.87 demonstrating good agreement. Moreover, 80% of RRA and 8% of NRA were concurrent with FLOW events. Furthermore, 56% of FLOW events were independent of RRA events. FLOW stratifies patients in traditional AHI categories with 50%/8% of AHI with ≥3% desaturations (AHI3)5 and 12%/63% of AHI35 in lowest/highest tertiles of AHI3 plus FLOW index.Scoring of FLOW after training is reliable. FLOW scores a high proportion of RRA and many currently unrepresented obstructive airflow disruptions. FLOW allows for stratification within the current normal-mild OSA category, which may better identify patients who will benefit from treatment.

Background Asymptomatic bacteriuria is frequent in kidney transplant recipients (KTRs). However, there is no consensus on diagnosis or management. We conducted a European survey to explore current practice related to the diagnosis and management of asymptomatic bacteriuria in adult KTRs. Methods A panel of experts from the European Renal Association-European Dialysis Transplant Association/Developing Education Science and Care for Renal Transplantation in European States working group and the European Study Group for Infections in Compromised Hosts of the European Society of Clinical Microbiology and Infectious Diseases designed this cross-sectional, questionnaire-based, self-administered survey. Invitations to participate were e-mailed to European physicians involved in the care of KTRs. Results Two hundred and forty-four participants from 138 institutions in 25 countries answered the survey (response rate 30%). Most participants [72% (176/244)] said they always screen for asymptomatic bacteriuria in KTRs. Six per cent (15/240) reported never treating asymptomatic bacteriuria with antibiotics. When antimicrobial treatment was used, 24% of the participants (53/224) said they would start with empirical antibiotics. For an episode of asymptomatic bacteriuria caused by a fully susceptible microorganism and despite no contraindications, a majority of participants (121/223) said they would use a fluoroquinolone (n = 56), amoxicillin/clavulanic acid (n = 38) or oral cephalosporins (n = 27). Conclusions Screening for and treating asymptomatic bacteriuria are common in KTRs despite uncertainties around the benefits and harms. In an era of antimicrobial resistance, further studies are needed to address the diagnosis and management of asymptomatic bacteriuria in these patients.

Primary endocrine therapy (PET) is a treatment option for elderly patients with ER-positive breast cancer enabling frail patients to avoid surgery. As a long-term treatment option, it has been shown to be inferior to surgery in controlling local disease. Decision-making in these patients is crucial in avoiding treatment failure. We examined the influence of decision-making on outcomes of PET failure as a secondary analysis as part of a large observational study. Consecutive patients treated with PET between 2005 and 2015 for operable breast cancers were included in a retrospective observational study in 3 breast centres in the North-East. Treatment decision processes were examined by case note review and outcomes of treatment success or failure recorded. 488 patients were included with mean follow-up of 31 months. Overall 63 (12%) experienced treatment failure. 227 (46.6%) were given a choice between surgery and PET at diagnosis. Logistic regression identified older age [OR 0.94 (0.91–0.96) p

Key Clinical Message Aorto‐esophageal fistula is often a terminal event in many patients. The commonest causes are thoracic aortic aneurysm and esophageal malignancy. To achieve a good outcome in this condition, a MDT approach is required that combines the expertize of vascular surgeons, radiologists, and emergency physicians.

Background: Restless legs syndrome (RLS) is a common sleep disorder, although it has a low prevalence in Asian populations. However, the reported RLS prevalence in ­Korean adults is mostly 4.5–12.1%, which is higher than that reported in other Asian populations. This study aimed to diagnose RLS and exclude mimicking conditions in 2 independent samples of Korean adults, and to compare its prevalence to that from previous studies performed in Asian countries. Methods: Study populations included a (1) nationwide stratified random sample (n = 2,824; age 19–79 years) and (2) community-based cohort (n = 2,685; age 47–79 years). We applied the Cambridge-Hopkins diagnostic questionnaire to diagnose RLS and differentiate it from RLS mimics. Sleep-related symptoms, mood, and medical conditions were compared between the RLS and non-RLS groups. Prior studies of the RLS prevalence in Asia were systematically reviewed and compared to our findings. Results: The adjusted RLS prevalence was 0.4 and 1.3% in populations 1 and 2, respectively. In both populations, subjects with RLS had more depression. The prevalence of RLS mimics was 5.1 and 2.6%, in populations 1 and 2, respectively. The RLS prevalence in Asia was higher when RLS was defined by the presence of essential clinical features and lower when a differential diagnosis was additionally implemented. Conclusions: The RLS prevalence in Korean adults considering RLS mimics is comparable to that in adults from other Asian countries (< 2%). The reported RLS prevalence varies depending on the diagnostic method employed.

Restless legs syndrome (RLS) is a common sensory-motor disorder characterized by a variety of uncomfortable sensations associated with an urge to move the legs, relief with movement, strong circadian modulation, and often occurring at sleep onset, impairing sleep quality and inducing insomnia and reduced quality of life. RLS often responds to dopaminergic treatment, but over time, augmentation develops. Some additional key features of the disorder include greater somatotrophic spread when severe or with augmentation, painful sensations, and an association with brain iron deficiency. These features across neurophysiologic subsystems suggest a neural network disorder.

Study objectives Ambulatory tracking of sleep and sleep pathology is rapidly increasing with the introduction of wearable devices. The objective of this study was to evaluate a wearable device which used novel computational analysis of the electrocardiogram (ECG), collected over multiple nights, as a method to track the dynamics of sleep quality in health and disease. Methods This study used the ECG as a primary signal, a wearable device, the M1, and an analysis of cardiopulmonary coupling to estimate sleep quality. The M1 measures trunk movements, the ECG, body position, and snoring vibrations. Data from three groups of patients were analyzed: healthy participants and people with sleep apnea and insomnia, obtained from multiple nights of recording. Analysis focused on summary measures and night-to-night variability, specifically the intraclass coefficient. Results Data were collected from 10 healthy participants, 18 people with positive pressure-treated sleep apnea, and 20 people with insomnia, 128, 65, and 121 nights, respectively. In any participant, all nights were consecutive. High-frequency coupling (HFC), the signal biomarker of stable breathing and stable sleep, showed high intraclass coefficients (ICCs) in healthy participants and people with sleep apnea (0.83, 0.89), but only 0.66 in people with insomnia. The only statistically significant difference between weekday and weekend in healthy subjects was HFC duration: 242.8 ± 53.8 vs. 275.8 ± 57.1 minutes (89 vs. 39 total nights), F(1,126) = 9.86, p = .002. Conclusions The M1 and similar wearable devices provide new opportunities to measure sleep in dynamic ways not possible before. These measurements can yield new biological insights and aid clinical management.

Objectives/Hypothesis To test the effect of upper airway surgery on sleep quality in adults with obstructive sleep apnea (OSA) and the potential usefulness of electrocardiogram (ECG)-based cardiopulmonary coupling (CPC) analysis as metrics of sleep quality. Study Design Retrospective outcome research. Methods A total of 62 consecutive adult patients with OSA, consisting of 36 with successful and 26 with unsuccessful outcomes, were included in the study. Mean age was 37.7 ± 8.9 years, and body mass index (BMI, kg/m2) was 26.9 ± 2.3. We compared clinical characteristics (age, BMI, and Epworth Sleepiness Scale [ESS]), sleep (sleep efficiency, stage non–rapid eye movement [N]1, N2, N3, rapid eye movement, and arousal index [ArI]), respiratory (apnea index [AI], apnea-hypopnea index [AHI], and minimum arterial oxygen saturation [SaO2]), and CPC (high-frequency coupling [HFC], low frequency coupling [LFC], very–low-frequency coupling, and elevated low-frequency coupling [e-LFC]) parameters between the success and nonsuccess groups before and after surgery. Surgical success was defined when the postoperative AHI was both

Objective:Sleep disturbance is common in dementia, although it is unclear whether differences in sleep architecture precede dementia onset. We examined the associations between sleep architecture and the prospective risk of incident dementia in the community-based Framingham Heart Study (FHS).Methods:Our sample comprised a subset of 321 FHS Offspring participants who participated in the Sleep Heart Health Study between 1995 and 1998 and who were aged over 60 years at the time of sleep assessment (mean age 67 ± 5 years, 50% male). Stages of sleep were quantified using home-based polysomnography. Participants were followed for a maximum of 19 years for incident dementia (mean follow-up 12 ± 5 years).Results:We observed 32 cases of incident dementia; 24 were consistent with Alzheimer disease dementia. After adjustments for age and sex, lower REM sleep percentage and longer REM sleep latency were both associated with a higher risk of incident dementia. Each percentage reduction in REM sleep was associated with approximately a 9% increase in the risk of incident dementia (hazard ratio 0.91; 95% confidence interval 0.86, 0.97). The magnitude of association between REM sleep percentage and dementia was similar following adjustments for multiple covariates including vascular risk factors, depressive symptoms, and medication use, following exclusions for persons with mild cognitive impairment at baseline and following exclusions for early converters to dementia. Stages of non-REM sleep were not associated with dementia risk.Conclusions:Despite contemporary interest in slow-wave sleep and dementia pathology, our findings implicate REM sleep mechanisms as predictors of clinical dementia.

Study Objectives Adaptive servo-ventilation (ASV) devices provide anticyclic pressure support for the treatment of central and/or complex sleep apnea, including heart failure patients. Variability in responses in the clinic and negative clinical trials motivated assessment of standard and novel signal biomarkers for ASV efficacy. Methods Multiple clinical databases were queried to assess potential signal biomarkers of ASV effectiveness, including the following: (1) attended laboratory adaptive ventilation titrations: 108, of which 66 had mainstream ETCO2 measurements; (2) AirView data in 98 participants, (3) complete data, from diagnostic polysomnogram (PSG) through review and prospective analysis of on-therapy data using SleepyHead freeware in 44 participants; and (4) hemodynamic data in the form of beat-to-beat blood pressure during ASV titration, using a Finometer in five participants. Results Signal biomarkers of reduced ASV efficacy were noted as follows: (1) an arousal index which markedly exceeded the respiratory event index during positive pressure titration; (2) persistent pressure cycling during long-term ASV therapy, visible in online review systems or reviewing data using freeware; (3) the ASV-associated pressure cycling induced arousals, sleep fragmentation, and blood pressure surges; and (4) elevated ratios of 95th percentile to median tidal volume, minute ventilation, and respiratory rate were associated with pressure cycling. High intraclass coefficients (>0.8) for machine apnea–hypopnea index and other extractable metrics were consistent with stability of patterns over multiple nights of use. Global clinical outcomes correlated negatively with pressure cycling. Conclusions Potential polysomnographic- and device-related signal biomarkers of ASV efficacy are described and may allow improved estimation of therapeutic effectiveness of adaptive ventilation.