Effect of obstructive sleep apnoea on retinal microvascular function: a randomised controlled trial.

PURPOSE: Retinal microvascular endothelial dysfunction is thought to be of importance in the development of ocular vascular diseases. Obstructive sleep apnoea (OSA) causes macrovascular endothelial dysfunction, but the effect of OSA on retinal microvascular endothelial function is not known. We aimed to determine the effect of OSA on retinal microvascular function. METHODS: We conducted a multi-centre, double-blind, randomised, parallel, controlled trial in patients with known moderate-to-severe OSA, established on continuous positive airway pressure (CPAP). Participants were randomised to 14 nights of either continued CPAP or sham CPAP to generate a return of OSA. Retinal vascular responses to flickering light were measured using dynamic vessel analysis both at baseline and after 14 nights of intervention. The primary outcome was the change from baseline to follow-up in the area under the curve of the arteriolar response to flickering light, sham CPAP versus continued CPAP. RESULTS: Nineteen patients were randomised to sham CPAP, and 18 patients were randomised to continued CPAP. There was no significant effect of CPAP withdrawal and return of OSA on retinal responses, with a change in the area under the curve of the arteriole response to flickering light of + 3.8 arbitrary units (95% CI - 10.6 to + 18.2, p = 0.59), sham CPAP versus continued CPAP. CONCLUSIONS: CPAP withdrawal and a return of OSA had no significant effect on retinal microvascular responses. This contrasts with the effect of CPAP withdrawal on macrovascular endothelial function and suggests that OSA has different effects on macrovascular and microvascular endothelial function. ISRCTN 78082983, 23/10/2014, Prospectively registered.

Development and Relevance of Hypercapnia in COPD.

Background: Identification of patients who may become hypercapnic, or develop acidotic hypercapnic respiratory failure (AHRF), is important in chronic obstructive pulmonary disease (COPD) to avoid hospital admission and select patients for use of home NIV. This study aimed to identify factors associated with presence and development of hypercapnia. Methods: 1224 patients, 637 with COPD and 587 with alpha 1 antitrypsin deficiency (AATD), from 4 previously established patient cohorts, were included in cross-sectional analyses of hypercapnia (PaCO2 ≥ 6.5 kPa or 48.8 mmHg), focusing on phenotypic features of COPD and mortality. Longitudinal associations of rising PaCO2 were also assessed. A second cohort of 160 COPD patients underwent sleep studies and 1-year follow-up, analysing in a similar way, incorporating additional information from their sleep studies if appropriate. Results: Hypercapnia was 15 times more common in usual COPD than AATD (p < 0.01) after adjustment for baseline differences by regression. Independent predictors of hypercapnia in COPD included FEV1 and current use of oxygen; these variables, together with lack of emphysema, explained 11% of variance in CO2. Increasing PaCO2 also associated with higher risk of death (p=0.03). 44/160 patients exhibited sleep disordered breathing. The sleep study cohort also showed an association of low FEV1 with hypercapnia. Prior hospital admission for AHRF was also clinically significant, being a feature of almost double the number of hypercapnic patients in both test and sleep study COPD cohorts. Conclusion: Lower FEV1 and prior AHRF are the main associations of hypercapnia in COPD, which carries a poor prognosis, particularly worsening over time.

The association between asthma and obstructive sleep apnea (OSA): A systematic review.

OBJECTIVE: Bronchial asthma and obstructive sleep apnoea (OSA) are common respiratory disorders that can co-exist. The strength of this association, and also the impact of OSA on asthma-related clinical outcomes remain unclear. DATA SOURCES: Literature review was performed in EMBASE and MEDLINE databases. Studies up to and including 2016 were selected. STUDY SELECTION: Studies were included if they contained; 1) a population with asthma AND 2) a prevalence of OSA reported using either polysomnography or validated questionnaires such as the Sleep Apnoea Scale of the Sleep Disorders Questionnaire (SA-SDQ), STOP BANG or the Berlin questionnaire. RESULTS: Nineteen studies were identified. Thirteen questionnaire-based studies met the inclusion/exclusion criteria and twelve of these demonstrated a prevalence of OSA in asthma of 8-52.6%, with one study showing no association between the two conditions. Six studies using polysomnography demonstrated a high prevalence of 19.2-60%; which was higher at 50-95% in severe asthma. Two polysomnography and four questionnaire studies found worse asthma-related clinical outcomes with co-existing OSA. One polysomnography and two questionnaire studies showed no difference. CONCLUSION: This systematic review suggests that there is a high prevalence of OSA in asthma, particularly within severe asthma populations and that co-diagnosis of OSA in asthma patients is associated with worse clinical outcomes. However this outcome was not uniform and the number of studies using polysomnography to confirm OSA was small. This weakens the conclusions that can be drawn and prompts the need for adequately powered and well-designed studies to confirm or refute these findings.

Does Continuous Positive Airway Pressure (CPAP) treatment of obstructive sleep apnoea (OSA) improve asthma-related clinical outcomes in patients with co-existing conditions?- A systematic review.

INTRODUCTION: A high prevalence of OSA has been observed in asthma populations, with detrimental impact on clinical outcomes. AIM: To determine if CPAP treatment of co-existing OSA improves asthma-related symptoms and quality of life. METHODS: Literature review of EMBASE and MEDLINE databases prior to July 2017. Study populations included asthmatics with co-existing OSA treated with CPAP, and ≥1 asthma-related clinical outcome measure. RESULTS: 12 studies; 8 prospective quasi-experimental and 4 observational. Mean CPAP duration; 19.5 (2-100) weeks. Meta-analysis demonstrated significant improvement in mean Asthma Quality of Life Questionnaire scores (AQLQ and mini-AQLQ); 0.59 (95%CI; 0.25, 0.92), p = 0.0006. No significant improvement was demonstrated in forced expiratory volume in 1 s (FEV1)% predicted; 0.32 (95%CI; -2.84, 3.47), p = 0.84. Asthma Control Test/Asthma Control Questionnaire improved in 2 studies, with no improvement in 1 study. 4 studies demonstrated improvement in asthma daytime/night-time symptoms, and 3 studies showed improved asthma severity. CONCLUSION: Asthmatics with co-existing OSA can experience improved quality of life with CPAP treatment. This effect appears more pronounced in severe OSA or poorly controlled asthma.

Systemic inflammatory disease resolution following cosmetic silicone breast implant removal.

A 37-year-old Caucasian woman presented with subacute, symmetrical inflammatory arthralgia, which was affecting her work. Apart from fatigue, she had no other constitutional symptoms. She had undergone cosmetic bilateral silicone breast implant surgery in 2008. Blood tests revealed erythrocyte sedimentation rate 53 mm/h, weakly positive antinuclear antibodies and IgG cardiolipin antibody, while breast ultrasound revealed a ruptured left silicone implant. The working diagnosis was systemic inflammatory disease of uncertain origin. She decided to have replacement, rather than removal, of her silicone breast implants privately, but her symptoms persisted postoperatively with a new erythema multiforme-like rash despite treatment with methotrexate and moderate dose prednisolone. Following further consultation with a National Health Service breast surgeon, her silicone implants were removed. Within 10 weeks of surgery, all immunomodulatory treatment was discontinued with complete symptom and inflammatory response resolution. This case illustrates that implant silicone can induce clinically significant systemic inflammatory disease and implant removal is essential for disease resolution.

Carbimazole-induced lupus.

We describe the case of a 50-year-old lady admitted with a 3-week history of dyspnoea and left-sided pleuritic pain associated with pleural effusion. This common clinical picture nevertheless gave rise to a significant diagnostic challenge. The medical history included a diagnosis of thyrotoxicosis made 6 months previously that was being treated with carbimazole by her general practitioner. Key-investigation results were as follows: (1) pleural fluid was sterile and exudative, with no malignant cells, (2) erythrocyte sedimentation rate, C reactive protein and D-dimer were raised, (3) antinuclear antibody, anti-dsDNA and antihistone antibodies were newly positive, (4) imaging revealed a large left ventricular mass consistent with thrombus in the absence of evidence of a myocardial infarction. Based on the above investigations we hypothesised that carbimazole had induced systemic lupus erythematosus, manifesting as serositis resulting in an exudative pleural effusion and a proinflammatory/prothrombotic state. Carbimazole was stopped. The patient's pleural effusion completely resolved and she remains asymptomatic.

Nodular 'fasciitis' presenting as a cutaneous polyp.

A polypoid cutaneous variant of 'nodular fasciitis' presenting on the upper arm of an 8-year-old girl is described. Nodular fasciitis is a reactive myofibroblastic proliferation that can be mistaken clinically as sarcoma, given its rapid growth. As its name implies, nodular fasciitis was originally described involving the fascia. Although rare dermal cases have been described, this is the first report of a dermal polypoid variant known to us, thus extending the presentations of this condition.

Management of leiomyosarcomas of the spermatic cord: the role of reconstructive surgery.

BACKGROUND: Leiomyosarcomas (LMS) of the spermatic cord are extremely rare. Radical inguinal orchiectomy and high ligation of the cord is the standard primary surgical procedure. The extent of surrounding soft tissue excision required and the precise role of adjuvant radiotherapy, however, remains unclear. In addition, recurrence is a commonly encountered problem which might necessitate further radical excision of adjacent soft tissues. METHODS: This article reviews the pathophysiology of spermatic cord leiomyosarcomas (LMS), and discusses the various reconstructive surgical options available to repair the inguinal region and the lower anterior abdominal wall after excision of the tumour and the adjacent soft tissues. RESULTS: There is paucity of literature on LMS of spermatic cord. The majority of paratesticular neoplasms are of mesenchymal origin and up to 30% of these are malignant. In adults, approximately 10% of spermatic cord sarcomas are LMS. Approximately 50% of these tumours recur loco-regionally following definitive surgery; however, the incidence decreases if resection is followed by adjuvant radiotherapy. CONCLUSION: It is therefore important to achieve negative histological margins during the primary surgical procedure, even if adjuvant radiotherapy is instituted. If extensive resection is required, either during the primary procedure or following recurrence, reconstructive surgery may become necessary. This article reviews the pathophysiology of spermatic cord LMS, the reasons for recurrence, and discusses the management options including the role of reconstructive surgery.

Decreased whole body endogenous nitric oxide production in patients with primary pulmonary hypertension.

Impaired pulmonary release of nitric oxide (NO) is one of the characteristic phenotypic changes of vascular cells in pulmonary hypertension. The aim of this study was to determine nitric oxide synthase (NOS)-dependent whole body NO production in patients with primary pulmonary hypertension. NOS-dependent whole body NO production was assessed by giving an intravenous infusion of L-[(15)N](2)-arginine (50 micromol/min for 30 min) and measuring isotopic urinary enrichment of (15)N-nitrite and (15)N-nitrate. Four female patients with no signs of infection were recruited and compared with 6 age-matched control subjects. Mean 12-hour excretion of (15)N-nitrite and (15)N-nitrate in the total urine over 36 h was smaller in patients than in control subjects (57.2 +/- 27.6 vs. 229.1 +/- 65.2 nmol/mmol creatinine, p < 0.01, Mann-Whitney U test, respectively). Neither mean 12-hour excretion of (14)N-nitrite and (14)N-nitrate (51.6 +/- 10.0 vs. 72.4 +/- 10.0 micromol/mmol creatinine, p = 0.3) nor glomerular filtration rates (84.5 +/- 15.8 vs. 129.7 +/- 16.0 ml/min, p = 0.1) were different between patients and control subjects. Our results suggest that either basal NOS-dependent whole body NO production is impaired or excess NO metabolism occurs in patients with primary pulmonary hypertension.