COPD exacerbation phenotypes in a real-world five year hospitalisation cohort

INTRODUCTION: COPD exacerbation phenotypes have been defined in research populations by predominantly infective or inflammatory aetiology. We sought to characterise this in patients admitted to our centre. MATERIALS AND METHODS: Case-notes of consecutive patients discharged alive after treatment for acute COPD exacerbations between December 2012 and January 2017 were analysed. Data were collected on treatment, length of stay, C-reactive protein (CRP), eosinophil count and bacterial sputum culture positivity for potentially pathogenic microorganisms (PPM). RESULTS: 1029 exacerbations were included. There was an inverse correlation between CRP and eosinophil count (rho = -0.277, p 100 mg/L (4d [3,8] vs 4d [2,7], p < 0.01) or when given antibiotics (4d [2,8] vs 3d [1,6], p < 0.001) and shorter if receiving corticosteroids (4d [2,6] vs 6d [3,7], p < 0.001). Being sputum culture positive on first exacerbation was associated with sputum culture positivity in subsequent exacerbations. Patients with PPM in sputum culture had a significantly higher median CRP than culture negative patients (38 mg/L [18.75, 57] v 18 mg/L [8.5,45.5] p < 0.05). Length of stay, eosinophil count and CRP were significantly correlated between exacerbation pairs. CONCLUSIONS: This real-world population found eosinophilic and high CRP exacerbations to be distinct and significantly stereotyped within individual patients across recurrent exacerbations. High CRP exacerbations are associated with greater healthcare utilisation and chance of sputum positivity with PPM. Eosinophilic exacerbations were associated with lower rate of readmission. Phenotype-driven treatment warrants further investigation in this population

The Blood Neutrophil Count After 1 Month of Treatment Predicts the Radiologic Severity of Lung Disease at Treatment End

BACKGROUND: Post-tuberculous lung disease confers significant morbidity. However, the determinants of persistent lung damage in tuberculosis are not well established. We investigated associations between tuberculosis-associated radiological changes and socio-demographic factors, surrogates of bacillary burden and blood inflammatory markers at initiation of therapy and after 1 month. RESEARCH QUESTION: What are the predictors of radiological severity at the end of tuberculosis treatment for tuberculosis? STUDY DESIGN AND METHODS: We collected data from patients treated for drug sensitive pulmonary tuberculosis at our centre over a 5.5-year period. We recorded age, sex, ethnicity, smoking status, symptom duration, sputum smear grade, time to culture positivity and blood results (C-reactive protein and neutrophil count) at baseline and after 1 month of treatment. Chest x-rays performed at baseline, 2 months and end of treatment were assessed independently by two radiologists and scored using a validated system. Relationships between predictor variables and radiological outcomes were assessed using linear or binary logistic regression. RESULTS: We assessed 154 individuals, mean age 37 years, 63% male. In multivariate analysis, baseline radiological severity correlated with sputum smear grade (p=0.003) and neutrophil count (p<0.001). At end of treatment, only the 1-month neutrophil count was significantly associated with overall radiological severity in multivariate analysis (r=0.34, p=0.003), and remained significant after controlling for baseline radiological scores. The 1-month neutrophil count was also the only independent correlate of volume loss and pleural thickening at end of treatment and was significantly higher in patients with persistent cavitation or effusion versus those without. INTERPRETATION: Persistent neutrophilic inflammation after 1 month of tuberculosis therapy is associated with poor radiological outcome, suggesting a target for interventions to minimise post-tuberculous lung disease

Experimental stroke differentially affects discrete subpopulations of splenic macrophages

Changes to the immune system after stroke are complex and can result in both pro-inflammatory and immunosuppressive consequences. Following ischemic stroke, brain resident microglia are activated and circulating monocytes are recruited to the injury site. In contrast, there is a systemic deactivation of monocytes/macrophages that may contribute to immunosuppression and the high incidence of bacterial infection experienced by stroke patients. The manipulation of macrophage subsets may be a useful therapeutic strategy to reduce infection and improve outcome in patients after stroke. Recent research has enhanced our understanding of the heterogeneity of macrophages even within the same tissue. The spleen is the largest natural reservoir of immune cells, many of which are mobilized to the site of injury after ischemic stroke and is notable for the diversity of its functionally distinct macrophage subpopulations associated with specific micro-anatomical locations. Here, we describe the effects of experimental stroke in mice on these distinct splenic macrophage subpopulations. Red pulp (RP) and marginal zone macrophages (MZM) specifically showed increases in density and alterations in micro-anatomical location. These changes were not due to increased recruitment from the bone marrow but may be associated with increases in local proliferation. Genes associated with phagocytosis and proteolytic processing were upregulated in the spleen after stroke with increased expression of the lysosome-associated protein lysosomal-associated membrane proteins specifically increased in RP and MZM subsets. In contrast, MHC class II expression was reduced specifically in these populations. Furthermore, genes associated with macrophage ability to communicate with other immune cells, such as co-stimulatory molecules and inflammatory cytokine production, were also downregulated in the spleen after stroke. These findings suggest that selective splenic macrophage functions could be impaired after stroke and the contribution of macrophages to stroke-associated pathology and infectious complications should be considered at a subset-specific level. Therefore, optimal therapeutic manipulation of macrophages to improve stroke outcome is likely to require selective targeting of functionally and spatially distinct subpopulations

Alcohol, smoking, recreational drug use and association with virological outcomes among people living with HIV: cross-sectional and longitudinal analyses

Objectives: There is increasing evidence to suggest that people living with HIV (PLWH) have significant morbidity from alcohol, recreational drug use and cigarette smoking. Our aim was to report associations of these factors with antiretroviral therapy (ART) non-adherence, viral non-suppression and subsequent viral rebound in PLWH. / Methods: The Antiretroviral Sexual Transmission Risk and Attitudes (ASTRA) study recruited PLWH attending eight outpatient clinics in England between February 2011 and December 2012. Data included self-reported excessive drinking (estimated consumption of > 20 units of alcohol/week), alcohol dependency (CAGE score ≥ 2 with current alcohol consumption), recreational drug use (including injection drug use in the past 3 months), and smoking status. Among participants established on ART, cross-sectional associations with ART non-adherence [missing ≥2 consecutive days of ART on ≥2 occasions in the past three months] and viral-non suppression [viral load (VL) > 50 copies/mL] were assessed using logistic regression. In participants from one centre, longitudinal associations with subsequent viral rebound (first VL > 200 copies/mL) in those on ART with VL ≤ 50 copies/mL at baseline were assessed using Cox regression during a 7-year follow-up. / Results: Among 3258 PLWH, 2248 (69.0%) were men who have sex with men, 373 (11.4%) were heterosexual men, and 637 (19.6%) were women. A CAGE score ≥ 2 was found in 568 (17.6%) participants, 325 (10.1%) drank > 20 units/week, 1011 (31.5%) currently smoked, 1242 (38.1%) used recreational drugs and 74 (2.3%) reported injection drug use. In each case, prevalence was much more common among men than among women. Among 2459 people on ART who started at least 6 months previously, a CAGE score ≥ 2, drinking > 20 units per week, current smoking, injection and non-injection drug use were all associated with ART non-adherence. After adjusting for demographic and socioeconomic factors, CAGE score ≥ 2 [adjusted odds ratio (aOR) = 1.52, 95% confidence interval (CI): 1.09–2.13], current smoking (aOR = 1.58, 95% CI: 1.10–2.17) and injection drug use (aOR = 2.11, 95% CI: 1.00–4.47) were associated with viral non-suppression. During follow-up of a subset of 592 people virally suppressed at recruitment, a CAGE score ≥ 2 [adjusted hazard ratio (aHR) = 1.66, 95% CI: 1.03–2.74], use of 3 or more non-injection drugs (aHR = 1.82, 95% CI: 1.12–3.57) and injection drug use (aHR = 2.73, 95% CI: 1.08–6.89) were associated with viral rebound. / Conclusions: Screening and treatment for alcohol, cigarette and drug use should be integrated into HIV outpatient clinics, while clinicians should be alert to the potential for poorer virological outcomes

Dicationic Alkylammonium Bromide Gemini Surfactants. Membrane Perturbation and Skin Irritation

Dicationic alkylammonium bromide gemini surfactants represent a class of amphiphiles potentially effective as skin permeation enhancers. However, only a limited number of studies has been dedicated to the evaluation of the respective cytotoxicity, and none directed to skin irritation endpoints. Supported on a cell viability study, the cytotoxicity of gemini surfactants of variable tail and spacer length was assessed. For this purpose, keratinocyte cells from human skin (NCTC 2544 cell line), frequently used as a model for skin irritation, were employed. The impact of the different gemini surfactants on the permeability and morphology of model vesicles was additionally investigated by measuring the leakage of calcein fluorescent dye and analyzing the NMR spectra of 31P, respectively. Detail on the interaction of gemini molecules with model membranes was also provided by a systematic differential scanning calorimetry (DSC) and molecular dynamics (MD) simulation. An irreversible impact on the viability of the NCTC 2544 cell line was observed for gemini concentrations higher than 25 mM, while no cytotoxicity was found for any of the surfactants in a concentration range up to 10 mM. A higher cytotoxicity was also found for gemini surfactants presenting longer spacer and shorter tails. The same trend was obtained in the calorimetric and permeability studies, with the gemini of longest spacer promoting the highest degree of membrane destabilization. Additional structural and dynamical characterization of the various systems, obtained by 31P NMR and MD, provide some insight on the relationship between the architecture of gemini surfactants and the respective perturbation mechanism

Genetic epidemiology of SARS-CoV-2 transmission in renal dialysis units - a high risk community-hospital interface

OBJECTIVES: Patients requiring haemodialysis are at increased risk of serious illness with SARS-CoV-2 infection. To improve the understanding of transmission risks in six Scottish renal dialysis units, we utilised the rapid whole-genome sequencing data generated by the COG-UK consortium. METHODS: We combined geographical, temporal and genomic sequence data from the community and hospital to estimate the probability of infection originating from within the dialysis unit, the hospital or the community using Bayesian statistical modelling and compared these results to the details of epidemiological investigations. RESULTS: Of 671 patients, 60 (8.9%) became infected with SARS-CoV-2, of whom 16 (27%) died. Within-unit and community transmission were both evident and an instance of transmission from the wider hospital setting was also demonstrated. CONCLUSIONS: Near-real-time SARS-CoV-2 sequencing data can facilitate tailored infection prevention and control measures, which can be targeted at reducing risk in these settings

Fundamental limits to quantum channel discrimination

What is the ultimate performance for discriminating two arbitrary quantum channels acting on a finite-dimensional Hilbert space? Here we address this basic question by deriving a general and fundamental lower bound. More precisely, we investigate the symmetric discrimination of two arbitrary qudit channels by means of the most general protocols based on adaptive (feedback-assisted) quantum operations. In this general scenario, we first show how port-based teleportation can be used to simplify these adaptive protocols into a much simpler non-adaptive form, designing a new type of teleportation stretching. Then, we prove that the minimum error probability affecting the channel discrimination cannot beat a bound determined by the Choi matrices of the channels, establishing a general, yet computable formula for quantum hypothesis testing. As a consequence of this bound, we derive ultimate limits and no-go theorems for adaptive quantum illumination and single-photon quantum optical resolution. Finally, we show how the methodology can also be applied to other tasks, such as quantum metrology, quantum communication and secret key generation

Neuroglial heterotopia presenting as a submental mass

Poster abstracts: P38.10This journal issue entitled: Special Issue: 18th World Congress on Ultrasound in Obstetrics and GynecologyA 32 year old para 0 lady was referred to our Prenatal Diagnostic Clinic for management of a left submental mass in the fetus. The mass was detected during routine morphology scan at 18 weeks of gestation. It was well demarcated and predominantly solid with minimal vascularity. No other abnormalities were seen. At 24 weeks, it measured 3.9 × 2.9 × 2.6 cm and located in the cervical region underneath the left mandible. On surface rendering with 3D ultrasound, the lower border of it was well away from the fetal chest and the facial features were not ...link_to_OA_fulltex