Novel computed tomographic chest metrics to detect pulmonary hypertension

<p>Abstract</p> <p>Background</p> <p>Early diagnosis of pulmonary hypertension (PH) can potentially improve survival and quality of life. Detecting PH using echocardiography is often insensitive in subjects with lung fibrosis or hyperinflation. Right heart catheterization (RHC) for the diagnosis of PH adds risk and expense due to its invasive nature. Pre-defined measurements utilizing computed tomography (CT) of the chest may be an alternative non-invasive method of detecting PH.</p> <p>Methods</p> <p>This study retrospectively reviewed 101 acutely hospitalized inpatients with heterogeneous diagnoses, who consecutively underwent CT chest and RHC during the same admission. Two separate teams, each consisting of a radiologist and pulmonologist, blinded to clinical and RHC data, individually reviewed the chest CT's.</p> <p>Results</p> <p>Multiple regression analyses controlling for age, sex, ascending aortic diameter, body surface area, thoracic diameter and pulmonary wedge pressure showed that a main pulmonary artery (PA) diameter ≥29 mm (odds ratio (OR) = 4.8), right descending PA diameter ≥19 mm (OR = 7.0), true right descending PA diameter ≥ 16 mm (OR = 4.1), true left descending PA diameter ≥ 21 mm (OR = 15.5), right ventricular (RV) free wall ≥ 6 mm (OR = 30.5), RV wall/left ventricular (LV) wall ratio ≥0.32 (OR = 8.8), RV/LV lumen ratio ≥1.28 (OR = 28.8), main PA/ascending aorta ratio ≥0.84 (OR = 6.0) and main PA/descending aorta ratio ≥ 1.29 (OR = 5.7) were significant predictors of PH in this population of hospitalized patients.</p> <p>Conclusion</p> <p>This combination of easily measured CT-based metrics may, upon confirmatory studies, aid in the non-invasive detection of PH and hence in the determination of RHC candidacy in acutely hospitalized patients.</p

Thyroid Hormone Signalling Genes Are Regulated by Photoperiod in the Hypothalamus of F344 Rats

Seasonal animals adapt their physiology and behaviour in anticipation of climate change to optimise survival of their offspring. Intra-hypothalamic thyroid hormone signalling plays an important role in seasonal responses in mammals and birds. In the F344 rat, photoperiod stimulates profound changes in food intake, body weight and reproductive status. Previous investigations of the F344 rat have suggested a role for thyroid hormone metabolism, but have only considered Dio2 expression, which was elevated in long day photoperiods. Microarray analysis was used to identify time-dependent changes in photoperiod responsive genes, which may underlie the photoperiod-dependent phenotypes of the juvenile F344 rat. The most significant changes are those related to thyroid hormone metabolism and transport. Using photoperiod manipulations and melatonin injections into long day photoperiod (LD) rats to mimic short day (SD), we show photoinduction and photosuppression gene expression profiles and melatonin responsiveness of genes by in situ hybridization; TSHβ, CGA, Dio2 and Oatp1c1 genes were all elevated in LD whilst in SD, Dio3 and MCT-8 mRNA were increased. NPY was elevated in SD whilst GALP increased in LD. The photoinduction and photosuppression profiles for GALP were compared to that of GHRH with GALP expression following GHRH temporally. We also reveal gene sets involved in photoperiodic responses, including retinoic acid and Wnt/ß-catenin signalling. This study extends our knowledge of hypothalamic regulation by photoperiod, by revealing large temporal changes in expression of thyroid hormone signalling genes following photoperiod switch. Surprisingly, large changes in hypothalamic thyroid hormone levels or TRH expression were not detected. Expression of NPY and GALP, two genes known to regulate GHRH, were also changed by photoperiod. Whether these genes could provide links between thyroid hormone signalling and the regulation of the growth axis remains to be investigated

Differential Modulation of Beta-Adrenergic Receptor Signaling by Trace Amine-Associated Receptor 1 Agonists

Trace amine-associated receptors (TAAR) are rhodopsin-like G-protein-coupled receptors (GPCR). TAAR are involved in modulation of neuronal, cardiac and vascular functions and they are potentially linked with neurological disorders like schizophrenia and Parkinson's disease. Subtype TAAR1, the best characterized TAAR so far, is promiscuous for a wide set of ligands and is activated by trace amines tyramine (TYR), phenylethylamine (PEA), octopamine (OA), but also by thyronamines, dopamine, and psycho-active drugs. Unfortunately, effects of trace amines on signaling of the two homologous β-adrenergic receptors 1 (ADRB1) and 2 (ADRB2) have not been clarified yet in detail. We, therefore, tested TAAR1 agonists TYR, PEA and OA regarding their effects on ADRB1/2 signaling by co-stimulation studies. Surprisingly, trace amines TYR and PEA are partial allosteric antagonists at ADRB1/2, whereas OA is a partial orthosteric ADRB2-antagonist and ADRB1-agonist. To specify molecular reasons for TAAR1 ligand promiscuity and for observed differences in signaling effects on particular aminergic receptors we compared TAAR, tyramine (TAR) octopamine (OAR), ADRB1/2 and dopamine receptors at the structural level. We found especially for TAAR1 that the remarkable ligand promiscuity is likely based on high amino acid similarity in the ligand-binding region compared with further aminergic receptors. On the other hand few TAAR specific properties in the ligand-binding site might determine differences in ligand-induced effects compared to ADRB1/2. Taken together, this study points to molecular details of TAAR1-ligand promiscuity and identified specific trace amines as allosteric or orthosteric ligands of particular β-adrenergic receptor subtypes

Association of Gender with Clinical Expression, Quality of Life, Disability, and Depression and Anxiety in Patients with Systemic Sclerosis

OBJECTIVES: To assess the association of gender with clinical expression, health-related quality of life (HRQoL), disability, and self-reported symptoms of depression and anxiety in patients with systemic sclerosis (SSc). METHODS: SSc patients fulfilling the American College of Rheumatology and/or the Leroy and Medsger criteria were assessed for clinical symptoms, disability, HRQoL, self-reported symptoms of depression and anxiety by specific measurement scales. RESULTS: Overall, 381 SSc patients (62 males) were included. Mean age and disease duration at the time of evaluation were 55.9 (13.3) and 9.5 (7.8) years, respectively. One-hundred-and-forty-nine (40.4%) patients had diffuse cutaneous SSc (dcSSc). On bivariate analysis, differences were observed between males and females for clinical symptoms and self-reported symptoms of depression and anxiety, however without reaching statistical significance. Indeed, a trend was found for higher body mass index (BMI) (25.0 [4.1] vs 23.0 [4.5], p = 0.013), more frequent dcSSc, echocardiography systolic pulmonary artery pressure >35 mmHg and interstitial lung disease in males than females (54.8% vs 37.2%, p = 0.010; 24.2% vs 10.5%, p = 0.003; and 54.8% vs 41.2%, p = 0.048, respectively), whereas calcinosis and self-reported anxiety symptoms tended to be more frequent in females than males (36.0% vs 21.4%, p = 0.036, and 62.3% vs 43.5%, p = 0.006, respectively). On multivariate analysis, BMI, echocardiography PAP>35 mmHg, and anxiety were the variables most closely associated with gender. CONCLUSIONS: In SSc patients, male gender tends to be associated with diffuse disease and female gender with calcinosis and self-reported symptoms of anxiety. Disease-associated disability and HRQoL were similar in both groups

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Facet-joint injections for non-specific low back pain: a feasibility RCT

Background: Pain of lumbar facet-joint origin is a common cause of low back pain in adults and may lead to chronic pain and disability, with associated health and socioeconomic implications. The socioeconomic burden includes an inability to return to work resulting in loss of productivity in addition to direct and indirect health-care utilisation costs. Lumbar facet-joints are paired synovial joints between the superior and inferior articular processes of consecutive lumbar vertebrae and between the fifth lumbar vertebra and the sacrum. Facet-joint pain is defined as pain that arises from any structure that is part of the facet-joints, including the fibrous capsule, synovial membrane, hyaline cartilage and bone. This pain may be treated by intra-articular injections with local anaesthetic and steroid, although this treatment is not standardised. At present, there is no definitive research to support the use of targeted lumbar facet-joint injections to manage this pain. Because of the lack of high-quality, robust clinical evidence, the National Institute for Health and Care Excellence (NICE) guidelines on the management of chronic low back pain [NICE. Low Back Pain in Adults: Early Management. Clinical guideline (CG88). London: NICE; 2009] did not recommend the use of spinal injections despite their perceived potential to reduce pain intensity and improve rehabilitation, with NICE calling for further research to be undertaken. The updated guidelines [NICE. Low Back Pain and Sciatica in Over 16s: Assessment and Management. NICE guideline (NG59). London: NICE; 2016] again do not recommend the use of spinal injections. Objectives: To assess the feasibility of carrying out a definitive study to evaluate the clinical effectiveness and cost-effectiveness of lumbar facet-joint injections compared with a sham procedure in patients with non-specific low back pain of > 3 months’ duration. Design: Blinded parallel two-arm pilot randomised controlled trial. Setting: Initially planned as a multicentre study involving three NHS trusts in the UK, recruitment took place in the pain and spinal orthopaedic clinics at Barts Health NHS Trust only. Participants: Adult patients referred by their GP to the specialist clinics with non-specific low back pain of at least 3 months’ duration despite NICE-recommended best non-invasive care (education and one of a physical exercise programme, acupuncture or manual therapy). Patients who had already received lumbar facet-joint injections or who had had previous back surgery were excluded. Interventions: Participants who had a positive result following a diagnostic test (single medial branch nerve blocks) were randomised and blinded to receive either intra-articular lumbar facet-joint injections with steroids (intervention group) or a sham procedure (control group). All participants were invited to attend a group-based combined physical and psychological (CPP) programme. Main outcome measures: In addition to the primary outcome of feasibility, questionnaires were used to assess a range of pain-related (including the Brief Pain Inventory and Short-Form McGill Pain Questionnaire version 2) and disability-related (including the EuroQol-5 Dimensions five-level version and Oswestry Low Back Pain Questionnaire) issues. Health-care utilisation and cost data were also assessed. The questionnaire visits took place at baseline and at 6 weeks, 3 months and 6 months post randomisation. The outcome assessors were blinded to the allocation groups. Results: Of 628 participants screened for eligibility, nine were randomised to receive the study intervention (intervention group, n = 5; sham group, n = 4), six completed the CPP programme and eight completed the study. Limitations: Failure to achieve our expected recruitment targets led to early closure of the study by the funder. Conclusions: Because of the small number of participants recruited to the study, we were unable to draw any conclusions about the clinical effectiveness or cost-effectiveness of intra-articular lumbar facet-joint injections in the management of non-specific low back pain. Although we did not achieve the target recruitment rate from the pain clinics, we demonstrated our ability to develop a robust study protocol and deliver the intended interventions safely to all nine randomised participants, thus addressing many of the feasibility objectives. Future work: Stronger collaborations with primary care may improve the recruitment of patients earlier in their pain trajectory who are suitable for inclusion in a future trial. Trial registration: EudraCT 2014-003187-20 and Current Controlled Trials ISRCTN12191542. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 21, No. 74. See the NIHR Journals Library website for further project information