Physiological performance and inflammatory markers as indicators of complications after oesophageal cancer surgery

Background The extent to which physiological factors influence outcome following oesophageal cancer surgery is poorly understood. This study aimed to evaluate the extent to which cardiorespiratory fitness and selected metabolic factors predicted complications after surgery for carcinoma. Methods Two hundred and twenty‐five consecutive patients underwent preoperative cardiopulmonary exercise testing to determine peak oxygen uptake (urn:x-wiley:24749842:media:bjs550328:bjs550328-math-0001o2peak), anaerobic threshold and the ventilatory equivalent for carbon dioxide (urn:x-wiley:24749842:media:bjs550328:bjs550328-math-0002e/urn:x-wiley:24749842:media:bjs550328:bjs550328-math-0003co2). Cephalic venous blood was assayed for serum C‐reactive protein (CRP) and albumin levels, and a full blood count was done. The primary outcome measure was the Morbidity Severity Score (MSS). Results One hundred and ninety‐eight patients had anatomical resection. A high MSS (Clavien–Dindo grade III or above) was found in 48 patients (24·2 per cent) and was related to an increased CRP concentration (area under the receiver operating characteristic (ROC) curve (AUC) 0·62, P = 0·001) and lower urn:x-wiley:24749842:media:bjs550328:bjs550328-math-0004o2peak (AUC 0·36, P = 0·003). Dichotomization of CRP levels (above 10 mg/l) and urn:x-wiley:24749842:media:bjs550328:bjs550328-math-0005o2peak (below 18·6 ml per kg per min) yielded adjusted odds ratios (ORs) for a high MSS of 2·86 (P = 0·025) and 2·92 (P = 0·002) respectively. Compared with a cohort with a low Combined Inflammatory and Physiology Score (CIPS), the OR was 1·70 (95 per cent c.i. 0·85 to 3·39) for intermediate and 27·47 (3·12 to 241·69) for high CIPS (P < 0·001). Conclusion CRP and urn:x-wiley:24749842:media:bjs550328:bjs550328-math-0006o2peak were independently associated with major complications after potentially curative oesophagectomy for cancer. A composite risk score identified a group of patients with a high risk of developing complications

Spectroscopic profiling variations in extracellular vesicle biochemistry in a model of myogenesis.

Extracellular vesicles (EVs) hold value as accessible biomarkers for understanding cellular differentiation and related pathologies. Herein, EV biomarkers in models of skeletal muscle dormancy and differentiation have been comparatively profiled using Raman spectroscopy (RS). Significant variations in the biochemical fingerprint of EVs were detected, with an elevation in peaks associated with lipid and protein signatures during early myogenic differentiation (day 2). Principal component analysis revealed a clear separation between the spectra of EVs derived from myogenic and senescent cell types, with non-overlapping interquartile ranges and population median. Observations aligned with nanoparticle tracking data, highlighting a significant early reduction in EV concentration in senescent myoblast cultures as well as notable variations in EV morphology and diameter. As differentiation progressed physical and biochemical differences in the properties of EVs became less pronounced. This study demonstrates the applicability of RS as a high-resolution analytical method for profiling biochemical changes in EVs during early myogenesis

Randomized controlled trial of intraoperative goal-directed fluid therapy in aerobically fit and unfit patients having major colorectal surgery.

BACKGROUND: Intraoperative fluid therapy regimens using oesophageal Doppler monitoring (ODM) to optimize stroke volume (SV) (goal-directed fluid therapy, GDT) have been associated with a reduction in length of stay (LOS) and complication rates after major surgery. We hypothesized that intraoperative GDT would reduce the time to surgical readiness for discharge (RfD) of patients having major elective colorectal surgery but that this effect might be less marked in aerobically fit patients. METHODS: In this double-blinded controlled trial, 179 patients undergoing major open or laparoscopic colorectal surgery were characterized as aerobically 'fit' (n=123) or 'unfit' (n=56) on the basis of their performance during a cardiopulmonary exercise test. Within these fitness strata, patients were randomized to receive a standard fluid regimen with or without ODM-guided intraoperative GDT. RESULTS: GDT patients received an average of 1360 ml of additional intraoperative colloid. The mean cardiac index and SV at skin closure were significantly higher in the GDT group than in controls. Times to RfD and LOS were longer in GDT than control patients but did not reach statistical significance (median 6.8 vs 4.9 days, P=0.09, and median 8.8 vs 6.7 days, P=0.09, respectively). Fit GDT patients had an increased RfD (median 7.0 vs 4.7 days; P=0.01) and LOS (median 8.8 vs 6.0 days; P=0.01) compared with controls. CONCLUSIONS: Intraoperative SV optimization conferred no additional benefit over standard fluid therapy. In an aerobically fit subgroup of patients, GDT was associated with detrimental effects on the primary outcome. TRIAL REGISTRY: UK NIHR CRN 7285, ISRCTN 14680495. http://public.ukcrn.org.uk/Search/StudyDetail.aspx?StudyID=7285

A prospective, multicentre, observational cohort study of analgesia and outcome after pneumonectomy

Background Meta-analysis and systematic reviews of epidural compared with paravertebral blockade analgesia techniques for thoracotomy conclude that although the analgesia is comparable, paravertebral blockade has a better short-term side-effect profile. However, reduction in major complications including mortality has not been proven. Methods The UK pneumonectomy study was a prospective observational cohort study in which all UK thoracic surgical centres were invited to participate. Data presented here relate to the mode of analgesia and outcome. Data were analysed for 312 patients having pneumonectomy at 24 UK thoracic surgical centres in 2005. The primary endpoint was a major complication. Results The most common type of analgesia used was epidural (61.1%) followed by paravertebral infusion (31%). Epidural catheter use was associated with major complications (odds ratio 2.2, 95% confidence interval 1.1–3.8; P=0.02) by stepwise logistic regression analysis. Conclusions An increased incidence of clinically important major post-pneumonectomy complications was associated with thoracic epidural compared with paravertebral blockade analgesia. However, this study is unable to provide robust evidence to change clinical practice for a better clinical outcome. A large multicentre randomized controlled trial is now needed to compare the efficacy, complications, and cost-effectiveness of epidural and paravertebral blockade analgesia after major lung resection with the primary outcome of clinically important major morbidity

Risk of opioid misuse in people with cancer and pain and related clinical considerations: a qualitative study of the perspectives of Australian general practitioners.

OBJECTIVE:To explore the perspectives of general practitioners (GPs) concerning the risk of opioid misuse in people with cancer and pain and related clinical considerations. DESIGN:A qualitative approach using semistructured telephone interviews. Analysis used an integrative approach. SETTING:Primary care. PARTICIPANTS:Australian GPs with experience of prescribing opioids for people with cancer and pain. RESULTS:Twenty-two GPs participated, and three themes emerged. Theme 1 (Misuse is not the main problem) contextualised misuse as a relatively minor concern compared with pain control and toxicity, and highlighted underlying systemic factors, including limitations in continuity of care and doctor expertise. Theme 2 ('A different mindset' for cancer pain) captured participants' relative comfort in prescribing opioids for pain in cancer versus non-cancer contexts, and acknowledgement that compassion and greater perceived community acceptance were driving factors, in addition to scientific support for mechanisms and clinical efficacy. Participant attitudes towards prescribing for people with cancer versus non-cancer pain differed most when cancer was in the palliative phase, when they were unconcerned by misuse. Participants were equivocal about the risk-benefit ratio of long-term opioid therapy in the chronic phase of cancer, and were reluctant to prescribe for disease-free survivors. Theme 3 ('The question is always, 'how lazy have you been?') captured participants' acknowledgement that they sometimes prescribed opioids for cancer pain as a default, easier option compared with more holistic pain management. CONCLUSIONS:Findings highlight the role of specific clinical considerations in distinguishing risk of opioid misuse in the cancer versus non-cancer population, rather than diagnosis per se. Further efforts are needed to ensure continuity of care where opioid prescribing is shared. Greater evidence is needed to guide opioid prescribing in disease-free survivors and the chronic phase of cancer, especially in the context of new treatments for metastatic disease

Cardiopulmonary fitness predicts postoperative major morbidity after esophagectomy for patients with cancer

Surgery for radical treatment of esophageal cancer (EC) carries significant inherent risk. The objective identification of patients who are at high risk of complications is of importance. In this study the prognostic value of cardiopulmonary fitness variables (CPF) derived from cardiopulmonary exercise testing (CPET) was assessed in patients undergoing potentially curative surgery for EC within an enhanced recovery program. OC patients underwent preoperative CPET using automated breath‐by‐breath respiratory gas analysis, with measurements taken during a ramped exercise test on a bicycle. The prognostic value of urn:x-wiley:2051817X:media:phy214174:phy214174-math-0001, Anaerobic Threshold (AT) and VE/VCO2 derived from CPET were studied in relation to post‐operative morbidity, which was collected prospectively, and overall survival. Consecutive 120 patients were included for analysis (median age 65 years, 100 male, 75 neoadjuvant therapy). Median AT in the cohort developing major morbidity (Clavien–Dindo classification >2) was 10.4 mL/kg/min compared with 11.3 mL/kg/min with no major morbidity (P = 0.048). Median urn:x-wiley:2051817X:media:phy214174:phy214174-math-0002 in the cohort developing major morbidity was 17.0 mL/kg/min compared with 18.7 mL/kg/min in the cohort (P = 0.009). urn:x-wiley:2051817X:media:phy214174:phy214174-math-0003 optimum cut‐off was 17.0 mL/kg/min (sensitivity 70%, specificity 53%) and for AT was 10.5 mL/kg/min (sensitivity 60%, specificity 44%). Multivariable analysis revealed urn:x-wiley:2051817X:media:phy214174:phy214174-math-0004 to be the only independent factor to predict major morbidity (OR 0.85, 95% CI 0.75–0.97, P = 0.018). Cumulative survival was associated with operative morbidity severity (χ2 = 4.892, df = 1, P = 0.027). These results indicate that urn:x-wiley:2051817X:media:phy214174:phy214174-math-0005 as derived from CPET is a significant predictor of major morbidity after oesophagectomy highlighting the physiological importance of cardiopulmonary fitness

An exploration of parents’ preferences for foot care in juvenile idiopathic arthritis: a possible role for the discrete choice experiment

Background: An increased awareness of patients’ and parents’ care preferences regarding foot care is desirable from a clinical perspective as such information may be utilised to optimise care delivery. The aim of this study was to examine parents’ preferences for, and valuations of foot care and foot-related outcomes in juvenile idiopathic arthritis (JIA).&lt;p&gt;&lt;/p&gt; Methods: A discrete choice experiment (DCE) incorporating willingness-to-pay (WTP) questions was conducted by surveying 42 parents of children with JIA who were enrolled in a randomised-controlled trial of multidisciplinary foot care at a single UK paediatric rheumatology outpatients department. Attributes explored were: levels of pain; mobility; ability to perform activities of daily living (ADL); waiting time; referral route; and footwear. The DCE was administered at trial baseline. DCE data were analysed using a multinomial-logit-regression model to estimate preferences and relative importance of attributes of foot care. A stated-preference WTP question was presented to estimate parents’ monetary valuation of health and service improvements.&lt;p&gt;&lt;/p&gt; Results: Every attribute in the DCE was statistically significant (p &#60; 0.01) except that of cost (p = 0.118), suggesting that all attributes, except cost, have an impact on parents’ preferences for foot care for their child. The magnitudes of the coefficients indicate that the strength of preference for each attribute was (in descending order): improved ability to perform ADL, reductions in foot pain, improved mobility, improved ability to wear desired footwear, multidisciplinary foot care route, and reduced waiting time. Parents’ estimated mean annual WTP for a multidisciplinary foot care service was £1,119.05.&lt;p&gt;&lt;/p&gt; Conclusions: In terms of foot care service provision for children with JIA, parents appear to prefer improvements in health outcomes over non-health outcomes and service process attributes. Cost was relatively less important than other attributes suggesting that it does not appear to impact on parents’ preferences.&lt;p&gt;&lt;/p&gt

Use of low-dose oral theophylline as an adjunct to inhaled corticosteroids in preventing exacerbations of chronic obstructive pulmonary disease: study protocol for a randomised controlled trial.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with high morbidity, mortality, and health-care costs. An incomplete response to the anti-inflammatory effects of inhaled corticosteroids is present in COPD. Preclinical work indicates that 'low dose' theophylline improves steroid responsiveness. The Theophylline With Inhaled Corticosteroids (TWICS) trial investigates whether the addition of 'low dose' theophylline to inhaled corticosteroids has clinical and cost-effective benefits in COPD. METHOD/DESIGN: TWICS is a randomised double-blind placebo-controlled trial conducted in primary and secondary care sites in the UK. The inclusion criteria are the following: an established predominant respiratory diagnosis of COPD (post-bronchodilator forced expiratory volume in first second/forced vital capacity [FEV1/FVC] of less than 0.7), age of at least 40 years, smoking history of at least 10 pack-years, current inhaled corticosteroid use, and history of at least two exacerbations requiring treatment with antibiotics or oral corticosteroids in the previous year. A computerised randomisation system will stratify 1424 participants by region and recruitment setting (primary and secondary) and then randomly assign with equal probability to intervention or control arms. Participants will receive either 'low dose' theophylline (Uniphyllin MR 200 mg tablets) or placebo for 52 weeks. Dosing is based on pharmacokinetic modelling to achieve a steady-state serum theophylline of 1-5 mg/l. A dose of theophylline MR 200 mg once daily (or placebo once daily) will be taken by participants who do not smoke or participants who smoke but have an ideal body weight (IBW) of not more than 60 kg. A dose of theophylline MR 200 mg twice daily (or placebo twice daily) will be taken by participants who smoke and have an IBW of more than 60 kg. Participants will be reviewed at recruitment and after 6 and 12 months. The primary outcome is the total number of participant-reported COPD exacerbations requiring oral corticosteroids or antibiotics during the 52-week treatment period. DISCUSSION: The demonstration that 'low dose' theophylline increases the efficacy of inhaled corticosteroids in COPD by reducing the incidence of exacerbations is relevant not only to patients and clinicians but also to health-care providers, both in the UK and globally. TRIAL REGISTRATION: Current Controlled Trials ISRCTN27066620 was registered on Sept. 19, 2013, and the first subject was randomly assigned on Feb. 6, 2014

A variational method based on weighted graph states

In a recent article [Phys. Rev. Lett. 97 (2006), 107206], we have presented a class of states which is suitable as a variational set to find ground states in spin systems of arbitrary spatial dimension and with long-range entanglement. Here, we continue the exposition of our technique, extend from spin 1/2 to higher spins and use the boson Hubbard model as a non-trivial example to demonstrate our scheme.Comment: 36 pages, 13 figure

Inhomogeneous superconductivity in organic conductors: role of disorder and magnetic field

Several experimental studies have shown the presence of spatially inhomogeneous phase coexistence of superconducting and non superconducting domains in low dimensional organic superconductors. The superconducting properties of these systems are found to be strongly dependent on the amount of disorder introduced in the sample regardless of its origin. The suppression of the superconducting transition temperature $T_c$ shows clear discrepancy with the result expected from the Abrikosov-Gor'kov law giving the behavior of $T_c$ with impurities. Based on the time dependent Ginzburg-Landau theory, we derive a model to account for the striking feature of $T_c$ in organic superconductors for different types of disorder by considering the segregated texture of the system. We show that the calculated $T_c$ quantitatively agrees with experiments. We also focus on the role of superconducting fluctuations on the upper critical fields $H_{c2}$ of layered superconductors showing slab structure where superconducting domains are sandwiched by non-superconducting regions. We found that $H_{c2}$ may be strongly enhanced by such fluctuations.Comment: to appear in Journal of Physics: Condensed Matte