The role of measuring exhaled breath biomarkers in sarcoidosis: A systematic review

Introduction: Sarcoidosis is a chronic granulomatous disease of unknown aetiology with a variable clinical course and prognosis. There is a growing need to identify non-invasive biomarkers to differentiate between clinical phenotypes, identify those at risk of disease progression and monitor response to treatment. Objectives: We undertook a systematic review and meta-analysis, to evaluate the utility of breath-based biomarkers in discriminating sarcoidosis from healthy controls, alongside correlation with existing non-breath based biomarkers used in clinical practice, radiological stage, markers of disease activity and response to treatment. Methods: Electronic searches were undertaken during November 2017 using PubMed, Ebsco, Embase and Web of Science to capture relevant studies evaluating breath-based biomarkers in adult patients with sarcoidosis. Results: 353 papers were screened; 21 met the inclusion criteria and assessed 25 different biomarkers alongside VOCs in exhaled breath gas or condensate. Considerable heterogeneity existed amongst the studies in terms of participant characteristics, sampling and analytical methods. Elevated biomarkers in sarcoidosis included 8-isoprostane, carbon monoxide, neopterin, TGF-β1, TNFα, CysLT and several metallic elements including chromium, silicon and nickel. Three studies exploring VOCs were able to distinguish sarcoidosis from controls. Meta-analysis of four studies assessing alveolar nitric oxide showed no significant difference between sarcoidosis and healthy controls (2.22ppb; 95% CI -0.83, 5.27) however, a high degree of heterogeneity was observed with an I2 of 93.4% (p<0.001). Inconsistent or statistically insignificant results were observed for correlations between several biomarkers and radiological stage, markers of disease activity or treatment. Conclusions: The evidence for using breath biomarkers to diagnose and monitor sarcoidosis remains inconclusive with many studies limited by small sample sizes and lack of standardisation. VOCs have shown promising potential but further research is required to evaluate their prognostic role

Most bowel cancer symptoms do not indicate colorectal cancer and polyps: a systematic review

<p>Abstract</p> <p>Background</p> <p>Bowel symptoms are often considered an indication to perform colonoscopy to identify or rule out colorectal cancer or precancerous polyps. Investigation of bowel symptoms for this purpose is recommended by numerous clinical guidelines. However, the evidence for this practice is unclear. The objective of this study is to systematically review the evidence about the association between bowel symptoms and colorectal cancer or polyps.</p> <p>Methods</p> <p>We searched the literature extensively up to December 2008, using MEDLINE and EMBASE and following references. For inclusion in the review, papers from cross sectional, case control and cohort studies had to provide a 2×2 table of symptoms by diagnosis (colorectal cancer or polyps) or sufficient data from which that table could be constructed. The search procedure, quality appraisal, and data extraction was done twice, with disagreements resolved with another reviewer. Summary ROC analysis was used to assess the diagnostic performance of symptoms to detect colorectal cancer and polyps.</p> <p>Results</p> <p>Colorectal cancer was associated with rectal bleeding (AUC 0.66; LR+ 1.9; LR- 0.7) and weight loss (AUC 0.67, LR+ 2.5, LR- 0.9). Neither of these symptoms was associated with the presence of polyps. There was no significant association of colorectal cancer or polyps with change in bowel habit, constipation, diarrhoea or abdominal pain. Neither the clinical setting (primary or specialist care) nor study type was associated with accuracy.</p> <p>Most studies had methodological flaws. There was no consistency in the way symptoms were elicited or interpreted in the studies.</p> <p>Conclusions</p> <p>Current evidence suggests that the common practice of performing colonoscopies to identify cancers in people with bowel symptoms is warranted only for rectal bleeding and the general symptom of weight loss. Bodies preparing guidelines for clinicians and consumers to improve early detection of colorectal cancer need to take into account the limited value of symptoms.</p

Synthesis and crystal structures of multifunctional tosylates as basis for star-shaped poly(2-ethyl-2-oxazoline)s

The synthesis of well-defined polymer architectures is of major importance for the development of complex functional materials. In this contribution, we discuss the synthesis of a range of multifunctional star-shaped tosylates as potential initiators for the living cationic ring-opening polymerization (CROP) of 2-oxazolines resulting in star-shaped polymers. The synthesis of the tosylates was performed by esterification of the corresponding alcohols with tosyl chloride. Recrystallization of these tosylate compounds afforded single crystals, and the X-ray crystal structures of di-, tetra- and hexa-tosylates are reported. The use of tetra- and hexa-tosylates, based on (di)pentaerythritol as initiators for the CROP of 2-ethyl-2-oxazoline, resulted in very slow initiation and ill-defined polymers, which is most likely caused by steric hindrance in these initiators. As a consequence, a porphyrin-cored tetra-tosylate initiator was prepared, which yielded a well-defined star-shaped poly(2-ethyl-2-oxazoline) by CROP as demonstrated by SEC with RI, UV and diode-array detectors, as well as by 1H NMR spectroscopy

Libraries of statistical hydroxypropyl acrylate containing copolymers with LCST properties prepared by NMP

The nitroxide-mediated copolymerization of 2-hydroxypropyl acrylate (HPA) with N-acryloylmorpholine (Amor) or N,N-dimethylacrylamide (DMA) was investigated using N-tert-butyl-N-(1′-diethylphosphono-2,2′-dimethylpropyl)-O-(2-carboxyl-prop-2-yl) (BlocBuilder) alkoxyamine initiator and additional free nitroxide (SG-1). Different reaction conditions, such as the concentration of additional SG-1, were tested to optimize the homopolymerizations using a Chemspeed ASW2000 automated parallel synthesizer. Best control for the homopolymerizations (polydispersity indices of 1.2−1.3) of all three monomers was achieved using 20% additional SG-1 (relative to the initiator) at a reaction temperature of 110 °C for 2 M solutions in N,N-dimethylformamide and a monomer/initiator ratio of 100/1. Libraries of P(Amor-stat-HPA) and P(DMA-stat-HPA) were synthesized with 0−100 mol % HPA with 10 mol % increments using the optimized conditions obtained for the homopolymerizations. The resulting polymers had narrow molecular weight distributions, and their compositions, determined using 1H NMR spectroscopy and elemental analysis, were close to the theoretical compositions. In addition, all copolymers of both libraries had single glass transition temperatures (Tg), and the transition temperatures decreased from the Tg of P(Amor) (147 °C) and P(DMA) (111 °C) to the Tg of P(HPA) (22 °C) with increasing HPA content. The cloud point of P(HPA) showed concentration dependence as well as a concentration dependent hysteresis. The cloud points of aqueous solutions of the copolymer libraries could be tuned from 21.4 to 88.0 °C and to 82.9 °C for P(Amor-stat-HPA) and P(DMA-stat-HPA), respectively, at a concentration of 1 wt %. LCST behavior was observed for copolymers with >40 wt % HPA in P(Amor-stat-HPA) and >55 wt % HPA in the P(DMA-stat-HPA) library

Libraries of methacrylic acid and oligo(ethylene glycol) methacrylate copolymers with LCST behavior

Homopolymers of methacrylic acid (MAA), monoethyleneglycol methyl ether methacrylate (MEOMA), diethyleneglycol methyl ether methacrylate (MEO2MA), oligo(ethyleneglycol) methyl ether methacrylate (OEGMA475 and OEGMA1100) and oligo(ethyleneglycol) ethyl ether methacrylate (OEGEMA246) were synthesized with various chain lengths via reversible addition fragmentation chain transfer (RAFT) polymerization. The homopolymers of MAA, MEOMA and OEGMA1100 did not show any cloud point (CP) in the range of 0–100 °C, whereas at a pH value of 7, the CPs were found to be 20.6, 93.7, and 20.0 °C for p(MEO2MA), p(OEGMA475) and p(OEGEMA246), respectively, with an initial monomer to initiator ratio of 50. Furthermore, statistical copolymer libraries of MAA with OEGMA475 and OEGMA1100 were prepared. The cloud points of the random copolymers of MAA and OEGMA475 were found to be in the range of 20–90 °C; surprisingly, even though the homopolymers of MAA and OEGMA1100 did not exhibit any LCST behavior, the copolymers of these monomers at certain molar ratios (up to 40% OEGMA1100) revealed a double responsive behavior for both temperature and pH. Finally, the cloud points were found to be in the range of 22–98 °C, measured at pH values of 2, 4, and 7, while no cloud point was detected at pH 10. © Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 7138–7147, 200