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Aim The aim of this work was to determine the factors associated with poor wound healing in patients with perianal Crohn's disease (pCD) who had undergone proctectomy in the era of biologic therapies. Method Case record review was performed on 103 patients with pCD who underwent proctectomy at St Mark's Hospital, Harrow and the Western General Hospital, Edinburgh between 2005 and 2017. Healing rates at 6 and 12 months post-proctectomy were considered; univariate analysis was performed. Results Sixty out of 103 patients (58.3%) had failure of wound healing at 6 months and 41/103 (39.8%) at 12 months. In total, 63.1% (65/103) patients received biologic therapies prior to proctectomy; however, exposure to biologics was not a significant factor in predicting failure of wound healing at 12 months (infliximab p = 0.255; adalimumab p = 0.889; vedolizumab p = 0.153). Male gender was the only variable associated with poor wound healing at 12 months on univariate analysis (p = 0.017). A lower pre-operative C-reactive protein was associated with early wound healing at 6 months compared with at 12 months (p = 0.041) on univariate analysis. Other parameters not associated with rates of wound healing included smoking status, corticosteroid exposure, thiopurine exposure, number of previous biologics, perianal sepsis on MRI within the last 12 months, duration of CD prior to proctectomy and pre-operative albumin. Conclusion More than a third of patients had unhealed wounds 12 months after proctectomy. We report that unhealed wounds are more common in male patients. Importantly, our results also suggest that exposure to biologics does not affect rates of wound healing.

Objectives Thoracostomy is often a required treatment in patients with thoracic trauma; however, performing a thoracostomy using traditional techniques can have complications. Ultrasound can be a beneficial tool for identifying the correct thoracostomy insertion site. We designed a randomized prospective study to assess if ultrasound guidance can improve thoracostomy site identification over traditional techniques. Methods Emergency medicine residents were randomly assigned to use palpation or ultrasound to identify a safe insertion site for thoracostomy placement. The target population comprised of hemodynamically stable trauma patients who received an extended focused assessment with sonography for trauma (EFAST) and a chest computed tomography (CT) exam. The resident placed a radiopaque marker on the skin of the patient where a safe intercostal space was believed to be located, either by palpation or ultrasound. Clinical ultrasound faculty reviewed the CT to confirm marker placement relative to the diaphragm. A Fischer's exact test was used to analyze the groups. Results One hundred and forty-seven patients were enrolled in the study, 75 in the ultrasound group and 72 in the landmark group. This resulted in the placement of 271 total thoracostomy site markers, 142 by ultrasound and 129 by palpation and landmarks. The ultrasound group correctly identified thoracostomy insertion sites above the diaphragm in 97.2% (138/142) of patients, while the palpation group identified a safe insertion site in 88.4% (114/129) of patients (P = .0073). Conclusion This study found that emergency medicine residents are more likely to identify a safe tube thoracostomy insertion site in trauma patients by using ultrasound, as compared to using landmarks and palpation.

Aim: Discussions regarding sex after colorectal and pelvic floor surgery are often overlooked by clinicians. This is the first patient designed and delivered study to explore sexual function and practices after colorectal surgery. The aim was to explore the questions about sex that matter to patients and their partners following colorectal or pelvic floor surgery through a patient and public involvement survey. The results of this work will underpin the creation of a sex patient reported outcome measure. Methods: An anonymous online survey tool (Survey Monkey™) was disseminated via social media (Twitter, Facebook). Thematic analysis was applied to 130 free text comments posted by participants to identify key themes. Results: Some 632 individuals completed the survey. Most respondents were women (80% n = 507), 49.5% (n = 312) were married and 14% (n = 87) identified as LGBT+ (lesbian, gay, bisexual and transgender +). Indications for surgery varied: 34% were treated for ulcerative colitis (n = 214); 31% Crohn's (n = 196); 17% (n = 109) cancer; and 17% (n = 110) for perianal fistula. For patients who had a stoma formed (85%, n = 540), over half (51%, n = 324) lived with their stoma for 1–5 years. Respondents reported substantial alterations to their preferences for sexual positions, sexual activity and body confidence following surgery. Most respondents indicated that they were not offered advice about sex by a healthcare professional. Conclusions: The survey showed a substantial impact on the mechanics of sex following colorectal surgery. Few patients were offered preoperative information regarding sex, which has implications for informed consent. This study demonstrates a clear unmet need, voiced by patients, that open dialogue is necessary preoperatively to discuss sexual (dys)function.

Dissolution dynamic nuclear polarisation (dDNP) of 13C-labelled pyruvate in magnetic resonance spectroscopy/imaging (MRS/MRSI) has the potential for monitoring tumour progression and treatment response. Pyruvate delivery, its metabolism to lactate and efflux were investigated in rat P22 sarcomas following simultaneous intravenous administration of hyperpolarised 13C-labelled pyruvate (13C1-pyruvate) and urea (13C-urea), a nonmetabolised marker. A general mathematical model of pyruvate-lactate exchange, incorporating an arterial input function (AIF), enabled the losses of pyruvate and lactate from tumour to be estimated, in addition to the clearance rate of pyruvate signal from blood into tumour, Kip, and the forward and reverse fractional rate constants for pyruvate-lactate signal exchange, kpl and klp. An analogous model was developed for urea, enabling estimation of urea tumour losses and the blood clearance parameter, Kiu. A spectral fitting procedure to blood time-course data proved superior to assuming a gamma-variate form for the AIFs. Mean arterial blood pressure marginally correlated with clearance rates. Kiu equalled Kip, indicating equivalent permeability of the tumour vasculature to urea and pyruvate. Fractional loss rate constants due to effluxes of pyruvate, lactate and urea from tumour tissue into blood (kpo, klo and kuo, respectively) indicated that T1s and the average flip angle, θ, obtained from arterial blood were poor surrogates for these parameters in tumour tissue. A precursor-product model, using the tumour pyruvate signal time-course as the input for the corresponding lactate signal time-course, was modified to account for the observed delay between them. The corresponding fractional rate constant, kavail, most likely reflected heterogeneous tumour microcirculation. Loss parameters, estimated from this model with different TRs, provided a lower limit on the estimates of tumour T1 for lactate and urea. The results do not support use of hyperpolarised urea for providing information on the tumour microcirculation over and above what can be obtained from pyruvate alone. The results also highlight the need for rigorous processes controlling signal quantitation, if absolute estimations of biological parameters are required.

Introduction The prognosis of dysplasia in patients with IBD is largely determined from observational studies from the pre-videoendoscopic era (pre-1990s) that does not reflect recent advances in endoscopic imaging and resection. Aims To better understand the risk of synchronous colorectal cancer and metachronous advanced neoplasia (ie high-grade dysplasia or cancer) associated with dysplasia diagnosed in the videoendoscopic era, and to stratify risk according to a lesion's morphology, endoscopic resection status or whether it was incidentally detected on biopsy of macroscopically normal colonic mucosa (ie invisible). Methods A systematic search of original articles published between 1990 and February 2020 was performed. Eligible studies reported on incidence of advanced neoplasia at follow-up colectomy or colonoscopy for IBD-dysplasia patients. Quantitative and qualitative analyses were performed. Results Thirty-three studies were eligible for qualitative analysis (five for the meta-analysis). Pooled estimated proportions of incidental synchronous cancers found at colectomy performed for a pre-operative diagnosis of visible high-grade dysplasia, invisible high-grade dysplasia, visible low-grade dysplasia and invisible low-grade dysplasia were 13.7% (95% CI 0.0-54.1), 11.4% (95% CI 4.6-20.3), 2.7% (95% CI 0.0-7.1) and 2.4% (95% CI 0.0-8.5) respectively. The lowest incidences of metachronous advanced neoplasia, for dysplasia not managed with immediate colectomy but followed up with surveillance, tended to be reported by the studies where high definition imaging and/or chromoendoscopy was used and endoscopic resection of visible dysplasia was histologically confirmed. Conclusions The prognosis of IBD-dysplasia diagnosed in the videoendoscopic era appears to have been improved but the quality of evidence remains low. Larger, prospective studies are needed to guide management. PROSPERO registration no: CRD42019105736.

Accurate assessment of SARS-CoV-2 immunity is critical in evaluating vaccine efficacy and devising public health policies. Whilst the exact nature of effective immunity remains incompletely defined, SARS-CoV-2-specific T-cell responses are a critical feature that will likely form a key correlate of protection against COVID-19. Here, we developed and optimized a high-throughput whole blood-based assay to determine the T-cell response associated with prior SARS-CoV-2 infection and/or vaccination amongst 231 healthy donors and 68 cancer patients. Following overnight in vitro stimulation with SARS-CoV-2-specific peptides, blood plasma samples were analysed for TH 1-type cytokines. Highly significant differential IFN-γ+ /IL-2+ SARS-CoV-2-specific T-cell responses were seen amongst previously infected COVID-19-positive healthy donors in comparison with unknown / naïve individuals (p < 0·0001). IFN-γ production was more effective at identifying asymptomatic donors, demonstrating higher sensitivity (96·0% vs. 83·3%) but lower specificity (84·4% vs. 92·5%) than measurement of IL-2. A single COVID-19 vaccine dose induced IFN-γ and/or IL-2 SARS-CoV-2-specific T-cell responses in 116 of 128 (90·6%) healthy donors, reducing significantly to 27 of 56 (48·2%) when measured in cancer patients (p < 0·0001). A second dose was sufficient to boost T-cell responses in the majority (90·6%) of cancer patients, albeit IFN-γ+ responses were still significantly lower overall than those induced in healthy donors (p = 0·034). Three-month post-vaccination T-cell responses also declined at a faster rate in cancer patients. Overall, this cost-effective standardizable test ensures accurate and comparable assessments of SARS-CoV-2-specific T-cell responses amenable to widespread population immunity testing, and identifies individuals at greater need of booster vaccinations.

Dissolution dynamic nuclear polarisation (dDNP) of 13 C-labelled pyruvate in magnetic resonance spectroscopy/imaging (MRS/MRSI) has the potential for monitoring tumour progression and treatment response. Pyruvate delivery, its metabolism to lactate and efflux were investigated in rat P22 sarcomas following simultaneous intravenous administration of hyperpolarised 13 C-labelled pyruvate (13 C1 -pyruvate) and urea (13 C-urea), a nonmetabolised marker. A general mathematical model of pyruvate-lactate exchange, incorporating an arterial input function (AIF), enabled the losses of pyruvate and lactate from tumour to be estimated, in addition to the clearance rate of pyruvate signal from blood into tumour, Kip , and the forward and reverse fractional rate constants for pyruvate-lactate signal exchange, kpl and klp . An analogous model was developed for urea, enabling estimation of urea tumour losses and the blood clearance parameter, Kiu . A spectral fitting procedure to blood time-course data proved superior to assuming a gamma-variate form for the AIFs. Mean arterial blood pressure marginally correlated with clearance rates. Kiu equalled Kip , indicating equivalent permeability of the tumour vasculature to urea and pyruvate. Fractional loss rate constants due to effluxes of pyruvate, lactate and urea from tumour tissue into blood (kpo , klo and kuo , respectively) indicated that T1 s and the average flip angle, θ, obtained from arterial blood were poor surrogates for these parameters in tumour tissue. A precursor-product model, using the tumour pyruvate signal time-course as the input for the corresponding lactate signal time-course, was modified to account for the observed delay between them. The corresponding fractional rate constant, kavail , most likely reflected heterogeneous tumour microcirculation. Loss parameters, estimated from this model with different TRs, provided a lower limit on the estimates of tumour T1 for lactate and urea. The results do not support use of hyperpolarised urea for providing information on the tumour microcirculation over and above what can be obtained from pyruvate alone. The results also highlight the need for rigorous processes controlling signal quantitation, if absolute estimations of biological parameters are required.

© 2018 The Authors. New Phytologist © 2018 New Phytologist Trust Almost all plant species interact with one or more symbioses somewhere within their distribution range. Bringing together plant trait data and growth responses to symbioses spanning 552 plant species, we provide for the first time on a large scale (597 studies) a quantitative synthesis on plant performance differences between eight major types of symbiosis, including mycorrhizas, N-fixing bacteria, fungal endophytes and ant–plant interactions. Frequency distributions of plant growth responses varied considerably between different types of symbiosis, in terms of both mean effect and ‘risk’, defined here as percentage of experiments reporting a negative effect of symbiosis on plants. Contrary to expectation, plant traits were poor predictors of growth response across and within all eight symbiotic associations. Our analysis showed no systematic additive effect when a host plant engaged in two functionally different symbioses. This synthesis suggests that plant species’ ecological strategies have little effect in determining the influence of a symbiosis on host plant growth. Reliable quantification of differences in plant performance across symbioses will prove valuable for developing general hypotheses on how species become engaged in mutualisms without a guarantee of net returns.