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  • Oxford University Press (OUP)  (48)
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  • 1
    Online Resource
    Online Resource
    l-Serine Reduces Spinal Cord Pathology in a Vervet Model of Preclinical ALS/MND
    Oxford University Press (OUP) ; 2020
    In:  Journal of Neuropathology & Experimental Neurology Vol. 79, No. 4 ( 2020-04-01), p. 393-406
    Details
    In: Journal of Neuropathology & Experimental Neurology, Oxford University Press (OUP), Vol. 79, No. 4 ( 2020-04-01), p. 393-406
    Abstract: The early neuropathological features of amyotrophic lateral sclerosis/motor neuron disease (ALS/MND) are protein aggregates in motor neurons and microglial activation. Similar pathology characterizes Guamanian ALS/Parkinsonism dementia complex, which may be triggered by the cyanotoxin β-N-methylamino-l-alanine (BMAA). We report here the occurrence of ALS/MND-type pathological changes in vervets (Chlorocebus sabaeus; n = 8) fed oral doses of a dry powder of BMAA HCl salt (210 mg/kg/day) for 140 days. Spinal cords and brains from toxin-exposed vervets were compared to controls fed rice flour (210 mg/kg/day) and to vervets coadministered equal amounts of BMAA and l-serine (210 mg/kg/day). Immunohistochemistry and quantitative image analysis were used to examine markers of ALS/MND and glial activation. UHPLC-MS/MS was used to confirm BMAA exposures in dosed vervets. Motor neuron degeneration was demonstrated in BMAA-dosed vervets by TDP-43+ proteinopathy in anterior horn cells, by reactive astrogliosis, by activated microglia, and by damage to myelinated axons in the lateral corticospinal tracts. Vervets dosed with BMAA + l-serine displayed reduced neuropathological changes. This study demonstrates that chronic dietary exposure to BMAA causes ALS/MND-type pathological changes in the vervet and coadministration of l-serine reduces the amount of reactive gliosis and the number of protein inclusions in motor neurons.
    Type of Medium: Online Resource
    ISSN: 0022-3069 , 1554-6578
    URL: Article
    DOI: 10.1093/jnen/nlaa002
    RVK:
    XA 55250
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 2033048-0
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  • 2
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    Online Resource
    Killing of Legionella pneumophila by nitric oxide in γ-interferon-activated macrophages
    Oxford University Press (OUP) ; 1992
    In:  Journal of Leukocyte Biology Vol. 52, No. 6 ( 1992-12-01), p. 625-629
    Details
    In: Journal of Leukocyte Biology, Oxford University Press (OUP), Vol. 52, No. 6 ( 1992-12-01), p. 625-629
    Abstract: The role of nitric oxide (NO) radicals in killing the intracellular bacterial pathogen Legionella pneumophila (Lp) was examined in infected macrophages. Murine (RAW 264.7) and human (HL-60) cell monolayers were treated with 100 U/mlγ-interferon (IFN) and cocultured with Lp in the presence and absence of NGMMA, a specific inhibitor of NO production. Viable Lp in IFN-treated RAW 264.7 cells decreased from 3.8 to 0.7 ± 0.12 log CFU/ml after 24 h incubation, whereas in IFN + NGMMA-treated RAW 264.7 cells, viable Lp persisted at 2.2 ± 0.2 log CFU/ml after 24 h. This increased survival corresponded with an inhibition of NO production (5.65 ± 2.99 μM with NGMMA vs. 58.6 ± 5.36 μM without NGMMA). Viable Lp were susceptible to killing, in a dose-dependent fashion, by 0, 2.5, and 5.0 mM sodium nitroprusside, a source of NO radicals. IFN-treated RAW 264.7 cells also had significantly decreased levels of intracellular iron (below assay limit) when compared to IFN + NGMMA-treated cells (72.0 ± 0.78 % of control). Normally permissive HL-60 cells treated with IFN were bacteriostatic rather than bactericidal, and NO production was not detected above background. Thus, NO radicals play a critical role in the bactericidal activity against Lp by IFN-treated RAW 264.7 cells, but the absence of NO production limits IFN-treated HL-60 cells to bac- teriostasis.
    Type of Medium: Online Resource
    ISSN: 0741-5400 , 1938-3673
    URL: Article
    DOI: 10.1002/jlb.52.6.625
    RVK:
    XA 10000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 1992
    detail.hit.zdb_id: 2026833-6
    SSG: 12
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  • 3
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    IMG-06. PREDICTING SURVIVAL FROM PERFUSION AND DIFFUSION MRI BY MACHINE LEARNING
    Oxford University Press (OUP) ; 2020
    In:  Neuro-Oncology Vol. 22, No. Supplement_3 ( 2020-12-04), p. iii356-iii356
    Details
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 22, No. Supplement_3 ( 2020-12-04), p. iii356-iii356
    Abstract: Magnetic Resonance Imaging (MRI) is routinely used in the assessment of children’s brain tumours. Reduced diffusion and increased perfusion on MRI are commonly associated with higher grade but there is a lack of quantitative data linking these parameters to survival. Machine learning is increasingly being used to develop diagnostic tools but its use in survival analysis is rare. In this study we combine quantitative parameters from diffusion and perfusion MRI with machine learning to develop a model of survival for paediatric brain tumours. METHOD: 69 children from 4 centres (Birmingham, Liverpool, Nottingham, Newcastle) underwent MRI with diffusion and perfusion (dynamic susceptibility contrast) at diagnosis. Images were processed to form ADC, cerebral blood volume (CBV) and vessel leakage correction (K2) parameter maps. Parameter mean, standard deviation and heterogeneity measures (skewness and kurtosis) were calculated from tumour and whole brain and used in iterative Bayesian survival analysis. The features selected were used for k-means clustering and differences in survival between clusters assessed by Kaplan-Meier and Cox-regression. RESULTS Bayesian analysis revealed the 5 top features determining survival to be tumour volume, ADC kurtosis, CBV mean, K2 mean and whole brain CBV mean. K-means clustering using these features showed two distinct clusters (high- and low-risk) which bore significantly different survival characteristics (Hazard Ratio = 5.6). DISCUSSION AND CONCLUSION Diffusion and perfusion MRI can be used to aid the prediction of survival in children’s brain tumours. Tumour perfusion played a particularly important role in predicting survival despite being less routinely measured than diffusion.
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    URL: Article
    DOI: 10.1093/neuonc/noaa222.342
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 2094060-9
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  • 4
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    Validation of the OAKS prognostic model for acute kidney injury after gastrointestinal surgery
    Oxford University Press (OUP) ; 2022
    In:  BJS Open Vol. 6, No. 1 ( 2022-01-06)
    Details
    In: BJS Open, Oxford University Press (OUP), Vol. 6, No. 1 ( 2022-01-06)
    Abstract: Postoperative acute kidney injury (AKI) is a common complication of major gastrointestinal surgery with an impact on short- and long-term survival. No validated system for risk stratification exists for this patient group. This study aimed to validate externally a prognostic model for AKI after major gastrointestinal surgery in two multicentre cohort studies. Methods The Outcomes After Kidney injury in Surgery (OAKS) prognostic model was developed to predict risk of AKI in the 7 days after surgery using six routine datapoints (age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker). Validation was performed within two independent cohorts: a prospective multicentre, international study (‘IMAGINE’) of patients undergoing elective colorectal surgery (2018); and a retrospective regional cohort study (‘Tayside’) in major abdominal surgery (2011–2015). Multivariable logistic regression was used to predict risk of AKI, with multiple imputation used to account for data missing at random. Prognostic accuracy was assessed for patients at high risk (greater than 20 per cent) of postoperative AKI. Results In the validation cohorts, 12.9 per cent of patients (661 of 5106) in IMAGINE and 14.7 per cent (106 of 719 patients) in Tayside developed 7-day postoperative AKI. Using the OAKS model, 558 patients (9.6 per cent) were classified as high risk. Less than 10 per cent of patients classified as low-risk developed AKI in either cohort (negative predictive value greater than 0.9). Upon external validation, the OAKS model retained an area under the receiver operating characteristic (AUC) curve of range 0.655–0.681 (Tayside 95 per cent c.i. 0.596 to 0.714; IMAGINE 95 per cent c.i. 0.659 to 0.703), sensitivity values range 0.323–0.352 (IMAGINE 95 per cent c.i. 0.281 to 0.368; Tayside 95 per cent c.i. 0.253 to 0.461), and specificity range 0.881–0.890 (Tayside 95 per cent c.i. 0.853 to 0.905; IMAGINE 95 per cent c.i. 0.881 to 0.899). Conclusion The OAKS prognostic model can identify patients who are not at high risk of postoperative AKI after gastrointestinal surgery with high specificity. Presented to Association of Surgeons in Training (ASiT) International Conference 2018 (Edinburgh, UK), European Society of Coloproctology (ESCP) International Conference 2018 (Nice, France), SARS (Society of Academic and Research Surgery) 2020 (Virtual, UK).
    Type of Medium: Online Resource
    ISSN: 2474-9842
    URL: Article
    DOI: 10.1093/bjsopen/zrab150
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 2902033-5
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  • 5
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    Safety and efficacy of non-steroidal anti-inflammatory drugs to reduce ileus after colorectal surgery
    Oxford University Press (OUP) ; 2020
    In:  British Journal of Surgery Vol. 107, No. 2 ( 2020-01-05), p. e161-e169
    Details
    In: British Journal of Surgery, Oxford University Press (OUP), Vol. 107, No. 2 ( 2020-01-05), p. e161-e169
    Abstract: Ileus is common after elective colorectal surgery, and is associated with increased adverse events and prolonged hospital stay. The aim was to assess the role of non-steroidal anti-inflammatory drugs (NSAIDs) for reducing ileus after surgery. Methods A prospective multicentre cohort study was delivered by an international, student- and trainee-led collaborative group. Adult patients undergoing elective colorectal resection between January and April 2018 were included. The primary outcome was time to gastrointestinal recovery, measured using a composite measure of bowel function and tolerance to oral intake. The impact of NSAIDs was explored using Cox regression analyses, including the results of a centre-specific survey of compliance to enhanced recovery principles. Secondary safety outcomes included anastomotic leak rate and acute kidney injury. Results A total of 4164 patients were included, with a median age of 68 (i.q.r. 57–75) years (54·9 per cent men). Some 1153 (27·7 per cent) received NSAIDs on postoperative days 1–3, of whom 1061 (92·0 per cent) received non-selective cyclo-oxygenase inhibitors. After adjustment for baseline differences, the mean time to gastrointestinal recovery did not differ significantly between patients who received NSAIDs and those who did not (4·6 versus 4·8 days; hazard ratio 1·04, 95 per cent c.i. 0·96 to 1·12; P = 0·360). There were no significant differences in anastomotic leak rate (5·4 versus 4·6 per cent; P = 0·349) or acute kidney injury (14·3 versus 13·8 per cent; P = 0·666) between the groups. Significantly fewer patients receiving NSAIDs required strong opioid analgesia (35·3 versus 56·7 per cent; P & lt; 0·001). Conclusion NSAIDs did not reduce the time for gastrointestinal recovery after colorectal surgery, but they were safe and associated with reduced postoperative opioid requirement.
    Type of Medium: Online Resource
    ISSN: 0007-1323 , 1365-2168
    URL: Article
    DOI: 10.1002/bjs.11326
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 2006309-X
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  • 6
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    Safety of hospital discharge before return of bowel function after elective colorectal surgery
    Oxford University Press (OUP) ; 2020
    In:  British Journal of Surgery Vol. 107, No. 5 ( 2020-03-18), p. 552-559
    Details
    In: British Journal of Surgery, Oxford University Press (OUP), Vol. 107, No. 5 ( 2020-03-18), p. 552-559
    Abstract: Ileus is common after colorectal surgery and is associated with an increased risk of postoperative complications. Identifying features of normal bowel recovery and the appropriateness for hospital discharge is challenging. This study explored the safety of hospital discharge before the return of bowel function. Methods A prospective, multicentre cohort study was undertaken across an international collaborative network. Adult patients undergoing elective colorectal resection between January and April 2018 were included. The main outcome of interest was readmission to hospital within 30 days of surgery. The impact of discharge timing according to the return of bowel function was explored using multivariable regression analysis. Other outcomes were postoperative complications within 30 days of surgery, measured using the Clavien–Dindo classification system. Results A total of 3288 patients were included in the analysis, of whom 301 (9·2 per cent) were discharged before the return of bowel function. The median duration of hospital stay for patients discharged before and after return of bowel function was 5 (i.q.r. 4–7) and 7 (6–8) days respectively (P & lt; 0·001). There were no significant differences in rates of readmission between these groups (6·6 versus 8·0 per cent; P = 0·499), and this remained the case after multivariable adjustment for baseline differences (odds ratio 0·90, 95 per cent c.i. 0·55 to 1·46; P = 0·659). Rates of postoperative complications were also similar in those discharged before versus after return of bowel function (minor: 34·7 versus 39·5 per cent; major 3·3 versus 3·4 per cent; P = 0·110). Conclusion Discharge before return of bowel function after elective colorectal surgery appears to be safe in appropriately selected patients.
    Type of Medium: Online Resource
    ISSN: 0007-1323 , 1365-2168
    URL: Article
    DOI: 10.1002/bjs.11422
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 2006309-X
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  • 7
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    Impact of postoperative acute kidney injury in patients undergoing major gastrointestinal surgery on 1-year survival and renal outcomes: a national multicentre cohort study
    Oxford University Press (OUP) ; 2021
    In:  BJS Open Vol. 5, No. 6 ( 2021-11-09)
    Details
    In: BJS Open, Oxford University Press (OUP), Vol. 5, No. 6 ( 2021-11-09)
    Abstract: The intermediate-term impact of acute kidney injury (AKI) in patients after major gastrointestinal and liver surgery has not been well characterized. This study aimed to evaluate the 1-year mortality rate and renal outcomes associated with postoperative AKI in a national prospective cohort. Methods This prospective multicentre, observational cohort with 1-year postoperative follow-up included adults undergoing major gastrointestinal and liver surgery across the UK and Ireland between 23 September and 18 November 2015. AKI was defined according to Kidney Disease Improving Global Outcomes (KDIGO) criteria. The primary outcome was death at 1-year after surgery, and the secondary outcome was Major Adverse Kidney Events (MAKE-365). Cox proportionate and multilevel logistic regression were used to account for case mix. Results Of 5745 patients across 173 centres, 1-year follow-up data was completed for 3504 patients (62.2 per cent, 126 centres), with attrition largely explained by centre non-participation (63.1 per cent). Some 13.6 per cent (475 of 3504) patients developed AKI by 7 days after surgery (stage 1: 9.2 per cent; stage 2/3: 4.3 per cent). At 1 year, 10.8 per cent (378 patients) experienced a MAKE-365 endpoint (303 patients had died, 61 had renal replacement therapy and 78 had renal dysfunction). Patients who experienced AKI by 7 days after surgery had a higher hazard of death at 1 year for KDIGO stage 1 (hazard ratio 1.50 (95 per cent c.i. 1.08 to 2.08), P = 0.016) and KDIGO stage 2/3 (hazard ratio 2.96 (95 per cent c.i. 2.02 to 4.33), P & lt; 0.001). Both KDIGO stage 1 (odds ratio 2.09 (95 per cent c.i. 1.50 to 2.92), P & lt; 0.001) and stage 2/3 (odds ratio 9.26 (95 per cent c.i. 6.31 to 13.59), P & lt; 0.001) AKI were independently associated with MAKE-365. Conclusion AKI events within 7 days after gastrointestinal or liver surgery are associated with significantly worse survival and renal outcomes at 1 year.
    Type of Medium: Online Resource
    ISSN: 2474-9842
    URL: Article
    DOI: 10.1093/bjsopen/zrab134
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 2902033-5
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  • 8
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    Death following pulmonary complications of surgery before and during the SARS-CoV-2 pandemic
    Oxford University Press (OUP) ; 2021
    In:  British Journal of Surgery Vol. 108, No. 12 ( 2021-12-01), p. 1448-1464
    Details
    In: British Journal of Surgery, Oxford University Press (OUP), Vol. 108, No. 12 ( 2021-12-01), p. 1448-1464
    Abstract: This study aimed to determine the impact of pulmonary complications on death after surgery both before and during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Methods This was a patient-level, comparative analysis of two, international prospective cohort studies: one before the pandemic (January–October 2019) and the second during the SARS-CoV-2 pandemic (local emergence of COVID-19 up to 19 April 2020). Both included patients undergoing elective resection of an intra-abdominal cancer with curative intent across five surgical oncology disciplines. Patient selection and rates of 30-day postoperative pulmonary complications were compared. The primary outcome was 30-day postoperative mortality. Mediation analysis using a natural-effects model was used to estimate the proportion of deaths during the pandemic attributable to SARS-CoV-2 infection. Results This study included 7402 patients from 50 countries; 3031 (40.9 per cent) underwent surgery before and 4371 (59.1 per cent) during the pandemic. Overall, 4.3 per cent (187 of 4371) developed postoperative SARS-CoV-2 in the pandemic cohort. The pulmonary complication rate was similar (7.1 per cent (216 of 3031) versus 6.3 per cent (274 of 4371); P = 0.158) but the mortality rate was significantly higher (0.7 per cent (20 of 3031) versus 2.0 per cent (87 of 4371); P  & lt; 0.001) among patients who had surgery during the pandemic. The adjusted odds of death were higher during than before the pandemic (odds ratio (OR) 2.72, 95 per cent c.i. 1.58 to 4.67; P  & lt; 0.001). In mediation analysis, 54.8 per cent of excess postoperative deaths during the pandemic were estimated to be attributable to SARS-CoV-2 (OR 1.73, 1.40 to 2.13; P  & lt; 0.001). Conclusion Although providers may have selected patients with a lower risk profile for surgery during the pandemic, this did not mitigate the likelihood of death through SARS-CoV-2 infection. Care providers must act urgently to protect surgical patients from SARS-CoV-2 infection.
    Type of Medium: Online Resource
    ISSN: 0007-1323 , 1365-2168
    URL: Article
    DOI: 10.1093/bjs/znab336
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 2006309-X
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  • 9
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    Machine learning risk prediction of mortality for patients undergoing surgery with perioperative SARS-CoV-2: the COVIDSurg mortality score
    Oxford University Press (OUP) ; 2021
    In:  British Journal of Surgery Vol. 108, No. 11 ( 2021-11-11), p. 1274-1292
    Details
    In: British Journal of Surgery, Oxford University Press (OUP), Vol. 108, No. 11 ( 2021-11-11), p. 1274-1292
    Abstract: To support the global restart of elective surgery, data from an international prospective cohort study of 8492 patients (69 countries) was analysed using artificial intelligence (machine learning techniques) to develop a predictive score for mortality in surgical patients with SARS-CoV-2. We found that patient rather than operation factors were the best predictors and used these to create the COVIDsurg Mortality Score (https://covidsurgrisk.app). Our data demonstrates that it is safe to restart a wide range of surgical services for selected patients.
    Type of Medium: Online Resource
    ISSN: 0007-1323 , 1365-2168
    URL: Article
    DOI: 10.1093/bjs/znab183
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 2006309-X
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  • 10
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    Preoperative nasopharyngeal swab testing and postoperative pulmonary complications in patients undergoing elective surgery during the SARS-CoV-2 pandemic
    Oxford University Press (OUP) ; 2021
    In:  British Journal of Surgery Vol. 108, No. 1 ( 2021-01-27), p. 88-96
    Details
    In: British Journal of Surgery, Oxford University Press (OUP), Vol. 108, No. 1 ( 2021-01-27), p. 88-96
    Abstract: Surgical services are preparing to scale up in areas affected by COVID-19. This study aimed to evaluate the association between preoperative SARS-CoV-2 testing and postoperative pulmonary complications in patients undergoing elective cancer surgery. Methods This international cohort study included adult patients undergoing elective surgery for cancer in areas affected by SARS-CoV-2 up to 19 April 2020. Patients suspected of SARS-CoV-2 infection before operation were excluded. The primary outcome measure was postoperative pulmonary complications at 30 days after surgery. Preoperative testing strategies were adjusted for confounding using mixed-effects models. Results Of 8784 patients (432 hospitals, 53 countries), 2303 patients (26.2 per cent) underwent preoperative testing: 1458 (16.6 per cent) had a swab test, 521 (5.9 per cent) CT only, and 324 (3.7 per cent) swab and CT. Pulmonary complications occurred in 3.9 per cent, whereas SARS-CoV-2 infection was confirmed in 2.6 per cent. After risk adjustment, having at least one negative preoperative nasopharyngeal swab test (adjusted odds ratio 0.68, 95 per cent confidence interval 0.68 to 0.98; P = 0.040) was associated with a lower rate of pulmonary complications. Swab testing was beneficial before major surgery and in areas with a high 14-day SARS-CoV-2 case notification rate, but not before minor surgery or in low-risk areas. To prevent one pulmonary complication, the number needed to swab test before major or minor surgery was 18 and 48 respectively in high-risk areas, and 73 and 387 in low-risk areas. Conclusion Preoperative nasopharyngeal swab testing was beneficial before major surgery and in high SARS-CoV-2 risk areas. There was no proven benefit of swab testing before minor surgery in low-risk areas.
    Type of Medium: Online Resource
    ISSN: 0007-1323 , 1365-2168
    URL: Article
    DOI: 10.1093/bjs/znaa051
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
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