Publications by authors named "Simon Ball"

89 Publications

Early observations on the impact of a healthcare worker COVID-19 vaccination programme at a major UK tertiary centre.

J Infect 2021 Apr 29. Epub 2021 Apr 29.

University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital Birmingham, Edgbaston, Birmingham, B15 2WB; Health Data Research UK, University of Birmingham, Edgbaston, Birmingham, UK. Electronic address:

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http://dx.doi.org/10.1016/j.jinf.2021.04.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8081749PMC
April 2021

Immunoglobulin isotype compositions of ABO specific antibodies are dependent on the individual patient blood group and blood group specificity: Results from a healthy donor cohort.

J Immunol Methods 2021 Apr 30;494:113053. Epub 2021 Apr 30.

Department of Histocompatibility and Immunogenetics, NHS Blood and Transplant, Birmingham, UK.

Antibodies specific for the blood group ABO system antigens are of clinical significance and immunological interest. Routine clinical methods typically employ direct or indirect haemagglutination methods to measure IgM and IgG, respectively. We have developed a simple, single tube method to quantify IgM, IgG, and IgA specific for A and B antigens in order to improve accuracy and reproducibility, and to investigate the relationships between ABO group antibody type, and antibody level. Plasma samples from 300 healthy blood donors were studied. Levels of IgM and IgG binding to reagent group A and B red cells were measure by agglutination (HA) and multi-colour flow cytometry (MC-FC). IgA was also measured by MC-FC. Our FC method was found to be significantly more reproducible than HA for the measurement of blood group A and B specific antibodies. We found statistically significant correlations between antibodies measured by GC-HA and MC-FC, but sufficient differences to indicate that these methods are not equivalent. By MC-FC, IgM, IgG and IgA levels and isotope profiles were found to be dependent on both the donor ABO type and the specificity of the antibody. This study demonstrated heterogeneity in the immunoglobulin class profiles of ABO-blood group specific antibodies within the healthy population. Differences in isotype profiles of ABO-blood group specific antibodies may indicate fundamental differences in the immune mechanisms that generate these antibodies. This is likely to be relevant to the clinical situations where management or diagnosis depend on ABO-specific antibody detection and measurement.
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http://dx.doi.org/10.1016/j.jim.2021.113053DOI Listing
April 2021

Improved characterisation of clinical text through ontology-based vocabulary expansion.

J Biomed Semantics 2021 04 12;12(1). Epub 2021 Apr 12.

Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, B15 2TT, UK.

Background: Biomedical ontologies contain a wealth of metadata that constitutes a fundamental infrastructural resource for text mining. For several reasons, redundancies exist in the ontology ecosystem, which lead to the same entities being described by several concepts in the same or similar contexts across several ontologies. While these concepts describe the same entities, they contain different sets of complementary metadata. Linking these definitions to make use of their combined metadata could lead to improved performance in ontology-based information retrieval, extraction, and analysis tasks.

Results: We develop and present an algorithm that expands the set of labels associated with an ontology class using a combination of strict lexical matching and cross-ontology reasoner-enabled equivalency queries. Across all disease terms in the Disease Ontology, the approach found 51,362 additional labels, more than tripling the number defined by the ontology itself. Manual validation by a clinical expert on a random sampling of expanded synonyms over the Human Phenotype Ontology yielded a precision of 0.912. Furthermore, we found that annotating patient visits in MIMIC-III with an extended set of Disease Ontology labels led to semantic similarity score derived from those labels being a significantly better predictor of matching first diagnosis, with a mean average precision of 0.88 for the unexpanded set of annotations, and 0.913 for the expanded set.

Conclusions: Inter-ontology synonym expansion can lead to a vast increase in the scale of vocabulary available for text mining applications. While the accuracy of the extended vocabulary is not perfect, it nevertheless led to a significantly improved ontology-based characterisation of patients from text in one setting. Furthermore, where run-on error is not acceptable, the technique can be used to provide candidate synonyms which can be checked by a domain expert.
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http://dx.doi.org/10.1186/s13326-021-00241-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042947PMC
April 2021

A fast, accurate, and generalisable heuristic-based negation detection algorithm for clinical text.

Comput Biol Med 2021 Mar 16;130:104216. Epub 2021 Jan 16.

College of Medical and Dental Sciences, Institute of Cancer and Genomic Sciences, University of Birmingham, UK; Institute of Translational Medicine, University Hospitals Birmingham, NHS Foundation Trust, UK; NIHR Experimental Cancer Medicine Centre, UK; NIHR Surgical Reconstruction and Microbiology Research Centre, UK; NIHR Biomedical Research Centre, UK; MRC Health Data Research UK (HDR UK) Midlands, UK; University Hospitals Birmingham NHS Foundation Trust, Edgbaston, Birmingham, UK.

Negation detection is an important task in biomedical text mining. Particularly in clinical settings, it is of critical importance to determine whether findings mentioned in text are present or absent. Rule-based negation detection algorithms are a common approach to the task, and more recent investigations have resulted in the development of rule-based systems utilising the rich grammatical information afforded by typed dependency graphs. However, interacting with these complex representations inevitably necessitates complex rules, which are time-consuming to develop and do not generalise well. We hypothesise that a heuristic approach to determining negation via dependency graphs could offer a powerful alternative. We describe and implement an algorithm for negation detection based on grammatical distance from a negatory construct in a typed dependency graph. To evaluate the algorithm, we develop two testing corpora comprised of sentences of clinical text extracted from the MIMIC-III database and documents related to hypertrophic cardiomyopathy patients routinely collected at University Hospitals Birmingham NHS trust. Gold-standard validation datasets were built by a combination of human annotation and examination of algorithm error. Finally, we compare the performance of our approach with four other rule-based algorithms on both gold-standard corpora. The presented algorithm exhibits the best performance by f-measure over the MIMIC-III dataset, and a similar performance to the syntactic negation detection systems over the HCM dataset. It is also the fastest of the dependency-based negation systems explored in this study. Our results show that while a single heuristic approach to dependency-based negation detection is ignorant to certain advanced cases, it nevertheless forms a powerful and stable method, requiring minimal training and adaptation between datasets. As such, it could present a drop-in replacement or augmentation for many-rule negation approaches in clinical text-mining pipelines, particularly for cases where adaptation and rule development is not required or possible.
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http://dx.doi.org/10.1016/j.compbiomed.2021.104216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910278PMC
March 2021

Evaluation and improvement of the National Early Warning Score (NEWS2) for COVID-19: a multi-hospital study.

BMC Med 2021 01 21;19(1):23. Epub 2021 Jan 21.

Department of Acute Medicine, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

Background: The National Early Warning Score (NEWS2) is currently recommended in the UK for the risk stratification of COVID-19 patients, but little is known about its ability to detect severe cases. We aimed to evaluate NEWS2 for the prediction of severe COVID-19 outcome and identify and validate a set of blood and physiological parameters routinely collected at hospital admission to improve upon the use of NEWS2 alone for medium-term risk stratification.

Methods: Training cohorts comprised 1276 patients admitted to King's College Hospital National Health Service (NHS) Foundation Trust with COVID-19 disease from 1 March to 30 April 2020. External validation cohorts included 6237 patients from five UK NHS Trusts (Guy's and St Thomas' Hospitals, University Hospitals Southampton, University Hospitals Bristol and Weston NHS Foundation Trust, University College London Hospitals, University Hospitals Birmingham), one hospital in Norway (Oslo University Hospital), and two hospitals in Wuhan, China (Wuhan Sixth Hospital and Taikang Tongji Hospital). The outcome was severe COVID-19 disease (transfer to intensive care unit (ICU) or death) at 14 days after hospital admission. Age, physiological measures, blood biomarkers, sex, ethnicity, and comorbidities (hypertension, diabetes, cardiovascular, respiratory and kidney diseases) measured at hospital admission were considered in the models.

Results: A baseline model of 'NEWS2 + age' had poor-to-moderate discrimination for severe COVID-19 infection at 14 days (area under receiver operating characteristic curve (AUC) in training cohort = 0.700, 95% confidence interval (CI) 0.680, 0.722; Brier score = 0.192, 95% CI 0.186, 0.197). A supplemented model adding eight routinely collected blood and physiological parameters (supplemental oxygen flow rate, urea, age, oxygen saturation, C-reactive protein, estimated glomerular filtration rate, neutrophil count, neutrophil/lymphocyte ratio) improved discrimination (AUC = 0.735; 95% CI 0.715, 0.757), and these improvements were replicated across seven UK and non-UK sites. However, there was evidence of miscalibration with the model tending to underestimate risks in most sites.

Conclusions: NEWS2 score had poor-to-moderate discrimination for medium-term COVID-19 outcome which raises questions about its use as a screening tool at hospital admission. Risk stratification was improved by including readily available blood and physiological parameters measured at hospital admission, but there was evidence of miscalibration in external sites. This highlights the need for a better understanding of the use of early warning scores for COVID.
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http://dx.doi.org/10.1186/s12916-020-01893-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817348PMC
January 2021

Atezolizumab Plus Chemotherapy for First-Line Treatment of Nonsquamous NSCLC: Results From the Randomized Phase 3 IMpower132 Trial.

J Thorac Oncol 2021 04 14;16(4):653-664. Epub 2020 Dec 14.

Department of Medical Oncology, AdventHealth Cancer Institute, Orlando, Florida.

Introduction: We report the final results of the phase 3 IMpower132 study evaluating atezolizumab plus carboplatin or cisplatin plus pemetrexed (APP) in patients with nonsquamous NSCLC.

Methods: Chemotherapy-naive patients with stage IV nonsquamous NSCLC without sensitizing EGFR or ALK genetic alterations were randomized in a one-to-one ratio to receive four or six cycles of carboplatin or cisplatin plus pemetrexed (PP) or APP every 3 weeks, followed by maintenance therapy with atezolizumab plus pemetrexed or pemetrexed alone. Co-primary end points were overall survival (OS) and investigator-assessed progression-free survival (PFS).

Results: The intention-to-treat population included 578 patients (APP, n = 292; PP, n = 286). At the primary PFS analysis (May 22, 2018; median follow-up, 14.8 mo), APP exhibited significant PFS improvement versus PP (median = 7.6 versus 5.2 mo, stratified hazard ratio [HR] = 0.60, 95% confidence interval [CI]: 0.49-0.72, p < 0.0001). OS for the APP group was numerically better but not statistically significant at the interim (May 22, 2018; median = 18.1 versus 13.6 mo, stratified HR = 0.81, 95% CI: 0.64-1.03, p = 0.0797) and final analyses (July 18, 2019; median = 17.5 versus 13.6 mo; stratified HR = 0.86, 95% CI: 0.71-1.06, p = 0.1546). The OS and PFS results favored APP versus PP across subgroups. Grade 3 or 4 treatment-related adverse events occurred in 54.6% (APP) and 40.1% (PP) of patients; grade 5 treatment-related events occurred in 3.8% and 2.9%, respectively.

Conclusions: IMpower132 met its co-primary PFS end point but not its co-primary OS end point, with numerical improvement for OS in the APP arm. APP had a manageable safety profile, with no new or unexpected safety signals identified.
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http://dx.doi.org/10.1016/j.jtho.2020.11.025DOI Listing
April 2021

Monitoring indirect impact of COVID-19 pandemic on services for cardiovascular diseases in the UK.

Heart 2020 12 5;106(24):1890-1897. Epub 2020 Oct 5.

The University of Edinburgh Usher Institute of Population Health Sciences and Informatics, Edinburgh, UK

Objective: To monitor hospital activity for presentation, diagnosis and treatment of cardiovascular diseases during the COVID-19) pandemic to inform on indirect effects.

Methods: Retrospective serial cross-sectional study in nine UK hospitals using hospital activity data from 28 October 2019 (pre-COVID-19) to 10 May 2020 (pre-easing of lockdown) and for the same weeks during 2018-2019. We analysed aggregate data for selected cardiovascular diseases before and during the epidemic. We produced an online visualisation tool to enable near real-time monitoring of trends.

Results: Across nine hospitals, total admissions and emergency department (ED) attendances decreased after lockdown (23 March 2020) by 57.9% (57.1%-58.6%) and 52.9% (52.2%-53.5%), respectively, compared with the previous year. Activity for cardiac, cerebrovascular and other vascular conditions started to decline 1-2 weeks before lockdown and fell by 31%-88% after lockdown, with the greatest reductions observed for coronary artery bypass grafts, carotid endarterectomy, aortic aneurysm repair and peripheral arterial disease procedures. Compared with before the first UK COVID-19 (31 January 2020), activity declined across diseases and specialties between the first case and lockdown (total ED attendances relative reduction (RR) 0.94, 0.93-0.95; total hospital admissions RR 0.96, 0.95-0.97) and after lockdown (attendances RR 0.63, 0.62-0.64; admissions RR 0.59, 0.57-0.60). There was limited recovery towards usual levels of some activities from mid-April 2020.

Conclusions: Substantial reductions in total and cardiovascular activities are likely to contribute to a major burden of indirect effects of the pandemic, suggesting they should be monitored and mitigated urgently.
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http://dx.doi.org/10.1136/heartjnl-2020-317870DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7536637PMC
December 2020

Elite and Professional sports facial injuries management - a consensus report.

Br J Oral Maxillofac Surg 2020 12 26;58(10):e254-e259. Epub 2020 Aug 26.

Consultant in Oral and Maxillofacial Surgery, University Hospitals Bristol NHS Trust, Bristol. Electronic address:

Whilst there have been great improvements in the management of elite and professional athletes with the formalisation of the clinical specialty of Sports and Exercise medicine, the management of facial injuries has perhaps lagged in this group. Professional athletic careers can be put in jeopardy due to unnecessarily long absences from training and competition after facial injuries. Professional and elite sports athletes can benefit from different approaches to the management of their facial injuries to reduce time away from competing but maximise their safety. On 6 December 2018, a consensus meeting of interested clinicians involved in the management of facial injuries of elite and professional athletes was held at the Royal Society of Medicine, London, UK to provide a contemporary review of the approaches to conservative, operative and recovery management of facial injuries. National experts with specialist experience of facial injuries presentation and athlete needs from a range of elite and professional sports led the day's programme and the discussions so that guidelines could be formulated. These are presented in this review paper.
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http://dx.doi.org/10.1016/j.bjoms.2020.08.046DOI Listing
December 2020

Ethnicity and risk of death in patients hospitalised for COVID-19 infection in the UK: an observational cohort study in an urban catchment area.

BMJ Open Respir Res 2020 09;7(1)

HDR-UK Midlands Physical Site, University Hospitals Birmingham, Birmingham, UK.

Background: Studies suggest that certain black and Asian minority ethnic groups experience poorer outcomes from COVID-19, but these studies have not provided insight into potential reasons for this. We hypothesised that outcomes would be poorer for those of South Asian ethnicity hospitalised from a confirmed SARS-CoV-2 infection, once confounding factors, health-seeking behaviours and community demographics were considered, and that this might reflect a more aggressive disease course in these patients.

Methods: Patients with confirmed SARS-CoV-2 infection requiring admission to University Hospitals Birmingham NHS Foundation Trust (UHB) in Birmingham, UK between 10 March 2020 and 17 April 2020 were included. Standardised admission ratio (SAR) and standardised mortality ratio (SMR) were calculated using observed COVID-19 admissions/deaths and 2011 census data. Adjusted HR for mortality was estimated using Cox proportional hazard model adjusting and propensity score matching.

Results: All patients admitted to UHB with COVID-19 during the study period were included (2217 in total). 58% were male, 69.5% were white and the majority (80.2%) had comorbidities. 18.5% were of South Asian ethnicity, and these patients were more likely to be younger and have no comorbidities, but twice the prevalence of diabetes than white patients. SAR and SMR suggested more admissions and deaths in South Asian patients than would be predicted and they were more likely to present with severe disease despite no delay in presentation since symptom onset. South Asian ethnicity was associated with an increased risk of death, both by Cox regression (HR 1.4, 95% CI 1.2 to 1.8), after adjusting for age, sex, deprivation and comorbidities, and by propensity score matching, matching for the same factors but categorising ethnicity into South Asian or not (HR 1.3, 95% CI 1.0 to 1.6).

Conclusions: Those of South Asian ethnicity appear at risk of worse COVID-19 outcomes. Further studies need to establish the underlying mechanistic pathways.
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http://dx.doi.org/10.1136/bmjresp-2020-000644DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7467523PMC
September 2020

Length-change patterns of the medial collateral ligament and posterior oblique ligament in relation to their function and surgery.

Knee Surg Sports Traumatol Arthrosc 2020 Dec 1;28(12):3720-3732. Epub 2020 Jun 1.

The Biomechanics Group, Department of Mechanical Engineering, Imperial College London, London, SW7 2AZ, UK.

Purpose: To define the length-change patterns of the superficial medial collateral ligament (sMCL), deep MCL (dMCL), and posterior oblique ligament (POL) across knee flexion and with applied anterior and rotational loads, and to relate these findings to their functions in knee stability and to surgical repair or reconstruction.

Methods: Ten cadaveric knees were mounted in a kinematics rig with loaded quadriceps, ITB, and hamstrings. Length changes of the anterior and posterior fibres of the sMCL, dMCL, and POL were recorded from 0° to 100° flexion by use of a linear displacement transducer and normalised to lengths at 0° flexion. Measurements were repeated with no external load, 90 N anterior draw force, and 5 Nm internal and 5 Nm external rotation torque applied.

Results: The anterior sMCL lengthened with flexion (p < 0.01) and further lengthened by external rotation (p < 0.001). The posterior sMCL slackened with flexion (p < 0.001), but was lengthened by internal rotation (p < 0.05). External rotation lengthened the anterior dMCL fibres by 10% throughout flexion (p < 0.001). sMCL release allowed the dMCL to become taut with valgus rotation (p < 0.001). The anterior and posterior POL fibres slackened with flexion (p < 0.001), but were elongated by internal rotation (p < 0.001).

Conclusion: The structures of the medial ligament complex react differently to knee flexion and applied loads. Structures attaching posterior to the medial epicondyle are taut in extension, whereas the anterior sMCL, attaching anterior to the epicondyle, is tensioned during flexion. The anterior dMCL is elongated by external rotation. These data offer the basis for MCL repair and reconstruction techniques regarding graft positioning and tensioning.
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http://dx.doi.org/10.1007/s00167-020-06050-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7669796PMC
December 2020

Effect of Optimized Immunosuppression (Including Rituximab) on Anti-Donor Alloresponses in Patients With Chronically Rejecting Renal Allografts.

Front Immunol 2020 5;11:79. Epub 2020 Feb 5.

Department of Inflammation Biology, MRC Centre for Transplantation, Guy's Hospital, King's College London, London, United Kingdom.

RituxiCAN-C4 combined an open-labeled randomized controlled trial (RCT) in 7 UK centers to assess whether rituximab could stabilize kidney function in patients with chronic rejection, with an exploratory analysis of how B cell-depletion influenced T cell anti-donor responses relative to outcome. Between January 2007 and March 2015, 59 recruits were enrolled after screening, 23 of whom consented to the embedded RCT. Recruitment was halted when in a pre-specified per protocol interim analysis, the RCT was discovered to be significantly underpowered. This report therefore focuses on the exploratory analysis, in which we confirmed that when B cells promoted CD4+ anti-donor IFNγ production assessed by ELISPOT, this associated with inferior clinical outcome; these patterns were inhibited by optimized immunosuppression but not rituximab. B cell suppression of IFNγ production, which associated with number of transitional B cells and correlated with slower declines in kidney function was abolished by rituximab, which depleted transitional B cells for prolonged periods. We conclude that in this patient population, optimized immunosuppression but not rituximab promotes anti-donor alloresponses associated with favorable outcomes. Registered with EudraCT (2006-002330-38) and www.ClinicalTrials.gov, identifier: NCT00476164.
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http://dx.doi.org/10.3389/fimmu.2020.00079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7012933PMC
March 2021

Current concepts in the management of patellofemoral pain - The role of alignment.

Knee 2020 Mar 31;27(2):280-286. Epub 2020 Jan 31.

Fortius Clinic London, United Kingdom of Great Britain and Northern Ireland.

Background: Patellofemoral pain is a prevalent and significant clinical problem that is often reported to persist even following evidence based intervention. It is clear therefore that there is much about this complex patient group that is not presently fully understood. This is particularly concerning given the reported links between patellofemoral pain in adolescence and the subsequent development of osteoarthritis and anxiety.

Assessment: Clinical assessment has historically focussed on biomechanical factors such as altered lower limb kinematics, muscle weakness and late muscle 'onset or activation' during activity. However when examined it is clear that study findings from patellofemoral populations are often inconsistent. Reasons for this are discussed and specifically the limitations around current 'gold standard' measurement methods, such as motion capture are outlined. A biomechanical approach is applied to demonstrate the importance of ensuring optimal patient alignment during rehabilitation, where optimal is defined as ensuring the most energy efficient muscle or muscles are used by the patient to perform a movement. This in turn ensures that the direction, magnitude and location of load applied to the skeleton during activity is optimal and therefore less likely to lead to injury.

Treatment: The role of alignment in patellofemoral pain and the importance of correcting this during rehabilitation is discussed, and examples provided. Validated, reliable, and reproducible methods of measuring skeletal geometry, muscle geometry, muscle force and direction, and kinematics of activity must be developed as a priority in order for us to further our understanding and improve outcomes in this complex clinical population.
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http://dx.doi.org/10.1016/j.knee.2019.12.006DOI Listing
March 2020

Trust compliance with best practice tariff criteria for total hip and knee replacement.

Br J Hosp Med (Lond) 2019 Sep;80(9):537-540

Consultant Orthopaedic Surgeon, Trauma and Orthopaedic Surgery Department, Chelsea and Westminster Hospital, London.

Background: Satisfaction of the best practice tariff criteria for primary hip and knee replacement enables on average an additional £560 of reimbursement per case. The Getting it Right First Time report highlighted poor awareness of these criteria among orthopaedic departments.

Methods: The authors investigated the reasons for non-compliance with the best practice tariff criteria at their trust and implemented a quality improvement approach to ensure successful adherence to the standards (a minimum National Joint Registry compliance rate of 85%, a National Joint Registry unknown consent rate below 15%, a patient-reported outcome measure participation rate of ≥50%, and an average health gain not significantly below the national average). This was investigated using quarterly online reports from the National Joint Registry and NHS Digital.

Results: Initially, the trust had a 31% patient-reported outcome measures participation rate arising from a systematic error in the submission of preoperative patient-reported outcome measure scores. Re-audit following the resubmission of patient-reported outcome measure data under the trust's correct organization data service code confirmed an improvement in patient-reported outcome measure compliance to 90% and satisfaction of all criteria resulting in over £450 000 of additional reimbursement to the trust.

Conclusions: The authors would urge others to review their compliance with these four best practice tariff criteria to ensure that they too are not missing out on this significant reimbursement sum.
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http://dx.doi.org/10.12968/hmed.2019.80.9.537DOI Listing
September 2019

Dietitians can improve accuracy of prescribing by interacting with electronic prescribing systems.

BMJ Health Care Inform 2019 Apr;26(1)

Department of Renal Medicine, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.

Background: Dietitians increasingly interact with electronic health records (EHRs) and use them to alert prescribers to medication inaccuracies.

Objective: To understand renal dietitians' use of electronic prescribing systems and influence on medication accuracy in inpatients. In outpatients to determine whether renal dietitians' use of the electronic medication recording might improve accuracy.

Methods: In inpatients we studied the impact of dietetic advice on medical prescribing before and after moving from paper recommendations to ePrescribing. In outpatients, when dietitians recommended changes in dialysis units, we assessed the time to patients receiving the new medications. We trained dietitians to use the ePrescribing system and assessed accuracy of medication lists at the start and end of the study period.

Results: Inpatients: before the use of EHRs, 25% of proposals were carried out and took an average of 20 days. This rose to 38% using an EHR and took an average of 4 days.Outpatients: in dialysis units dietitians recommend initiating and stopping medications and advise on repeat medications. Most recommendations were during multidisciplinary team (MDT) meetings; the average time to receive medications was 10 days. Drug histories updated by dietitians increased after the start of the study and accuracy of medication lists improved from 2.4 discrepancies/patient to 0.4.

Conclusion: Dietitians can make medication suggestions directly using EHR, delivering more timely change to patient care and improving accuracy of patients' medication lists. Allowing the whole of the MDT to contribute to the EHR improves data completeness and therefore patient care is likely to be enhanced.
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http://dx.doi.org/10.1136/bmjhci-2019-000019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7062321PMC
April 2019

Diagnostic accuracy of whole-body MRI versus standard imaging pathways for metastatic disease in newly diagnosed non-small-cell lung cancer: the prospective Streamline L trial.

Lancet Respir Med 2019 06 9;7(6):523-532. Epub 2019 May 9.

Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, UK.

Background: Whole-body magnetic resonance imaging (WB-MRI) could be an alternative to multi-modality staging of non-small-cell lung cancer (NSCLC), but its diagnostic accuracy, effect on staging times, number of tests needed, cost, and effect on treatment decisions are unknown. We aimed to prospectively compare the diagnostic accuracy and efficiency of WB-MRI-based staging pathways with standard pathways in NSCLC.

Methods: The Streamline L trial was a prospective, multicentre trial done in 16 hospitals in England. Eligible patients were 18 years or older, with newly diagnosed NSCLC that was potentially radically treatable on diagnostic chest CT (defined as stage IIIb or less). Exclusion criteria were severe systemic disease, pregnancy, contraindications to MRI, or histologies other than NSCLC. Patients underwent WB-MRI, the result of which was withheld until standard staging investigations were complete and the first treatment decision made. The multidisciplinary team recorded its treatment decision based on standard investigations, then on the WB-MRI staging pathway (WB-MRI plus additional tests generated), and finally on all tests. The primary outcome was difference in per-patient sensitivity for metastases between standard and WB-MRI staging pathways against a consensus reference standard at 12 months, in the per-protocol population. Secondary outcomes were difference in per-patient specificity for metastatic disease detection between standard and WB-MRI staging pathways, differences in treatment decisions, staging efficiency (time taken, test number, and costs) and per-organ sensitivity and specificity for metastases and per-patient agreement for local T and N stage. This trial is registered with the International Standard Randomised Controlled Trial registry, number ISRCTN50436483, and is complete.

Findings: Between Feb 26, 2013, and Sept 5, 2016, 976 patients were screened for eligibility. 353 patients were recruited, 187 of whom completed the trial; 52 (28%) had metastasis at baseline. Pathway sensitivity was 50% (95% CI 37-63) for WB-MRI and 54% (41-67) for standard pathways, a difference of 4% (-7 to 15, p=0·73). No adverse events related to imaging were reported. Specificity did not differ between WB-MRI (93% [88-96]) and standard pathways (95% [91-98], p=0·45). Agreement with the multidisciplinary team's final treatment decision was 98% for WB-MRI and 99% for the standard pathway. Time to complete staging was shorter for WB-MRI (13 days [12-14]) than for the standard pathway (19 days [17-21]); a 6-day (4-8) difference. The number of tests required was similar WB-MRI (one [1-1]) and standard pathways (one [1-2]). Mean per-patient costs were £317 (273-361) for WBI-MRI and £620 (574-666) for standard pathways.

Interpretation: WB-MRI staging pathways have similar accuracy to standard pathways, and reduce the staging time and costs.

Funding: UK National Institute for Health Research.
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http://dx.doi.org/10.1016/S2213-2600(19)30090-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6529610PMC
June 2019

Combined liver-kidney transplantation versus liver transplant alone based on KDIGO stratification of estimated glomerular filtration rate: data from the United Kingdom Transplant registry - a retrospective cohort study.

Transpl Int 2019 09 28;32(9):918-932. Epub 2019 Mar 28.

The Liver Unit, Queen Elizabeth Hospital Birmingham, Birmingham, UK.

Patient selection for combined liver-kidney transplantation (CLKT) is a current issue on the background of organ shortage. This study aimed to compare outcomes and post-transplant renal function for patients receiving CLKT and liver transplantation alone (LTA) based on native renal function using estimated glomerular filtration rate (eGFR) stratification. Using the UK National transplant database (NHSBT) 6035 patients receiving a LTA (N = 5912; 98%) or CLKT (N = 123; 2%) [2001-2013] were analysed, and stratified by KDIGO stages of eGFR at transplant (eGFR group-strata). There was no difference in patient/graft survival between LTA and CLKT in eGFR group-strata (P > 0.05). Of 377 patients undergoing renal replacement therapy (RRT) at time of transplantation, 305 (81%) and 72 (19%) patients received LTA and CLKT respectively. A significantly greater proportion of CLKT patients had severe end-stage renal disease (eGFR < 30 ml/min/1.73 m ) at 1 year post-transplant compared to LTA (9.5% vs. 5.7%, P = 0.001). Patient and graft survival benefit for patients on RRT at transplantation was favouring CLKT versus LTA (P = 0.038 and P = 0.018, respectively) but the renal function of the long-term survivors was not superior following CLKT. The data does not support CLKT approach based on eGFR alone, and the advantage of CLKT appear to benefit only those who are on established RRT at the time of transplant.
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http://dx.doi.org/10.1111/tri.13413DOI Listing
September 2019

A prospective multicenter observational study of cell-mediated immunity as a predictor for cytomegalovirus infection in kidney transplant recipients.

Am J Transplant 2019 09 15;19(9):2505-2516. Epub 2019 Mar 15.

Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts.

T cell immunity is essential for the control of cytomegalovirus (CMV) infection after transplantation. We evaluated a CMV-specific peptide-based enzyme-linked immunosorbent spot (ELISPOT) assay to determine whether assay results could predict subsequent CMV events. Adult kidney transplant recipients at 43 centers underwent ELISPOT testing to enumerate interferon gamma (IFN-γ) binding spot-forming units (sfu) after stimulation of cells with an overlapping peptide pool of CMV phosphoprotein 65 (pp65) and immediate early-1 (IE-1) protein at the end of antiviral prophylaxis (EOP) and various time points thereafter. The primary outcome was a CMV event in the first posttransplant year. In 583 kidney transplant recipients (260 seropositive donor [D+]/seronegative recipient [R-] and 277 R+), CMV events occurred in 44 of 368 eligible patients (11.8%) at a median of 227 days (range 92-360) posttransplant. A cutoff value of >40 sfu/2.5 × 10  cells for either IE-1 or pp65 was derived as a threshold for positivity, with a negative predictive value of >97% for CMV events. CMV events were significantly lower in assay positive vs assay negative patients (3.0% vs 19.5%, P < .0001 for pp65). Time to CMV event post-EOP was significantly greater in those with sfu >40 at EOP (P < .0001). In this large, multicenter trial of kidney transplant recipients, we show that an assessment of CMV-specific immunity using a novel ELISPOT assay is able to predict protection from CMV infection.
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http://dx.doi.org/10.1111/ajt.15315DOI Listing
September 2019

Cardiovascular, thromboembolic and renal outcomes in IgA vasculitis (Henoch-Schönlein purpura): a retrospective cohort study using routinely collected primary care data.

Ann Rheum Dis 2019 02 28;78(2):261-269. Epub 2018 Nov 28.

Institute of Applied Health Research, University of Birmingham, Birmingham, UK.

Background: IgA vasculitis (IgAV, Henoch-Schönlein purpura) is a small-vessel vasculitis most common in children but also occurring in adults. Case series have suggested that IgAV may be associated with cardiovascular disease and venous thromboembolism, but this has not been evaluated in population-based studies. Renal disease and hypertension are possible complications of the disease with unknown incidence.

Methods: Using a large UK primary care database, we conducted an open retrospective matched cohort study of cardiovascular, venous thrombotic and renal outcomes in adult-onset and childhood-onset IgAV. Control participants were selected at a 2:1 ratio, matched for age and sex. Adjusted HRs (aHRs) were calculated using Cox proportional hazards models.

Results: 2828 patients with adult-onset IgAV and 10 405 patients with childhood-onset IgAV were compared with age-matched and sex-matched controls. There was significantly increased risk of hypertension (adult-onset aHR 1.42, 95% CI 1.19 to 1.70, p < 0.001; childhood-onset aHR 1.52, 95% CI 1.22 to 1.89, p < 0.001) and stage G3-G5 chronic kidney disease (adult-onset aHR 1.54, 95% CI 1.23 to 1.93, p < 0.001; childhood-onset aHR 1.89, 95% CI 1.16 to 3.07, p=0.010). There was no evidence of association with ischaemic heart disease, cerebrovascular disease or venous thromboembolism. All-cause mortality was increased in the adult-onset IgAV cohort compared with controls (aHR 1.27, 95% CI 1.07 to 1.50, p=0.006).

Conclusions: Patients with IgAV are at increased risk of hypertension and chronic kidney disease (CKD) compared with individuals without IgAV; analysis restricted to adult-onset IgAV patients showed increased mortality. Appropriate surveillance and risk factor modification could improve long-term outcomes in these patients.
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http://dx.doi.org/10.1136/annrheumdis-2018-214142DOI Listing
February 2019

Contributions of patient and citizen researchers to 'Am I the right way up?' study of balance in posterior cortical atrophy and typical Alzheimer's disease.

Dementia (London) 2018 Nov;17(8):1011-1022

Created Out of Mind, The Hub, Wellcome Collection, London, UK; Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, University College London, London, UK.

The current report describes the journey from the sharing of a single, extraordinary experience during a support group conversation to the development of a novel scientific investigation of balance problems in a rarer form of dementia. The story centres around the involvement of people living with or caring for someone with posterior cortical atrophy (often referred to as the visual variant of Alzheimer's disease) in highlighting hitherto under-appreciated consequences of their condition upon their ability to know 'Am I the right way up?'. We describe how comments and descriptions of these balance symptoms were collated and communicated, and the involvement of people with posterior cortical atrophy in shaping a series of scientific hypotheses and developing and adapting appropriate experimental materials and procedures. We also reflect more broadly on how we might better recognise, acknowledge and encourage different forms of involvement, and describe several engagement-inspired extensions to the research involving people living with dementia, scientists and artists.
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http://dx.doi.org/10.1177/1471301218789296DOI Listing
November 2018

It is safe and effective to use all inside meniscal repair devices for posteromedial meniscal 'ramp' lesions.

Knee Surg Sports Traumatol Arthrosc 2018 Aug 12;26(8):2310-2316. Epub 2018 May 12.

Fortius Clinic, 17 Fitzhardinge Street, London, W1H 6EQ, UK.

Purpose: Recently, it has been recognized that meniscocapsular ('ramp') lesions of the posterior one-third of the medial meniscus frequently occur during injuries causing ACL rupture, and that these lesions are easily missed at arthroscopy. Furthermore, it is clear that these lesions are biomechanically significant, adding to the deficits caused by ACL rupture, and that their repair can reverse this. The efficacy of an all inside repair technique has been questioned by some authors and by those who advocate a suture shuttle technique via an accessory posteromedial portal. The use of Ultra FastFix and FastFix 360 meniscal repair devices to repair posteromedial meniscocapsular separations was investigated in terms of safe deployment and the effectiveness.

Methods: Twenty cadaveric fresh frozen knees were used-ten in each of two groups. A ramp lesion was created using a Beaver knife. The lesion was then repaired with either 4 Ultra FastFix (Smith and Nephew) or 4 FastFix 360 (Smith and Nephew) meniscal repair devices. The knees were put through a standardized loading cycle consisting of 10 Lachman's tests and ten maximum loading manual anterior drawer tests at 90° of flexion. Each knee was then flexed and extended fully ten times. The specimens were sectioned just proximal to the menisci and each suture anchor identified and its position recorded and photographed.

Results: In the Ultra FastFix group, a single anchor was found to be in an intra-articular position-a failure rate of 2.5%. In the FastFix 360 group, 5 anchors failed-a 12.5% failure rate. In all cases, the anchors were attached to their suture and so not truly loose within the joint.

Conclusions: This study confirms the safe and effective deployment of an all inside repair device for repair of medial meniscal 'ramp' lesions, and therefore its use is advocated in treating these difficult lesions. Ultra FastFix had the lower failure rate of 2.5%, which the authors believe is acceptable, and makes this device preferable to the FastFix360.
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http://dx.doi.org/10.1007/s00167-018-4976-5DOI Listing
August 2018

The infrapatellar fat pad is a dynamic and mobile structure, which deforms during knee motion, and has proximal extensions which wrap around the patella.

Knee Surg Sports Traumatol Arthrosc 2018 Nov 20;26(11):3515-3524. Epub 2018 Apr 20.

Fortius Clinic, 17 Fitzhardinge St, London, W1H 6EQ, UK.

Purpose: The infrapatellar fat pad (IFP) is a common cause of knee pain and loss of knee flexion and extension. However, its anatomy and behavior are not consistently defined.

Methods: Thirty-six unpaired fresh frozen knees (median age 34 years, range 21-68) were dissected, and IFP attachments and volume measured. The rectus femoris was elevated, suprapatellar pouch opened and videos recorded looking inferiorly along the femoral shaft at the IFP as the knee was flexed. The patellar retinacula were incised and the patella reflected distally. The attachment of the ligamentum mucosum (LMuc) to the intercondylar notch was released from the anterior cruciate ligament (ACL), both menisci and to the tibia via meniscotibial ligaments. IFP strands projecting along both sides of the patella were elevated and the IFP dissected from the inferior patellar pole. Magnetic resonance imaging (MRI) of one knee at ten flexion angles was performed and the IFP, patella, tibia and femur segmented.

Results: In all specimens the IFP attached to the inferior patellar pole, femoral intercondylar notch (via the LMuc), proximal patellar tendon, intermeniscal ligament, both menisci and the anterior tibia via the meniscotibial ligaments. In 30 specimens the IFP attached to the anterior ACL fibers via the LMuc, and in 29 specimens it attached directly to the central anterior tibia. Proximal IFP extensions were identified alongside the patella in all specimens and visible on MRI [medially (100% of specimens), mean length 56.2 ± 8.9 mm, laterally (83%), mean length 23.9 ± 6.2 mm]. Mean IFP volume was 29.2 ± 6.1 ml. The LMuc, attached near the base of the middle IFP lobe, acting as a 'tether' drawing it superiorly during knee extension. The medial lobe consistently had a pedicle superomedially, positioned between the patella and medial trochlea. MRI scans demonstrated how the space between the anterior tibia and patellar tendon ('the anterior interval') narrowed during knee flexion, displacing the IFP superiorly and posteriorly as it conformed to the trochlear and intercondylar notch surfaces.

Conclusion: Proximal IFP extensions are a novel description. The IFP is a dynamic structure, displacing significantly during knee motion, which is, therefore, vulnerable to interference from trauma or repetitive overload. Given that this trauma is often surgical, it may be appropriate that surgeons learn to minimize injury to the fat pad at surgery.
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http://dx.doi.org/10.1007/s00167-018-4943-1DOI Listing
November 2018

Assessment of the T-SPOT.CMV interferon-γ release assay in renal transplant recipients: A single center cohort study.

PLoS One 2018 20;13(3):e0193968. Epub 2018 Mar 20.

Department of Nephrology, Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom.

Background: The measurement of CMV specific cellular immunity in organ transplant recipients could contribute additional acuity to serology based, CMV infection risk stratification, facilitating optimisation of immunosuppression and anti-viral prophylaxis.

Methods: A pilot study of renal transplant recipient (RTR's) responses in the T-SPOT.CMV ELISPOT based assay. 108 RTR's were recruited 3 months post-transplantation, immediately prior to the cessation of stratified anti-viral prophylaxis, used in recipients from seropositive donors. RTR's were monitored for CMV viremia and disease. Cellular responses to peptides derived from CMV IE1 and pp65 were measured, using the T-SPOT.CMV assay.

Results: At recruitment, no CMV specific cellular immunity was detected by T-SPOT.CMV in CMV seronegative recipients (IE1 ≤ 1spot / 2.5x105 PBMC's; pp65 ≤ 3 spots / 2.5x105 PBMC's). At recruitment, CMV sero-positive recipients who made a robust response to both IE1 (>25 spots / 2.5x105 PBMC's) and pp65 (>50 spots / 2.5x105 PBMC's), were less likely to develop high level viremia than those who responded to one or neither antigen (0/28 vs 5/25; p<0.02).

Conclusions: In CMV seronegative RTR's, CMV specific cellular immunity measured by T-SPOT.CMV was not detected prior to cessation of anti-viral prophylaxis. This differs from recent reports of CMV specific cellular immunity in a proportion of CMV seronegative RTR's, associated with protection from CMV infection. In seropositive RTR's, a dual response to IE1 and pp65 at recruitment, was associated with protection from subsequent viremia. This suggests that assessing the diversity of response to CMV antigens, may enhance risk stratification in this group.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0193968PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5860728PMC
June 2018

Leg length discrepancy: the importance of a complete history and examination.

BMJ Case Rep 2017 Dec 2;2017. Epub 2017 Dec 2.

Hand Surgery Unit, Chelsea and Westminster Hospital NHS Foundation Trust, London, UK.

A 26-year-old woman with a 1-year history of right knee pain had failed to respond to analgesia and activity modification in the community. Her general practitioner referred her to the orthopaedic department for specialist review. A thorough history revealed that she had multiple orthopaedic interventions as a child. The patient had significant postoperative infection of the left knee following knee surgery at 7 years of age. Examination demonstrated the presence of a limp, scoliosis and suspected leg length discrepancy. Plain film radiography confirmed the presence of leg length discrepancy, with the right limb measuring 30 mm longer than the left. The leg length discrepancy was likely secondary to a growth arrest of the left knee following the postoperative infection in childhood. The patient was managed with physiotherapy and heel raises and received regular orthopaedic follow-up.
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http://dx.doi.org/10.1136/bcr-2017-220985DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5720277PMC
December 2017

Bioequivalence of twice-daily oral tacrolimus in transplant recipients: More evidence for consensus?

Authors:
Simon Ball

PLoS Med 2017 11 14;14(11):e1002429. Epub 2017 Nov 14.

Department of Nephrology, Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom.

In this Perspective on the clinical trial by Rita Alloway and colleagues, Simon Ball explains the benefits to healthcare systems and individual patients of the bioequivalence established between generic and brand-name formulations of an immunosuppressive drug in transplant recipients.
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http://dx.doi.org/10.1371/journal.pmed.1002429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5685474PMC
November 2017

Hospital acquired Acute Kidney Injury is associated with increased mortality but not increased readmission rates in a UK acute hospital.

BMC Nephrol 2017 Oct 20;18(1):317. Epub 2017 Oct 20.

University Hospitals Birmingham, Birmingham, UK.

Background: Acute Kidney Injury (AKI) has evoked much interest over the past decade and is reported to be associated with high inpatient mortality. Preventable death and increased readmission rates related to AKI have been the focus of considerable interest.

Methods: We studied hospital acquired AKI in all emergency hospital admissions, except transfers from ICU to ICU or patients known to renal services, to ascertain mortality and readmission rates, and trackable modifiable factors for death, using cox regression and Kaplan Meier survival curves. Data was extracted from the electronic patient records and a series of case notes reviewed. Admissions were included between April 2006 and March 2010 (and patients followed up until September 2011).

Results: Overall incidence of AKI was 2.2%, (AKI stage 1, 61%, stage 2,27% and stage 3, 12%). In patients who sustain in-hospital AKI, 34% die in hospital, 42% are dead at 90 days and 48% at 1 year post discharge, compared to 12% 1 year mortality in patients without AKI. In multivariable analyses, AKI is an independent risk factor for in-hospital mortality (Hazard Ratio 1.6: 95% confidence intervals 1.43-1.75: P < 0.001), death within 90 days of discharge (Hazard Ratio 1.5: 95% confidence intervals 1.3-1.9: P < 0.001) and subsequent mortality beyond 90 days (Hazard Ratio 2.9: 95% confidence intervals 2.7-3.1: P < 0.001) after adjustment for co-morbidities and peak C-reactive protein. Thirty percent of the patients who died in the first 90 days post discharge and had AKI, also had malignancy. Readmission rates at 30 and 90 days were not increased by AKI after adjustment for co-morbidities and peak C-reactive protein.

Conclusions: A significant proportion of deaths in the first 90 days post-discharge may not be avoidable, due to malignancy and other end-stage disease. Readmission rates were not higher in patients who had had AKI.
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http://dx.doi.org/10.1186/s12882-017-0729-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5651577PMC
October 2017

The UK National Registry of ABO and HLA Antibody Incompatible Renal Transplantation: Pretransplant Factors Associated With Outcome in 879 Transplants.

Transplant Direct 2017 Jul 26;3(7):e181. Epub 2017 Jun 26.

Renal and Transplant Unit, University Hospitals Coventry and Warwickshire, Coventry, United Kingdom.

Background: ABO and HLA antibody incompatible (HLAi) renal transplants (AIT) now comprise around 10% of living donor kidney transplants. However, the relationship between pretransplant factors and medium-term outcomes are not fully understood, especially in relation to factors that may vary between centers.

Methods: The comprehensive national registry of AIT in the United Kingdom was investigated to describe the donor, recipient and transplant characteristics of AIT. Kaplan-Meier analysis was used to compare survival of AIT to all other compatible kidney transplants performed in the United Kingdom. Cox proportional hazards regression modeling was used to determine which pretransplant factors were associated with transplant survival in HLAi and ABOi separately. The primary outcome was transplant survival, taking account of death and graft failure.

Results: For 522 HLAi and 357 ABO incompatible (ABOi) transplants, 5-year transplant survival rates were 71% (95% confidence interval [CI], 66-75%) for HLAi and 83% (95% CI, 78-87%) for ABOi, compared with 88% (95% CI, 87-89%) for 7290 standard living donor transplants, and 78% (95% CI, 77-79%) for 15 322 standard deceased donor transplants ( < 0.0001). Increased chance of transplant loss in HLAi was associated with increasing number of donor specific HLA antibodies, center performing the transplant, antibody level at the time of transplant, and an interaction between donor age and dialysis status. In ABOi, transplant loss was associated with no use of IVIg, cytomegalovirus seronegative recipient, 000 HLA donor-recipient mismatch; and increasing recipient age.

Conclusions: Results of AIT were acceptable, certainly in the context of a choice between living donor AIT and an antibody compatible deceased donor transplant. Several factors were associated with increased chance of transplant loss, and these can lead to testable hypotheses for further improving therapy.
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http://dx.doi.org/10.1097/TXD.0000000000000695DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5498022PMC
July 2017

Aggregating Marginal Gains in Posttransplant CMV Risk Stratification.

Authors:
Simon Ball

Transplantation 2017 10;101(10):2273-2274

1 Institute of Translational Medicine, Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom.

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http://dx.doi.org/10.1097/TP.0000000000001869DOI Listing
October 2017

The scientific rationale for lateral tenodesis augmentation of intra-articular ACL reconstruction using a modified 'Lemaire' procedure.

Knee Surg Sports Traumatol Arthrosc 2017 Apr 9;25(4):1339-1344. Epub 2017 Apr 9.

Imperial College London, London, UK.

Purpose: The purpose of this work was to develop the rationale for adding a lateral extra-articular tenodesis to an ACL reconstruction in a knee with an injury that included both the ACL and anterolateral structures, and to show the early clinical picture.

Methods: The paper includes a review of recent anatomical and biomechanical studies of the anterolateral aspect of the knee. It then provides a detailed description of a modified Lemaire tenodesis technique. A short-term clinical follow-up of a case and control group was performed, with two sequential groups of patients treated by isolated ACL reconstruction, and by combined ACL plus lateral tenodesis.

Results: The anatomical and biomechanical literature guide the surgeon towards a procedure based on the ilio-tibial band. The clinical study found a reduction in pivot-shift instability in the group of patients with the combined procedure.

Conclusion: The evidence suggests that it should be appropriate to add a lateral extra-articular procedure to an ACL reconstruction in selected cases, but it was concluded that further data are required before definitive guidelines on the use of a lateral tenodesis can be established.

Level Of Evidence: III.
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http://dx.doi.org/10.1007/s00167-017-4537-3DOI Listing
April 2017

Sulforaphane promotes ER stress, autophagy, and cell death: implications for cataract surgery.

J Mol Med (Berl) 2017 05 12;95(5):553-564. Epub 2017 Jan 12.

School of Biological Sciences, Norwich Research Park, University of East Anglia, Norwich, NR4 7TJ, UK.

Posterior capsule opacification (PCO) commonly develops following cataract surgery and is a wound-healing response that can ultimately lead to secondary visual loss. Improved management of this problem is required. The isothiocyanate, sulforaphane (SFN), is reported to exert cytoprotective and cytotoxic actions, and the latter may be exploited to treat/prevent PCO. SFN concentrations of 10 μM and above significantly impaired wound-healing in a human lens capsular bag model. A similar pattern of response was also seen with a human lens cell line, FHL124. SFN treatment promoted increased expression of endoplasmic reticulum (ER) stress genes, which also corresponded with protein expression. Evidence of autophagy was observed in response to SFN as determined by increased microtubule-associated protein 1A/1B-light chain 3 (LC3)-II levels and detection of autophagic vesicles. This response was disrupted by established autophagy inhibitors chloroquine and 3-MA. SFN was found to promote MAPK signaling, and inhibition of ERK activation using U0126 prevented SFN-induced LC3-II elevation and vesicle formation. SFN also significantly increased levels of reactive oxygen species. Taken together, our findings suggest that SFN is capable of reducing lens cell growth and viability and thus could serve as a putative therapeutic agent for PCO.

Key Message: SFN reduces lens epithelial cell growth, migration, and viability. SFN can promote ER stress and autophagy in lens cells. SFN promotes MAPK signaling, and inhibition of MEK can suppress SFN-induced autophagy. ER stress and autophagy in lens cells are likely promoted by ROS production. SFN may help prevent posterior capsule opacification after cataract surgery.
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http://dx.doi.org/10.1007/s00109-016-1502-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5403866PMC
May 2017

Defining Priorities for Future Research: Results of the UK Kidney Transplant Priority Setting Partnership.

PLoS One 2016 24;11(10):e0162136. Epub 2016 Oct 24.

Centre for Evidence in Transplantation, Clinical Effectiveness Unit, Royal College of Surgeons of England, London, United Kingdom.

Background: It has been suggested that the research priorities of those funding and performing research in transplantation may differ from those of end service users such as patients, carers and healthcare professionals involved in day-to-day care. The Kidney Transplant Priority Setting Partnership (PSP) was established with the aim of involving all stakeholders in prioritising future research in the field.

Methods: The PSP methodology is as outlined by the James Lind Alliance. An initial survey collected unanswered research questions from patients, carers and clinicians. Duplicate and out-of-scope topics were excluded and the existing literature searched to identify topics answered by current evidence. An interim prioritisation survey asked patients and professionals to score the importance of the remaining questions to create a ranked long-list. These were considered at a final consensus workshop using a modified nominal group technique to agree a final top ten.

Results: The initial survey identified 497 questions from 183 respondents, covering all aspects of transplantation from assessment through to long-term follow-up. These were grouped into 90 unanswered "indicative" questions. The interim prioritisation survey received 256 responses (34.8% patients/carers, 10.9% donors and 54.3% professionals), resulting in a ranked list of 25 questions that were considered during the final workshop. Participants agreed a top ten priorities for future research that included optimisation of immunosuppression (improved monitoring, choice of regimen, personalisation), prevention of sensitisation and transplanting the sensitised patient, management of antibody-mediated rejection, long-term risks to live donors, methods of organ preservation, induction of tolerance and bioengineering of organs. There was evidence that patient and carer involvement had a significant impact on shaping the final priorities.

Conclusions: The final list of priorities relates to all stages of the transplant process, including access to transplantation, living donation, organ preservation, post-transplant care and management of the failing transplant. This list of priorities will provide an invaluable resource for researchers and funders to direct future activity.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0162136PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5077146PMC
June 2017