Leeds Teaching Hospitals National Health Service Trust

Leeds, United Kingdom

Leeds Teaching Hospitals National Health Service Trust

Leeds, United Kingdom
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Mircsof D.,University of Zürich | Langouet M.,University of Paris Pantheon Sorbonne | Rio M.,University of Paris Pantheon Sorbonne | Moutton S.,University of Paris Pantheon Sorbonne | And 25 more authors.
Nature Neuroscience | Year: 2015

The NONO protein has been characterized as an important transcriptional regulator in diverse cellular contexts. Here we show that loss of NONO function is a likely cause of human intellectual disability and that NONO-deficient mice have cognitive and affective deficits. Correspondingly, we find specific defects at inhibitory synapses, where NONO regulates synaptic transcription and gephyrin scaffold structure. Our data identify NONO as a possible neurodevelopmental disease gene and highlight the key role of the DBHS protein family in functional organization of GABAergic synapses. © 2015 Nature America, Inc.


Caroff X.J.,Beaujon Hospital | Mihalea C.,Beaujon Hospital | Mihalea C.,Victor Babes University of Medicine and Pharmacy Timisoara | Klisch J.,Helios General Hospital | And 12 more authors.
American Journal of Neuroradiology | Year: 2015

BACKGROUND AND PURPOSE: The safety and efficiency of the dual-layer Woven EndoBridge (WEB) device has already been published. However, this international multicenter study sought to evaluate the safety of single-layer devices, which are the newest generation of the WEB intrasaccular flow-disrupter family. They have been designed to offer smaller-sized devices with a lower profile to optimize navigability and delivery, which may, in turn, broaden their range of use. MATERIALS AND METHODS: Data from all consecutive patients treated with a single-layer WEB device, in 10 European centers from June 2013 to May 2014 were included. Clinical presentations, technical details, intra-and perioperative complications, and outcomes at discharge were recorded. Clinical and angiographic data at last follow-up were also analyzed when available. RESULTS: Ninety patients with 98 WEB-treated aneurysms were included in this study. In 93 cases (95%), WEB placement was possible. Complete occlusion at the end of the procedure was obtained in 26 instances (26%). Additional treatment during the procedure (coiling and/or stent placement) was necessary in 12 cases (12.7%). Procedure-related complications occurred in 13 cases, leading to permanent neurologic deficits in 4 patients (4.4%). Early vascular imaging follow-up data were available for 44 patients (57%), with an average time interval of 3.3 months. Treatment-related morbidity and mortality rates at last follow-up were 2.2% and 1.1%, respectively. CONCLUSIONS: In this study, the feasibility and safety of the single-layer WEB device was comparable with that of the double-layer. However, further studies are needed to evaluate long-term efficacies.


PubMed | Birmingham Center, Guys and St Thomas Hospital, Queen Elizabeth Hospital, Sheffield Teaching Hospitals and 2 more.
Type: | Journal: Transfusion | Year: 2016

ABO blood group-incompatible kidney transplantation (ABOiKTx) outcomes are good, but complications are more common than in conventional transplantation. Regimens that use extracorporeal antibody removal therapy (EART) and enhanced immunosuppression are guided by titration of ABO blood group antibodies (using hemagglutination [HA] dilution assays), and these assays vary significantly in performance between centers. This study aims to describe the differences in titer measurement and the effect on clinical practice and outcomes.This multicentre, prospective cohort study of 100 ABOiKTx recipients assessed treatment and outcome data, including HA assay results measured retrospectively in a single central laboratory.Patient and allograft survival at 1 year was 99% and 94%, respectively. There were significant differences in the number of pretransplantation EART sessions in centers undertaking plasma exchange (PEx), compared with immunoadsorption (IA) (median, 6 vs. 4 sessions; p=0.007). The pre-EART HA titer in both groups was the same when centrally assayed. The local HA assay used to guide treatment yielded significantly higher titers in centers undertaking PEx compared with IA (median, 128 vs. 32; p<0.005). Patients undergoing PEx rather than IA were significantly more likely to suffer postoperative hematoma (12.9% vs. 1.8%; p=0.05) or any perioperative collection requiring drainage (19.4% vs. 3.6%; p=0.02).The colinearity of HA assay sensitivity with the receipt of PEx and EART limits some conclusions regarding the likely direction of causation. However, the association of differences in clinical practice with recognized perioperative complications of ABOiKTx identifies targets for further investigation and quality improvement.


Calvert P.A.,National United University | Calvert P.A.,University of Cambridge | Calvert P.A.,Papworth Hospital National Health Service Foundation Trust | Cockburn J.,University of Sussex | And 18 more authors.
Circulation | Year: 2014

Background-Postinfarction ventricular septal defect carries a grim prognosis. Surgical repair offers reasonable outcomes in patients who survive a healing phase. Percutaneous device implantation represents a potentially attractive early alternative. Methods and Results-Postinfarction ventricular septal defect closure was attempted in 53 patients from 11 centers (1997-2012; aged 72±11 years; 42% female). Nineteen percent had previous surgical closure. Myocardial infarction was anterior (66%) or inferior (34%). Time from myocardial infarction to closure procedure was 13 (first and third quartiles, 5-54) days. Devices were successfully implanted in 89% of patients. Major immediate complications included procedural death (3.8%) and emergency cardiac surgery (7.5%). Immediate shunt reduction was graded as complete (23%), partial (62%), or none (15%). Median length of stay after the procedure was 5.0 (2.0-9.0) days. Fifty-eight percent survived to discharge and were followed up for 395 (63-1522) days, during which time 4 additional patients died (7.5%). Factors associated with death after postinfarction ventricular septal defect closure included the following: age (hazard ratio [HR]=1.04; P=0.039), female sex (HR=2.33; P=0.043), New York Heart Association class IV (HR=4.42; P=0.002), cardiogenic shock (HR=3.75; P=0.003), creatinine (HR=1.007; P=0.003), defect size (HR=1.09; P=0.026), inotropes (HR=4.18; P=0.005), and absence of revascularization therapy for presenting myocardial infarction (HR=3.28; P=0.009). Prior surgical closure (HR=0.12; P=0.040) and immediate shunt reduction (HR=0.49; P=0.037) were associated with survival. Conclusions- Percutaneous closure of postinfarction ventricular septal defect is a reasonably effective treatment for these extremely high-risk patients. Mortality remains high, but patients who survive to discharge do well in the longer term. (Circulation. 2014;129:2395-2402.) © 2014 American Heart Association, Inc.


Kirby A.,Leeds Teaching Hospitals National Health Service Trust | Herbert A.,Pennine Acute National Health Service Trust
PLoS ONE | Year: 2013

Objectives: The aim of this study is to investigate if correlations exist between income inequality and antimicrobial resistance. This study's hypothesis is that income inequality at the national level is positively correlated with antimicrobial resistance within developed countries. Data collection and analysis: Income inequality data were obtained from the Standardized World Income Inequality Database. Antimicrobial resistance data were obtained from the European antimicrobial Resistance Surveillance Network and outpatient antimicrobial consumption data, measured by Defined daily Doses per 1000 inhabitants per day, from the European Surveillance of antimicrobial Consumption group. Spearman's correlation coefficient (r) defined strengths of correlations of: > 0.8 as strong, > 0.5 as moderate and > 0.2 as weak. Confidence intervals and p values were defined for all r values. Correlations were calculated for the time period 2003-10, for 15 European countries. Results: Income inequality and antimicrobial resistance correlations which were moderate or strong, with 95% confidence intervals > 0, included the following. Enterococcus faecalis resistance to aminopenicillins, vancomycin and high level gentamicin was moderately associated with income inequality (r= ≥0.54 for all three antimicrobials). Escherichia coli resistance to aminoglycosides, aminopenicillins, third generation cephalosporins and fluoroquinolones was moderately-strongly associated with income inequality (r= ≥0.7 for all four antimicrobials). Klebsiella pneumoniae resistance to third generation cephalosporins, aminoglycosides and fluoroquinolones was moderately associated with income inequality (r= ≥0.5 for all three antimicrobials). Staphylococcus aureus methicillin resistance and income inequality were strongly associated (r=0.87). Conclusion: As income inequality increases in European countries so do the rates of antimicrobial resistance for bacteria including E. faecalis E. coli, K. pneumoniae and S. aureus. Further studies are needed to confirm these findings outside Europe and investigate the processes that could causally link income inequality and antimicrobial resistance. © 2013 Kirby et al.


PubMed | Tufts University, University of Zürich, ETH Zurich, Leeds Teaching Hospitals National Health Service Trust and University of Paris Pantheon Sorbonne
Type: Case Reports | Journal: Nature neuroscience | Year: 2015

The NONO protein has been characterized as an important transcriptional regulator in diverse cellular contexts. Here we show that loss of NONO function is a likely cause of human intellectual disability and that NONO-deficient mice have cognitive and affective deficits. Correspondingly, we find specific defects at inhibitory synapses, where NONO regulates synaptic transcription and gephyrin scaffold structure. Our data identify NONO as a possible neurodevelopmental disease gene and highlight the key role of the DBHS protein family in functional organization of GABAergic synapses.


Hayashi T.,Kanagawa Cancer Center | Yoshikawa T.,Kanagawa Cancer Center | Bonam K.,University of Leeds | Sue-Ling H.M.,Leeds Teaching Hospitals National Health Service Trust | And 5 more authors.
Cancer | Year: 2013

BACKGROUND: The objective of this study was to investigate whether the seventh edition of the American Joint Committee on Cancer/International Union Against Cancer TNM classification (TNM7) had superior discriminatory ability over the sixth edition of the TNM classification (TNM6) in patients with gastric cancer regardless of their country of origin. METHODS: In total, 538 patients from the Kanagawa Cancer Center Hospital (Yokohama, Japan) (KCCH) and 519 patients from the Leeds Teaching Hospitals National Health Service Trust (Leeds, United Kingdom) (LTHT) who underwent surgery for gastric cancer were selected. Overall survival was used for statistical analysis. Hazard ratios (HRs) were estimated with disease stage as a continuous variable to evaluate the discriminatory ability of the TNM stage groups. The estimates of log HRs (logHRs) for the TNM6 and the TNM7 stage groups were compared. RESULTS: In the KCCH cohort, 82 patients (15%) were upstaged, and 26 patients (5%) were downstaged between TNM6 and TNM7 compared with 253 patients (49%) and 53 patients (10%), respectively, in the LTHT cohort. The logHRs for a 1-stage increase within TNM6 and TNM7 were 1.06 and 1.16, respectively, in the KCCH cohort and 0.57 and 0.79, respectively, in the LTHT cohort. The differences in logHRs between TNM6 and TNM7 were significant in each cohort (KCCH: logHR, 0.11; P =.024; LTHT: logHR, 0.21; P =.0002) and between the 2 cohorts. CONCLUSIONS: TNM7 had superior discriminatory ability compared with TNM6 in both cohorts. The improved ability to discriminate patients with different survival probability when using TNM7 was greater in the LTHT cohort. The current findings indicated that the discriminatory ability of the TNM stage groups may depend on the baseline survival characteristics of the patient cohort. Cancer 2013. © 2013 American Cancer Society. The seventh edition of the American Joint Committee on Cancer/International Union Against Cancer TNM classification (TNM7) demonstrates superior discriminatory ability compared with the sixth edition in 2 cohorts (a Japanese cohort and a United Kingdom cohort) of patients with gastric cancer. When using TNM7, the improvement in the ability to discriminate patients with different survival probability is greater in the United Kingdom cohort than in the Japanese cohort. Copyright © 2012 American Cancer Society.


Best E.L.,Leeds Teaching Hospitals National Health Service Trust | Fawley W.N.,Leeds Teaching Hospitals National Health Service Trust | Parnell P.,Leeds Teaching Hospitals National Health Service Trust | Wilcox M.H.,Leeds Teaching Hospitals National Health Service Trust | Wilcox M.H.,University of Leeds
Clinical Infectious Diseases | Year: 2010

Background. The high transmissibility and widespread environmental contamination by Clostridium difficile suggests the possibility of airborne dissemination of spores. We measured airborne and environmental C. difficile adjacent to patients with symptomatic C. difficile infection (CDI). Methods. We conducted air sampling adjacent to 63 patients with CDI for 180 h in total and for 101 h in control settings. Environmental samples were obtained from surfaces adjacent to the patient and from communal areas of the ward. C. difficile isolates were characterized by ribotyping and multilocus variable-number tandemrepeat analysis to determine relatedness. Results. Of the first 50 patients examined (each for 1 h), only 12% had positive air samples, most frequently those with active symptoms of CDI (10%, vs 2% for those with no symptoms). We intensively sampled the air around 10 patients with CDI symptoms, each for 10 h over 2 days, as well as a total of 346 surface sites. C. difficile was isolated from the air in the majority of these cases (7 of 10 patients tested) and from the surfaces around 9 of the patients; 60% of patients had both air and surface environments that were positive for C. difficile. Molecular characterization confirmed an epidemiological link between airborne dispersal, environmental contamination, and CDI cases. Conclusions. Aerosolization of C. difficile occurs commonly but sporadically in patients with symptomatic CDI. This may explain the widespread dissemination of epidemic strains. Our results emphasize the importance of single-room isolation as soon as possible after the onset of diarrhea to limit the dissemination of C. difficile. © 2010 by the Infectious Diseases Society of America. All rights reserved.


Vital E.M.,University of Leeds | Dass S.,University of Leeds | Buch M.H.,University of Leeds | Henshaw K.,University of Leeds | And 6 more authors.
Arthritis and Rheumatism | Year: 2011

Objective Rituximab appears to be effective in many studies of systemic lupus erythematosus (SLE), with variable initial clinical response and time to relapse. However, results of a randomized controlled trial of rituximab were negative. This study was undertaken to evaluate the effectiveness of rituximab in SLE, using highly sensitive flow cytometry (HSFC), which can define B cell numbers 50-100 times lower than conventional techniques and predicts responses in rheumatoid arthritis. Methods Thirty-nine patients with active SLE were started on a standard regimen of rituximab with intravenous and oral steroids. Clinical response and relapse were defined using the British Isles Lupus Assessment Group (BILAG) index with criteria for major clinical response, partial clinical response, and nonresponse. HSFC, including analysis of B cell subsets, was performed. Results There was a significant reduction from baseline in global BILAG score at all time points analyzed (P < 0.0001), and major clinical response and partial clinical response rates were 51% and 31%, respectively. Time to relapse was highly variable. Fifty percent of the patients relapsed after 6-18 months (earlier relapse); the remainder relapsed at a slower rate (later relapse). B cell depletion and repopulation were variable and were predictive of these clinical outcomes. There was a persistent B cell presence in 21 patients after 2 infusions of rituximab, which included all 7 patients with no response (P = 0.012 versus patients with complete depletion of B cells). Memory B cell (P = 0.02) and plasmablast (P < 0.001) repopulation after 26 weeks was markedly faster in patients with earlier relapse versus patients with later relapse. Conclusion Our findings indicate that rituximab is effective in SLE, and clinical responses are supported by close correlation with B cell numbers. HSFC is a valuable tool in the assessment and prediction of response in SLE. Copyright © 2011 by the American College of Rheumatology.


Bird-Lieberman G.,Leeds Teaching Hospitals National Health Service Trust | Sethi K.,Harrogate National Health Service Trust | Childs A.-M.,Leeds Teaching Hospitals National Health Service Trust | Chumas P.,Leeds Teaching Hospitals National Health Service Trust | And 3 more authors.
Journal of Neurosurgery: Pediatrics | Year: 2011

The authors describe the clinical and radiological features in 3 children with a diffuse hemispheric dysembryoplastic neuroepithelial tumor (DNET) presenting with severe epilepsy and a previously unreported and characteristic MR imaging appearance. The DNET is a well-recognized cause of focal epilepsy, usually with a very good response to resection. These tumors are usually intracortical, and most commonly arise in the temporal lobe or frontal lobes. Radiologically they are usually sharply demarcated, and show little contrast enhancement. Three children (2 boys and 1 girl) presented at 14, 17, and 22 months of age with epileptic seizures. The seizures were focal motor or complex focal. One patient had epileptic spasms. The response to antiepileptic drug therapy was poor. Motor and cognitive development was delayed in all patients. One patient developed a severe epileptic encephalopathy, with regression of motor and cognitive skills. Her electroencephalogram obtained at that time showed hypsarhythmia. Admission MR imaging showed a diffuse unilateral abnormality involving frontal, temporal, and parietal lobes with little or no mass effect. There was involvement of both gray and white matter, with a striking sparing of the internal capsule in spite of apparent tumor throughout the basal ganglia and thalamus. In 2 patients there was prominent expansion of cortical gyri by tumor. In 1 child the initial radiological diagnosis was a middle cerebral artery infarct. On subsequent review the radiological diagnosis was thought to be low-grade glioma in all patients. The first patient underwent 2 limited resections involving the temporal lobe. He has continued to have poorly controlled seizures and severe behavioral and cognitive problems. The other patients had subtotal resection to the level of the internal capsule. One patient is currently seizure free 24 months postsurgery, but remains cognitively impaired. The patient in Case 3 is having some seizures 3.5 years postsurgery and remains hemiplegic, but the regression has reversed and she is making steady developmental progress. The pathological specimens showed the typical features of a DNET in all cases. This striking radiological pattern has not previously been described as a feature of a DNET. Recognition of this radiological pattern in young children with epilepsy will allow early consideration for resection, which may lead to improved long-term cognitive outcome.

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