International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways (2015)

Type of publication:
Journal article

Author(s):
Cordell H.J., Han Y., Mells G.F., Li Y., Hirschfield G.M., Greene C.S., Xie G., Juran B.D., Zhu D., Qian D.C., Floyd J.A.B., Morley K.I., Prati D., Lleo A., Cusi D., Gershwin M.E., Anderson C.A., Lazaridis K.N., Invernizzi P., Seldin M.F., Sandford R.N., Amos C.I., Siminovitch K.A., Schlicht E.M., Lammert C., Atkinson E.J., Chan L.L., De Andrade M., Balschun T., Mason A.L., Myers R.P., Zhang J., Milkiewicz P., Qu J., Odin J.A., Luketic V.A., Bacon B.R., Bodenheimer H.C., Liakina V., Vincent C., Levy C., Gregersen P.K., Almasio P.L., Alvaro D., Andreone P., Andriulli A., Barlassina C., Battezzati P.M., Benedetti A., Bernuzzi F., Bianchi I., Bragazzi M.C., Brunetto M., Bruno S., Casella G., Coco B., Colli A., Colombo M., Colombo S., Cursaro C., Croce L.S., Crosignani A., Donato M.F., Elia G., Fabris L., Ferrari C., Floreani A., Foglieni B., Fontana R., Galli A., Lazzari R., Macaluso F., Malinverno F., Marra F., Marzioni M., Mattalia A., Montanari R., Morini L., Morisco F., Mousa Hani S., Muratori L., Muratori P., Niro G.A., Palmieri V.O., Picciotto A., Podda M., Portincasa P., Ronca V., Rosina F., Rossi S., Sogno I., Spinzi G., Spreafico M., Strazzabosco M., Tarallo S., Tarocchi M., Tiribelli C., Toniutto P., Vinci M., Zuin M., Ch'Ng C.L., Rahman M., Yapp T., Sturgess R., Healey C., Czajkowski M., Gunasekera A., Gyawali P., Premchand P., Kapur K., Marley R., Foster G., Watson A., Dias A., Subhani J., Harvey R., McCorry R., Ramanaden D., Gasem J., Evans R., Mathialahan T., Shorrock C., Lipscomb G., Southern P., Tibble J., Gorard D., Palegwala A., Carbone M., Dawwas M., Alexander G., Dolwani S., Prince M., Foxton M., Elphick D., Mitchison H., Gooding I., Karmo M., Saksena S., Mendall M., Patel M., Ede R., Austin A., Sayer J., Hankey L., Hovell C., Fisher N., Carter M., Koss K., Piotrowicz A., Grimley C., Neal D., Lim G., Levi S., Ala A., Broad A., Saeed A., Wood G., Brown J., Wilkinson M., Gordon H., Ramage J., Ridpath J., Ngatchu T., Grover B., Shaukat S., Shidrawi R., Abouda G., Ali F., Rees I., Salam I., Narain M., Brown A., Taylor-Robinson S., Williams S., Grellier L., Banim P., Das D., Chilton A., Heneghan M., Curtis H., Gess M., Drake I., Aldersley M., Davies M., Jones R., McNair A., Srirajaskanthan R., Pitcher M., Sen S., Bird G., Barnardo A., Kitchen P., Yoong K., Chirag O., Sivaramakrishnan N., MacFaul G., Jones D., Shah A., Evans C., Saha S., Pollock K., Bramley P., Mukhopadhya A., Fraser A., Mills P., Shallcross C., Campbell S., Bathgate A., Shepherd A., Dillon J., Rushbrook S., Przemioslo R., Macdonald C., Metcalf J., Shmueli U., Davis A., Naqvi A., Lee T., Stephen D., Collier J., Klass H., Ninkovic M., Cramp M., Sharer N., Aspinall R., Goggin P., Ghosh D., Douds A., Hoeroldt B., Booth J., Williams E., Hussaini H., Stableforth W., Ayres R., Thorburn D., Marshall E., Burroughs A., Mann S., Lombard M., Richardson P., Patanwala I., Maltby J., Brookes M., Mathew R., Vyas S., Singhal S., Gleeson D., Misra S., *Butterworth J., George K., Harding T., Douglass A., Panter S., Shearman J., Bray G., Butcher G., Forton D., McLindon J., Cowan M., Whatley G., Mandal A., Gupta H., Sanghi P., Jain S., Pereira S., Prasad G., Watts G., Wright M., Neuberger J., Gordon F., Unitt E., Grant A., Delahooke T., Higham A., Brind A., Cox M., Ramakrishnan S., King A., Collins C., Whalley S., Li A., Fraser J., Bell A., Wong V.S., Singhal A., Gee I., Ang Y., Ransford R., Gotto J., Millson C., Bowles J., Harrison M., Galaska R., Kendall J., Whiteman J., Lawlor C., Gray C., Elliott K., Mulvaney-Jones C., Hobson L., Van Duyvenvoorde G., Loftus A., Seward K., Penn R., Maiden J., Damant R., Hails J., Cloudsdale R., Silvestre V., Glenn S., Dungca E., Wheatley N., Doyle H., Kent M., Hamilton C., Braim D., Wooldridge H., Abrahams R., Paton A., Lancaster N., Gibbins A., Hogben K., Desousa P., Muscariu F., Musselwhite J., McKay A., Tan L., Foale C., Brighton J., Flahive K., Nambela E., Townshend P., Ford C., Holder S., Palmer C., Featherstone J., Nasseri M., Sadeghian J., Williams B., Thomas C., Rolls S.-A., Hynes A., Duggan C., Jones S., Crossey M., Stansfield G., MacNicol C., Wilkins J., Wilhelmsen E., Raymode P., Lee H.-J., Durant E., Bishop R., Ncube N., Tripoli S., Casey R., Cowley C., Miller R., Houghton K., Ducker S., Wright F., Bird B., Baxter G., Keggans J., Hughes M., Grieve E., Young K., Williams D., Ocker K., Hines F., Innes C., Valliani T., Fairlamb H., Thornthwaite S., Eastick A., Tanqueray E., Morrison J., Holbrook B., Browning J., Walker K., Congreave S., Verheyden J., Slininger S., Stafford L., O'Donnell D., Ainsworth M., Lord S., Kent L., March L., Dickson C., Simpson D., Longhurst B., Hayes M., Shpuza E., White N., Besley S., Pearson S., Wright A., Jones L., Gunter E., Dewhurst H., Fouracres A., Farrington L., Graves L., Marriott S., Leoni M., Tyrer D., Martin K., Dali-Kemmery L., Lambourne V., Green M., Sirdefield D., Amor K., Colley J., Shinder B., Jones J., Mills M., *Carnahan M., Taylor N., Boulton K., Tregonning J., Brown C., Clifford G., Archer E., Hamilton M., Curtis J., Shewan T., Walsh S., Warner K., Netherton K., Mupudzi M., Gunson B., Gitahi J., Gocher D., Batham S., Pateman H., Desmennu S., Conder J., Clement D., Gallagher S., Orpe J., Chan P., Currie L., O'Donohoe L., Oblak M., Morgan L., Quinn M., Amey I., Baird Y., Cotterill D., Cumlat L., Winter L., Greer S., Spurdle K., Allison J., Dyer S., Sweeting H., Kordula J.

Citation:
Nature Communications, September 2015, vol./is. 6/, 2041-1723

Abstract:
Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined5 x 108) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist.

Vein graft aneurysms following popliteal aneurysm repair are more common than we think (2015)

Type of publication:
Journal article

Author(s):
*Sharples A., *Kay M., *Sykes T., *Fox A., *Houghton A.

Citation:
Vascular, October 2015, vol./is. 23/5(494-497)

Abstract:
True infrainguinal vein graft aneurysms are reported infrequently in the literature. We sought to identify the true incidence of these graft aneurysms after popliteal aneurysm repair and identify factors which may increase the risk of such aneurysms developing. Using a prospectively compiled database, we identified patients who underwent a popliteal aneurysm repair between January 1996 and January 2011 at a single district general hospital. Patients were routinely followed up in a graft surveillance programme. Out of 45 patients requiring repair of a popliteal aneurysm over a 15-year period, four (8.8%) patients developed aneurysmal graft disease. Of the patients who developed graft aneurysms, all had aneurysmal disease at other sites compared with 18 (45.0%) patients who did not develop graft aneurysms. Patients with graft aneurysms had a mean of 1.60 aneurysms elsewhere compared to 0.58 in patients with non-aneurysmal grafts (P = 0.005). True vein graft aneurysms occur in a significant number of patients following popliteal aneurysm repair. Our data would suggest this to be more likely in patients who have aneurysms elsewhere and therefore a predisposition to aneurysmal disease. It may be appropriate for patients with aneurysms at other sites to undergo more prolonged post-operative graft surveillance.

Endocervical Crypt Involvement by CIN2-3 as a Predictor of Cytology Recurrence After Excisional Cervical Treatment. (2015)

Type of publication:
Journal article

Author(s):
*Papoutsis, Dimitrios, *Panikkar, Jane, *Underwood, Martyn, Blundell, Sue, *Sahu, Banchita, *Blackmore, Jill, *Reed, Nicholas

Citation:
Journal of Lower Genital Tract Disease, Oct 2015, vol. 19, no. 4, p. 311-318

Abstract:
The primary objective was to determine whether endocervical crypt involvement (ECI) by cervical intraepithelial neoplasia (CIN) on the excised cervical tissue after large loop excision of the transformation zone (LLETZ) represents a predictor of cytology recurrence. Secondary objective was to identify the ability of a pretreatment cervical punch biopsy to predict cytology recurrence. This was a case series study conducted in an NHS hospital. Women with LLETZ treatment performed over a 2-year period (2010-2011) were identified through our colposcopy database. Women with previous cervical treatment, cervical cancer on cone histopathology, or missing follow-up data were excluded. A group of 526 eligible women was identified over the study period. Crypt involvement was not a predictor of recurrence in the total sample. However, in the subgroup of women with CIN2-3 on pretreatment punch biopsy and with ECI on cone specimen in comparison to those without ECI, we identified an increased risk for overall cytology recurrence (HR, 3.1; 95% CI, 1.04-9.28; P = 0.043) and a trend for increased risk of high-grade cytology recurrence (HR, 4.62; 95% CI, 0.84-25.28; P = 0.07). A pretreatment punch biopsy showing crypt involvement by CIN2-3 was indicative of women at risk for abnormal cytology after excision. In women with CIN2-3 on pretreatment punch biopsy and ECI on excised tissue, the high-grade cytology recurrence was significantly reduced if more than 1.9 cm of cervix was removed. It seems that the presence of crypt involvement on the excised cervix in the subgroup of women with CIN2-3 on pretreatment punch biopsy is predictive of cytology recurrence.

Protein biomarkers in the rectal mucosa: a novel test for colorectal cancer? (2015)

Type of publication:
Conference abstract

Author(s):
*Lacy-Colson J., Norwood M., Murray C., Booth J.

Citation:
Gut, June 2015, vol./is. 64/(A529-A530)

Abstract:
Introduction: Earlier detection of colorectal cancer is a clinical priority. Currently very high numbers of patients are referred for colonoscopy under the 2 week rule system, with a pick up rate for cancer of 1:20 or less putting a major strain on endoscopy units investigating large numbers of the worried well. The aim of this study was to assess the correlation of protein biomarkers captured from the rectal mucosa with the presence or absence of colorectal cancer. Method We conducted a case control study of 20 patients with colorectal cancer, and 20 controls. All patients had been referred to colorectal outpatients with potentially worrying symptoms; presence or absence of cancer was determined by colonoscopy or CT virtual colonoscopy. A novel sampling device, OriColTM, was employed to collect samples of rectal mucosa for biomarker analysis. The device incorporates a nitrile membrane which, following insertion into the unprepared rectum via a standard proctoscope, is inflated to make contact with the rectal mucosa for a period of 10 s. Upon deflation and retraction of the membrane, a preservation buffer is added to preserve the sample prior to analysis. Sampling can be performed in an outpatient setting in under 2 min and has been shown to be well tolerated in >2500 patients. The levels of various antibodies, haemoglobin and carcinoembryonic antigen were analysed using conventional ELISA techniques. Statistical analysis of the trial results was performed using the Wilcoxon test for non-parametric comparisons with two sided p values. The area under the receiver operating characteristic (ROC) curve for distinguishing between the two diagnostic groups, together with its confidence interval, was calculated for each biomarker. Logistic regression analyses were used to investigate the performance of different combinations of biomarkers. This study was conducted with appropriate research ethics committee approval. Results Univariate analyses identified five candidate predictive biomarkers for colorectal cancer. All combinations of two and three predictors were investigated using logistic regression. The best performing combination of biomarkers was haemoglobin and IgA. The area under the ROC curve for this best linear combination was 0.86. Conclusion We suggest that ELISA analysis protein biomarkers collected with the OriColTM device offers a potentially useful and cost-effective pre-colonoscopy screening tool in patients referred under the 2 week rule criteria. Data from this pilot study suggests that a sensitivity of >95% can be achieved while massively reducing the number of patients requiring urgent colonoscopy to exclude a diagnosis of cancer.

Link to full-text: http://gut.bmj.com/content/64/Suppl_1/A529.2.full.pdf+html

An unusual cause of fetomaternal distress at term: uterine vessel rupture in pregnancy (2015)

Type of publication:
Journal article

Author(s):
Calcott G.A., Gaber M., Freedman J., Patni S.

Citation:
BMJ Case Reports, August 2015, vol./is. 2015

Abstract:
This report describes a case of spontaneous bleeding from uterine vessels presenting as hyperstimulation and fetomaternal distress at term. A 40-week primigravid woman underwent an emergency caesarean section for fetal distress, which unexpectedly revealed a spontaneous haemoperitoneum. Clinical assessment and investigations postoperatively gave a diagnosis of a rightsided uterine artery aneurysm that, it was believed, had ruptured, causing the haemoperitoneum. This was successfully treated postnatally using interventional radiological techniques leading to expeditious maternal recovery and discharge home.

Link to full-text: http://casereports.bmj.com/content/2015/bcr-2014-209004.full.pdf

Validation of the English translation of the low anterior resection syndrome score (2015)

Type of publication:
Journal article

Author(s):
Juul T., Christensen P., Janjua A.Z., Laurberg S., Emmertsen K.J., Moran B., Khan R.B., Kurasz C., Waldron E., Battersby N.J., Janjau Z., Moran B.J., Shahir T., Chan K., Glynne-Jones R., Kelly S., Evans K., Hughes R., Smith F., Heath B., Leinhardt D., Norton A., Jayne D., Moriarty C., Laing E., Mawdsley S., Bourner L., Narula N., Ward J., *Lacy-Colson J., *Moore H., *Potts S., Branagan G., Bell L., Chave H., Carter V., Mirza N., Pereira G., Williams J.G., Last K., Todd J., Woodcock N.

Citation:
Colorectal Disease, October 2015, vol./is. 17/10(908-916)

Abstract:
Aim: Many patients having anterior resection for rectal cancer suffer from severe long-term bowel dysfunction, known as low anterior resection syndrome (LARS). The LARS score was developed in Denmark, and Swedish, Spanish and German versions have been validated. The aim of this study was to validate the English translation of the LARS score in British rectal cancer patients. Method: Rectal cancer patients who underwent an anterior resection in 12 UK centres received the LARS score questionnaire, the EORTC QLQ-C30 and a single ad hoc quality of life question. A subgroup of patients received the LARS score questionnaire twice. Results: The response rate was 80% and 451 patients were included in the analyses. A strong association between LARS score and quality of life (convergent validity) was found (P < 0.01), discriminative validity was good (P < 0.02) and the test-retest reliability was high (intraclass correlation coefficient 0.83). Conclusion: The English translation of the LARS score has shown good psychometric properties comparable with recently published results from an international multicentre study. Thus, the English translation of the LARS score can be considered a valid and reliable tool for measuring LARS.

Thrombolysis for stroke in pregnancy at 39 weeks gestation with a subsequent normal delivery (2015)

Type of publication:
Journal article

Author(s):
*Ritchie J., *Lokman M., *Panikkar J.

Citation:
BMJ Case Reports, August 2015, vol./is. 2015

Abstract:
Stroke during pregnancy is fortunately a rare event, however, it can have severe consequences, with 9.5% of all maternal deaths being related to stroke. The most common presentation is an ischaemic stroke. There has been much debate as to the correct treatment for such cases' and whether thrombolysis can be used safely in pregnancy. Our case describes a 28-year-old woman with a previous normal vaginal delivery presenting in her third trimester with a sudden onset of dense left hemiparesis. She was successfully treated with alteplase, an intravenous recombinant tissue-type plasminogen activator, and made a full recovery after normal delivery of a healthy infant. This case report highlights one of the first documented successful outcomes from thrombolysis for this condition in the UK and may help inform future management of these women.

Link to full-text: http://casereports.bmj.com/content/2015/bcr-2015-209563.full.pdf

Understanding the needs of people with dementia and family carers (2015)

Type of publication:
Journal article

Author(s):
Bray, Jennifer, Evans, Simon, Thompson, Rachel, Bruce, Mary, Carter, Christine, Brooker, Dawn, Milosevic, Sarah, *Coleman, Helen, *McSherry, Wilf

Citation:
Nursing Older People, 01 September 2015, vol./is. 27/7 (18-23)

Abstract:
This is the first in a short series that presents case study examples of the positive work achieved by trusts who participated in the Royal College of Nursing's development programme to improve dementia care in acute hospitals. When a person with dementia is in hospital, poor understanding of individual needs and preferences can contribute to a lack of person-centred care. Similarly, the needs of family carers can often be overlooked and staff do not always appreciate these needs at such a stressful time. This article illustrates how three NHS trusts have addressed these issues. To help staff get to know patients with dementia, Salford Royal NHS Foundation Trust has implemented a patient passport. Similarly, The Shrewsbury and Telford Hospital NHS Trust has implemented a carer passport that overcomes the restrictions imposed by hospital visiting hours. Royal Devon and Exeter NHS Foundation Trust also focused on carers, holding a workshop to elicit feedback on what was important to them. This was a useful means of engaging with carers and helped staff to realise that even simple changes can have a significant effect.

Percutaneous endoscopic gastrostomy (PEG) in disabled children - a bench marking exercise (2015)

Type of publication:
Conference abstract

Author(s):
*Saran S.S., *Wasala D.W., *Ayub N.A.

Citation:
Archives of Disease in Childhood, April 2015, vol./is. 100/(A196)

Abstract:
Background: The Paediatric Gastroenterology Unit based at the Royal Shrewsbury Hospital provides a service for two hospitals. Its subsequent management is supported by the Community Paediatric Nurses. A benchmarking exercise of the PEG Service was undertaken and audited against the European Society for Parenteral and Enteral Nutrition (ESPEN) Guidelines. Methods All children with a PEG in-situ were identified from the Community Nurses PEG database. The electronic records of these patients were accessed for relevant data and input into a Microsoft Excel 2010 database by a single researcher. The ESPEN standards were used to audit the service in the relevant domains. Results 53 children with a PEG were identified. There was a clearly documented indication for a PEG in 96%, with neurologically disabled children at risk of aspiration comprising the largest group (47%). Feeding difficulties and Failure to thrive (FTT) made up 30% while other indications were Sensory Feeding Disorder in combination with other primary disorders (13%) dysmotility (4%) and metabolic causes (2%). The primary diagnosis was neurological in 55%, gastrointestinal 11%, renal 4% and cardiovascular, respiratory and endocrine 2% each. There were multiple diagnoses in 11% Nasogastric feeds were instituted and documented prior to the PEG in 94% and may have been used in a further 2% but not documented. More than half the children had their PEG sited at the age of 13-36 months (52%), a further 15% under 13 months while 20% were after the age of 36 months. Almost one third of the children (29%) had no complications from the PEG. Localised infection was the commonest complication (28%) with granulation tissue (13%), mechanical problems (dislodgement 8%, blockage 4%), skin ulceration (10%) and leakage (8%) as other complications. PEG feeds were succesful in improving the weight centiles of these patients. Parental satisfaction with the service could not be evaluated retrospectively. Conclusions The PEG Service at the Shrewsbury and Telford Hospitals NHS Trust adheres to ESPEN standards in the majority of patients and is associated with a low complication rate. Parental Satisfaction with the service should be sought prospectively.

Link to full-text: http://adc.bmj.com/content/100/Suppl_3/A196.1.full.pdf+html