The analysis of gut microbiota in patients with bile acid diarrhoea treated with colesevelam (2023)

Type of publication:
Journal article

Author(s):
Kumar A; Quraishi MN; Al-Hassi HO; El-Asrag ME; Segal JP; Jain M; Steed H; Butterworth J; Farmer A; Mclaughlin J; Beggs A; Brookes MJ Authors Full Name Kumar, Aditi; Quraishi, Mohammed Nabil; Al-Hassi, Hafid O; El-Asrag, Mohammed E; Segal, Jonathan P; Jain, Manushri; Steed, Helen; *Butterworth, Jeffrey; Farmer, Adam; Mclaughlin, John; Beggs, Andrew; Brookes, Matthew

Citation:
Frontiers in Microbiology. 14:1134105, 2023. [epub ahead of print]

Abstract:
Introduction: Bile acid diarrhoea (BAD) is a common disorder that results from an increased loss of primary bile acids and can result in a change in microbiome. The aims of this study were to characterise the microbiome in different cohorts of patients with BAD and to determine if treatment with a bile acid sequestrant, colesevelam, can alter the microbiome and improve microbial diversity. Materials and methods: Patients with symptoms of diarrhoea underwent 75-selenium homocholic acid (75SeHCAT) testing and were categorised into four cohorts: idiopathic BAD, post-cholecystectomy BAD, post-operative Crohn's disease BAD and 75SeHCAT negative control group. Patients with a positive 75SeHCAT (<15%) were given a trial of treatment with colesevelam. Stool samples were collected pre-treatment, 4-weeks, 8-weeks and 6-12 months post-treatment. Faecal 16S ribosomal RNA gene analysis was undertaken. Results: A total of 257 samples were analysed from 134 patients. alpha-diversity was significantly reduced in patients with BAD and more specifically, in the idiopathic BAD cohort and in patients with severe disease (SeHCAT <5%); p < 0.05. Colesevelam did not alter bacterial alpha/beta-diversity but patients who clinically responded to treatment had a significantly greater abundance of Fusobacteria and Ruminococcus, both of which aid in the conversion of primary to secondary bile acids. Conclusion: This is the first study to examine treatment effects on the microbiome in BAD, which demonstrated a possible association with colesevelam on the microbiome through bile acid modulation in clinical responders. Larger studies are now needed to establish a causal relationship with colesevelam and the inter-crosstalk between bile acids and the microbiome.

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Detailed Sub-study Analysis of the SECRAB Trial: Quality of Life, Cosmesis and Chemotherapy Dose Intensity (2023)

Type of publication:
Journal article

Author(s):
Fernando IN; Lax S; Bowden SJ; Ahmed I; Steven JH; Churn M; Brunt AM; *Agrawal RK; Canney P; Stevens A; Rea DW Authors Full Name Fernando, I N; Lax, S; Bowden, S J; Ahmed, I; Steven, J H; Churn, M; Brunt, A M; Agrawal, R K; Canney, P; Stevens, A; Rea, D W.

Citation:
Clinical Oncology (Royal College of Radiologists). Volume 35, pages 397-407, 2023 Mar 20.

Abstract:
AIMS: SECRAB was a prospective, open-label, multicentre, randomised phase III trial comparing synchronous to sequential chemoradiotherapy (CRT). Conducted in 48 UK centres, it recruited 2297 patients (1150 synchronous and 1146 sequential) between 2 July 1998 and 25 March 2004. SECRAB reported a positive therapeutic benefit of using adjuvant synchronous CRT in the management of breast cancer; 10-year local recurrence rates reduced from 7.1% to 4.6% (P = 0.012). The greatest benefit was seen in patients treated with anthracycline-cyclophosphamide, methotrexate, 5-fluorouracil (CMF) rather than CMF. The aim of its sub-studies reported here was to assess whether quality of life (QoL), cosmesis or chemotherapy dose intensity differed between the two CRT regimens. MATERIALS AND METHODS: The QoL sub-study used EORTC QLQ-C30, EORTC QLQ-BR23 and the Women's Health Questionnaire. Cosmesis was assessed: (i) by the treating clinician, (ii) by a validated independent consensus scoring method and (iii) from the patients' perspective by analysing four cosmesis-related QoL questions within the QLQ-BR23. Chemotherapy doses were captured from pharmacy records. The sub-studies were not formally powered; rather, the aim was that at least 300 patients (150 in each arm) were recruited and differences in QoL, cosmesis and dose intensity of chemotherapy assessed. The analysis, therefore, is exploratory in nature. RESULTS: No differences were observed in the change from baseline in QoL between the two arms assessed up to 2 years post-surgery (Global Health Status: -0.05; 95% confidence interval -2.16, 2.06; P = 0.963). No differences in cosmesis were observed (via independent and patient assessment) up to 5 years post-surgery. The percentage of patients receiving the optimal course-delivered dose intensity (>=85%) was not significantly different between the arms (synchronous 88% versus sequential 90%; P = 0.503). CONCLUSIONS: Synchronous CRT is tolerable, deliverable and significantly more effective than sequential, with no serious disadvantages identified when assessing 2-year QoL or 5-year cosmetic differences.

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Intussusception of the appendix in a young adult: an important differential diagnosis of abdominal pain in cystic fibrosis patients? (2023)

Type of publication:
Journal article

Author(s):
*Venkatasami, Meena; *Cobby, Ellen.

Citation:
Journal of Surgical Case Reports. 2023(3):117, 2023 Mar.

Abstract:
Cystic fibrosis (CF) is commonly associated with gastrointestinal manifestations from infancy to adulthood. Distal intestinal obstruction syndrome (DIOS) affects 20% of CF patients, where intussusception can be a rare complication. A 20-year-old CF male was diagnosed with a 3-day history of right iliac fossa pain and diarrhoea. Clinical examination revealed a tender palpable mass in the right iliac fossa and raised serum inflammatory markers. Contrast computerized-tomography of the abdomen-pelvis suggested intussusception of the appendix and further confirmed on histological analyses. The patient underwent an open appendicectomy where the intussusception had self-resolved. The literature review indicated a scarcity of data with 10 cases reported of intussusception in adult CF patients. Our case was in line with previous research of transient intussusception. This rare case highlights an importance to carry a higher index of suspicion for gastrointestinal manifestations in CF patients where differential diagnoses of DIOS and intussusception should be considered in the acute presentation.

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The association between menstrual cycle characteristics and cardiometabolic outcomes in later life: a retrospective matched cohort study of 704,743 women from the UK (2023)

Type of publication:
Journal article

Author(s):
Okoth, Kelvin; *Parry Smith, William; Thomas, G Neil; Nirantharakumar, Krishnarajah; Adderley, Nicola J

Citation:
BMC Medicine, 2023, 21, Article number: 104

Abstract:
Background
Female reproductive factors are gaining prominence as factors that enhance cardiovascular disease (CVD) risk; nonetheless, menstrual cycle characteristics are under-recognized as a factor associated with CVD. Additionally, there is limited data from the UK pertaining to menstrual cycle characteristics and CVD risk.

Methods
A UK retrospective cohort study (1995–2021) using data from a nationwide database (The Health Improvement Network). Women aged 18–40 years at index date were included. 252,325 women with history of abnormal menstruation were matched with up to two controls. Two exposures were examined: regularity and frequency of menstrual cycles; participants were assigned accordingly to one of two separate cohorts. The primary outcome was composite cardiovascular disease (CVD). Secondary outcomes were ischemic heart disease (IHD), cerebrovascular disease, heart failure (HF), hypertension, and type 2 diabetes mellitus (T2DM). Cox proportional hazards regression models were used to derive adjusted hazard ratios (aHR) of cardiometabolic outcomes in women in the exposed groups compared matched controls.

Results
During 26 years of follow-up, 20,605 cardiometabolic events occurred in 704,743 patients. Compared to women with regular menstrual cycles, the aHRs (95% CI) for cardiometabolic outcomes in women with irregular menstrual cycles were as follows: composite CVD 1.08 (95% CI 1.00–1.19), IHD 1.18 (1.01–1.37), cerebrovascular disease 1.04 (0.92–1.17), HF 1.30 (1.02–1.65), hypertension 1.07 (1.03–1.11), T2DM 1.37 (1.29–1.45). The aHR comparing frequent or infrequent menstrual cycles to menstrual cycles of normal frequency were as follows: composite CVD 1.24 (1.02–1.52), IHD 1.13 (0.81–1.57), cerebrovascular disease 1.43 (1.10–1.87), HF 0.99 (0.57–1.75), hypertension 1.31 (1.21–1.43), T2DM 1.74 (1.52–1.98).

Conclusions
History of either menstrual cycle irregularity or frequent or infrequent cycles were associated with an increased risk of cardiometabolic outcomes in later life. Menstrual history may be a useful tool in identifying women eligible for periodic assessment of their cardiometabolic health.

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The Perils of Riding Motocross: A Summary of this Extensive, Prospective Study (2023)

Type of publication:Journal article

Author(s):Hay B; *Singh R; Hay S

Citation:Indian Journal of Orthopaedics. 1-6, 2023 Feb 07

Abstract:Background: Motocross is a high-risk form of motorbiking where serious injuries occur regularly, although little data have been collected to illustrate this relationship. Over 5 years, teams from RJAH Oswestry and RSH sought to demonstrate the impact of Motocross on orthopaedic presentation and workload. Method: Data were collected prospectively over 5 years including 615 orthopaedic injuries associated with both recreational and competitive motocross. Results: An increase in injury and operation frequency was observed, young males were identified as the highest risk participant. This was evident over winter and weekends, during the competitive racing season. A variety of injuries have been implicated, some with life threatening or disabling consequences. Conclusion: Motocross has seen exponential growth in popularity with increases in injuries and operations. This implicates major impacts on finances and healthcare, especially at times of seasonal vulnerability. The authors encourage event organisers to explore the avenues of rider safety in this increasingly popular sport.

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Bariatric surgeons' experiences of working in the first year of the pandemic (2022)

Type of publication:
Journal article

Author(s):
Graham Y.N.H.; Mahawar K.; Singhal R.; Madhok B.; Yang W.; *Riera M.; Martinez-Duartez P.; Pouwels S.; Sharma M.; Hayes C.

Citation:
Obesity Science and Practice. (no pagination), 2022. Date of Publication: 2022 [epub ahead of print]

Abstract:
Background: The first year of the Covid-19 pandemic saw drastic changes to bariatric surgical practice, including postponement of procedures, altered patient care and impacting on the role of bariatric surgeons. The consequences of this both personally and professionally amongst bariatric surgeons has not as yet been explored. Aim(s): The aim of this research was to understand bariatric surgeons' perspectives of working during the first year of the pandemic to explore the self-reported personal and professional impact. Method(s): Using a retrospective, two phased, study design with global participants recruited from closed, bariatric surgical units. The first phase used a qualitative thematic analytic framework to identify salient areas of importance to surgeons. Themes informed the construction of an on-line, confidential survey to test the potential generalizability of the interview findings with a larger representative population from the global bariatric surgical community. Finding(s): Findings of the study revealed that the first year of the pandemic had a detrimental effect on bariatric surgeons both personally and professionally globally. Conclusion(s): This study has identified the need to build resilience of bariatric surgeons so that the practice of self-care and the encouragement of help-seeking behaviors can potentially be normalized, which will in turn increase levels of mental health and wellbeing.

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A Retrospective Comparative Study of Long-Term Outcomes Following Cervical Total Disc Replacement Versus Anterior Cervical Discectomy and Fusion (2022)

Type of publication:
Journal article

Author(s):
Eseonu, Kelechi; Laurent, Edward; *Bishi, Habeeb; Raja, Hassan; Ravi, Kuppuswamy; Dannawi, Zaher

Citation:
Cureus.14(12):e32399, 2022 Dec.

Abstract:
Introduction: The traditional treatment for patients with radiculopathy and myelopathy caused by degenerative disc disease was anterior cervical discectomy and fusion (ACDF). However, a documented complication of ACDF is adjacent segment degeneration (ASD). An alternative that was developed was total disc replacement (TDR). The aim of this study was to determine and compare the short- and medium-to-long-term outcomes after a TDR or ACDF. Methods: A retrospective review of 154 patients who had single and two-level ACDFs and 90 TDRs performed by a single surgeon between 2011 and 2017 was conducted. Parameters for comparisons include both radiological evaluation and patient-reported outcome measures (PROMS) at six weeks, one year, and two years postoperatively. The Neck Disability Index (NDI) and the visual analogue scale (VAS) for neck and arm pain are used to evaluate pain, function, patient satisfaction, and overall clinical success. Results: TDR and ACDF showed significant improvement in NDI and VAS when compared to pre- and post-operatively at both six weeks (p<0.05 & P=0.032, respectively) and two years (p<0.05 & 0=0.026, respectively). TDR vs. ACDF showed no significant difference (p<0.05). VAS scores after ACDF showed improvement from 13.41 to 3.94 at two years (p<0.001). TDR showed similar scores of 12.5 to 3.55 (p<0.001). The radiological fusion rate at 12 or 24 months showed no significant difference between the two groups. There were two cases that required re-operation after ACDF (1.2%), and two that required TDR (2.2%). Conclusion: Both TDR and ACDF lead to clinically significant improvements in pain and function scores. We did not find a statistically significant difference in NDI and VAS in the neck and arm. The results are in agreement with others' assessments of these two treatment modalities. Our conclusions supplement the literature about these operative options for degenerative disc disease of the cervical spine and are a useful addition to the armamentarium in the assessment of patients with degenerative pathology of the c-spine.

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Whole-genome sequencing reveals host factors underlying critical COVID-19 (2022)

Type of publication:
Journal article

Author(s):
Kousathanas A.; Pairo-Castineira E.; Rawlik K.; Stuckey A.; Odhams C.A.; Russell C.D.; Malinauskas T.; Wu Y.; Shen X.; Elliott K.S.; Griffiths F.; Oosthuyzen W.; Morrice K.; Keating S.; Wang B.; Rhodes D.; Klaric L.; Zechner M.; Parkinson N.; Siddiq A.; Goddard P.; Donovan S.; Maslove D.; Nichol A.; Semple M.G.; Zainy T.; Maleady-Crowe F.; Todd L.; Salehi S.; Knight J.; Elgar G.; Chan G.; Arumugam P.; Patch C.; Rendon A.; Bentley D.; Kingsley C.; Kosmicki J.A.; Horowitz J.E.; Baras A.; Abecasis G.R.; Ferreira M.A.R.; Justice A.; Mirshahi T.; Oetjens M.; Rader D.J.; Ritchie M.D.; Verma A.; Fowler T.A.; Shankar-Hari M.; Summers C.; Hinds C.; Horby P.; McAuley D.; Montgomery H.; Openshaw P.J.M.; Elliott P.; Walsh T.; Tenesa A.; Fawkes A.; Rowan K.; Ponting C.P.; Vitart V.; Wilson J.F.; Yang J.; Bretherick A.D.; Scott R.H.; Hendry S.C.; Moutsianas L.; Law A.; Caulfield M.J.; Baillie J.K.; Begg C.; Ling L.; Millar J.; Pereira A.C.; Aravindan L.; Armstrong R.; Biggs H.; Boz C.; Clark R.; Coutts A.; Coyle J.; Cullum L.; Das S.; Day N.; Donnelly L.; Finernan P.; Fourman M.H.; Furlong A.; Furniss J.; Gallagher B.; Gilchrist T.; Golightly A.; Hafezi K.; Hamilton D.; Hendry R.; Law D.; Law R.; Law S.; Lidstone-Scott R.; Macgillivray L.; Maclean A.; Mal H.; McCafferty S.; McMaster E.; Meikle J.; Moore S.C.; Murphy S.; Hellen M.; Zheng C.; Chen J.; Paterson T.; Schon K.; Stenhouse A.; Das M.; Swets M.; Szoor-McElhinney H.; Taneski F.; Turtle L.; Wackett T.; Ward M.; Weaver J.; Wrobel N.; Arbane G.; Bociek A.; Campos S.; Grau N.; Jones T.O.; Lim R.; Marotti M.; Ostermann M.; Whitton C.; Alldis Z.; Astin-Chamberlain R.; Bibi F.; Biddle J.; Blow S.; Bolton M.; Borra C.; Bowles R.; Burton M.; Choudhury Y.; Cox A.; Easthope A.; Ebano P.; Fotiadis S.; Gurasashvili J.; Halls R.; Hartridge P.; Kallon D.; Kassam J.; Lancoma-Malcolm I.; Matharu M.; May P.; Mitchelmore O.; Newman T.; Patel M.; Pheby J.; Pinzuti I.; Prime Z.; Prysyazhna O.; Shiel J.; Tierney C.; Wood S.; Zak A.; Zongo O.; Bonner S.; Hugill K.; Liggett S.; Headlam E.; Bandla N.; Gellamucho M.; Davies M.; Thompson C.; Abdelrazik M.; Bakthavatsalam D.; Elhassan M.; Ganesan A.; Haldeos A.; Moreno-Cuesta J.; Purohit D.; Vincent R.; Xavier K.; Frater A.; Saleem M.; Carter D.; Lamond Z.; Wall A.; Fernandez-Roman J.; Hamilton D.O.; Johnson E.; Johnston B.; Martinez M.L.; Mulla S.; Shaw D.; Waite A.A.C.; Waugh V.; Welters I.D.; Williams K.; Cavazza A.; Cockrell M.; Corcoran E.; Depante M.; Finney C.; Jerome E.; McPhail M.; Nayak M.; Noble H.; O'Reilly K.; Pappa E.; Saha S.; Knighton A.; Antcliffe D.; Banach D.; Brett S.; Coghlan P.; Fernandez Z.; Gordon A.; Rojo R.; Arias S.S.; Templeton M.; Meredith M.; Morris L.; Ryan L.; Clark A.; Sampson J.; Peters C.; Dent M.; Langley M.; Ashraf S.; Wei S.; Andrew A.; Bashyal A.; Davidson N.; Hutton P.; McKechnie S.; Wilson J.; Baptista D.; Crowe R.; Fernandes R.; Herdman-Grant R.; Joseph A.; O'Connor D.; Allen M.; Loveridge A.; McKenley I.; Morino E.; Naranjo A.; Simms R.; Sollesta K.; Swain A.; Venkatesh H.; Khera J.; Fox J.; Andrew G.; Barclay L.; Callaghan M.; Campbell R.; Clark S.; Hope D.; Marshall L.; McCulloch C.; Briton K.; Singleton J.; Birch S.; Brimfield L.; Daly Z.; Pogson D.; Rose S.; Nown A.; Battle C.; Brinkworth E.; Harford R.; Murphy C.; Newey L.; Rees T.; Williams M.; Arnold S.; Polgarova P.; Stroud K.; Meaney E.; Jones M.; Ng A.; Agrawal S.; Pathan N.; White D.; Daubney E.; Elston K.; Grauslyte L.; Hussain M.; Phull M.; Pogreban T.; Rosaroso L.; Salciute E.; Franke G.; Wong J.; George A.; de Gordoa L.O.-R.; Peasgood E.; Phillips C.; Bates M.; Dasgin J.; Gill J.; Nilsson A.; Scriven J.; Collins A.; Khaliq W.; Gude E.T.; Delgado C.C.; Dawson D.; Ding L.; Durrant G.; Ezeobu O.; Farnell-Ward S.; Kanu R.; Leaver S.; Maccacari E.; Manna S.; Saluzzio R.P.; Queiroz J.; Samakomva T.; Sicat C.; Texeira J.; Da Gloria E.F.; Lisboa A.; Rawlins J.; Mathew J.; Kinch A.; Hurt W.J.; Shah N.; Clark V.; Thanasi M.; Yun N.; Patel K.; Bennett S.; Goodwin E.; Jackson M.; Kent A.; Tibke C.; Woodyatt W.; Zaki A.; Abraheem A.; Bamford P.; Cawley K.; Dunmore C.; Faulkner M.; Girach R.; Jeffrey H.; Jones R.; London E.; Nagra I.; Nasir F.; Sainsbury H.; Smedley C.; Patel T.; Smith M.; Chukkambotla S.; Kazi A.; Hartley J.; Dykes J.; Hijazi M.; Keith S.; Khan M.; Ryan-Smith J.; Springle P.; Thomas J.; Truman N.; Saad S.; Coleman D.; Fine C.; Matt R.; Gay B.; Dalziel J.; Ali S.; Goodchild D.; Harling R.; Bhatterjee R.; Goddard W.; Davison C.; Duberly S.; Hargreaves J.; Bolton R.; Davey M.; Golden D.; Seaman R.; Cherian S.; Cutler S.; Heron A.E.; Roynon-Reed A.; Szakmany T.; Williams G.; Richards O.; Cheema Y.; Brooke H.; Buckley S.; Suarez J.C.; Charlesworth R.; Hansson K.; Norris J.; Poole A.; Rose A.; Sandhu R.; Sloan B.; Smithson E.; Thirumaran M.; Wagstaff V.; Metcalfe A.; Brunton M.; Caterson J.; Coles H.; Frise M.; Rai S.G.; Jacques N.; Keating L.; Tilney E.; Bartley S.; Bhuie P.; Gibson S.; Lyle A.; McNeela F.; Radhakrishnan J.; Hughes A.; Yates B.; Reynolds J.; Campbell H.; Thompsom M.; Dodds S.; Duffy S.; Greer S.; Shuker K.; Tridente A.; Khade R.; Sundar A.; Tsinaslanidis G.; Birkinshaw I.; Carter J.; Howard K.; Ingham J.; Joy R.; Pearson H.; Roche S.; Scott Z.; Bancroft H.; Bellamy M.; Carmody M.; Daglish J.; Moore F.; Rhodes J.; Sangombe M.; Kadiri S.; Croft M.; White I.; Frost V.; Aquino M.; Jha R.; Krishnamurthy V.; Lim L.; Combes E.; Joefield T.; Monnery S.; Beech V.; Trotman S.; Christine Almaden-Boyle; Austin P.; Cabrelli L.; Cole S.; Casey M.; Chapman S.; Whyte C.; Baird Y.; Butler A.; Chadbourn I.; Folkes L.; Fox H.; Gardner A.; Gomez R.; Hobden G.; Hodgson L.; King K.; Margarson M.; Martindale T.; Meadows E.; Raynard D.; Thirlwall Y.; Helm D.; Margalef J.; Criste K.; Cusack R.; Golder K.; Golding H.; Jones O.; Leggett S.; Male M.; Marani M.; Prager K.; Williams T.; Roberts B.; Salmon K.; Anderson P.; Archer K.; Austin K.; Davis C.; Durie A.; Kelsall O.; Thrush J.; Vigurs C.; Wild L.; Wood H.-L.; Tranter H.; Harrison A.; Cowley N.; McAlindon M.; Burtenshaw A.; Digby S.; Low E.; Morgan A.; Cother N.; Rankin T.; Clayton S.; McCurdy A.; Ahmed C.; Baines B.; Clamp S.; Colley J.; Haq R.; Hayes A.; Hulme J.; Hussain S.; Joseph S.; Kumar R.; Maqsood Z.; Purewal M.; Benham L.; Bradshaw Z.; Brown J.; Caswell M.; Cupitt J.; Melling S.; Preston S.; Slawson N.; Stoddard E.; Warden S.; Deacon B.; Lynch C.; Pothecary C.; Howe G.S.; Singh J.; Turner K.; Ellis H.; Stroud N.; Dearden J.; Dobson E.; Drummond A.; Mulcahy M.; Munt S.; O'Connor G.; Philbin J.; Rishton C.; Tully R.; Winnard S.; Cathcart S.; Duffy K.; Puxty A.; Puxty K.; Turner L.; Ireland J.; Semple G.; Long K.; Whiteley S.; Wilby E.; Ogg B.; Cowton A.; Kay A.; Kent M.; Potts K.; Wilkinson A.; Campbell S.; Brown E.; Melville J.; Naisbitt J.; Joseph R.; Lazo M.; Walton O.; Neal A.; Alexander P.; Allen S.; Bradley-Potts J.; Brantwood C.; Egan J.; Felton T.; Padden G.; Ward L.; Moss S.; Glasgow S.; Abel L.; Brett M.; Digby B.; Gemmell L.; Hornsby J.; MacGoey P.; O'Neil P.; Price R.; Rodden N.; Rooney K.; Sundaram R.; Thomson N.; Hopkins B.; Thrasyvoulou L.; Willis H.; Coulding M.; Jude E.; McCormick J.; Mercer O.; Potla D.; Rehman H.; Savill H.; Turner V.; Downes C.; Holding K.; Riches K.; Hilton M.; Hayman M.; Subramanian D.; Daniel P.; Adanini O.; Bhatia N.; Msiska M.; Collins R.; Clement I.; Gulati A.; Hays C.; Webster K.; Hudson A.; Webster A.; Stephenson E.; McCormack L.; Slater V.; Nixon R.; Hanson H.; Fearby M.; Kelly S.; Bridgett V.; Robinson P.; Camsooksai J.; Humphrey C.; Jenkins S.; Reschreiter H.; Wadams B.; Death Y.; Bastion V.; Clarke D.; David B.; Kent H.; Lorusso R.; Lubimbi G.; Murdoch S.; Penacerrada M.; Valentine J.; Vochin A.; Wulandari R.; Djeugam B.; Bell G.; English K.; Katary A.; Wilcox L.; Bruce M.; Connolly K.; Duncan T.; Michael H.T.; Lindergard G.; Hey S.; Fox C.; Alfonso J.; Durrans L.J.; Guerin J.; Blackledge B.; Harris J.; Hruska M.; Eltayeb A.; Lamb T.; Hodgkiss T.; Cooper L.; Rothwell J.; Allan A.; Anderson F.; Kaye C.; Liew J.; Medhora J.; Scott T.; Trumper E.; Botello A.; Lankester L.; Nikitas N.; Wells C.; Stowe B.; Spencer K.; Brandwood C.; Smith L.; Kolakaluri L.; Baines D.; Sukumaran A.; Apetri E.; Basikolo C.; Catlow L.; Charles B.; Dark P.; Doonan R.; Harvey A.; Horner D.; Knowles K.; Lee S.; Lomas D.; Lyons C.; Marsden T.; McLaughlan D.; McMorrow L.; Pendlebury J.; Perez J.; Poulaka M.; Proudfoot N.; Slaughter M.; Slevin K.; Thomas V.; Walker D.; Michael A.; Collis M.; Cosier T.; Millen G.; Richardson N.; Schumacher N.; Weston H.; Rand J.; Baxter N.; Henderson S.; Kennedy-Hay S.; Rooney L.; Sim M.; McCreath G.; Akeroyd L.; Bano S.; Bromley M.; Gurr L.; Lawton T.; Morgan J.; Sellick K.; Warren D.; Wilkinson B.; McGowan J.; Ledgard C.; Stacey A.; Pye K.; Bellwood R.; Bentley M.; Bewley J.; Garland Z.; Grimmer L.; Gumbrill B.; Johnson R.; Sweet K.; Webster D.; Efford G.; Convery K.; Fottrell-Gould D.; Hudig L.; Keshet-Price J.; Randell G.; Stammers K.; Bokhari M.; Linnett V.; Lucas R.; McCormick W.; Ritzema J.; Sanderson A.; Wild H.; Rostron A.; Roy A.; Woods L.; Cornell S.; Wakinshaw F.; Rogerson K.; Jarmain J.; Parker R.; Reddy A.; Turner-Bone I.; Harding P.; Abernathy C.; Foster L.; Gratrix A.; Martinson V.; Parkinson P.; Stones E.; Carbral-Ortega L.; Bercades G.; Brealey D.; Hass I.; MacCallum N.; Martir G.; Raith E.; Reyes A.; Smyth D.; Zitter L.; Benyon S.; Marriott S.; Park L.; Keenan S.; Gordon E.; Quinn H.; Baines K.; Cagova L.; Fofano A.; Garner L.; Holcombe H.; Mepham S.; Mitchell A.M.; Mwaura L.; Praman K.; Vuylsteke A.; Zamikula J.; Purewal B.; Rivers V.; Bell S.; Blakemore H.; Borislavova B.; Faulkner B.; Gendall E.; Goff E.; Hayes K.; Thomas M.; Worner R.; Smith K.; Stephens D.; Mew L.; Mwaura E.; Stewart R.; Williams F.; Wren L.; Sutherland S.-B.; Bevan E.; Martin J.; Trodd D.; Watson G.; Brown C.W.; Akinkugbe O.; Bamford A.; Beech E.; Belfield H.; Bell M.; Davies C.; Jones G.A.L.; McHugh T.; Meghari H.; O'Neill L.; Peters M.J.; Ray S.; Tomas A.L.; Burn I.; Hambrook G.; Manso K.; Penn R.; Shanmugasundaram P.; Tebbutt J.; Thornton D.; Davies R.; Duffin D.; Hill H.; Player B.; Thomas E.; Griffin D.; Muchenje N.; Mupudzi M.; Partridge R.; Conyngham J.-A.; Thomas R.; Wright M.; Corral M.A.; Jacob R.; Jones C.; Denmade C.; Beavis S.; Dale K.; Gascoyne R.; Hawes J.; Pritchard K.; Stevenson L.; Whileman A.; Doble P.; Hutter J.; Pawley C.; Shovelton C.; Vaida M.; Butcher D.; O'Sullivan S.; Butterworth-Cowin N.; Ahmad N.; Barker J.; Bauchmuller K.; Bird S.; Cawthron K.; Harrington K.; Jackson Y.; Kibutu F.; Lenagh B.; Masuko S.; Mills G.H.; Raithatha A.; Wiles M.; Willson J.; Newell H.; Lye A.; Nwafor L.; Jarman C.; Rowland-Jones S.; Foote D.; Cole J.; Thompson R.; Watson J.; Hesseldon L.; Macharia I.; Chetam L.; Ford A.; Birchall K.; Housley K.; Walker S.; Milner L.; Hanratty H.; Trower H.; Phillips P.; Oxspring S.; Donne B.; Jardine C.; Williams D.; Hay A.; Flanagan R.; Hughes G.; Latham S.; McKenna E.; Anderson J.; Hull R.; Rhead K.; Cruz C.; Pattison N.; Charnock R.; McFarland D.; Cosgrove D.; Ahmed A.; Morris A.; Jakkula S.; Nune A.; Brady M.; Dale S.; Dance A.; Gledhill L.; Greig J.; Hanson K.; Holdroyd K.; Home M.; Kelly D.; Kitson R.; Matapure L.; Melia D.; Mellor S.; Nortcliffe T.; Pinnell J.; Robinson M.; Shaw L.; Shaw R.; Thomis L.; Wilson A.; Wood T.; Bayo L.-A.; Merwaha E.; Ishaq T.; Hanley S.; Hibbert M.; Tetla D.; Woodford C.; Durga L.; Kennard-Holden G.; Branney D.; Frankham J.; Pitts S.; Laha S.; Verlander M.; Altabaibeh A.; Alvaro A.; Gilbert K.; Ma L.; Mostoles L.; Parmar C.; Jetha C.; Booker L.; Pratley A.; Adams C.; Agasou A.; Arden T.; Bowes A.; Boyle P.; Beekes M.; Button H.; Capps N.; Carnahan M.; Carter A.; Childs D.; Donaldson D.; Hard K.; Hurford F.; Hussain Y.; Javaid A.; Jones J.; Jose S.; Leigh M.; Martin T.; Millward H.; Motherwell N.; Rikunenko R.; Stickley J.; Summers J.; Ting L.; Tivenan H.; *Tonks L.; *Wilcox R.; Skinner D.; Gaylard J.; Mullan D.; Newman J.; Holland M.; Keenan N.; Lyons M.; Wassall H.; Marsh C.; Mahenthran M.; 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Chasman D.I.; Buring J.E.; Ridker P.M.; Franco G.; Sesso H.D.; Manson J.E.; Glessner J.R.; Hakonarson H.; Medina-Gomez C.; Uitterlinden A.G.; Ikram M.A.; Kristiansson K.; Koskelainen S.; Perola M.; Donner K.; Kivinen K.; Palotie A.; Ripatti S.; Ruotsalainen S.; Kaunisto M.; Nakanishi T.; Butler-Laporte G.; Forgetta V.; Morrison D.R.; Ghosh B.; Laurent L.; Belisle A.; Henry D.; Abdullah T.; Adeleye O.; Mamlouk N.; Kimchi N.; Afrasiabi Z.; Rezk N.; Vulesevic B.; Bouab M.; Guzman C.; Petitjean L.; Tselios C.; Xue X.; Schurr E.; Afilalo J.; Afilalo M.; Oliveira M.; Brenner B.; Lepage P.; Ragoussis J.; Auld D.; Brassard N.; Durand M.; Chasse M.; Kaufmann D.E.; Lathrop G.M.; Mooser V.; Richards J.B.; Li R.; Adra D.; Rahmouni S.; Georges M.; Moutschen M.; Misset B.; Darcis G.; Guiot J.; Guntz J.; Azarzar S.; Gofflot S.; Beguin Y.; Claassen S.; Malaise O.; Huynen P.; Meuris C.; Thys M.; Jacques J.; Leonar P.; Frippiat F.; Giot J.-B.; Sauvage A.-S.; von Frenckell C.; Belhaj Y.; Lambermont B.; Pigazzini S.; Daya M.; Shortt J.; Rafaels N.; Wicks S.J.; Crooks K.; Barnes K.C.; Gignoux C.R.; Chavan S.; Laisk T.; Lall K.; Lepamets M.; Magi R.; Esko T.; Reimann E.; Milani L.; Alavere H.; Metsalu K.; Puusepp M.; Metspalu A.; Naaber P.; Laane E.; Pesukova J.; Peterson P.; Kisand K.; Tabri J.; Allos R.; Hensen K.; Starkopf J.; Ringmets I.; Tamm A.; Kallaste A.; Bochud P.-Y.; Rivolta C.; Bibert S.; Quinodoz M.; Kamdar D.; Boillat N.; Nussle S.G.; Albrich W.; Suh N.; Neofytos D.; Erard V.; Voide C.; de Cid R.; Galvan-Femenia I.; Blay N.; Carreras A.; Cortes B.; Farre X.; Sumoy L.; Moreno V.; Mercader J.M.; Guindo-Martinez M.; Torrents D.; Kogevinas M.; Garcia-Aymerich J.; Castano-Vinyals G.; Dobano C.; Renieri A.; Mari F.; Fallerini C.; Daga S.; Benetti E.; Baldassarri M.; Fava F.; Frullanti E.; Valentino F.; Doddato G.; Giliberti A.; Tita R.; Amitrano S.; Bruttini M.; Croci S.; Meloni I.; Mencarelli M.A.; Rizzo C.L.; Pinto A.M.; Beligni G.; Tommasi A.; Sarno L.D.; Palmieri M.; Carriero M.L.; Alaverdian D.; Busani S.; Bruno R.; Vecchia M.; Belli M.A.; Picchiotti N.; Sanarico M.; Gori M.; Furini S.; Mantovani S.; Ludovisi S.; Mondelli M.U.; Castelli F.; Quiros-Roldan E.; Antoni M.D.; Zanella I.; Vaghi M.; Rusconi S.; Siano M.; Montagnani F.; Emiliozzi A.; Fabbiani M.; Rossetti B.; Bargagli E.; Bergantini L.; D'Alessandro M.; Cameli P.; Bennett D.; Anedda F.; Marcantonio S.; Scolletta S.; Franchi F.; Mazzei M.A.; Guerrini S.; Conticini E.; Cantarini L.; Frediani B.; Tacconi D.; Spertilli C.; Feri M.; Donati A.; Scala R.; Guidelli L.; Spargi G.; Corridi M.; Nencioni C.; Croci L.; Bandini M.; Caldarelli G.P.; Piacentini P.; Desanctis E.; Cappelli S.; Canaccini A.; Verzuri A.; Anemoli V.; Ognibene A.; Pancrazzi A.; Lorubbio M.; Monforte A.D.; Miraglia F.G.; Girardis M.; Venturelli S.; Cossarizza A.; Antinori A.; Vergori A.; Gabrieli A.; Riva A.; Francisci D.; Schiaroli E.; Paciosi F.; Scotton P.G.; Andretta F.; Panese S.; Scaggiante R.; Gatti F.; Parisi S.G.; Baratti S.; Monica M.D.; Piscopo C.; Capasso M.; Russo R.; Andolfo I.; Iolascon A.; Fiorentino G.; Carella M.; Castori M.; Merla G.; Squeo G.M.; Aucella F.; Raggi P.; Marciano C.; Perna R.; Bassetti M.; Biagio A.D.; Sanguinetti M.; Masucci L.; Valente S.; Mandala M.; Giorli A.; Salerni L.; Zucchi P.; Parravicini P.; Menatti E.; Trotta T.; Giannattasio F.; Coiro G.; Lena F.; Coviello D.A.; Mussini C.; Martinelli E.; Mancarella S.; Tavecchia L.; Crotti L.; Gabbi C.; Rizzi M.; Maggiolo F.; Ripamonti D.; Bachetti T.; Rovere M.T.L.; Sarzi-Braga S.; Bussotti M.; Ceri S.; Pinoli P.; Raimondi F.; Biscarini F.; Stella A.; Zguro K.; Capitani K.; Suardi C.; Dei S.; Parati G.; Ravaglia S.; Artuso R.; Botta G.; Di Domenico P.; Rancan I.; Perrella A.; Bianchi F.; Romani D.; Bergomi P.; Catena E.; Colombo R.; Tanfoni M.; Vincenti A.; Ferri C.; Grassi D.; Pessina G.; Tumbarello M.; Di Pietro M.; Sabrina R.; Luchi S.; Barbieri C.; Acquilini D.; Andreucci E.; Segala F.V.; Tiseo G.; Falcone M.; Lista M.; Poscente M.; De Vivo O.; Petrocelli P.; Guarnaccia A.; Baroni S.; Smith A.V.; Boughton A.P.; Li K.W.; LeFaive J.; Annis A.; Chittoor G.; Josyula N.S.; Leader J.B.; Carey D.J.; Gass M.C.; Cantor M.N.; Yadav A.; van Heel D.A.; Hunt K.A.; Mason D.; Huang Q.Q.; Finer S.; Trivedi B.; Griffiths C.J.; Martin H.C.; Wright J.; Trembath R.C.; Soranzo N.; Zhao J.H.; Butterworth A.S.; Danesh J.; Di Angelantonio E.; Franke L.; Boezen M.; Deelen P.; Claringbould A.; Lopera E.; Warmerdam R.; Vonk J.M.; van Blokland I.; Lanting P.; Ori A.P.S.; Zollner S.; Wang J.; Beck A.; Peloso G.; Ho Y.-L.; Sun Y.V.; Huffman J.E.; O'Donnell C.J.; Cho K.; Tsao P.; Gaziano J.M.; Nivard M.; de Geus E.; Bartels M.; Hottenga J.J.; Weiss S.T.; Karlson E.W.; Smoller J.W.; Green R.C.; Feng Y.-C.A.; Mercader J.; Murphy S.N.; Meigs J.B.; Woolley A.E.; Perez E.F.; Rader D.; Li B.; Verma S.S.; Lucas A.; Bradford Y.; Zeberg H.; Frithiof R.; Hultstrom M.; Lipcsey M.; Nkambul L.; Tardif N.; Rooyackers O.; Grip J.; Maricic T.; Karczewski K.J.; Atkinson E.G.; Tsuo K.; Baya N.; Turley P.; Gupta R.; Callier S.; Walters R.K.; Palmer D.S.; Sarma G.; Cheng N.; Lu W.; Bryant S.; Churchhouse C.; Cusick C.; Goldstein J.I.; King D.; Seed C.; Finucane H.; Martin A.R.; Satterstrom F.K.; Wilson D.J.; Armstrong J.; Rudkin J.K.; Band G.; Earle S.G.; Lin S.-K.; Arning N.; Crook D.W.; Wyllie D.H.; O'Connell A.M.; Spencer C.C.A.; Koelling N.; Fowler T.; Pasko D.; Ball C.A.; Hong E.L.; Rand K.; Girshick A.; Guturu H.; Baltzell A.H.; Roberts G.; Park D.; Coignet M.; McCurdy S.; Knight S.; Partha R.; Rhead B.; Zhang M.; Berkowitz N.; Gaddis M.; Noto K.; Ruiz L.; Pavlovic M.; Sloofman L.G.; Charney A.W.; Beckmann N.D.; Schadt E.E.; Jordan D.M.; Thompson R.C.; Gettler K.; Abul-Husn N.S.; Ascolillo S.; Buxbaum J.D.; Chaudhary K.; Cho J.H.; Itan Y.; Kenny E.E.; Belbin G.M.; Sealfon S.C.; Sebra R.P.; Salib I.; Collins B.L.; Levy T.; Britvan B.; Keller K.; Tang L.; Peruggia M.; Hiester L.L.; Niblo K.; Aksentijevich A.; Labkowsky A.; Karp A.; Zlatopolsky M.; Preuss M.; Loos R.J.F.; Nadkarni G.N.; Do R.; Hoggart C.; Choi S.; Underwood S.J.; O'Reilly P.; Huckins L.M.; Zyndorf M.; Daly M.J.; Neale B.M.; Ganna A.

Citation:
Nature, 2022. Vol 607(7917) (pp 97-103)

Abstract:
Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2-4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes-including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)-in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease.

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Stent diameter and stent-related symptoms, does size matter? A systematic review and meta-analysis (2022)

Type of publication:
Systematic Review

Author(s):
Ehsanullah S.A.; Bruce A.; Juman C.; *Krishan A.; Higginbottom J.; Khashaba S.; Alnaib Z.

Citation:
Urology Annals. 14(4) (pp 295-302), 2022. Date of Publication: October 2022.

Abstract:
The ureteral insertion of a silicone tube was first performed in 1967. A validated ureteral stent symptom questionnaire (USSQ) is used for an objective assessment of patient-reported stent-related symptoms. As the impact of stent diameter on the incidence of stent-related symptoms is unclear, we aimed to perform a systematic review and meta-analysis comparing USSQ reported outcomes when using a 6 Fr diameter ureteric stent, versus smaller diameter stents (4.7-5 Fr) when inserted for ureteric stones. All randomized control trials and comparative studies of 6 Fr versus 4.7-5 Fr ureteric stents were reviewed. The USSQ outcomes were considered as the primary outcome measures while stent migration was considered as a secondary outcome measure. A total of 61 articles were identified of which four studies met the eligibility criteria. There was a statistically significant association between the use of wider (6 Fr) diameter stents and the incidence of urinary symptoms as measured by the urinary index score. Larger stent diameters were associated with a statistically significant increase in the pain index score. There was no statistically significant difference in the scores between the compared stent diameters with regard to work performance score, general health index score, additional problems index score, and stent migration. There were insufficient reported outcomes to perform a meta-analysis of sexual matters index score. Our meta-analysis shows that using smaller diameter ureteric stents is associated with reduced urinary symptoms and patient-reported pain. Other USSQ parameter outcomes are statistically similar in the 6 Fr ureteric stent cohort versus the 4.7-5 Fr ureteric stent cohort. Our meta-analysis was limited due to the limited number of studies and gross heterogeneity of reporting parameters in various studies. We hope a large-scale homogeneous randomized control trial will further shed more insight into the stent symptoms response to stent diameter

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Patient experiences of weight loss and eating after bariatric surgery: A Systematic Review and Qualitative Synthesis (2022)

Type of publication:Journal article

Author(s):*Ansari M; Serjeant S

Citation:Journal of human nutrition and dietetics : the official journal of the British Dietetic Association, 2022 Nov 30 [epub ahead of print]

Abstract:Background: An estimated 26% of men and 29% of women in the UK are living with obesity according to recent statistics. Bariatric Surgery (BS) can induce significant weight loss and improve co-morbidity status. However previous studies highlight challenges in maintaining dietary changes and weight loss. This systematic review aimed to investigate patient experiences of weight loss and eating in the first two years following surgery, to provide clinical recommendations to support this group.Methods: Ethical approval was granted by the University. A systematic search was conducted in four databases. Studies were selected according to the predefined eligibility criteria and methodological quality, assessed via the CASP tool. Data were extracted and analysed using a thematic synthesis method. Rigour was enhanced via use of a data extraction tool, a validated method for data synthesis, peer-review and transparent reporting.Results: In total, 507 records were screened; nine studies met the inclusion criteria. The thematic synthesis yielded four, interlinked analytical themes based on 154 patients' experiences: relationship with food, relationship with oneself, relationship with others and unfinished journey. Positive experiences were reported including development of healthy eating behaviours and significant weight loss, improving physical and psychosocial wellbeing. On the other hand, challenges in adjusting to life after surgery were also reported.Conclusions: This study highlighted the need for personalised dietary advice, addressing the psychological aspects of eating. Support should be extended to the family. Ongoing psychological support must be incorporated in the post-surgery care pathway to help patients deal with the negative outcomes of surgery such as excess skin.

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