Mitral valve prolapse presenting as a missed myocardial infarction (2023)

Type of publication:Conference abstract

Author(s):*Champaneri K.; *Miller A.

Citation:Journal of the Intensive Care Society. Conference: Intensive Care Society State of the Art Congress, SOA 2023. Birmingham United Kingdom. 24(2 Supplement) (pp 194), 2023. Date of Publication: August 2023.

Abstract:Introduction: An elderly but very active gentleman presented overnight with progressive shortness of breath and leg swelling, two weeks after experiencing chest pain while lifting heavy objects in the garden. The presumed diagnosis was a missed myocardial infarction leading to heart failure exacerbated by a new diagnosis of atrial fibrillation. Despite diuresis and rate control, he became progressively more hypoxic and was taken to ICU for non-invasive ventilation. An initial POCUS scan of heart and lungs by an ultrasound fellow undertaking FUSIC accreditation showed a hyperdynamic heart, pulmonary oedema, and bilateral pleural effusions. The echocardiogram was reviewed and repeated by an advanced level operator which dramatically altered the patient's diagnosis and management. Main body: A gentleman in his early 80s presented to the Emergency Department in type one respiratory failure with a high work of breathing. Examination and investigations demonstrated raised inflammatory markers, new atrial fibrillation with a rate of 140, large bilateral plural effusions, and pitting oedema to the groin. Troponin was normal, and the BNP was 4500. ECG showed no ischaemic changes and CXR was consistent with fluid overload and/or pneumonia. Initial management consisted of supplemental oxygen, diuretics, heart rate control, and antibiotics. Despite this his oxygenation deteriorated and he was admitted to the ICU for CPAP, and metaraminol for his hypotension. An initial FUSIC heart scan did not show any signs of ventricular failure. In fact, the heart was hyperdynamic which was more consistent with sepsis. A lung ultrasound did however demonstrate large bilateral plural effusions and the significant pitting oedema of the lower limbs found on clinical examination still suggested a cardiac cause and so help was asked of an advanced level operator. A review of the images and a repeat scan revealed a severe prolapse of the posterior mitral valve leaflet with free, eccentric mitral regurgitation. The leaflet prolapse was not visible on the 1st set of images and was only discovered by more comprehensive scanning. The patient was reviewed by a cardiologist within 30 minutes and transfer to a tertiary centre for emergency mitral valve repair was arranged. <br/>Conclusion(s): Standard history, examination, and investigations of this patient led to a presumed diagnosis of ischaemic ventricular failure. While a basic heart ultrasound did not reveal the pathology, it did demonstrate signs not consistent with the suspected diagnosis prompting a request for a more comprehensive ultrasound assessment. This revealed the underlying pathology, significantly altering the patient's management. This was all done by intensive care clinicians at the bedside, significantly shortening the time to diagnosis and correct management. This case is a good example of why Intensive Care clinicians should be trained in point of care ultrasound at both basic and advanced levels.

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Experience as an international mammographer working in the UK comparing practice between Nigeria and UK (2023)

Type of publication:Conference abstract

Author(s):*Okeke C.R.; *Njoku G.

Citation:Breast Cancer Research. Conference: Symposium Mammographicum Conference 2023. Glasgow United Kingdom. 25(Supplement 2) (no pagination), 2023. Date of Publication: October 2023.

Abstract:Breast cancer affects women of all races without exception even though severity and survival rate are often diverse. In Nigeria about two thirds of women with breast cancer are diagnosed at an advanced stage, with the possibility of metastatic spread (Akaro- Anthony et al., 2010). A mammographer performs breast imaging techniques that produce mammographic radiographs for diagnosis (American Society of Radiologic Technologist, 2017). In Nigeria, the breast screening programme is performed by radiographers with the additional mammogram-specific training which is comparable to what is found in the United Kingdom; however, the UK screening programme also makes use of trained assistant practitioners which is not obtainable in Nigeria (Lawal et al., 2015). The breast screening programme in Nigeria invites women between the ages of 40 to 70 years, and this is justified by the fear that in Nigeria, a higher percentage of breast cancer cases are seen in younger age groups than in developed world ((Jedy-Agba et al., 2012). The mode of invitation is through public awareness campaigns, but majority of the women in the population do not frequently participate in mammography screening due to high cost and religious belief. The screening programme in Nigeria encourages women to get screened every two years (Lawal et al., 2012). However, the UK breast screening programme advice women to have breast screening mammogram, once every 3 years and is currently inviting women between the ages of 50 and 70 years for breast screening.

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Increased detection of pericardial effusion during the COVID-19 pandemic (2023)

Type of publication:Conference abstract

Author(s):*Wilson A.; *Ellis C.; *Lee E.

Citation:Echo Research and Practice. Conference: British Society of Echocardiography Annual Meeting, BSEcho 2022. London United Kingdom. 10(Supplement 1) (no pagination), 2023. Date of Publication: September 2023.

Abstract:Background: Pericardial effusions (PE) occur when there is an excess of fluid accumulating within the pericardial space. We have observed an increase in the number of PE's detected amongst all transthoracic echocardiography (TTE) scans performed since the start of the COVID- 19 pandemic irrespective of cause for referral. This is interesting given that the most common cause of PE's in the Western World is considered to be post-viral infection. Aim(s): Validate a significant increase in the rate of PE detection via TTE from January 2020-December 2021 compared to the previous 3 years and compare PE detection with national COVID-19 infection data. Method(s): All TTE scans performed between January 2017 and December 2021 were utilised to generate rates of PE detection. A t-test was performed to assess for a significant difference in PE detection pre-COVID-19 (January 2017-December 2019) and during the pandemic (January 2020-December 2021). Data on the incidence of COVID-19 cases in the UK was gathered from the Gov.uk website. Result(s): A total of 37,069 TTE's were performed pre-COVID-19 and 24,125 scans post-COVID-19. Majority of the 2020-2021 TTE's were performed in low risk COVID-19 patients. There were significantly more PE's detected post-COVID-19 compared with pre-COVID-19 with rates of detection of 0.14 and 0.05 respectively (p < 0.001). Detection of PE's increased from 2017-2021 despite a decrease in total scans performed post-COVID-19 (Figure 1). Comparison with national COVID-19 infection data shows a peak in PE incidence following a peak in infections (Figure 2). Conclusion(s): We have noticed a significant increase in PE detection since the start of the COVID-19 pandemic. This appeared to track the incidence of national COVID-19 infections.

Is the 3 mm tolerance for axillary node biopsy still adequate for indication of axillary disease? Retrospective audit (2023)

Type of publication:Conference abstract

Author(s):Deane L.; Cielecki L.; Williams S.; Metelko M.; Alkouly M.; Aksoy U.; Vaughan J.; Burley S.; Barlow E.; Cobby E.

Citation:Breast Cancer Research. Conference: Symposium Mammographicum Conference 2023. Glasgow United Kingdom. 25(Supplement 2) (no pagination), 2023. Date of Publication: October 2023.

Abstract:Background: A 3 mm tolerance for cortical thickness on axillary lymph nodes is a standard measurement used as one of the thresholds to decide if potentially suspicious for disease. Our department conducted an audit of the ultrasound outcomes for lymph node involvement in the axilla after several unexpected positive post-surgical cases with previously negative axillae on ultrasound, were obtained. This could impact the patient directly if further axillary surgery was required. Method(s): 12 months of ultrasound results were compared to the pathology results for surgical axillary biopsy, lymph node sampling and surgical axillary clearance. Result(s): Forty-seven cases out of 388 cases were false negative. Sensitivity was 41.25% and specificity was 91.56%. Analysis: Nineteen cases were excluded due to morphological data unavailable at the time of the audit. Twenty-eight cases analysed either revealed disease too small to be visualised, positive nodes not in the axilla, not biopsied by a second consultant when returning for biopsy procedure and learning difficulties. All these cases were conducted by different consultants on different ultrasound units. No identifiable trend was seen. Conclusion(s): The sensitivity is in keeping with peer review investigations and therefore the 3 mm threshold for identifying possible disease is still adequate. Any learning points from individual cases were taken forward to aid with service improvement.

Prevalence of Dyslipidemia and the Association With Levels of TSH and T4 Hormones Among Patients in South Region of Jordan (2023)

Type of publication:Journal article

Author(s):Atrooz O.M.; *Hiresh M.N.; Alghonmeen R.D.; Atrooz M.O.; Hiresh G.N.; Alasoufi A.M.; Atrooz I.O.

Citation:Journal of Medical Biochemistry. 42(4) (pp 706-713), 2023.

Abstract:Background: Glycolipid metabolism disorders (dysglycolipidemia) are characterized by elevated levels of glycolipid profile components and fasting blood glucose. Dysglycolipidemia are major threats to human health and life. Therefore, the aim of this cross-sectional study is to estimate the prevalence of dysglycolipidemia and the existence of association of TSH and T4 and glycolipid profiles. Method(s): Cross-sectional data were obtained from the medical laboratory of Ma'an Governmental Hospital. A total of 141 patients' results were collected (18-60 years). Differences in the glycolipidemic profiles according to age and sex and TSH and T4 were compared. Different statistical analyses were used to analyze the prevalence of dysglycolipidemia and the correlation with the levels of TSH and T4. Result(s): The study involved results of 141 patients (54.7% males and 45.3% females) in Ma'an Province (Jordan), who visited the internal medicine clinic at Ma'an Governmental Hospital. Patients have overweight and BMI of more than 25 kg/m<sup>2</sup>. The overall results of the prevalence of dyslipidemia indicated that patients have 42.5% of hypercholesterolemia, 48.2% of high LDL-C, 34.1% of hypertriglyceridemia, and 41.8% of low HDL-C. The prevalence of isolated lipid profiles showed that 10 patients have mixed dyslipidemia. The association of dyslipidemia with age indicated a positive significance between triglyceride and older people (>=40 years), while HDL levels have a significance with gender (p=0.025). The overall ANOVA model yielded non-statistical significant results between levels of any components of lipid profile and levels of TSH and T4 hormones. Welch test (p=0.036) showed positive significance between levels of fasting blood glucose and triglyceride levels. Conclusion(s): Our results showed and confirmed the presence of a high percentage of hyperlipidemia in Ma'an province and there was no relationship with levels of TSH and T4. A relationship exists between levels of triglycerides and blood glucose concentrations.

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The impact of community teaching sessions on onward referral to specialist diabetic foot services (2024)

Type of publication:Journal article

Author(s):Al-Saadi, Nina; *Beard, Nichola; Al-Hashimi, Khalid; Suttenwood, Helen; Wall, Michael; *Jones, Steven; Merriman, *Catherine

Citation:Primary care diabetes. 18(1):79-83, 2024 Feb.

Abstract:INTRODUCTION: Prompt referral of patients with diabetic foot ulceration (DFU) to specialist services can lead to more timely assessment of these patients and subsequent improved rates of limb salvage and patient outcomes. In this study we wanted to determine the impact of education in the primary care setting on onward referrals to our specialist Diabetic Foot multi-disciplinary team (MDT) clinic. METHODS: As part of a Diabetic Foot Roadshow, four teaching sessions were delivered in primary care settings across Shropshire by our specialist team from 17th March to the 25th May 2022. Attendees included podiatrists, tissue viability nurses, district nurses and wound care practitioners. Hospital records were used to identify all onward referrals to our Diabetic Foot MDT clinic in the weeks before and after delivery of the roadshow education sessions. RESULTS: 184 referrals were made to the diabetic foot clinic from January to July 2022. There were 0.3 referrals per day in the months prior to the commencement of the education sessions, compared to 1.5 referrals per day following the commencement of the teaching sessions. This increase in referrals was statistically significant (p < 0.0001). CONCLUSION: Teaching sessions delivered to community specialist healthcare professionals significantly increase onward referral of patients to specialist services, facilitating more timely assessment and management of patients with DFUs.

GWAS and meta-analysis identifies 49 genetic variants underlying critical COVID-19 (2023)

Type of publication:
Journal article

Author(s):
Pairo-Castineira E.; Rawlik K.; Bretherick A.D.; Qi T.; Wu Y.; Nassiri I.; McConkey G.A.; Klaric L.; Kousathanas A.; Richmond A.; Malinauskas T.; Thwaites R.; Morrice K.; Maslove D.; Semple M.G.; Knight J.; Hinds C.; Horby P.; Ling L.; McAuley D.; Montgomery H.; Openshaw P.J.M.; Begg C.; Walsh T.; Tenesa A.; Flores C.; Riancho J.A.; Rojas-Martinez A.; Clohisey S.; Millar J.; Aitkin E.; Aravindan L.; Armstrong R.; Biggs H.; Boz C.; Chikowore P.; Coutts A.; Coyle J.; Cullum L.; Das S.; Day N.; Donnelly L.; Duncan E.; Finernan P.; Fourman M.H.; Furlong A.; Furniss J.; Gallagher B.; Gilchrist T.; Golightly A.; Griffiths F.; Hafezi K.; Hamilton D.; Hendry R.; Kearns N.; Law D.; Law R.; Law S.; Lidstone-Scott R.; Lauder C.; Macgillivray L.; Maclean A.; Mal H.; McCafferty S.; McMaster E.; Meikle J.; Murphy S.; Mybaya H.; Oosthuyzen W.; Zheng C.; Chen J.; Parkinson N.; Paterson T.; Tucker P.; Schon K.; Stenhouse A.; Das M.; Swets M.; Szoor-McElhinney H.; Taneski F.; Turtle L.; Wackett T.; Ward M.; Weaver J.; Wrobel N.; Zechner M.; Pan J.; Grau N.; Jones T.O.; Lim R.; Marotti M.; Whitton C.; Bociek A.; Campos S.; Arbane G.; Shankar-Hari M.; Ostermann M.; Cha M.; DAmato F.; Kosifidou E.; Lorah S.; Morera K.; Brady L.; Hugill K.; Henning J.; Bonner S.; Headlam E.; List A.; Morley J.; Welford A.; Kamangu B.; Ratnakumar A.; Shoremekun A.; Alldis Z.; Astin-Chamberlain R.; Bibi F.; Biddle J.; Blow S.; Bolton M.; Borra C.; Bowles R.; Burton M.; Choudhury Y.; Cox 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.; Zongo O.; Zak A.; Mundy M.; Thompson C.; Pritchard L.; Gellamucho M.; Cartlidge D.; Bandla N.; Bailey L.; Delaney J.; Scott L.; Abdelrazik M.; Alasdair F.; Carter D.; Elhassan M.; Ganesan A.; Lamond Z.; Purohit D.; Rohit K.; Saleem M.; Wall A.; Xavier K.; Bakthavatsalam D.; Gehad K.; Gnanapragasam P.; Jain K.; Jain S.; Malik A.; Pappachan N.; Moreno-Cuesta J.; Haldeos A.; Vincent R.; Oziegb M.; Cavazza A.; Cockrell M.; Corcoran E.; Depante M.; Finney C.; Jerome E.; Knighton A.; Nayak M.; Pappa E.; Saha S.; Dodd A.; O'Reilly K.; McPhail M.; Clarey E.; Noble H.; Coghlan P.; Brett S.; Gordon A.; Templeton M.; Antcliffe D.; Banach D.; Darnell S.; Fernandez Z.; Jepson E.; Mohammed A.; Rojo R.; Arias S.S.; Gurung A.T.; Fernandez-Roman J.; Hamilton D.O.; Johnson E.; Johnston B.; Martinez M.L.; Mulla S.; Waite A.A.C.; Williams K.; Waugh V.; Welters I.; Emblem J.; Norris M.; Shaw D.; Bashyal A.; Beer S.; Hutton P.; McKechnie S.; Davidson N.; Readion G.; Ryu J.; Wilson J.; Agrawal S.; Elston K.; Jones M.; Meaney E.; Polgarova P.; Elbehery M.; Summers C.; Daubney E.; Ng A.; Marshall J.; Pathan N.; Stroud K.; White D.; Andrew A.; Ashraf S.; Dent M.; Langley M.; Peters C.; Ryan L.; Sampson J.; Wei S.; Baddeley A.; Meredith M.; Morris L.; Gibbons A.; McLoughlin L.; Delgado C.C.; Clark V.; Dawson D.; Ding L.; Durrant G.; Ezeobu O.; Hurt W.J.; Kanu R.; Kinch A.; Leaver S.; Lisboa A.; Mathew J.; Patel K.; Saluzzio R.P.; Rawlins J.; Samakomva T.; Shah N.; Sicat C.; Texeira J.; De Queiroz J.G.; Da Gloria E.F.; Maccacari E.; Yun N.; Manna S.; Farnell-Ward S.; Maizcordoba M.; Thanasi M.; Ali H.H.; Hastings J.; Grauslyte L.; Hussain M.; Ruge B.; King S.; Pogreban T.; Rosaroso L.; Smith H.; Phull M.-K.; *Adams N.; Franke G.; George A.; Salciute E.; Wong J.; Dunne K.; Flower L.; Sharland E.; Sra S.; Andrew G.; Callaghan M.; Barclay L.; Baillie K.; Hope D.; Mcculloch C.; Allen M.; Baptista D.; Crowe R.; Fox J.; Khera J.; Loveridge A.; McKenley I.; Morino E.; Naranjo A.; O'Connor D.; Simms R.; Sollesta K.; Swain A.; Herdman-Grant R.; Joseph A.; Nown A.; Rose S.; Pogson D.; Boxall H.; Brimfield L.; Claridge H.; Daly Z.; George S.; Gribbin A.; Cheema Y.; Cutler S.; Richards O.; Roynon-Reed A.; Cherian S.; Heron A.E.; Williams G.; Szakmany T.; Waters A.; Dunhill J.; Jones F.; Morris R.; Ship L.; Cardwell A.; Ali S.; Bhatterjee R.; Bolton R.; Chukkambotla S.; Coleman D.; Dalziel J.; Dykes J.; Fine C.; Gay B.; Goddard W.; Goodchild D.; Harling R.; Hijazi M.; Keith S.; Khan M.; Matt R.; Ryan-Smith J.; Saad S.; Springle P.; Thomas J.; Truman N.; Kazi A.; Smith M.; Collier H.; Davison C.; Duberley S.; Hargreaves J.; Hartley J.; Patel T.; Kent A.; Goodwin E.; Zaki A.; Tibke C.; Hopkins S.; Gerrard H.; Jackson M.; Bennett S.; Mills R.; Bell J.; Campbell H.; Dawson A.; Dodds S.; Duffy S.; Gallagher L.; McCafferty G.; Short S.; Thomas K.; Walker C.; Reynolds J.; Yates B.; McKie H.; Panteli M.; Thompson M.; Waddell G.; De Beger S.; Abraheem A.; Dunmore C.; Girach R.; Jones R.; London E.; Nagra I.; Nasir F.; Sainsbury H.; Smedley C.; Brearey S.; Burchett C.; Faulkner M.; Jeffrey H.; Bamford P.; Shaikh F.; Slack L.; Davies A.; Brooke H.; Suarez J.C.; Charlesworth R.; Hansson K.; Norris J.; Poole A.; Sandhu R.; Smithson E.; Thirumaran M.; Wagstaff V.; Buckley S.; Sloan B.; Rose A.; Major A.; Metcalfe A.; Almaden-Boyle C.; Austin P.; Chapman S.; Eros A.; Cabrelli L.; Cole S.; Whyte C.; Casey M.; Bafitis V.; Tsinaslanidis G.; George C.; Khade R.; Black C.; Ashok S.R.; Farley S.; Brinkworth E.; Harford R.; Murphy C.; Williams M.; Newey L.; Toghill H.; Lewis S.; Rees T.; Battle C.; Baker M.; Travers J.; Chesters K.; Baxter N.; Arnott A.; McCreath G.; Rooney L.; Sim M.; Henderson S.; Dalton C.; Kennedy-Hay S.; O'Donohoe L.; O'Hare M.; Orlikowska I.; McNeela F.; Lyle A.; Hughes A.; Radhakrishnan J.; Gibson S.; Bancroft H.; Bellamy M.; Daglish J.; Kadiri S.; Moore F.; Rhodes J.; Sangombe M.; Peterkin Z.; Carmody M.; Cottle J.; Peasgood E.; de Gordoa L.O.-R.; Cinquina Z.; Howard K.; Joy R.; Roche S.; Birkinshaw I.; Carter J.; Ingham J.; Marshall N.; Pearson H.; Scott Z.; Dasgin J.; Gill J.; Nilsson A.; Hull D.; Ahmadhaider N.; Bates M.; McGhee C.; Ellis H.; Howe G.S.; Singh J.; Stroud N.; Lynch C.; Krishnamurthy V.; Lim L.; Jha R.; Egan J.; Felton T.; Glasgow S.; Padden G.; Choudhr O.; Moss S.; Lingeswaran S.; Alexander P.; Fiouni S.; Ward L.; Allen S.; Shaw J.; Smith C.; Adanini O.; Collins R.; Msiska M.; Ofori L.; Bhatia N.; Dolan H.; Brunton M.; Caterson J.; Coles H.; Keating L.; Tilney E.; Jacques N.; Frise M.; Armistead J.; Bartley S.; Bhuie P.; Rai S.; Tomkova G.; Greer S.; Shuker K.; Tridente A.; Dobson E.; Tully R.; Dearden J.; Drummond A.; Kamath P.; Mulcahy M.; Munt S.; O'Connor G.; Philbin J.; Rishton C.; Scott C.; Winnard S.; Hasni N.; Gascoyne R.; Hawes J.; Pritchard K.; Stevenson L.; Whileman A.; Beavis S.; Bishop L.; Cart C.; Dale K.; Kelly-Baxter M.; Mendelski A.; Moakes E.; Smith R.; Woodward J.; Wright S.; Allan A.; Botello A.; Liew J.; Medhora J.; Trumper E.; Savage F.; Scott T.; Place M.; Kaye C.; Benyon S.; Marriott S.; Park L.; Quinn H.; Skyes D.; Zitter L.; Baines K.; Gordon E.; Keenan S.; Pitt A.; Duffy K.; Ireland J.; Semple G.; Turner L.; Cathcart S.; Rimmer D.; Puxty A.; Puxty K.; Hurst A.; Miller J.; Speirs S.; Bradshaw Z.; Brown J.; Melling S.; Preston S.; Slawson N.; Warden S.; Beasley A.; Stoddard E.; Benham L.; Cupitt J.; Caswell M.; Elawamy L.; Wignall A.; Roberts B.; Golding H.; Leggett S.; Male M.; Marani M.; Prager K.; Williams T.; Golder K.; Jones O.; Cusack R.; Bolger C.; Burnish R.; Carter M.; Jackson S.; Salmon K.; Biss J.; Aquino M.; Croft M.; Frost V.; White I.; Govender K.; Webb N.; Stapleton L.; Wells C.; Nikitas N.; Sanchez-Rodriguez A.; Spencer K.; Stowe B.; Izzard Y.; Poole M.; Monnery S.; Trotman S.; Beech V.; Combes E.; Joefield T.; Covernton P.; Savage S.; Woodward E.; Camsooksai J.; Reschreiter H.; Barclay C.; DeAth Y.; Dube J.; Humphrey C.; Jenkins S.; Langridge E.; Milne R.; Wadams B.; Woolcock M.; Brett M.; Digby B.; Gemmell L.; Hornsby J.; MacGoey P.; O'Neil P.; Price R.; Sundaram R.; Abel L.; Rodden N.; Thomson N.; Rooney K.; Currie S.; Parker N.; Walker L.; Henderson P.; Ogg B.; Whiteley S.; Wilby L.; Long K.; Matthew S.; Salada S.; Trott S.; Watts S.; Friar Z.; Speight A.; Bastion V.; Chandna H.; Djeugam B.; Haseeb M.; Kent H.; Lubimbi G.; Murdoch S.; David B.; Lorusso R.; Vochin A.; Penacerrada M.; Wulandari R.; Heath C.; Jakkula S.; Morris A.; Ahmed A.; Nune A.; Buttriss C.; Whitaker E.; Davey M.; Golden D.; Acklery A.; Fernandes F.; Seaman B.; Earl V.; Collins A.; Adam R.; Treus E.; Holland S.; Alfonso J.; Bruce M.; Durrans L.J.; Eltayeb A.; Hey S.; Hruska M.; Lamb T.; Rothwell J.; Fitzgerald A.; Lindergard G.; T-Michael H.; Duncan T.; Baxter-Dore S.; Fox C.; Guerin J.; Hodgkiss T.; Connolly K.; McAlinden P.; Bridgett V.; Fearby M.; Gulati A.; Hanson H.; Kelly S.; McCormack L.; Nixon R.; Robinson P.; Slater V.; Stephenson E.; Webster A.; Webster K.; Hays C.; Hudson A.; Clement I.; Davis J.; Francis S.; Jerry D.; Abernathy C.; Foster L.; Gratrix A.; Cabral-Ortega L.; Hines M.; Martinson V.; Stones E.; Winter K.; Barrow E.; Wylie K.; Baines D.; Kolakaluri L.; Clark R.; Sukumaran A.; Brandwood C.; Barker M.; Paripoorani D.; Taylor C.; Downes C.; Hayman M.; Riches K.; Daniel P.; Subramanian D.; Holding K.; Hilton M.; McDonald C.; Richardson G.; Halladay G.; Harding P.; Reddy A.; Turner-Bone I.; Wilding L.; Parker R.; Lloyd M.; Smith L.; Kelly C.; Lazo M.; Neal A.; Walton O.; Melville J.; Naisbitt J.; Bullock E.; Joseph R.; Callam S.; Hudig L.; Keshet-Price J.; Stammers K.; Convery K.; Randell G.; Fottrell-Gould D.; Mwaura E.; Sutherland S.-B.; Stewart R.; Mew L.; Wren L.; Thrasyvoulou L.; Willis H.; Scriven J.; Hopkins B.; Lenton D.; Roberts A.; Bokhari M.; Lucas R.; McCormick W.; Ritzema J.; Linnett V.; Sanderson A.; Wild H.; Flanagan R.; Hull R.; Rhead K.; McKenna E.; Hughes G.; Anderson J.; Jones K.; Latham S.; Riley H.; Coulding M.; Mercer O.; Potla D.; Rehman H.; Savill H.; Turner V.; Jude E.; Kilroy S.; Apetri E.; Basikolo C.; Blackledge B.; Catlow L.; Collis M.; Doonan R.; Harris J.; Harvey A.; Knowles K.; Lee S.; Lomas D.; Lyons C.; McMorrow L.; Michael A.; Pendlebury J.; Perez J.; Poulaka M.; Proudfoot N.; Slevin K.; Thomas V.; Walker D.; Dark P.; Charles B.; McLaughlan D.; Slaughter M.; Horner D.; Cawley K.; Marsden T.; Andrews J.; Beech E.; Akinkugbe O.; Bamford A.; Belfield H.; Jones G.A.L.; McHugh T.; Meghari H.; Ray S.; Tomas A.L.; O'Neill L.; Peters M.; Bell M.; Benkenstein S.; Chisholm C.; Kupiec K.; Payne C.; Halls J.; Blakemore H.; Goff E.; Hayes K.; Smith K.; Stephens D.; Worner R.; Borislavova B.; Faulkner B.; Thomas M.; Cookson R.; Gendall E.; Larman G.; Pope R.; Smalira A.; Priestley V.; Cosier T.; Millen G.; Rand J.; Schumacher N.; Sandhar R.; Weston H.; Richardson N.; Cooper L.; Jones C.; Huang Y.-W.J.; Jacob R.; Denmade C.; McIntyre L.; Trodd D.; Martin J.; Watson G.; Bevan E.; Wreybrown C.; Bano S.; Bellwood R.; Bentley M.; Bromley M.; Gurr L.; Ledgard C.; McGowan J.; Pye K.; Sellick K.; Stacey A.; Warren D.; Wilkinson B.; Akeroyd L.; Shafique H.; Morgan J.; Shorter S.; Swinger R.; Waters E.; Lawton T.; Allan E.; Darlington K.; Davies F.; Davies L.; Easton J.; Kumar S.; Lean R.; Mackay C.; Pugh R.; Qiu X.; Rees S.; Scanlon J.; Lewis J.; Menzies D.; Bolger A.; Davies G.; Davies J.; Garrod E.; Jones H.; Manley R.; Williams H.; Frankham J.; Pitts S.; Branney D.; Tiller H.; Efford G.; Garland Z.; Grimmer L.; Gumbrill B.; Johnson R.; Sweet K.; Bewley J.; Coleman C.; Corcoran K.; Morano E.M.H.; Shiel R.; Webster D.; Bonnici J.; Daniel E.; Dell A.; Kent M.; Wilkinson A.; Brown E.; Kay A.; Campbell S.; Cowton A.; Greenaway V.; Potts K.; Hutton C.; Shepperson A.; Forsey M.; Vertue M.; Riches J.; Kaliappan A.; MacCallum N.; Bercades G.; Hass I.; Martir G.; Reyes A.; Smyth D.; Zapatamartinez M.; Alvaro A.; Jetha C.; Ma L.; Booker L.; Mostoles L.; Pratley A.; Altabaibeh A.; Parmar C.; Gilbert K.; Ferguson S.; Shepherd A.; Morris S.; Singleton J.; Baruah R.; Amamio M.; Birch S.; Briton K.; Clark S.; Doverman K.; Marshall L.; Simpson S.; Lloyd G.; Bell S.; Rivers V.; Purewal B.; Hammerton K.; Oleary R.; Cornell S.; Jarmain J.; Rogerson K.; Wakinshaw F.; Woods L.; Rostron A.; Elcioglu Z.; Roy A.; Bell G.; Dickson H.; Wilcox L.; Katary A.; English K.; Hutter J.; Pawley C.; Doble P.; Shovelton C.; Vaida M.; Purnell R.; Cagova L.; Fofano A.; Holcombe H.; Mitchell A.M.; Mwaura L.; Raman K.P.; Garnr L.; Mepham S.; Paques K.; Vuylsteke A.; Mackie J.; Pearn C.; Zamikula J.; Birt M.; Gude E.T.; Nyirenda M.; Capozzi L.; Reece-Anthony R.; Khaliq W.; Noor H.; Nilo A.C.; Grove M.; Daniel A.; Finn J.; White N.; Saha R.; Badal B.; Ixer K.; Duffin D.; Player B.; Hill H.; Davies M.; Davies R.; Hunt L.; Thomas E.; Oblak M.; Thankachen M.; Irisari J.; Sayan A.; Popescu M.; Finch C.; Jamieson A.; Quinn A.; Cooper J.; Liderth S.; Waddington N.; Burn I.; Manso K.; Penn R.; Tebbutt J.; Thornton D.; Winchester J.; Hambrook G.; Shanmugasundaram P.; Craig J.; Simpson K.; Sibbett L.; Paine S.; Conyngham J.-A.; Mupudzi M.D.; Thomas R.; Wright M.; Griffin D.; Partridge R.; Corral M.A.; Muchenje N.; Sitonik M.; Brown C.W.; Butler A.; Folkes L.; Fox H.; Gardner A.; Helm D.; Hobden G.; King K.; Margalef J.; Margarson M.; Martindale T.; Meadows E.; Raynard D.; Thirlwall Y.; Baird Y.; Gomez R.; Hodgson L.; Corin C.; Sidall E.; Szabo D.; Floyd S.; Davies H.; Austin K.; Kelsall O.; Wood H.; Anderson P.; Archer K.; Burtenshaw A.; Clayton S.; Cother N.; Cowley N.; Davis C.; Digby S.; Durie A.; Harrison A.; Low E.; McAlindon M.; McCurdy A.; Morgan A.; Rankin T.; Thrush J.; Tranter H.; Vigurs C.; Wild L.; Cornell T.; Ralph K.; Bean S.; Burt K.; Spivey M.; Richards C.; Tedstone R.; Carmody S.; Zhao X.; Page V.; Guanco M.L.; Hoxha E.; Zorloni C.; Dean C.; Jones E.; Carter E.; Dunn J.; Kong T.; Mahenthran M.; Marsh C.; Holland M.; Keenan N.; Mahmoud M.; Lyons M.; Bradley-Potts J.; Wassall H.; Young M.; Bradley P.; Burda D.; Donlon S.; Harden L.; Harris C.; Mayangao I.; Montaser R.; Mtuwa S.; Piercy C.; Smith E.; Stone S.; Verula J.; Blackman H.; Marriott C.; Michalak N.; Creagh-Brown B.; Salberg A.; Boyer N.; Pristopan V.; Walker R.; Hormis A.; Collier D.; Graham C.; Maynard V.; McCormick J.; Warrington J.; Cosgrove D.; McFarland D.; Ratcliffe J.; 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Citation:
Nature. 617(7962) (pp 764-768), 2023. Date of Publication: 25 May 2023.

Abstract:
Critical illness in COVID-19 is an extreme and clinically homogeneous disease phenotype that we have previously shown<sup>1</sup> to be highly efficient for discovery of genetic associations<sup>2</sup>. Despite the advanced stage of illness at presentation, we have shown that host genetics in patients who are critically ill with COVID-19 can identify immunomodulatory therapies with strong beneficial effects in this group<sup>3</sup>. Here we analyse 24,202 cases of COVID-19 with critical illness comprising a combination of microarray genotype and whole-genome sequencing data from cases of critical illness in the international GenOMICC (11,440 cases) study, combined with other studies recruiting hospitalized patients with a strong focus on severe and critical disease: ISARIC4C (676 cases) and the SCOURGE consortium (5,934 cases). To put these results in the context of existing work, we conduct a meta-analysis of the new GenOMICC genome-wide association study (GWAS) results with previously published data. We find 49 genome-wide significant associations, of which 16 have not been reported previously. To investigate the therapeutic implications of these findings, we infer the structural consequences of protein-coding variants, and combine our GWAS results with gene expression data using a monocyte transcriptome-wide association study (TWAS) model, as well as gene and protein expression using Mendelian randomization. We identify potentially druggable targets in multiple systems, including inflammatory signalling (JAK1), monocyte-macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

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Magnetic resonance imaging before breast cancer surgery: results of an observational multicenter international prospective analysis (MIPA) (2022)

Type of publication:Journal article

Author(s):Sardanelli F, Trimboli RM, Houssami N, Gilbert FJ, Helbich TH, Álvarez Benito M, Balleyguier C, Bazzocchi M, Bult P, Calabrese M, Camps Herrero J, Cartia F, Cassano E, Clauser P, Cozzi A, de Andrade DA, de Lima Docema MF, Depretto C, Dominelli V, Forrai G, Girometti R, Harms SE, Hilborne S, Ienzi R, Lobbes MBI, Losio C, Mann RM, Montemezzi S, Obdeijn IM, *Ozcan Umit A, Pediconi F, Pinker K, Preibsch H, Raya Povedano JL, Sacchetto D, Scaperrotta GP, Schiaffino S, Schlooz M, Szabó BK, Taylor DB, Ulus ÖS, Van Goethem M, Veltman J, Weigel S, Wenkel E, Zuiani C, Di Leo G.

Citation:European Radiology. 2022 Mar;32(3):1611-1623.

Abstract:Objectives: Preoperative breast magnetic resonance imaging (MRI) can inform surgical planning but might cause overtreatment by increasing the mastectomy rate. The Multicenter International Prospective Analysis (MIPA) study investigated this controversial issue. Methods: This observational study enrolled women aged 18-80 years with biopsy-proven breast cancer, who underwent MRI in addition to conventional imaging (mammography and/or breast ultrasonography) or conventional imaging alone before surgery as routine practice at 27 centers. Exclusion criteria included planned neoadjuvant therapy, pregnancy, personal history of any cancer, and distant metastases. Results: Of 5896 analyzed patients, 2763 (46.9%) had conventional imaging only (noMRI group), and 3133 (53.1%) underwent MRI that was performed for diagnosis, screening, or unknown purposes in 692/3133 women (22.1%), with preoperative intent in 2441/3133 women (77.9%, MRI group). Patients in the MRI group were younger, had denser breasts, more cancers ≥ 20 mm, and a higher rate of invasive lobular histology than patients who underwent conventional imaging alone (p < 0.001 for all comparisons). Mastectomy was planned based on conventional imaging in 22.4% (MRI group) versus 14.4% (noMRI group) (p < 0.001). The additional planned mastectomy rate in the MRI group was 11.3%. The overall performed first- plus second-line mastectomy rate was 36.3% (MRI group) versus 18.0% (noMRI group) (p < 0.001). In women receiving conserving surgery, MRI group had a significantly lower reoperation rate (8.5% versus 11.7%, p < 0.001). Conclusions: Clinicians requested breast MRI for women with a higher a priori probability of receiving mastectomy. MRI was associated with 11.3% more mastectomies, and with 3.2% fewer reoperations in the breast conservation subgroup. Key points: • In 19% of patients of the MIPA study, breast MRI was performed for screening or diagnostic purposes. • The current patient selection to preoperative breast MRI implies an 11% increase in mastectomies, counterbalanced by a 3% reduction of the reoperation rate. • Data from the MIPA study can support discussion in tumor boards when preoperative MRI is under consideration and should be shared with patients to achieve informed decision-making.

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Solving the preoperative breast MRI conundrum: design and protocol of the MIPA study (2020)

Type of publication:Journal article

Author(s):Sardanelli F, Trimboli RM, Houssami N, Gilbert FJ, Helbich TH, Alvarez Benito M, Balleyguier C, Bazzocchi M, Bult P, Calabrese M, Camps Herrero J, Cartia F, Cassano E, Clauser P, de Andrade DA, de Lima Docema MF, Depretto C, Forrai G, Girometti R, Harms SE, Hilborne S, Ienzi R, Lobbes MBI, Losio C, Mann RM, Montemezzi S, Obdeijn IM, *Ozcan, Umit A., Pediconi F, Preibsch H, Raya-Povedano JL, Sacchetto D, Scaperrotta GP, Schlooz M, Szabo BK, Ulus OS, Taylor DB, Van Goethem M, Veltman J, Weigel S, Wenkel E, Zuiani C, Di Leo G.

Citation:European Radiology. 2020 Oct;30(10):5427-5436.

Abstract:Despite its high diagnostic performance, the use of breast MRI in the preoperative setting is controversial. It has the potential for personalized surgical management in breast cancer patients, but two of three randomized controlled trials did not show results in favor of its introduction for assessing the disease extent before surgery. Meta-analyses showed a higher mastectomy rate in women undergoing preoperative MRI compared to those who do not. Nevertheless, preoperative breast MRI is increasingly used and a survey from the American Society of Breast Surgeons showed that 41% of respondents ask for it in daily practice. In this context, a large-scale observational multicenter international prospective analysis (MIPA study) was proposed under the guidance of the European Network for the Assessment of Imaging in Medicine (EuroAIM). The aims were (1) to prospectively and systematically collect data on consecutive women with a newly diagnosed breast cancer, not candidates for neoadjuvant therapy, who are offered or not offered breast MRI before surgery according to local practice; (2) to compare these two groups in terms of surgical and clinical endpoints, adjusting for covariates. The underlying hypotheses are that MRI does not cause additional mastectomies compared to conventional imaging, while reducing the reoperation rate in all or in subgroups of patients. Ninety-six centers applied to a web-based call; 36 were initially selected based on volume and quality standards; 27 were active for enrollment. On November 2018, the target of 7000 enrolled patients was reached. The MIPA study is presently at the analytic phase. Key Points • Breast MRI has a high diagnostic performance but its utility in the preoperative setting is controversial. • A large-scale observational multicenter prospective study was launched to compare women receiving with those not receiving preoperative MRI. • Twenty-seven centers enrolled more than 7000 patients. The study is presently at the analytic phase.

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