Hypoglycaemia in adrenal insufficiency (2023)

Type of publication:Journal article

Author(s):*Lee, Shien Chen; Baranowski, Elizabeth S; *Sakremath, Rajesh; Saraff, Vrinda; Mohamed, Zainaba

Citation:Frontiers in Endocrinology. 2023. [epub ahead of print]

Abstract:Adrenal insufficiency encompasses a group of congenital and acquired disorders that lead to inadequate steroid production by the adrenal glands, mainly glucocorticoids, mineralocorticoids and androgens. These may be associated with other hormone deficiencies. Adrenal insufficiency may be primary, affecting the adrenal gland's ability to produce cortisol directly; secondary, affecting the pituitary gland's ability to produce adrenocorticotrophic hormone (ACTH); or tertiary, affecting corticotrophin-releasing hormone (CRH) production at the level of the hypothalamus. Congenital causes of adrenal insufficiency include the subtypes of Congenital Adrenal Hyperplasia, Adrenal Hypoplasia, genetic causes of Isolated ACTH deficiency or Combined Pituitary Hormone Deficiencies, usually caused by mutations in essential transcription factors. The most commonly inherited primary cause of adrenal insufficiency is Congenital Adrenal Hyperplasia due to 21-hydroxylase deficiency; with the classical form affecting 1 in 10,000 to 15,000 cases per year. Acquired causes of adrenal insufficiency can be subtyped into autoimmune (Addison's Disease), traumatic (including haemorrhage or infarction), infective (e.g. Tuberculosis), infiltrative (e.g. neuroblastoma) and iatrogenic. Iatrogenic acquired causes include the use of prolonged exogenous steroids and post-surgical causes, such as the excision of a hypothalamic-pituitary tumour or adrenalectomy. Clinical features of adrenal insufficiency vary with age and with aetiology. They are often non-specific and may sometimes become apparent only in times of illness. Features range from those related to hypoglycaemia such as drowsiness, collapse, jitteriness, hypothermia and seizures. Features may also include signs of hypotension such as significant electrolyte imbalances and shock. Recognition of hypoglycaemia as a symptom of adrenal insufficiency is important to prevent treatable causes of sudden deaths. Cortisol has a key role in glucose homeostasis, particularly in the counter-regulatory mechanisms to prevent hypoglycaemia in times of biological stress. Affected neonates particularly appear susceptible to the compromise of these counter-regulatory mechanisms but it is recognised that affected older children and adults remain at risk of hypoglycaemia. In this review, we summarise the pathogenesis of hypoglycaemia in the context of adrenal insufficiency. We further explore the clinical features of hypoglycaemia based on different age groups and the burden of the disease, focusing on hypoglycaemic-related events in the various aetiologies of adrenal insufficiency. Finally, we sum up strategies from published literature for improved recognition and early prevention of hypoglycaemia in adrenal insufficiency, such as the use of continuous glucose monitoring or modifying glucocorticoid replacement.

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Both gastrocnemius aponeurosis flaps and semitendinosus tendon grafts are effective in the treatment of chronic Achilles tendon ruptures - a systematic review (2023)

Type of publication:Journal article

Author(s):Nilsson N.; Stensota I.; Nilsson Helander K.; Brorsson A.; *Carmont M.R.; Concaro S.

Citation:BMC Musculoskeletal Disorders. 24(1) (no pagination), 2023. Article Number: 951. Date of Publication: December 2023.

Abstract:Introduction: A chronic Achilles tendon rupture (ATR) is defined as an ATR that has been left untreated for more than four weeks following rupture. This systematic review aims to summarize the outcomes of chronic ATR treated using either a gastrocnemius aponeurosis flap or semitendinosus tendon graft. Method(s): A systematic search was conducted in three databases (PubMed, Scopus and Cochrane), for studies describing outcomes after surgical treatment of chronic ATR using gastrocnemius aponeurosis flaps or semitendinosus tendon grafts with more than 10 patients included. The studies were assessed for quality and risk of bias using the Methodological Items used to assess risk of bias in Non-Randomized Studies (MINORS). Result(s): Out of the 818 studies identified with the initial search, a total of 36 studies with 763 individual patients were included in this systematic review. Gastrocnemius aponeurosis flap was used in 21 and semitendinosus tendon graft was used in 13 of the studies. The mean (SD) postoperative Achilles tendon Total Rupture Score (ATRS) for patients treated with a gastrocnemius aponeurosis flap was 83 (14) points and the mean (SD) American Orthopaedic Foot and Ankle Score (AOFAS) was 96 (1.7) points compared with ATRS 88 (6.9) points and AOFAS 92 (5.6) points for patients treated with a semitendinosus tendon graft. The included studies generally had low-quality according to MINORS, with a median of 8 (range 2-13) for all studies. Conclusion(s): Both gastrocnemius aponeurosis flaps and semitendinosus tendon grafts give acceptable results with minimal complications and are valid methods for treating chronic ATR. The main difference is more wound healing complications in patients treated with a gastrocnemius aponeurosis flap and more sural nerve injuries in patients treated with a semitendinosus grafts. The current literature on the subject is of mainly low quality and the absence of a patient-related outcome measure validated for chronic ATR makes comparisons between studies difficult. Level of Evidence: Level IV.

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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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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.; Charnock R.; Wynter I.; Gill M.; Kirk J.; Paul P.; Ratnam V.; Shelton S.; Jardine C.; Hay A.; Williams D.; Deacon B.; Durga L.; Hibbert M.; Kennard-Holden G.; Woodford C.; Pothecary C.; Tetla D.; Agravante K.; Smeaton J.; Price A.; Thomas A.; Thorpe C.; Knights E.; Ward D.; Laha S.; Verlander M.; Williams A.; Prout R.; Langton H.; Watters M.; Hunt C.; Novis C.; Arif S.; Cunningham A.; Hewitt C.; Hindale J.; Jackson-Lawrence K.; Shepardson S.; Wills M.; Butler S.; Tavares S.; Barber R.; Hilldrith A.; Hubbard K.; Egginton D.; Clark M.; Purvis S.; Sinclair S.; Collins V.; Landeg B.; Sell C.; Coetzee S.; Gales A.; Icke B.; Raj M.; Williams C.; Williams J.; Hill L.; Kayani A.; Masunda B.; Gondo P.; Atayeva N.; Cruz C.; Pattison N.; Burnett C.; Hatton J.; Heeney E.; Newton M.; Al-Moasseb H.; Behan T.; Stead R.; Mitra A.; Humphreys S.; Cockerill H.; Tampsett R.; Postovalova E.; Coventry T.; Fowler S.; Macmahon M.; Cochrane P.; Pirie S.; Hanley S.; Ali A.; Brady M.; Dale S.; Dance A.; Gledhill L.; Greig J.; Hanson K.; Holdroyd K.; Home M.; Ishaq T.; Kelly D.; Matapure L.; Melia D.; Mellor S.; Merwaha E.; Nortcliffe T.; Shaw L.; Shaw R.; Wood T.; Bayo L.-A.; Usher M.; Wilson A.; Kitson R.; Pinnell J.; Robinson M.; Boltwood K.; Birch J.; Bough L.; Tutton R.; Winter-Goodwin B.; Goodsell J.; Taylor K.; Williams P.; Williams S.; Cave A.; Rees J.; Imeson-Wood J.; Amin V.; Karthik K.; Kausar R.; Anastasescu E.; Reid K.; Anumakonda V.; Stoddart E.; Demetriou C.; Eckbad C.; Howie L.; Mitchard S.; Ramos L.; White K.; Hierons S.; Kelly F.; Serrano-Ruiz A.; Evans G.; Nicol L.; Wilkins J.; Hulacka K.; Debreceni G.; Crickmore V.; Hill K.; Kannan T.; Dagutao Z.; Beesley K.; Lewis A.; Perry J.; Antony S.; Board S.; Buckley C.; Pippard L.; Tanate A.; Wood D.; Kubisz-Pudelko A.; Gouda A.; Auld F.; Donnachie J.; Murdoch E.; Prentice L.; Runciman N.; Senaratne D.; Short A.; Sweeney L.; Symon L.; Todd A.; Turner P.; McCann E.; Salutous D.; Edmond I.; Whitelaw L.; Venkatesh H.; Bland Y.; Kajtor I.; Kavanagh L.; Singler K.; Linfield-Brown G.; Moore L.S.P.; Vizcaychipi M.; Martins L.; Moore L.; Bull R.; Carungcong J.; Allen L.; Beranova E.; Knight A.; Price C.; Tilbey S.; Turney S.; Hazelton T.; Tutt G.; Arora M.; Turki S.; Sinfield E.; Deery J.; Ramos H.; Cristiano D.; Dormand N.; Farzad Z.; Gummadi M.; Salmi S.; Sloane G.; Varghese M.; Patel B.; Kamal L.; Zborowski A.C.; Coe R.; Anderson M.; Beadle J.; Coates C.; Collins K.; Crowley M.; Johnson L.; King L.; Paramsothy R.; Sargeant J.; Silva P.; Stuart C.; Taylor J.; Tyl D.; Wakefield P.; Kamundi C.; Olufuwa O.; Belagodu Z.; Gherman A.; Oakley N.; Allan J.; Geary T.; Meikle A.; O'Brien P.; Wood S.; Clark A.; Houston G.; Black K.; Clarkson M.; D'Sylva S.; Morrison A.; Norman K.; Taylor M.; Clements S.; Cohrane C.; Gonzalez N.; Strachan D.; Moar K.; Smythe M.; Nichol A.; Brickell K.; Ali I.A.M.; Beaumont K.; Elsaadany M.; Fernandes K.; Ally S.M.; Rangarajan H.; Sarathy V.; Selvanayagam S.; Vedage D.; White M.; Coton Z.; Joshy A.; Blunt M.; Curgenven H.; 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de la Horra C.; de la Hoz A.B.; De Martino-Rodriguez A.; de Sousa Alves Neri J.L.; del Campo-Perez V.; Delgado-Cuesta J.; Diaz-Caneja C.M.; Diaz-Perez A.; de Bustamante A.D.; Dietl B.; Diz-de Almeida S.; Alves M.M.; Dominguez-Garrido E.; dos Santos K.A.; Duarte A.M.; Echave-Sustaeta J.; Eiros R.; Enciso-Olivera C.O.; Escudero G.; Espana P.P.; Sanabria G.M.E.; Farinas M.C.; Fernandes M.R.; Fernandez R.; Fernandez-Caballero L.; Fernandez-Cruz A.; Fernandez-Nestosa M.J.; Fernandez-Robelo U.; Fernandez-Rodriguez A.; Fernandez-Sampedro M.; Fernandez-Sanchez R.; Fernandez-Villa T.; Ferrero S.F.; Martinez Y.F.; Capitan C.F.; Flores-Perez P.; Friaza V.; Fuenmayor-Hernandez L.; Nunez M.F.; Fumado V.; Gadea I.; Gagliardi L.; Gago-Dominguez M.; Gallego N.; Galoppo C.; Garcia I.; Garcia M.; Garcia L.; Garcia-Cerrada C.; Garcia-de-Vicuna A.; Garcia-Garcia J.; Garcia-Garcia I.; Garcia-Ibarbia C.; Garcia-Montero A.C.; Garcia-Soidan A.; Garcia-Vazquez E.; Torrejon M.C.G.; Garza-Frias E.; Gentile A.; Gil-Fournier B.; 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Villoslada-Blanco P.; Virseda-Berdices A.; Yanez Z.; Zapatero-Gaviria A.; Zarate R.; Zazo S.; de Heredia M.L.; Mendes I.; Moreno R.; Sande E.; Lapunzina P.; Alex B.; Andrikopoulos P.; Bach B.; Barclay W.S.; Bogaert D.; Chand M.; Chechi K.; Cooke G.S.; da Silva Filipe A.; de Silva T.; Docherty A.B.; dos Santos Correia G.; Dumas M.-E.; Dunning J.; Fletcher T.; Green C.A.; Greenhalf W.; Griffin J.; Gupta R.K.; Harrison E.M.; Ho A.Y.W.; Holden K.; Horby P.W.; Ijaz S.; Khoo S.; Klenerman P.; Lewis M.; Liggi S.; Lim W.S.; Maslen L.; Mentzer A.J.; Merson L.; Meynert A.M.; Moore S.C.; Noursadeghi M.; Olanipekun M.; Osagie A.; Palmarini M.; Palmieri C.; Paxton W.A.; Pollakis G.; Price N.; Rambaut A.; Robertson D.L.; Russell C.D.; Sancho-Shimizu V.; Sands C.; Scott J.T.; Sigfrid L.; Solomon T.; Sriskandan S.; Stuart D.; Swann O.V.; Takats Z.; Takis P.; Tedder R.S.; Thompson A.A.R.; Thomson E.C.; Thwaites R.S.; Turtle L.C.W.; Zambon M.; Carson G.; Drake T.M.; Fairfield C.J.; Knight S.R.; Mclean K.A.; 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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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The Impact of Artificial Intelligence on Optimizing Diagnosis and Treatment Plans for Rare Genetic Disorders (2023)

Type of publication:Journal article

Author(s):Abdallah, Shenouda; Sharifa, Mouhammad; I Kh Almadhoun, Mohammed Khaleel; Khawar, Muhammad Muneeb Sr; Shaikh, Unzla; Balabel, Khaled M; Saleh, Inam; Manzoor, Amima; Mandal, Arun Kumar; *Ekomwereren, Osatohanmwen; Khine, Wai Mon; Oyelaja, Oluwaseyi T.

Citation:Cureus. 15(10):e46860, 2023 Oct.

Abstract:Rare genetic disorders (RDs), characterized by their low prevalence and diagnostic complexities, present significant challenges to healthcare systems. This article explores the transformative impact of artificial intelligence (AI) and machine learning (ML) in addressing these challenges. It emphasizes the need for accurate and early diagnosis of RDs, often hindered by genetic and clinical heterogeneity. This article discusses how AI and ML are reshaping healthcare, providing examples of their effectiveness in disease diagnosis, prognosis, image analysis, and drug repurposing. It highlights AI's ability to efficiently analyze extensive datasets and expedite diagnosis, showcasing case studies like Face2Gene. Furthermore, the article explores how AI tailors treatment plans for RDs, leveraging ML and deep learning (DL) to create personalized therapeutic regimens. It emphasizes AI's role in drug discovery, including the identification of potential candidates for rare disease treatments. Challenges and limitations related to AI in healthcare, including ethical, legal, technical, and human aspects, are addressed. This article underscores the importance of data ethics, privacy, and algorithmic fairness, as well as the need for standardized evaluation techniques and transparency in AI research. It highlights second-generation AI systems that prioritize patient-centric care, efficient patient recruitment for clinical trials, and the significance of high-quality data. The integration of AI with telemedicine, the growth of health databases, and the potential for personalized therapeutic recommendations are identified as promising directions for the field. In summary, this article provides a comprehensive exploration of how AI and ML are revolutionizing the diagnosis and treatment of RDs, addressing challenges while considering ethical implications in this rapidly evolving healthcare landscape.

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Improving the Outcome of Patients With Heart Failure: Assessment of Iron Deficiency and Intravenous Iron Replacement (2023)

Type of publication:Journal article

Author(s):*Yera, Hassan O; Khan, Ahsan; Akinlade, Olawale M; Champsi, Asgher; Glouzon, Van Nam J; Spencer, Charles.

Citation:Cureus. 15(10):e47027, 2023 Oct.

Abstract:Background Iron deficiency (ID) has been shown to be a significant co-morbidity in patients with heart failure (HF), independent of their anaemia status. Correction of ID has been shown to improve quality of life, recurrent heart failure hospitalizations and morbidity. A quality improvement project was designed to improve the assessment and treatment of iron deficiency in HFatients in our tertiary care centre. Methods and results An initial baseline dataset was collected, followed by two cycles of interventions to help improve the care of HF patients admitted to our hospital over a two-month period. The Plan-Do-Study-Act (PDSA) cycle approach was applied, with the first intervention involving raising awareness of the importance and need to assess the iron status of HF patients through education provided to doctors, nurses and patients. Furthermore, information leaflets were produced and disseminated across the medical wards and through social media forums. The post-intervention datasets were collected and compared to the baseline outcomes. Baseline data showed that only four (20%) of heart failure patients had their iron status checked. Following the interventions, screening for ID increased to 80% (16), of which 85% (11) of those who identified as iron deficient received intravenous iron replacement. Conclusion The project was successful in improving the practice of screening for iron deficiency and intravenous replacement of iron in patients with HF.

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The development and acceptability of an educational and training intervention for recruiters to neonatal trials: the TRAIN project (2023)

Type of publication:Journal article

Author(s):Smith, V; Delaney, H; Hunter, A; Torgerson, D; Treweek, S; Gamble, C; Mills, N; Stanbury, K; Dempsey, E; Daly, M; O'Shea, J; Weatherup, K; *Deshpande, S; Ryan, M A; Lowe, J; Black, G; Devane, D.

Citation:BMC Medical Research Methodology. 23(1):265, 2023 Nov 11.

Abstract:BACKGROUND: Suboptimal or slow recruitment affects 30-50% of trials. Education and training of trial recruiters has been identified as one strategy for potentially boosting recruitment to randomised controlled trials (hereafter referred to as trials). The Training tRial recruiters, An educational INtervention (TRAIN) project was established to develop and assess the acceptability of an education and training intervention for recruiters to neonatal trials. In this paper, we report the development and acceptability of TRAIN. METHODS: TRAIN involved three sequential phases, with each phase contributing information to the subsequent phase(s). These phases were 1) evidence synthesis (systematic review of the effectiveness of training interventions and a content analysis of the format, content, and delivery of identified interventions), 2) intervention development using a Partnership (co-design/co-creation) approach, and 3) intervention acceptability assessments with recruiters to neonatal trials. RESULTS: TRAIN, accompanied by a comprehensive intervention manual, has been designed for online or in-person delivery. TRAIN can be offered to recruiters before trial recruitment begins or as refresher sessions during a trial. The intervention consists of five core learning outcomes which are addressed across three core training units. These units are the trial protocol (Unit 1, 50 min, trial-specific), understanding randomisation (Unit 2, 5 min, trial-generic) and approaching and engaging with parents (Unit 3, 70 min, trial-generic). Eleven recruiters to neonatal trials registered to attend the acceptability assessment training workshops, although only four took part. All four positively valued the training Units and resources for increasing recruiter preparedness, knowledge, and confidence. More flexibility in how the training is facilitated, however, was noted (e.g., training divided across two workshops of shorter duration). Units 2 and 3 were considered beneficial to incorporate into Good Clinical Practice Training or as part of induction training for new staff joining neonatal units. CONCLUSION: TRAIN offers a comprehensive co-produced training and education intervention for recruiters to neonatal trials. TRAIN was deemed acceptable, with minor modification, to neonatal trial recruiters. The small number of recruiters taking part in the acceptability assessment is a limitation. Scale-up of TRAIN with formal piloting and testing foreffectiveness in a large cluster randomised trial is required.

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Echocardiographic Assessment of the Left Ventricle in Young Prehypertensive Nigerians (2023)

Type of publication:Journal article

Author(s):Oboirien, Isa O; *Yera, Hassan O; Akinlade, Olawale M; Omoniyi, Oluwamayowa N; Umar, Hayatu; Sani, Mahmoud U.

Citation:Cureus. 15(10):e46740, 2023 Oct

Abstract:BACKGROUND: Prehypertension is associated with an increased risk of cardiovascular morbidity and mortality. This risk could partly be explained by the early compromise in left ventricular (LV) structure and function. This study investigated the LV geometry and function in young black prehypertensive subjects. METHODS AND RESULTS: This cross-sectional descriptive study was conducted at the Usmanu Danfodiyo University Teaching Hospital, Sokoto, Nigeria. Echocardiography-derived LV geometry and function were assessed using standardized methods. Prehypertensive subjects had higher mean systolic blood pressure (BP) (130.78 +/- 3.57 mmHg vs 111.42 +/- 3.54 mmHg, P<0.001), diastolic BP (79.32 +/- 4.13 mmHg vs 66.39 +/- 4.42 mmHg, P<0.001), body mass index (BMI) (26.24 +/- 3.45 kg/m2 vs 22.20 +/- 2.21 kg/m2, P<0.001), waist circumference (WC) (86.93 +/- 8.73 cm vs 76.73 +/- 6.66 cm, P<0.001), fasting blood glucose (FBG) (93.84 +/- 7.28 mg/dl vs 90.08 +/- 6.26 mg/dl, P<0.001), and dyslipidemia (21.5% vs 6%. P<0.001) compared to normotensive subjects. LV mass index (LVMI) was greater in prehypertensive subjects compared to normotensive subjects {male (106.84 +/- 12.34 g/m2 vs 76.07 +/- 10.25 g/m2, P<0.001); female (92.06 +/- 8.80 g/m2 vs 66.53 +/- 7.21 g/m2, P<0.001)}, with abnormal LV geometry recorded in 17.5%. Linear regression analysis showed that waist circumference, systolic BP, serum creatinine level, and urea level were determinants of LVMI. The prevalence of LV diastolic dysfunction was higher in prehypertensive subjects than in normotensive subjects (14.5% vs. 0.5%, P<0.001), with systolic BP {odds ratio (OR) 0.928, confidence interval (CI) 0.834 – 0.969; P=0.016)} and diastolic BP (OR 0.832, CI 0.722 – 0.958; P=0.011) being independent predictors. CONCLUSION: This study showed that prehypertension in young Black subjects was associated with altered LV geometry and impaired diastolic function, and these changes demonstrated linear progression with increasing systolic BP

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Endocervical crypt involvement by high-grade cervical intraepithelial neoplasia and its association with high-grade histopathological recurrence after cervical excision in women with negative excision margins: a systematic review and meta-analysis (2023)

Type of publication:
Journal article

Author(s):
*Papoutsis, Dimitrios; *Underwood, Martyn; *Parry-Smith, William; Tzavara, Chara.

Citation:
Archives of Gynecology & Obstetrics. 2023 Oct 11.

Abstract:
BACKGROUND: There is a growing body of evidence suggesting that endocervical crypt involvement by high-grade cervical intraepithelial neoplasia (CIN) may represent a risk factor for disease recurrence after cervical treatment. OBJECTIVES: To provide a systematic review and meta-analysis on whether endocervical crypt involvement by high-grade CIN on the excised cervical specimen is associated with high-grade histopathological recurrence during the follow-up of women after cervical excisional treatment. SEARCH STRATEGY: We searched the Medline, Scopus, Central, and Clinical Trials.gov databases from inception till May 2023. SELECTION CRITERIA: Studies that reported on women with a single cervical treatment with any method of excision for CIN2 or CIN3 lesion, negative excision margins, and whose recurrence was defined histopathologically were included. DATA COLLECTION AND ANYSIS: Two reviewers independently evaluated study eligibility. We used the fixed effects model for meta-analysis. MAIN RESULTS: There were 4 eligible studies included in the present systematic review that evaluated 1088 women treated with either large loop excision of the transformation zone (LLETZ) or with cold knife conization (CKC). We found no significant association of endocervical crypt involvement by CIN2-3 with high-grade histopathological recurrence at follow-up after cervical excision (OR 1.93; 95% CI 0.51-3.35). The subgroup analysis of women with LLETZ cervical excision showed again no significant association with high-grade histopathological recurrence at follow-up (OR 2.00; 95% CI 0.26-3.74). CONCLUSION: Endocervical crypt involvement by high-grade CIN does not seem to be a risk factor for high-grade histopathological recurrence after cervical excision with negative excision margins.

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