A rare case of isolated laryngeal metastasis 23 years after nephrectomy for clear cell renal carcinoma (2021)

Type of publication:
Journal article

Author(s):
*Eastwood, Michael J ; *Ahsan, Syed F; *Harris, Richard

Citation:
British Journal of Hospital Medicine; Aug 2021; vol. 82 (no. 8); p. 1-3

Abstract:
The article describes the case of isolated laryngeal metastasis 23 years after nephrectomy for clear cell renal
carcinoma in an 84-year-old man.

An international genome-wide meta-analysis of primary biliary cholangitis: Novel risk loci and candidate drugs (2021)

Type of publication:
Systematic Review

Author(s):
Cordell H.J.; Fryett J.J.; Darlay R.; Ueno K.; Khor S.-S.; Kawai Y.; Tokunaga K.; Aiba Y.; Nakamura M.; Hitomi Y.; Kawashima M.; Nishida N.; Gervais O.; Nagasaki M.; Tang R.; Ma X.; Shi Y.; Li Z.; Juran B.D.; Cheung A.; Lazaridis K.N.; Atkinson E.J.; de Andrade M.; Gerussi A.; Carbone M.; Invernizzi P.; Cristoferi L.; D’Amato D.; Malinverno F.; Mancuso C.; Massironi S.; Milani C.; Ronca V.; Asselta R.; Baras A.; Horowitz J.; Ferreira M.A.R.; Sun D.; Jones D.E.; Flack S.; Spicer A.; Mulcahy V.L.; Sandford R.N.; Mells G.F.; Byan J.; Han Y.; Amos C.I.; Hirschfield G.M.; Seldin M.F.; Siminovitch K.A.; Mason A.; Vincent C.; Xie G.; Zhang J.; Affronti A.; Almasio P.L.; Alvaro D.; Andreone P.; Andriulli A.; Azzaroli F.; Battezzati P.M.; Benedetti A.; Bragazzi M.; Brunetto M.; Bruno S.; Calvaruso V.; Cardinale V.; Casella G.; Cazzagon N.; Ciaccio A.; Coco B.; Colli A.; Colloredo G.; Colombo M.; Colombo S.; Cursaro C.; Croce L.S.; Crosignani A.; Donato F.; Elia G.; Ferrari C.; Fabris L.; Fagiuoli S.; Floreani A.; Galli A.; Marra F.; Giannini E.; Grattagliano I.; Lampertico P.; Lleo A.; Marzioni M.; Mattalia A.; Miele L.; Morini L.; Morisco F.; Muratori L.; Muratori P.; Niro G.A.; O’Donnell S.; Picciotto A.; Portincasa P.; Rigamonti C.; Rosina F.; Spinzi G.; Strazzabosco M.; Tarocchi M.; Tiribelli C.; Toniutto P.; Valenti L.; Vinci M.; Zuin M.; Nakamura H.; Abiru S.; Nagaoka S.; Komori A.; Yatsuhashi H.; Ishibashi H.; Ito M.; Migita K.; Ohira H.; Katsushima S.; Naganuma A.; Sugi K.; Komatsu T.; Mannami T.; Matsushita K.; Yoshizawa K.; Makita F.; Nikami T.; Nishimura H.; Kouno H.; Ota H.; Komura T.; Nakamura Y.; Shimada M.; Hirashima N.; Komeda T.; Ario K.; Nakamuta M.; Yamashita T.; Furuta K.; Kikuchi M.; Naeshiro N.; Takahashi H.; Mano Y.; Tsunematsu S.; Yabuuchi I.; Shimada Y.; Yamauchi K.; Sugimoto R.; Sakai H.; Mita E.; Koda M.; Tsuruta S.; Kamitsukasa H.; Sato T.; Masaki N.; Kobata T.; Fukushima N.; Ohara Y.; Muro T.; Takesaki E.; Takaki H.; Yamamoto T.; Kato M.; Nagaoki Y.; Hayashi S.; Ishida J.; Watanabe Y.; Kobayashi M.; Koga M.; Saoshiro T.; Yagura M.; Hirata K.; Tanaka A.; Takikawa H.; Zeniya M.; Abe M.; Onji M.; Kaneko S.; Honda M.; Arai K.; Arinaga-Hino T.; Hashimoto E.; Taniai M.; Umemura T.; Joshita S.; Nakao K.; Ichikawa T.; Shibata H.; Yamagiwa S.; Seike M.; Honda K.; Sakisaka S.; Takeyama Y.; Harada M.; Senju M.; Yokosuka O.; Kanda T.; Ueno Y.; Kikuchi K.; Ebinuma H.; Himoto T.; Yasunami M.; Murata K.; Mizokami M.; Kawata K.; Shimoda S.; Miyake Y.; Takaki A.; Yamamoto K.; Hirano K.; Ichida T.; Ido A.; Tsubouchi H.; Chayama K.; Harada K.; Nakanuma Y.; Maehara Y.; Taketomi A.; Shirabe K.; Soejima Y.; Mori A.; Yagi S.; Uemoto S.; H E.; Tanaka T.; Yamashiki N.; Tamura S.; Sugawara Y.; Kokudo N.; Chalasani N.; Luketic V.; Odin J.; Chopra K.; Abecasis G.; Cantor M.; Coppola G.; Economides A.; Lotta L.A.; Overton J.D.; Reid J.G.; Shuldiner A.; Beechert C.; Forsythe C.; Fuller E.D.; Gu Z.; Lattari M.; Lopez A.; Schleicher T.D.; Padilla M.S.; Toledo K.; Widom L.; Wolf S.E.; Pradhan M.; Manoochehri K.; Ulloa R.H.; Bai X.; Balasubramanian S.; Barnard L.; Blumenfeld A.; Eom G.; Habegger L.; Hawes A.; Khalid S.; Maxwell E.K.; Salerno W.; Staples J.C.; Jones M.B.; Mitnaul L.J.; Sturgess R.; Healey C.; Yeoman A.; Gunasekera A.V.; Kooner P.; Kapur K.; Sathyanarayana V.; Kallis Y.; Subhani J.; Harvey R.; McCorry R.; Rooney P.; Ramanaden D.; Evans R.; Mathialahan T.; Gasem J.; Shorrock C.; Bhalme M.; Southern P.; Tibble J.A.; Gorard D.A.; Jones S.; Mells G.; Mulcahy V.; Srivastava B.; Foxton M.R.; Collins C.E.; Elphick D.; Karmo M.; Porras-Perez F.; Mendall M.; Yapp T.; Patel M.; Ede R.; Sayer J.; Jupp J.; Fisher N.; Carter M.J.; Koss K.; Shah J.; Piotrowicz A.; Scott G.; Grimley C.; Gooding I.R.; Williams S.; Tidbury J.; Lim G.; Cheent K.; Levi S.; Mansour D.; Beckley M.; Hollywood C.; Wong T.; Marley R.; Ramage J.; Gordon H.M.; Ridpath J.; Ngatchu T.; Bob Grover V.P.; Shidrawi R.G.; Abouda G.; Corless L.; Narain M.; Rees I.; Brown A.; Taylor-Robinson S.; Wilkins J.; Grellier L.; Banim P.; Das D.; Heneghan M.A.; Curtis H.; Matthews H.C.; Mohammed F.; Aldersley M.; Srirajaskanthan R.; Walker G.; McNair A.; Sharif A.; Sen S.; Bird G.; Prince M.I.; Prasad G.; Kitchen P.; Barnardo A.; Oza C.; Sivaramakrishnan N.N.; Gupta P.; Shah A.; Evans C.D.; Saha S.; Pollock K.; Bramley P.; Mukhopadhya A.; Barclay S.T.; McDonald N.; Bathgate A.J.; Palmer K.; Dillon J.F.; Rushbrook S.M.; Przemioslo R.; McDonald C.; Millar A.; Tai C.; Mitchell S.; Metcalf J.; Shaukat S.; Ninkovic M.; Shmueli U.; Davis A.; Naqvi A.; Lee T.J.; Ryder S.; Collier J.; Klass H.; Cramp M.E.; Sharer N.; Aspinall R.; Ghosh D.; Douds A.C.; Booth J.; Williams E.; Hussaini H.; Christie J.; Mann S.; Thorburn D.; Marshall A.; Patanwala I.; Ala A.; Maltby J.; Matthew R.; Corbett C.; Vyas S.; Singhal S.; Gleeson D.; Misra S.; *Butterworth J.; George K.; Harding T.; Douglass A.; Mitchison H.; Panter S.; Shearman J.; Bray G.; Roberts M.; Butcher G.; Forton D.; Mahmood Z.; Cowan M.; Ch’ng C.L.; Rahman M.; Whatley G.C.A.; Wesley E.; Mandal A.; Jain S.; Pereira S.P.; Wright M.; Trivedi P.; Gordon F.H.; Unitt E.; Palejwala A.; Austin A.; Vemala V.; Grant A.; Higham A.D.; Brind A.; Mathew R.; Cox M.; Ramakrishnan S.; King A.; Whalley S.; Fraser J.; Thomson S.J.; Bell A.; Wong V.S.; Kia R.; Gee I.; Keld R.; Ransford R.; Gotto J.; Millson C.

Citation:
Journal of Hepatology; 2021

Abstract:
Backgrounds & Aims: Primary biliary cholangitis (PBC) is a chronic liver disease in which autoimmune destruction of the small intrahepatic bile ducts eventually leads to cirrhosis. Many patients have inadequate response to licensed medications, motivating the search for novel therapies. Previous genome-wide association studies (GWAS) and meta-analyses (GWMA) of PBC have identified numerous risk loci for this condition, providing insight into its aetiology. We undertook the largest GWMA of PBC to date, aiming to identify additional risk loci and prioritise candidate genes for in silico drug efficacy screening.
Method(s): We combined new and existing genotype data for 10,516 cases and 20,772 controls from 5 European and 2 East Asian cohorts.
Result(s): We identified 56 genome-wide significant loci (20 novel) including 46 in European, 13 in Asian, and 41 in combined cohorts; and a 57th genome-wide significant locus (also novel) in conditional analysis of the European cohorts. Candidate genes at newly identified loci include FCRL3, INAVA, PRDM1, IRF7, CCR6, CD226, and IL12RB1, which each play key roles in immunity. Pathway analysis reiterated the likely importance of pattern recognition receptor and TNF signalling, JAK-STAT signalling, and differentiation of T helper (TH)1 and TH17 cells in the pathogenesis of this disease. Drug efficacy screening identified several medications predicted to be therapeutic in PBC, some of which are well-established in the treatment of other autoimmune
disorders.
Conclusion(s): This study has identified additional risk loci for PBC, provided a hierarchy of agents that could be trialled in this condition, and emphasised the value of genetic and genomic approaches to drug discovery in complex disorders. Lay summary: Primary biliary cholangitis (PBC) is a chronic liver disease that eventually leads to cirrhosis. In this study, we analysed genetic information from 10,516 people with PBC and 20,772 healthy individuals recruited in Canada, China, Italy, Japan, the UK, or the USA. We identified several genetic regions associated with PBC. Each of these regions contains several genes. For each region, we used diverse sources of evidence to help us choose the gene most likely to be involved in causing PBC. We used these
‘candidate genes’ to help us identify medications that are currently used for treatment of other conditions, which might also be useful for treatment of PBC.

Variable clinical presentations of renal cyst and diabetes (RCAD) syndrome in two patients (2019)

Type of publication:
Conference abstract

Author(s):
*Al-Salihi A.; *Kandaswamy L.; *Qamar S.; *Rangan S.; *Moulik P.; *Singh P.K.

Citation:
Diabetic Medicine; Mar 2019; vol. 36 ; p. 86

Abstract:
Maturity onset diabetes of the young Type 5 (MODY 5), known as RCAD syndrome, results from mutations in the hepatocyte nuclear factor 1-beta (HNF1B), most commonly 17q12 deletion. We present two patients with this syndrome: Patient 1: A 31 year old male presented with symptomatic hyperglycaemia. He was diagnosed with diabetes three months previously and had been treated with a sulphonylurea. His past medical history included deranged liver function tests (LFT), azoospermia and a single functioning dysplastic kidney. He had a family history of diabetes in first-degree relatives. Genetic tests confirmed HNF1B heterozygous whole gene deletion. Patient 2: A 34 year old male with diabetes diagnosed two years previously was referred for his
complex medical background. He had a history of renal problems (renal agenesis on right and cysts on left), gout and deranged LFT. His glycaemic control was adequate on Linagliptin monotherapy. Despite the absence of relevant family history, he has been referred for genetic testing.
Discussion(s): RCAD syndrome comprises 2% of all cases of MODY and features renal cysts and diabetes alongside a spectrum of other conditions such as renal dysplasia/hypoplasia/agenesis, reproductive tract anomalies, psychiatric problems, deranged LFTs and other metabolic abnormalities in various combinations. Genetic mutations can be inherited or sporadic. Absence of family history and variability in clinical manifestations can lead to delayed recognition.
Conclusion(s): Patients with RCAD syndrome can present with a varied combination of clinical features. Clinical suspicion, irrespective of family history, is key to diagnosis and management.

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