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1. Respiratory problems associated with liver disease in children

Author

Jordache Ellis, Tassos Grammatikopoulos, James Cook, and Akash Deep

Subjects
Diseases of the respiratory system, RC705-779
Abstract

Respiratory manifestations of chronic liver disease have a profound impact on patient clinical outcomes. Certain conditions within paediatric liver disease have an associated respiratory pathology. This overlap between liver and respiratory manifestations can result in complex challenges when managing patients and requires clinicians to be able to recognise when referral to specialists is required. While liver transplantation is at the centre of treatment, it opens up further potential for respiratory complications. It is established that these complications place patients at risk of longer stays in hospital and reduced survival. Additionally, late post-transplant complications can occur, including post-transplant lymphoproliferative disease and immunosuppression-induced interstitial lung disease. Although rare, it is important for clinicians to recognise these conditions to allow for prompt management. Finally, as liver disease progresses in children, respiratory complications can occur. Hepatopulmonary syndrome can occur in the context of portal hypertension, resulting in increased mortality and poorer quality of life for patients. Another consequence is portopulmonary hypertension, which can be associated with poor survival. Failure to recognise these complications in children may result in poorer outcomes and therefore it is vital that clinicians can establish when referral to a paediatric respiratory medicine specialist is required.

Published
2024
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2. Transient elastography and von Willebrand factor as predictors of portal hypertension and decompensation in children

Author

Akshat Goel, Robert Hegarty, Shweta Dixit, Bethany Tucker, Abdel Douiri, Eirini Kyrana, Vandana Jain, Anil Dhawan, and Tassos Grammatikopoulos

Subjects
Biomarkers, Clinically significant varices, Variceal Bleeding, Liver Stiffness, Spleen Stiffness, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Background & Aims: Von Willebrand factor antigen (vWFAg), a protein measured to test the level of vWF released from the vascular endothelium has gained much attention as a marker for portal hypertension (PHT) severity. The objectives of this study were to investigate the use of vWFAg as a biomarker along with liver and spleen stiffness measurements by transient elastography as potential predictors of clinically significant varices (CSV), variceal bleeding (VB) and decompensation in children with PHT. Methods: This observational prospective cohort study included 117 children (median age 10 [IQR 6-14] years) who underwent oesophagogastroduodenoscopy between January’2012 to November’2021 and a validation group of 33 children who underwent the same procedure between December’2021 to March’2023. Measurements of vWFAg and glycoprotein Ib binding activity of VWF (GPIbR) were available in 97 patients in the study group and in all patients in the validation group.Results: vWFAg and GPIbR were significantly higher in children with CSV (223 IU/dl and 166 IU/dl; p = 0.015 and p = 0.04, respectively) and VB (218 IU/dl and 174 IU/dl; p = 0.077 and p = 0.03, respectively) than in those without CSV or VB, respectively. Ninety-six patients had liver and spleen stiffness measurements. Spleen stiffness was significantly higher in patients with CSV compared to those without CSV (p = 0.003). In a chronic liver disease subgroup, a predictive scoring tool based on vWFAg, GPIbR, platelet count, and spleen/liver stiffness measurements could predict CSV with an AUROC of 0.76 (p = 0.04). Conclusions: This study suggests the predictive value of vWF for CSV and VB increases when combined with spleen stiffness, with AUROCs of 0.88 and 0.82, respectively. Hence, a combination of biomarkers could assist clinicians in diagnosing CSV, preventing unnecessary invasive procedures. Impacts and implications: Surveillance endoscopies in children with portal hypertension (PHT) have their own risks and non-invasive markers, such as von Willebrand factor antigen, glycoprotein Ib binding activity of VWF (GPIbR), and transient elastography could be used to predict clinically significant varices, variceal bleeding and disease compensation in children with PHT. Such non-invasive markers for PHT and varices are lacking in the paediatric population. The results show that von Willebrand factor and GPIbR along with transient elastography can be used to formulate a scoring system which can be used as a clinical tool by paediatric hepatologists to monitor the progression of PHT and risk of bleeding, and hence to stratify the performance of invasive endoscopic procedures under general anaesthesia. However, there is a need to validate the scoring system in children with portal vein thrombosis and for hepatic decompensation in a multi-centre registry in the future.

Published
2023
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3. Noble metal catalyst detection in rocks using machine-learning: The future to low-cost, green energy materials?

Author

Elena Ifandi, Daphne Teck Ching Lai, Stavros Kalaitzidis, Muhammad Saifullah Abu Bakar, Tassos Grammatikopoulos, Chun-Kit Lai, and Basilios Tsikouras

Subjects
Medicine, Science
Abstract

Abstract Carbon capture and catalytic conversion to methane is promising for carbon–neutral energy production. Precious metals catalysts are highly efficient; yet they have several significant drawbacks including high cost, scarcity, environmental impact from the mining and intense processing requirements. Previous experimental studies and the current analytical work show that refractory grade chromitites (chromium rich rocks with Al2O3 > 20% and Cr2O3 + Al2O3 > 60%) with certain noble metal concentrations (i.e., Ir: 17–45 ppb, Ru: 73–178 ppb) catalyse Sabatier reactions and produce abiotic methane; a process which has not been investigated at the industrial scale. Thus, a natural source (chromitites) hosting noble metals might be used instead of concentrating noble metals for catalysis. Stochastic machine-learning algorithms show that among the various phases, the noble metal alloys are natural methanation catalysts. Such alloys form when pre-existing platinum group minerals (PGM) are chemically destructed. Chemical destruction of existing PGM results to mass loss forming locally a nano-porous surface. The chromium-rich spinel phases, hosting the PGM inclusions, are subsequently a second-tier support. The current work is the first multi-disciplinary research showing that noble metal alloys within chromium-rich rocks are double-supported, Sabatier catalysts. Thus, such sources could be a promising material in the search of low-cost, sustainable materials for green energy production.

Published
2023
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4. Interim results from an ongoing, open-label, single-arm trial of odevixibat in progressive familial intrahepatic cholestasis

Author

Richard J. Thompson, Reha Artan, Ulrich Baumann, Pier Luigi Calvo, Piotr Czubkowski, Buket Dalgic, Lorenzo D’Antiga, Angelo Di Giorgio, Özlem Durmaz, Emmanuel Gonzalès, Tassos Grammatikopoulos, Girish Gupte, Winita Hardikar, Roderick H.J. Houwen, Binita M. Kamath, Saul J. Karpen, Florence Lacaille, Alain Lachaux, Elke Lainka, Kathleen M. Loomes, Cara L. Mack, Jan P. Mattsson, Patrick McKiernan, Quanhong Ni, Hasan Özen, Sanjay R. Rajwal, Bertrand Roquelaure, Eyal Shteyer, Etienne Sokal, Ronald J. Sokol, Nisreen Soufi, Ekkehard Sturm, Mary Elizabeth Tessier, Wendy L. van der Woerd, Henkjan J. Verkade, Jennifer M. Vittorio, Terese Wallefors, Natalie Warholic, Qifeng Yu, Patrick Horn, and Lise Kjems

Subjects
Liver diseases, Bile acids and salts, Clinical trial, Enterohepatic circulation, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Background & Aims: PEDFIC 2, an ongoing, open-label, 72-week study, evaluates odevixibat, an ileal bile acid transporter inhibitor, in patients with progressive familial intrahepatic cholestasis. Methods: PEDFIC 2 enrolled and dosed 69 patients across two cohorts; all received odevixibat 120 μg/kg per day. Cohort 1 comprised children from PEDFIC 1, and cohort 2 comprised new patients (any age). We report data through 15 July 2020, with Week 24 of PEDFIC 2 the main time point analysed. This represents up to 48 weeks of cumulative exposure for patients treated with odevixibat from the 24-week PEDFIC 1 study (cohort 1A) and up to 24 weeks of treatment for those who initiated odevixibat in PEDFIC 2 (patients who received placebo in PEDFIC 1 [cohort 1B] or cohort 2 patients). Primary endpoints for this prespecified interim analysis were change from baseline to Weeks 22–24 in serum bile acids (sBAs) and proportion of positive pruritus assessments (≥1-point drop from PEDFIC 2 baseline in pruritus on a 0–4 scale or score ≤1) over the 24-week period. Safety monitoring included evaluating treatment-emergent adverse events (TEAEs). Results: In cohort 1A, mean change from PEDFIC 1 baseline to Weeks 22–24 of PEDFIC 2 in sBAs was -201 μmol/L (p

Published
2023
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5. Physical Separations for Rare-Earth Beneficiation of the Nechalacho Deposit

Author

Christopher Marion, Justin Paris, Tassos Grammatikopoulos, Ronghao Li, Ozan Kökkılıç, Ray Langlois, Neil A. Rowson, and Kristian E. Waters

Subjects
rare-earth elements, gravity separation, magnetic separation, QEMSCAN, Mineralogy, QE351-399.2
Abstract

The rare-earth elements (REEs) are strategic metals which are indispensable to the development of modern defence systems, electronic applications, and green technologies. The growing economic and strategic importance of these sectors, coupled with uncertainty in the global supply, has led to the development of many new deposits around the world. Many of these deposits, such as the Nechalacho deposit, are complex and contain multiple rare-earth element-bearing minerals (REMs) for which there is limited processing knowledge. This study explores a physical-separations-based flowsheet to beneficiate the Nechalacho deposit, which employs a spiral concentrator to preconcentrate the ore at a relatively coarse particle size (d80 = 120 μm), before further size reduction (d100 = 53 μm) and separation using a Mozley laboratory shaking table and two stages (low- and high-intensity) of magnetic separation. QEMSCAN was used to understand the effectiveness of each stage of separation and provide recommendations to improve the process. Although optimisation would be required, the results demonstrate that the physical-separations-based flowsheet could be an effective method of beneficiation.

Published
2023
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6. Liver Disease and Risk of Hepatocellular Carcinoma in Children With Mutations in TALDO1

Author

Tassos Grammatikopoulos, Nedim Hadzic, Pierre Foskett, Sandra Strautnieks, Marianne Samyn, Roshni Vara, Anil Dhawan, Jozef Hertecant, Fatma Al Jasmi, Obydur Rahman, University of Washington Center for Mendelian Genomics, Maesha Deheragoda, Laura N. Bull, and Richard J Thompson

Subjects
Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Mutations in the transaldolase 1 (TALDO1) gene have been described in a limited number of cases. Several organs can be affected and clinical manifestations are variable, but often include liver dysfunction and/or hepatosplenomegaly. We report 4 patients presenting with liver disease: 2 with early‐onset hepatocellular carcinoma (HCC). Patients with cholestasis and mutations in TALDO1 were identified by next‐generation sequencing. Clinical, laboratory, and histological data were collected. Four (1 male) patients were identified with variants predicted to be damaging in TALDO1. Three patients were homozygous (two protein truncating/one missense mutations), 1 one was compound heterozygous (two missense mutations). Median age at presentation was 4 months (range, 2‐210 days) with jaundice (3), hepatosplenomegaly (3), and pancytopaenia (1). The diagnosis was corroborated by detection of minimal transaldolase enzyme activity in skin fibroblasts in two cases and raised urine polyols in the third. Three patients underwent liver transplantation (LT), 2 of whom had confirmed HCC on explanted liver. One patient suddenly died shortly after LT. The nontransplanted case has a chronic liver disease with multiple dysplastic liver nodules, but normal liver biochemistry and alpha‐fetoprotein. Median follow‐up was 4 years (range, 1‐21). Conclusion: Transaldolase deficiency can include early‐onset normal gamma‐glutamyltransferase liver disease with multisystem involvement and variable progression. Patients with this disease are at risk of early‐onset HCC and may require early LT.

Published
2022
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7. Use and safety of prophylactic endoscopy from a single center serving urban and rural children with portal hypertension

Author

Voytek Slowik, Anissa Bernardez, Heather Wasserkrug, Ryan T. Fischer, James F. Daniel, and Tassos Grammatikopoulos

Subjects
Medicine, Science
Abstract

Abstract Prophylactic endoscopy is routine in adults with portal hypertension (PHTN), but there is limited data in pediatrics. We sought to describe our experience with prophylactic endoscopy in pediatric PHTN. This is a retrospective study of 87 children who began surveillance endoscopy prior to gastrointestinal bleeding (primary prophylaxis) and 52 who began after an episode of bleeding (secondary prophylaxis) from 01/01/1994 to 07/01/2019. Patients who underwent primary prophylaxis had a lower mean number of endoscopies (3.897 vs 6.269, p = 0.001). The primary prophylaxis group was less likely to require a portosystemic shunt (6% vs 15%, p

Published
2022
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8. Genotype-phenotype relationships of truncating mutations, p.E297G and p.D482G in bile salt export pump deficiency

Author

Antonia Felzen, Daan B.E. van Wessel, Emmanuel Gonzales, Richard J. Thompson, Irena Jankowska, Benjamin L. Shneider, Etienne Sokal, Tassos Grammatikopoulos, Agustina Kadaristiana, Emmanuel Jacquemin, Anne Spraul, Patryk Lipiński, Piotr Czubkowski, Nathalie Rock, Mohammad Shagrani, Dieter Broering, Emanuele Nicastro, Deirdre Kelly, Gabriella Nebbia, Henrik Arnell, Björn Fischler, Jan B.F. Hulscher, Daniele Serranti, Cigdem Arikan, Esra Polat, Dominique Debray, Florence Lacaille, Cristina Goncalves, Loreto Hierro, Gema Muñoz Bartolo, Yael Mozer-Glassberg, Amer Azaz, Jernej Brecelj, Antal Dezsőfi, Pier Luigi Calvo, Enke Grabhorn, Steffen Hartleif, Wendy J. van der Woerd, Binita M. Kamath, Jian-She Wang, Liting Li, Özlem Durmaz, Nanda Kerkar, Marianne Hørby Jørgensen, Ryan Fischer, Carolina Jimenez-Rivera, Seema Alam, Mara Cananzi, Noemie Laverdure, Cristina Targa Ferreira, Felipe Ordoñez Guerrero, Heng Wang, Valerie Sency, Kyung Mo Kim, Huey-Ling Chen, Elisa de Carvalho, Alexandre Fabre, Jesus Quintero Bernabeu, Aglaia Zellos, Estella M. Alonso, Ronald J. Sokol, Frederick J. Suchy, Kathleen M. Loomes, Patrick J. McKiernan, Philip Rosenthal, Yumirle Turmelle, Simon Horslen, Kathleen Schwarz, Jorge A. Bezerra, Kasper Wang, Bettina E. Hansen, and Henkjan J. Verkade

Subjects
BSEP, PFIC2, compound heterozygosity, interruption of the enterohepatic circulation, genotype, phenotype, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Background & Aims: Bile salt export pump (BSEP) deficiency frequently necessitates liver transplantation in childhood. In contrast to two predicted protein truncating mutations (PPTMs), homozygous p.D482G or p.E297G mutations are associated with relatively mild phenotypes, responsive to surgical interruption of the enterohepatic circulation (siEHC). The phenotype of patients with a compound heterozygous genotype of one p.D482G or p.E297G mutation and one PPTM has remained unclear. We aimed to assess their genotype-phenotype relationship. Methods: From the NAPPED database, we selected patients with homozygous p.D482G or p.E297G mutations (BSEP1/1; n = 31), with one p.D482G or p.E297G, and one PPTM (BSEP1/3; n = 30), and with two PPTMs (BSEP3/3; n = 77). We compared clinical presentation, native liver survival (NLS), and the effect of siEHC on NLS. Results: The groups had a similar median age at presentation (0.7-1.3 years). Overall NLS at age 10 years was 21% in BSEP1/3 vs. 75% in BSEP1/1 and 23% in BSEP3/3 (p

Published
2023
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9. Novel compound heterozygous STN1 variants are associated with Coats Plus syndrome

Author

Tanvi Acharya, Helen V. Firth, Shilpa Dugar, Tassos Grammatikopoulos, Luis Seabra, Angharad Walters, Yanick J. Crow, and Alasdair P. J. Parker

Subjects
coats plus, leukodystrophy, stn1, Genetics, QH426-470
Abstract

Abstract Aim Coats plus syndrome (CP) is a rare autosomal recessive disorder, characterised by retinal telangiectasia exudates (Coats disease), leukodystrophy, distinctive intracranial calcification and cysts, as well as extra‐neurological features including abnormal vasculature of the gastrointestinal tract, portal hypertension and osteopenia with a tendency to fractures. CP most frequently occurs due to loss‐of‐function mutations in CTC1. The encoded protein CTC1 constitutes part of the CST (CTC1‐STN1‐TEN1) complex, and three patients have been described with CP due to biallelic mutations in STN1. Together with the identification of homozygosity for a specific loss‐of‐function mutation in POT1 in a sibling pair, these observations highlight a defect in the maintenance of telomere integrity as the cause of CP, although the precise mechanism leading to the micro‐vasculopathy seen at a pathological level remains unclear. Here, we present the investigation of a fourth child who presented to us with retinal exudates, intracranial calcifications and developmental delay, in keeping with a diagnosis of CP, and later went on to develop pancytopenia and gastrointestinal bleeding. Genome sequencing revealed compound heterozygous variants in STN1 as the likely genetic cause of CP in this present case. Methods We assessed the phenotype to be CP and undertook targeted sequencing. Results Whilst sequencing of CTC1 and POT1 was normal, we identified novel compound heterozygous variants in STN1 (previous gene symbol OBFC1): one loss‐of‐function––c.894dup (p.(Asp299Argfs*58)); and one missense––c.707T>C (p.(Leu236Pro)). Conclusion Given the clinical phenotype and identified variants we suggest that this is only the fourth patient reported to date with CP due to mutations in STN1.

Published
2021
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10. The Recovery and Concentration of Spodumene Using Dense Media Separation

Author

Charlotte E. Gibson, Massoud Aghamirian, Tassos Grammatikopoulos, Darren L. Smith, and Lindsay Bottomer

Subjects
lithium, spodumene, beneficiation, dense media separation, Mineralogy, QE351-399.2
Abstract

In coming years, global lithium production is expected to increase as the result of widespread electric vehicle adoption. To meet the expected increase in demand, lithium must be sourced from both brine and hard-rock deposits. Heavy liquid separation (HLS) and dense media separation (DMS) tests were conducted on the pegmatites from Hidden Lake, NWT, Canada to demonstrate the potential role of this technology in the concentration of spodumene (LiAlSi2O6) from hard-rock sources. A continuously operated DMS circuit test, conducted on +840 µm material, produced a concentrate grading 6.11% Li2O with ~50% lithium recovery. The circuit rejected 50% of the original mass to tailings, with only 8% lithium losses. Sensitivity analysis showed that minor changes (+/−0.05) in the DMS-specific gravity cut point resulted in significant changes to the mass rejected and to the concentrate grade produced; this may limit the feasibility and operability of the downstream grinding and flotation circuits. The results demonstrate the potential for DMS in the concentration of spodumene from the Hidden Lake pegmatites, and by extension, the potential for DMS in the concentration of spodumene from other hard-rock occurrences.

Published
2021
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11. Eliopoulosite, V7S8, A New Sulfide from the Podiform Chromitite of the Othrys Ophiolite, Greece

Author

Luca Bindi, Federica Zaccarini, Paola Bonazzi, Tassos Grammatikopoulos, Basilios Tsikouras, Chris Stanley, and Giorgio Garuti

Subjects
eliopoulosite, sulfide, chromitite, agios stefanos mine, othrys, ophiolite, greece, Mineralogy, QE351-399.2
Abstract

The new mineral species, eliopoulosite, V7S8, was discovered in the abandoned chromium mine of Agios Stefanos of the Othrys ophiolite, located in central Greece. The investigated samples consist of massive chromitite hosted in a strongly altered mantle tectonite, and are associated with nickelphosphide, awaruite, tsikourasite, and grammatikopoulosite. Eliopoulosite is brittle and has a metallic luster. In plane-reflected polarized light, it is grayish-brown and shows no internal reflections, bireflectance, and pleochroism. It is weakly anisotropic, with colors varying from light to dark greenish. Reflectance values of mineral in air (Ro, Re’ in %) are: 34.8−35.7 at 470 nm, 38−39 at 546 nm, 40−41.3 at 589 nm, and 42.5−44.2 at 650 nm. Electron-microprobe analyses yielded a mean composition (wt.%) of: S 41.78, V 54.11, Ni 1.71, Fe 1.1, Co 0.67, and Mo 0.66, totali 100.03. On the basis of Σatoms = 15 apfu and taking into account the structural data, the empirical formula of eliopoulosite is (V6.55Ni0.19Fe0.12Co0.07Mo0.04)Σ = 6.97S8.03. The simplified formula is (V, Ni, Fe)7S8 and the ideal formula is V7S8, which corresponds to V 58.16%, S 41.84%, total 100 wt.%. The density, based on the empirical formula and unit-cell volume refined form single-crystal structure XRD data, is 4.545 g·cm−3. The mineral is trigonal, space group P3221, with a = 6.689(3) Å, c = 17.403(6) Å, V = 674.4(5) Å3, Z = 3, and exhibits a twelve-fold superstructure (2a × 2a × 3c) of the NiAs-type subcell with V-atoms octahedrally coordinated by S atoms. The distribution of vacancies is discussed in relation to other pyrrhotite-like compounds. The mineral name is for Dr. Demetrios Eliopoulos (1947−2019), a geoscientist at the Institute of Geology and Mineral Exploration (IGME) of Greece and his widow, Prof. Maria Eliopoulos (nee Economou, 1947), University of Athens, Greece, for their contributions to the knowledge of ore deposits of Greece and to the mineralogical, petrographic, and geochemical studies of ophiolites, including the Othrys complex. The mineral and its name have been approved by the Commission of New Minerals, Nomenclature, and Classification of the International Mineralogical Association (No. 2019-96).

Published
2020
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12. Tsikourasite, Mo3Ni2P1+x (x < 0.25), a New Phosphide from the Chromitite of the Othrys Ophiolite, Greece

Author

Federica Zaccarini, Luca Bindi, Elena Ifandi, Tassos Grammatikopoulos, Chris Stanley, Giorgio Garuti, and Daniela Mauro

Subjects
tsikourasite, phosphide, chromitite, Agios Stefanos mine, Othrys, ophiolite, Greece, Mineralogy, QE351-399.2
Abstract

Tsikourasite, Mo3Ni2P1+x (x < 0.25), is a new phosphide discovered in a mantle-hosted podiform chromitite collected in the abandoned mine of Agios Stefanos (Othrys ophiolite), Central Greece. It forms tiny grains (from a few μm up to about 80 μm) and occurs as isolated grains or associated with other known minerals such as nickelphosphide and awaruite, and with undetermined minerals such as Ni-allabogdanite or Ni-barringerite and a V-sulphide. Tsikourasite is brittle and has a metallic luster. In plane-polarized light, tsikourasite is white yellow and it shows no bireflectance, anisotropism or pleochroism. Internal reflections were not observed, Reflectance values of tsikourasite in air (R in %) are: 55.7 at 470 nm, 56.8 at 546 nm, 57.5 at 589 nm and 58.5 at 650 nm. Five spot analyses of tsikourasite give the average composition: P 7.97, S 0.67, V 14.13, Fe 14.37, Co 7.59, Ni 23.9, and Mo 44.16, total 99.60 wt.%, corresponding to the empirical formula (Mo1.778V1.071Fe0.082Co0.069)Σ3.000(Ni1.572Co0.428)Σ2.000(P0.981S0.079)Σ1.060, on the basis of Σ(Mo +V + Fe + Co + Ni) = 5 apfu and taking into account the structural results. The simplified formula is Mo3Ni2P1+x (x < 0.25). The density, which was calculated based on the empirical formula and single-crystal data, is 9.182 g/cm3. The mineral is cubic, space group F-43m, with a = 10.8215(5) Å and Z = 16. Although tsikourasite is similar in composition to those of monipite (MoNiP), polekhovskyite (MoNiP2), and the synthetic compound MoNiP2, all these phases are hexagonal and not cubic like tsikourasite. It exhibits the same structure as the cubic Mo3Ni2P1.18 compound [space group F-43m, a = 10.846(2) Å] synthesized at 1350 °C. The mineral and its name have been approved by the Commission of New Minerals, Nomenclature and Classification of the International Mineralogical Association (No. 2018-156). The mineral honors Professor Basilios Tsikouras of the Universiti Brunei Darussalam.

Published
2019
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13. Primary Biliary Cirrhosis-Specific Antimitochondrial Antibodies in Neonatal Haemochromatosis

Author

Daniel S. Smyk, Maria G. Mytilinaiou, Tassos Grammatikopoulos, A. S. Knisely, Giorgina Mieli-Vergani, Dimitrios P. Bogdanos, and Diego Vergani

Subjects
Immunologic diseases. Allergy, RC581-607
Abstract

Background and Aim. Neonatal hemochromatosis (NH) is characterised by severe liver injury and extrahepatic siderosis sparing the reticuloendothelial system. Its aetiology is obscure, although it has been proposed as an alloimmune disease, resulting from immunological reaction to self-antigens (alloantigens) which the body recognizes as foreign. We studied an infant with NH and his mother whose sera contained antimitochondrial antibody (AMA), the hallmark of primary biliary cirrhosis (PBC). Material and Methods. To investigate the origin of AMA in the infant, we studied isotype distributions in serum from the mother and infant. Serum samples were obtained at diagnosis of NH, after liver transplantation (LT; age 1 month), and over the ensuing 17 months. Results. At NH diagnosis, infant and maternal serum contained AMA of the IgG isotype, predominantly of the G3 and G1 subclasses. AMA strongly reacted against the pyruvate dehydrogenase complex E2 subunit (PDC-E2), the major PBC-specific AMA autoantigen. Anti-PDC-E2 responses in both infant and mother declined over time, being present 2 months after LT (mother and child) and absent 10 months later (mother) and 17 months later (child). Conclusion. The association of maternally transferred IgG1 and IgG3 subclass AMA with the appearance of liver damage in an infant with NH may suggest a causal link between antibody and liver damage.

Published
2013
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14. Odevixibat treatment in progressive familial intrahepatic cholestasis

Author

Richard J Thompson, Henrik Arnell, Reha Artan, Ulrich Baumann, Pier Luigi Calvo, Piotr Czubkowski, Buket Dalgic, Lorenzo D'Antiga, Özlem Durmaz, Björn Fischler, Emmanuel Gonzalès, Tassos Grammatikopoulos, Girish Gupte, Winita Hardikar, Roderick H J Houwen, Binita M Kamath, Saul J Karpen, Lise Kjems, Florence Lacaille, Alain Lachaux, Elke Lainka, Cara L Mack, Jan P Mattsson, Patrick McKiernan, Hasan Özen, Sanjay R Rajwal, Bertrand Roquelaure, Mohammad Shagrani, Eyal Shteyer, Nisreen Soufi, Ekkehard Sturm, Mary Elizabeth Tessier, Henkjan J Verkade, Patrick Horn, and Center for Liver, Digestive and Metabolic Diseases (CLDM)

Subjects
Cholestasis, Adolescent, Hepatology, Pruritus, Medizin, Gastroenterology, Infant, Cholestasis, Intrahepatic, Bile Acids and Salts, Benzodiazepines, Butyrates, Child, Preschool, Humans, Child
Abstract

BACKGROUND: Progressive familial intrahepatic cholestasis (PFIC) is a group of inherited paediatric liver diseases resulting from mutations in genes that impact bile secretion. We aimed to evaluate the effects of odevixibat, an ileal bile acid transporter inhibitor, versus placebo in children with PFIC.METHODS: Patients eligible for this 24-week, randomised, double-blind, completed, phase 3 study were paediatric outpatients diagnosed with PFIC1 or PFIC2 who had pruritus and elevated serum bile acids at screening. Patients were randomly assigned (1:1:1) using an interactive web-based system to once a day oral placebo, odevixibat 40 μg/kg, or odevixibat 120 μg/kg. Randomisation was done in a block size of six and stratified by PFIC type and patient age; patients, clinicians, and study staff were blinded to treatment allocation. Patients were enrolled at one of 33 global sites. Two primary endpoints were evaluated: proportion of positive pruritus assessments (PPAs; ie, scratching score of ≤1 or ≥1-point decrease as assessed by caregivers using the Albireo observer-reported outcome [ObsRO] PRUCISION instrument) over 24 weeks, and proportion of patients with serum bile acid response (ie, serum bile acids reduced by ≥70% from baseline or concentrations of ≤70 μmol/L) at week 24. Efficacy and safety were analysed in randomly allocated patients who received one or more doses of study drug. This study is registered with ClinicalTrials.gov, NCT03566238.FINDINGS: Between June 21, 2018, and Feb 10, 2020, 62 patients (median age 3·2 [range 0·5-15·9] years) were randomly allocated to placebo (n=20), odevixibat 40 μg/kg per day (n=23), or odevixibat 120 μg/kg per day (n=19). Model-adjusted (least squares) mean proportion of PPAs was significantly higher with odevixibat versus placebo (55% [SE 8] in the combined odevixibat group [58% in the 40 μg/kg per day group and 52% in the 120 μg/kg per day group] vs 30% [SE 9] in the placebo group; model-adjusted mean difference 25·0% [95% CI 8·5-41·5]; p=0·0038). The percentage of patients with serum bile acid response was also significantly higher with odevixibat versus placebo (14 [33%] of 42 patients in the combined odevixibat group [10 in the 40 μg/kg per day group and four in the 120 μg/kg per day group] vs none of 20 in the placebo group; adjusting for stratification factor [PFIC type], the proportion difference was 30·7% [95% CI 12·6-48·8; p=0·0030]). The most common treatment-emergent adverse events (TEAEs) were diarrhoea or frequent bowel movements (13 [31%] of 42 for odevixibat vs two [10%] of 20 for placebo) and fever (12 [29%] of 42 vs five [25%] of 20); serious TEAEs occurred in three (7%) of 42 odevixibat-treated patients and in five (25%) of 20 placebo-treated patients.INTERPRETATION: In children with PFIC, odevixibat effectively reduced pruritus and serum bile acids versus placebo and was generally well tolerated. Odevixibat, administered as once a day oral capsules, is a non-surgical, pharmacological option to interrupt the enterohepatic circulation in patients with PFIC.FUNDING: Albireo Pharma.

Published
2022

19. SARS-CoV-2-specific nasal IgA wanes 9 months after hospitalisation with COVID-19 and is not induced by subsequent vaccination

Author

Felicity Liew, Shubha Talwar, Andy Cross, Brian J. Willett, Sam Scott, Nicola Logan, Matthew K. Siggins, Dawid Swieboda, Jasmin K. Sidhu, Claudia Efstathiou, Shona C. Moore, Chris Davis, Noura Mohamed, Jose Nunag, Clara King, A.A. Roger Thompson, Sarah L. Rowland-Jones, Annemarie B. Docherty, James D. Chalmers, Ling-Pei Ho, Alexander Horsley, Betty Raman, Krisnah Poinasamy, Michael Marks, Onn Min Kon, Luke Howard, Daniel G. Wootton, Susanna Dunachie, Jennifer K. Quint, Rachael A. Evans, Louise V. Wain, Sara Fontanella, Thushan I. de Silva, Antonia Ho, Ewen Harrison, J. Kenneth Baillie, Malcolm G. Semple, Christopher Brightling, Ryan S. Thwaites, Lance Turtle, Peter J.M. Openshaw, Beatrice Alex, Petros Andrikopoulos, Benjamin Bach, Wendy S. Barclay, Debby Bogaert, Meera Chand, Kanta Chechi, Graham S. Cooke, Ana da Silva Filipe, Thushan de Silva, Gonçalo dos Santos Correia, Marc-Emmanuel Dumas, Jake Dunning, Tom Fletcher, Christopher A. Green, William Greenhalf, Julian Griffin, Rishi K. Gupta, Ewen M. Harrison, Antonia Y.W. Ho, Karl Holden, Peter W. Horby, Samreen Ijaz, Say Khoo, Paul Klenerman, Andrew Law, Matthew Lewis, Sonia Liggi, Wei Shen Lim, Lynn Maslen, Alexander J. Mentzer, Laura Merson, Alison M Meynert, Mahdad Noursadeghi, Michael Olanipekun, Anthonia Osagie, Massimo Palmarini, Carlo Palmieri, William A. Paxton, Georgios Pollakis, Nicholas Price, Andrew Rambaut, David L Robertson, Clark D. Russell, Vanessa Sancho-Shimizu, Caroline Sands, Janet T. Scott, Louise Sigfrid, Tom Solomon, Shiranee Sriskandan, David Stuart, Charlotte Summers, Olivia V. Swann, Zoltan Takats, Panteleimon Takis, Richard S. Tedder, Emma C. Thomson, Lance C.W. Turtle, Maria Zambon, Thomas M. Drake, Cameron J. Fairfield, Stephen R. Knight, Kenneth A. Mclean, Derek Murphy, Lisa Norman, Riinu Pius, Catherine A. Shaw, Marie Connor, Jo Dalton, Carrol Gamble, Michelle Girvan, Sophie Halpin, Janet Harrison, Clare Jackson, James Lee, Laura Marsh, Daniel Plotkin, Stephanie Roberts, Egle Saviciute, Sara Clohisey, Ross Hendry, Susan Knight, Eva Lahnsteiner, Gary Leeming, Lucy Norris, James Scott-Brown, Sarah Tait, Murray Wham, Richard Clark, Audrey Coutts, Lorna Donelly, Angie Fawkes, Tammy Gilchrist, Katarzyna Hafezi, Louise MacGillivray, Alan Maclean, Sarah McCafferty, Kirstie Morrice, Lee Murphy, Nicola Wrobel, Gail Carson, Kayode Adeniji, Daniel Agranoff, Ken Agwuh, Dhiraj Ail, Erin L. Aldera, Ana Alegria, Sam Allen, Brian Angus, Abdul Ashish, Dougal Atkinson, Shahedal Bari, Gavin Barlow, Stella Barnass, Nicholas Barrett, Christopher Bassford, Sneha Basude, David Baxter, Michael Beadsworth, Jolanta Bernatoniene, John Berridge, Colin Berry, Nicola Best, Pieter Bothma, Robin Brittain-Long, Naomi Bulteel, Tom Burden, Andrew Burtenshaw, Vikki Caruth, David Chadwick, Duncan Chambler, Nigel Chee, Jenny Child, Srikanth Chukkambotla, Tom Clark, Paul Collini, Catherine Cosgrove, Jason Cupitt, Maria-Teresa Cutino-Moguel, Paul Dark, Chris Dawson, Samir Dervisevic, Phil Donnison, Sam Douthwaite, Andrew Drummond, Ingrid DuRand, Ahilanadan Dushianthan, Tristan Dyer, Cariad Evans, Chi Eziefula, Chrisopher Fegan, Adam Finn, Duncan Fullerton, Sanjeev Garg, Atul Garg, Effrossyni Gkrania-Klotsas, Jo Godden, Arthur Goldsmith, Clive Graham, Tassos Grammatikopoulos, Elaine Hardy, Stuart Hartshorn, Daniel Harvey, Peter Havalda, Daniel B. Hawcutt, Maria Hobrok, Luke Hodgson, Anil Hormis, Joanne Howard, Michael Jacobs, Susan Jain, Paul Jennings, Agilan Kaliappan, Vidya Kasipandian, Stephen Kegg, Michael Kelsey, Jason Kendall, Caroline Kerrison, Ian Kerslake, Oliver Koch, Gouri Koduri, George Koshy, Shondipon Laha, Steven Laird, Susan Larkin, Tamas Leiner, Patrick Lillie, James Limb, Vanessa Linnett, Jeff Little, Mark Lyttle, Michael MacMahon, Emily MacNaughton, Ravish Mankregod, Huw Masson, Elijah Matovu, Katherine McCullough, Ruth McEwen, Manjula Meda, Gary Mills, Jane Minton, Kavya Mohandas, Quen Mok, James Moon, Elinoor Moore, Patrick Morgan, Craig Morris, Katherine Mortimore, Samuel Moses, Mbiye Mpenge, Rohinton Mulla, Michael Murphy, Thapas Nagarajan, Megan Nagel, Mark Nelson, Lillian Norris, Matthew K. O'Shea, Marlies Ostermann, Igor Otahal, Mark Pais, Selva Panchatsharam, Danai Papakonstantinou, Padmasayee Papineni, Hassan Paraiso, Brij Patel, Natalie Pattison, Justin Pepperell, Mark Peters, Mandeep Phull, Stefania Pintus, Tim Planche, Frank Post, David Price, Rachel Prout, Nikolas Rae, Henrik Reschreiter, Tim Reynolds, Neil Richardson, Mark Roberts, Devender Roberts, Alistair Rose, Guy Rousseau, Bobby Ruge, Brendan Ryan, Taranprit Saluja, Sarah Sarah, Matthias Schmid, Aarti Shah, Manu Shankar-Hari, Prad Shanmuga, Anil Sharma, Anna Shawcross, Jagtur Singh Pooni, Jeremy Sizer, Richard Smith, Catherine Snelson, Nick Spittle, Nikki Staines, Tom Stambach, Richard Stewart, Pradeep Subudhi, Tamas Szakmany, Kate Tatham, Jo Thomas, Chris Thompson, Robert Thompson, Ascanio Tridente, Darell Tupper-Carey, Mary Twagira, Nick Vallotton, Rama Vancheeswaran, Rachel Vincent, Lisa Vincent-Smith, Shico Visuvanathan, Alan Vuylsteke, Sam Waddy, Rachel Wake, Andrew Walden, Ingeborg Welters, Tony Whitehouse, Paul Whittaker, Ashley Whittington, Meme Wijesinghe, Martin Williams, Lawrence Wilson, Stephen Winchester, Martin Wiselka, Adam Wolverson, Daniel G Wootton, Andrew Workman, Bryan Yates, Peter Young, Sarah E. McDonald, Victoria Shaw, Katie A. Ahmed, Jane A. Armstrong, Milton Ashworth, Innocent G. Asiimwe, Siddharth Bakshi, Samantha L Barlow, Laura Booth, Benjamin Brennan, Katie Bullock, Nicola Carlucci, Emily Cass, Benjamin W.A. Catterall, Jordan J. Clark, Emily A. Clarke, Sarah Cole, Louise Cooper, Helen Cox, Christopher Davis, Oslem Dincarslan, Alejandra Doce Carracedo, Chris Dunn, Philip Dyer, Angela Elliott, Anthony Evans, Lorna Finch, Lewis W.S. Fisher, Lisa Flaherty, Terry Foster, Isabel Garcia-Dorival, Philip Gunning, Catherine Hartley, Anthony Holmes, Rebecca L. Jensen, Christopher B. Jones, Trevor R. Jones, Shadia Khandaker, Katharine King, Robyn T. Kiy, Chrysa Koukorava, Annette Lake, Suzannah Lant, Diane Latawiec, Lara Lavelle-Langham, Daniella Lefteri, Lauren Lett, Lucia A Livoti, Maria Mancini, Hannah Massey, Nicole Maziere, Sarah McDonald, Laurence McEvoy, John McLauchlan, Soeren Metelmann, Nahida S. Miah, Joanna Middleton, Joyce Mitchell, Ellen G Murphy, Rebekah Penrice-Randal, Jack Pilgrim, Tessa Prince, Will Reynolds, P. Matthew Ridley, Debby Sales, Victoria E. Shaw, Rebecca K. Shears, Benjamin Small, Krishanthi S. Subramaniam, Agnieska Szemiel, Aislynn Taggart, Jolanta Tanianis-Hughes, Jordan Thomas, Erwan Trochu, Libby van Tonder, Eve Wilcock, J. Eunice Zhang, Seán Keating, Cara Donegan, Rebecca G. Spencer, Chloe Donohue, Fiona Griffiths, Hayley Hardwick, Wilna Oosthuyzen, K. Abel, H. Adamali, D. Adeloye, O. Adeyemi, R. Adrego, L.A. Aguilar Jimenez, S. Ahmad, N. Ahmad Haider, R. Ahmed, N. Ahwireng, M. Ainsworth, B. Al-Sheklly, A. Alamoudi, M. Ali, M. Aljaroof, A.M. All, L. Allan, R.J. Allen, L. Allerton, L. Allsop, P. Almeida, D. Altmann, M. Alvarez Corral, S. Amoils, D. Anderson, C. Antoniades, G. Arbane, A. Arias, C. Armour, L. Armstrong, N. Armstrong, D. Arnold, H. Arnold, A. Ashish, A. Ashworth, M. Ashworth, S. Aslani, H. Assefa-Kebede, C. Atkin, P. Atkin, R. Aul, H. Aung, L. Austin, C. Avram, A. Ayoub, M. Babores, R. Baggott, J. Bagshaw, D. Baguley, L. Bailey, J.K. Baillie, S. Bain, M. Bakali, M. Bakau, E. Baldry, D. Baldwin, M. Baldwin, C. Ballard, A. Banerjee, B. Bang, R.E. Barker, L. Barman, S. Barratt, F. Barrett, D. Basire, N. Basu, M. Bates, A. Bates, R. Batterham, H. Baxendale, H. Bayes, M. Beadsworth, P. Beckett, M. Beggs, M. Begum, P. Beirne, D. Bell, R. Bell, K. Bennett, E. Beranova, A. Bermperi, A. Berridge, C. Berry, S. Betts, E. Bevan, K. Bhui, M. Bingham, K. Birchall, L. Bishop, K. Bisnauthsing, J. Blaikely, A. Bloss, A. Bolger, C.E. Bolton, J. Bonnington, A. Botkai, C. Bourne, M. Bourne, K. Bramham, L. Brear, G. Breen, J. Breeze, A. Briggs, E. Bright, C.E. Brightling, S. Brill, K. Brindle, L. Broad, A. Broadley, C. Brookes, M. Broome, A. Brown, J. Brown, J.S. Brown, M. Brown, V. Brown, T. Brugha, N. Brunskill, M. Buch, P. Buckley, A. Bularga, E. Bullmore, L. Burden, T. Burdett, D. Burn, G. Burns, A. Burns, J. Busby, R. Butcher, A. Butt, S. Byrne, P. Cairns, P.C. Calder, E. Calvelo, H. Carborn, B. Card, C. Carr, L. Carr, G. Carson, P. Carter, A. Casey, M. Cassar, J. Cavanagh, M. Chablani, T. Chalder, J.D. Chalmers, R.C. Chambers, F. Chan, K.M. Channon, K. Chapman, A. Charalambou, N. Chaudhuri, A. Checkley, J. Chen, Y. Cheng, L. Chetham, C. Childs, E.R. Chilvers, H. Chinoy, A. Chiribiri, K. Chong-James, G. Choudhury, N. Choudhury, P. Chowienczyk, C. Christie, M. Chrystal, D. Clark, C. Clark, J. Clarke, S. Clohisey, G. Coakley, Z. Coburn, S. Coetzee, J. Cole, C. Coleman, F. Conneh, D. Connell, B. Connolly, L. Connor, A. Cook, B. Cooper, J. Cooper, S. Cooper, D. Copeland, T. Cosier, M. Coulding, C. Coupland, E. Cox, T. Craig, P. Crisp, D. Cristiano, M.G. Crooks, A. Cross, I. Cruz, P. Cullinan, D. Cuthbertson, L. Daines, M. Dalton, P. Daly, A. Daniels, P. Dark, J. Dasgin, A. David, C. David, E. Davies, F. Davies, G. Davies, G.A. Davies, K. Davies, M.J. Davies, J. Dawson, E. Daynes, A. De Soyza, B. Deakin, A. Deans, C. Deas, J. Deery, S. Defres, A. Dell, K. Dempsey, E. Denneny, J. Dennis, A. Dewar, R. Dharmagunawardena, N. Diar-Bakerly, C. Dickens, A. Dipper, S. Diver, S.N. Diwanji, M. Dixon, R. Djukanovic, H. Dobson, S.L. Dobson, A.B. Docherty, A. Donaldson, T. Dong, N. Dormand, A. Dougherty, R. Dowling, S. Drain, K. Draxlbauer, K. Drury, P. Dulawan, A. Dunleavy, S. Dunn, C. Dupont, J. Earley, N. Easom, C. Echevarria, S. Edwards, C. Edwardson, H. El-Taweel, A. Elliott, K. Elliott, Y. Ellis, A. Elmer, O. Elneima, D. Evans, H. Evans, J. Evans, R. Evans, R.A. Evans, R.I. Evans, T. Evans, C. Evenden, L. Evison, L. Fabbri, S. Fairbairn, A. Fairman, K. Fallon, D. Faluyi, C. Favager, T. Fayzan, J. Featherstone, T. Felton, J. Finch, S. Finney, J. Finnigan, L. Finnigan, H. Fisher, S. Fletcher, R. Flockton, M. Flynn, H. Foot, D. Foote, A. Ford, D. Forton, E. Fraile, C. Francis, R. Francis, S. Francis, A. Frankel, E. Fraser, R. Free, N. French, X. Fu, J. Fuld, J. Furniss, L. Garner, N. Gautam, J.R. Geddes, J. George, P. George, M. Gibbons, M. Gill, L. Gilmour, F. Gleeson, J. Glossop, S. Glover, N. Goodman, C. Goodwin, B. Gooptu, H. Gordon, T. Gorsuch, M. Greatorex, P.L. Greenhaff, W. Greenhalf, A. Greenhalgh, N.J. Greening, J. Greenwood, H. Gregory, R. Gregory, D. Grieve, D. Griffin, L. Griffiths, A-M. Guerdette, B. Guillen Guio, M. Gummadi, A. Gupta, S. Gurram, E. Guthrie, Z. Guy, H. H Henson, K. Hadley, A. Haggar, K. Hainey, B. Hairsine, P. Haldar, I. Hall, L. Hall, M. Halling-Brown, R. Hamil, A. Hancock, K. Hancock, N.A. Hanley, S. Haq, H.E. Hardwick, E. Hardy, T. Hardy, B. Hargadon, K. Harrington, E. Harris, V.C. Harris, E.M. Harrison, P. Harrison, N. Hart, A. Harvey, M. Harvey, M. Harvie, L. Haslam, M. Havinden-Williams, J. Hawkes, N. Hawkings, J. Haworth, A. Hayday, M. Haynes, J. Hazeldine, T. Hazelton, L.G. Heaney, C. Heeley, J.L. Heeney, M. Heightman, S. Heller, M. Henderson, L. Hesselden, M. Hewitt, V. Highett, T. Hillman, T. Hiwot, L.P. Ho, A. Hoare, M. Hoare, J. Hockridge, P. Hogarth, A. Holbourn, S. Holden, L. Holdsworth, D. Holgate, M. Holland, L. Holloway, K. Holmes, M. Holmes, B. Holroyd-Hind, L. Holt, A. Hormis, A. Horsley, A. Hosseini, M. Hotopf, L. Houchen-Wolloff, K. Howard, L.S. Howard, A. Howell, E. Hufton, A.D. Hughes, J. Hughes, R. Hughes, A. Humphries, N. Huneke, E. Hurditch, J. Hurst, M. Husain, T. Hussell, J. Hutchinson, W. Ibrahim, F. Ilyas, J. Ingham, L. Ingram, D. Ionita, K. Isaacs, K. Ismail, T. Jackson, J. Jacob, W.Y. James, W. Jang, C. Jarman, I. Jarrold, H. Jarvis, R. Jastrub, B. Jayaraman, R.G. Jenkins, P. Jezzard, K. Jiwa, C. Johnson, S. Johnson, D. Johnston, C.J. Jolley, D. Jones, G. Jones, H. Jones, I. Jones, L. Jones, M.G. Jones, S. Jones, S. Jose, T. Kabir, G. Kaltsakas, V. Kamwa, N. Kanellakis, s. Kaprowska, Z. Kausar, N. Keenan, S. Kelly, G. Kemp, S. Kerr, H. Kerslake, A.L. Key, F. Khan, K. Khunti, S. Kilroy, B. King, C. King, L. Kingham, J. Kirk, P. Kitterick, P. Klenerman, L. Knibbs, S. Knight, A. Knighton, O. Kon, S. Kon, S.S. Kon, S. Koprowska, A. Korszun, I. Koychev, C. Kurasz, P. Kurupati, C. Laing, H. Lamlum, G. Landers, C. Langenberg, D. Lasserson, L. Lavelle-Langham, A. Lawrie, C. Lawson, A. Layton, A. Lea, O.C. Leavy, D. Lee, J-H. Lee, E. Lee, K. Leitch, R. Lenagh, D. Lewis, J. Lewis, K.E. Lewis, V. Lewis, N. Lewis-Burke, X. Li, T. Light, L. Lightstone, W. Lilaonitkul, L. Lim, S. Linford, A. Lingford-Hughes, M. Lipman, K. Liyanage, A. Lloyd, S. Logan, D. Lomas, N.I. Lone, R. Loosley, J.M. Lord, H. Lota, W. Lovegrove, A. Lucey, E. Lukaschuk, A. Lye, C. Lynch, S. MacDonald, G. MacGowan, I. Macharia, J. Mackie, L. Macliver, S. Madathil, G. Madzamba, N. Magee, M.M. Magtoto, N. Mairs, N. Majeed, E. Major, F. Malein, M. Malim, G. Mallison, W.D.-C. Man, S. Mandal, K. Mangion, C. Manisty, R. Manley, K. March, S. Marciniak, P. Marino, M. Mariveles, M. Marks, E. Marouzet, S. Marsh, B. Marshall, M. Marshall, J. Martin, A. Martineau, L.M. Martinez, N. Maskell, D. Matila, W. Matimba-Mupaya, L. Matthews, A. Mbuyisa, S. McAdoo, H. McAllister-Williams, A. McArdle, P. McArdle, D. McAulay, G.P. McCann, H.J.C. drury, J. McCormick, W. McCormick, P. McCourt, L. McGarvey, C. McGee, K. Mcgee, J. McGinness, K. McGlynn, A. McGovern, H. McGuinness, I.B. McInnes, J. McIntosh, E. McIvor, K. McIvor, L. McLeavey, A. McMahon, M.J. McMahon, L. McMorrow, T. Mcnally, M. McNarry, J. McNeill, A. McQueen, H. McShane, C. Mears, C. Megson, S. Megson, P. Mehta, J. Meiring, L. Melling, M. Mencias, D. Menzies, M. Merida Morillas, A. Michael, C. Miller, L. Milligan, C. Mills, N.L. Mills, L. Milner, S. Misra, J. Mitchell, A. Mohamed, N. Mohamed, S. Mohammed, P.L. Molyneaux, W. Monteiro, S. Moriera, A. Morley, L. Morrison, R. Morriss, A. Morrow, A.J. Moss, P. Moss, K. Motohashi, N. Msimanga, E. Mukaetova-Ladinska, U. Munawar, J. Murira, U. Nanda, H. Nassa, M. Nasseri, A. Neal, R. Needham, P. Neill, S. Neubauer, D.E. Newby, H. Newell, T. Newman, A. Newton-Cox, T. Nicholson, D. Nicoll, A. Nikolaidis, C.M. Nolan, M.J. Noonan, C. Norman, P. Novotny, J. Nunag, L. Nwafor, U. Nwanguma, J. Nyaboko, C. O'Brien, K. O'Donnell, D. O'Regan, L. O'Brien, N. Odell, G. Ogg, O. Olaosebikan, C. Oliver, Z. Omar, P.J.M. Openshaw, L. Orriss-Dib, L. Osborne, R. Osbourne, M. Ostermann, C. Overton, J. Owen, J. Oxton, J. Pack, E. Pacpaco, S. Paddick, S. Painter, A. Pakzad, S. Palmer, P. Papineni, K. Paques, K. Paradowski, M. Pareek, D. Parekh, H. Parfrey, C. Pariante, S. Parker, M. Parkes, J. Parmar, S. Patale, B. Patel, M. Patel, S. Patel, D. Pattenadk, M. Pavlides, S. Payne, L. Pearce, J.E. Pearl, D. Peckham, J. Pendlebury, Y. Peng, C. Pennington, I. Peralta, E. Perkins, Z. Peterkin, T. Peto, N. Petousi, J. Petrie, P. Pfeffer, J. Phipps, J. Pimm, K. Piper Hanley, R. Pius, H. Plant, S. Plein, T. Plekhanova, M. Plowright, K. Poinasamy, O. Polgar, L. Poll, J.C. Porter, J. Porter, S. Portukhay, N. Powell, A. Prabhu, J. Pratt, A. Price, C. Price, D. Price, L. Price, A. Prickett, J. Propescu, S. Prosper, S. Pugmire, S. Quaid, J. Quigley, J. Quint, H. Qureshi, I.N. Qureshi, K. Radhakrishnan, N.M. Rahman, M. Ralser, B. Raman, A. Ramos, H. Ramos, J. Rangeley, B. Rangelov, L. Ratcliffe, P. Ravencroft, A. Reddington, R. Reddy, H. Redfearn, D. Redwood, A. Reed, M. Rees, T. Rees, K. Regan, W. Reynolds, C. Ribeiro, A. Richards, E. Richardson, M. Richardson, P. Rivera-Ortega, K. Roberts, E. Robertson, E. Robinson, L. Robinson, L. Roche, C. Roddis, J. Rodger, A. Ross, G. Ross, J. Rossdale, A. Rostron, A. Rowe, A. Rowland, J. Rowland, M.J. Rowland, S.L. Rowland-Jones, K. Roy, M. Roy, I. Rudan, R. Russell, E. Russell, G. Saalmink, R. Sabit, E.K. Sage, T. Samakomva, N. Samani, C. Sampson, K. Samuel, R. Samuel, A. Sanderson, E. Sapey, D. Saralaya, J. Sargant, C. Sarginson, T. Sass, N. Sattar, K. Saunders, R.M. Saunders, P. Saunders, L.C. Saunders, H. Savill, W. Saxon, A. Sayer, J. Schronce, W. Schwaeble, J.T. Scott, K. Scott, N. Selby, M.G. Semple, M. Sereno, T.A. Sewell, A. Shah, K. Shah, P. Shah, M. Shankar-Hari, M. Sharma, C. Sharpe, M. Sharpe, S. Shashaa, A. Shaw, K. Shaw, V. Shaw, A. Sheikh, S. Shelton, L. Shenton, K. Shevket, A. Shikotra, J. Short, S. Siddique, S. Siddiqui, J. Sidebottom, L. Sigfrid, G. Simons, J. Simpson, N. Simpson, A. Singapuri, C. Singh, S. Singh, S.J. Singh, D. Sissons, J. Skeemer, K. Slack, A. Smith, D. Smith, S. Smith, J. Smith, L. Smith, M. Soares, T.S. Solano, R. Solly, A.R. Solstice, T. Soulsby, D. Southern, D. Sowter, M. Spears, L.G. Spencer, F. Speranza, L. Stadon, S. Stanel, N. Steele, M. Steiner, D. Stensel, G. Stephens, L. Stephenson, M. Stern, I. Stewart, R. Stimpson, S. Stockdale, J. Stockley, W. Stoker, R. Stone, W. Storrar, A. Storrie, K. Storton, E. Stringer, S. Strong-Sheldrake, N. Stroud, C. Subbe, C.L. Sudlow, Z. Suleiman, C. Summers, C. Summersgill, D. Sutherland, D.L. Sykes, R. Sykes, N. Talbot, A.L. Tan, L. Tarusan, V. Tavoukjian, A. Taylor, C. Taylor, J. Taylor, A. Te, H. Tedd, C.J. Tee, J. Teixeira, H. Tench, S. Terry, S. Thackray-Nocera, F. Thaivalappil, B. Thamu, D. Thickett, C. Thomas, D.C. Thomas, S. Thomas, A.K. Thomas, T. Thomas-Woods, T. Thompson, A.A.R. Thompson, T. Thornton, M. Thorpe, R.S. Thwaites, J. Tilley, N. Tinker, G.F. Tiongson, M. Tobin, J. Tomlinson, C. Tong, M. Toshner, R. Touyz, K.A. Tripp, E. Tunnicliffe, A. Turnbull, E. Turner, S. Turner, V. Turner, K. Turner, S. Turney, L. Turtle, H. Turton, J. Ugoji, R. Ugwuoke, R. Upthegrove, J. Valabhji, M. Ventura, J. Vere, C. Vickers, B. Vinson, E. Wade, P. Wade, L.V. Wain, T. Wainwright, L.O. Wajero, S. Walder, S. Walker, E. Wall, T. Wallis, S. Walmsley, J.A. Walsh, S. Walsh, L. Warburton, T.J.C. Ward, K. Warwick, H. Wassall, S. Waterson, E. Watson, L. Watson, J. Watson, J. Weir McCall, C. Welch, H. Welch, B. Welsh, S. Wessely, S. West, H. Weston, H. Wheeler, S. White, V. Whitehead, J. Whitney, S. Whittaker, B. Whittam, V. Whitworth, A. Wight, J. Wild, M. Wilkins, D. Wilkinson, B. Williams, N. Williams, J. Williams, S.A. Williams-Howard, M. Willicombe, G. Willis, J. Willoughby, A. Wilson, D. Wilson, I. Wilson, N. Window, M. Witham, R. Wolf-Roberts, C. Wood, F. Woodhead, J. Woods, D.G. Wootton, J. Wormleighton, J. Worsley, D. Wraith, C. Wrey Brown, C. Wright, L. Wright, S. Wright, J. Wyles, I. Wynter, M. Xu, N. Yasmin, S. Yasmin, T. Yates, K.P. Yip, B. Young, S. Young, A. Young, A.J. Yousuf, A. Zawia, L. Zeidan, B. Zhao, B. Zheng, O. Zongo, Investigators, ISARIC4C, group, PHOSP-COVID collaborative, Sigfrid, L, ISARIC4C Investigators, and PHOSP-COVID collaborative group

Subjects
SARS-CoV-2 variants, Mucosal immunity, Nasal antibody, SDG 3 - Good Health and Well-being, Biochemistry, Genetics and Molecular Biology(all), SARS-CoV-2 immunity, Vaccination, COVID-19, General Medicine, Convalescent, General Biochemistry, Genetics and Molecular Biology
Abstract

Data sharing statement This is an Open Access article under the CC BY 4.0 license The ISARIC4C protocol, data sharing and publication policy are available at https://isaric4c.net. ISARIC4C's Independent Data and Material Access Committee welcomes applications for access to data and materials (https://isaric4c.net). The PHOSP-COVID protocol, consent form, definition and derivation of clinical characteristics and outcomes, training materials, regulatory documents, information about requests for data access, and other relevant study materials are available online: https://phosp.org/resource/. Access to these materials can be granted by contacting phosp@leicester.ac.uk and Phospcontracts@leicester.ac.uk. All data used in this study is available within ODAP and accessible under reasonable request. Data access criteria and information about how to request access is available online: https://phosp.org/resource/. If criteria are met and a request is made, access can be gained by signing the eDRIS user agreement. Supplementary data are available online at https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(22)00584-9/fulltext#supplementaryMaterial . Copyright © 2022 The Author(s). Background: Most studies of immunity to SARS-CoV-2 focus on circulating antibody, giving limited insights into mucosal defences that prevent viral replication and onward transmission. We studied nasal and plasma antibody responses one year after hospitalisation for COVID-19, including a period when SARS-CoV-2 vaccination was introduced. Methods: In this follow up study, plasma and nasosorption samples were prospectively collected from 446 adults hospitalised for COVID-19 between February 2020 and March 2021 via the ISARIC4C and PHOSP-COVID consortia. IgA and IgG responses to NP and S of ancestral SARS-CoV-2, Delta and Omicron (BA.1) variants were measured by electrochemiluminescence and compared with plasma neutralisation data. Findings: Strong and consistent nasal anti-NP and anti-S IgA responses were demonstrated, which remained elevated for nine months (p < 0.0001). Nasal and plasma anti-S IgG remained elevated for at least 12 months (p < 0.0001) with plasma neutralising titres that were raised against all variants compared to controls (p < 0.0001). Of 323 with complete data, 307 were vaccinated between 6 and 12 months; coinciding with rises in nasal and plasma IgA and IgG anti-S titres for all SARS-CoV-2 variants, although the change in nasal IgA was minimal (1.46-fold change after 10 months, p = 0.011) and the median remained below the positive threshold determined by pre-pandemic controls. Samples 12 months after admission showed no association between nasal IgA and plasma IgG anti-S responses (R = 0.05, p = 0.18), indicating that nasal IgA responses are distinct from those in plasma and minimally boosted by vaccination. Interpretation: The decline in nasal IgA responses 9 months after infection and minimal impact of subsequent vaccination may explain the lack of long-lasting nasal defence against reinfection and the limited effects of vaccination on transmission. These findings highlight the need to develop vaccines that enhance nasal immunity. Funding: This study has been supported by ISARIC4C and PHOSP-COVID consortia. ISARIC4C is supported by grants from the National Institute for Health and Care Research and the Medical Research Council. Liverpool Experimental Cancer Medicine Centre provided infrastructure support for this research. The PHOSP-COVD study is jointly funded by UK Research and Innovation and National Institute of Health and Care Research. The funders were not involved in the study design, interpretation of data or the writing of this manuscript. This work is supported by the following grants: The PHOSP-COVD study is jointly funded by UK Research and Innovation and National Institute for Health and Care Research (grant references: MR/V027859/1 and COV0319). ISARIC4C is supported by grants from the National Institute for Health and Care Research (award CO-CIN-01) and the Medical Research Council (grant MC_PC_19059) Liverpool Experimental Cancer Medicine Centre provided infrastructure support for this research (grant reference: C18616/A25153). Other grants which have supported this work include: the UK Coronavirus Immunology Consortium [funder reference:1257927], the Imperial Biomedical Research Centre (NIHR Imperial BRC, grant IS-BRC-1215-20013), the Health Protection Research Unit (HPRU) in Respiratory Infections at Imperial College London and NIHR HPRU in Emerging and Zoonotic Infections at University of Liverpool, both in partnership with Public Health England, [NIHR award 200907], Wellcome Trust and Department for International Development [215091/Z/18/Z], Health Data Research UK (HDR UK) [grant code: 2021.0155], Medical Research Council [grant code: MC_UU_12014/12], and NIHR Clinical Research Network for providing infrastructure support for this research. FL is supported by an MRC clinical training fellowship [award MR/W000970/1]. LPH is supported by Oxford NIHR Biomedical Research Centre. AART is supported by a BHF Intermediate Clinical Fellowship (FS/18/13/33281). SLRJ receives support from UKRI, GCRF, Rosetrees Trust, BHIVA, EDCTP, Globvac. JDC has grants from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Gilead Sciences, Grifols, Novartis and Insmed. RAE holds a NIHR Clinician Scientist Fellowship (CS-2016-16-020). AH is currently supported by UK Research and Innovation. NIHR and NIHR Manchester BRC. BR receives support from BHF Oxford Centre of Research Excellence, NIHR Oxford BRC and MRC. SJD is funded by an NIHR Global Research Professorship [NIHR300791]. DW is supported by an NIHR Advanced Fellowship. AH has received support from MRC and the Coronavirus Immunology Consortium (MR/V028448/1). LVW has received support from UKRI, GSK/Asthma + Lung UK and NIHR for this study. MGS has received support from NIHR UK, MRC UK and Health Protection Research Unit in Emerging & Zoonotic Infections, University of Liverpool. JKB is supported by the Wellcome Trust (223164/Z/21/Z) and UKRI (MC_PC_20004, MC_PC_19025, MC_PC_1905, MRNO2995X/1, and MC_PC_20029). PJMO is supported by a NIHR Senior Investigator Award [award 201385]. LT is supported by the Wellcome Trust [clinical career development fellowship grant number 205228/Z/16/Z], the Centre of Excellence in Infectious Diseases Research (CEIDR) and the Alder Hey Charity.

Published
2022

20. Study of Acute Liver Failure in Children Using Next Generation Sequencing Technology

Author

Melissa Sambrotta, Sandra Strautnieks, S. Lillis, Sanjay Bansal, Tassos Grammatikopoulos, Robert Hegarty, Sian Ellard, Richard J. Thompson, Anil Dhawan, Roshni Vara, P. S. Gibson, Julia Baptista, and Pierre Foskett

Subjects
Male, Pediatrics, medicine.medical_specialty, Candidate gene, Compound heterozygosity, DNA sequencing, Cohort Studies, 03 medical and health sciences, Liver disease, 0302 clinical medicine, 030225 pediatrics, Humans, Medicine, 030212 general & internal medicine, Child, MPV17, Survival rate, Exome sequencing, business.industry, Infant, Newborn, High-Throughput Nucleotide Sequencing, Infant, Liver Failure, Acute, medicine.disease, Child, Preschool, Pediatrics, Perinatology and Child Health, Etiology, Female, business
Abstract

Objective To use next generation sequencing (NGS) technology to identify undiagnosed, monogenic diseases in a cohort of children who suffered from acute liver failure (ALF) without an identifiable etiology. Study design We identified 148 under 10 years of age admitted to King's College Hospital, London, with ALF of indeterminate etiology between 2000 and 2018. A custom NGS panel of 64 candidate genes known to cause ALF and/or metabolic liver disease was constructed. Targeted sequencing was carried out on 41 children in whom DNA samples were available. Trio exome sequencing was performed on 4 children admitted during 2019. A comparison of the clinical characteristics of those identified with biallelic variants against those without biallelic variants was then made. Results Homozygous and compound heterozygous variants were identified in 8 out of 41 children (20%) and 4 out of 4 children (100%) in whom targeted and exome sequencing were carried out, respectively. The genes involved were NBAS (3 children); DLD (2 children); and CPT1A, FAH, LARS1, MPV17, NPC1, POLG, SUCLG1, and TWINK (1 each). The 12 children who were identified with biallelic variants were younger at presentation and more likely to die in comparison with those who did not: median age at presentation of 3 months and 30 months and survival rate 75% and 97%, respectively. Conclusions NGS was successful in identifying several specific etiologies of ALF. Variants in NBAS and mitochondrial DNA maintenance genes were the most common findings. In the future, a rapid sequencing NGS workflow could help in reaching a timely diagnosis and facilitate clinical decision making in children with ALF.

Published
2021

22. Acute Pancreatitis: Diagnosis and Treatment

Author

Peter Szatmary, Tassos Grammatikopoulos, Wenhao Cai, Wei Huang, Rajarshi Mukherjee, Chris Halloran, Georg Beyer, and Robert Sutton

Subjects
Ethanol, Lipase, Anti-Bacterial Agents, C-Reactive Protein, Glucose, Pancreatitis, Acute Disease, Amylases, Humans, Pharmacology (medical), Calcium, Child, Triglycerides, Aged
Abstract

Acute pancreatitis is a common indication for hospital admission, increasing in incidence, including in children, pregnancy and the elderly. Moderately severe acute pancreatitis with fluid and/or necrotic collections causes substantial morbidity, and severe disease with persistent organ failure causes significant mortality. The diagnosis requires two of upper abdominal pain, amylase/lipase ≥ 3 ×upper limit of normal, and/or cross-sectional imaging findings. Gallstones and ethanol predominate while hypertriglyceridaemia and drugs are notable among many causes. Serum triglycerides, full blood count, renal and liver function tests, glucose, calcium, transabdominal ultrasound, and chest imaging are indicated, with abdominal cross-sectional imaging if there is diagnostic uncertainty. Subsequent imaging is undertaken to detect complications, for example, if C-reactive protein exceeds 150 mg/L, or rarer aetiologies. Pancreatic intracellular calcium overload, mitochondrial impairment, and inflammatory responses are critical in pathogenesis, targeted in current treatment trials, which are crucially important as there is no internationally licenced drug to treat acute pancreatitis and prevent complications. Initial priorities are intravenous fluid resuscitation, analgesia, and enteral nutrition, and when necessary, critical care and organ support, parenteral nutrition, antibiotics, pancreatic exocrine and endocrine replacement therapy; all may have adverse effects. Patients with local complications should be referred to specialist tertiary centres to guide further management, which may include drainage and/or necrosectomy. The impact of acute pancreatitis can be devastating, so prevention or reduction of the risk of recurrence and progression to chronic pancreatitis with an increased risk of pancreas cancer requires proactive management that should be long term for some patients.

Published
2022

24. L3 Effects on serum bile acids, pruritus, and safety with up to 72 weeks of odevixibat treatment: pooled data from the PEDFIC 1 and PEDFIC 2 studies in children with progressive familial intrahepatic cholestasis

Author

Kathleen M Loomes, Henkjan J Verkade, Richard J Thompson, Binita M Kamath, Winita Hardikar, Florence Lacaille, Yael Mozer-Glassberg, Eyal Shteyer, Pier Luigi Calvo, Buket Dalgic, Tassos Grammatikopoulos, Sanjay R Rajwal, Jennifer M Vittorio, Nisreen Soufi, Patrick McKiernan, Mary Elizabeth Tessier, Qifeng Yu, Lise Kjems, and Patrick Horn

Published
2022

26. O12 Hepatic parameters, growth, and sleep with responders and nonresponders to odevixibat treatment: pooled data from the PEDFIC 1 and PEDFIC 2 studies in children with progressive familial intrahepatic cholestasis

Author

Patrick McKiernan, Ekkehard Sturm, Binita M Kamath, Richard J Thompson, Emmanuel Gonzalès, Alain Lachaux, Ulrich Baumann, Eyal Shteyer, Piotr Czubkowski, Reha Artan, Buket Dalgic, Hasan Özen, Girish Gupte, Tassos Grammatikopoulos, Saul J Karpen, Quanhong Ni, Lise Kjems, and Patrick Horn

Published
2022

27. Clinical management of sickle cell liver disease in children and young adults

Author

Girish Gupte, Fulvio Mavilio, Anita Verma, Baba Inusa, Valentine Brousse, Tassos Grammatikopoulos, Eirini Kyrana, Mark Davenport, Subarna Chakravorty, Marki Velangi, Florence Lacaille, Anil Dhawan, Maria E. Sellars, Nigel Heaton, Maesha Deheragoda, Jonathan Hind, Emma Drasar, Sue Height, Marianne Samyn, Emer Fitzpatrick, Abid Suddle, David C. Rees, and Nedim Hadzic

Subjects
Pediatrics, medicine.medical_specialty, Iron Overload, Adolescent, Digestive System Diseases, medicine.medical_treatment, gastroenterology, Context (language use), Anemia, Sickle Cell, Disease, Liver transplantation, adolescent health, jaundice, Article, Young Adult, 03 medical and health sciences, Liver disease, 0302 clinical medicine, polycyclic compounds, medicine, Humans, heterocyclic compounds, Young adult, Child, Monitoring, Physiologic, business.industry, organic chemicals, Incidence, Liver Diseases, Hematopoietic Stem Cell Transplantation, Jaundice, medicine.disease, United Kingdom, Liver Transplantation, carbohydrates (lipids), Transplantation, 030220 oncology & carcinogenesis, Pediatrics, Perinatology and Child Health, Interdisciplinary Communication, medicine.symptom, Complication, business, 030215 immunology
Abstract

Liver involvement in sickle cell disease (SCD) is often referred to as sickle cell hepatopathy (SCH) and is a complication of SCD which may be associated with significant mortality. This review is based on a round-table workshop between paediatric and adult hepatologists and haematologists and review of the literature. The discussion was prompted by the lack of substantial data and guidance in managing these sometimes very challenging cases. This review provides a structured approach for the diagnosis and management of SCH in children and young adults. The term SCH describes any hepatobiliary dysfunction in the context of SCD. Diagnosis and management of biliary complications, acute hepatic crisis, acute hepatic sequestration and other manifestations of SCH are discussed, as well as the role of liver transplantation and haemopoietic stem cell transplantation in the management of SCH.

Published
2020

28. A coordinated national UK liver transplant program response, prioritizing waitlist recipients with the highest need, provided excellent outcomes during the first wave of the COVID‐19 pandemic

Author

Steven Masson, Rhiannon Taylor, Julie Whitney, Anya Adair, Magdy Attia, Paul Gibbs, Tassos Grammatikopoulos, John Isaac, Aileen Marshall, Darius Mirza, Andreas Prachalias, Sarah Watson, Derek Manas, John Forsythe, and Douglas Thorburn

Subjects
Adult, Transplantation, Carcinoma, Hepatocellular, Waiting Lists, Liver Neoplasms, COVID-19, Humans, Child, Pandemics, Transplant Recipients, United Kingdom, Liver Transplantation
Abstract

Healthcare provision has been severely affected by COVID-19, with specific challenges in organ transplantation. Here, we describe the coordinated response to, and outcomes during the first wave, across all UK liver transplant (LT) centers.Several policy changes affecting the liver transplant processes were agreed upon. These included donor age restrictions and changes to offering. A "high-urgency" (HU) category was established, prioritizing only those with UKELD 60, HCC reaching transplant criteria, and others likely to die within 90 days. Outcomes were compared with the same period in 2018 and 2019.The retrieval rate for deceased donor livers (71% vs. 54%; P .0001) and conversion from offer to completed transplant (63% vs. 48%; P .0001) was significantly higher. Pediatric LT activity was maintained; there was a significant reduction in adult (42%) and total (36%) LT. Almost all adult LT were super-urgent (n = 15) or HU (n = 133). We successfully prioritized those with highest illness severity with no reduction in 90-day patient (P = .89) or graft survival (P = .98). There was a small (5% compared with 3%; P = .0015) increase in deaths or removals from the waitlist, mainly amongst HU cohort.We successfully prioritized LT recipients in highest need, maintaining excellent outcomes, and waitlist mortality was only marginally increased.

Published
2022

29. Analysis of quality of life, hepatic biochemical markers, and sleep in patients with progressive familial intrahepatic cholestasis who had a pruritus response with odevixibat treatment

Author

Girish Gupte, Richard J. Thompson, Lorenzo D’Antiga, Tassos Grammatikopoulos, Emmanuel Gonzalès, Florence Lacaille, Alain Lachaux, Bertrand Roquelaure, Ulrich Baumann, Elke Lainka, Ekkehard Sturm, Eyal Shteyer, Piotr Czubkowski, Reha Artan, Buket Dalgic, Hasan Ozen, Kathleen M. Loomes, Jennifer M. Vittorio, Saul J. Karpen, Patrick McKiernan, Cara L. Mack, Angelo Di Giorgio, Qifeng Yu, Lise Kjems, and Patrick Horn

Subjects
Hepatology, Medizin
Abstract

Poster-Abstract

Published
2022

30. Use and safety of prophylactic endoscopy from a single center serving urban and rural children with portal hypertension

Author

Ryan T. Fischer, James F. Daniel, Heather Wasserkrug, Tassos Grammatikopoulos, Voytek Slowik, and Anissa Bernardez

Subjects
Male, Rural Population, Adolescent, Urban Population, Science, Diseases, Single Center, Article, Endoscopy, Gastrointestinal, Medical research, Hypertension, Portal, medicine, Secondary Prevention, Humans, Child, Retrospective Studies, Multidisciplinary, medicine.diagnostic_test, business.industry, Gastroenterology, medicine.disease, Endoscopy, Medicine, Portal hypertension, Female, Medical emergency, business, Gastrointestinal Hemorrhage
Abstract

Prophylactic endoscopy is routine in adults with portal hypertension (PHTN), but there is limited data in pediatrics. We sought to describe our experience with prophylactic endoscopy in pediatric PHTN. This is a retrospective study of 87 children who began surveillance endoscopy prior to gastrointestinal bleeding (primary prophylaxis) and 52 who began after an episode of bleeding (secondary prophylaxis) from 01/01/1994 to 07/01/2019. Patients who underwent primary prophylaxis had a lower mean number of endoscopies (3.897 vs 6.269, p = 0.001). The primary prophylaxis group was less likely to require a portosystemic shunt (6% vs 15%, p

Published
2022

35. Liver Disease and Risk of Hepatocellular Carcinoma in Children With Mutations in TALDO1

Author

Jozef Hertecant, Anil Dhawan, Roshni Vara, Maesha Deheragoda, Pierre Foskett, Tassos Grammatikopoulos, Sandra Strautnieks, Nedim Hadzic, Marianne Samyn, Fatma Al Jasmi, Obydur Rahman, Laura N. Bull, and Richard J. Thompson

Subjects
Male, medicine.medical_specialty, Carcinoma, Hepatocellular, medicine.medical_treatment, Hepatosplenomegaly, Liver transplantation, Chronic liver disease, Transaldolase deficiency, Compound heterozygosity, Gastroenterology, Liver disease, Internal medicine, medicine, Humans, Hepatology, business.industry, Liver Neoplasms, Infant, Newborn, Infant, Jaundice, medicine.disease, Transaldolase, Hepatocellular carcinoma, Mutation, Female, medicine.symptom, business, Carbohydrate Metabolism, Inborn Errors
Abstract

Mutations in the transaldolase 1 (TALDO1) gene have been described in a limited number of cases. Several organs can be affected and clinical manifestations are variable, but often include liver dysfunction and/or hepatosplenomegaly. We report 4 patients presenting with liver disease: 2 with early-onset hepatocellular carcinoma (HCC). Patients with cholestasis and mutations in TALDO1 were identified by next-generation sequencing. Clinical, laboratory, and histological data were collected. Four (1 male) patients were identified with variants predicted to be damaging in TALDO1. Three patients were homozygous (two protein truncating/one missense mutations), 1 one was compound heterozygous (two missense mutations). Median age at presentation was 4 months (range, 2-210 days) with jaundice (3), hepatosplenomegaly (3), and pancytopaenia (1). The diagnosis was corroborated by detection of minimal transaldolase enzyme activity in skin fibroblasts in two cases and raised urine polyols in the third. Three patients underwent liver transplantation (LT), 2 of whom had confirmed HCC on explanted liver. One patient suddenly died shortly after LT. The nontransplanted case has a chronic liver disease with multiple dysplastic liver nodules, but normal liver biochemistry and alpha-fetoprotein. Median follow-up was 4 years (range, 1-21). Conclusion: Transaldolase deficiency can include early-onset normal gamma-glutamyltransferase liver disease with multisystem involvement and variable progression. Patients with this disease are at risk of early-onset HCC and may require early LT.

Published
2021

36. Optimal timing of endoscopy in pediatric variceal hemorrhage - How urgent is urgent?

Author

Voytek Slowik and Tassos Grammatikopoulos

Subjects
medicine.medical_specialty, Hepatology, medicine.diagnostic_test, business.industry, General surgery, Gastroenterology, Endoscopy, Variceal hemorrhage, Esophageal and Gastric Varices, Endoscopy, Gastrointestinal, Varicose Veins, medicine, Humans, business, Child, Gastrointestinal Hemorrhage
Published
2021

37. Unsupervised hyperspectral stimulated Raman microscopy image enhancement: denoising and segmentation via one-shot deep learning

Author

Andrew Ridsdale, Gavin Resch, François Légaré, Pedram Abdolghader, Albert Stolow, Isaac Tamblyn, Adrian F. Pegoraro, and Tassos Grammatikopoulos

Subjects
Signal Processing (eess.SP), Raman scattering, Computer science, Image quality, Noise reduction, ComputingMethodologies_IMAGEPROCESSINGANDCOMPUTERVISION, FOS: Physical sciences, 02 engineering and technology, Applied Physics (physics.app-ph), 01 natural sciences, 010309 optics, optical imaging, Optics, 0103 physical sciences, FOS: Electrical engineering, electronic engineering, information engineering, image quality, Segmentation, image enhancement, Electrical Engineering and Systems Science - Signal Processing, Cluster analysis, Artificial neural network, business.industry, photonic crystal fibers, Deep learning, Hyperspectral imaging, Pattern recognition, Physics - Applied Physics, Image segmentation, nonlinear microscopy, 021001 nanoscience & nanotechnology, Atomic and Molecular Physics, and Optics, ComputingMethodologies_PATTERNRECOGNITION, Artificial intelligence, 0210 nano-technology, business, Physics - Optics, Optics (physics.optics)
Abstract

Hyperspectral stimulated Raman scattering (SRS) microscopy is a label-free technique for biomedical and mineralogical imaging which can suffer from low signal-to-noise ratios. Here we demonstrate the use of an unsupervised deep learning neural network for rapid and automatic denoising of SRS images: UHRED (Unsupervised Hyperspectral Resolution Enhancement and Denoising). UHRED is capable of “one-shot” learning; only one hyperspectral image is needed, with no requirements for training on previously labelled datasets or images. Furthermore, by applying a k-means clustering algorithm to the processed data, we demonstrate automatic, unsupervised image segmentation, yielding, without prior knowledge of the sample, intuitive chemical species maps, as shown here for a lithium ore sample.

Published
2021

38. P091 A coordinated national response maintained a safe and effective UK liver transplant program during the first year of the COVID-19 pandemic

Author

Aileen Marshall, Douglas Thorburn, Anya Adair, Steven Masson, Rhiannon Taylor, Andreas Prachalis, Derek Manas, Sarah Watson, Magdy Attia, Paul Gibbs, Tassos Grammatikopoulos, John Isaac, Darius F. Mirza, Raj Prasad, Maxine Tapp, Michael Allison, Julie Whitney, and John L. R. Forsythe

Subjects
medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), business.industry, Pandemic, Emergency medicine, medicine, business
Published
2021

39. Impact of Genotype, Serum Bile Acids, and Surgical Biliary Diversion on Native Liver Survival in FIC1 Deficiency

Author

Liting Li, Jian-She Wang, Ozlem Durmaz, Felipe Ordonez, Wikrom Karnsakul, Seema Alam, Cristina Targa Ferreira, Natural Course, Bettina E. Hansen, Kyung Mo Kim, Etienne Sokal, Ryan T. Fischer, Valerie Sency, Estella M. Alonso, Simon Horslen, Elisa de Carvalho, Piotr Czubkowski, Emanuele Nicastro, Nanda Kerkar, Dieter C. Broering, Björn Fischler, Dorothee Krebs-Schmitt, Kathleen M. Loomes, Dominique Debray, Marianne Hørby Jørgensen, Benjamin L. Shneider, Emmanuel Gonzales, Cigdem Arikan, Nathalie Rock, Antal Dezsőfi, Tassos Grammatikopoulos, Steffen Hartleif, Mara Cananzi, Talal Algoufi, Ronald J. Sokol, Jan B F Hulscher, Carolina Jimenez-Rivera, Emmanuel Jacquemin, Anne Spraul, Henkjan J. Verkade, Patryk Lipiński, Daan B E van Wessel, Nejat Mazhar, Maria Rogalidou, Deirdre Kelly, Alexandre Fabre, Daniele Serranti, Pier Luigi Calvo, Yael Mozer-Glassberg, Richard J. Thompson, Cristina Goncalves, Yumirle P. Turmelle, Jesus Quintero Bernabeu, Agustina Kadaristiana, Florence Lacaille, Loreto Hierro, Mohammad Shagrani, Patrick J. McKiernan, Girish S. Rao, Gema Muñoz Bartolo, Huey-Ling Chen, Wendy L. van der Woerd, Irena Jankowska, Amer Azaz, Philip J. Rosenthal, Frederick J. Suchy, Jernej Brecelj, Gabriella Nebbia, Noemie Laverdure, Henrik Arnell, Binita M. Kamath, Heng Wang, Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de pédiatrie multidisciplinaire [Hôpital de la Timone Enfants - APHM], Hôpital de la Timone [CHU - APHM] (TIMONE), Arıkan, Çiğdem (ORCID 0000-0002-0794-2741 & YÖK ID 240198), van Wessel, D. B. E., Thompson, R. J., Gonzales, E., Jankowska, I., Shneider, B. L., Sokal, E., Grammatikopoulos, T., Kadaristiana, A., Jacquemin, E., Spraul, A., Lipiński, P., Czubkowski, P., Rock, N., Shagrani, M., Broering, D., Algoufi, T., Mazhar, N., Nicastro, E., Kelly, D., Nebbia, G., Arnell, H., Fischler, B., Hulscher, J. B. F., Serranti, D., Debray, D., Lacaille, F., Goncalves, C., Hierro, L., Muñoz Bartolo, G., Mozer-Glassberg, Y., Azaz, A., Brecelj, J., Dezsőfi, A., Luigi Calvo, P., Krebs-Schmitt, D., Hartleif, S., van der Woerd, W. L., Wang, J. S., Li, L. T., Durmaz, Ö., Kerkar, N., Hørby Jørgensen, M., Fischer, R., Jimenez-Rivera, C., Alam, S., Cananzi, M., Laverdure, N., Ferreira, C. T., Ordonez, F., Wang, H., Sency, V., Kim, K. M., Chen, H. L., Carvalho, E., Fabre, A., Quintero Bernabeu, J., Alonso, E. M., Sokol, R. J., Suchy, F. J., Loomes, K. M., McKiernan, P. J., Rosenthal, P., Turmelle, Y., Rao, G. S., Horslen, S., Kamath, B. M., Rogalidou, M., Karnsakul, W. W., Hansen, B., Verkade, H. J., Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM), School of Medicine, Center for Liver, Digestive and Metabolic Diseases (CLDM), UCL - SSS/IREC/PEDI - Pôle de Pédiatrie, and UCL - (SLuc) Service de gastro-entérologie et hépatologie pédiatrique

Subjects
0301 basic medicine, Male, [SDV]Life Sciences [q-bio], CHILDREN, Compound heterozygosity, Gastroenterology, PFIC1, DISEASE, 0302 clinical medicine, Genotype, Medicine, Prospective Studies, Prospective cohort study, Child, ComputingMilieux_MISCELLANEOUS, Adenosine Triphosphatases, ATP8B1 GENE, Bile acid, Progressive familial intrahepatic cholestasis, Prognosis, Treatment Outcome, Codon, Nonsense, Child, Preschool, Cohort, 030211 gastroenterology & hepatology, Female, Original Article, EXPRESSION, medicine.medical_specialty, Adolescent, medicine.drug_class, Cholestasis, Intrahepatic, Risk Assessment, Frameshift mutation, Bile Acids and Salts, 03 medical and health sciences, Young Adult, FAMILIAL INTRAHEPATIC CHOLESTASIS, Internal medicine, Humans, ABCB11 MUTATIONS, Survival analysis, TYPE-1, ATP8B1, FIC1 deficiency, Serum bile acids, Surgical biliary diversion, Retrospective Studies, [SDV.GEN]Life Sciences [q-bio]/Genetics, Hepatology, business.industry, Infant, Original Articles, medicine.disease, Survival Analysis, Liver Transplantation, SALT EXPORT PUMP, 030104 developmental biology, Bile Ducts, Intrahepatic, Autoimmune, Cholestatic and Biliary Disease, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Follow-Up Studies
Abstract

Mutations in ATP8B1 can lead to familial intrahepatic cholestasis type 1 (FIC1) deficiency, or progressive familial intrahepatic cholestasis type 1 (PFIC1). The rarity of FIC1 deficiency has largely prevented a detailed analysis of its natural history, effects of predicted protein truncating mutations (PPTMs), and possible associations of serum bile acid (sBA) concentrations and surgical biliary diversion (SBD) with long-term outcome. We aimed to provide novel insights by using the largest genetically defined cohort of FIC1 deficiency patients to date. This multicenter, combined retrospective and prospective study included 130 patients with compound heterozygous or homozygous predicted pathogenic ATP8B1 variants. Patients were categorized according to the number of PPTMs (i.e., splice site, frameshift due to deletion or insertion, nonsense, duplication); FIC1-A (n=67; no PPTM), FIC1-B (n=29; one PPTM) or FIC1-C (n=34; two PPTMs). Survival analysis showed an overall native liver survival (NLS) of 44% at age 18y. NLS was comparable between FIC1-A, FIC1-B, and FIC1-C (%NLS at age 10y: 67%, 41%, and 59%, respectively; P=0.12), despite FIC1-C undergoing SBD less often (%SBD at age 10y: 65%, 57%, and 45%, respectively; P=0.03). sBAs at presentation were negatively associated with NLS (NLS at age 10y; sBAs, University of Colorado; Baylor College of Medicine; Children’s Hospital of Philadelphia; Children’s Hospital of Pittsburgh; St Louis Children’s Hospital; Riley Hospital for Children; Seattle Children’s Hospital; M.D./Ph.D. Scholarship from the University of Groningen; European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) Networking Grant 2019; ChilDReN National Institutes of Health Grants; Ann & Robert H. Lurie Children’s Hospital; Albireo and Mirum Pharmaceuticals

Published
2021

40. Two cases of DCDC2-related neonatal sclerosing cholangitis with developmental delay and literature review

Author

Ruth De Bruyne, Patrick Verloo, Tassos Grammatikopoulos, Bert Callewaert, Stephanie Van Biervliet, Anne Hoorens, Myriam Van Winckel, Maesha Deheragoda, Sofie Symoens, Hannes Syryn, and Saskia Vande Velde

Subjects
Microcephaly, Pathology, medicine.medical_specialty, Genotype, Biopsy, Developmental Disabilities, Cholangitis, Sclerosing, DNA Mutational Analysis, Context (language use), Ciliopathies, Consanguinity, Nephronophthisis, Biliary atresia, Exome Sequencing, Genetics, medicine, Humans, Genetic Predisposition to Disease, Global developmental delay, Age of Onset, Genetics (clinical), Alleles, Genetic Association Studies, business.industry, Infant, Newborn, medicine.disease, Ciliopathy, Phenotype, Mutation, Congenital hepatic fibrosis, business, Microtubule-Associated Proteins
Abstract

Ciliopathies are a group of clinical and molecular heterogeneous conditions with pleiotropic manifestations affecting the central nervous system, renal, liver, skeletal, and ocular systems. Biallelic pathogenic variants in DCDC2 cause a ciliopathy primarily presenting with neonatal sclerosing cholangitis (NSC). Pathogenic variants in DCDC2 have further been reported in the context of nephronophthisis and non-syndromic recessive deafness. Polymorphisms in DCDC2 have also been associated with dyslexia and DCDC2 has a role in neuronal development. We report on two unrelated patients with DCDC2-related NSC with additional central nervous system impairment manifesting as microcephaly, global developmental delay, and axial hypotonia. Histological findings of our patients can mimic biliary atresia or congenital hepatic fibrosis. We further show that transmission electron microscopy in patients with NSC does not always show absence of primary cilia. Hence patients with DCDC2 pathogenic variants should also undergo an evaluation of neuromotor development. Review of all reported patients further reveals a risk for supra-aortic arterial aneurysms.

Published
2021

41. Novel compound heterozygous STN1 variants are associated with Coats Plus syndrome

Author

Angharad Walters, Shilpa Dugar, Helen V. Firth, Luis Seabra, Tanvi Acharya, Yanick J. Crow, Tassos Grammatikopoulos, Alasdair Parker, Acharya, Tanvi [0000-0003-0330-6585], and Apollo - University of Cambridge Repository

Subjects
Male, Models, Molecular, 0301 basic medicine, Pathology, leukodystrophy, Protein Conformation, DNA Mutational Analysis, 030105 genetics & heredity, QH426-470, Compound heterozygosity, medicine.disease_cause, Leukoencephalopathies, Medicine, Coats' disease, Central Nervous System Cysts, Child, Genetics (clinical), CLINICAL REPORTS, Mutation, Gastrointestinal tract, Brain Neoplasms, stn1, coats plus, Calcinosis, Phenotype, Pancytopenia, Retinal telangiectasia, Muscle Spasticity, CLINICAL REPORT, Heterozygote, medicine.medical_specialty, Telomere-Binding Proteins, Neuroimaging, Structure-Activity Relationship, 03 medical and health sciences, Retinal Diseases, Seizures, Genetics, Humans, Genetic Predisposition to Disease, Molecular Biology, Alleles, Genetic Association Studies, business.industry, Leukodystrophy, medicine.disease, 030104 developmental biology, Ataxia, Tomography, X-Ray Computed, business, Magnetic Resonance Angiography
Abstract

Funder: Wellcome, Aim: Coats plus syndrome (CP) is a rare autosomal recessive disorder, characterised by retinal telangiectasia exudates (Coats disease), leukodystrophy, distinctive intracranial calcification and cysts, as well as extra‐neurological features including abnormal vasculature of the gastrointestinal tract, portal hypertension and osteopenia with a tendency to fractures. CP most frequently occurs due to loss‐of‐function mutations in CTC1. The encoded protein CTC1 constitutes part of the CST (CTC1‐STN1‐TEN1) complex, and three patients have been described with CP due to biallelic mutations in STN1. Together with the identification of homozygosity for a specific loss‐of‐function mutation in POT1 in a sibling pair, these observations highlight a defect in the maintenance of telomere integrity as the cause of CP, although the precise mechanism leading to the micro‐vasculopathy seen at a pathological level remains unclear. Here, we present the investigation of a fourth child who presented to us with retinal exudates, intracranial calcifications and developmental delay, in keeping with a diagnosis of CP, and later went on to develop pancytopenia and gastrointestinal bleeding. Genome sequencing revealed compound heterozygous variants in STN1 as the likely genetic cause of CP in this present case. Methods: We assessed the phenotype to be CP and undertook targeted sequencing. Results: Whilst sequencing of CTC1 and POT1 was normal, we identified novel compound heterozygous variants in STN1 (previous gene symbol OBFC1): one loss‐of‐function––c.894dup (p.(Asp299Argfs*58)); and one missense––c.707T>C (p.(Leu236Pro)). Conclusion: Given the clinical phenotype and identified variants we suggest that this is only the fourth patient reported to date with CP due to mutations in STN1.

Published
2021

42. Pancreatoblastoma: A rare indication for liver transplantation in children

Author

Hector Vilca-Melendez, Tassos Grammatikopoulos, Sucheta Vaidya, Maria Mercadal-Hally, Nigel Heaton, and Anil Dhawan

Subjects
Pediatrics, medicine.medical_specialty, Hepatology, business.industry, medicine.medical_treatment, Gastroenterology, MEDLINE, Pancreatoblastoma, Medicine, Liver transplantation, business, medicine.disease
Published
2020

43. Autoimmune pancreatitis in children: A single centre experience in diagnosis, management and long term follow up

Author

Nedim Hadzic, Maria E. Sellars, John Devlin, Maesha Deheragoda, Tassos Grammatikopoulos, Huey Miin Lee, Phil Harrison, and Anil Dhawan

Subjects
Male, Pediatrics, medicine.medical_specialty, Adolescent, Long term follow up, Endocrinology, Diabetes and Metabolism, Azathioprine, Disease, Autoimmune Diseases, 03 medical and health sciences, 0302 clinical medicine, Humans, Medicine, Child, Retrospective Studies, Autoimmune pancreatitis, Hepatology, business.industry, Gastroenterology, medicine.disease, Ulcerative colitis, Treatment Outcome, Gene Expression Regulation, Pancreatitis, 030220 oncology & carcinogenesis, Radiological weapon, Chronic Disease, Cohort, Female, 030211 gastroenterology & hepatology, business, medicine.drug
Abstract

Objectives Autoimmune pancreatitis (AIP) is a rare form of chronic pancreatitis and data is limited in the paediatric population. We aim to describe in detail a cohort of paediatric patients with AIP including their presentation, investigations that led to their diagnosis, management and long-term follow up. Methods We retrospectively reviewed the data of 6 patients diagnosed with AIP over an 10-year period. Data including demographics, clinical information, laboratory parameters, serological markers, radiological and histological findings as well as longitudinal follow up were collected. Results Out of the six patients, one was diagnosed with definitive Type 1 AIP, two with definitive Type 2 AIP, two with probable Type 2 AIP and one with suspected Type 2 AIP. Median time of follow up was 3.9 years (range 2.6–10.1). 4 patients had pancreatic biopsies with 2 of these patients showing granulocytic epithelial lesions (GELs). 4 patients received steroids and two of them developed ulcerative colitis. Azathioprine was commenced on the patient with Type 1 AIP to help her wean off steroids that caused significant side effects on her. Only two patients developed exocrine insufficiency. Conclusions The long term follow up of our cohort of paediatric AIP shows good prognosis. More follow up data on patients with AIP is needed to help further characterize and define the disease.

Published
2019

45. Hyperspectral Stimulated Raman Scattering Image Enhancement, Denoising and Segmentation via a Deep Neural-Net

Author

Pedram Abdolghader, Andy Ridsdale, Isaac Tamblyn, Adrian F. Pegoraro, François Légaré, Tassos Grammatikopoulos, and Albert Stolow

Subjects
Computer Science::Machine Learning, Computer science, Noise reduction, Computer Science::Neural and Evolutionary Computation, Statistics::Machine Learning, symbols.namesake, Segmentation, image enhancement, raman scattering, image segmentation, noise reduction, deep convolutional neural net, Quantitative Biology::Neurons and Cognition, Artificial neural network, business.industry, pattern recognition, Hyperspectral imaging, Pattern recognition, Image segmentation, Image enhancement, neural networks, Autoencoder, image recognition, classification, Computer Science::Computer Vision and Pattern Recognition, microscopy, symbols, Artificial intelligence, business, stimulated Raman Scattering microscopy, Raman scattering
Abstract

We demonstrate the use of an unsupervised convolutional autoencoder neural network to denoise and segment hyperspectral Stimulated Raman Scattering images., 2021 Photonics North (PN), 2021-05-31 - 2021-06-02, Toronto, ON, Canada

Published
2021

47. O3 The UK paediatric liver transplant programme during the COVID-19 pandemic

Author

Julie Whitney, Douglas Thorburn, Nigel Heaton, Sanjay Rajwal, Derek Manas, Magdy Attia, Rhiannon Taylor, Darius F. Mirza, Anil Dhawan, John Forsythe, John Isaac, Jane Hartley, Tassos Grammatikopoulos, and Sarah Watson

Subjects
Hepatoblastoma, Pediatrics, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), business.industry, medicine.medical_treatment, Perioperative, Liver transplantation, medicine.disease, Full recovery, Intensive care, Pandemic, medicine, Organ donation, business
Abstract

Introduction The UK has been severely affected by the COVID-19 pandemic. The impact on the adult population has been disproportionately higher when compared to children with consequent challenges to organ donation and liver transplantation (LT). Across the three UK paediatric liver centres there has only been a very small number of patients who tested positive for COVID-19 and all made a speedy and full recovery. We report here the response during the pandemic across the 3 paediatric LT centres. Methods A series of nationally agreed policy changes affecting the liver procurement, listing and transplant process were agreed during regular meetings with LT centre directors and NHSE. Actions at a local and national level were agreed to protect and maintain the paediatric LT programmes. Data were collected from 27/03/20 until 26/11/20 and compared with same time period for the years 2016–19. Results During the study period, there was a significant reduction in the adult population in the mean number of weekly liver offers, donors and LTs compared to before the pandemic with signs of recovery between the 1st and 2nd UK lockdown periods (figure 1). More specifically the number of livers offered nationally was reduced from an average 30–40/week to only Overall, 65–80 paediatric LTs are performed annually across the UK’s 3 paediatric centres. From March-November 2020 there were 58(82%) elective and 13(18%) super urgent (acute liver failure & hepatoblastoma) paediatric LTs performed. Donor Brain Dead (DBD) and Donor Cardiac Dead (DCDC) LTs were 54(76%) and 3(4%), respectively. Living related LT (LRLT) programme was sustained comprising 20% of LTs performed. The number of paediatric LTs performed during the pandemic was comparable to those performed yearly since 2016. The number of LT per paediatric centre for King’s College Hospital (KCH), Birmingham Children’s Hospital (BCH) and Leeds Liver Unit were 40 (56%), 15(21%) and 16(23%), respectively with excellent outcome. A 15-year-old girl from KCH diagnosed with Wilson disease presented with liver failure and became COVID-19 positive whilst listed. She underwent LT soon after becoming COVID-19 negative. No perioperative mortality was reported with excellent outcome so far in all. Conclusion The current COVID-19 pandemic had a significant impact on the UK adult LT programme. The paediatric programme LT was preserved despite a decrease in organ offering and retrieval nationally plus limitations on adult intensive care resources at a regional level. Overall, paediatric LT outcome remained very good.

Published
2021

48. EP1232: ODEVIXIBAT EFFECTS ON CHOLESTASIS-RELATED PARAMETERS: ANALYSIS OF POOLED DATA FROM THE PEDFIC 1 AND PEDFIC 2 STUDIES IN CHILDREN WITH PROGRESSIVE FAMILIAL INTRAHEPATIC CHOLESTASIS

Author

Richard J. Thompson, Reha Artan, Ulrich Baumann, Piotr Czubkowski, Buket Dalgic, Özlem Durmaz, Emmanuel Gonzalès, Tassos Grammatikopoulos, Girish Gupte, Patrick Horn, Alain Lachaux, Patrick Mckiernan, Hasan Özen, Sanjay R. Rajwal, Bertrand Roquelaure, Ekkehard Sturm, Henkjan J. Verkade, Qifeng Yu, and Lise Kjems

Subjects
Hepatology, Gastroenterology
Published
2022

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