A case of successful late steroid withdrawal after ABO-incompatible kidney transplantation
Few data exist regarding steroid withdrawal in ABO-incompatible (ABO-i) kidney transplantation (KT). Here, we report a case of steroid withdrawal after ABO-i KT. A 46-year-old man diagnosed with Henoch-Schonlein purpura received ABO-i KT from his 42-year-old sister. The recipient and donor blood typ...
Saved in:
Published in: | Clinical transplantation and research Vol. 34; no. 2; pp. 121 - 125 |
---|---|
Main Authors: | , , , , , |
Format: | Journal Article |
Language: | English |
Published: |
The Korean Society for Transplantation
30-06-2020
Korean Society for Transplantation 대한이식학회 |
Subjects: | |
Online Access: | Get full text |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
Abstract | Few data exist regarding steroid withdrawal in ABO-incompatible (ABO-i) kidney transplantation (KT). Here, we report a case of steroid withdrawal after ABO-i KT. A 46-year-old man diagnosed with Henoch-Schonlein purpura received ABO-i KT from his 42-year-old sister. The recipient and donor blood types were O and AB, respectively. His preoperative ABO antibody titers were anti-A of 1:16 and anti-B of 1:8 in isoagglutinin test. HLA mismatch was 0 and he received a single 325 mg/m
2
dose of intravenous (IV) rituximab 4 weeks before KT. Three sessions of plasma exchange were undertaken before KT and low-dose IV immunoglobulin of 0.1 g/kg was administered after plasma exchange. On the day of the operation, ABO antibody titer decreased to anti-A of 1:4 and anti-B of 1:2. Renal function remained stable after KT. The patient wished to stop steroid treatment despite the risk of rejection after withdrawal. Steroid tapering was initiated at 20 months and accomplished at 26 months after KT. At that time, serum creatinine level was 1.13 mg/dL, and anti-A and anti-B titers were 1:8 and 1:2, respectively. No issues were observed after steroid withdrawal. At 48 months after KT, serum creatinine level was 1.21 mg/dL, and anti-A and anti-B antibody titers were 1:32 and 1:2, respectively. Steroid withdrawal in ABO-i KT might be considered in immunologically low-risk patients. |
---|---|
AbstractList | Few data exist regarding steroid withdrawal in ABO-incompatible (ABO-i) kidney transplantation (KT). Here, we report a case of steroid withdrawal after ABO-i KT. A 46-year-old man diagnosed with Henoch-Schonlein purpura received ABO-i KT from his 42-year-old sister. The recipient and donor blood types were O and AB, respectively. His preoperative ABO antibody titers were anti-A of 1:16 and anti-B of 1:8 in isoagglutinin test. HLA mismatch was 0 and he received a single 325 mg/m
2
dose of intravenous (IV) rituximab 4 weeks before KT. Three sessions of plasma exchange were undertaken before KT and low-dose IV immunoglobulin of 0.1 g/kg was administered after plasma exchange. On the day of the operation, ABO antibody titer decreased to anti-A of 1:4 and anti-B of 1:2. Renal function remained stable after KT. The patient wished to stop steroid treatment despite the risk of rejection after withdrawal. Steroid tapering was initiated at 20 months and accomplished at 26 months after KT. At that time, serum creatinine level was 1.13 mg/dL, and anti-A and anti-B titers were 1:8 and 1:2, respectively. No issues were observed after steroid withdrawal. At 48 months after KT, serum creatinine level was 1.21 mg/dL, and anti-A and anti-B antibody titers were 1:32 and 1:2, respectively. Steroid withdrawal in ABO-i KT might be considered in immunologically low-risk patients. Few data exist regarding steroid withdrawal in ABO-incompatible (ABO-i) kidney transplantation (KT). Here, we report a case of steroid withdrawal after ABO-i KT. A 46-year-old man diagnosed with Henoch-Schonlein purpura received ABO-i KT from his 42-year-old sister. The recipient and donor blood types were O and AB, respectively. His preoperative ABO antibody titers were anti-A of 1:16 and anti-B of 1:8 in isoagglutinin test. HLA mismatch was 0 and he received a single 325 mg/m2 dose of intravenous (IV) rituximab 4 weeks before KT. Three sessions of plasma exchange were undertaken before KT and low-dose IV immunoglobulin of 0.1 g/kg was administered after plasma exchange. On the day of the operation, ABO antibody titer decreased to anti-A of 1:4 and anti-B of 1:2. Renal function remained stable after KT. The patient wished to stop steroid treatment despite the risk of rejection after withdrawal. Steroid tapering was initiated at 20 months and accomplished at 26 months after KT. At that time, serum creatinine level was 1.13 mg/dL, and anti-A and anti-B titers were 1:8 and 1:2, respectively. No issues were observed after steroid withdrawal. At 48 months after KT, serum creatinine level was 1.21 mg/dL, and anti-A and anti-B antibody titers were 1:32 and 1:2, respectively. Steroid withdrawal in ABO-i KT might be considered in immunologically low-risk patients. Few data exist regarding steroid withdrawal in ABO-incompatible (ABO-i) kidney transplantation (KT). Here, we report a case of steroid withdrawal after ABO-i KT. A 46-year-old man diagnosed with Henoch-Schonlein purpura received ABO-i KT from his 42-year-old sister. The recipient and donor blood types were O and AB, respectively. His preoperative ABO antibody titers were anti-A of 1:16 and anti-B of 1:8 in isoagglutinin test. HLA mismatch was 0 and he received a single 325 mg/m2 dose of intravenous (IV) rituximab 4 weeks before KT. Three sessions of plasma exchange were undertaken before KT and low-dose IV immunoglobulin of 0.1 g/kg was administered after plasma exchange. On the day of the operation, ABO antibody titer decreased to anti-A of 1:4 and anti-B of 1:2. Renal function remained stable after KT. The patient wished to stop steroid treatment despite the risk of rejection after withdrawal. Steroid tapering was initiated at 20 months and accomplished at 26 months after KT. At that time, serum creatinine level was 1.13 mg/dL, and anti-A and anti-B titers were 1:8 and 1:2, respectively. No issues were observed after steroid withdrawal. At 48 months after KT, serum creatinine level was 1.21 mg/dL, and anti-A and anti-B antibody titers were 1:32 and 1:2, respectively. Steroid withdrawal in ABO-i KT might be considered in immunologically low-risk patients. KCI Citation Count: 0 |
Author | Jo, Hyung Ah Jun, Heungman Han, Kum Hyun Kim, Han-Seong Han, Sang Youb Cho, Jeong Min |
AuthorAffiliation | 1 Department of Internal Medicine, Inje University College of Medicine, Ilsan Paik Hospital, Goyang, Korea 3 Department of Pathology, Inje University College of Medicine, Ilsan Paik Hospital, Goyang, Korea 2 Department of Surgery, Inje University College of Medicine, Ilsan Paik Hospital, Goyang, Korea |
AuthorAffiliation_xml | – name: 3 Department of Pathology, Inje University College of Medicine, Ilsan Paik Hospital, Goyang, Korea – name: 1 Department of Internal Medicine, Inje University College of Medicine, Ilsan Paik Hospital, Goyang, Korea – name: 2 Department of Surgery, Inje University College of Medicine, Ilsan Paik Hospital, Goyang, Korea |
Author_xml | – sequence: 1 givenname: Jeong Min orcidid: 0000-0001-7643-994X surname: Cho fullname: Cho, Jeong Min organization: Department of Internal Medicine, Inje University College of Medicine, Ilsan Paik Hospital, Goyang, Korea – sequence: 2 givenname: Heungman orcidid: 0000-0003-2530-4388 surname: Jun fullname: Jun, Heungman organization: Department of Surgery, Inje University College of Medicine, Ilsan Paik Hospital, Goyang, Korea – sequence: 3 givenname: Hyung Ah orcidid: 0000-0002-5574-554X surname: Jo fullname: Jo, Hyung Ah organization: Department of Internal Medicine, Inje University College of Medicine, Ilsan Paik Hospital, Goyang, Korea – sequence: 4 givenname: Kum Hyun orcidid: 0000-0003-3700-0066 surname: Han fullname: Han, Kum Hyun organization: Department of Internal Medicine, Inje University College of Medicine, Ilsan Paik Hospital, Goyang, Korea – sequence: 5 givenname: Han-Seong orcidid: 0000-0003-3740-0588 surname: Kim fullname: Kim, Han-Seong organization: Department of Pathology, Inje University College of Medicine, Ilsan Paik Hospital, Goyang, Korea – sequence: 6 givenname: Sang Youb orcidid: 0000-0003-3312-0597 surname: Han fullname: Han, Sang Youb organization: Department of Internal Medicine, Inje University College of Medicine, Ilsan Paik Hospital, Goyang, Korea |
BackLink | https://www.kci.go.kr/kciportal/ci/sereArticleSearch/ciSereArtiView.kci?sereArticleSearchBean.artiId=ART002603163$$DAccess content in National Research Foundation of Korea (NRF) |
BookMark | eNpVkU1rHDEMhk1JadI0P6A3X3uYqb9mbF8K29CPhUCgpJdejOyxE-_O2os925B_X2e3LQQEEq-kB6H3LTpLOXmE3lPSC6aGj9vN0jPCSM9Fz3rK6Ct0wUZJO6WIOPtXS03O0VWtG0IIGyhlZHyDzvkgR82FvkC_VthB9TgHXA_O-VrDYcYzLB7XxZccJ_wYl4epwCPMGELT8OrzbReTy7s9LNHOHm_jlPwTXgqkup8hLU3P6R16HWCu_upvvkQ_v365u_7e3dx-W1-vbjrHKaEds9pRN0plFdhgh5EzrUdHBUghCNVEWc2Et6rdD9I7RaQamJJSkcGNYeKX6MOJm0owWxdNhnjM99lsi1n9uFsbPdAWrM2uT7NTho3Zl7iD8nRcOAq53BsoS3SzN4pJaylwZS0RQJUKXIEMVjhKuA2ysT6dWPuD3fnJ-dQeML-Avuyk-NBu-m10g2mmGoCeAK7kWosP_3cpMc8em-axefbYcGGYaR7zP10ImwE |
Cites_doi | 10.1159/000355855 10.1097/TP.0b013e3181880c0f 10.1002/14651858.CD005632.pub3 10.1111/tri.12735 10.1097/TP.0b013e3181c9cc67 10.1111/j.1600-6143.2004.00464.x 10.1097/TP.0b013e318245b2af 10.2215/CJN.04880516 10.1681/ASN.2019040416 10.1097/SLA.0b013e318187d1da 10.1016/j.intimp.2006.07.018 10.1016/j.krcp.2015.08.005 10.1016/S0140-6736(18)32091-9 10.1016/j.kint.2019.02.041 10.1111/j.1600-6143.2010.03103.x |
ContentType | Journal Article |
Copyright | 2020 The Korean Society for Transplantation 2020 |
Copyright_xml | – notice: 2020 The Korean Society for Transplantation 2020 |
DBID | AAYXX CITATION 5PM DOA ACYCR |
DOI | 10.4285/kjt.2020.34.2.121 |
DatabaseName | CrossRef PubMed Central (Full Participant titles) Directory of Open Access Journals Korean Citation Index |
DatabaseTitle | CrossRef |
DatabaseTitleList | |
Database_xml | – sequence: 1 dbid: DOA name: Directory of Open Access Journals url: http://www.doaj.org/ sourceTypes: Open Website |
DeliveryMethod | fulltext_linktorsrc |
EISSN | 2671-8804 3022-7712 |
EndPage | 125 |
ExternalDocumentID | oai_kci_go_kr_ARTI_9519512 oai_doaj_org_article_827bb1a38bb04a188f38a7fb4c103bf7 10_4285_kjt_2020_34_2_121 |
GroupedDBID | AAYXX ALMA_UNASSIGNED_HOLDINGS CITATION GROUPED_DOAJ M~E PGMZT RPM 5PM ACYCR |
ID | FETCH-LOGICAL-c3101-2b9c1c678b8abfb5632996c14a74401908b924eb8025a7ec807852877805c6fd3 |
IEDL.DBID | RPM |
ISSN | 2671-8790 3022-6783 |
IngestDate | Fri Nov 01 03:38:40 EDT 2024 Tue Oct 22 15:07:53 EDT 2024 Tue Sep 17 21:15:50 EDT 2024 Fri Aug 23 03:45:18 EDT 2024 |
IsDoiOpenAccess | true |
IsOpenAccess | true |
IsPeerReviewed | true |
IsScholarly | true |
Issue | 2 |
Language | English |
License | This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
LinkModel | DirectLink |
MergedId | FETCHMERGED-LOGICAL-c3101-2b9c1c678b8abfb5632996c14a74401908b924eb8025a7ec807852877805c6fd3 |
ORCID | 0000-0003-3700-0066 0000-0003-3740-0588 0000-0003-3312-0597 0000-0003-2530-4388 0000-0001-7643-994X 0000-0002-5574-554X |
OpenAccessLink | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9188928/ |
PMID | 35769349 |
PageCount | 5 |
ParticipantIDs | nrf_kci_oai_kci_go_kr_ARTI_9519512 doaj_primary_oai_doaj_org_article_827bb1a38bb04a188f38a7fb4c103bf7 pubmedcentral_primary_oai_pubmedcentral_nih_gov_9188928 crossref_primary_10_4285_kjt_2020_34_2_121 |
PublicationCentury | 2000 |
PublicationDate | 2020-06-30 |
PublicationDateYYYYMMDD | 2020-06-30 |
PublicationDate_xml | – month: 06 year: 2020 text: 2020-06-30 day: 30 |
PublicationDecade | 2020 |
PublicationTitle | Clinical transplantation and research |
PublicationYear | 2020 |
Publisher | The Korean Society for Transplantation Korean Society for Transplantation 대한이식학회 |
Publisher_xml | – name: The Korean Society for Transplantation – name: Korean Society for Transplantation – name: 대한이식학회 |
References | ref13 ref12 ref15 ref14 ref11 ref10 ref2 ref1 ref8 ref7 ref9 ref4 ref3 ref6 ref5 |
References_xml | – ident: ref15 doi: 10.1159/000355855 – ident: ref3 doi: 10.1097/TP.0b013e3181880c0f – ident: ref12 doi: 10.1002/14651858.CD005632.pub3 – ident: ref1 doi: 10.1111/tri.12735 – ident: ref2 doi: 10.1097/TP.0b013e3181c9cc67 – ident: ref7 doi: 10.1111/j.1600-6143.2004.00464.x – ident: ref5 doi: 10.1097/TP.0b013e318245b2af – ident: ref13 doi: 10.2215/CJN.04880516 – ident: ref10 doi: 10.1681/ASN.2019040416 – ident: ref9 doi: 10.1097/SLA.0b013e318187d1da – ident: ref4 doi: 10.1016/j.intimp.2006.07.018 – ident: ref6 doi: 10.1016/j.krcp.2015.08.005 – ident: ref8 doi: 10.1016/S0140-6736(18)32091-9 – ident: ref11 doi: 10.1016/j.kint.2019.02.041 – ident: ref14 doi: 10.1111/j.1600-6143.2010.03103.x |
SSID | ssj0002511206 ssj0003307727 |
Score | 2.1635993 |
Snippet | Few data exist regarding steroid withdrawal in ABO-incompatible (ABO-i) kidney transplantation (KT). Here, we report a case of steroid withdrawal after ABO-i... |
SourceID | nrf doaj pubmedcentral crossref |
SourceType | Open Website Open Access Repository Aggregation Database |
StartPage | 121 |
SubjectTerms | Case Report kidney transplantation; abo blood-group system; blood group incompatibility; steroid; withholding treatment 의학일반 |
SummonAdditionalLinks | – databaseName: Directory of Open Access Journals dbid: DOA link: http://sdu.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwrV09T8MwELWAiQWBAFG-ZCEmpEASu44ztkAFCwyAhFgsnz-gtKSopUL8e-6SgigLC1OkJJadd4nenXP3jrFDG4TzTtsEPEjarVIJlJFy3FPh0tIHr6lQ-OKmuLrXZ-ckk_Pd6otywhp54Aa4E50XAJkVGiCVNtM6Cm2LCNJlqYDY1JGnqgmmqJOcKjL8xMvZL0z0rtsng2fKmswxQJXHOekpzJFQrdWP1FKN4-_MyB9U01tlKzMfkXeata2xhVCts4cOd8g4fBT5ZFp3OYzTIR-iq8hJ62DU95z2VP3YvuPYuvU373SvE1JfeKG0aRgGPuj7Knzwt1rRfGibsqNqg931zm9PL5JZY4TEoTeWJTmULnNIM6AtRGgrgaSiXCYtyf0hxWvAsCqARofGFsGRpnwbQyPqX-BU9GKTLVWjKmwxjrAqBVY5WWgpodRBWIxyfESErSh8ix19IWVeG_0Lg3EDwWoQVkOwGiFNbhDWFusSlt83knR1fQINamYGNX8ZtMUO0BJm4Pr1eDo-jsxgbNDBvzQlqeFkeYsVc4aam3L-StV_qlWzS5yqzPX2f6xxhy3Tgzd5g7ts6W08DXtsceKn-_V7-AlcnuRr priority: 102 providerName: Directory of Open Access Journals |
Title | A case of successful late steroid withdrawal after ABO-incompatible kidney transplantation |
URI | https://pubmed.ncbi.nlm.nih.gov/PMC9188928 https://doaj.org/article/827bb1a38bb04a188f38a7fb4c103bf7 https://www.kci.go.kr/kciportal/ci/sereArticleSearch/ciSereArtiView.kci?sereArticleSearchBean.artiId=ART002603163 |
Volume | 34 |
hasFullText | 1 |
inHoldings | 1 |
isFullTextHit | |
isPrint | |
ispartofPNX | Clinical Transplantation and Research, 2020, 34(2), , pp.121-125 |
link | http://sdu.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1Lj9MwELboHtBeEAgQ5bGyECektE3sxM6xu-xqOfCQAAlxsTx-LNmmySq7FeLfM-OmqOXIKVISy_E3TmbG-fwNY29sEM47bTPwIGm1qsqgjsRxXwi3qH3wmjYKX35RH7_rd-ckk1Pu9sIk0r6DZta161nX_Ezcypu1m-94YvPPH87qXOu60PMJm2BsuJei0-eXYuYi1dQsKpXj216PfzMx0C7nq2siUBaYq8pZQdIKx-y-KKkgIKlp7rmmpOCPDqcb4r98yT0HdPGQPRgjR77cPuEjdi90j9mPJXfoh3gf-e0m1T6Mm5a3GEByUkDoG89ppdUP9he2TQXB-fL0U0aaDGsiU0Mb-KrxXfjN75LOeWu3m5G6J-zbxfnXs8tsLJeQOYzR8qyA2uUOnQ9oCxHKSqCrqVwuLYkAouPXgMlWAI0QWRUcKc2XmDBRVQNXRS-esqOu78IzxjVAVYGtnFRaSqh1EBZzHx8jSCuUn7K3O6TMzVYVw2A2QQgbRNgQwkZIUxhEeMpOCcu_N5KgdTrRD1dmNKvRhQLIrcCeF9KifaPQVmF3Ll8IiGrKXqMlzMo1qT0dr3qzGgyG_e9NTRo5eTFl6sBQB10eXsGplbS0x6n0_L9bvmDHNNothfAlO7obNuEVm9z6zUnK70_S7PwDBkLo9Q |
link.rule.ids | 230,315,729,782,786,866,887,2106,27933,27934,53800,53802 |
linkProvider | National Library of Medicine |
linkToHtml | http://sdu.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1Lb9QwELZokaCXAgLEUh4W4oSU3STOwzluS6utaAsSRUJcLI8fJWw2qdKuEP-eGW8W7XLsKVIcy8l8cWbG-fwNY--1E8YaqSOwkNFqVRFB5YnjHgsTV9ZZSRuFZ1_Li-_y4zHJ5OTrvTCBtG-gHrfNYtzWPwO38nphJmue2OTL-VGVSFmlcrLD7uN8jeONJJ0-wBQ1p6GqZlqUCc73avifiaF2Ppn_IgplitlqNk5JXGGPPRA5lQQkPc0N5xQ0_NHltL3_nzG54YJOHt3x5h-z_SHm5NNV8xN2z7VP2Y8pN-jBeOf5zTJUTfTLhjcYenLSTuhqy2mN1vb6N_YNpcT59PBzRGoOC6JhQ-P4vLat-8Nvg0J6o1fbmNpn7NvJ8eXRLBoKLUQGo7skSqEyiUG3BVKDh7wQ6KQKk2Sa5AMxZJCAaZoDiabVpTOkUZ9jqkX1EEzhrXjOdtuudS8YlwBFAbowWSmzDCrphMasyXoPmRalHbEPawur65WehsI8hJBRiIwiZJTIVKoQmRE7JAz-XUhS2OFE11-pwaZKpiVAogWOHGcajeuF1CUOZ5JYgC9H7B0iqOamDv3peNWpea8wYThVFanrJOmIlVsAbw253YK4BhXuAceXd-75lj2cXZ6fqbPTi08HbI-efEVEfMV2b_ule812buzyTXi3_wKWFv2V |
linkToPdf | http://sdu.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV1Lb9QwELZokapeShEgti3UQpyQsknsPJzj9rFqBZRKgIS4WH6WsNlklXaF-PfMeNNqlyOcIiW2LM8XZ2acz98Q8lY5bqwRKtJWZ7hbVUS68shxT7hJKuuswIPCF5_Lq2_i7Bxlch5KfQXSvtH1uG3m47b-EbiVi7mJ73li8fXH0yoVomIiXlgfb5HHsGYTtpao40cYI2cWKmuyokxhzVfDP00It_N49hNplAwy1mzMUGBhl-zwHMsCoqbmmoMKOv7gdtre_82aXHND0yf_MYF9sjfEnnSyavKUPHLtM_J9Qg14Mtp5ersM1RP9sqENhKAUNRS62lLcq7W9-gV9Q0lxOjn5FKGqwxzp2LpxdFbb1v2md0EpvVGr40ztc_J1ev7l9CIaCi5EBqK8NGK6MqkB96WF0l7nBQdnVZg0UygjCKGD0JCuOQ3mzlXpDGrV55ByYV0EU3jLX5DttmvdS0KF1kWhVWGyUmSZroTjCrIn673OFC_tiLy7t7JcrHQ1JOQjiI4EdCSiI3kmmQR0RuQEcXhoiJLY4UbX38jBrlKwUutUcRg5yRQY2HOhShjOpAnXvhyRN4CinJk69MfrTSdnvYTE4VJWqLKTshEpN0DeGHLzCWAb1LgHLA_-uecx2bk-m8oPl1fvD8kuTnzFRzwi23f90r0iW7d2-Tq83n8AmT4AJA |
openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=A+case+of+successful+late+steroid+withdrawal+after+ABO-incompatible+kidney+transplantation&rft.jtitle=Korean+journal+of+transplantation+%28Online%29&rft.au=Cho%2C+Jeong+Min&rft.au=Jun%2C+Heungman&rft.au=Jo%2C+Hyung+Ah&rft.au=Han%2C+Kum+Hyun&rft.date=2020-06-30&rft.pub=The+Korean+Society+for+Transplantation&rft.issn=2671-8790&rft.eissn=2671-8804&rft.volume=34&rft.issue=2&rft.spage=121&rft.epage=125&rft_id=info:doi/10.4285%2Fkjt.2020.34.2.121&rft_id=info%3Apmid%2F35769349&rft.externalDBID=PMC9188928 |
thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=2671-8790&client=summon |
thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=2671-8790&client=summon |
thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=2671-8790&client=summon |