{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T10:34:02Z","timestamp":1715596442627},"reference-count":58,"publisher":"Georg Thieme Verlag KG","issue":"13","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Horm Metab Res"],"published-print":{"date-parts":[[2015,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Identification and management of patients with primary aldosteronism are of\n                    utmost importance because it is a frequent cause of endocrine hypertension, and\n                    affected patients display an increase of cardio- and cerebro-vascular events,\n                    compared to essential hypertensives. Distinction of primary aldosteronism\n                    subtypes is of particular relevance to allocate the patients to the appropriate\n                    treatment, represented by mineralocorticoid receptor antagonists for bilateral\n                    forms and unilateral adrenalectomy for patients with unilateral aldosterone\n                    secretion. Subtype differentiation of confirmed hyperaldosteronism comprises\n                    adrenal CT scanning and adrenal venous sampling. In this review, we will discuss\n                    different clinical scenarios where execution, interpretation of adrenal vein\n                    sampling and subsequent patient management might be challenging, providing the\n                    clinician with useful information to help the interpretation of controversial\n                    procedures.<\/jats:p>","DOI":"10.1055\/s-0035-1565089","type":"journal-article","created":{"date-parts":[[2015,11,18]],"date-time":"2015-11-18T00:07:10Z","timestamp":1447805230000},"page":"959-966","source":"Crossref","is-referenced-by-count":5,"title":["Subtype Diagnosis of Primary Aldosteronism: Approach to Different\n                    Clinical Scenarios"],"prefix":"10.1055","volume":"47","author":[{"given":"J.","family":"Burrello","sequence":"first","affiliation":[{"name":"Division of Internal Medicine and Hypertension, University of Torino,\n                    Torino, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Monticone","sequence":"first","affiliation":[{"name":"Division of Internal Medicine and Hypertension, University of Torino,\n                    Torino, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Tetti","sequence":"first","affiliation":[{"name":"Division of Internal Medicine and Hypertension, University of Torino,\n                    Torino, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D.","family":"Rossato","sequence":"first","affiliation":[{"name":"Division of Radiology, University of Torino, Torino,\n                    Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K.","family":"Versace","sequence":"first","affiliation":[{"name":"Division of Radiology, University of Torino, Torino,\n                    Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"I.","family":"Castellano","sequence":"first","affiliation":[{"name":"Division of Pathology, Department of Medical Sciences, University of\n                    Torino, Torino, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T. A.","family":"Williams","sequence":"first","affiliation":[{"name":"Division of Internal Medicine and Hypertension, University of Torino,\n                    Torino, Italy"},{"name":"Medizinische Klinik und Poliklinik IV (T.A.W.), Klinikum der\n                    Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen, Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F.","family":"Veglio","sequence":"first","affiliation":[{"name":"Division of Internal Medicine and Hypertension, University of Torino,\n                    Torino, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P.","family":"Mulatero","sequence":"additional","affiliation":[{"name":"Division of Internal Medicine and Hypertension, University of Torino,\n                    Torino, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2015,11,17]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1161\/01.HYP.0000079505.25750.11","article-title":"Primary aldosteronism and hypertensive disease","volume":"42","author":"L Mosso","year":"2003","journal-title":"Hypertension"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1161\/01.HYP.0000040261.30455.B6","article-title":"Hyperaldosteronism among black and white subjects with resistant\n                    hypertension","volume":"40","author":"D A Calhoun","year":"2002","journal-title":"Hypertension"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1055\/s-0031-1295438","article-title":"Prevalence of primary aldosteronism in patient\u2019s cohorts and in population-based\n                    studies \u2013 a review of the current literature","volume":"44","author":"A Hannemann","year":"2012","journal-title":"Horm Metab Res"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"4826","DOI":"10.1210\/jc.2013-2805","article-title":"Long-term cardio- and cerebrovascular events in patients with primary\n                    aldosteronism","volume":"98","author":"P Mulatero","year":"2013","journal-title":"J Clin Endocrinol Metab"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1161\/HYPERTENSIONAHA.113.01060","article-title":"Cardiovascular complications associated with primary aldosteronism: a controlled\n                    cross-sectional study","volume":"62","author":"S Savard","year":"2013","journal-title":"Hypertension"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1001\/archinternmed.2007.33","article-title":"Cardiovascular outcomes in patients with primary aldosteronism after\n                    treatment","volume":"168","author":"C Catena","year":"2008","journal-title":"Arch Intern Med"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"3266","DOI":"10.1210\/jc.2008-0104","article-title":"Endocrine Society. Case detection, diagnosis, and treatment of patients with\n                    primary aldosteronism: an endocrine society clinical practice guideline","volume":"93","author":"J W Funder","year":"2008","journal-title":"J Clin Endocrinol Metab"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"S143","DOI":"10.1148\/rg.25si055514","article-title":"Adrenal vein sampling: how to make it quick, easy, and successful","volume":"25","author":"N Daunt","year":"2005","journal-title":"Radiographics"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"60","DOI":"10.5152\/dir.2014.14026","article-title":"CT mapping of the vertebral level of right adrenal vein","volume":"21","author":"C Degenhart","year":"2015","journal-title":"Diagn Interv Radiol"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"329","DOI":"10.7326\/0003-4819-151-5-200909010-00007","article-title":"Systematic review: diagnostic procedures to differentiate unilateral from\n                    bilateral adrenal abnormality in primary aldosteronism","volume":"151","author":"M J Kempers","year":"2009","journal-title":"Ann Intern Med"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1111\/j.1365-2265.2008.03450.x","article-title":"What are the keys to successful adrenal venous sampling (AVS) in patients with\n                    primary aldosteronism?","volume":"70","author":"W F Young","year":"2009","journal-title":"Clin Endocrinol"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/S2213-8587(14)70069-5","article-title":"Adrenal vein sampling in primary aldosteronism: towards a standardised\n                    protocol","volume":"3","author":"S Monticone","year":"2015","journal-title":"Lancet Diabetes Endocrinol"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1161\/HYPERTENSIONAHA.109.134759","article-title":"Impact of accessory hepatic veins on adrenal vein sampling for identification of\n                    surgically curable primary aldosteronism","volume":"54","author":"D Miotto","year":"2009","journal-title":"Hypertension"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1007\/s00270-009-9722-4","article-title":"Adrenal Venous Sampling: Where Is the Aldosterone Disappearing to?","volume":"33","author":"M Solar","year":"2010","journal-title":"Cardiovasc Intervent Radiol"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1530\/EJE-14-1161","article-title":"Progress in primary aldosteronism: Is there a role for segmental adrenal venous\n                    sampling and adrenal sparing surgery in patients with primary\n                    aldosteronism?","volume":"173","author":"F Satoh","year":"2015","journal-title":"Eur J Endocrinol"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1148\/radiology.198.2.8596821","article-title":"Hyperaldosteronism: sampling the adrenal veins","volume":"198","author":"J L Doppman","year":"1996","journal-title":"Radiology"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1161\/HYPERTENSIONAHA.108.128553","article-title":"Adrenocorticotropic hormone stimulation during adrenal vein sampling for\n                    identifying surgically curable subtypes of primary aldosteronism: comparison of\n                    3 different protocols","volume":"53","author":"T M Seccia","year":"2009","journal-title":"Hypertension"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1161\/HYPERTENSIONAHA.111.189548","article-title":"Effect of adrenocorticotropic hormone stimulation during adrenal vein sampling\n                    in primary aldosteronism","volume":"59","author":"S Monticone","year":"2012","journal-title":"Hypertension"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1056\/NEJM196711162772002","article-title":"Diagnosis and localization of aldosterone-producing adenomas by adrenal-vein\n                    cateterization","volume":"277","author":"J C Melby","year":"1967","journal-title":"N Engl J Med"},{"key":"ref20","first-page":"2149","article-title":"High rate of detection of primary aldosteronism, including surgically treatable\n                    forms, after \u2018non-selective\u2019 screening of hypertensive patients","volume":"21","author":"M Stowasser","year":"2003","journal-title":"J Hypertens"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1016\/j.surg.2004.06.051","article-title":"Role for adrenal venous sampling in primary aldosteronism","volume":"136","author":"W F Young","year":"2004","journal-title":"Surgery"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"1366","DOI":"10.1210\/jc.2007-2055","article-title":"Roles of clinical criteria, computed tomography scan, and adrenal vein sampling\n                    in differential diagnosis of primary aldosteronism subtypes","volume":"93","author":"P Mulatero","year":"2008","journal-title":"J Clin Endocrinol Metab"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1016\/j.surg.2012.07.007","article-title":"Modification of the protocol for selective adrenal venous sampling results in\n                    both a significant increase in the accuracy and necessity of the procedure in\n                    the management of patients with primary hyperaldosteronism","volume":"152","author":"A Harvey","year":"2012","journal-title":"Surgery"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"1450","DOI":"10.2214\/AJR.10.4547","article-title":"Adrenal imaging","volume":"194","author":"M A Blake","year":"2010","journal-title":"Am J Roentgenol"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.jvir.2007.08.022","article-title":"Is adrenal venous sampling necessary in all patients with hyperaldosteronism\n                    before adrenalectomy?","volume":"19","author":"R Zarnegar","year":"2008","journal-title":"J Vasc Interv Radiol"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"1816","DOI":"10.1097\/HJH.0b013e3283060f0c","article-title":"Blood pressure outcome of adrenalectomy in patients with primary\n                    hyperaldosteronism with or without unilateral adenoma","volume":"26","author":"E Letavernier","year":"2008","journal-title":"J Hypertens"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1161\/HYPERTENSIONAHA.113.02097","article-title":"An expert consensus statement on use of adrenal vein sampling for the subtyping\n                    of primary aldosteronism","volume":"63","author":"G P Rossi","year":"2014","journal-title":"Hypertension"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1055\/s-0030-1252060","article-title":"What we still do not know about adrenal vein sampling for primary\n                    aldosteronism","volume":"42","author":"R J Auchus","year":"2010","journal-title":"Horm Metab Res"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"1606","DOI":"10.1210\/jc.2011-2830","article-title":"The Adrenal Vein Sampling International Study (AVIS) for identifying the major\n                    subtypes of primary aldosteronism","volume":"97","author":"G P Rossi","year":"2012","journal-title":"J Clin Endocrinol Metab"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1161\/HYPERTENSIONAHA.109.146613","article-title":"Impact of different diagnostic criteria during adrenal vein sampling on\n                    reproducibility of subtype diagnosis in patients with primary aldosteronism","volume":"55","author":"P Mulatero","year":"2010","journal-title":"Hypertension"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1007\/s11906-009-0038-1","article-title":"Differential diagnosis of primary aldosteronism subtypes","volume":"11","author":"P Mulatero","year":"2009","journal-title":"Curr Hypertens Rep"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"3637","DOI":"10.1210\/jc.2002-022051","article-title":"Predicting surgically remedial primary aldosteronism: role of adrenal scanning,\n                    posture testing, and adrenal vein sampling","volume":"88","author":"E A Espiner","year":"2003","journal-title":"J Clin Endocrinol Metab"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"2437","DOI":"10.1210\/jc.2008-2803","article-title":"Role of unilateral adrenalectomy in bilateral primary aldosteronism: a 22-year\n                    single center experience","volume":"94","author":"N Sukor","year":"2009","journal-title":"J Clin Endocrinol Metab"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1148\/radiology.184.3.1509049","article-title":"Distinction between hyperaldosteronism due to bilateral hyperplasia and\n                    unilateral aldosteronoma: reliability of CT","volume":"184","author":"J L Doppman","year":"1992","journal-title":"Radiology"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"4158","DOI":"10.1210\/jc.2014-2345","article-title":"Aldosterone suppression on contralateral adrenal during adrenal vein sampling\n                    does not predict blood pressure response after adrenalectomy","volume":"99","author":"S Monticone","year":"2014","journal-title":"J Clin Endocrinol Metab"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.1210\/jc.2014-3676","article-title":"Does contralateral suppression at adrenal venous sampling predict outcome\n                    following unilateral adrenalectomy for primary aldosteronism? A retrospective\n                    study","volume":"100","author":"M J Wolley","year":"2015","journal-title":"J Clin Endocrinol Metab"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"2712","DOI":"10.1210\/jc.2013-4146","article-title":"Accuracy of adrenal imaging and adrenal venous sampling in predicting surgical\n                    cure of primary aldosteronism","volume":"99","author":"V Lim","year":"2014","journal-title":"J Clin Endocrinol Metab"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1210\/jc.2013-3789","article-title":"Age below 40 or a recently proposed clinical prediction score cannot bypass\n                    adrenal venous sampling in primary aldosteronism: results of the Else\n                    Kr\u00f6ner-Fresenius Hyperaldosteronismus Registry","volume":"99","author":"A Riester","year":"2014","journal-title":"J Clin Endocrinol Metab"},{"key":"ref39","first-page":"460","article-title":"Incidentally discovered adrenal masses","volume":"16","author":"R T Kloos","year":"1995","journal-title":"Endocr Rev"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1586\/eem.12.65","article-title":"Primary aldosteronism: comparison between guidelines of the Japanese and the US\n                    Endocrine Society","volume":"7","author":"T Nishikawa","year":"2012","journal-title":"Exp Rev Endocrinol Metab"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1507\/endocrj.EJ11-0210","article-title":"Supper-selective ACTH-stimulated adrenal vein sampling is necessary for\n                    detecting precisely functional state of various lesions in unilateral and\n                    bilateral adrenal disorders, inducing primary aldosteronism with subclinical\n                    Cushing\u2019s syndrome","volume":"58","author":"M Omura","year":"2011","journal-title":"Endocr J"},{"key":"ref42","first-page":"142159","article-title":"Intra-adrenal Aldosterone Secretion: Segmental Adrenal Venous Sampling for\n                    Localization","volume":"6","author":"N Satani","year":"2015","journal-title":"Radiology"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"2005","DOI":"10.1097\/HJH.0b013e328362add3","article-title":"Repeating adrenal vein sampling when neither aldosterone\/cortisol ratio exceeds\n                    peripheral yields a high incidence of aldosterone-producing adenoma","volume":"31","author":"M Wolley","year":"2013","journal-title":"J Hypertens"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.mce.2015.04.022","article-title":"Immunohistochemical, genetic and clinical characterization of sporadic\n                    aldosterone-producing adenomas","volume":"411","author":"S Monticone","year":"2015","journal-title":"Mol Cell Endocrinol"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"1578","DOI":"10.1016\/j.juro.2010.12.051","article-title":"Long-term results of a prospective, randomized trial comparing\n                    retroperitoneoscopic partial versus total adrenalectomy for aldosterone\n                    producing adenoma","volume":"185","author":"B Fu","year":"2011","journal-title":"J Urol"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1007\/s00268-008-9513-0","article-title":"Retroperitoneoscopic adrenalectomy in Conn\u2019s syndrome caused by adrenal adenomas\n                    or nodular hyperplasia","volume":"32","author":"M K Walz","year":"2008","journal-title":"World J Surg"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1097\/01.ju.0000162045.68387.c3","article-title":"Laparoscopic partial versus total adrenalectomy for aldosterone producing\n                    adenoma","volume":"174","author":"S Ishidoya","year":"2005","journal-title":"J Urol"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"1968","DOI":"10.1373\/clinchem.2007.092080","article-title":"Rapid cortisol assay during adrenal vein sampling in patients with primary\n                    aldosteronism","volume":"53","author":"G Mengozzi","year":"2007","journal-title":"Clin Chem"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1530\/EJE-11-0287","article-title":"Adrenal vein sampling using rapid cortisol assays in primary aldosteronism is\n                    useful in centers with low success rates","volume":"165","author":"M J Betz","year":"2011","journal-title":"Eur J Endocrinol"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1097\/SLA.0b013e3181961d77","article-title":"Rapid cortisol assays improve the success rate of adrenal vein sampling for\n                    primary aldosteronism","volume":"249","author":"R J Auchus","year":"2009","journal-title":"Ann Surg"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1210\/jcem.86.3.7287","article-title":"Identification of the etiology of primary aldosteronism with adrenal vein\n                    sampling in patients with equivocal computed tomography and magnetic resonance\n                    findings: results in 104 consecutive cases","volume":"86","author":"G P Rossi","year":"2001","journal-title":"J Clin Endocrinol Metab"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1530\/EJE-09-0217","article-title":"Adrenal venous sampling in primary aldosteronism: a low dilution of adrenal\n                    venous blood is crucial for a correct interpretation of the results","volume":"162","author":"J Ceral","year":"2010","journal-title":"Eur J Endocrinol"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1038\/ng.2716","article-title":"Somatic mutations in ATP1A1 and CACNA1D underlie a common subtype of adrenal\n                    hypertension","volume":"45","author":"E A Azizan","year":"2013","journal-title":"Nat Genet"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"1773","DOI":"10.1097\/HJH.0b013e32834937f3","article-title":"Concurrent primary aldosteronism and subclinical cortisol hypersecretion: a\n                    prospective study","volume":"29","author":"F Fallo","year":"2011","journal-title":"J Hypertens"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1507\/endocrj.K10E-402","article-title":"Clinico-pathological features of primary aldosteronism associated with\n                    subclinical Cushing\u2019s syndrome","volume":"58","author":"K Hiraishi","year":"2011","journal-title":"Endocr J"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1530\/EJE-10-1070","article-title":"Aldosterone- and cortisol-co-secreting adrenal tumors: the lost subtype of\n                    primary aldosteronism","volume":"164","author":"M Sp\u00e4th","year":"2011","journal-title":"Eur J Endocrinol"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1161\/HYPERTENSIONAHA.113.01601","article-title":"Plasma metanephrine for assessing the selectivity of adrenal venous\n                    sampling","volume":"62","author":"T Dekkers","year":"2013","journal-title":"Hypertension"},{"key":"ref58","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1210\/jc.2010-2172","article-title":"Chromogranin a measurement for assessing the selectivity of adrenal venous\n                    sampling in primary aldosteronism","volume":"96","author":"T M Seccia","year":"2011","journal-title":"J Clin Endocrinol Metab"}],"container-title":["Hormone and Metabolic Research"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/s-0035-1565089.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,22]],"date-time":"2022-02-22T23:52:19Z","timestamp":1645573939000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/s-0035-1565089"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,11,17]]},"references-count":58,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2015,12,14]]},"published-print":{"date-parts":[[2015,12]]}},"URL":"https:\/\/doi.org\/10.1055\/s-0035-1565089","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0018-5043","1439-4286"],"issn-type":[{"value":"0018-5043","type":"print"},{"value":"1439-4286","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,11,17]]}}}