Dataset Information

Endogenous Calcification Inhibitors in the Prevention of Vascular Calcification: A Consensus Statement From the COST Action EuroSoftCalcNet.

ABSTRACT: The physicochemical deposition of calcium-phosphate in the arterial wall is prevented by calcification inhibitors. Studies in cohorts of patients with rare genetic diseases have shed light on the consequences of loss-of-function mutations for different calcification inhibitors, and genetic targeting of these pathways in mice have generated a clearer picture on the mechanisms involved. For example, generalized arterial calcification of infancy (GACI) is caused by mutations in the enzyme ecto-nucleotide pyrophosphatase/phosphodiesterase-1 (eNPP1), preventing the hydrolysis of ATP into pyrophosphate (PPi). The importance of PPi for inhibiting arterial calcification has been reinforced by the protective effects of PPi in various mouse models displaying ectopic calcifications. Besides PPi, Matrix Gla Protein (MGP) has been shown to be another potent calcification inhibitor as Keutel patients carrying a mutation in the encoding gene or Mgp-deficient mice develop spontaneous calcification of the arterial media. Whereas PPi and MGP represent locally produced calcification inhibitors, also systemic factors contribute to protection against arterial calcification. One such example is Fetuin-A, which is mainly produced in the liver and which forms calciprotein particles (CPPs), inhibiting growth of calcium-phosphate crystals in the blood and thereby preventing their soft tissue deposition. Other calcification inhibitors with potential importance for arterial calcification include osteoprotegerin, osteopontin, and klotho. The aim of the present review is to outline the latest insights into how different calcification inhibitors prevent arterial calcification both under physiological conditions and in the case of disturbed calcium-phosphate balance, and to provide a consensus statement on their potential therapeutic role for arterial calcification.

SUBMITTER: Back M

PROVIDER: S-EPMC6345677 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Endogenous Calcification Inhibitors in the Prevention of Vascular Calcification: A Consensus Statement From the COST Action EuroSoftCalcNet.

Bäck Magnus M Aranyi Tamas T Cancela M Leonor ML Carracedo Miguel M Conceição Natércia N Leftheriotis Georges G Macrae Vicky V Martin Ludovic L Nitschke Yvonne Y Pasch Andreas A Quaglino Daniela D Rutsch Frank F Shanahan Catherine C Sorribas Victor V Szeri Flora F Valdivielso Pedro P Vanakker Olivier O Kempf Hervé H

Frontiers in cardiovascular medicine 20190118

The physicochemical deposition of calcium-phosphate in the arterial wall is prevented by calcification inhibitors. Studies in cohorts of patients with rare genetic diseases have shed light on the consequences of loss-of-function mutations for different calcification inhibitors, and genetic targeting of these pathways in mice have generated a clearer picture on the mechanisms involved. For example, generalized arterial calcification of infancy (GACI) is caused by mutations in the enzyme ecto-nucl ...[more]

PMID: 30713844

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Project description:ImportanceThere is a paucity of evidence to guide physicians regarding prevention strategies for cutaneous squamous cell carcinoma (CSCC) in solid organ transplant recipients (SOTRs).ObjectiveTo examine the development and results of a Delphi process initiated to identify consensus-based medical management recommendations for prevention of CSCC in SOTRs.Evidence reviewDermatologists with more than 5 years' experience treating SOTRs were invited to participate. A novel actinic damage and skin cancer index (AD-SCI), consisting of 6 ordinal stages corresponding to an increasing burden of actinic damage and CSCC, was used to guide survey design. Three sequential web-based surveys were administered from January 1, 2019, to December 31, 2020. Pursuant to Delphi principles, respondents thoroughly reviewed all peer responses between rounds. Supplemental questions were also asked to better understand panelists' rationale for their responses.FindingsThe Delphi panel comprised 48 dermatologists. Respondents represented 13 countries, with 27 (56%) from the US. Twenty-nine respondents (60%) were Mohs surgeons. Consensus was reached with 80% or higher concordance among respondents when presented with a statement, question, or management strategy pertaining to prevention of CSCC in SOTRs. A near-consensus category of 70% to less than 80% concordance was also defined. The AD-SCI stage-based recommendations were established if consensus or near-consensus was achieved. The panel was able to make recommendations for 5 of 6 AD-SCI stages. Key recommendations include the following: cryotherapy for scattered actinic keratosis (AK); field therapy for AK when grouped in 1 anatomical area, unless AKs are thick in which case field therapy and cryotherapy were recommended; combination lesion directed and field therapy with fluorouracil for field cancerized skin; and initiation of acitretin therapy and discussion of immunosuppression reduction or modification for patients who develop multiple skin cancers at a high rate (10 CSCCs per year) or develop high-risk CSCC (defined by a tumor with approximately ≥20% risk of nodal metastasis). No consensus recommendation was achieved for SOTRs with a first low risk CSCC.Conclusions and relevancePhysicians may consider implementation of panel recommendations for prevention of CSCC in SOTRs while awaiting high-level-of-evidence data. Additional clinical trials are needed in areas where consensus was not reached.

Project description:An American Hepato-Pancreato-Biliary Association (AHPBA)-sponsored consensus meeting of expert panellists met on 15 January 2014 to review current evidence on the management of intrahepatic cholangiocarcinoma (ICC) in order to establish practice guidelines and to agree on consensus statements. The treatment of ICC requires a coordinated, multidisciplinary approach to optimize survival. Biopsy is not necessary if the surgeon suspects ICC and is planning curative resection, although biopsy should be obtained before systemic or locoregional therapies are initiated. Assessment of resectability is best accomplished using cross-sectional imaging [computed tomography (CT) or magnetic resonance imaging (MRI)], but the role of positron emission tomography (PET) is unclear. Resectability in ICC is defined by the ability to completely remove the disease while leaving an adequate liver remnant. Extrahepatic disease, multiple bilobar or multicentric tumours, and lymph node metastases beyond the primary echelon are contraindications to resection. Regional lymphadenectomy should be considered a standard part of surgical therapy. In patients with high-risk features, the routine use of diagnostic laparoscopy is recommended. The preoperative diagnosis of combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC) by imaging studies is extremely difficult. Surgical resection remains the mainstay of treatment, but survival is worse than in HCC alone. There are no adequately powered, randomized Phase III trials that can provide definitive recommendations for adjuvant therapy for ICC. Patients with high-risk features (lymphovascular invasion, multicentricity or satellitosis, large tumours) should be encouraged to enrol in clinical trials and to consider adjuvant therapy. Cisplatin plus gemcitabine represents the standard-of-care, front-line systemic therapy for metastatic ICC. Genomic analyses of biliary cancers support the development of targeted therapeutic interventions.

Dataset Information

Endogenous Calcification Inhibitors in the Prevention of Vascular Calcification: A Consensus Statement From the COST Action EuroSoftCalcNet.

Publications

Endogenous Calcification Inhibitors in the Prevention of Vascular Calcification: A Consensus Statement From the COST Action EuroSoftCalcNet.

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