Rebleeding in Variceal and Nonvariceal Gastrointestinal Bleeds in Cirrhotic Patients Using Vitamin K1: The LIVER-K Study.

BACKGROUND: Gastroesophageal varices are the most common cause of upper gastrointestinal bleeding (UGIB) in patients with cirrhosis. Vitamin K1 is commonly administered to patients presenting with UGIB and elevated international normalized ratio, despite limited evidence to support this practice. OBJECTIVES: The primary objective was to describe the incidence of rebleeding within 30 days after vitamin K1 administration in patients with cirrhosis and UGIB. The secondary objective was to describe prescribing patterns for vitamin K1. METHODS: This retrospective, descriptive multicentre study involved patients with cirrhosis and UGIB who were admitted to any of the 4 adult acute care hospitals in Calgary, Alberta, from January 1, 2014, to December 31, 2016. Patients were divided into 2 groups: those who received vitamin K1 and those who did not. RESULTS: A total of 370 patients met the inclusion criteria, of whom 243 received vitamin K1 and 127 did not. Baseline characteristics were similar between the groups. Greater proportions of patients in the vitamin K1 group received transfusions of packed red blood cells, fresh frozen plasma, platelets, cryoprecipitate, or prothrombin concentrate during their admissions. There was no significant difference in the duration of octreotide and pantoprazole infusions. Among patients in the vitamin K1 group, there were more admissions to the intensive care unit and longer lengths of stay. More patients in the no vitamin K1 group had esophageal varices evident on endoscopy that required endoscopic treatment. Forty of the patients (16.5%) in the vitamin K1 group and 7 (5.5%) in the no vitamin K1 group had rebleeding within 30 days of the initial bleed. The median total vitamin K1 dose administered was 25 mg. CONCLUSIONS: The study results suggest that vitamin K1 does not reduce the incidence of rebleeding within 30 days of the initial bleed in patients with cirrhosis and UGIB.

CONTEXTE: Les varices oesophagiennes sont la cause la plus fréquente de l'hémorragie gastro-intestinale supérieure (HGIS) parmi les patients atteints de cirrhose. On administre communément de la vitamine K1 aux patients présentant une HGIS et dont la mesure du rapport international normalisé (RIN) est élevée, malgré le manque de preuves soutenant cette pratique. OBJECTIFS: L'objectif principal consistait à décrire la fréquence de la reprise du saignement dans les 30 jours après l'administration de la vitamine K1 à des patients atteints de cirrhose et de HGIS. L'objectif secondaire consistait à décrire les schémas de prescription de la vitamine K1. MÉTHODE: Cette étude multicentrique, descriptive et rétrospective comprenait des patients atteints de cirrhose et de HGIS, ayant été admis à n'importe lesquels des quatre hôpitaux de soins actifs pour adultes de Calgary, Alberta, du 1er janvier 2014 au 31 décembre 2016. Les patients étaient répartis en deux groupes : ceux ayant reçu de la vitamine K1 et ceux n'en ayant pas reçu. RÉSULTATS: Le nombre total de 370 patients correspondait aux critères d'inclusion. Parmi ceux-ci, 243 avaient reçu de la vitamine K1 et 127 n'en n'avaient pas reçu. Les caractéristiques de base étaient similaires entre les groupes. Un plus grand nombre de patients du groupe « Vitamine K1 "avaient reçu une transfusion d'un concentré de globules rouges, de plasma frais congelé, de plaquettes, de cryoprécipité ou de concentré de prothrombine au cours de leur séjour hospitalier. On n'a noté aucune différence significative dans la durée des injections de pantoprazole et d'octréotide. Le nombre d'admissions de patients du groupe « Vitamine K1 ¼ à l'unité de soins intensifs était plus élevé et le séjour de ceux-ci était plus long. L'endoscopie a montré qu'un plus grand nombre de patients du groupe « Sans vitamine K1 ¼ présentaient des varices oesophagiennes nécessitant un traitement endoscopique. Dans les 30 jours après le saignement initial, quarante (16,5 %) patients du groupe « Vitamine K1 ¼ et 7 (5,5 %) du groupe « Sans vitamine K1 ¼ ont subi une nouvelle hémorragie. La dose moyenne totale de vitamine K1 administrée était de 25 mg. CONCLUSIONS: Les résultats de l'étude tendent à démontrer que la vitamine K1 ne réduit pas la fréquence de la reprise du saignement dans les 30 jours qui suivent le saignement initial parmi les patients atteints de cirrhose et de HGIS.

The human urine metabolome.

Urine has long been a "favored" biofluid among metabolomics researchers. It is sterile, easy-to-obtain in large volumes, largely free from interfering proteins or lipids and chemically complex. However, this chemical complexity has also made urine a particularly difficult substrate to fully understand. As a biological waste material, urine typically contains metabolic breakdown products from a wide range of foods, drinks, drugs, environmental contaminants, endogenous waste metabolites and bacterial by-products. Many of these compounds are poorly characterized and poorly understood. In an effort to improve our understanding of this biofluid we have undertaken a comprehensive, quantitative, metabolome-wide characterization of human urine. This involved both computer-aided literature mining and comprehensive, quantitative experimental assessment/validation. The experimental portion employed NMR spectroscopy, gas chromatography mass spectrometry (GC-MS), direct flow injection mass spectrometry (DFI/LC-MS/MS), inductively coupled plasma mass spectrometry (ICP-MS) and high performance liquid chromatography (HPLC) experiments performed on multiple human urine samples. This multi-platform metabolomic analysis allowed us to identify 445 and quantify 378 unique urine metabolites or metabolite species. The different analytical platforms were able to identify (quantify) a total of: 209 (209) by NMR, 179 (85) by GC-MS, 127 (127) by DFI/LC-MS/MS, 40 (40) by ICP-MS and 10 (10) by HPLC. Our use of multiple metabolomics platforms and technologies allowed us to identify several previously unknown urine metabolites and to substantially enhance the level of metabolome coverage. It also allowed us to critically assess the relative strengths and weaknesses of different platforms or technologies. The literature review led to the identification and annotation of another 2206 urinary compounds and was used to help guide the subsequent experimental studies. An online database containing the complete set of 2651 confirmed human urine metabolite species, their structures (3079 in total), concentrations, related literature references and links to their known disease associations are freely available at http://www.urinemetabolome.ca.

HMDB 3.0--The Human Metabolome Database in 2013.

The Human Metabolome Database (HMDB) (www.hmdb.ca) is a resource dedicated to providing scientists with the most current and comprehensive coverage of the human metabolome. Since its first release in 2007, the HMDB has been used to facilitate research for nearly 1000 published studies in metabolomics, clinical biochemistry and systems biology. The most recent release of HMDB (version 3.0) has been significantly expanded and enhanced over the 2009 release (version 2.0). In particular, the number of annotated metabolite entries has grown from 6500 to more than 40,000 (a 600% increase). This enormous expansion is a result of the inclusion of both 'detected' metabolites (those with measured concentrations or experimental confirmation of their existence) and 'expected' metabolites (those for which biochemical pathways are known or human intake/exposure is frequent but the compound has yet to be detected in the body). The latest release also has greatly increased the number of metabolites with biofluid or tissue concentration data, the number of compounds with reference spectra and the number of data fields per entry. In addition to this expansion in data quantity, new database visualization tools and new data content have been added or enhanced. These include better spectral viewing tools, more powerful chemical substructure searches, an improved chemical taxonomy and better, more interactive pathway maps. This article describes these enhancements to the HMDB, which was previously featured in the 2009 NAR Database Issue. (Note to referees, HMDB 3.0 will go live on 18 September 2012.).

Multi-platform characterization of the human cerebrospinal fluid metabolome: a comprehensive and quantitative update.

BACKGROUND: Human cerebral spinal fluid (CSF) is known to be a rich source of small molecule biomarkers for neurological and neurodegenerative diseases. In 2007, we conducted a comprehensive metabolomic study and performed a detailed literature review on metabolites that could be detected (via metabolomics or other techniques) in CSF. A total of 308 detectable metabolites were identified, of which only 23% were shown to be routinely identifiable or quantifiable with the metabolomics technologies available at that time. The continuing advancement in analytical technologies along with the growing interest in CSF metabolomics has led us to re-visit the human CSF metabolome and to re-assess both its size and the level of coverage than can be achieved with today's technologies. METHODS: We used five analytical platforms, including nuclear magnetic resonance (NMR), gas chromatography-mass spectrometry (GC-MS), liquid chromatography-mass spectrometry (LC-MS), direct flow injection-mass spectrometry (DFI-MS/MS) and inductively coupled plasma-mass spectrometry (ICP-MS) to perform quantitative metabolomics on multiple human CSF samples. This experimental work was complemented with an extensive literature review to acquire additional information on reported CSF compounds, their concentrations and their disease associations. RESULTS: NMR, GC-MS and LC-MS methods allowed the identification and quantification of 70 CSF metabolites (as previously reported). DFI-MS/MS allowed the quantification of 78 metabolites (6 acylcarnitines, 13 amino acids, hexose, 42 phosphatidylcholines, 2 lyso-phosphatidylcholines and 14 sphingolipids), while ICP-MS provided quantitative results for 33 metal ions in CSF. Literature analysis led to the identification of 57 more metabolites. In total, 476 compounds have now been confirmed to exist in human CSF. CONCLUSIONS: The use of improved metabolomic and other analytical techniques has led to a 54% increase in the known size of the human CSF metabolome over the past 5 years. Commonly available metabolomic methods, when combined, can now routinely identify and quantify 36% of the 'detectable' human CSF metabolome. Our experimental works measured 78 new metabolites that, as per our knowledge, have not been reported to be present in human CSF. An updated CSF metabolome database containing the complete set of 476 human CSF compounds, their concentrations, related literature references and links to their known disease associations is freely available at the CSF metabolome database.