7 research outputs found

    Large-scale genome-wide analysis identifies genetic variants associated with cardiac structure and function

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    BACKGROUND: Understanding the genetic architecture of cardiac structure and function may help to prevent and treat heart disease. This investigation sought to identify common genetic variations associated with inter-individual variability in cardiac structure and function. METHODS: A GWAS meta-analysis of echocardiographic traits was performed, including 46,533 individuals from 30 studies (EchoGen consortium). The analysis included 16 traits of left ventricular (LV) structure, and systolic and diastolic function. RESULTS: The discovery analysis included 21 cohorts for structural and systolic function traits (n = 32,212) and 17 cohorts for diastolic function traits (n = 21,852). Replication was performed in 5 cohorts (n = 14,321) and 6 cohorts (n = 16,308), respectively. Besides 5 previously reported loci, the combined meta-analysis identified 10 additional genome-wide significant SNPs: rs12541595 near MTSS1 and rs10774625 in ATXN2 for LV end-diastolic internal dimension; rs806322 near KCNRG, rs4765663 in CACNA1C, rs6702619 near PALMD, rs7127129 in TMEM16A, rs11207426 near FGGY, rs17608766 in GOSR2, and rs17696696 in CFDP1 for aortic root diameter; and rs12440869 in IQCH for Doppler transmitral A-wave peak velocity. Findings were in part validated in other cohorts and in GWAS of related disease traits. The genetic loci showed associations with putative signaling pathways, and with gene expression in whole blood, monocytes, and myocardial tissue. CONCLUSION: The additional genetic loci identified in this large meta-analysis of cardiac structure and function provide insights into the underlying genetic architecture of cardiac structure and warrant follow-up in future functional studies. FUNDING: For detailed information per study, see Acknowledgments.This work was supported by a grant from the US National Heart, Lung, and Blood Institute (N01-HL-25195; R01HL 093328 to RSV), a MAIFOR grant from the University Medical Center Mainz, Germany (to PSW), the Center for Translational Vascular Biology (CTVB) of the Johannes Gutenberg-University of Mainz, and the Federal Ministry of Research and Education, Germany (BMBF 01EO1003 to PSW). This work was also supported by the research project Greifswald Approach to Individualized Medicine (GANI_MED). GANI_MED was funded by the Federal Ministry of Education and Research and the Ministry of Cultural Affairs of the Federal State of Mecklenburg, West Pomerania (contract 03IS2061A). We thank all study participants, and the colleagues and coworkers from all cohorts and sites who were involved in the generation of data or in the analysis. We especially thank Andrew Johnson (FHS) for generation of the gene annotation database used for analysis. We thank the German Center for Cardiovascular Research (DZHK e.V.) for supporting the analysis and publication of this project. RSV is a member of the Scientific Advisory Board of the DZHK. Data on CAD and MI were contributed by CARDIoGRAMplusC4D investigators. See Supplemental Acknowledgments for consortium details. PSW, JFF, AS, AT, TZ, RSV, and MD had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis

    Interventions To Improve Hemodialysis Adequacy: Protocols Based On Real-Time Monitoring Of Dialysate Solute Clearance

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    Background: The monitoring of dialysate ultraviolet (UV) absorbance is a validated technology to measure hemodialysis adequacy and allows for continuous and real-time tracking every session as opposed to the typical once-monthly assessments. Clinical care guidelines are needed to interpret the findings so as to troubleshoot problematic absorbance patterns and intervene during an individual treatment as needed. Methods: When paired with highly structured clinical care protocols that allow autonomous nursing actions, this technology has the potential to improve treatment outcomes. These devices measure the UV absorbance of dialysate solutes to calculate and then display the delivered as well as predicted clearance for that session. Various technical factors can affect the course of dialysate absorbance, confound the device\u27s readout of clearance results and thus lead to challenges for the dialysis unit staff to properly monitor dialysis adequacy. We analyze optimal and problematic patterns to the device\u27s \u27clearance\u27 display (e.g. due to thrombosis of hollow fibers, inadequate access blood flow or recirculation) and provide specific interventions to ensure delivery of an adequate dialysis dose. A rigorous algorithm is presented with representative device monitor display profiles from actual hemodialysis sessions. Procedural rationale and interventions are described for each individual scenario. Conclusion: Real-time hemodialysate UV absorbance patterns can be used for protocol-based intradialytic interventions to optimize solute clearance

    Postoperative Hyperkalemia

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    Hyperkalemia occurs frequently in hospitalized patients and is of particular concern for those who have undergone surgery, with postoperative care provided by clinicians of many disciplines. This review describes the normal physiology and how multiple perioperative factors can disrupt potassium homeostasis and lead to severe elevations in plasma potassium concentration. The pathophysiologic basis of diverse causes of hyperkalemia was used to broadly classify etiologies into those with altered potassium distribution (e.g. increased potassium release from cells or other transcellular shifts), reduced urinary excretion (e.g. reduced sodium delivery, volume depletion, and hypoaldosteronism), or an exogenous potassium load (e.g. blood transfusions). Surgical conditions of particular concern involve: rhabdomyolysis from malpositioning, trauma or medications; bariatric surgery; vascular procedures with tissue ischemia; acidosis; hypovolemia; and volume or blood product resuscitation. Certain acute conditions and chronic co-morbidities present particular risk. These include chronic kidney disease, diabetes mellitus, many outpatient preoperative medications (e.g. beta blockers, salt substitutes), and inpatient agents (e.g. succinylcholine, hyperosmolar volume expanders). Clinicians need to be aware of these pathophysiologic mechanisms for developing perioperative hyperkalemia as many of the risks can be minimized or avoided

    Postoperative hyperkalemia

    No full text
    Hyperkalemia occurs frequently in hospitalized patients and is of particular concern for those who have undergone surgery, with postoperative care provided by clinicians of many disciplines. This review describes the normal physiology and how multiple perioperative factors can disrupt potassium homeostasis and lead to severe elevations in plasma potassium concentration. The pathophysiologic basis of diverse causes of hyperkalemia was used to broadly classify etiologies into those with altered potassium distribution (e.g. increased potassium release from cells or other transcellular shifts), reduced urinary excretion (e.g. reduced sodium delivery, volume depletion, and hypoaldosteronism), or an exogenous potassium load (e.g. blood transfusions). Surgical conditions of particular concern involve: rhabdomyolysis from malpositioning, trauma or medications; bariatric surgery; vascular procedures with tissue ischemia; acidosis; hypovolemia; and volume or blood product resuscitation. Certain acute conditions and chronic co-morbidities present particular risk. These include chronic kidney disease, diabetes mellitus, many outpatient preoperative medications (e.g. beta blockers, salt substitutes), and inpatient agents (e.g. succinylcholine, hyperosmolar volume expanders). Clinicians need to be aware of these pathophysiologic mechanisms for developing perioperative hyperkalemia as many of the risks can be minimized or avoided

    Pancreatic surgery outcomes: multicentre prospective snapshot study in 67 countries

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