Bioreactance and Apelin in the Management of Severe Hyponatremia

Hyponatremia is a severe electrolyte disturbance associated with substantial morbidity and mortality. It often poses a diagnostic and therapeutic challenge. Accurate assessment of patient fluid-volume status is central to effective management. This pilot study aimed to evaluate the usefulness of the Cheetah NICOM bioreactance system and apelin in early differentiation between hypo- and euvolemia in patients with severe hyponatremia. Methods: Patients > 50 years of age with a serum sodium ≤ 125 mmol/L were eligible for inclusion after written informed consent. Blood- and urine analyses of cardiovascular load (NT-proBNP), osmotic stress (copeptin, apelin, osmolality, sodium), mineralocorticoid status (aldosterone, renin) and sympathetic activity (methoxycathecholamines) were analysed at baseline and after isotonic sodium chloride infusion. Bedside bioreactance examination was used to visualise parameters, including stroke volume before and after passive leg raise test. Classification of volume status was made retrospectively blinded for biomarker and bioreactance results. Results: 8 patients (4 hypovolemic and 4 euvolemic), 79 years old, median plasma sodium 120 mmol/L were included. At the Emergency Department volume status was misclassified in all hypo- and in 2 of 4 euvolemic patients. Apelin was significantly higher in hypovolemic patients ((299 vs. 175 ng/ml), p = 0.021). All hypovolemic, but none of the euvolemic, patients had a level above 250 ng/ml. Copeptin did not differ between groups. All patients in the hypovolemic group increased their stroke volume after passive leg raise. Conclusions: Apelin seems to be a promising future biomarker in the early management of severe hyponatremia. Bioreactance measurements may offer a supplement to bedside evaluation of volume status.

Hyponatremia in the Emergency Department: Could Biomarkers Help in Diagnosis and Treatment?

Objective: Hyponatremia is the most common electrolyte imbalance. The initial treatment decision is based on clinical evaluation of patient volume status but an accurate assessment is difficult, particularly differentiating mild hypovolemia from euvolemia. The aim of this study is to examine if biomarkers are valuable in the early determination of volume status and SIADH diagnosis. Methods: Blood samples were collected from an unselected patient population at entry to the Emergency Department. If the plasma sodium level (P-Na) was ≤125 mmol/L, the sample was frozen for further analysis. Mid-regional pro-atrial natriuretic peptide (MR-proANP), proadrenomedullin (MR-proADM), C-terminal prepro-vasopressin (copeptin), pro-endothelin-1 (proET-1) and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels were analysed. A comprehensive assessment of volume status and underlying causes was made after discharge blinded for biomarker results. Results: A total of 81 patients were included. A well substa ntiated volemic state (hypo/eu/hypervolemia) was established in 72 patients (mean age 76 years, 65% women, median P-Na 119 mmol/L). A significant association was observed between MR-proANP levels and volemic state (p = 0.0001). Data was specifically analysed with respect to distinguishing hypo- from euvolemia (n = 59) using logistic regression. In a crude analysis, MR-proANP was significantly related to euvolemia (OR: 2.54 per SD of MR-proANP, 95% CI 1.32 - 4.86, p = 0.005) and remained so after the multivariate backward elimination model (OR: 2.45 per SD of MRproANP, 95% CI 1.22 - 4.91, p = 0.012.), whereas the other studied biomarkers were not. Copeptin levels were not associated with a diagnosis of SIADH. Conclusions: MR-proANP may be of value in early determination of volume status in hyponatremic patients.

Comprehensive functional annotation of susceptibility variants identifies genetic heterogeneity between lung adenocarcinoma and squamous cell carcinoma

Although genome-wide association studies have identified more than eighty genetic variants associated with non-small cell lung cancer(NSCLC)risk,biological mechanisms of these variants remain largely unknown.By integrating a large-scale genotype data of 15581 lung adenocarcinoma(AD)cases,8350 squamous cell carcinoma(SqCC)cases,and 27355 controls,as well as multiple transcriptome and epigenomic databases,we conducted histology-specific meta-analyses and functional annotations of both reported and novel susceptibility variants.We identified 3064 credible risk variants for NSCLC,which were overrepresented in enhancer-like and promoter-like histone modification peaks as well as DNase I hypersensitive sites.Transcription factor enrichment analysis revealed that USF1 was AD-specific while CREB1 was SqCC-specific.Functional annotation and genebased analysis implicated 894 target genes,including 274 specifics for AD and 123 for SqCC,which were overrepresented in somatic driver genes(ER=1.95,P=0.005).Pathway enrichment analysis and Gene-Set Enrichment Analysis revealed that AD genes were primarily involved in immune-related pathways,while SqCC genes were homologous recombination deficiency related.Our results illustrate the molecular basis of both wellstudied and new susceptibility loci of NSCLC,providing not only novel insights into the genetic heterogeneity between AD and SqCC but also a set of plausible gene targets for post-GWAS functional experiments.

麦角硫因或可降低心血管疾病发生及死亡风险

目的近期研究发现一种健康饮食模式(HCFP)与降低心脏代谢疾病风险相关,但导致这种相关性的分子机制尚不明确。该研究旨在发现与这种饮食模式相关的血浆代谢物,并研究其与心脏代谢疾病发生和死亡风险的相关性。方法从全人群马尔默饮食和癌症研究中,筛选出3236名无心血管疾病和糖尿病史的参与者。运用液相色谱-质谱法对他们的112种血浆代谢物进行检测。通过多元线性回归和Bonfcrroni校正分析,发现其中与该饮食模式相关的代谢物。使用多变量Cox比例风险模型进行长期随访分析后,发现这些健康饮食的生物标志物与心脏代谢疾病的发生和死亡风险相关。结果平均随访21.4年期间,603人患心血管疾病,362人患糖尿病,843人死亡。基线资料中,5种健康饮食标志物与该饮食模式相关(P<0.0004),其中4种与至少一项研究终点相关(P<0.05)。麦角硫因是与该饮食模式相关性最强的代谢物,并且与降低冠心病风险(危害比0.85,P=0.01)、心血管死亡风险(危害比0.79,P=0.002)、全因死亡风险(麦角硫因每增加一个标准差的危害比,危害比0.86,P=4e-5)相关。结论我们发现高麦角硫因含量是降低心脏代谢疾病发生和死亡风险的独立标志物。而这种高含量很可能是由某种特殊的饮食方式造成的。