Faculty Bibliography

Current management practices for hyponatremia (HN) are incompletely understood. The HN Registry has recorded diagnostic measures, utilization, efficacy, and outcomes of therapy for eu- or hypervolemic HN. To better understand current practices, we analyzed data from 3087 adjudicated adult patients in the registry with serum sodium concentration of 130 mEq/l or less from 225 sites in the United States and European Union. Common initial monotherapy treatments were fluid restriction (35%), administration of isotonic (15%) or hypertonic saline (2%), and tolvaptan (5%); 17% received no active agent. Median (interquartile range) mEq/l serum sodium increases during the first day were as follows: no treatment, 1.0 (0.0-4.0); fluid restriction, 2.0 (0.0-4.0); isotonic saline, 3.0 (0.0-5.0); hypertonic saline, 5.0 (1.0-9.0); and tolvaptan, 4.0 (2.0-9.0). Adjusting for initial serum sodium concentration with logistic regression, the relative likelihoods for correction by 5 mEq/l or more (referent, fluid restriction) were 1.60 for hypertonic saline and 2.55 for tolvaptan. At discharge, serum sodium concentration was under 135 mEq/l in 78% of patients and 130 mEq/l or less in 49%. Overly rapid correction occurred in 7.9%. Thus, initial HN treatment often uses maneuvers of limited efficacy. Despite an association with poor outcomes and availability of effective therapy, most patients with HN are discharged from hospital still hyponatremic. Studies to assess short- and long-term benefits of correction of HN with effective therapies are needed.Kidney International advance online publication, 11 February 2015; doi:10.1038/ki.2015.4.

PURPOSE: The purpose of this study was to estimate perfusion metrics in healthy and cirrhotic liver with pharmacokinetic modeling of high-temporal resolution reconstruction of continuously acquired free-breathing gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced acquisition in patients undergoing clinically indicated liver magnetic resonance imaging. SUBJECTS AND METHODS: In this Health Insurance Portability and Accountability Act-compliant prospective study, 9 cirrhotic and 10 noncirrhotic patients underwent clinical magnetic resonance imaging, which included continuously acquired radial stack-of-stars 3-dimensional gradient recalled echo sequence with golden-angle ordering scheme in free breathing during contrast injection. A total of 1904 radial spokes were acquired continuously in 318 to 340 seconds. High-temporal resolution data sets were formed by grouping 13 spokes per frame for temporal resolution of 2.2 to 2.4 seconds, which were reconstructed using the golden-angle radial sparse parallel technique that combines compressed sensing and parallel imaging. High-temporal resolution reconstructions were evaluated by a board-certified radiologist to generate gadolinium concentration-time curves in the aorta (arterial input function), portal vein (venous input function), and liver, which were fitted to dual-input dual-compartment model to estimate liver perfusion metrics that were compared between cirrhotic and noncirrhotic livers. RESULTS: The cirrhotic livers had significantly lower total plasma flow (70.1 +/- 10.1 versus 103.1 +/- 24.3 mL/min per 100 mL; P < 0.05), lower portal venous flow (33.4 +/- 17.7 versus 89.9 +/- 20.8 mL/min per 100 mL; P < 0.05), and higher arterial perfusion fraction (52.0% +/- 23.4% versus 12.4% +/- 7.1%; P < 0.05). The mean transit time was higher in the cirrhotic livers (24.4 +/- 4.7 versus 15.7 +/- 3.4 seconds; P < 0.05), and the hepatocellular uptake rate was lower (3.03 +/- 2.1 versus 6.53 +/- 2.4 100/min; P < 0.05). CONCLUSIONS: Liver perfusion metrics can be estimated from free-breathing dynamic acquisition performed for every clinical examination without additional contrast injection or time. This is a novel paradigm for dynamic liver imaging.

Purpose: TIPS creation fails to control ascites in 40% or more of patients, but the variables predicting outcome are unclear, with prior studies highlighting pre-TIPS portosystemic gradient (PSG) (Nair et al 2004; JVIR 15:1431). We studied which variables predict outcome of TIPS for refractory ascites. Materials and Methods: We retrospectively identified patients who underwent TIPS for refractory ascites between 1/12 and 5/14, yielding 40 patients. We excluded 17 patients due to insufficient peri-procedural documentation or technical failures, leaving 23 patients (16 men, 7 women, mean age 60 +/-2 yrs) for assessment of variables influencing osmotic (albumin and sodium levels) and hydrostatic (pre- and post- TIPS PSG and large varices) pressure. Responders were defined as those requiring fewer or no paracenteses; nonresponders had persistent ascites, with similar pre-TIPS frequency of therapeutic paracentesis. Complications within 1 month requiring hospitalization were noted. Multiple logistic regression, Mann-Whitney U tests, and one-tailed chi² tests assessed group differences. Results: Ten patients (43%: responders) had documented improvement in ascites. Multiple logistic regression including pre- and post-TIPS PSG significantly impacted outcome (p=0.04). Post- but not pre-TIPS PSG predicted outcome (p=0.04 vs. p=0.84). Responders had significantly lower post- TIPS gradient (5.8) compared with non-responders (7.6) (p=0.02). In contrast, responders and non-responders did not differ in albumin (2.7 vs. 2.7) or sodium (136 vs. 134) levels, or pre-TIPS gradient (13.9 vs. 14.7 mmHg) (p>0.05). Similar numbers of responders (50%) had large varices compared to non-responders (61%) (p=0.3). Responders (50%) had significantly more complications compared to non-responders (15%) (p=0.04), mostly encephalopathy (85%) requiring hospitalization. Conclusion: Only post-TIPS PSG predicted which patients had significantly reduced ascites, in contrast to prior studies suggesting importance of pre-TIPS gradient. Findings suggest aggressively lowering the gradient below 6 mmHg may be the most reliable technique to improve outcomes, although with expected higher risk of complications

Therapeutic options for gastric variceal bleeding in the presence of extensive portal vein thrombosis associated with a myeloproliferative disorder are limited. We report a case of a young woman who presented with gastric variceal bleeding secondary to extensive splanchnic venous thrombosis due to a Janus kinase 2 mutation associated myeloproliferative disorder that was managed effectively with partial splenic embolization.

Background: CTP and MELD scores predict 6-week mortality in patients with AVH. However, their relative value has yet to be evaluated in the U.S. The vapreotide trial was a prospective cohort study of patients with AVH treated with current standard of care with a vasoactive agent (vapreotide, a somatostatin analogue), endoscopic band ligation and antibiotics. Aims: To 1) report outcomes of patients presenting with AVH using a large U.S. cohort; 2) describe predictors of 6-week mortality; and 3) validate a recent "recalibrated" MELD model (Reverter. Gastroenterology 2014). Results: Seventy patients with cirrhosis and endoscopically-proven AVH were enrolled between August 2006 and April 2008 at 15 U.S. centers. Eighteen (26%) died within 6 weeks of index bleed. Data at baseline and univariate analysis comparing survivors and non-survivors are shown in the table. Multivariate models including parameters significant on univariate analysis and either CTP or MELD, showed admission CTP and MELD as independent predictors of survival. The discriminative values of CTP (AUROC 0.75, 95%CI: 0.63-0.87) and MELD (AUROC 0.79, 95%CI: 0.68-0.90) were good and not significantly different (p=0.26). However, calibration (the correlation between observed and predicted mortality), as determined by the Hosmer- Lemeshow Goodness-of-Fit test (in which the smaller the p value, the greater the disagreement between observed and predicted mortality) was significantly better for CTP (p=0.45) than for MELD (p=0.02), with the Reverter model having the worst agreement (p=0.0006). Predicted mortality for CTP-A was <10%, CTP-B 10%-30%, and CTP-C >30%. Conclusions: AVH mortality of 26% in the U.S. is in the upper range limit of recent series (6 to 33%). CTP score has the best overall performance in the prediction of 6-week mortality and should continue to be used in risk stratification and in the application of individualized therapy. (Table Presented)