Research Spotlight

Fallahzadeh, M. A., B. Dormanesh, M. K. Fallahzadeh, J. Roozbeh, M. H. Fallahzadeh and M. M. Sagheb (2017). “Acetazolamide and hydrochlorothiazide followed by furosemide versus furosemide and hydrochlorothiazide followed by furosemide for the treatment of adults with nephrotic edema: A randomized trial.” Am J Kidney Dis 69(3): 420-427.

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BACKGROUND: Nephrotic edema is considered refractory if it does not respond to maximum or near-maximum doses of loop diuretics. This condition can be treated with loop diuretics and thiazides. However, animal studies show that the simultaneous downregulation of pendrin with acetazolamide and inhibition of the sodium-chloride cotransporter with hydrochlorothiazide generates significant diuresis, and furosemide administration following a pendrin inhibitor potentiates furosemide’s diuretic effect. Therefore, we performed this study to compare the efficacy of acetazolamide and hydrochlorothiazide followed by furosemide versus furosemide and hydrochlorothiazide followed by furosemide for treatment of refractory nephrotic edema. STUDY DESIGN: Randomized, double-blind, 2-arm, parallel trial. SETTING & PARTICIPANTS: 20 patients with refractory nephrotic edema despite treatment with 80mg of furosemide daily and creatinine clearance > 60mL/min. INTERVENTION: Patients were randomly assigned to 2 groups: group 1 (n=10) received 250mg of acetazolamide and 50mg of hydrochlorothiazide daily and group 2 (n=10) received 40mg of furosemide and 50mg of hydrochlorothiazide daily for 1 week in phase 1. In phase 2, both groups received 40mg of furosemide daily for 2 weeks. OUTCOMES: The primary outcome was absolute change in weight before and at the end of each phase. MEASUREMENTS: Weight and 24-hour urine volume at baseline and the end of each phase. RESULTS: The mean weight decrease was of significantly larger magnitude in group 1 compared with group 2 at the end of phase 1 (-1.4+/-0.52 [SD] vs -0.65+/-0.41kg; P=0.001) and phase 2 (-1.6+/-0.84 vs -0.5+/-0.47kg; P=0.005). The increase in 24-hour urine volume was also significantly higher in group 1 at the end of phase 2. LIMITATIONS: Small sample size, short follow-up duration, and lack of serum bicarbonate and chloride measurement. CONCLUSIONS: Acetazolamide and hydrochlorothiazide followed by furosemide is more effective than furosemide and hydrochlorothiazide followed by furosemide for the treatment of refractory nephrotic edema.

Ryals, R. C., M. D. Andrews, S. Datta, A. S. Coyner, C. M. Fischer, Y. Wen, M. E. Pennesi and T. J. McGill (2017). “Long-term characterization of retinal degeneration in royal college of surgeons rats using spectral-domain optical coherence tomography.” Invest Ophthalmol Vis Sci 58(3): 1378-1386.

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Purpose: Prospective treatments for age-related macular degeneration and inherited retinal degenerations are commonly evaluated in the Royal College of Surgeons (RCS) rat before translation into clinical application. Historically, retinal thickness obtained through postmortem anatomic assessments has been a key outcome measure; however, utility of this measurement is limited because it precludes the ability to perform longitudinal studies. To overcome this limitation, the present study was designed to provide a baseline longitudinal quantification of retinal thickness in the RCS rat by using spectral-domain optical coherence tomography (SD-OCT). Methods: Horizontal and vertical linear SD-OCT scans centered on the optic nerve were captured from Long-Evans control rats at P30, P60, P90 and from RCS rats between P17 and P90. Total retina (TR), outer nuclear layer+ (ONL+), inner nuclear layer (INL), and retinal pigment epithelium (RPE) thicknesses were quantified. Histologic sections of RCS retina obtained from P21 to P60 were compared to SD-OCT images. Results: In RCS rats, TR and ONL+ thickness decreased significantly as compared to Long-Evans controls. Changes in INL and RPE thickness were not significantly different between control and RCS retinas. From P30 to P90 a subretinal hyperreflective layer (HRL) was observed and quantified in RCS rats. After correlation with histology, the HRL was identified as disorganized outer segments and the location of accumulated debris. Conclusions: Retinal layer thickness can be quantified longitudinally throughout the course of retinal degeneration in the RCS rat by using SD-OCT. Thickness measurements obtained with SD-OCT were consistent with previous anatomic thickness assessments. This study provides baseline data for future longitudinal assessment of therapeutic agents in the RCS rat.

Olson, D. M., C. Parcon, A. Santos, G. Santos, R. Delabar and S. E. Stutzman (2017). “A novel approach to explore how nursing care affects intracranial pressure.” Am J Crit Care 26(2): 136-139.

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BACKGROUND: Intracranial pressure is measured continuously, and nursing behaviors have been associated with variations in the measurements. METHODS: A prospective pilot observational study was done to develop a comprehensive list of nursing behaviors that affect patients’ intracranial pressure. Data on nurses were obtained by self-reports and video recording. Patient-level data were collected via chart abstraction, video recording, and patients’ monitors. RESULTS: Data on 9 patients and 32 nurses were analyzed. A total of 6244 minutes of data were video recorded. Intracranial pressure was changed because of a nursing intervention during 3394 observations. Compared with baseline levels, intracranial pressure was significantly higher if a nursing intervention was performed (odds ratio, 1.96; 95% CI, 1.71-2.24; P < .001). CONCLUSION: Studying nursing behaviors is feasible. Synchronizing and analyzing mutually exclusive and exhaustive behaviors indicated that nursing behaviors have an effect on patients' intracranial pressure.

Arnold, S. V., J. A. Spertus, S. Vemulapalli, Z. Li, R. A. Matsouaka, S. J. Baron, A. N. Vora, M. J. Mack, M. R. Reynolds, J. S. Rumsfeld and D. J. Cohen (2017). “Quality-of-life outcomes after transcatheter aortic valve replacement in an unselected population: A report from the sts/acc transcatheter valve therapy registry.” JAMA Cardiol: 2017 Feb [Epub ahead of print].

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Importance: In clinical trials, transcatheter aortic valve replacement (TAVR) has been shown to improve symptoms and quality of life. As this technology moves into general clinical practice, evaluation of the health status outcomes among unselected patients treated with TAVR is of critical importance. Objective: To examine the short- and long-term health status outcomes of surviving patients after TAVR in the context of an unselected population. Design, Setting, and Participants: This observational cohort study included patients with severe aortic stenosis who underwent TAVR in the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy (TVT) Registry from November 1, 2011, to March 31, 2016, at more than 450 clinical sites. Main Outcomes and Measures: Disease-specific health status was assessed at baseline and at 30 days and 1 year after TAVR using the Kansas City Cardiomyopathy Questionnaire overall summary (KCCQ-OS) score (range, 0-100 points; higher scores indicate less symptom burden and better quality of life). Factors associated with health status at 1 year after TAVR were examined using multivariable linear regression, with adjustment for baseline health status and accounting for clustering of patients within sites. Results: The 30-day analytic sample included 31 636 patients, and the 1-year cohort included 7014 surviving patients (3454 women [49.2%] and 3560 men [50.8%]; median [interquartile range] age, 84 [78-88] years). The mean (SD) baseline KCCQ-OS score was 42.3 (23.7), indicating substantial health status impairment. Surviving patients had, on average, large improvements in health status at 30 days that persisted to 1 year, with a mean improvement in the KCCQ-OS score of 27.6 (95% CI, 27.3-27.9) points at 30 days and 31.9 (95% CI, 31.3-32.6) points at 1 year. Worse baseline health status, older age, higher ejection fraction, lung disease, home oxygen use, lower mean aortic valve gradients, prior stroke, diabetes, pacemaker use, atrial fibrillation, slow gait speed, and nonfemoral access were significantly associated with worse health status at 1 year. Overall, 62.3% of patients had a favorable outcome at 1 year (alive with reasonable quality of life [KCCQ-OS score, >/=60] and no significant decline [>/=10 points] from baseline), with the lowest rates seen among patients with severe lung disease (51.4%), those undergoing dialysis (47.7%), or those with very poor baseline health status (49.2%). Conclusions and Relevance: In a national, contemporary clinical practice cohort of unselected patients, improvement in health status after TAVR was similar to that seen in the pivotal clinical trials. Although the health status results were favorable for most patients, approximately 1 in 3 still had a poor outcome 1 year after TAVR. Continued efforts are needed to improve patient selection and procedural/postprocedural care to maximize health status outcomes of this evolving therapy.

Kim, P. T., H. Fernandez, A. Gupta, G. Saracino, M. Ramsay, G. J. McKenna, G. Testa, T. Anthony, N. Onaca, R. M. Ruiz and G. B. Klintmalm (2017). “Low measured hepatic artery flow increases rate of biliary strictures in deceased donor liver transplantation: An age-dependent phenomenon.” Transplantation 101(2): 332-340.

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BACKGROUND: This study was conducted to determine effect of lower measured hepatic arterial (HA) flow (<400 mL/min) on biliary complications and graft survival after deceased donor liver transplantation. Hepatic artery is the main blood supply to bile duct and lack of adequate HA flow is thought to be a risk factor for biliary complications. METHODS: A retrospective review of 1300 patients who underwent deceased donor liver transplantation was performed. Patients with arterial complications were excluded to eliminate potential contribution to biliary complications from HA thrombosis. Patients were divided into low (<400 mL/min; N = 201) and high (>/=400 mL/min; N = 1099) HA flow groups. Incidence of biliary complications and graft survival were analyzed. RESULTS: HA flows less than 400 mL/min were associated with increased rate of biliary strictures in younger donors (<50 years old), and in patients with duct-to-duct anastomoses (P = 0.028). Lower HA flows were associated with decreased graft survival (P = 0.013). Donor older than 50 years was associated with increased rate of biliary strictures (hazard ratio [HR], 1.67; 95% confidence interval [CI], 1.14-2.45; P = 0.0085) and graft failure (HR, 1.68; 95% CI, 1.35-2.1; P <0.0001) on multivariate analyses. HA flow less than 400 mL/min was associated with biliary strictures (HR, 1.53; 95% CI, 1.04-2.24; P = 0.0297) on univariate analysis only. CONCLUSIONS: HA flow less than 400 mL/min was associated with higher rate of biliary strictures in younger donors with duct-to-duct reconstruction and lower graft survival. A consideration should be given to increase the intraoperative HA flow to prevent biliary strictures in such patients.