Research Spotlight

Fallahzadeh, M. A., B. Dormanesh, M. K. Fallahzadeh, J. Roozbeh, M. H. Fallahzadeh and M. M. Sagheb (2016). “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: 2016 Dec [Epub ahead of print].

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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.

Hunt, J. C., M. Sapp, C. Walker, A. M. Warren, K. Brasel and T. A. deRoon-Cassini (2017). “Utility of the injured trauma survivor screen to predict ptsd and depression during hospital admission.” J Trauma Acute Care Surg 82(1): 93-101.

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BACKGROUND: The brief, easily administered screen, the Injured Trauma Survivor Screen (ITSS), was created to identify trauma survivors at risk for development of posttraumatic stress disorder (PTSD) and depression. METHODS: An item pool of PTSD risk factors was created and given, along with a previously created screen, to patients admitted to two Level 1 trauma centers. The Clinician Administered PTSD Scale for DSM-5, the PTSD Checklist for DSM-5, and the Center for Epidemiological Studies Depression Scale Revised were given during a 1-month follow-up. A total of 139 participants were included (n = 139; mu age = 41.06; 30.9% female; 47.5% White/Caucasian; 39.6% Black/African American; 10.1% Latino/Hispanic; 1.4% American Indian; and 1.4% other). Stepwise bivariate logistic regression was used to determine items most strongly associated with PTSD and depression diagnosis 1 month after injury. RESULTS: Forty participants met criteria for a PTSD diagnosis and 28 for depression at follow-up (22 comorbid). ROC curve analysis was used to determine sensitivity (PTSD = 75.00, Depression = 75.00), specificity (PTSD = 93.94, Depression = 95.5), NPV (PTSD = 90.3, Depression = 80.8), and PPV (PTSD = 83.3, Depression = 93.8) of the final nine-item measure. CONCLUSIONS: This study provides evidence for the utility of a predictive screen, the ITSS, to predict which injured trauma survivors admitted to the hospital are at the most risk for developing symptoms of PTSD and depression 1 month after injury. The ITSS is a short, easily administered tool that can aid in reducing the untreated cases of PTSD and depression.

Jiang, Y., Y. Zhu, W. Qiu, Y. J. Liu, G. Cheng, Z. J. Liu and S. Ouyang (2016). “Structural and functional analyses of human ddx41 dead domain.” Protein Cell: 2016 Dec [Epub ahead of print].

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DEAD-box proteins, which are named after the strictly conserved amino acid sequence Asp-Glu-Ala-Asp, were first identified as a distinct family in the late 1980s when alignments based on eight homologues of the yeast eIF4A highlighted the presence of several conserved motifs (Linder et al., 1989). DEAD-box proteins are widely distributed in different life forms, ranging from bacteria to human and constitute the largest RNA helicase family (Jiang et al.,2016). They are involved in many aspects of RNA metabolism, such as splicing, mRNA export, transcriptional and translational regulation, ribosome biogenesis and RNA decay (Rocak and Linder, 2004). The core of DEAD-box proteins is organized into two major domains. Domain 1 (DEAD domain) consists of motifs Q, I (Walker A, P-loop), II (Walker B, DEAD-box), Ia, GG, Ib and III, whereas domain 2 (Helicase domain) consists of motifs IV, V and VI. Different motifs are involved in nucleotide binding (Q, I and II), RNA binding (Ia, Ib, IV and V) and ATP hydrolysis (III and possibly VI). Compared with the two conserved domains, the N- and C-terminal regions are variable and divergent. Their functions are not fully characterized, but they are thought to confer their own specificity on different proteins (Hogbom et al., 2007).

Joseph, S. M. (2016). “Lvads and contemplations on a flood.” J Card Fail: 2016 Dec [Epub ahead of print].

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Physicist Max Planck wrote that “the new scientific truth does not triumph by convincing its opponents and making them see the light, but rather because its opponents eventually die, and a new generation grows up that is familiar with it.”1 We are living in a very exciting time in cardiovascular medicine and especially in heart failure. It’s remarkable to think of how far we’ve come in such a short a period of time in our understanding of the physiology and application of durable continuous-flow ventricular assist devices. Even compared to 10 years ago, there has been a cultural change, albeit gradual, regarding the ways by which mechanical assist options are perceived. Therapies like extracorporeal life support (ECMO) and other percutaneous assist devices were commonly thought of as salvage therapy with a dismal prognosis, a heroic “hail Mary” last-ditch effort when all else failed. Now, these therapies are starting to be employed more widely and practitioners are becoming more acclimated to the complexities and nuances of managing a patient with non-physiologic circulation. Is it because scientific truth has converted the opponents? Or is it because, as our Editor-in-Chief Paul Hauptman suggested before, that HF as a specialty is “hot right now…”2, attracting a generation of HF doctors who were trained in the context of the rapid-growth phase of utilization of these devices, making it culturally part of their [our] fabric?

Keller, D. S., C. P. Delaney, A. J. Senagore and L. S. Feldman (2016). “Uptake of enhanced recovery practices by sages members: A survey.” Surg Endosc: 2016 Dec [Epub ahead of print].

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BACKGROUND: The SAGES Surgical Multimodal Accelerated Recovery Trajectory (SMART) Enhanced Recovery Task Force aims to increase awareness and provide tools for members to successfully implement enhanced recovery pathways (ERPs) to improve clinical outcomes and patient satisfaction. An initial step was to survey SAGES member on their knowledge, use, and impediments to enhanced recovery. METHODS: An online survey designed by SMART committee members to define SAGES member’s awareness and use of enhanced recovery principles and practice was emailed to all SAGES members. Reminders were sent 2 and 3 weeks later, encouraging completion of the survey. The web-based survey included 48 questions and took an estimated 20 min to complete. RESULTS: A total of 229 members completed the survey. Respondents were primarily general/MIS surgeons (82.6%) working in an urban location (85.5%), with a bell-shaped age distribution (median 35-44). Almost half regularly used some elements of ERPs (48.7%), but 30% were unfamiliar with the concept. Wide variety in the specific ERP elements used and discharge criteria were reported. The majority had to create and implement their own plan (70.4%). Roadblocks to implementation were inconsistencies with partners/covering physicians (56.3%), nursing education (46.6%), and resources (34.7%). When implemented, members saw improvements in length of stay (88%), patient satisfaction (54.7%), postoperative pain (53.3%), time to return of bowel function (52.7%), and readmissions (16.7%). A need for education and standardization was especially seen in preoperative care, with 74.4% fasting patients from midnight the night before surgery. Wide variations were also reported in pain management practices. An overwhelming majority (89%) reported that having a protocol endorsed by a national organization, such as SAGES, would help with implementation. CONCLUSIONS: From this survey of SAGES members, there is a need for education, tools, and standardized protocols to increase awareness, support implementation, and encourage wider utilization of ERP. The overwhelming majority stated having a protocol endorsed by a national organization, such as SAGES, would facilitate implementation.