Research Spotlight

Adelmann, D., K. Kronish and M. A. Ramsay (2017). “Anesthesia for liver transplantation.” Anesthesiol Clin 35(3): 491-508.

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The provision of anesthesia for a liver transplant program requires a dedicated team of anesthesiologists. Liver transplant anesthesiologists must have an understanding of liver physiology and anatomy; the spectrum of clinical disease associated with liver dysfunction; the impact of warm and cold ischemia times, surgical techniques in liver transplantation, and the impact of ischemia-reperfusion syndrome; and optimal practices to protect the liver. The team must provide a 24-hour service, be actively involved in the selection committee process, and stay current with advances in the subspecialty.

Bastarrachea, R. A., J. Chen, J. W. Kent, Jr., E. J. Nava-Gonzalez, E. Rodriguez-Ayala, M. M. Daadi, B. Jorge, H. Laviada-Molina, A. G. Comuzzie, S. Chen and P. A. Grayburn (2017). “Engineering brown fat into skeletal muscle using ultrasound-targeted microbubble destruction gene delivery in obese zucker rats: Proof of concept design.” IUBMB Life: 2017 Jul [Epub ahead of print].

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Ultrasound-targeted microbubble destruction (UTMD) is a novel means of tissue-specific gene delivery. This approach systemically infuses transgenes precoupled to gas-filled lipid microbubbles that are burst within the microvasculature of target tissues via an ultrasound signal resulting in release of DNA and transfection of neighboring cells within the tissue. Previous work has shown that adenovirus containing cDNA of UCP-1, injected into the epididymal fat pads in mice, induced localized fat depletion, improving glucose tolerance, and decreasing food intake in obese diabetic mice. Our group recently demonstrated that gene therapy by UTMD achieved beta cell regeneration in streptozotocin (STZ)-treated mice and baboons. We hypothesized that gene therapy with BMP7/PRDM16/PPARGC1A in skeletal muscle (SKM) of obese Zucker diabetic fatty (fa/fa) rats using UTMD technology would produce a brown adipose tissue (BAT) phenotype with UCP-1 overexpression. This study was designed as a proof of concept (POC) project. Obese Zucker rats were administered plasmid cDNA contructs encoding a gene cocktail with BMP7/PRDM16/PPARGC1A incorporated within microbubbles and intravenously delivered into their left thigh. Controls received UTMD with plasmids driving a DsRed reporter gene. An ultrasound transducer was directed to the thigh to disrupt the microbubbles within the microcirculation. Blood samples were drawn at baseline, and after treatment to measure glucose, insulin, and free fatty acids levels. SKM was harvested for immunohistochemistry (IHC). Our IHC results showed a reliable pattern of effective UTMD-based gene delivery in enhancing SKM overexpression of the UCP-1 gene. This clearly indicates that our plasmid DNA construct encoding the gene combination of PRDM16, PPARGC1A, and BMP7 reprogrammed adult SKM tissue into brown adipose cells in vivo. Our pilot established POC showing that the administration of the gene cocktail to SKM in this rat model of genetic obesity using UTMD gene therapy, engineered a BAT phenotype with UCP-1 over-expression.

Bernstein, R. A., H. Kamel, C. B. Granger, R. C. Kowal, P. D. Ziegler and L. H. Schwamm (2017). “Stroke of known cause and underlying atrial fibrillation (stroke-af) randomized trial: Design and rationale.” Am Heart J 190: 19-24.

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BACKGROUND: Approximately 20% of ischemic strokes are associated with clinically apparent atrial fibrillation (AF). Regardless of stroke etiology, detection of AF in patients with ischemic strokes often changes antithrombotic treatment from anti-platelet to oral anticoagulation therapy. The role and the optimum duration of cardiac monitoring to detect AF in patients with strokes presumed due to large vessel atherosclerosis or small vessel disease is unknown. This manuscript describes the design and rationale of the STROKE-AF trial. STUDY DESIGN: STROKE-AF is a randomized, controlled, open-label, post-market clinical trial. Detection of AF will be evaluated using continuous arrhythmia monitoring with an insertable cardiac monitor (ICM) compared with standard of care follow-up in patients with stroke (within the prior 10 days) that is presumed due to large vessel cervical or intracranial atherosclerosis, or to small vessel disease. Approximately 500 patients will be enrolled at approximately 40 centers in the United States. Patients will be randomized 1:1 to arrhythmia monitoring with an ICM (continuous monitoring arm) or standard of care follow-up (control arm). Subjects will be followed for >/=12 months and up to 3 years. OUTCOMES: The primary objective is to compare the incidence rate of detected AF through 12 months of follow-up between the two arms. CONCLUSION: This trial will provide information on the value of ICMs to detect subclinical AF in patients with stroke presumed due to large vessel atherosclerosis or small vessel disease, which will have implications for guiding treatment with oral anticoagulation for secondary stroke prevention.

K, C. B., E. Mejia-Lopez, P. McCullough, K. Breathett, J. L. Kennedy, J. Tallaj, J. Bergin, S. Pamboukian, M. Abuannadi and S. Mazimba (2017). “Clinical impact of changes in hemodynamic indices of contractile function during treatment of acute decompensated heart failure.” J Card Fail: 2017 Jul [Epub ahead of print].

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BACKGROUND: The objective was to determine the impact of improving right ventricular versus left ventricular stroke work indices (RVSWI v. LVSWI) during therapy for acute decompensated heart failure (ADHF). METHODS AND RESULTS: Cox proportional hazards regression and logistic regression was used to analyze key factors associated with outcomes in 175 patients (age 56.7 +/- 13.6 years, 29.1% female) with hemodynamic data from the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial. In this cohort, 28.6% and 69.7%, respectively, experienced the outcomes of death, transplant, or ventricular assist device (DVADTX) and DVADTX or HF rehospitalization (DVADTXHF) during 6 months of follow-up. Increasing RVSWI (DeltaRVSWI) from baseline to discharge was associated with a decrease in DVADTXHF (HR 0.923 [95% CI 0.871-0.979] per 0.1 mmHg*L/m2 increase); however, increasing LVSWI (DeltaLVSWI) only had a non-significant association with decreased DVADTXHF (P=0.11) In a multivariable model, patients with DeltaRVSWI

Carmichael, J. C., D. S. Keller, G. Baldini, L. Bordeianou, E. Weiss, L. Lee, M. Boutros, J. McClane, S. R. Steele and L. S. Feldman (2017). “Clinical practice guideline for enhanced recovery after colon and rectal surgery from the american society of colon and rectal surgeons (ascrs) and society of american gastrointestinal and endoscopic surgeons (sages).” Surg Endosc: 2017 Aug [Epub ahead of print].

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This clinical practice guideline represents a collaborative effort between the American Society of Colon and Rectal Surgeons (ASCRS) and Society of American Gastrointestinal and Endoscopic Surgeons (SAGES). The Clinical Practice Guidelines Committee of the ASCRS is composed of society members who are chosen because they have demonstrated expertise in the specialty of colon and rectal surgery. In a collaborative effort, the ASCRS Clinical Practice Guidelines Committee and members of the SAGES SMART (Surgical Multimodal Accelerated Recovery Trajectory) Enhanced Recovery Task Force and Guidelines Committee have joined together to produce this guideline written and approved by both societies. The combined ASCRS/SAGES panel worked together to develop the statements in this guideline and approved these final recommendations. Through this effort, the ASCRS and SAGES continue their dedication to ensuring high quality perioperative patient care.