Research Spotlight

Howden, E. J., C. East, J. S. Lawley, A. S. L. Stickford, M. Verhees, Q. Fu and B. D. Levine (2017). “Integrative blood pressure response to upright tilt post renal denervation.” Am J Hypertens 30(6): 632-641.

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BACKGROUND: Whether renal denervation (RDN) in patients with resistant hypertension normalizes blood pressure (BP) regulation in response to routine cardiovascular stimuli such as upright posture is unknown. We conducted an integrative study of BP regulation in patients with resistant hypertension who had received RDN to characterize autonomic circulatory control. METHODS: Twelve patients (60 +/- 9 [SD] years, n = 10 males) who participated in the Symplicity HTN-3 trial were studied and compared to 2 age-matched normotensive (Norm) and hypertensive (unmedicated, HTN) control groups. BP, heart rate (HR), cardiac output (Qc), muscle sympathetic nerve activity (MSNA), and neurohormonal variables were measured supine, and 30 degrees (5 minutes) and 60 degrees (20 minutes) head-up-tilt (HUT). Total peripheral resistance (TPR) was calculated from mean arterial pressure and Qc. RESULTS: Despite treatment with RDN and 4.8 (range, 3-7) antihypertensive medications, the RDN had significantly higher supine systolic BP compared to Norm and HTN (149 +/- 15 vs. 118 +/- 6, 108 +/- 8 mm Hg, P < 0.001). When supine, RDN had higher HR, TPR, MSNA, plasma norepinephrine, and effective arterial elastance compared to Norm. Plasma norepinephrine, Qc, and HR were also higher in the RDN vs. HTN. During HUT, BP remained higher in the RDN, due to increases in Qc, plasma norepinephrine, and aldosterone. CONCLUSION: We provide evidence of a possible mechanism by which BP remains elevated post RDN, with the observation of increased Qc and arterial stiffness, as well as plasma norepinephrine and aldosterone levels at approximately 2 years post treatment. These findings may be the consequence of incomplete ablation of sympathetic renal nerves or be related to other factors.

Gupta, N., J. V. Brill, M. Canto, D. DeMarco, B. M. Fennerty, L. Laine, D. Lieberman, C. Lightdale, E. Montgomery, R. Odze, D. Rex, P. Sharma, J. L. Tokar and M. L. Kochman (2017). “Aga white paper: Training and implementation of endoscopic image enhancement technologies.” Clin Gastroenterol Hepatol 15(6): 820-826.

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Endoscopic image-enhancement technologies provide opportunities to visualize normal and abnormal tissues within the gastrointestinal (GI) tract in a manner that complements conventional white light endoscopic imaging. The additional information that is obtained enables the endoscopist to better identify, delineate, and characterize lesions and can facilitate targeted biopsies or, in some cases, eliminate the need to send samples for histologic analysis. Some of these technologies have been available for more than a decade, but despite this fact, there is limited use of these technologies by endoscopists. Lack of formalized training in their use and a scarcity of guidelines on implementation of these technologies into clinical practice are contributing factors. In November 2014, the American Gastroenterological Association’s Center for GI Innovation and Technology conducted a 2-day workshop to discuss endoscopic image-enhancement technologies. This article represents the third of 3 separate documents generated from the workshop and discusses the published literature pertaining to training and outlines a proposed framework for the implementation of endoscopic image-enhancement technologies in clinical practice. There was general agreement among participants in the workshop on several key considerations. Training and competency assessment for endoscopic image-enhancement technologies should incorporate competency-based education paradigms. To facilitate successful training, multiple different educational models that can cater to variations in learning styles need to be developed, including classroom-style and self-directed programs, in-person and web-based options, image and video atlases, and endoscopic simulator programs. To ensure safe and appropriate use of these technologies over time, refresher courses, skill maintenance programs, and options for competency reassessment should be established. Participants also generally agreed that although early adopters of novel endoscopic image-enhancement modalities can successfully implement these technologies by pursuing training and ensuring self-competency, widespread implementation is likely to require support from GI societies and buy-in from other key stakeholders including payors/purchasers and patients. Continued work by manufacturers and the GI societies in providing training programs and patient education, working with payors and purchasers, and creating environments and policies that motivate endoscopists to adopt new practices is essential in creating widespread implementation.

Garcia Aroz, S., I. Tzvetanov, E. A. Hetterman, H. Jeon, J. Oberholzer, G. Testa, E. John and E. Benedetti (2017). “Long-term outcomes of living-related small intestinal transplantation in children: A single-center experience.” Pediatr Transplant 21(4).

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Pediatric patients with irreversible intestinal failure present a significant challenge to meet the nutritional needs that promote growth. From 2002 to 2013, 13 living-related small intestinal transplantations were performed in 10 children, with a median age of 18 months. Grafts included isolated living-related intestinal transplantation (n=7), and living-related liver and small intestine (n=6). The immunosuppression protocol consisted of induction with thymoglobulin and maintenance therapy with tacrolimus and steroids. Seven of 10 children are currently alive with a functioning graft and good quality of life. Six of the seven children who are alive have a follow-up longer than 10 years. The average time to initiation of oral diet was 32 days (range, 13-202 days). The median day for ileostomy takedown was 77 (range, 18-224 days). Seven children are on an oral diet, and one of them is on supplements at night through a g-tube. We observed an improvement in growth during the first 3 years post-transplant and progressive weight gain throughout the first year post-transplantation. Growth catch-up and weight gain plateaued after these time periods. We concluded that living donor intestinal transplantation potentially offers a feasible, alternative strategy for long-term treatment of irreversible intestinal failure in children.

Wells, K. and P. E. Wise (2017). “Hereditary colorectal cancer syndromes.” Surg Clin North Am 97(3): 605-625.

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Awareness of hereditary colorectal cancer syndromes is important to facilitate their identification because affected patients are at increased risk for early onset, synchronous, and metachronous colorectal malignancies, and certain extracolonic malignancies depending on the syndrome. Identification of an affected individual allows for screening and early interventions for patients and their at-risk kindred. Genetic counseling and testing is important to the care of these patients. As knowledge of the genetic basis of these syndromes grows, unique genotype-phenotype profiles allow clinicians to tailor surveillance and treatment strategies based on individual risk.

Reilly, C. R., D. V. Babushok, K. Martin, J. L. Spivak, M. Streiff, R. Bahirwani, J. Mondschein, B. Stein, A. Moliterno and E. O. Hexner (2017). “Multicenter analysis of the use of transjugular intrahepatic portosystemic shunt (tips) for management of mpn-associated portal hypertension.” Am J Hematol: 2017 May [Epub ahead of print].

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BCR-ABL1-negative myeloproliferative neoplasms (MPNs) are clonal stem cell disorders defined by proliferation of one or more myeloid lineages, and carry an increased risk of vascular events and progression to myelofibrosis and leukemia. Portal hypertension (pHTN) occurs in 7-18% of MPN patients via both thrombotic and nonthrombotic mechanisms and portends a poor prognosis. Transjugular intrahepatic portosystemic shunt (TIPS) has been used in the management of MPN-associated pHTN; however, data on long-term outcomes of TIPS in this setting is limited and the optimal management of medically refractory MPN-associated pHTN is not known. In order to assess the efficacy and long-term outcomes of TIPS in MPN-associated pHTN, we performed a retrospective analysis of 29 MPN patients who underwent TIPS at three academic medical centers between 1997 and 2016. The majority of patients experienced complete clinical resolution of pHTN and its clinical sequelae following TIPS. One, two, three, and four-year overall survival post-TIPS was 96.4%, 92.3%, 84.6%, and 71.4%, respectively. However, despite therapeutic anticoagulation, in-stent thrombosis occurred in 31.0% of patients after TIPS, necessitating additional interventions. In conclusion, TIPS can be an effective intervention for MPN-associated pHTN regardless of etiology. However, TIPS thrombosis is a frequent complication in the MPN population and indefinite anticoagulation post-TIPS should be considered.