Research Spotlight

Rosenthal, R. L. (2017). “Electronic stethoscope for coronary stenosis detection.” Am J Med 130(5): e225.

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I read with interest the report by Azimpour et al1 on the ability of an electronic stethoscope to detect turbulent diastolic flow in coronary arteries associated with coronary stenosis by the use of a signal processing algorithm. Instead of the “gold standard” of percentage coronary stenosis they adopt as the reference standard, it would be more physiologically pertinent to explore the relationship to fractional flow reserve or some other similar measure of trans-stenotic flow gradient, such as the instantaneous wave-free ratio.

Sorokin, I., S. L. Stevens and J. A. Cadeddu (2017). “Periarterial papaverine to treat renal artery vasospasm during robot-assisted laparoscopic partial nephrectomy.” J Robot Surg: Apr [Epub ahead of print].

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Renal artery vasospasm can be a troublesome complication during robot-assisted laparoscopic partial nephrectomy. Urologists performing this procedure, especially if utilizing selective arterial vascular microdissection, should be aware of using papaverine for both prevention and treatment of renal artery vasospasm. We present a 33-year-old male who developed severe renal artery vasospasm just with hilar dissection causing the kidney to become ischemic. Papaverine was topically applied on the renal arteries resulting in vasodilation and reperfusion of the kidney. Our objective of this report is to raise awareness of this complication as well as to review the literature on periarterial papaverine use and the dosing for topical applications.

Souza, R. F. (2017). “Reflux esophagitis and its role in the pathogenesis of barrett’s metaplasia.” J Gastroenterol: Apr [Epub ahead of print].

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Reflux esophagitis damages the squamous epithelium that normally lines the esophagus, and promotes replacement of the damaged squamous lining by the intestinal metaplasia of Barrett’s esophagus, the precursor of esophageal adenocarcinoma. Therefore, to prevent the development of Barrett’s metaplasia and esophageal adenocarcinoma, the pathogenesis of reflux esophagitis must be understood. We have reported that reflux esophagitis, both in a rat model and in humans, develops as a cytokine-mediated inflammatory injury (i.e., cytokine sizzle), not as a caustic chemical injury (i.e., acid burn), as traditionally has been assumed. Moreover, reflux induces activation of hypoxia inducible factor (HIF)-2alpha, which enhances the transcriptional activity of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB) causing increases in pro-inflammatory cytokines and in migration of T lymphocytes, an underlying molecular mechanism for this cytokine-mediated injury. In some individuals, reflux esophagitis heals with Barrett’s metaplasia. A number of possibilities exist for the origin of the progenitor cells that give rise to this intestinal metaplasia including those of the esophagus, the proximal stomach, or the bone marrow. However, intestinal cells are not normally found in the esophagus, the stomach, or the bone marrow. Thus, the development of Barrett’s intestinal metaplasia must involve some molecular reprogramming of key developmental transcription factors within the progenitor cell, a process termed transcommitment, which may be initiated by the noxious components of the gastric refluxate. This review will highlight recent studies on the pathogenesis of reflux esophagitis and on reflux-related molecular reprogramming of esophageal squamous epithelial cells in the pathogenesis of Barrett’s metaplasia.

O’Leary, J. G., C. Smith, J. Cai, B. Hart, L. W. Jennings, M. Everly, G. B. Klintmalm and A. J. Demetris (2017). “Chronic amr in liver transplant: Validation of the 1-year camr score’s ability to determine long-term outcome.” Transplantation: Apr [Epub ahead of print].

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BACKGROUND: A proposed chronic antibody-mediated rejection (AMR) score has recently predicted 50%10-year death censored allograft loss in patients with Donor Specific Alloantibodies (DSA) Mean Florescence Intensity (MFI) >10 000 and requires confirmation in patients with lower MFI (1000-10 000). METHODS: All patients who underwent liver transplantation (LT) from 1/00-4/09, had DSA (MFI >/=1000) in serum 10-14 months post-LT, and had a protocolized liver biopsy were evaluated (n=230). The previously proposed chronic AMR (cAMR) score was used to risk-stratify putative chronic AMR in DSA+ patients with MFI from 1000-10 000. RESULTS: The MFI distribution of DSA+ recipients were as follows: 66% had MFI 1000-4999, 14% had MFI 5000-10 000 and 20% had MFI >10 000. The cAMR score distribution on 1-year protocol liver biopsy was found to be: 41% had a score <13; 27% a score 13-27.5 and 32% a score >27.5. MFI correlated with 1-year cAMR category (<13, 46% vs. 21% and >27.5, 29% vs. 42% when MFI was 1000-10 000 vs. MFI >10 000; p=0.047). In patients with a cAMR score <13, 10-year death censored allograft survival was 96-100% regardless of MFI (p=NS). The risk of allograft loss increased in patients with a cAMR score >13 (p=0.004) in DSA+ patients with MFI 1000-10 000. DSA MFI>10 000 vs. MFI 1000-10 000 at 1-year was also more likely to persist at 5-years (95% vs. 68%; p<0.0001). CONCLUSIONS: Validation of the previously proposed cAMR score in a separate cohort predicts death-censored long-term allograft failure in DSA+ patients regardless of MFI, and higher MFI at 1-year predicts DSA persistence at 5-years.

Packer, M. (2017). “Response by packer to letter regarding article, “development and evolution of a hierarchical clinical composite end point for the evaluation of drugs and devices for acute and chronic heart failure: A 20-year perspective”.” Circulation 135(15): e892-e893.

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The hierarchical clinical composite end point (HCCE) was developed to address 2 important goals in the analysis of clinical trial data: (1) to minimize the bias inherent in the censoring of important adverse events when the primary end point was focused entirely on a patient benefit, and (2) to expand the range of responses when the primary end point was focused entirely on the risk of an adverse event. Over the past 20 years, the hierarchical clinical composite has succeeded with respect to both goals, and yet, as I described in my article,1 the HCCE still has important limitations and remains a work in progress.