Research Spotlight

McCullough, P. A., J. P. Choi, G. A. Feghali, J. M. Schussler, R. M. Stoler, R. C. Vallabahn and A. Mehta (2016). “Contrast-induced acute kidney injury.” J Am Coll Cardiol 68(13): 1465-1473.

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Coronary angiography and percutaneous intervention rely on the use of iodinated intravascular contrast for vessel and chamber imaging. Despite advancements in imaging and interventional techniques, iodinated contrast continues to pose a risk of contrast-induced acute kidney injury (CI-AKI) for a subgroup of patients at risk for this complication. There has been a consistent and graded signal of risk for associated outcomes including need for renal replacement therapy, rehospitalization, and death, according to the incidence and severity of CI-AKI. This paper reviews the epidemiology, pathophysiology, prognosis, and management of CI-AKI as it applies to the cardiac catheterization laboratory.

Tran, C. and J. R. Griffin (2016). “Simple method for microscopic confirmation of previous biopsy site.” Am J Dermatopathol 38(10): 791-792.

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Aluminum chloride is commonly used by dermatologists as a hemostatic agent after minor surgical procedures such as shave skin biopsies. Two studies have reported that aluminum chloride induces proliferation of histiocytes with aluminum-containing basophilic cytoplasmic granules in biopsy sites.1,2 These aluminum granulomas can be used to identify specimens obtained from previous biopsy sites, such as a reexcision specimen.1 However, the granules may be difficult to visualize with routine hematoxylin and eosin staining.2 The ability to identify that a specimen is from a previous biopsy site is important because rebiopsied tissue may not be labeled as such when submitted for histologic analysis.

Zaydfudim, V. M., N. Vachharajani, G. B. Klintmalm, W. R. Jarnagin, A. W. Hemming, M. B. Doyle, K. M. Cavaness, W. C. Chapman and D. M. Nagorney (2016). “Liver resection and transplantation for patients with hepatocellular carcinoma beyond milan criteria.” Ann Surg 264(4): 650-658.

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OBJECTIVES: To assess survival after liver resection and transplantation in patients with hepatocellular carcinoma (HCC) beyond Milan criteria. BACKGROUND: The role of liver resection and transplantation remains controversial for patients with HCC beyond Milan criteria. Resection of advanced tumors and transplantation using extended-criteria are pursued at select high-volume center. METHODS: Patients from 5 liver cancer centers in the United States who had liver resection or transplantation for HCC beyond Milan criteria between 1990 and 2011 were included in the study. Multivariable and propensity-matching analyses estimated the effects of clinical factors and operative selection on survival. RESULTS: Of 608 patients beyond Milan without vascular invasion, 480 (79%) patients underwent resection and 128 (21%) underwent transplantation. Clinicopathologic profiles between resection and transplant patients differed significantly. Hepatitis C and cirrhosis were more prevalent in transplantation group (P < 0.001). Resection patients had larger tumors [median 9 cm, interquartile range (IQR): 6.5-12.9 cm vs. median 4.1, IQR: 3.4-5.3 cm, P < 0.001]; transplant patients were more likely to have multiple tumors (78% vs 28%, P < 0.001).Overall (OS) and disease-free survival (DFS) were both greater after tumor downstaging and transplantation than resection (all P < 0.001). OS did not differ between liver transplant recipients who were not pretreated or pretreated and failed to downstage compared with propensity-matched liver resection patients (P >/= 0.176); DFS in this propensity matched cohort was greater after liver transplantation. CONCLUSIONS: Liver resection and transplantation provide curative options for patients with HCC beyond Milan criteria. Further treatment strategies aimed at the efficiency and durability of tumor downstaging and expansion of the role of transplantation among suitable candidates could improve outcomes in patients with large or multifocal HCC.

Yeramaneni, S., D. O. Kleindorfer, H. Sucharew, K. Alwell, C. J. Moomaw, M. L. Flaherty, D. Woo, O. Adeoye, S. Ferioli, F. de Los Rios La Rosa, S. Martini, J. Mackey, P. Khatri, B. M. Kissela and J. C. Khoury (2016). “Hyperlipidemia is associated with lower risk of poststroke mortality independent of statin use: A population-based study.” Int J Stroke: 2016 Sep [Epub ahead of print].

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BACKGROUND: Although statin therapy is associated with reduced stroke and mortality risk, some studies report that higher lipid levels are associated with improved outcomes following ischemic stroke. AIMS: We examined the association of hyperlipidemia (HLD) combined with statin therapy on all-cause mortality in stroke patients. METHODS: All stroke patients in the Greater Cincinnati Northern Kentucky region of approximately 1.3 million were identified using ICD-9 discharge codes in 2005 and 2010. Stroke patients with and without HLD were categorized based on their reported statin use at baseline or discharge into three groups: no-HLD/no-statins, HLD/no-statins, and HLD/on-statins. Cox proportional hazards model was used to estimate the risk of mortality at 30 days, 1 year, and 3 years poststroke. RESULTS: Overall, 77% (2953) of the 3813 ischemic stroke patients were diagnosed with HLD and 72% (n = 2123) of those patients were on statin medications. The mean age was 70.0 +/- 14.6 years, 56% were women, and 21% were black. In adjusted analyses, the HLD/no-statins group showed 35% (adjusted hazard ratio (aHR) = 0.65, 95% CI: 0.46-0.92), 27% (aHR = 0.73, 95% CI: 0.59-0.90), and 17% (aHR = 0.83, 95% CI: 0.70-0.97) reduced risk of mortality at 30 days, 1 year, and 3 years, respectively, poststroke, compared with no-HLD/no-statins group. The HLD/on-statins group showed an additional 17% significant survival benefit at 3 years poststroke compared with HLD/no-statins group. CONCLUSIONS: A diagnosis of HLD in ischemic stroke patients is associated with reduced short- and long-term mortality, irrespective of statin use. Statin therapy is associated with significant, additional long-term survival benefit.

Zhong, X. Z., X. Sun, Q. Cao, G. Dong, R. Schiffmann and X. P. Dong (2016). “Bk channel agonist represents a potential therapeutic approach for lysosomal storage diseases.” Sci Rep 16(1): 503.

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Efficient lysosomal Ca2+ release plays an essential role in lysosomal trafficking. We have recently shown that lysosomal big conductance Ca2+-activated potassium (BK) channel forms a physical and functional coupling with the lysosomal Ca2+ release channel Transient Receptor Potential Mucolipin-1 (TRPML1). BK and TRPML1 forms a positive feedback loop to facilitate lysosomal Ca2+ release and subsequent lysosome membrane trafficking. However, it is unclear whether the positive feedback mechanism is common for other lysosomal storage diseases (LSDs) and whether BK channel agonists rescue abnormal lysosomal storage in LSDs. In this study, we assessed the effect of BK agonist, NS1619 and NS11021 in a number of LSDs including NPC1, mild cases of mucolipidosis type IV (ML4) (TRPML1-F408), Niemann-Pick type A (NPA) and Fabry disease. We found that TRPML1-mediated Ca2+ release was compromised in these LSDs. BK activation corrected the impaired Ca2+ release in these LSDs and successfully rescued the abnormal lysosomal storage of these diseases by promoting TRPML1-mediated lysosomal exocytosis. Our study suggests that BK channel activation stimulates the TRPML1-BK positive reinforcing loop to correct abnormal lysosomal storage in LSDs. Drugs targeting BK channel represent a potential therapeutic approach for LSDs.