Research Spotlight

Navas, M. C., S. Glaser, H. Dhruv, S. Celinski, G. Alpini and F. Meng (2019). “Hepatitis C virus infection and cholangiocarcinoma: An insight into epidemiological evidences and hypothetical mechanisms of oncogenesis.” Am J Pathol Apr 3. [Epub ahead of print].

Full text of this article.

Hepatitis C Virus (HCV) infection is a global public health problem since it is a main cause of liver cirrhosis and hepatocellular carcinoma (HCC). This human oncogenic virus is also associated with the development of non-Hodgkin lymphoma and cholangiocarcinoma (CCA). The association between HCV infection and CCA has been examined in a number of epidemiological studies. However, in vivo and in vitro results demonstrating the oncogenic mechanisms of HCV in CCA development and progression are insufficient. Here, we review the epidemiological association of HCV and CCA and recent publications of studies of HCV infection of cholangiocytes and CCA cell lines as well as studies of viral infection performed with liver samples obtained from patients. In addition, we also discuss the preliminary results of in vitro assays of HCV protein expression in CCA cell lines. Finally, we discuss the hypothetical role of HCV infection in CCA development by induction of epithelial-mesenchymal transition and up-regulation of hedgehog signaling, and consequently biliary tree inflammation and liver fibrosis. Further studies are required to demonstrate these hypothesis and therefore to elucidate the mechanisms of HCV as a risk factor for CCA.

Myhre, P. L., M. Vaduganathan, B. Claggett, M. Packer, A. S. Desai, J. L. Rouleau, M. R. Zile, K. Swedberg, M. Lefkowitz, V. Shi, J. J. V. McMurray and S. D. Solomon (2019). “B-Type Natriuretic Peptide During Treatment With Sacubitril/Valsartan: The PARADIGM-HF Trial.” J Am Coll Cardiol 73(11): 1264-1272.

Full text of this article.

BACKGROUND: Natriuretic peptides are substrates of neprilysin; hence, B-type natriuretic peptide (BNP) concentrations rise with neprilysin inhibition. Thus, the clinical validity of measuring BNP in sacubitril/valsartan-treated patients has been questioned, and use of N-terminal pro-B-type natriuretic peptides (NT-proBNP) has been preferred and recommended. OBJECTIVES: The purpose of this study was to determine the prognostic performance of BNP measurements before and during treatment with sacubitril/valsartan. METHODS: BNP and NT-proBNP were measured before and after 4 to 6 weeks, 8 to 10 weeks, and 9 months of treatment with sacubitril/valsartan in the PARADIGM-HF (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial. We assessed the association of levels of these natriuretic peptides with the subsequent risk of cardiovascular death or hospitalization for HF. RESULTS: Median BNP concentration (before treatment: 202 ng/l [Q1 to Q3: 126 to 335 ng/l]) increased to 235 ng/l (Q1 to Q3: 128 to 422 ng/l) after 8 to 10 weeks of treatment. BNP concentrations doubled in 141 (18%) patients and tripled in 49 (6%) patients during the first 8 to 10 weeks of sacubitril/valsartan. In contrast, such striking increases in NT-proBNP following the use of the neprilysin inhibitor were extremely rare. Treatment with sacubitril/valsartan caused a rightward shift in the distribution of BNP when compared with NT-proBNP, but both peptides retained their prognostic accuracy (C-statistics of 63% to 67% for BNP and C-statistics of 64% to 70% for NT-proBNP) with no difference between the 2 biomarkers. Increases in both BNP and NT-proBNP during 8 to 10 weeks of sacubitril/valsartan were associated with worse outcomes (p = 0.003 and p = 0.005, respectively). CONCLUSIONS: Circulating levels of BNP may increase meaningfully early after initiation of sacubitril/valsartan. In comparison, NT-proBNP is not a substrate of neprilysin inhibition, and thus may lead to less clinical confusion when measured within 8 to 10 weeks of drug initiation. However, during treatment, either biomarker predicts the risk of major adverse outcomes in patients treated with angiotensin receptor-neprilysin inhibitors. (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure [PARADIGM-HF]; NCT01035255).

Misra, S. M., C. Garcia, P. Swamy, S. Kumar, J. Chavez, Jr. and A. Gupta (2019). “Reaching Uninsured Overweight and Obese Children Through the FitKids Mobile Lifestyle Modification Program: Lessons Learned.” J Community Health 44(2): 208-214.

Full text of this article.

The US prevalence of childhood obesity remains high with ~ 1 in five children diagnosed with obesity, and rates of obesity are likely higher in uninsured and Medicaid populations than in those with private insurance. To understand the impact of an obesity intervention, an established mobile clinic program conducted a study to determine whether a FitKids Mobile Lifestyle Modification Program could reach overweight and obese uninsured children. Eighty-six children (ages 8-18 years) participated in the FitKids study over two trial periods. The first trial consisted of four total visits, but subsequent visits after the initial visit had poor turnout. Through telephonic interviews, parents described positive aspects of the program: (1) providers’ individual attention to their child, (2) increased knowledge about obesity, nutrition, and diet, (3) and parent and child were motivated to be more active. The most common barriers noted for return visits were (1) personal/family factors, (2) scheduling issues, and (3) distance to the clinic. As quality improvement, for the second trial, total number of visits was reduced from 4 to 3 visits and reminder calls were instituted. Percentage of children who returned for the third visit (67.5% for Trial 1 and 62.5% for Trial 2) was not improved despite quality improvement interventions. Mobile clinics provide a unique solution to reach underserved overweight and obese children to help them create a more active and healthy lifestyle, but more research is needed to understand how best to optimize programs.

Michelson, E., J. S. Huff, J. Garrett and R. Naunheim (2019). “Triage of Mild Head-Injured Intoxicated Patients Could Be Aided by Use of an Electroencephalogram-Based Biomarker.” J Neurosci Nurs 51(2): 62-66.

Full text of this article.

OBJECTIVE: Drug and alcohol (DA)-related emergency department (ED) visits represent an increasing fraction the head-injured population seen in the ED. Such patients present a challenge to the evaluation of head injury and determination of need for computed tomographic (CT) scan and further clinical path. This effort examined whether an electroencephalogram (EEG)-based biomarker could aid in reducing unnecessary CT scans in the intoxicated ED population. METHOD: This is a retrospective secondary study of an independent prospective US Food and Drug Administration validation trial that demonstrated the efficacy of (1) an automatic Structural Injury Classifier for the likelihood of injury visible on a CT (CT+) and (2) an EEG-based Brain Function Index to assess functional impairment in minimally impaired, head-injured adults presenting within 3 days of injury. Impact on the biomarker performance in patients who presented with or without DA was studied. RESULTS: Structural Injury Classifier sensitivity was not significantly impacted by the presence of DA. Although specificity decreased, it remained several times higher than obtained using standard CT decision rules. Furthermore, the potential to reduce the number of unnecessary scans by approximately 30% was demonstrated when the Structural Injury Classifier was integrated into CT clinical triage. The Brain Function Index was demonstrated to be independent of the presence of DA. CONCLUSION: This EEG-based assessment technology used to identify the likelihood of structural or functional brain injury in mildly head-injured patients represents an objective way to aid in triage patients with DA on presentation, with the potential to decrease overscanning while not sacrificing sensitivity to injuries visible on CT.E

Menter, A., B. E. Strober, D. H. Kaplan, D. Kivelevitch, E. F. Prater, B. Stoff, A. W. Armstrong, C. Connor, K. M. Cordoro, D. M. R. Davis, B. E. Elewski, J. M. Gelfand, K. B. Gordon, A. B. Gottlieb, A. Kavanaugh, M. Kiselica, N. J. Korman, D. Kroshinsky, M. Lebwohl, C. L. Leonardi, J. Lichten, H. W. Lim, N. N. Mehta, A. S. Paller, S. L. Parra, A. L. Pathy, R. N. Rupani, M. Siegel, E. B. Wong, J. J. Wu, V. Hariharan and C. A. Elmets (2019). “Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with biologics.” J Am Acad Dermatol 80(4): 1029-1072.

Full text of this article.

Psoriasis is a chronic, inflammatory multisystem disease that affects up to 3.2% of the US population. This guideline addresses important clinical questions that arise in psoriasis management and care, providing recommendations based on the available evidence. The treatment of psoriasis with biologic agents will be reviewed, emphasizing treatment recommendations and the role of the dermatologist in monitoring and educating patients regarding benefits as well as associated risks.