Research Spotlight

Elbadawi, A., Elgendy, I.Y., Megaly, M., Ugwu, J., Shahin, H.I., Al-Azizi, K., Garcia, S., Abbott, J.D., Gafoor, S., Kleiman, N.S. and Goel, S.S. (2021). “Trends and Outcomes of Transcatheter Aortic Valve Implantation Among Solid Organ Transplant Recipients.” Am J Cardiol 138: 122-124.

Full text of this article.

Transcatheter aortic valve implantation (TAVI) has become an alternative treatment option for patients with severe aortic stenosis irrespective of their surgical risk. 1 With advances in surgical techniques, organ matching, and immune therapy, the number of solid-organ transplant recipients has exponentially increased, as well as the median survival time. 2 Traditional cardiovascular risk factors are more prevalent in the aging transplant recipients population, and they are at high risk for severe aortic stenosis. 2 Solid-organ transplant recipients are at higher risk for mortality and morbidity with surgical aortic valve replacement. 2 There is a paucity of data on the outcomes of TAVI in solid-organ transplant recipients, since they have been excluded from the pivotal trials. Hence, we aimed to examine the trends and outcomes of TAVI in solid organ receipts using a nationally representative database.

Dougherty, U., Mustafi, R., Zhu, H., Zhu, X., Deb, D., Meredith, S.C., Ayaloglu-Butun, F., Fletcher, M., Sanchez, A., Pekow, J., Deng, Z., Amini, N., Konda, V.J., Rao, V.L., Sakuraba, A., Kwesi, A., Kupfer, S.S., Fichera, A., Joseph, L., Hart, J., He, F., He, T.C., West-Szymanski, D., Li, Y.C. and Bissonnette, M. (2020). “Upregulation of polycistronic microRNA-143 and microRNA-145 in colonocytes suppresses colitis and inflammation-associated colon cancer.” Epigenetics Dec 28;1-18. [Epub ahead of print].

Full text of this article.

Because ADAM17 promotes colonic tumorigenesis, we investigated potential miRNAs regulating ADAM17; and examined effects of diet and tumorigenesis on these miRNAs. We also examined pre-miRNA processing and tumour suppressor roles of several of these miRNAs in experimental colon cancer. Using TargetScan, miR-145, miR-148a, and miR-152 were predicted to regulate ADAM17. miR-143 was also investigated as miR-143 and miR-145 are co-transcribed and associated with decreased tumour growth. HCT116 colon cancer cells (CCC) were co-transfected with predicted ADAM17-regulating miRNAs and luciferase reporters controlled by ADAM17-3’UTR. Separately, pre-miR-143 processing by colonic cells was measured. miRNAs were quantified by RT-PCR. Tumours were induced with AOM/DSS in WT and transgenic mice (Tg) expressing pre-miR-143/miR-145 under villin promoter. HCT116 transfection with miR-145, -148a or -152, but not scrambled miRNA inhibited ADAM17 expression and luciferase activity. The latter was suppressed by mutations in ADAM17-3’UTR. Lysates from colonocytes, but not CCC, processed pre-miR-143 and mixing experiments suggested CCC lacked a competency factor. Colonic miR-143, miR-145, miR-148a, and miR-152 were downregulated in tumours and more moderately by feeding mice a Western diet. Tg mice were resistant to DSS colitis and had significantly lower cancer incidence and tumour multiplicity. Tg expression blocked up-regulation of putative targets of miR-143 and miR-145, including ADAM17, K-Ras, XPO5, and SET. miR-145, miR-148a, and miR-152 directly suppress colonocyte ADAM17 and are down-regulated in colon cancer. This is the first direct demonstration of tumour suppressor roles for miR-143 and miR-145 in an in vivo model of colonic tumorigenesis.

Collier, T.E., Farrell, L.B., Killian, A.D. and Kataria, V.K. (2020). “Effect of Adjunctive Dexmedetomidine in the Treatment of Alcohol Withdrawal Compared to Benzodiazepine Symptom-Triggered Therapy in Critically Ill Patients: The EvADE Study.” J Pharm Pract Dec 10;897190020977755. [Epub ahead of print].

Full text of this article.

OBJECTIVE: This study evaluated the safety and efficacy of adjunctive dexmedetomidine for alcohol withdrawal syndrome (AWS) treatment compared to symptom-triggered benzodiazepine therapy. METHODS: This single-center, retrospective, cohort study evaluated patients admitted to an intensive care unit (ICU) with AWS. Patients were divided into 2 groups: adjunctive dexmedetomidine or symptom-triggered therapy (control). Primary outcome was change in Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) score. Secondary outcomes assessed cumulative ICU benzodiazepine requirement and ICU/hospital length of stay (LOS). Safety outcomes evaluated incidence of adverse events, new onset seizures, and intubation. Propensity matching was performed to minimize differences between study groups. RESULTS: Overall, 147 patients were included, 56 in the dexmedetomidine group and 91 in the control group. Patient demographics were similar, however baseline CIWA-Ar score was statistically higher in the dexmedetomidine group. Following propensity matching, 55 patients were included in each group. No significant difference was noted for change in CIWA-Ar score (median, IQR) [3.8 (-0.4-12.3) dexmedetomidine vs. 5.4 (1.4-12.9) control, p = 0.223]. Secondary endpoints revealed increased benzodiazepine requirements (p = 0.001), prolonged ICU LOS (p = 0.050), and more frequent use of physical restraints (p = 0.001) in the dexmedetomidine group. While not statistically significant, the development of new onset seizures (p = 0.775) and intubation (p = 0.294) occurred more frequently in the dexmedetomidine group. CONCLUSION: The addition of dexmedetomidine to symptom-triggered benzodiazepines for AWS did not produce a significant change in CIWA-Ar scores from baseline compared to symptom-triggered therapy alone. The increased rate of new onset seizures and intubation warrant further investigation into the safety of dexmedetomidine in AWS.

Colbert, G.B., Abra, G. and Lerma, E.V. (2020). “Update and review of renal artery stenosis.” Dis Mon Dec 7;101118. [Epub ahead of print].

Full text of this article.

According to Carey et al., “resistant hypertension (RH) is defined as above-goal elevated blood pressure (BP) in a patient despite the concurrent use of 3 antihypertensive drug classes, commonly including a long-acting calcium channel blocker, a blocker of the renin-angiotensin system (RAAS) (angiotensin-converting enzyme inhibitor or angiotensin receptor blocker), and a diuretic”.1 The causes of RH are: non-adherence with dietary salt restriction, drugs (prescription and non-prescription), obstructive sleep apnea, and secondary hypertension.[No abstract; excerpt from article].

Cardenas, J., Balaji, U. and Gu, J. (2020). “Cerina: systematic circRNA functional annotation based on integrative analysis of ceRNA interactions.” Sci Rep 10(1): 22165.

Full text of this article.

Circular RNAs, a family of covalently circularized RNAs with tissue-specific expression, were recently demonstrated to play important roles in mammalian biology. Regardless of extensive research to predict, quantify, and annotate circRNAs, our understanding of their functions is still in its infancy. In this study, we developed a novel computational tool: Competing Endogenous RNA for INtegrative Annotations (Cerina), to predict biological functions of circRNAs based on the competing endogenous RNA model. Pareto Frontier Analysis was employed to integrate ENCODE mRNA/miRNA data with predicted microRNA response elements to prioritize tissue-specific ceRNA interactions. Using data from several circRNA-disease databases, we demonstrated that Cerina significantly improved the functional relevance of the prioritized ceRNA interactions by several folds, in terms of precision and recall. Proof-of-concept studies on human cancers and cardiovascular diseases further showcased the efficacy of Cerina on predicting potential circRNA functions in human diseases.