Research Spotlight

Dehmer, G. J. (2018). “Seeking Quality Cardiac Care: Is Public Reporting the Answer?” JACC Cardiovasc Interv 11(4): 351-353.

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Letter to the Editor; no abstract available.

Chiruvolu, A., E. Elliott, D. Rich, G. L. Stone, H. Qin and R. W. Inzer (2018). “Effect of delay in cord clamping 45 versus 60s on very preterm singleton infants.” Early Hum Dev 119: 15-18.

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BACKGROUND: In the range of timing suggested by American College of Obstetricians and Gynecologists 30 to 60s, preterm infants may potentially derive more short and long-term benefits with delayed cord clamping (DCC) for at least 60s. However, there are concerns with longer resuscitation delay in this vulnerable population. OBJECTIVE: To compare the clinical consequences of 45 versus 60s delay in umbilical cord clamping in singleton infants born between 23(0/7) to 31(6/7) weeks gestation. STUDY DESIGN: We implemented DCC process in very preterm singleton infants, initially for 45s and later, modified the policy to increase the delay to 60s. We compared the infants born and received DCC (n=60) during the 45s study period (DCC-45 cohort), from Aug.19, 2013, to Aug.18, 2014 to the infants born and received DCC (n=63) during the 60s study period (DCC-60 cohort), from Feb.1, 2015, to Jan.31, 2016. RESULTS: The incidence of necrotizing enterocolitis in DCC-60 cohort was 0% compared to 8% in the DCC-45 cohort (P=0.02). Similarly, incidence of culture-positive sepsis was significantly lower in the DCC-60 cohort compared to DCC-45 cohort (8% versus 18%; P=0.04). Incidence of mortality and other major morbidities were similar between both groups. Length of stay was significantly lower in DCC-60 cohort compared to DCC-45 cohort. CONCLUSION: DCC for 60s in very preterm singleton infants was safe, feasible and not associated with any adverse maternal or neonatal short-term outcomes compared to DCC for 45s.

Charlton, M., J. Levitsky, B. Aqel, J. O’Grady, J. Hemibach, R. I. M, M. Ghabril, R. Thomason, P. Burra, E. C. Little, M. Berenguer, A. Shaked, J. Trotter, J. Roberts, M. Rodriguez-Davalos, M. Rela, E. Pomfret and F. Saliba (2018). “International Liver Transplant Society Consensus Statement on IMMUNOSUPPRESSION IN LIVER TRANSPLANT RECIPIENTS.” Transplantation. 2018 Feb 26. [Epub ahead of print]

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Immunosuppression and Malignancies: Hepatocellular carcinoma (HCC): Beyond generally minimizing overall immunosuppression, the optimal immunosuppression strategy for minimizing the frequency and severity of recurrence of HCC, including the use of mTOR inhibitors, has not been determined Skin cancers (SCCa): There is evidence that sirolimus reduces the risk of non-melanoma skin cancer recurrence in kidney transplant patients. Whether the same effects occur with everolimus, which is approved in liver transplantation, is not known but seems likely. Non-HCC, Non-SCCa malignancies: There is no direct evidence that mTOR inhibitors prevent other (non-skin, non-HCC) malignancies in liver transplant recipients, although patients with NET or RCC may benefit from everolimus-based immunosuppression. (Excerpt from text, p. 27, advanced text; no abstract available.)

Chang, C. A., B. Akinbobuyi, J. M. Quintana, G. Yoshimatsu, B. Naziruddin and R. R. Kane (2018). “Ex-vivo generation of drug-eluting islets improves transplant outcomes by inhibiting TLR4-Mediated NFkB upregulation.” Biomaterials 159: 13-24.

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The systemic administration of immunosuppressive and anti-inflammatory drugs is routinely employed in organ transplantation to minimize graft rejection and improve graft survival. Localized drug delivery has the potential to improve transplant outcomes by providing sustained exposure to efficacious drug concentrations while avoiding systemic immunosuppression and off-target effects. Here, we describe the synthesis of a novel prodrug and its direct covalent conjugation to pancreatic islets via a cleavable linker. Post-transplant, linker hydrolysis results in the release of a potent anti-inflammatory antagonist of TLR4, localized to the site of implantation. This covalent islet modification significantly reduces the time and the minimal effective dose of islets necessary to achieve normoglycemia in a murine transplantation model. In streptozotocin-induced diabetic C57BL/6 mice a syngeneic transplant of approximately 100 modified islets achieved a 100% cure rate by the end of a 4-week monitoring period, compared to a 0% cure rate for untreated control islets. Overall, this direct prodrug conjugation to islets is well tolerated and preserves their functionality while affording significantly superior transplant outcomes. The development of drug-eluting tissues that deliver sustained and localized doses of small-molecule therapeutics represents a novel pathway for enhancing success in transplantation.

Carpenter, J. K., L. A. Andrews, S. M. Witcraft, M. B. Powers, J. A. J. Smits and S. G. Hofmann (2018). “Cognitive behavioral therapy for anxiety and related disorders: A meta-analysis of randomized placebo-controlled trials.” Depress Anxiety. Feb 16. [Epub ahead of print].

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The purpose of this study was to examine the efficacy of cognitive behavioral therapy (CBT) for anxiety-related disorders based on randomized placebo-controlled trials. We included 41 studies that randomly assigned patients (N = 2,843) with acute stress disorder, generalized anxiety disorder (GAD), obsessive compulsive disorder (OCD), panic disorder (PD), posttraumatic stress disorder (PTSD), or social anxiety disorder (SAD) to CBT or a psychological or pill placebo condition. Findings demonstrated moderate placebo-controlled effects of CBT on target disorder symptoms (Hedges’ g = 0.56), and small to moderate effects on other anxiety symptoms (Hedges’ g = 0.38), depression (Hedges’ g = 0.31), and quality of life (Hedges’ g = 0.30). Response rates in CBT compared to placebo were associated with an odds ratio of 2.97. Effects on the target disorder were significantly stronger for completer samples than intent-to-treat samples, and for individuals compared to group CBT in SAD and PTSD studies. Large effect sizes were found for OCD, GAD, and acute stress disorder, and small to moderate effect sizes were found for PTSD, SAD, and PD. In PTSD studies, dropout rates were greater in CBT (29.0%) compared to placebo (17.2%), but no difference in dropout was found across other disorders. Interventions primarily using exposure strategies had larger effect sizes than those using cognitive or cognitive and behavioral techniques, though this difference did not reach significance. Findings demonstrate that CBT is a moderately efficacious treatment for anxiety disorders when compared to placebo. More effective treatments are especially needed for PTSD, SAD, and PD.