Research Spotlight

Yoshimatsu, G., F. Kunnathodi, P. B. Saravanan, R. Shahbazov, C. Chang, C. M. Darden, S. Zurawski, G. Boyuk, M. A. Kanak, M. F. Levy, B. Naziruddin and M. C. Lawrence (2017). “Pancreatic beta cell-derived ip-10/cxcl10 isletokine mediates early loss of graft function in islet cell transplantation.” Diabetes: 2017 Aug [Epub ahead of print].

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Pancreatic islets produce and secrete cytokines and chemokines in response to inflammatory and metabolic stress. The physiological role of these “isletokines” in health and disease is largely unknown. We observed that islets release multiple inflammatory mediators in patients undergoing islet transplants within hours of infusion. The proinflammatory cytokine interferon gamma-induced protein 10 (IP-10/CXCL10) was among the highest released, and high levels correlated with poor islet transplant outcomes. Transgenic mouse studies confirmed that donor islet-specific expression of IP-10 contributed to islet inflammation and loss of beta-cell function in islet grafts. The effects of islet-derived IP-10 could be blocked by treatment of donor islets and recipient mice with anti-IP-10 neutralizing monoclonal antibody. In vitro studies showed induction of the IP-10 gene was mediated by calcineurin-dependent NFAT signaling in pancreatic beta cells in response to oxidative or inflammatory stress. Sustained association of NFAT and p300 histone acetyltransferase with the IP-10 gene required p38 and JNK MAP kinase (MAPK) activity, which differentially regulated IP-10 expression and subsequent protein release. Overall, these findings elucidate an NFAT-MAPK signaling paradigm for induction of isletokine expression in beta-cells and reveal IP-10 as a primary therapeutic target to prevent beta-cell-induced inflammatory loss of graft function after islet cell transplantation.

Testa, G., T. Anthony, G. McKenna, E. C. Koon, K. Wallis, G. B. Klintmalm, J. C. Reese and L. Johannesson (2017). “Deceased donor uterus retrieval: A novel technique and workflow.” Am J Transplant: 2017 Aug [Epub ahead of print].

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Uterus transplantation has proven successful when performed with a living donor. Subsequently, interest in the novel field of reproductive transplantation is growing. The procedure is still considered experimental, with fewer than 25 cases performed worldwide, and the techniques of both uterus procurement and transplantation are still developing. We detail a new approach to deceased donor uterus procurement. In contrast to reported techniques and our own initial experience, in which the deceased donor uterus was procured post cross-clamp and after other organs were procured, our approach now is to perform the uterus procurement prior to the procurement of other organs in a multiorgan donor and hence prior to cross-clamp. We describe our practical experience in developing and implementing the logistical workflow for deceased donor uterus procurement in a deceased multiorgan donor setting.

Al-Moraissi, E. A., L. M. Wolford, D. Perez, D. M. Laskin and E. Ellis, 3rd (2017). “Does orthognathic surgery cause or cure temporomandibular disorders? A systematic review and meta-analysis.” J Oral Maxillofac Surg 75(9): 1835-1847.

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PURPOSE: There is still controversy about whether orthognathic surgery negatively or positively affects temporomandibular disorders (TMDs). The purpose of this study was to determine whether orthognathic surgery has a beneficial or deleterious effect on pre-existing TMDs. MATERIALS AND METHODS: A systematic review and meta-analysis were conducted based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched 3 major databases to locate all pertinent articles published from 1980 to March 2016. All subjects in the various studies were stratified a priori into 9 categories based on subdiagnoses of TMDs. The predictor variables were those patients with pre-existing TMDs who underwent orthognathic surgery in various subgroups. The outcome variables were maximal mouth opening and signs and symptoms of a TMD before and after orthognathic surgery based on the type of osteotomy. The meta-analysis was performed using Comprehensive Meta-Analysis software (Biostat, Englewood, NJ). RESULTS: A total of 5,029 patients enrolled in 29 studies were included in this meta-analysis. There was a significant reduction in TMDs in patients with a retrognathic mandible after bilateral sagittal split osteotomy (BSSO) (P = .014), but no significant difference after bimaxillary surgery (BSSO and Le Fort I osteotomy) (P = .336). There was a significant difference in patients with prognathism after isolated BSSO or intraoral vertical ramus osteotomy and after combined BSSO and Le Fort I osteotomy (P = .001), but no significant difference after BSSO (P = .424) or bimaxillary surgery (intraoral vertical ramus osteotomy and Le Fort I osteotomy) (P = .728). CONCLUSIONS: Orthognathic surgery caused a decrease in TMD symptoms for many patients who had symptoms before surgery, but it created symptoms in a smaller group of patients who were asymptomatic before surgery. The presence of presurgical TMD symptoms or the type of jaw deformity did not identify which patients’ TMDs would improve, remain the same, or worsen after surgery.

Bayer, J., C. A. Moulton, K. Monden, R. M. Goldstein, G. J. McKenna, G. Testa, R. M. Ruiz, T. L. Anthony, N. Onaca, G. B. Klintmalm and P. T. W. Kim (2017). “The role of multiorgan procurement for abdominal transplant in general surgery resident education.” Am J Surg.

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BACKGROUND: To assess the impact of participation of multiorgan procurement (MP) by general surgery (GS) residents on surgical knowledge and skills, a prospective cohort study of GS residents during transplant surgery rotation was performed. METHODS: Before and after participation in MPs, assessment of knowledge was performed by written pre and post tests and surgical skills by modified Objective Structured Assessment of Technical Skill (OSATS) score. Thirty-nine residents performed 84 MPs. RESULTS: Significant improvement was noted in the written test scores (63.3% vs 76.7%; P < 0.001). Better surgical score was associated with female gender (15.4 vs 13.3, P = <0.01), prior MP experience (16.2 vs 13.7, P = 0.03), and senior level resident (15.1 vs 13.0, P = 0.03). Supraceliac aortic dissection (P = 0.0017) and instrument handling (P = 0.041) improved with more MP operations. CONCLUSIONS: Participation in MP improves residents' knowledge of abdominal anatomy and surgical technique.

Chamblee, T. B., S. Smith, M. H. Shuster and K. Haight (2017). “Looking beyond the first impression: Malnutrition in the hospital setting.” Clin Nurse Spec 31(5): 235-236.

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In the United States, the increased focus on cost and quality of care is bringing the issue of malnutrition in hospitalized patients to the forefront. To address this issue, in 2014, the National Association of Clinical Nurse Specialists (NACNS) convened a task force to investigate malnutrition and recommend key clinical nurse specialist (CNS) practices that focus on promoting nutrition and/or preventing malnutrition among hospitalized adult patients. In addition, the task force was charged with clarifying the role of the CNS as a member of the interdisciplinary clinical team related to assessment, planning, and management of the nutrition care of malnourished hospitalized adults or those at risk for developing malnutrition.