Research Spotlight

Mencio, M. A., E. Ontiveros, J. S. Burdick and S. G. Leeds (2018). “Use of a novel technique to manage gastrointestinal leaks with endoluminal negative pressure: a single institution experience.” Surg Endosc. Jan 23. [Epub ahead of print].

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BACKGROUND: Perforations and anastomotic leaks of the gastrointestinal tract are severe complications, which carry high morbidity and mortality and management of these is a multi-disciplinary challenge. The use of endoluminal vacuum (EVAC) therapy has recently proven to be a useful technique to manage these complications. We report our institution’s experience with this novel technique in the chest, abdomen, and pelvis. METHODS: This is a retrospective review of an IRB approved registry of all EVAC therapy patients from July 2013 to December 2016. A total of 55 patients were examined and 49 patients were eligible for inclusion: 15 esophageal, 21 gastric, 3 small bowel, and 10 colorectal defects. The primary endpoint was closure rate of the GI tract defect with EVAC therapy. RESULTS: Fifteen (100%) esophageal defects closed with EVAC therapy. Mean duration of therapy was 27 days consisting of an average of 6 endosponge changes every 4.8 days. Eighteen (86%) gastric defects closed with EVAC therapy. Mean duration of therapy was 38 days with a mean of 9 endosponge changes every 5.3 days. Three (100%) small bowel defects closed with EVAC therapy. Mean duration of therapy was 13.7 days with a mean of 2.7 endosponge changes every 4.4 days. Six (60%) colorectal defects closed with EVAC therapy. Mean duration of therapy was 23.2 days, consisting of a mean of 6 endosponge changes every 4.0 days. There were two deaths, which were not directly related to EVAC therapy and occurred outside the measured 30-day mortality. CONCLUSION: Our experience demonstrates that EVAC therapy is feasible and effective for the management of gastrointestinal perforations/leaks throughout the GI tract and can be considered as a safe alternative to surgical intervention in select cases.

Kwong, A. J. and S. K. Asrani (2018). “Artificial neural networks and liver transplantation: Are we ready for self-driving cars?” Liver Transpl 24(2): 161-163.

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The persistent shortage of donor organs has motivated efforts to predict posttransplant outcome, maximize survival benefit, and encourage the appropriate allocation of donor organs. Machine learning, a branch of statistics and computer science that has revolutionized the analysis of large and complex data sets, and its application to medicine has accelerated in recent years. Not only have machine-learning algorithms been used to develop the technology for Google Home, Siri, and self-driving cars, they have also been used to predict hospitalization in patients with heart failure, remission in patients with inflammatory bowel disease, and graft failure after solid organ transplantation. In this issue of Liver Transplantation, Ayllón et al. applied an artificial neural network (ANN), a type of machine-learning algorithm, to a cohort of 858 liver transplantation (LT) recipients from 2002 to 2010 at King’s College Hospital (KCH) using 55 donor, procurement, and recipient variables. This ANN had been previously used to develop a model in a Spanish multicenter cohort (Model for Allocation of Donor and Recipient in España [MADR-E]) of 1003 LT recipients with an area under the curve (AUC), or c-statistic, of 0.82 for 3-month graft failure. The KCH model was developed using the same ANN architecture (although the predictive model was different) used for the MADR-E study, which is designed to maximize the accuracy of graft survival by the correct classification rate (CCR) and the sensitivity of graft failure by minimum sensitivity (MS). In the KCH cohort, the ANN resulted in an AUC of 0.94 for 3-month graft failure, superior to other published models. This result implies that for 2 randomly drawn grafts, 1 of graft survival and 1 of graft failure, the model would correctly assign higher 3-month graft risk to the failed graft 94% of the time—compared with AUCs of 0.73 for donor Model for End-Stage Liver Disease (D-MELD), 0.82 for survival outcomes following liver transplantation (SOFT), and 0.84 for balance of risk (BAR), in this cohort. The ANN was also trained to predict 1-year graft failure and resulted in an AUC of 0.82, also superior to previously developed scores (AUCs of 0.63 for D-MELD, 0.65 for SOFT, and 0.71 for BAR). Variables reported to have the highest weight in the KCH model included pretransplant status, Model for End-Stage Liver Disease (MELD) at transplant, time on waiting list, etiology of liver disease, cold ischemia time, and donor hypertension, cause of death, and aspartate aminotransferase (AST) levels. [Excerpt from text of this commentary; abstract unavailable.]

Mazharuddin, S., A. Chattopadhyay, M. Y. Levy and R. L. Redner (2018). “IRF2BP2-RARA t(1;17)(q42.3;q21.2) APL blasts differentiate in response to all-trans retinoic acid.” Leuk Lymphoma: Jan 19: 1-4. [Epub ahead of print].

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To date 11 variant translocations have been characterized in acute promyelocytic leukemia (APL), all of which share the same C-terminal domains of RARA as in t(15;17)(q24;q21) PML-RARA [1 de The H, Lavau C, Marchio A, et al. The PML-RAR alpha fusion mRNA generated by the t(15;17) translocation in acute promyelocytic leukemia encodes a functionally altered RAR. To date three reports of IRF2BP2-RARA have been published. Herein, we describe the fourth case of t(1;17) APL. A 34-year-old white male presented in March 2016 with WBC 4100 × 106/L, hemoglobin 9.3 g/dL, and platelets 23,000 × 106/L with 40% neutrophils, 9% bands, 45% lymphocytes, 2% monocytes, and 4% blasts. Prothrombin time (PT) was 15.9 s, d-dimer 37.21 mg/L, fibrinogen 397 mg/dL. Over the first week of his hospitalization, the patient was given single agent ATRA 24 mg/m2 daily while the diagnosis of APL was being confirmed. Over this time, the white blood cells (WBC) rose to over 30,000 × 106/L. A bone marrow aspirate and biopsy revealed 89% immature cells expressing CD13, CD33, CD38(dim), CD45, CD117, CD123(dim), and myeloperoxidase[bright]; negative for HLA-DR. Cytogenetics revealed 45, X, -Y, t(1;17)(q42;q21), i(8)(q19). FISH and PCR did not reveal PML-RARA rearrangement. FISH using Vysis LSI RARA Dual Color, Break Apart Rearrangement Probe revealed one orange, one green and one fusion (1O1G1F) signal pattern, consistent with a variant RARA rearrangement. FISH also revealed a gain of RUNX1T1, consistent with the finding of iso(8)(q19). We confirmed the presence of an IRF2BP2-RARA fusion in our patient by RT-PCR and sequencing of the amplified transcript.[Excerpt from text; abstract unavailable.]

Ko, J. M., K. M. Tecson, V. A. Rashida, S. Sodhi, J. Saef, M. Mufti, K. S. White, P. A. Ludbrook and A. M. Cedars (2018). “Clinical and Psychological Drivers of Perceived Health Status in Adults With Congenital Heart Disease.” Am J Cardiol 121(3): 377-381.

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The factors having the greatest impact on self-reported health status in adults with congenital heart disease (ACHD) remain incompletely studied. We conducted a single-site, cross-sectional study of ACHD patients followed at the Center for ACHD at Washington University School of Medicine, including retrospectively gathered clinical data and psychometric and health status assessments completed at the time of enrollment. To identify primary drivers of perceived health status, we investigated the impact of the demographic, clinical, and psychological variables on self-reported health status as assessed using the Rand 36-Item Short Form Health Survey. Variables with significant associations within each domain were considered jointly in multivariable models constructed via stepwise selection. There was domain-specific heterogeneity in the variables having the greatest effect on self-reported health status. Depression was responsible for the greatest amount of variability in health status in all domains except physical functioning. In the physical functioning domain, depression remained responsible for 5% of total variability, the third most significant variable in the model. In every domain, depression more strongly influenced health status than did any cardiac-specific variable. In conclusion, depression was responsible for a significant amount of heterogeneity in all domains of self-perceived health status. Psychological variables were better predictors of health status than clinical variables.

Khoynezhad, A., J. DelaRosa, M. R. Moon, W. T. Brinkman, R. B. Thompson, N. D. Desai, S. C. Malaisrie, L. N. Girardi, J. E. Bavaria and T. B. Reece (2018). “Facilitating Hemostasis After Proximal Aortic Surgery – Results of The PROTECT Trial.” Ann Thorac Surg. Jan 11. [Epub ahead of print].

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BACKGROUND: This study intended to evaluate the safety and hemostatic efficacy of a novel vascular sealant (Tridyne , Neomend, Inc., Irvine, CA) compared to an accepted adjunctive hemostatic agent applied to aortotomy and sutures lines in cardiovascular surgery. METHODS: Subjects undergoing aortic valve replacement, ascending aortic replacement and/or aortic root replacement were randomized 2:1 to Tridyne (n =107) or Gelfoam(R)+ (Gelfoam(R)+, Baxter Healthcare Corp., Hayward, CA) (n=51). These groups were similar with regard to age, gender, race, medical history, duration of bypass and cross-clamping, and number of suture lines treated. Suture lines were treated after confirmation of some leakage but before formal removal of the clamp. RESULTS: The median bleeding time was significantly lower for Tridyne vs Gelfoam(R)+ (0 vs 10.0 min; p < 0.0001). Immediate hemostasis was achieved in 59.4% Tridyne vs 16.0% Gelfoam(R)+ (p<0.0001). A significantly greater proportion of subjects in the Tridyne group achieved successful hemostasis at the aortic suture line compared to Gelfoam(R)+ (85.7% vs 40.0%, p < 0.0001). The Clinical Events Committee adjudicated seven subjects with possible device-related serious adverse events: 3(2.9%) for Tridyne vs 4(8.2%) for Gelfoam(R)+ (p=0.2097). CONCLUSIONS: Tridyne was safe and effective when used as an adjunct to conventional hemostasis to treat high-pressure vessels in subjects who are anti-coagulated, in reducing time to hemostasis, as well as promoting both immediate and persistent hemostasis.