Research Spotlight

Sudhakaran, S. and P. A. McCullough (2019). “Common laboratory parameters as indicators of multi-organ dysfunction in acute heart failure.” Eur J Heart Fail Apr 11. [Epub ahead of print].

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Understanding of diagnosis, classification, pathophysiology, prognosis, and treatment of heart failure remains of major interest in clinical cardiology. There are approximately 23 million people with heart failure worldwide, and that estimate is expected to increase by roughly 772 000 by the year 2040. Patients on average have a 5‐year mortality of 50% after the diagnosis is established, most commonly in the setting of hospitalization for acute heart failure (AHF), and clinically, prognostication when admitted to the inpatient setting is challenging. In this issue of the Journal, the retrospective analysis by Zymliński et al.demonstrates how multi‐organ dysfunction as reflected by commonly measured laboratory parameters impacts AHF outcomes. The authors evaluated worsening heart failure and 1‐year mortality in AHF stratified by laboratory evidence of concomitant multi‐organ failure (namely cardiac, kidney, and liver injury/dysfunction) . . . The data presented by Zymliński et al. incites numerous areas of future direction that warrant further investigation. The sample size was small at 284 for multiple comparisons, and thus, it would be beneficial to validate these findings in a larger, prospective cohort. Finally, utilizing these data to delineate a scoring system for prognostication and to assess disease acuity, similar to Acute Physiologic Assessment and Chronic Health Evaluation (APACHE) or Sequential Organ Failure Assessment (SOFA), but tailored specifically for AHF, would be a practical tool for those involved in the care of patients with AHF. (Excerpts from text, p. 1, 2; no abstract available; commenting on a study in the same issue, Zymliński R, et al., Multi‐organ dysfunction/injury on admission identifies acute heart failure patients at high risk of poor outcome; no abstract available.)

Snyder, P., K. Dunbar, D. J. Cipher, R. F. Souza, S. J. Spechler and V. J. A. Konda (2019). “Aberrant p53 Immunostaining in Barrett’s Esophagus Predicts Neoplastic Progression: Systematic Review and Meta-Analyses.” Dig Dis Sci 64(5): 1089-1097.

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Risk stratification of patients with Barrett’s esophagus (BE) presently relies on the histopathologic grade of dysplasia found in esophageal biopsies, which is limited by sampling error and inter-pathologist variability. p53 immunostaining of BE biopsies has shown promise as an adjunct tool but is not recommended by American gastroenterology societies, who cite insufficient evidence of its prognostic value. We have conducted a systematic review and meta-analyses to clarify this value. We searched for studies that: (1) used immunohistochemistry to assess p53 expression in esophageal biopsies of BE patients and (2) reported subsequent neoplastic progression. We performed separate meta-analyses of case-control studies and cohort studies. We identified 14 relevant reports describing 8 case-control studies comprising 1435 patients and 7 cohort studies comprising 582 patients. In the case-control study meta-analysis of the risk of neoplasia with aberrant p53 expression, the fixed- and random-effect estimates of average effect size with aberrant p53 expression were OR 3.84, p < .001 (95% CI 2.79-5.27) and OR 5.95, p < .001 (95% CI 2.68-13.22), respectively. In the cohort study meta-analysis, the fixed- and random-effect estimates of average effect size were RR = 17.31, p < .001 (95% CI 9.35-32.08) and RR = 14.25, p < .001 (95% CI 6.76-30.02), respectively. Separate meta-analyses of case-control and cohort studies of BE patients who had baseline biopsies with p53 immunostaining revealed consistent, strong, and significant associations between aberrant p53 immunostaining and progression to high-grade dysplasia or esophageal adenocarcinoma. These findings support the use of p53 immunostaining as an adjunct to routine clinical diagnosis for dysplasia in BE patients.

Smith, M. S., B. Cash, V. Konda, A. J. Trindade, S. Gordon, S. DeMeester, V. Joshi, D. Diehl, E. Ganguly, H. Mashimo, S. Singh, B. Jobe, M. McKinley, M. Wallace, Y. Komatsu, S. Thakkar, F. Schnoll-Sussman, R. Sharaiha, M. Kahaleh, P. Tarnasky, H. Wolfsen, R. Hawes, J. Lipham, H. Khara, D. Pleskow, U. Navaneethan, P. Kedia, M. Hasan, A. Sethi, J. Samarasena, U. D. Siddiqui, F. Gress, R. Rodriguez, C. Lee, T. Gonda, I. Waxman, S. Hyder, J. Poneros, K. Sharzehi, J. A. Di Palma, D. V. Sejpal, D. Oh, J. Hagen, R. Rothstein, M. Sawhney, T. Berzin, Z. Malik and K. Chang (2019). “Volumetric laser endomicroscopy and its application to Barrett’s esophagus: results from a 1,000 patient registry.” Dis Esophagus Apr 30. [Epub ahead of print].

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Volumetric laser endomicroscopy (VLE) uses optical coherence tomography (OCT) for real-time, microscopic cross-sectional imaging. A US-based multi-center registry was constructed to prospectively collect data on patients undergoing upper endoscopy during which a VLE scan was performed. The objective of this registry was to determine usage patterns of VLE in clinical practice and to estimate quantitative and qualitative performance metrics as they are applied to Barrett’s esophagus (BE) management. All procedures utilized the NvisionVLE Imaging System (NinePoint Medical, Bedford, MA) which was used by investigators to identify the tissue types present, along with focal areas of concern. Following the VLE procedure, investigators were asked to answer six key questions regarding how VLE impacted each case. Statistical analyses including neoplasia diagnostic yield improvement using VLE was performed. One thousand patients were enrolled across 18 US trial sites from August 2014 through April 2016. In patients with previously diagnosed or suspected BE (894/1000), investigators used VLE and identified areas of concern not seen on white light endoscopy (WLE) in 59% of the procedures. VLE imaging also guided tissue acquisition and treatment in 71% and 54% of procedures, respectively. VLE as an adjunct modality improved the neoplasia diagnostic yield by 55% beyond the standard of care practice. In patients with no prior history of therapy, and without visual findings from other technologies, VLE-guided tissue acquisition increased neoplasia detection over random biopsies by 700%. Registry investigators reported that VLE improved the BE management process when used as an adjunct tissue acquisition and treatment guidance tool. The ability of VLE to image large segments of the esophagus with microscopic cross-sectional detail may provide additional benefits including higher yield biopsies and more efficient tissue acquisition. Clinicaltrials.gov NCT02215291.

Shaked, A., M. R. DesMarais, H. Kopetskie, S. Feng, J. D. Punch, J. Levitsky, J. Reyes, G. B. Klintmalm, A. J. Demetris, B. E. Burrell, A. Priore, N. D. Bridges and P. H. Sayre (2019). “Outcomes of immunosuppression minimization and withdrawal early after liver transplantation.” Am J Transplant 19(5): 1397-1409.

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The Immune Tolerance Network ITN030ST A-WISH assessed immunosuppression withdrawal in liver transplant recipients with hepatitis C or nonimmune nonviral liver disease. Of 275 recipients enrolled before transplantation, 95 were randomly assigned 4:1 to withdrawal (n = 77) or maintenance (n = 18) 1- to 2-years posttransplant. Randomization eligibility criteria included stable immunosuppression monotherapy; adequate liver and kidney function; /=8 weeks per level. Fifty-two of 77 subjects (67.5%) reduced to /=1 year. Acute rejection and/or abnormal liver tests were treated with increased immunosuppression; 5 of 32 rejection episodes required a methylprednisolone bolus. The composite end point (death or graft loss; grade 4 secondary malignancy or opportunistic infection; Ishak stage >/=3; or >25% decrease in glomerular filtration rate within 24 months of randomization) occurred in 12 of 66 (18%) and 4 of 13 (31%) subjects in the withdrawal and maintenance groups. Early immunosuppression minimization is feasible in selected liver recipients, while complete withdrawal is successful in only a small proportion. The composite end point comparison was inconclusive for noninferiority of the withdrawal to the maintenance group.

Shahbazov, R., B. Naziruddin, O. Salam, G. Saracino, M. F. Levy, E. Beecherl and N. Onaca (2019). “The impact of surgical complications on the outcome of total pancreatectomy with islet autotransplantation.” Am J Surg Apr 15. [Epub ahead of print].

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Total pancreatectomy with islet autotransplantation is a promising treatment for refractory chronic pancreatitis. We analyzed postoperative complications in 83 TPIAT patients and their impact on islet graft function. We examined patient demographics, preoperative risk factors, intraoperative variables, and 30- and 90-day postoperative morbidity and mortality. Daily insulin requirement, HbA1c, C-peptide levels, and narcotic requirements were analyzed before and after surgery. Adverse events were recorded, with postoperative complications graded according to the Clavien-Dindo classification. There was no mortality in this patient group. Postoperative complications occurred in 38 patients (45.7%). Patients with postoperative complications were readmitted significantly more often within 30 days (p=0.01) and 90 days posttransplant (p<0.0003) and had a significantly longer hospital stay (p=0.004) and intensive care unit stay (p=0.001). Insulin dependence and graft function assessed by HbA1c, C-Peptide and insulin requirements did not differ significantly by these complications. Postoperative complications after TPIAT are associated with longer hospital and intensive care unit stay and with readmission; however, the surgical complications do not affect islet graft function.