Research Spotlight

Gupta, A. and S. K. Asrani (2019). “Role of living donor liver transplantation in acute liver failure.” Liver Transpl Jul 25. [Epub ahead of print].

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The etiology of acute liver failure (ALF) varies widely, with drug toxicity being the leading cause in Western countries while viral hepatitis predominates in Asia.(1, 2)Th varying etiology may lead to a different phenotype and clinical course of ALF by location. Without liver transplantation (LT), ALF is frequently fatal with due to cerebral edema and multi-system organ failure. In the West, where LT with deceased donors is well established, most eligible ALF patients receive whole liver allografts, often with the highest priority on the waitlist. As a result, live donor liver transplant (LDLT) is rarely undertaken for ALF patients. In contrast, many countries in the Far East do not have access to adequate deceased donors, and thus rely on LDLT for almost all patients, including those with ALF. (Excerpt from text, p. 1308; no abstract available.)

Fleshman, J. (2019). “Response to Comment on ‘Letter to the Editor for Z6051 (Revised 11/14/18).'” Ann Surg 270(2): e53-e54.

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Dr Martinez-Perez et al have identified some of the difficulties in performing randomized controlled trials in a surgical world that is constantly evolving. The Steering Committee of Z6051, meeting weekly throughout the early days of the trial and then monthly as time went on, have dealt with all of the questions that Dr Martinez-Perez raises in the letter to the editor. I wish to thank them for their comments and their attempt to bring to light the issues. In the Z6051 study comparing laparoscopic and open resection of rectal cancer we indeed chose to use the composite primary endpoint of the oncologic specimen findings to expedite the result of the technical issues with laparoscopic resection of rectal cancer. The focus on the specimen and the pathology evaluation is meant to serve as a means to determining the performance of good surgery and avoid waiting for 5 years to identify a detrimental effect on the long-term oncologic outcomes. The noninferiority analysis of the primary end point yielded a difference that prevented us from concluding noninferiority 3 years ago and raised the level of awareness of the potential hazards of treating low rectal cancer with laparoscopic techniques. This has impacted my practice and I have used hybrid laparoscopic operations to ensure good technique in the deep pelvis. The secondary endpoint of survival and disease-free survival (DFS), which is influenced by the combined treatment impact of the neoadjuvant therapy and the surgical therapy, has shown that our worries about harming patients may not need to be as significant as feared. The 2-year DFS, which has been reported as Kaplan–Meier curves including a large number of patients followed out 5 years, has shown no difference between the groups of patients. Low rectal cancer, especially those treated with Abdominoperineal resection (APR) in both groups, has shown a worse survival than those treated for higher rectal cancer with low anterior resection. I must agree that longer follow-up is needed in patients receiving neoadjuvant chemoradiation since recurrence has been seen at, or beyond, 10 years of follow-up. (Excerpt from text of the response to a letter regarding author’s article, Fleshman J, Branda ME, Sargent DJ, et al. Disease-free survival and local recurrence for laparoscopic resection compared with open resection of stage II to III rectal cancer: follow-up results of the ACOSOG Z6051 randomized controlled trial. Ann Surg. 2018 doi:10.1097/SLA0000000000003002.)

Elewski, B., A. Menter, J. Crowley, S. Tyring, Y. Zhao, S. Lowry, S. Rozzo, A. M. Mendelsohn, J. Parno and K. Gordon (2019). “Sustained and continuously improved efficacy of tildrakizumab in patients with moderate-to-severe plaque psoriasis.” J Dermatolog Treat Jul 22. [Epub ahead of print].

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Background: Tildrakizumab is a high-affinity, humanized, IgG1 kappa, anti-interleukin-23 monoclonal antibody approved for moderate-to-severe plaque psoriasis. Objectives: This analysis examined whether tildrakizumab’s week-28 efficacy can be sustained or improved to week 52. Methods: Psoriasis patients on the same-dose tildrakizumab (100 or 200 mg) in the first 52 weeks achieving week-28 PASI >/=50 were pooled from two phase-3 randomized controlled trials, and grouped into four mutually exclusive week-28 PASI response groups. Patients’ week-52 PASI responses were compared to their week-28 PASI responses. Results: Of 352 patients receiving 100-mg tildrakizumab, 10.5%, 25.3%, 38.4%, and 25.9% achieved PASI 50-74, 75-89, 90-99, and 100 at week 28, respectively. Among patients achieving PASI >/=90, >/=75, or >/=50 at week 28, 89.4%, 91.1%, or 97.4% maintained their week-28 PASI responses at week 52, respectively. Among patients achieving PASI 50-74, 75-89, or 90-99 at week 28, 64.8%, 33.7%, or 25.2% improved their week-28 PASI responses at week 52, respectively. Limitations: This post hoc analysis may be less robust than an a priori analysis. Conclusions: Most tildrakizumab-treated patients with week-28 PASI >/=75 maintained their week-28 PASI improvement at week 52. More than half of week-28 partial responders (PASI 50-74) improved their PASI responses to PASI >/=75 at week 52. Clinicaltrials.gov identifiers: NCT01722331, NCT01729754.

Edgerton, J. R. (2019). “Invited Commentary.” Ann Thorac Surg 108(2): 450-451.

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In this issue of The Annals of Thoracic Surgery, the Washington University group reports the results of surgical ablation of atrial fibrillation (AF) in 34 patients with tachycardia-induced cardiomyopathy (TIC) defined as left ventricular ejection fraction less than 41% and absent another etiology. Excluding 1 death, 33 patients were available for follow-up, and 27 of these patients had an evaluable echocardiogram at approximately 12 months. At 12 months, 94% of patients were free of atrial tachyarrhythmias with or without antiarrhythmic drugs. Mean left ventricular ejection fraction improved from 32% to 55%. Of 11 patients in New York Hearth Association Class III/IV, 8 patients improved to Class I/II. These changes reached statistical significance. It is important to note that LV function improved in all patients, and it improved to greater than 55% in 19 of 27 patients. The prognostic significance of the presence of fibrosis (inhibits recovery of function), as reported in the CAMERA-MRI (Catheter Ablation Versus Medical Rate Control in Atrial Fibrillation and Systolic Dysfunction) study and reiterated in this report, should be stressed. In patient selection, it is important to differentiate between TIC and a dilated cardiomyopathy with secondary AF. The patient with TIC is likely to be helped by performing a Maze whereas the patient with a dilated cardiomyopathy secondary to AF is not. To differentiate, the authors perform a cardiac magnetic resonance imaging (MRI) to assess for myocardial viability and the degree of left ventricular fibrosis by late gadolinium enhancement. On multivariate analysis, only the absence of late gadolinium enhancement was found to predict left ventricular ejection fraction normalization. Any presence of fibrosis rules the patient out as a candidate for surgical ablation. If there is any other abnormality on cardiac MRI, or a high index of suspicion, endomyocardial biopsies are performed. Thus, preoperative MRI will help the clinician in deciding whether to operate for TIC. Although the numbers of patients are small, documenting these findings is significant. It would be easy for a reader to dismiss this article as a small retrospective series of little significance. This would be a grave error. Yes, the numbers are small, but few groups have adequate volume to accumulate this many patients, and most lack the investigatory rigor to document the postoperative course in such detail. In addition, few groups have preoperative MRI for these patients. As the authors point out, current guideline statements on the treatment of TIC, “include only non-surgical rhythm control strategies.” This is the true significance of this article. Considering the findings documented here, a Class IIa, Level of Evidence B-NR is justified for surgical ablation of AF in patients with TIC who are undergoing cardiac surgery for another reason or who have failed antiarrhythmic drugs and catheter ablation. Future guideline committees need to consider this work when revising current guidelines. (Full text of this commentary.)

Driver, S., S. Juengst, M. Reynolds, E. McShan, C. L. Kew, M. Vega, K. Bell and R. Dubiel (2019). “Healthy lifestyle after traumatic brain injury: a brief narrative.” Brain Inj 33(10): 1299-1307.

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Individuals living with traumatic brain injury (TBI) are at an increased risk for developing chronic conditions such as diabetes, heart disease, and hypertension compared to the non-injured population. Furthermore, TBI-specific challenges such as physical limitations, pain, mood, and impaired cognition make it difficult to live a healthy lifestyle. Key health behaviors that contribute to overall health and well-being after TBI include physical activity and healthy eating, sleep, participation, eliminating substance abuse, and managing stress. The objectives of this narrative are to (1) describe the key components of a healthy lifestyle for individuals with a TBI, (2) identify the challenges that individuals with TBI face when attempting to establish these health behaviors, and (3) discuss approaches and supports to achieve these health behaviors after TBI, including the role of self-management.