Research Spotlight

Lai, J.C., Ganger, D.R., Volk, M.L., Dodge, J.L., Dunn, M.A., Duarte-Rojo, A., Kappus, M.R., Rahimi, R.S., Ladner, D.P., Boyarsky, B., McAdams-DeMarco, M., Segev, D.L., McCulloch, C.E. and Verna, E.C. (2020). “Association of Frailty and Sex With Wait List Mortality in Liver Transplant Candidates in the Multicenter Functional Assessment in Liver Transplantation (FrAILT) Study.” JAMA Surg DEc 30. [Epub ahead of print].

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IMPORTANCE: Female liver transplant candidates experience higher rates of wait list mortality than male candidates. Frailty is a critical determinant of mortality in patients with cirrhosis, but how frailty differs between women and men is unknown. OBJECTIVE: To determine whether frailty is associated with the gap between women and men in mortality among patients with cirrhosis awaiting liver transplantation. DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study enrolled 1405 adults with cirrhosis awaiting liver transplant without hepatocellular carcinoma seen during 3436 ambulatory clinic visits at 9 US liver transplant centers. Data were collected from January 1, 2012, to October 1, 2019, and analyzed from August 30, 2019, to October 30, 2020. EXPOSURES: At outpatient evaluation, the Liver Frailty Index (LFI) score was calculated (grip strength, chair stands, and balance). MAIN OUTCOMES AND MEASURES: The risk of wait list mortality was quantified using Cox proportional hazards regression by frailty. Mediation analysis was used to quantify the contribution of frailty to the gap in wait list mortality between women and men. RESULTS: Of 1405 participants, 578 (41%) were women and 827 (59%) were men (median age, 58 [interquartile range (IQR), 50-63] years). Women and men had similar median scores on the laboratory-based Model for End-stage Liver Disease incorporating sodium levels (MELDNa) (women, 18 [IQR, 14-23]; men, 18 [IQR, 15-22]), but baseline LFI was higher in women (mean [SD], 4.12 [0.85] vs 4.00 [0.82]; P = .005). Women displayed worse balance of less than 30 seconds (145 [25%] vs 149 [18%]; P = .003), worse sex-adjusted grip (mean [SD], -0.31 [1.08] vs -0.16 [1.08] kg; P = .01), and fewer chair stands per second (median, 0.35 [IQR, 0.23-0.46] vs 0.37 [IQR, 0.25-0.49]; P = .04). In unadjusted mixed-effects models, LFI was 0.15 (95% CI, 0.06-0.23) units higher in women than men (P = .001). After adjustment for other variables associated with frailty, LFI was 0.16 (95% CI, 0.08-0.23) units higher in women than men (P < .001). In unadjusted regression, women experienced a 34% (95% CI, 3%-74%) increased risk of wait list mortality than men (P = .03). Sequential covariable adjustment did not alter the association between sex and wait list mortality; however, adjustment for LFI attenuated the mortality gap between women and men. In mediation analysis, an estimated 13.0% (IQR, 0.5%-132.0%) of the gender gap in wait list mortality was mediated by frailty. CONCLUSIONS AND RELEVANCE: These findings demonstrate that women with cirrhosis display worse frailty scores than men despite similar MELDNa scores. The higher risk of wait list mortality that women experienced appeared to be explained in part by frailty.

Jones, B.P., Kasaven, L., Vali, S., Saso, S., Jalmbrant, M., Bracewell-Milnes, T., Thum, M.Y., Quiroga, I., Friend, P., Diaz-Garcia, C., Ghaem-Maghami, S., Yazbek, J., Lees, C., Testa, G., Johannesson, L., Jones, B. and Smith, J.R. (2020). “Uterine Transplantation; Review of Livebirths and Reproductive Implications.” Transplantation Dec 10. [Epub ahead of print].

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Uterine transplantation (UTx) is a fertility restoring treatment for women with absolute uterine factor infertility. At a time when there is no question of the procedure’s feasibility, and as the number of livebirths begins to increase exponentially, various important reproductive, fetal and maternal medicine implications have emerged. Detailed outcomes from 17 livebirths following UTx are now available, which are reviewed herein, along with contextualized extrapolation from pregnancy outcomes in other solid organ transplants. Differences in recipient demographics and reproductive aspirations between UTx and other transplant recipients make extrapolating management strategies and outcomes in other solid organ transplants inappropriate. Whereas preterm delivery remains prominent, small for gestational age or hypertensive disorders do not appear to be as prevalent following UTx when compared to other solid organ transplants. Given the primary objective of undertaking UTx is to achieve a livebirth, publication of reproductive outcomes is essential at this early stage, to reflect upon and optimize the management of future cases.

Johnson, B.A., Waddimba, A.C., Ogola, G.O., Fleshman, J.W., Jr. and Preskitt, J.T. (2020). “A systematic review and meta-analysis of surgery delays and survival in breast, lung and colon cancers: Implication for surgical triage during the COVID-19 pandemic.” Am J Surg Dec 8;S0002-9610(20)30793-5. [Epub ahead of print].

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BACKGROUND: Thousands of cancer surgeries were delayed during the peak of the COVID-19 pandemic. This study examines if surgical delays impact survival for breast, lung and colon cancers. METHODS: PubMed/MEDLINE, EMBASE, Cochrane Library and Web of Science were searched. Articles evaluating the relationship between delays in surgery and overall survival (OS), disease-free survival (DFS) or cancer-specific survival (CSS) were included. RESULTS: Of the 14,422 articles screened, 25 were included in the review and 18 (totaling 2,533,355 patients) were pooled for meta-analyses. Delaying surgery for 12 weeks may decrease OS in breast (HR 1.46, 95%CI 1.28-1.65), lung (HR 1.04, 95%CI 1.02-1.06) and colon (HR 1.24, 95%CI 1.12-1.38) cancers. When breast cancers were analyzed by stage, OS was decreased in stages I (HR 1.27, 95%CI 1.16-1.40) and II (HR 1.13, 95%CI 1.02-1.24) but not in stage III (HR 1.20, 95%CI 0.94-1.53). CONCLUSION: Delaying breast, lung and colon cancer surgeries during the COVID-19 pandemic may decrease survival.

Johannesson, L., Wall, A., Tzakis, A., Quintini, C., Richards, E.G., O’Neill, K., Porrett, P.M. and Testa, G. (2020). “Life underneath the VCA umbrella: perspectives from the United States Uterus Transplant Consortium.” Am J Transplant Dec 14. [Epub ahead of print].

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The parallel emergence of uterus transplantation (UTx) and other transplantation innovations including face and hand transplantation led to the categorization of the uterus as a vascular composite allograft (VCA). With >60 transplants and >20 births worldwide, UTx is transitioning rapidly from a research endeavor to an effective treatment option for women with uterine-factor infertility. While it originally made sense to group the innovations under one umbrella, it is time to revisit the designation of UTx as a VCA. We describe how UTx needs unique policy, procedural codes, insurance contracts and educational initiatives. We contend that separating UTx from VCAs may become necessary in the future to avoid hindering the growth and regulation of this field.

Johannesson, L., Koon, E.C., Bayer, J., McKenna, G.J., Wall, A., Fernandez, H., Martinez, E.J., Gupta, A., Ruiz, R., Onaca, N. and Testa, G. (2021). “Dallas UtErus Transplant Study: Early Outcomes and Complications of Robot-assisted Hysterectomy for Living Uterus Donors.” Transplantation 105(1): 225-230.

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BACKGROUND: Uterus transplantation is a treatment for absolute uterine infertility and can be performed with living and deceased donors. Given the safety and increased utilization of robotic assistance with other gynecologic and transplant donor operations, we adopted a robot-assisted approach to donor hysterectomy. This study compared early outcomes and morbidity of the robot-assisted approach to donor hysterectomy with the traditionally performed open approach and addressed whether the robot-assisted approach is safe and offers advantages for the donor. METHODS: Our institution has performed 18 living donor hysterectomies for uterus transplantation. This retrospective review compared the last 5 cases utilizing a robot-assisted technique and vaginal extraction of the uterus graft with the first 13 cases performed with an open laparotomy technique. Demographic, intraoperative, and postoperative data were examined. RESULTS: There were no differences between the robot-assisted and the open living donor group with respect to age, body mass index, or gynecological history. Although the median operative time was shorter for the open approach (6.27 versus 10.46 h), the donors’ median estimated blood loss, length of hospital stay, and length of sick leave were less with the robot-assisted approach. There was no conversion to open hysterectomy in the robot-assisted cases, and the incidence of complications was similar between the 2 groups. There was no difference in early graft function. CONCLUSIONS: These preliminary results show that robot-assisted living donor hysterectomy is feasible and safe for the donors; it allows a faster postoperative recovery and the same early graft function.