Research Spotlight

Wall, A.E., Johannesson, L., Sok, M., Warren, A.M., Gordon, E.J. and Testa, G. (2021). “Decision making and informed consent in uterus transplant recipients: A mixed-methods study of the Dallas uterus transplant study (DUETS) participants.” Am J Surg Feb 4;S0002-9610(21)00057-X. [Epub ahead of print].

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BACKGROUND: Uterus transplantation (Utx) has achieved clinical success but little is known about motivations and experiences of UTx recipients. METHODS: We conducted semi-structured interviews with 20 UTx recipients in addition to collecting quantitative demographic and clinical data. Closed-ended interview questions were treated as categorical variables. Thematic analysis was performed on qualitative data. Bivariate analysis tested associations between categorical variables. RESULTS: Themes that emerged included: the decision to pursue UTx is a process, primary motivations for UTx are specific to the experience of gestation, and alternative options did not offer the same value as UTx. There was no association between disease etiology, clinical status, or perception of UTx risk with information needs or donor preference. CONCLUSIONS: Our findings suggest that UTx is a unique treatment option that some women with AUFI find preferable to adoption and surrogacy and, as such, should be discussed as a parenthood option with women diagnosed with AUFI.

Heimbach, J.K., Trotter, J.F., Pomposelli, J., Cafarella, M. and Noreen, S.M. (2021). “A Tale Full of Sound and Fury.” Liver Transpl Jan 18. [Epub ahead of print].

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In the current issue of Liver Transplantation, Chyou et al present an analysis of the new Acuity Circle (AC) distribution model for liver transplantation in the United States. (1) The authors analyzed Organ Procurement and Transplantation Network (OPTN) data from the six month period prior to the adoption of the policy (8/8/2019-2/3/2020), compared to the six months after the policy began (3/5/2020-8/31/2020), excluding status 1A, pediatric, living donor transplants, and transplants performed within the month of February to allow for a one-month “adjustment period.”

Fam, N.P., von Bardeleben, R.S., Hensey, M., Kodali, S.K., Smith, R.L., Hausleiter, J., Ong, G., Boone, R., Ruf, T., George, I., Szerlip, M., Näbauer, M., Ali, F.M., Moss, R., Bapat, V., Schnitzler, K., Kreidel, F., Ye, J., Deva, D.P., Mack, M.J., Grayburn, P.A., Peterson, M.D., Leon, M.B., Hahn, R.T. and Webb, J.G. (2021). “Transfemoral Transcatheter Tricuspid Valve Replacement With the EVOQUE System: A Multicenter, Observational, First-in-Human Experience.” JACC Cardiovasc Interv Feb 5;S1936-8798(20)32387-6. [Epub ahead of print].

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OBJECTIVES: The purpose of this observational first-in-human experience was to investigate the feasibility and safety of the EVOQUE tricuspid valve replacement system and its impact on short-term clinical outcomes. BACKGROUND: Transcatheter tricuspid intervention is a promising option for selected patients with severe tricuspid regurgitation (TR). Although transcatheter leaflet repair is an option for some, transcatheter tricuspid valve replacement (TTVR) may be applicable to a broader population. METHODS: Twenty-five patients with severe TR underwent EVOQUE TTVR in a compassionate-use experience. The primary outcome was technical success, with NYHA (NYHA) functional class, TR grade, and major adverse cardiac and cerebrovascular events assessed at 30-day follow-up. RESULTS: All patients (mean age 76 ± 3 years, 88% women) were at high surgical risk (mean Society of Thoracic Surgeons risk score 9.1 ± 2.3%), with 96% in NYHA functional class III or IV. TR etiology was predominantly functional, with mean tricuspid annular diameter of 44.8 ± 7.8 mm and mean tricuspid annular plane systolic excursion of 16 ± 2 mm. Technical success was 92%, with no intraprocedural mortality or conversion to surgery. At 30-day follow-up, mortality was 0%, 76% of patients were in NYHA functional class I or II, and TR grade was ≤2+ in 96%. Major bleeding occurred in 3 patients (12%), 2 patients (8%) required pacemaker implantation, and 1 patient (4%) required dialysis. CONCLUSIONS: This first-in-human experience evaluating EVOQUE TTVR demonstrated high technical success, acceptable safety, and significant clinical improvement. Larger prospective studies are needed to confirm durability and safety and the impact on long-term clinical outcomes.

Swanson, G.P., Lenz, L., Stone, S. and Cohen, T. (2021). “Cell-cycle risk score more accurately determines the risk for metastases and death in prostatectomy patients compared with clinical features alone.” Prostate 81(4): 261-267.

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BACKGROUND: Prostate cancer treatment aims to prevent metastases and disease-specific mortality. Pathologic parameters have limited ability to predict these outcomes, but biomarkers can improve risk discrimination. We evaluated the ability of cell-cycle progression and combined cell-cycle risk scores to predict metastases and disease-specific mortality after prostatectomy. METHODS: Eligibility included (1) treatment with radical prostatectomy (1985-1997); (2) cell-cycle progression score; (3) preoperative prostate-specific antigen; (4) no neoadjuvant therapy; and (5) clinical follow-up (N = 360). Cancer of the prostate risk assessment postsurgical score was combined with cell cycle progression into the prespecified combined cell-cycle risk score. Hazard ratios (HRs) are reported per unit score. RESULTS: In total, 11% (41/360) developed metastases and 9% (33/360) experienced disease-specific mortality. Combined cell-cycle risk score predicted metastases and disease-specific mortality post-radical prostatectomy (p < 1 × 10(-8) ). Adjusting for cancer of the prostate risk assessment postsurgical score, the combined cell-cycle risk score remained a predictor of metastases (HR = 3.03 [95% confidence interval (CI): 1.49, 6.20]; p = .003] and disease-specific mortality (HR = 3.40 [95% CI: 1.52, 7.59]; p = .004). Of patients with biochemical recurrence, 25% (41/163) developed metastases. Cancer of the prostate risk assessment postsurgical score was predictive of metastases postbiochemical recurrence but was improved by the addition of cell cycle progression (HR = 1.70 [95% CI: 1.14, 2.53]; p = .012). The combined cell-cycle risk was also prognostic of metastases post-biochemical recurrence (HR = 1.56 [95% CI: 1.20, 2.03]; p = .001). CONCLUSION: Combined cell-cycle risk and cell cycle progression scores predict metastases and disease-specific mortality post-radical prostatectomy and should help identify patients at greatest risk of treatment failure who might benefit from earlier intervention.

Srivastava, S., Cirrincione, K.N., Deshpande, D. and Gumbo, T. (2020). “Tedizolid, Faropenem, and Moxifloxacin Combination With Potential Activity Against Nonreplicating Mycobacterium tuberculosis.” Front Pharmacol 11: 616294.

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Background: Mycobacterium tuberculosis [Mtb] could be present in different metabolic population in the lung lesions, and nonreplicating persisters [NRP], associated with latent tuberculosis [TB], are the most difficult to kill. Objective: Test the combination of tedizolid, moxifloxacin, and faropenem for activity against NRP using Mtb SS18b in the hollow fiber model [HFS-TB]. Methods: Tedizolid and moxifloxacin were tested as, first, two-drug combination against log-phase growth [LPG] and, second, slowly replicating bacilli [SRB] under acidic condition and with faropenem to create a three-drug combination regimen. Finally, standard regimen [isoniazid-rifampin-pyrazinamide] was used as comparator in the HFS-TB experiment with NRP Mtb. HFS-TB units were sampled for drug-concentration measurement as well as for estimation of bacterial burden using solid agar and mycobacterial growth indicator tube [MGIT] method. Linear regression was used to calculate the kill slopes with each treatment regimen and analysis of variance (ANOVA) to compare the regimen. Results: Tedizolid at standard dose in combination with high-dose moxifloxacin killed 3.05 log(10) CFU/ml LPG Mtb and 7.37 log(10) CFU/ml SRB in the bactericidal and sterilizing activity HFS-TB experiments, respectively. There was no statistical difference between tedizolid-moxifloxacin-faropenem combination and the standard regimen as both killed 7.35 log(10) CFU/ml NRP Mtb in 21 days. There was no emergence of resistance to any of the drugs studied in the three HFS-TB experiments. Conclusion: The experimental regimen of tedizolid, moxifloxacin, and faropenem could effectively kill NRP population of Mtb, and given the efficacy against different metabolic population of Mtb could serve as a pan-TB regimen. Clinical studies are warranted to validate the in vitro findings.