Impact of kidney transplant on post-operative morbidity and mortality in patients with pre-operative cardiac dysfunction.

BACKGROUND: Several studies show an increase in complications, both cardiac and non-cardiac, and a higher mortality in patients with preexisting cardiac disease when they undergo elective surgery. Due to the high incidence of cardiac dysfunction in patients with concomitant chronic kidney disease, we wanted to determine if the same negative impact is demonstrated in patients undergoing kidney transplantation. METHODS: A retrospective analysis was done on 582 patients who underwent kidney transplant from a single transplant center between 2014 and 2019. Participants for this study were divided into two groups based on cardiac ejection fraction: normal EF (≥40%) (n = 540) and low EF (<40%) (n = 33); exclusion criteria included patients undergoing multi-organ transplants (n = 9). Characteristics and outcomes of patients were compared before and after transplant using chi-square tests for categorical measures, and either Kruskal-Wallis or paired Student's t tests for continuous measures. Overall survival (OS) between groups was assessed using the Kaplan-Meier test. We compared outcomes between the normal EF and low EF groups using logistic regression in raw data, and propensity score matched sample and inverse-probability-weighting to mitigate selection bias. RESULTS: There was no significant difference in survival between patients in the low EF and normal EF groups (p = .33). Among patients with low EF, mean EF after transplant significantly improved (mean: 55.83% ± 5.75%) compared to mean EF before transplant (38.28% ± 7.35%), (p = < .0001). Of the patients with a low EF before transplant, 1 in 5 had a history of CAD, compared to only 1 in 10 among those patients with a normal EF, p = .0657. Post-transplant complications were comparable between the groups. CONCLUSION: Patients undergoing kidney transplantation with a low ejection fraction do not demonstrate an increased incidence of morbidity or mortality in the peri- and post-transplant follow-up compared with patients with a normal ejection fraction. Cardiac events post-transplantation is also comparable between the two groups. Of note, patients with a low EF have a significantly improved EF after kidney transplant which is likely a function of improvement in their physiologic state after the kidney transplant.

Light sheet microscopy of the gerbil cochlea.

Light sheet fluorescence microscopy (LSFM) provides a rapid and complete three-dimensional image of the cochlea. The method retains anatomical relationships-on a micrometer scale-between internal structures such as hair cells, basilar membrane (BM), and modiolus with external surface structures such as the round and oval windows. Immunolabeled hair cells were used to visualize the spiraling BM in the intact cochlea without time intensive dissections or additional histological processing; yet material prepared for LSFM could be rehydrated, the BM dissected out and reimaged at higher resolution with the confocal microscope. In immersion-fixed material, details of the cochlear vasculature were seen throughout the cochlea. Hair cell counts (both inner and outer) as well as frequency maps of the BM were comparable to those obtained by other methods, but with the added dimension of depth. The material provided measures of angular, linear, and vector distance between characteristic frequency regions along the BM. Thus, LSFM provides a unique ability to rapidly image the entire cochlea in a manner applicable to model and interpret physiological results. Furthermore, the three-dimensional organization of the cochlea can be studied at the organ and cellular level with LSFM, and this same material can be taken to the confocal microscope for detailed analysis at the subcellular level.

High aurora kinase expression identifies patients with muscle-invasive bladder cancer who have poor survival after neoadjuvant chemotherapy.

OBJECTIVES: Overexpression of aurora kinase A (AURKA) confers a poor prognosis in patients with urothelial carcinoma of the bladder. The prognostic value of high aurora kinase B (AURKB) expression in local bladder cancer is not well defined, and whether the prognostic value of either AURKA or AURKB is affected by the use of chemotherapy is unknown. We sought to characterize the impact of high AURKA and AURKB expression on clinical outcome in patients with muscle-invasive bladder cancer (MIBC) who received neoadjuvant chemotherapy (NAC). MATERIALS AND METHODS: Immunohistochemistry for AURKA and AURKB was performed on pretreatment diagnostic transurethral resection of bladder tumor (TURBT) and matched cystectomy specimens in 50 subjects with MIBC who received NAC. Receiver operator characteristic curves (ROC) were calculated to assess the impact of AURKA and AURKB expression on pathologic response rate. Kaplan-Meier techniques and Cox proportional hazards models were used to assess the association with relapse-free survival (RFS) and overall survival (OS). RESULTS: Twenty-two of 50 [44%] patients had residual muscle-invasive (ypT2-4) urothelial carcinoma after NAC. Neither baseline tumor expression of AURKA (ROC = 0.57, P = 0.46) nor AURKB (ROC = 0.56, P = 0.87) predicted for ypT2-4 status. However, baseline expression of AURKA above the 75th percentile for this cohort was associated with an inferior RFS, (HR = 3.88, P = 0.008) and OS, (HR = 6.10, P < 0.001). Similar trends for worse survival outcomes were also observed for high AURKB levels (RFS, [HR = 2.2, P = 0.13] and OS, (HR = 2.25, P = 0.09). CONCLUSIONS: High baseline tumor AURKA and AURKB expression identified MIBC patients with inferior RFS and OS despite the use of NAC and may identify patients who should be prioritized for clinical trial enrollment rather than standard cisplatin-based chemotherapy.

Discordance of high PD-L1 expression in primary and metastatic urothelial carcinoma lesions.

Immune checkpoint inhibitors (ICI) targeting PD-(L)1 are effective in select patients with advanced urothelial carcinoma (UC). High PD-L1 expression enriches for response to ICIs; however, the predictive value of PD-L1 expression is limited, which may be due in part to dynamic expression of PD-L1 in the tumor environment. We sought to characterize PD-L1 expression in primary UC and paired metastatic lesions to gain insight into the potential discordance of tumor PD-L1 expression during the metastatic process. MATERIALS AND METHODS: Immunohistochemical staining for PD-L1 using the SP-142 antibody was performed on primary tumors and matched metastatic specimens in 77 evaluable subjects with advanced UC. Immunohistochemical staining was scored for the percentage of cells positive (<5%, ≥5%) in tumor cell (TC) and immune cell (IC) compartments. Correlation of PD-L1 expression in TCs and ICs was estimated using Spearman's correlation coefficients (rho, ρ). Cohen's kappa statistics (κ) were utilized to assess the agreement in PD-L1 expression between groups. RESULTS: High (≥5%) PD-L1 expression in primary and metastatic biopsies, respectively, was observed in 6.0% and 7.7% of TCs and in 14.5% and 11.5% of ICs. IC PD-L1 expression in primary tumors was not correlated with IC PD-L1 expression in paired metastatic lesions (ρ = 0.05, P = 0.67) and there was poor agreement in high expression rates between primary and metastatic lesions in the IC compartment (κ= 0.086). CONCLUSION: High PD-L1 IC expression is temporally and spatially discordant between primary and metastatic UC lesions. Future studies of PD-(L)1 targeted therapies in patients with metastatic UC may benefit from use of fresh biopsies of metastatic lesions to define PD-L1 expression when feasible.