Enhanced immunosuppression improves early allograft function in a porcine kidney transplant model of donation after circulatory death.

It remains controversial whether renal allografts from donation after circulatory death (DCD) have a higher risk of acute rejection (AR). In the porcine large animal kidney transplant model, we investigated the AR and function of DCD renal allografts compared to the non-DCD renal allografts and the effects of increased immunosuppression. We found that the AR was significantly increased along with elevated MHC-I expression in the DCD transplants receiving low-dose immunosuppression; however, AR and renal function were significantly improved when given high-dose immunosuppressive therapy postoperatively. Also, high-dose immunosuppression remarkably decreased the mRNA levels of ifn-g, il-6, tgf-b, il-4, and tnf-a in the allograft at day 5 and decreased serum cytokines levels of IFN-g and IL-17 at day 4 and day 5 after operation. Furthermore, Western blot analysis showed that higher immunosuppression decreased phosphorylation of signal transducer and activator of transcription 3 and nuclear factor kappa-light-chain-enhancer of activated B cells-p65, increased phosphorylation of extracellular-signal-regulated kinase, and reduced the expression of Bcl-2-associated X protein and caspase-3 in the renal allografts. These results suggest that the DCD renal allograft seems to be more vulnerable to AR; enhanced immunosuppression reduces DCD-associated AR and improves early allograft function in a preclinical large animal model.

Implementation and Effectiveness of a Veterans Affairs-Based Comprehensive Lung Cancer Survivorship Program.

PURPOSE: Few programs exist to address persistent impairment in functional status, quality of life, and mental health in lung cancer survivors. We aimed to determine whether a 12-wk multimodal survivorship program imparts clinical benefit. METHODS: Any patient at the Durham Veterans Affairs Medical Center with lung cancer and a Karnofsky score of ≥60 could participate. Chronic obstructive pulmonary disease medications were optimized at the enrollment visit. Participants with a Hospital Anxiety and Depression Scale (HADS) score of >8 were offered pharmacotherapy and mental health referral. Participants did home-based exercise with a goal of 1 hr/d, 5 d/wk. They were called weekly to assess exercise progress and review depression/anxiety symptoms. Participants were offered pharmacotherapy for smoking cessation. RESULTS: Twenty-three (50%) of the first 46 enrollees completed the full 12-wk program. Paired changes from enrollment to completion (mean ± SD) were observed in 6-min walk test (73.6 ± 96.9 m, P = .002), BODE (Body mass index, airflow Obstruction, Dyspnea, and Exercise) index (-1.45 ± 1.64 points, P < .001), Duke Activity Status Index (3.84 ± 7.12 points, P = .02), Fried Frailty Index (-0.588 ± 0.939 points, P = .02), modified Medical Research Council dyspnea scale (-0.619 ± 1.284 points, P = .04), Functional Assessment of Cancer Therapy-Lung Emotional subscale score (1.52 ± 2.96 points, P = .03), HADS total score (-2.63 ± 4.34 points, P = .02), and HADS Anxiety subscale score (-1.47 ± 2.29 points, P = .01). CONCLUSIONS: A comprehensive Lung Cancer Survivorship Program provides clinically meaningful improvements in functional status, quality of life, and mental health.