Research Spotlight

Carey, S. A., K. M. Tecson, A. K. Jamil, J. Felius, T. K. Wolf-Doty and S. A. Hall (2018). “Gene expression profiling scores in dual organ transplant patients are similar to those in heart-only recipients.” Transpl Immunol. Mar 26. [Epub ahead of print].

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BACKGROUND: Serial gene expression profiling (GEP) may reduce the need for endomyocardial biopsies for detecting acute cellular rejection (ACR) after transplantation, but its performance in dual organ transplant recipients is currently unknown. METHODS: We analyzed 18months of follow-up in a national cohort of 27 dual organ recipients (18 heart-kidney, 8 heart-liver, 1 heart-lung) matched to 54 heart-only recipients for gender, age, and time to first GEP (AlloMap(R)) test. ACR, antibody-mediated rejection (AMR), cytomegalovirus infections, biopsies, and longitudinal GEP scores were evaluated. RESULTS: During the first 90days post-transplant, the mean GEP score for dual organ recipients was 25.2+/-9.1, vs. 23.5+/-7.7 for heart-only recipients (P=0.48), with final GEP scores being 29.1+/-6.1 and 32.3+/-3.4, respectively (P=0.34). GEP scores increased over time (P<0.001) at a similar rate (P=0.33) for both groups. One heart-only recipient had treated ACR (GEP score=17). Fourteen subjects had cytomegalovirus infection, 8 of whom were dual-organ. During follow-up, mean GEP score among patients with cytomegalovirus infection was 32.3, compared to 26.7 (p<0.001) in patients without cytomegalovirus. Only 4 (2%) of 233 biopsies were positive for mild AMR; all occurring in 2 heart-only recipients (GEP scores=18-33). CONCLUSIONS: This largest cohort to date suggests that dual organ transplantation alone should not be reason to omit GEP testing from post-transplant medical management, as the two groups' scores did not differ significantly. Confirming that GEP scores increase over time for heart-only and dual organ recipients and in the presence of cytomegalovirus infection, our work shows promise for the use of serial GEP testing in dual organ recipients.

Betts, A. C., K. Froehlich-Grobe, S. Driver, D. Carlton and M. K. Kramer (2018). “Reducing barriers to healthy weight: Planned and responsive adaptations to a lifestyle intervention to serve people with impaired mobility.” Disabil Health J 11(2): 315-323.

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BACKGROUND: People with impaired mobility (IM) disabilities have a higher prevalence of obesity and obesity-related chronic conditions; however, lifestyle interventions that address the unique needs of people with IM are lacking. OBJECTIVE: This paper describes an adapted evidence-based lifestyle intervention developed through community-based participatory research (CBPR). METHODS: Individuals with IM, health professionals, disability group representatives, and researchers formed an advisory board to guide the process of thoroughly adapting the Diabetes Prevention Program Group Lifestyle Balance (DPP GLB) intervention after a successful pilot in people with IM. The process involved two phases: 1) planned adaptations to DPP GLB content and delivery, and 2) responsive adaptations to address issues that emerged during intervention delivery. RESULTS: Planned adaptations included combining in-person sessions with conference calls, providing arm-based activity trackers, and adding content on adaptive cooking, adaptive physical activity, injury prevention, unique health considerations, self-advocacy, and caregiver support. During the intervention, participants encountered numerous barriers, including health and mental health issues, transportation, caregivers, employment, adjusting to disability, and functional limitations. We addressed barriers with responsive adaptations, such as supporting electronic self-monitoring, offering make up sessions, and adding content and activities on goal setting, problem solving, planning, peer support, reflection, and motivation. CONCLUSIONS: Given the lack of evidence on lifestyle change in people with disabilities, it is critical to involve the community in intervention planning and respond to real-time barriers as participants engage in change. A randomized controlled trial (RCT) is underway to examine the usability, feasibility, and preliminary effectiveness of the adapted intervention.

Bertisch, S. M., B. D. Pollock, M. A. Mittleman, D. J. Buysse, L. A. Bazzano, D. J. Gottlieb and S. Redline (2018). “Insomnia with Objective Short Sleep Duration and Risk of Incident Cardiovascular Disease and All-Cause Mortality: Sleep Heart Health Study.” Sleep. Mar 7. [Epub ahead of print].

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Study Objectives: To quantify the association between insomnia/poor sleep with objective short sleep and incident cardiovascular disease (CVD) and mortality in the general population. Methods: We conducted a time-to-event analysis of Sleep Heart Health Study data. Questionnaires and at-home polysomnography were performed between 1994 -1998. Participants were followed for a median 11.4 years (Q1-Q3, 8.8-12.4 years) until death or last contact. The primary exposure was insomnia or poor sleep with short sleep defined as: difficulty falling asleep, difficulty returning to sleep, early morning awakenings, or sleeping pill use, 16-30 nights/month; and total sleep <6 hours on polysomnography (PSG). We used proportional hazards models to estimate the association between insomnia/poor sleep with short sleep and CVD, as well as all-cause mortality. Results: Among 4,994 participants (mean age 64.0 +/- 11.1 years), 14.1% reported insomnia or poor sleep, of which 50.3% slept <6 hours. Among 4,437 CVD-free participants at baseline, we observed 818 incident CVD events. After propensity-adjustment, there was a 29% higher risk of incident CVD in the insomnia/poor sleep with short sleep group compared with the reference group (HR, 1.29, 95% CI, 1.00, 1.66), but neither the insomnia/poor sleep only nor short sleep only groups were associated with higher incident CVD. Insomnia/poor sleep with objective short sleep was not significantly associated with all-cause mortality (HR, 1.07, 95% CI, 0.86, 1.33). Conclusions: Insomnia/poor sleep with PSG-short sleep was associated with higher risk of incident CVD. Future studies should evaluate the impact of interventions to improve insomnia with PSG-short sleep on CVD.

Augestad, K. M., D. S. Keller, P. M. Bakaki, J. Rose, S. M. Koroukian, T. Oresland and C. P. Delaney (2018). “The impact of rectal cancer tumor height on recurrence rates and metastatic location: A competing risk analysis of a national database.” Cancer Epidemiol 53: 56-64.

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BACKGROUND: The impact of rectal cancer tumor height on local recurrence and metastatic spread is unknown. The objective was to evaluate the impact of rectal cancer tumor height from the anal verge on metastatic spread and local recurrence patterns. METHODS: The Norwegian nationwide surgical quality registry was reviewed for curative rectal cancer resections from 1/1/1996-12/15/2006. Cancers were stratified into five height groups: 0-3cm, >3-5cm, >5-9cm, >9-12cm, 12cm-HI. Competing risk and proportional hazards models assessed the relationship between tumor height and patterns of metastasis and survival. RESULTS: 6859 patients were analyzed. After median follow-up of 52 months (IQR 20-96), 26.7% (n=1835) experienced recurrence. With tumors >12cm, the risk of liver metastases increased (crude HR 1.49, p=0.03), while lung metastases decreased (crude HR 0.66, p=0.03), and risk of death decreased (crude HR 0.81, p=0.001) The cumulative incidence of pelvic recurrence were highest for the low tumors (p=0.01). Median time to liver metastases was 14months (IQR 7-24), lung metastases 25months (IQR 13-39), pelvic recurrence 19months (IQR10-32), (p<0.0001). Time to metastases in liver and lungs were significantly associated with tumor height (p<0.001) CONCLUSION: There are distinct differences in metastatic recurrence patterns and time to recurrence from different anatomic areas of the rectum. In crude analyses, tumor height impacted metastatic spread to the liver and lungs. However, when adjusting for treatment variables, the hazard of metastatic spread to the liver and lungs are limited. Nevertheless, time to metastases in liver and lungs is significantly impacted by tumor height. Venous drainage of the rectal cancer may be a significant contributor of rectal cancer metastatic spread, but further research is warranted.

Aguilar, P. R., D. Carpenter, J. Ritter, R. D. Yusen, C. A. Witt, D. E. Byers, T. Mohanakumar, D. Kreisel, E. P. Trulock and R. R. Hachem (2018). “The role of C4d deposition in the diagnosis of antibody-mediated rejection after lung transplantation.” Am J Transplant 18(4): 936-944.

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Antibody-mediated rejection (AMR) is an increasingly recognized form of lung rejection. C4d deposition has been an inconsistent finding in previous reports and its role in the diagnosis has been controversial. We conducted a retrospective single-center study to characterize cases of C4d-negative probable AMR and to compare these to cases of definite (C4d-positive) AMR. We identified 73 cases of AMR: 28 (38%) were C4d-positive and 45 (62%) were C4d-negative. The two groups had a similar clinical presentation, and although more patients in the C4d-positive group had neutrophilic capillaritis (54% vs. 29%, P = .035), there was no significant difference in the presence of other histologic findings. Despite aggressive antibody-depleting therapy, 19 of 73 (26%) patients in the overall cohort died within 30 days, but there was no significant difference in freedom from chronic lung allograft dysfunction (CLAD) or survival between the two groups. We conclude that AMR may cause allograft failure, but that the diagnosis requires a multidisciplinary approach and a high index of suspicion. C4d deposition does not appear to be a necessary criterion for the diagnosis, and although some cases may respond initially to therapy, there is a high incidence of CLAD and poor survival after AMR.