Research Spotlight

Potter, S.R., Hinojosa, R., Miles, C.D., O’Brien, D. and Ross, D.J. (2020). “Remote monitoring using donor-derived, cell-free DNA after kidney transplantation during the coronavirus disease 2019 pandemic.” Kidney Res Clin Pract 39(4): 495-500.

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BACKGROUND: Donor-derived, cell-free DNA (dd-cfDNA) level correlates with allograft injury with clinical validity and utility for quiescence and active acute rejection (AR) in kidney transplant recipients. We analyzed trends in dd-cfDNA level immediately preceding and during the coronavirus disease 2019 (COVID-19) pandemic with implemented “shelter in place” and a tele-health strategy with remote home phlebotomy to limit COVID-19 exposure. METHODS: During COVID-19 in the United States (US), we surveyed weekly (January 6, 2020-May 25, 2020) metrics for dd-cfDNA corresponding to both a low risk for active rejection (dd-cfDNA < 0.5%) and cohorts with indeterminate levels of 0.5% to 1.0% and > 1.0%. During the study timeframe, over 11,000 patient samples (67%) from 150 kidney transplantation centers were transitioned from standard facility-based to remote phlebotomy. RESULTS: The proportion of dd-cfDNA samples, analyzed in 21 weekly aggregated cohorts by risk-stratification category, was unchanged during the COVID-19 escalation in the US. Linearized slopes for numbers of samples corresponding to indeterminate risk for AR cohorts of > 1.0% and 0.5% to 1.0% were -0.31 and -0.12, respectively; indicating that prevalence of these “at risk for AR cohorts” decreased during remote surveillance. Approximately 73% of samples corresponded to low risk of AR (dd-cfDNA < 0.5%), while an additional 15% of samples had dd-cfDNA level ≤ 1.0%. CONCLUSION: The combination of remote home phlebotomy including dd-cfDNA analysis and a tele-health program offer a new paradigm that may substantially improve patient compliance and assuage anxiety regarding the state of kidney allograft health during the COVID-19 pandemic. Further prospective multi-center studies with robust outcomes data are warranted.

Pham, P.H., Stalter, L.N., Martinez, E.J., Wang, J.F., Welch, B.M., Leverson, G., Marka, N., Al-Qaoud, T., Mandelbrot, D., Parajuli, S., Sollinger, H.W., Kaufman, D., Redfield, R.R., 3rd and Odorico, J.S. (2020). “Large Single Center Results of Simultaneous Pancreas-Kidney Transplantation in Patients with Type 2 Diabetes.” Am J Transplant Dec 22. [Epub ahead of print].

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Studies have found similar outcomes of Simultaneous Pancreas-Kidney transplantation (SPKT) in patients with Type 2 (T2D) and Type 1 diabetes (T1D). However, there are few data evaluating the association of recipient factors such as age, BMI, or pre-transplant insulin requirements with outcomes, thus the criteria for the optimal recipient selection remains unclear. In this study, 284 T1D and 39 T2D patients, who underwent SPKT between 2006-2017 with 1 year of follow-up at minimum, were assessed for potential relationship of pre-transplant BMI and insulin requirements with post-transplant diabetes and pancreatic graft failure. Kaplan-Meier analysis showed similar rates of freedom from post-transplant diabetes (94.7% T2D vs. 92.3% T1D at 1 yr, and 88.1% T2D vs. 81.1% T1D at 5 yrs) and graft survival (89.7% T2D vs. 90.4% T1D at 1 yr, and 89.7% T2D vs. 81.2% T1D at 5 yrs). There was no significant association between BMI or pre-transplant insulin requirements with post-transplant diabetes occurrence in either T1D (p = 0.10, 0.43, respectively) or T2D (p = 0.12, 0.63) patients in the cohort; or with graft failure (T1D: p = 0.40, 0.09; T2D: p = 0.71, 0.28). These observations suggest a less restricted approach to selective use of SPKT in patients with T2D.

Pennington, M.L., Ylitalo, K.R., Lanning, B.A., Dolan, S.L. and Gulliver, S.B. (2021). “An epidemiologic study of suicide among firefighters: Findings from the National Violent Death Reporting System, 2003 – 2017.” Psychiatry Res 295: 113594

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Suicide is a significant concern among fire service due to high rates of suicide behaviors. The aim of this study was to describe suicides among firefighters using national suicide death data. Data from the National Violent Death Reporting System for 722 firefighters and 192,430 non-firefighters were analyzed to compare sociodemographics and risk factors between firefighter and non-firefighter decedents; and among firefighters based on suicide means. A greater proportion of firefighter decedents died by firearm compared to non-firefighters. Firefighter decedents were less likely to have been diagnosed with depression, but more likely to have been diagnosed with post-traumatic stress disorder compared to non-firefighters. A greater percentage of firefighter decedents had a relationship or physical health problem prior to death, but a lower percentage had a history of suicide thoughts/attempts. Among firefighter decedents, multivariate analysis showed physical health problems and disclosing suicide intent predicted death by firearm. Greater awareness of risk factors, reduced access to lethal means, and ensuring access to behavioral health services may aide in decreasing suicide mortality in this population. These findings should be interpreted with caution due to limitations concerning report accuracy, generalizability, small female sample size, and inclusion of data only for lethal suicide attempts.

Pannia, E., Hammoud, R., Simonian, R., Arning, E., Ashcraft, P., Wasek, B., Bottiglieri, T., Pausova, Z., Kubant, R. and Anderson, G.H. (2020). “[6S]-5-Methyltetrahydrofolic Acid and Folic Acid Pregnancy Diets Differentially Program Metabolic Phenotype and Hypothalamic Gene Expression of Wistar Rat Dams Post-Birth.” Nutrients 13(1).

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[6S]-5-methyltetrahydrofolic acid (MTHF) is a proposed replacement for folic acid (FA) in diets and prenatal supplements. This study compared the effects of these two forms on maternal metabolism and hypothalamic gene expression. Pregnant Wistar rats received an AIN-93G diet with recommended FA (1X, 2 mg/kg, control), 5X-FA or equimolar levels of MTHF. During lactation they received the control diet and then a high fat diet for 19-weeks post-weaning. Body weight, adiposity, food intake, energy expenditure, plasma hormones, folate, and 1-carbon metabolites were measured. RNA-sequencing of the hypothalamus was conducted at parturition. Weight-loss from weaning to 1-week post-weaning was less in dams fed either form of the 5X vs. 1X folate diets, but final weight-gain was higher in 5X-MTHF vs. 5X-FA dams. Both doses of the MTHF diets led to 8% higher food intake and associated with lower plasma leptin at parturition, but higher leptin at 19-weeks and insulin resistance at 1-week post-weaning. RNA-sequencing revealed 279 differentially expressed genes in the hypothalamus in 5X-MTHF vs. 5X-FA dams. These findings indicate that MTHF and FA differ in their programing effects on maternal phenotype, and a potential adverse role of either form when given at the higher doses.

Ong, G., Pibarot, P., Redfors, B., Weissman, N.J., Jaber, W.A., Makkar, R.R., Lerakis, S., Gopal, D., Khalique, O., Kodali, S.K., Thourani, V.H., Anwaruddin, S., McAndrew, T., Zhang, Y., Alu, M.C., Douglas, P.S. and Hahn, R.T. (2020). “Diastolic Function and Clinical Outcomes After Transcatheter Aortic Valve Replacement: PARTNER 2 SAPIEN 3 Registry.” J Am Coll Cardiol 76(25): 2940-2951.

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BACKGROUND: Few studies have evaluated if diastolic function could predict outcomes in patients with aortic stenosis. OBJECTIVES: The authors aimed to assess the association between diastolic dysfunction (DD) and outcomes in patients with aortic stenosis undergoing transcatheter aortic valve replacement (TAVR). METHODS: Baseline, 30-day, and 1- and 2-year transthoracic echocardiograms from the PARTNER (Placement of Aortic Transcatheter Valves) 2 SAPIEN 3 registry were analyzed by a consortium of core laboratories and divided into the American Society of Echocardiography DD groups. RESULTS: Among the 1,750 included, 682 (54.4%) had grade 1 DD, 352 (28.1%) had grade 2 DD, 168 (13.4%) had grade 3 DD, and 51 (4.1%) had indeterminate DD grade. Incremental baseline grades of DD were associated with an increase in combined 1- and 2-year cardiovascular (CV) death/rehospitalization (all p < 0.002) and all-cause death at 2 years (p = 0.01) but not at 1 year. Improvement in DD grade/grade 1 DD at 30 days post-TAVR was seen in 70.8% patients. Patients with improvement in ≥1 grade of DD/grade 1 DD had reduced 1-year CV death/rehospitalization (p < 0.001) and increased 2-year survival (p = 0.01). Baseline grade 3 DD was a predictor of 1-year CV death/rehospitalization (hazard ratio: 2.73; 95% confidence interval: 1.07 to 6.98; p = 0.04). Improvement in DD grade/grade 1 DD at 30 days was protective for 1-year CV death/rehospitalizations (hazard ratio: 0.39; 95% confidence interval: 0.19 to 0.83; p = 0.01). CONCLUSIONS: In the PARTNER 2 SAPIEN 3 registry, baseline DD was a predictor of up to 2 years clinical outcomes in patients who underwent TAVR. Improvement in DD grade at 30 days was associated with improvement in short-term clinical outcomes. (The PARTNER II Trial: Placement of AoRTic TraNscathetER Valves II - PARTNER II - PARTNERII - S3 Intermediate [PARTNERII S3i]; NCT03222128; PARTNER II Trial: Placement of AoRTic TraNscathetER Valves II - High Risk and Nested Registry 7 [PII S3HR/NR7]; NCT03222141).