Research Spotlight

Hammoud, R., C. S. Liao, E. Pannia, M. Ho, N. Yang, R. Kubant, D. Chatterjee, E. Arning, T. Bottiglieri, Z. Pausova and G. H. Anderson (2019). “Choline and Folic Acid Balance in Diets During Pregnancy Programs Food Intake Regulation in Wistar Rat Offspring (FS08-05-19).” Curr Dev Nutr Jun 13: 3(Suppl 1). [Epub ahead of print].

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Objectives: High gestational folic acid (FA) induces an obesogenic phenotype in male Wistar rat offspring. Imbalances between FA and other methyl-nutrients (i.e., choline) leading to perturbations in the 1-carbon cycle may account for the effects of high FA diets. Canadian women consume high (2-7-fold) intakes of FA, but most are not meeting recommended adequate intakes for choline. Choline is also absent from Canadian prenatal supplements. The objective of this study is to evaluate the effects of the interaction between choline and FA in maternal diets of rats on the 1-carbon cycle, and the programming of food intake, body weight gain and biomarkers of obesity in the offspring later in life. Methods: Pregnant Wistar rat dams were fed the AIN-93 G diet with recommended (1X) choline and FA (RCRF, control), or a 5X FA diet with either 0.5X choline (LCHF), 1X choline (RCHF), or 2.5X choline (HCHF). Brain and blood were collected at birth. At weaning one male pup/dam from all groups was maintained on the control diet for 20 weeks then terminated. Dependent measures include weekly body weight-gain and food intake, plasma glucoregulatory hormones and 1-carbon metabolites at birth and post-weaning. Results: Increasing choline content to 2.5-fold in a high (5-fold) gestational FA diet (HCHF) led to lower plasma insulin and leptin levels at birth compared to the LCHF and RCHF diets, respectively (P < 0.05). It also led to lower (25%, P = 0.03) plasma 5-methyltetrahydrofolate concentrations at birth compared to the RCHF diet, suggesting more efficient utilization of FA. Offspring born to dams maintained on a high folic acid diet with either low or recommended choline had higher weekly food intake (6%, P < 0.05) and body weight-gain (9%, P < 0.01). In contrast, offspring from dams fed the HCHF gestational diet were not different from those born to dams fed the RCRF (control) diet, highlighting the mitigating effects of a balanced choline and FA gestational diet. Conclusions: Increased intakes of choline mitigate the effects of high FA diets. Maternal dietary choline interacts with FA on the long-term programming of food intake regulation in the offspring; emphasizing a need for more attention to improving choline intakes by women of child-bearing age. Funding Sources: This research was funded by the Canadian Institute of Health Research, Institute of Nutrition, Metabolism and Diabetes (CIHR-INMD).

Hammond, F. M., J. D. Corrigan, J. M. Ketchum, J. F. Malec, K. Dams-O’Connor, T. Hart, T. A. Novack, J. Bogner, M. N. Dahdah and G. G. Whiteneck (2019). “Prevalence of Medical and Psychiatric Comorbidities Following Traumatic Brain Injury.” J Head Trauma Rehabil 34(4): E1-e10.

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OBJECTIVE: To examine the prevalence of selected medical and psychiatric comorbidities that existed prior to or up to 10 years following traumatic brain injury (TBI) requiring acute rehabilitation. DESIGN: Retrospective cohort. SETTING: Six TBI Model Systems (TBIMS) centers. PARTICIPANTS: In total, 404 participants in the TBIMS National Database who experienced TBI 10 years prior. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Self-reported medical and psychiatric comorbidities and the onset time of each endorsed comorbidity. RESULTS: At 10 years postinjury, the most common comorbidities developing postinjury, in order, were back pain, depression, hypertension, anxiety, fractures, high blood cholesterol, sleep disorders, panic attacks, osteoarthritis, and diabetes. Comparing those 50 years and older to those younger than 50 years, diabetes (odds ratio [OR] = 3.54; P = .0016), high blood cholesterol (OR = 2.04; P = .0092), osteoarthritis (OR = 2.02; P = .0454), and hypertension (OR = 1.84; P = .0175) were significantly more prevalent in the older cohort while panic attacks (OR = 0.33; P = .0022) were significantly more prevalent in the younger cohort. No significant differences in prevalence rates between the older and younger cohorts were found for back pain, depression, anxiety, fractures, or sleep disorders. CONCLUSIONS: People with moderate-severe TBI experience other medical and mental health comorbidities during the long-term course of recovery and life after injury. The findings can inform further investigation into comorbidities associated with TBI and the role of medical care, surveillance, prevention, lifestyle, and healthy behaviors in potentially modifying their presence and/or prevalence over the life span.

Hamandi, M., R. L. Smith, W. H. Ryan, P. A. Grayburn, A. Vasudevan, T. J. George, J. M. DiMaio, K. A. Hutcheson, W. Brinkman, M. Szerlip, D. O. Moore and M. J. Mack (2019). “Outcomes of Isolated Tricuspid Valve Surgery Have Improved in the Modern Era.” Ann Thorac Surg 108(1): 11-15.

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BACKGROUND: Surgery for isolated tricuspid valve (TV) disease remains relatively infrequent because of significant patient comorbidities and poor surgical outcomes. This study reviewed the experience with isolated TV surgery in the current era to determine whether outcomes have improved. METHODS: From 2007 through 2017, 685 TV operations were performed in a single institution, of which 95 (13.9%) operations were isolated TV surgery. Patients were analyzed for disease origin, risk factors, operative mortality and morbidity, and long-term survival. RESULTS: A total of 95 patients underwent isolated TV surgery, an average of 9 patients per year increasing from an average of 5 per year to 15 per year during the study period. Surgery was reoperative in 41% (38 of 95) of patients, including 11.6% (11 of 95) with prior coronary artery bypass grafting and 29.4% (28 of 95) with prior valve surgery (9 TV, 11 mitral, 2 aortic, 5 mitral and aortic, and 1 mitral and TV). Repair was performed in 71.6% (68 of 95) of patients, and replacement was performed in 28.4% (27 of 95). Operative mortality was 3.2% (3 of 95), with no mortality in the most recent 73 patients over the last 6 years. Stroke occurred in 2.1% (2 of 95) of patients, acute kidney injury requiring dialysis in 5.3% (5 of 95), and the need for new permanent pacemaker in 16.8% (16 of 95). CONCLUSIONS: In the current era with careful patient selection and periprocedural management, isolated TV surgery can be performed with lower morbidity and mortality than has traditionally been reported with good long-term survival. These outcomes can also serve as a benchmark for catheter-based TV intervention outcomes.

Goraya, N., J. Simoni, L. N. Sager, A. Mamun, N. E. Madias and D. E. Wesson (2019). “Urine citrate excretion identifies changes in acid retention as eGFR declines in patients with chronic kidney disease.” Am J Physiol Renal Physiol Jun 19. [Epub ahead of print].

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We examined as secondary analysis if increased acid (H(+)) retention occurring as eGFR decreases in patients with chronic kidney disease (CKD) stage 2 eGFR (60-89 ml(.)min-1.73m-2) (CKD 2) without metabolic acidosis and followed over ten years is predicted by changes in 8 hour urine citrate excretion (UcitrateV). We randomized 120 CKD 2 non-diabetic, hypertension-associated nephropathy patients with plasma total CO2 (PTCO2) > 24 mM to receive 0.5 mEq/kg bw/day NaHCO3 (HCO3(-), n=40), 0.5 mEq/kg bw/day NaCl (NaCl, n=40), or Usual Care (UC, n=40). We assessed eGFR (CKD-EPI) and H(+) retention by comparing observed to expected PTCO2 increase 2 hours after oral NaHCO3 bolus (0.5 mEq/kg bw). Although 10-year vs. baseline eGFR was lower for each group, 10-year eGFR was higher (p<0.01) in HCO3(-) (59.6+/-4.8 ml(.)min-1.73m-2) than NaCl and UC (52.1+/-5.9 and 52.3+/-4.1 ml(.)min-1.73m-2, respectively). Less eGFR preservation was associated with higher 10-year vs. baseline H(+) retention in NaCl (26.5+/-13.1 vs. 18.2+/-15.3 mmol, p<0.01) and UC (24.8+/-11.3 vs. 17.7+/-10.9 mmol, p<0.01) and with lower 10-year vs. baseline UcitrateV for NaCl (162+/-47 vs. 196+/-52 mg, respectively, p<0.01) and UC (153+/-41 vs. 186+/-42 mg, respectively, p<0.01). Conversely, better eGFR preservation in HCO3(-) was associated with no differences in 10-year vs. baseline H(+) retention (14.2+/-13.5 vs. 16.1+/-15.1 mmol, p=1.00) or UcitrateV (212+/-45 vs. 203+/-49 mg, respectively, p=0.74). An overall generalized linear model for repeated measures showed that UcitrateV predicted H(+) retention (p<0.01). Less eGFR preservation in CKD 2 patients without metabolic acidosis was associated with increased H(+) retention that was predicted by decreased UcitrateV.

Goldsweig, A. M., H. J. Tak, L. W. Chen, H. D. Aronow, B. Shah, D. S. Kolte, P. Velagapudi, N. Desai, M. Szerlip and J. D. Abbott (2019). “The Evolving Management of Aortic Valve Disease: 5-Year Trends in SAVR, TAVR, and Medical Therapy.” Am J Cardiol Jun 7. [Epub ahead of print].

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Aortic stenosis (AS) and regurgitation (AR) may be treated with surgical aortic valve replacement (SAVR), transcatheter AVR (TAVR), or medical therapy (MT). Data are lacking regarding the usage of SAVR, TAVR, and MT for patients hospitalized with aortic valve disease and the characteristics of the patients and hospitals associated with each therapy. From the Nationwide Readmissions Database, we determined utilization trends for SAVR, TAVR, and MT in patients with aortic valve disease admitted from 2012 to 2016 for valve replacement, heart failure, unstable angina, non-ST-elevation myocardial infarction, or syncope. We also performed multinomial logistic regressions to investigate associations between patient and hospital characteristics and treatment. Among 366,909 patients hospitalized for aortic valve disease, there was a 48.1% annual increase from 2012 through 2016. Overall, 19.9%, 6.7%, and 73.4% of patients received SAVR, TAVR, and MT, respectively. SAVR decreased from 21.9% in 2012 to 18.5% in 2016, whereas TAVR increased from 2.6% to 12.5%, and MT decreased from 75.5% to 69.0%. Older age, female sex, greater severity of illness, more admission diagnoses, not-for-profit hospitals, large hospitals, and urban teaching hospitals were associated with greater use of TAVR. In multivariable analysis, likelihood of TAVR relative to SAVR increased 4.57-fold (95% confidence interval 4.21 to 4.97). TAVR has increased at the expense of both SAVR and MT, a novel finding. However, this increase in TAVR was distributed inequitably, with certain patients more likely to receive TAVR certain hospitals more likely to provide TAVR. With the expected expansion of indications, inequitable access to TAVR must be addressed.