Baylor Research Institute

McCullough, P. A., A. Vasudevan, L. R. Lopez, C. Swift, M. Peterson, J. Bennett-Firmin, R. Schiffmann and T. Bottiglieri (2016). “Oxidative stress reflected by increased f2-isoprostanes is associated with increasing urinary 11-dehydro thromboxane b2 levels in patients with coronary artery disease.” Thromb Res 148: 85-88.

Full text of this article.

Acetylsalicylic acid (ASA, aspirin) is widely prescribed as an aid in primary and secondary prevention of coronary artery disease (CAD) as it inhibits > 95% of platelet cyclooxygenase-1 (COX-1) activity, reducing the production of thromboxane A2 (TxA2) [1]. However, the non-platelet inflammatory COX-2 pathway remains active minimally affected by ASA. Based on the clinical development of complications or on laboratory tests, an inadequate response to ASA has been referred to as “aspirin resistance” [2] which is associated with increased risk of adverse outcomes [3]. Oxidative stress has been recently recognized as a relevant underlying mechanism to explain incomplete ASA response. Along with the enzymatic pathways (COX-1; COX-2), there is a non-enzymatic arachidonic acid pathway that produces F2-isoprostanes by oxidative stress damage which can directly activate platelets by stimulating platelet thromboxane prostanoid receptors (TPR) [4] and is not affected by ASA [5]. 8-isoprostaglandin-F2α (8-isoPGF2α) is considered a reliable laboratory biomarker of in vivo oxidative stress and a reliable noninvasive measurement of lipid peroxidation [6]. We investigated the association of oxidative stress (urinary 8-isoPGF2α) and the adequacy of inhibition of COX-1 (urinary 11-dehydro thromboxane B2 [11dhTxB2]).

Shahbazov, R., G. Yoshimatsu, W. Z. Haque, O. S. Khan, G. Saracino, M. C. Lawrence, P. T. Kim, N. Onaca, B. Naziruddin and M. F. Levy (2016). “Clinical effectiveness of a pylorus-preserving procedure on total pancreatectomy with islet autotransplantation.” Am J Surg: 2016 Oct [Epub ahead of print].

Full text of this article.

BACKGROUND: The impact of pylorus preserving procedures (PP) on total pancreatectomy with islet autotransplantation (TPIAT) has not been examined. This study aimed to investigate the clinical impact of the PP on TPIAT. METHODS: The Baylor Simmons Transplant Institute database was queried to identify seventy-three patients who underwent TPIAT from 2006 to 2014. All patients were investigated in postoperative complications, long-term nutritional status, and graft function. RESULTS: Patients with PP did not face worse outcomes in terms of delayed gastric emptying and length of hospital stay. Also, nutritional status and metabolic outcome, such as body weight, serum albumin level, serum vitamin level, HbA1c level, graft survival rate and insulin independent rate, were similar between both groups. CONCLUSIONS: Clinical results including the graft function indicated that patients undergoing TPIAT with PP did not amplify surgical complications such as delayed gastric emptying and showed no significant advantage of nutrition and metabolic outcome.

Salisbury, D., S. J. Driver, M. Reynolds, M. Bennett, L. B. Petrey and A. M. Warren (2016). “Hospital-based health care after traumatic brain injury.” Arch Phys Med Rehabil: 2016 Oct [Epub ahead of print].

Full text of this article.

OBJECTIVE: To investigate trends of hospital-based health care utilization after admission to a Level 1 trauma center following acute traumatic brain injury (TBI). DESIGN: Retrospective review. SETTING: Large urban trauma hospital and a hospital council data registry consisting of 88 member institutions (>150 hospitals) covering 15,000 square miles. PARTICIPANTS: All patients admitted to a Level I trauma center between January 2006 – June 2014 who experienced an acute TBI based on ICD-9 coding. INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: Included the incidence and type of select hospital-based services received. Analyses were also categorized based on demographic and injury-related information. RESULTS: There were 5,291 patients with newly acquired TBI admitted; 512 died, leaving 4,779 patients for inclusion into the final analysis. Additional healthcare utilization from January 2006-June 2014 was recorded for 3,158 patients (66%), totaling 12,307 encounters with a median of 3 encounters (IQR: 1-5), and a maximum of 102 encounters. The vast majority of non-admission urgent or procedural visits (96%) and inpatient encounters (93%) occurred in the first year. Of all the additional encounters, 9,769 visits were non-admission urgent or procedural visits (79%) with a median charge of $1,955, and most common type of encounter being elective (46%), followed by medical emergency (29%). Of the remaining 2,538 (21%) inpatient encounters, the mean length of stay was 6 days with median charge of $28,450, and medical emergency (39%) and elective admissions (33%) again being the most common encounter type. CONCLUSIONS: This analysis encompasses healthcare utilization across the range of TBI severity and numerous hospital systems allowing for a more comprehensive and objective identification of reasons for readmission. This represents an initial step to developing a preventative intervention to manage secondary complications post-injury.

Christensen, K. E., W. Hou, R. H. Bahous, L. Deng, O. V. Malysheva, E. Arning, T. Bottiglieri, M. A. Caudill, L. A. Jerome-Majewska and R. Rozen (2016). “Moderate folic acid supplementation and mthfd1-synthetase deficiency in mice, a model for the r653q variant, result in embryonic defects and abnormal placental development.” Am J Clin Nutr 104(5): 1459-1469.

Full text of this article.

BACKGROUND: Moderately high folic acid intake in pregnant women has led to concerns about deleterious effects on the mother and fetus. Common polymorphisms in folate genes, such as methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase-formyltetrahydrofolate synthetase (MTHFD1) R653Q, may modulate the effects of elevated folic acid intake. OBJECTIVES: We investigated the effects of moderate folic acid supplementation on reproductive outcomes and assessed the potential interaction of the supplemented diet with MTHFD1-synthetase (Mthfd1S) deficiency in mice, which is a model for the R653Q variant. DESIGN: Female Mthfd1S+/+ and Mthfd1S+/- mice were fed a folic acid-supplemented diet (FASD) (5-fold higher than recommended) or control diets before mating and during pregnancy. Embryos and placentas were assessed for developmental defects at embryonic day 10.5 (E10.5). Maternal folate and choline metabolites and gene expression in folate-related pathways were examined. RESULTS: The combination of FASD and maternal MTHFD1-synthetase deficiency led to a greater incidence of defects in E10.5 embryos (diet x maternal genotype, P = 0.0016; diet x embryonic genotype, P = 0.054). The methylenetetrahydrofolate reductase (MTHFR) protein and methylation potential [ratio of S-adenosylmethionine (major methyl donor):S-adenosylhomocysteine) were reduced in maternal liver. Although 5-methyltetrahydrofolate (methylTHF) was higher in maternal circulation, the methylation potential was lower in embryos. The presence of developmental delays and defects in Mthfd1S+/- embryos was associated with placental defects (P = 0.003). The labyrinth layer failed to form properly in the majority of abnormal placentas, which compromised the integration of the maternal and fetal circulation and presumably the transfer of methylTHF and other nutrients. CONCLUSIONS: Moderately higher folate intake and MTHFD1-synthetase deficiency in pregnant mice result in a lower methylation potential in maternal liver and embryos and a greater incidence of defects in embryos. Although maternal circulating methylTHF was higher, it may not have reached the embryos because of abnormal placental development; abnormal placentas were observed predominantly in abnormally developed embryos. These findings have implications for women with high folate intakes, particularly if they are polymorphic for MTHFD1 R653Q.

Swank, C., S. Shearin, S. Cleveland and S. Driver (2016). “Auditing the physical activity and parkinson disease literature using the behavioral epidemiologic framework.” Pm r: 2016 Oct [Epub ahead of print].

Full text of this article.

Motor and non-motor symptoms associated with Parkinson’s disease (PD) place individuals at greater risk of sedentary behaviors and comorbidities. Physical activity is one modifiable means to improving health and reducing risk of morbidity. We applied a behavioral framework to classify existing research on physical activity and PD to describe the current evolution and inform knowledge gaps in this area. Research placed in Phase 1 establishes links between physical activity and health-related outcomes; Phase 2 develops approaches to quantify physical activity behavior; Phase 3 identifies factors associated with implementation of physical activity behaviors; Phase 4 assesses the effectiveness of interventions to promote activity; Phase 5 disseminates evidence-based recommendations. Peer reviewed literature was identified by searching PubMed, Google Scholar, and EBSCO-host. We initially identified 266 potential articles. After further review we excluded 109 articles leaving 178 included articles. Of these, 75.84% were categorized into Phase 1 (n=135), 10.11% in Phase 2 (n=18), 9.55% into Phase 3 (n=17), 3.37% into Phase 4 (n=6), and 1.12% into Phase 5 (n=2). By applying the behavioral framework to the physical activity literature for people with PD, we suggest this area of research is nascent with more than 75% of the literature in Phase 1.