Browsing by Author "Lyssikatos, Charalampos"

Now showing 1 - 4 of 4
  • Thumbnail Image
    Item
    Copeptin Levels Before and After Transsphenoidal Surgery for Cushing Disease: A Potential Early Marker of Remission
    (Endocrine Society, 2022-04-06) Flippo, Chelsi; Tatsi, Christina; Sinaii, Ninet; De La Luz Sierra, Maria; Belyavskaya, Elena; Lyssikatos, Charalampos; Keil, Meg; Spanakis, Elias; Stratakis, Constantine A.; Pathology and Laboratory Medicine, School of Medicine
    Context: Arginine-vasopressin and CRH act synergistically to stimulate secretion of ACTH. There is evidence that glucocorticoids act via negative feedback to suppress arginine-vasopressin secretion. Objective: Our hypothesis was that a postoperative increase in plasma copeptin may serve as a marker of remission of Cushing disease (CD). Design: Plasma copeptin was obtained in patients with CD before and daily on postoperative days 1 through 8 after transsphenoidal surgery. Peak postoperative copeptin levels and Δcopeptin values were compared among those in remission vs no remission. Results: Forty-four patients (64% female, aged 7-55 years) were included, and 19 developed neither diabetes insipidus (DI) or syndrome of inappropriate anti-diuresis (SIADH). Thirty-three had follow-up at least 3 months postoperatively. There was no difference in peak postoperative copeptin in remission (6.1 pmol/L [4.3-12.1]) vs no remission (7.3 pmol/L [5.4-8.4], P = 0.88). Excluding those who developed DI or SIADH, there was no difference in peak postoperative copeptin in remission (10.2 pmol/L [6.9-21.0]) vs no remission (5.4 pmol/L [4.6-7.3], P = 0.20). However, a higher peak postoperative copeptin level was found in those in remission (14.6 pmol/L [±10.9] vs 5.8 (±1.4), P = 0.03]) with parametric testing. There was no difference in the Δcopeptin by remission status. Conclusions: A difference in peak postoperative plasma copeptin as an early marker to predict remission of CD was not consistently present, although the data point to the need for a larger sample size to further evaluate this. However, the utility of this test may be limited to those who develop neither DI nor SIADH postoperatively.
  • Thumbnail Image
    Item
    Fracture discrimination capability of ulnar flexural rigidity measured via Cortical Bone Mechanics Technology: study protocol for The STRONGER Study
    (Oxford University Press, 2024-01-04) Warden, Stuart J.; Dick, Andrew; Simon, Janet E.; Manini, Todd M.; Russ, David W.; Lyssikatos, Charalampos; Clark, Leatha A.; Clark, Brian C.; Physical Therapy, School of Health and Human Sciences
    Osteoporosis is characterized by low bone mass and structural deterioration of bone tissue, which leads to bone fragility (ie, weakness) and an increased risk for fracture. The current standard for assessing bone health and diagnosing osteoporosis is DXA, which quantifies areal BMD, typically at the hip and spine. However, DXA-derived BMD assesses only one component of bone health and is notably limited in evaluating the bone strength, a critical factor in fracture resistance. Although multifrequency vibration analysis can quickly and painlessly assay bone strength, there has been limited success in advancing a device of this nature. Recent progress has resulted in the development of Cortical Bone Mechanics Technology (CBMT), which conducts a dynamic 3-point bending test to assess the flexural rigidity (EI) of ulnar cortical bone. Data indicate that ulnar EI accurately estimates ulnar whole bone strength and provides unique and independent information about cortical bone compared to DXA-derived BMD. Consequently, CBMT has the potential to address a critical unmet need: Better identification of patients with diminished bone strength who are at high risk of experiencing a fragility fracture. However, the clinical utility of CBMT-derived EI has not yet been demonstrated. We have designed a clinical study to assess the accuracy of CBMT-derived ulnar EI in discriminating post-menopausal women who have suffered a fragility fracture from those who have not. These data will be compared to DXA-derived peripheral and central measures of BMD obtained from the same subjects. In this article, we describe the study protocol for this multi-center fracture discrimination study (The STRONGER Study).
  • Thumbnail Image
    Item
    L-β-aminoisobutyric acid, L-BAIBA, a marker of bone mineral density and body mass index, and D-BAIBA of physical performance and age
    (Springer Nature, 2023-10-11) Lyssikatos, Charalampos; Wang, Zhiying; Liu, Ziyue; Warden, Stuart J.; Brotto, Marco; Bonewald, Lynda; Biostatistics and Health Data Science, School of Medicine
    As both L- and D-BAIBA are increased with exercise, we sought to determine if circulating levels would be associated with physical performance. Serum levels of L- and D-BAIBA were quantified in 120 individuals (50% female) aged 20-85 years and categorized as either a "low" (LP), "average" (AP) or "high" performing (HP). Association analysis was performed using Spearman (S) and Pearson (P) correlation. Using Spearman correlation, L-BAIBA positively associated with (1) body mass index BMI (0.23) and total fat mass (0.19) in the 120 participants, (2) total fat mass in the 60 males (0.26), and (3) bone mineral density, BMD, (0.28) in addition to BMI (0.26) in the 60 females. In HP females, L-BAIBA positively associated with BMD (0.50) and lean mass (0.47). D-BAIBA was positively associated with (1) age (P 0.20) in the 120 participants, (2) age (P 0.49) in the LP females and (3) with gait speed (S 0.20) in the 120 participants. However, in HP males, this enantiomer had a negative association with appendicular lean/height (S - 0.52) and in the AP males a negative correlation with BMD (S - 0.47). No associations were observed in HP or AP females, whereas, in LP females, a positive association was observed with grip strength (S 0.45), but a negative with BMD (P - 0.52, S - 0.63) and chair stands (P - 0.47, S - 0.51). L-BAIBA may play a role in BMI and BMD in females, not males, whereas D-BAIBA may be a marker for aging and physical performance. The association of L-BAIBA with BMI and fat mass may reveal novel, not previously described functions for this enantiomer.
  • Thumbnail Image
    Item
    γ-Aminobutyric acids (GABA) and serum GABA/AABA (G/A) ratio as potential biomarkers of physical performance and aging
    (Springer Nature, 2023-10-10) Lyssikatos, Charalampos; Wang, Zhiying; Liu, Ziyue; Warden, Stuart J.; Bonewald, Lynda; Brotto, Marco; Biostatistics and Health Data Science, School of Medicine
    Declining physical performance with age and disease is an important indicator of declining health. Biomarkers that identify declining physical performance would be useful in predicting treatment outcomes and identifying potential therapeutics. γ-aminobutyric acid (GABA), a muscle autocrine factor, is a potent inhibitor of muscle function and works as a muscle relaxant. L-α-aminobutyric acid (L-AABA) is a biomarker for malnutrition, liver damage, and depression. We sought to determine if GABA and L-AABA may be useful for predicting physical performance. Serum levels of GABA and L-AABA were quantified in 120 individuals divided by age, sex, and physical capacity into low, average, and high performer groups. Analyses explored correlations between serum levels and physical performance. Both GABA and the ratio of GABA/AABA (G/A), but not AABA, were highly positively associated with age (Pearson correlations r = 0.35, p = 0.0001 for GABA, r = 0.31, p = 0.0007 for G/A, n = 120). GABA showed negative associations in the whole cohort with physical performance [fast gait speed, 6 min walk test (6MWT), PROMIS score, and SF36PFS raw score] and with subtotal and femoral neck bone mineral density. L-AABA was positively associated with usual gait speed, 6MWT, total SPPB score, and SF36PFS raw score in the total cohort of 120 human subjects, also with 6MWT and SF36PFS raw score in the 60 male subjects, but no associations were observed in the 60 females. As both GABA and L-AABA appear to be indicative of physical performance, but in opposite directions, we examined the G/A ratio. Unlike GABA, the G/A ratio showed a more distinct association with mobility tests such as total SPPB score, usual and fast gait speed, 6MWT, and SF36PFS raw score in the males, regardless of age and metabolic status. Serum G/A ratio could be potentially linked to physical performance in the male population. Our findings strongly suggest that GABA, L-AABA, and the G/A ratio in human serum may be useful markers for both age and physical function. These new biomarkers may significantly enhance the goal of identifying universal biomarkers to accurately predict physical performance and the beneficial effects of exercise training for older adults.