Browsing by Author "Sun, Seungyup"

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    Association of Socioeconomic Status With Relapse After Ponseti Method Treatment of Idiopathic Clubfeet
    (Sage, 2022-08-26) Akinyoola, Lawrence A.; Gunderson, Zachary; Sun, Seungyup; Fitzgerald, Ryan; Caltoum, Christine B.; Christman, Tyler W.; Bielski, Robert; Loder, Randall T.; Medicine, School of Medicine
    Background: The Ponseti method is today's standard treatment of idiopathic talipes equinovarus (ITEV). Compliance with foot abduction bracing (FABO) and socioeconomic factors have been shown to impact treatment outcome. We wished to further study socioeconomic factors using the Area Deprivation Index (ADI), a more comprehensive way to evaluate socioeconomic status, which has not been done before. Methods: All TEV patients from 2010 through 2019 treated with the Ponseti method were reviewed. Standard demographic variables, as well as the number of casts to complete initial correction, FABO compliance, and occurrence of relapse were tabulated. Socioeconomic level was quantified with the 2018 ADI. Results: There were 168 children; 151 had typical and 17 complex TEV. Average follow-up was 4.3 ± 1.8 years; relapse occurred in 46%. There were no significant differences in the percentage of relapse by sex, race, or ADI. FABO noncompliance was present in 46%. Relapse increased with increasing time of follow-up and FABO noncompliance (76% vs 21%, P < 10-6). Multivariate logistic regression analysis revealed that only FABO compliance and length of follow-up were associated with relapse. The OR of relapse for FABO noncompliance was 17.9 (7.6, 42.4, P < 10-6) and for follow-up >4 years the OR was 4.97 (2.1, 11.70, P = .0003). Conclusion: The outcome of the Ponseti method for TEV treatment is dependent on local circumstances. In our state, socioeconomic status, as determined by the ADI, was not associated with the occurrence of relapse. Thus, each center needs to assess its results, and analyze its own reasons for relapse. There were no other demographic variables associated with relapse except FABO compliance and length of follow-up. Parents should be strongly advised that FABO compliance and follow-up appears paramount to achieving the best results, and that complex TEV are at greater risk for relapse.
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    The Effects of High Fat Diet, Bone Healing, and BMP-2 Treatment on Endothelial Cell Growth and Function
    (Elsevier, 2021-05) Bhatti, Fazal Ur Rehman; Dadwal, Ushashi C.; Valuch, Conner R.; Tewari, Nikhil P.; Awosanya, Olatundun D.; Staut, Caio de Andrade; Sun, Seungyup; Mendenhall, Stephen K.; Perugini, Anthony J., III; Nagaraj, Rohit U.; Battini, Hanisha L.; Nazzal, Murad K.; Blosser, Rachel J.; Maupin, Kevin A.; Childress, Paul J.; Li, Jiliang; Kacena, Melissa A.; Orthopaedic Surgery, School of Medicine
    Angiogenesis is a vital process during the regeneration of bone tissue. The aim of this study was to investigate angiogenesis at the fracture site as well as at distal locations from obesity-induced type 2 diabetic mice that were treated with bone morphogenetic protein-2 (BMP-2, local administration at the time of surgery) to heal a femoral critical sized defect (CSD) or saline as a control. Mice were fed a high fat diet (HFD) to induce a type 2 diabetic-like phenotype while low fat diet (LFD) animals served as controls. Endothelial cells (ECs) were isolated from the lungs (LECs) and bone marrow (BMECs) 3 weeks post-surgery, and the fractured femurs were also examined. Our studies demonstrate that local administration of BMP-2 at the fracture site in a CSD model results in complete bone healing within 3 weeks for all HFD mice and 66.7% of LFD mice, whereas those treated with saline remain unhealed. At the fracture site, vessel parameters and adipocyte numbers were significantly increased in BMP-2 treated femurs, irrespective of diet. At distal sites, LEC and BMEC proliferation was not altered by diet or BMP-2 treatment. HFD increased the tube formation ability of both LECs and BMECs. Interestingly, BMP-2 treatment at the time of surgery reduced tube formation in LECs and humeri BMECs. However, migration of BMECs from HFD mice treated with BMP-2 was increased compared to BMECs from HFD mice treated with saline. BMP-2 treatment significantly increased the expression of CD31, FLT-1, and ANGPT2 in LECs and BMECs in LFD mice, but reduced the expression of these same genes in HFD mice. To date, this is the first study that depicts the systemic influence of fracture surgery and local BMP-2 treatment on the proliferation and angiogenic potential of ECs derived from the bone marrow and lungs.
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    The Effects of SRT1720 Treatment on Endothelial Cells Derived from the Lung and Bone Marrow of Young and Aged, Male and Female Mice
    (MDPI, 2021-10-14) Dadwal, Ushashi Chand; Bhatti, Fazal Ur Rehman; Awosanya, Olatundun Dupe; Staut, Caio de Andrade; Nagaraj, Rohit U.; Perugini, Anthony Joseph, III.; Tewari, Nikhil Prasad; Valuch, Conner Riley; Sun, Seungyup; Mendenhall, Stephen Kyle; Zhou, Donghui; Mostardo, Sarah Lyn; Blosser, Rachel Jean; Li, Jiliang; Kacena, Melissa Ann; Orthopaedic Surgery, School of Medicine
    Angiogenesis is critical for successful fracture healing. Age-related alterations in endothelial cells (ECs) may cause impaired bone healing. Therefore, examining therapeutic treatments to improve angiogenesis in aging may enhance bone healing. Sirtuin 1 (SIRT1) is highly expressed in ECs and its activation is known to counteract aging. Here, we examined the effects of SRT1720 treatment (SIRT1 activator) on the growth and function of bone marrow and lung ECs (BMECs and LECs, respectively), derived from young (3-4 month) and old (20-24 month) mice. While aging did not alter EC proliferation, treatment with SRT1720 significantly increased proliferation of all LECs. However, SRT1720 only increased proliferation of old female BMECs. Vessel-like tube assays showed similar vessel-like structures between young and old LECs and BMECs from both male and female mice. SRT1720 significantly improved vessel-like structures in all LECs. No age, sex, or treatment differences were found in migration related parameters of LECs. In males, old BMECs had greater migration rates than young BMECs, whereas in females, old BMECs had lower migration rates than young BMECs. Collectively, our data suggest that treatment with SRT1720 appears to enhance the angiogenic potential of LECs irrespective of age or sex. However, its role in BMECs is sex- and age-dependent.
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    Idiopathic Slipped Capital Femoral Epiphysis: Demographic Differences and Similarities between Stable, Unstable, and Valgus Types
    (MDPI, 2023-09-15) Loder, Randall T.; Gunderson, Zachary; Sun, Seungyup; Orthopaedic Surgery, School of Medicine
    Idiopathic slipped capital femoral epiphysis (SCFE) is a known disorder in pre/adolescent children with vague hip/knee pain. We wished to study the demographic differences between stable varus, unstable varus, and valgus idiopathic SCFEs using a retrospective review over a 10-year period of SCFE children seen at a tertiary children’s hospital. Standard demographic data was collected, and radiographs were measured to determine the Southwick angle and status of the tri-radiate cartilage. There were 190 patients; 138 had stable varus SCFEs, 45 unstable varus SCFEs, and 7 valgus SCFEs. All unstable SCFEs were varus, and all valgus SCFEs were stable. There were significant differences between the three groups by age at diagnosis, sex, race, SCFE severity, weight percentile, and duration of symptoms. The average age at diagnosis was 11.0 ± 1.2, 11.8 ± 1.8, and 12.3 ± 1.7 years for the valgus, unstable varus, and stable varus groups (p = 0.019), and similarly, SCFE severity was 25° ± 15°, 48° ± 18°, and 35° ± 19° (p = 0.0002) for the three same groups. Patients with valgus SCFEs were mostly female (86%) compared to the stable varus (39.9%) and unstable (47%) groups (p = 0.05) and mostly non-White (86%) (0.011). The duration of symptoms was 4.1 ± 4.1, 2.3 ± 5.0, and 4.5 ± 5.0 months for the valgus, unstable varus, and stable varus groups (p = 0.00005). These three types of idiopathic SCFEs demonstrated differences by age at diagnosis, sex, race, weight percentile, and duration of symptoms.
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    No pain, no gain? The effects of pain-promoting neuropeptides and neurotrophins on fracture healing
    (Elsevier, 2020-02) Sun, Seungyup; Diggins, Nicklaus H.; Gunderson, Zachary J.; Fehrenbacher, Jill C.; White, Fletcher A.; Kacena, Melissa A.; Orthopaedic Surgery, School of Medicine
    Neuropeptides and neurotrophins are key regulators of peripheral nociceptive nerves and contribute to the induction, sensitization, and maintenance of pain. It is now known that these peptides also regulate non-neuronal tissues, including bone. Here, we review the effects of numerous neuropeptides and neurotrophins on fracture healing. The neuropeptides calcitonin-gene related peptide (CGRP), substance P (SP), vasoactive intestinal peptide (VIP), and pituitary adenylate cyclase-activating peptide (PACAP) have varying effects on osteoclastic and osteoblastic activity. Ultimately, CGRP and SP both accelerate fracture healing, while VIP and PACAP seem to negatively impact healing. Unlike the aforementioned neuropeptides, the neurotrophins nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) have more uniform effects. Both factors upregulate osteoblastic activity, osteoclastic activity, and, in vivo, stimulate osteogenesis to promote fracture healing. Future research will need to clarify the exact mechanism by which the neuropeptides and neurotrophins influence fracture healing. Specifically, understanding the optimal expression patterns for these proteins in the fracture healing process may lead to therapies that can maximize their bone-healing capabilities and minimize their pain-promoting effects. Finally, further examination of protein-sequestering antibodies and/or small molecule agonists and antagonists may lead to new therapies that can decrease the rate of delayed union/nonunion outcomes and fracture-associated pain.
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    Slipped Capital Femoral Epiphysis Associated With Athletic Activity
    (Sage, 2023) Loder, Randall T.; Gunderson, Zachary J.; Sun, Seungyup; Liu, Raymond W.; Novais, Eduardo V.; Orthopaedic Surgery, School of Medicine
    Background: Little data exist regarding the association of slipped capital femoral epiphysis (SCFE) and sporting activities. Hypothesis: There is no association between SCFE and sporting activities. Study design: Retrospective review of all SCFE cases at our institution from 2010 through March 2021. Level of evidence: Level 3. Methods: All patients with idiopathic SCFE were reviewed looking for the presence/absence of sporting activities and symptom onset. Also collected were the age, symptom duration, and weight/height of the patient, sex, race, and stable/unstable nature of the SCFE. The severity of the SCFE was measured using the lateral epiphyseal-shaft angle. Results: There were 193 children (110 boys, 83 girls) with idiopathic SCFEs. The SCFE was stable in 147, unstable in 45, and unknown in 1. The average age was 12.1 ± 1.8 years, average SCFE angle 38° ± 20° and symptom duration 4.0 ± 5.1 months. An association with a sporting activity was present in 64 (33%). The sporting activity was basketball (18), football (11), baseball/softball (10), and others (23). Football, basketball, and soccer predominated in boys, baseball and running sports were equal between boys and girls, and cheerleading/gymnastics/dancing predominated in girls. Differences showed that those involved in sports had a slightly lower body mass index (BMI) (88th percentile vs 95th percentile, P = 0.00). There were no differences between those involved and those not those involved in sporting activities for symptom duration, SCFE severity, sex, race, or stable/unstable SCFE type. Conclusion: Sporting activities are associated with the onset of symptoms in 1 of 3 of patients with SCFE, refuting the null hypothesis. Clinical relevance: A high level of suspicion for SCFE should be given when any peripubertal athlete presents with hip or knee pain regardless of BMI/obesity status, and appropriate imaging performed.
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    The Effects of Bone Morphogenetic Protein 2 and Thrombopoietin Treatment on Angiogenic Properties of Endothelial Cells Derived from the Lung and Bone Marrow of Young and Aged, Male and Female Mice
    (Wiley, 2021) Dadwal, Ushashi C.; Bhatti, Fazal Ur Rehman; Awosanya, Olatundun D.; Nagaraj, Rohit U.; Perugini, Anthony J., III.; Sun, Seungyup; Valuch, Conner R.; Staut, Caio de Andrade; Mendenhall, Stephen K.; Tewari, Nikhil P.; Mostardo, Sarah L.; Nazzal, Murad K.; Battina, Hanisha L.; Zhou, Donghui; Kanagasabapathy, Deepa; Blosser, Rachel J.; Mulcrone, Patrick L.; Li, Jiliang; Kacena, Melissa A.; Orthopaedic Surgery, School of Medicine
    With an aging world population, there is an increased risk of fracture and impaired healing. One contributing factor may be aging-associated decreases in vascular function; thus, enhancing angiogenesis could improve fracture healing. Both bone morphogenetic protein 2 (BMP-2) and thrombopoietin (TPO) have pro-angiogenic effects. The aim of this study was to investigate the effects of treatment with BMP-2 or TPO on the in vitro angiogenic and proliferative potential of endothelial cells (ECs) isolated from lungs (LECs) or bone marrow (BMECs) of young (3-4 months) and old (22-24 months), male and female, C57BL/6J mice. Cell proliferation, vessel-like structure formation, migration, and gene expression were used to evaluate angiogenic properties. In vitro characterization of ECs generally showed impaired vessel-like structure formation and proliferation in old ECs compared to young ECs, but improved migration characteristics in old BMECs. Differential sex-based angiogenic responses were observed, especially with respect to drug treatments and gene expression. Importantly, these studies suggest that NTN1, ROBO2, and SLIT3, along with angiogenic markers (CD31, FLT-1, ANGPT1, and ANGP2) differentially regulate EC proliferation and functional outcomes based on treatment, sex, and age. Furthermore, treatment of old ECs with TPO typically improved vessel-like structure parameters, but impaired migration. Thus, TPO may serve as an alternative treatment to BMP-2 for fracture healing in aging owing to improved angiogenesis and fracture healing, and the lack of side effects associated with BMP-2.