Browsing by Author "Miller, James"
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Item Changes of the Nasolabial Angle Due to Orthodontic Treatment and Facial Growth(1987) Sessions, Jeffrey D.; Garner, LaForrest; Miller, James; Nelson, Charles; Shanks, James; Barton, PaulThis study addressed the quantitative changes of the Nasolabial angle, lip retraction and columellar changes due to treatment with concomitant growth. Sixty initial and final lateral headplates were examined on prepubertal children who underwent comprehensive orthodontic treatment. The angular changes in the Nasolabial angle (△NLA), Labial angle (△A) and Nasal angle (△B) were measured along with the horizontal (△H) and vertical (△V) linear changes of maxillary central incisor. Each of these five measurement changes was tested for the effects of extraction and gender. Correlations were drawn between the △NLA: △AH, △NLA: △V, NLA: △A, △NLA: △B, and △A: △H. Analysis of variance showed that extraction therapy exhibited a larger treatment change than non-extraction therapy for the NLA and upper lip, with the NLA increasing in magnitude and the Labial angle showing upper lip retraction. There was also a sex difference for the treatment change in the lower border of the nose. The only high correlation found was between the opening of the NLA and the retraction of the upper lip (NLA: △A gave r = -0.84). The other correlations were significant but low. These findings could aid in orthodontic treatment planning when changes in the upper lip and NLA will affect the facial esthetics.Item Efficacy of pre-operative stereotactic radiosurgery followed by surgical resection and correlative radiobiological analysis for patients with 1-4 brain metastases: study protocol for a phase II trial(Biomed Central, 2018-12-20) Huff, Wei X.; Agrawal, Namita; Shapiro, Scott; Miller, James; Kulwin, Charles; Shah, Mitesh; Savage, Jesse J.; Payner, Troy; Vortmeyer, Alexander; Watson, Gordon; Dey, Mahua; Neurological Surgery, School of MedicineBACKGROUND: Stereotactic radiosurgery (SRS) has emerged as a common adjuvant modality used with surgery for resectable brain metastases (BMs). However, the optimal sequence of the multi-modality therapy has not been established. The goal of the study is to evaluate 6-month local control utilizing pre-operative SRS followed by surgical resection for patients with 1-4 brain metastases. METHODS: This prospective, single arm, phase II trial will recruit patients with up to 4 brain metastases and at least one resectable lesion. All lesions will be treated with SRS and symptomatic lesions will be resected within 1-4 days after SRS. Patients will be monitored for 6-month local control, in-brain progression free survival, distant in-brain failure, rate of leptomeningeal spread, radiation necrosis and overall survival. Additionally, we will also perform correlative radiobiological molecular studies to assess the effect of radiation dosing on the tumor tissue and clinical outcomes. We expect that pre-operative SRS to the gross tumor prior to surgical resection will improve local control and decrease leptomeningeal failure. DISCUSSION: Our study is the second prospective trial to investigate the efficacy of pre-operative SRS in the treatment of multiple BMs. In addition, the correlative molecular studies will be the first to investigate early response of BMs at a cellular and genetic level in response to radiation doses and potentially provide molecular prognostic markers for local control and overall survival.Item Genomic analysis of human brain metastases treated with stereotactic radiosurgery reveals unique signature based on treatment failure(Elsevier, 2024-03-27) Shireman, Jack M.; White, Quinn; Ni, Zijian; Mohanty, Chitrasen; Cai, Yujia; Zhao, Lei; Agrawal, Namita; Gonugunta, Nikita; Wang, Xiaohu; Mccarthy, Liam; Kasulabada, Varshitha; Pattnaik, Akshita; Ahmed, Atique U.; Miller, James; Kulwin, Charles; Cohen-Gadol, Aaron; Payner, Troy; Lin, Chih-Ta; Savage, Jesse J.; Lane, Brandon; Shiue, Kevin; Kamer, Aaron; Shah, Mitesh; Iyer, Gopal; Watson, Gordon; Kendziorski, Christina; Dey, Mahua; Radiation Oncology, School of MedicineStereotactic radiosurgery (SRS) has been shown to be efficacious for the treatment of limited brain metastasis (BM); however, the effects of SRS on human brain metastases have yet to be studied. We performed genomic analysis on resected brain metastases from patients whose resected lesion was previously treated with SRS. Our analyses demonstrated for the first time that patients possess a distinct genomic signature based on type of treatment failure including local failure, leptomeningeal spread, and radio-necrosis. Examination of the center and peripheral edge of the tumors treated with SRS indicated differential DNA damage distribution and an enrichment for tumor suppressor mutations and DNA damage repair pathways along the peripheral edge. Furthermore, the two clinical modalities used to deliver SRS, LINAC and GK, demonstrated differential effects on the tumor landscape even between controlled primary sites. Our study provides, in human, biological evidence of differential effects of SRS across BM's.Item Genomic Analysis of Human Brain Metastases Treated with Stereotactic Radiosurgery Under the Phase-II Clinical Trial (NCT03398694) Reveals DNA Damage Repair at the Peripheral Tumor Edge(medRxiv, 2023-04-24) Shireman, Jack M.; White, Quinn; Agrawal, Namita; Ni, Zijian; Chen, Grace; Zhao, Lei; Gonugunta, Nikita; Wang, Xiaohu; Mccarthy, Liam; Kasulabada, Varshitha; Pattnaik, Akshita; Ahmed, Atique U.; Miller, James; Kulwin, Charles; Cohen-Gadol, Aaron; Payner, Troy; Lin, Chih-Ta; Savage, Jesse J.; Lane, Brandon; Shiue, Kevin; Kamer, Aaron; Shah, Mitesh; Iyer, Gopal; Watson, Gordon; Kendziorski, Christina; Dey, Mahua; Radiation Oncology, School of MedicineStereotactic Radiosurgery (SRS) is one of the leading treatment modalities for oligo brain metastasis (BM), however no comprehensive genomic data assessing the effect of radiation on BM in humans exist. Leveraging a unique opportunity, as part of the clinical trial (NCT03398694), we collected post-SRS, delivered via Gamma-knife or LINAC, tumor samples from core and peripheral-edges of the resected tumor to characterize the genomic effects of overall SRS as well as the SRS delivery modality. Using these rare patient samples, we show that SRS results in significant genomic changes at DNA and RNA levels throughout the tumor. Mutations and expression profiles of peripheral tumor samples indicated interaction with surrounding brain tissue as well as elevated DNA damage repair. Central samples show GSEA enrichment for cellular apoptosis while peripheral samples carried an increase in tumor suppressor mutations. There are significant differences in the transcriptomic profile at the periphery between Gamma-knife vs LINAC.Item Intraoperative detection of isocitrate dehydrogenase mutations in human gliomas using a miniature mass spectrometer(SpringerLink, 2019-12) Brown, Hannah Marie; Pu, Fan; Dey, Mahua; Miller, James; Shah, Mitesh V.; Shapiro, Scott A.; Ouyang, Zheng; Cohen-Gadol, Aaron A.; Cooks, R. Graham; Neurological Surgery, School of MedicineKnowledge of the isocitrate dehydrogenase (IDH) mutation status of glioma patients could provide insights for decision-making during brain surgery. However, pathology is not able to provide such information intraoperatively. Here we describe the first application of a miniature mass spectrometer (MS) to the determination of IDH mutation status in gliomas intraoperatively. The instrumentation was modified to be compatible with use in the operating room. Tandem MS was performed on the oncometabolite, 2-hydroxyglutarate, and a reference metabolite, glutamate, which is not involved in the IDH mutation. Ratios of fragment ion intensities were measured to calculate an IDH mutation score, which was used to differentiate IDH mutant and wild-type tissues. The results of analyzing 25 biopsies from 13 patients indicate that reliable determination of IDH mutation status was achieved (p = 0.0001, using the Kruskal-Wallis non-parametric test). With its small footprint and low power consumption and noise level, this application of miniature mass spectrometers represents a simple and cost-effective platform for an important intraoperative measurement.Item Local and distant brain control in melanoma and NSCLC brain metastases with concurrent radiosurgery and immune checkpoint inhibition(Springer, 2022-07) Le, Amy; Mohammadi, Homan; Mohammed, Toka; Burney, Heather; Zang, Yong; Frye, Douglas; Shiue, Kevin; Lautenschlaeger, Tim; Miller, James; Radiation Oncology, School of MedicineIntroduction The treatment of brain metastases with stereotactic radiosurgery (SRS) in combination with immune checkpoint inhibitors (ICI) has become more common in recent years, but there is a lack of prospective data on cancer control outcomes when these therapies are administered concurrently. Methods Data were retrospectively reviewed for patients with non-small cell lung cancer (NSCLC) and melanoma brain metastases treated with SRS at a single institution from May 2008 to January 2017. A parametric proportional hazard model is used to detect the effect of concurrent ICI within 30, 60, or 90 days of ICI administration on local control and distant in-brain control. Other patient and lesion characteristics are treated as covariates and adjusted in the regression. A frailty term is added in the baseline hazard to capture the within-patient correlation. Results We identified 144 patients with 477 total lesions, including 95 NSCLC patients (66.0%), and 49 (34.0%) melanoma patients. On multivariate analysis, concurrent SRS and ICI (SRS within 30 days of ICI administration) was not associated with local control but was associated with distant brain control. When controlling for prior treatment to lesion, number of lesions, and presence of extracranial metastases, patients receiving this combination had a statistically significant decrease in distant brain failure compared to patients that received non-concurrent ICI or no ICI (HR 0.15; 95% CI 0.05–0.47, p = 0.0011). Conclusion Concurrent ICI can enhance the efficacy of SRS. Prospective studies would allow for stronger evidence to support the impact of concurrent SRS and ICI on disease outcomes.Item Prevalence, Clinical Presentation, and Associated Sociodemographic Characteristics of Molar Hypomineralization in Indiana, USA(2020-05) Ahmed, Azza Tagelsir Mohamed; Martinez Mier, E. Angeles; Dean, Jeffrey; Soto, Amanda; Lippert, Frank; Mohammed, Aghareed; Miller, JamesMolar Hypomineralization (MH) of the first permanent molars (FPMs) and the second primary molars (SPMs) is a common developmental defect of enamel, with global prevalence of 14% and 5% respectively. Children with MH represent a special pediatric population because their affected molars have extreme susceptibility to enamel breakdown, decay and tooth sensitivity. Although the problem of MH has been described almost twenty years ago mainly through reports from Europe, there is very little information about the problem from the USA. In this dissertation, MH was explored both from the perspectives of pediatric dentists’ (PDs) and at population level. The majority of the survey respondents perceived MH prevalence to be <10% in their clinical practice (62%). The most cited clinical challenge in managing MH teeth was “long-term success of restorations” (79%). When analyzed individually, responses differed significantly for different demographics and educational characteristics of the respondents (p<0.05). At population level, MH of the FPMs (Molar Incisor Hypomineralization (MIH) cohort: 337 schoolchildren, average age 9 years) and of the SPMs (Hypomineralized Second Primary Molar (HSPM) cohort: 423 schoolchildren, average age 7 years) had prevalence estimates of 13% and 6% respectively. In the MIH cohort, water fluoridation or non-Hispanic Black race/ethnicity was significantly associated with higher collective prevalence of enamel defect (EDs) (P<0.05), but not with the prevalence of MH of the FPMs. In the HSPM cohort, race/ethnicity was significantly associated with higher overall prevalence of EDs of SPMs, but not with the HSPM prevalence. Older age group (>10 years), living in central Indiana, and water fluoridation were significantly associated with higher overall prevalence of EDs (P<0.01), but not with the HSPM prevalence. Caries experience was significantly higher in children with MH of FPMs and/or SPMs than in the group without MH. We concluded that USA pediatric dentists’ respondents were well aware of the MH problem, but demonstrated discrepancies in different aspects of the MH problem. At population level, MIH and HSPM were common presentation with prevalence estimates similar to the global figures. Certain demographic characteristics were significantly associated with the overall prevalence of the enamel defects of the examined teeth.Item Proactive, Recovery-Oriented Treatment Navigation to Engage Racially Diverse Veterans in Mental Healthcare (PARTNER-MH), a Peer-Led Patient Navigation Intervention for Racially and Ethnically Minoritized Veterans in Veterans Health Administration Mental Health Services: Protocol for a Mixed Methods Randomized Controlled Feasibility Study(JMIR, 2022-09-06) Eliacin, Johanne; Burgess, Diana J.; Rollins, Angela L.; Patterson, Scott; Damush, Teresa; Bair, Matthew J.; Salyers, Michelle P.; Spoont, Michele; Slaven, James E.; O'Connor, Caitlin; Walker, Kiara; Zou, Denise S.; Austin, Emily; Akins, John; Miller, James; Chinman, Matthew; Matthias, Marianne S.; Psychology, School of ScienceBackground: Mental health care disparities are persistent and have increased in recent years. Compared with their White counterparts, members of racially and ethnically minoritized groups have less access to mental health care. Minoritized groups also have lower engagement in mental health treatment and are more likely to experience ineffective patient-provider communication, which contribute to negative mental health care experiences and poor mental health outcomes. Interventions that embrace recovery-oriented practices to support patient engagement and empower patients to participate in their mental health care and treatment decisions may help reduce mental health care disparities. Designed to achieve this goal, the Proactive, Recovery-Oriented Treatment Navigation to Engage Racially Diverse Veterans in Mental Healthcare (PARTNER-MH) is a peer-led patient navigation intervention that aims to engage minoritized patients in mental health treatment, support them to play a greater role in their care, and facilitate their participation in shared treatment decision-making. Objective: The primary aim of this study is to assess the feasibility and acceptability of PARTNER-MH delivered to patients over 6 months. The second aim is to evaluate the preliminary effects of PARTNER-MH on patient activation, patient engagement, and shared decision-making. The third aim is to examine patient-perceived barriers to and facilitators of engagement in PARTNER-MH as well as contextual factors that may inhibit or promote the integration, sustainability, and scalability of PARTNER-MH using the Consolidated Framework for Implementation Research. Methods: This pilot study evaluates the feasibility and acceptability of PARTNER-MH in a Veterans Health Administration (VHA) mental health setting using a mixed methods, randomized controlled trial study design. PARTNER-MH is tested under real-world conditions using certified VHA peer specialists (peers) selected through usual VHA hiring practices and assigned to the mental health service line. Peers provide PARTNER-MH and usual peer support services. The study compares the impact of PARTNER-MH versus a wait-list control group on patient activation, patient engagement, and shared decision-making as well as other patient-level outcomes. PARTNER-MH also examines organizational factors that could impact its future implementation in VHA settings. Results: Participants (N=50) were Veterans who were mostly male (n=31, 62%) and self-identified as non-Hispanic (n=44, 88%) and Black (n=35, 70%) with a median age of 45 to 54 years. Most had at least some college education, and 32% (16/50) had completed ≥4 years of college. Randomization produced comparable groups in terms of characteristics and outcome measures at baseline, except for sex. Conclusions: Rather than simply documenting health disparities among vulnerable populations, PARTNER-MH offers opportunities to evaluate a tailored, culturally sensitive, system-based intervention to improve patient engagement and patient-provider communication in mental health care for racially and ethnically minoritized individuals.Item Toxicity of Radiosurgery for Brainstem Metastases(Elsevier, 2018) Patel, Ajay; Dong, Tuo; Ansari, Shaheryar; Cohen-Gadol, Aaron; Watson, Gordon; de Moraes, Fabio Ynoe; Nakamura, Masaki; Murovic, Judith; Chang, Steven D.; Hatiboglu, Mustafa Aziz; Chung, Caroline; Miller, James; Lautenschlaeger, Tim; Radiation Oncology, School of MedicineBackground Although stereotactic radiosurgery (SRS) is an effective modality in the treatment of brainstem metastases (BSM), radiation-induced toxicity remains a critical concern. To better understand how severe or life-threatening toxicity is affected by the location of lesions treated in the brainstem, a review of all available studies reporting SRS treatment for BSM was performed. Methods Twenty-nine retrospective studies investigating SRS for BSM were reviewed. Results The rates of grade 3 or greater toxicity, based on the Common Terminology Criteria for Adverse Events, varied from 0 to 9.5% (mean 3.4 ± 2.9%). Overall, the median time to toxicity after SRS was 3 months, with 90% of toxicities occurring before 9 months. A total of 1243 cases had toxicity and location data available. Toxicity rates for lesions located in the medulla were 0.8% (1/131), compared with midbrain and pons, respectively, 2.8% (8/288) and 3.0% (24/811). Conclusions Current data suggest that brainstem substructure location does not predict for toxicity and lesion volume within this cohort with median tumor volumes 0.04–2.8 cc does not predict for toxicity.