Inclusion Criteria Research Articles

12369 Clinical Experience With Inclisiran At An Academic Center

Abstract Disclosure: L. Chavez Marin: None. M. Gonzalez: None. M.F. Linton: None. B.G. Carranza Leon: None. Background: Inclisiran, a small interfering RNA (siRNA) molecule designed to inhibit proprotein convertase subtilisin/kexin type 9 (PCSK9), is the only siRNA approved for management of elevated low-density lipoprotein cholesterol (LDL-C) in both primary (for patients with familial hypercholesterolemia) and secondary prevention of cardiovascular disease. In clinical trials, Inclisiran has been shown to reduce LDL-C by more than 50% in populations at high cardiovascular risk. However, real world data about its tolerability and efficacy is still limited. Methods: We conducted an electronic medical record search to identify subjects who were prescribed Inclisiran at a lipid clinic within Vanderbilt University Medical Center (Nashville, USA). Subjects were included if they received at least one dose of Inclisiran and had pre- and post- LDL-C levels. Subjects taking other LDL-C lowering medications like statins, ezetimibe, bempedoic acid, and PCSK-9 inhibitors were included. Pre- and post- LDL-C averages were calculated and analyzed with 95% confidence intervals. The reasons for medication discontinuation were also examined. Results: Out of 69 subjects identified, only 19 met criteria for inclusion, while 32 never received a dose due to cost burden and insurance denial. The other 18 subjects were not included due to inadequate lab results at the time of data collection. In subjects who received at least one dose of Inclisiran, average pre-LDL-C was 142 mg/dL [CI: 34.7] while post-LDL-C was 77 mg/dL [CI: 24.0], notable for a 46% decrease in LDL-C levels. These subjects were also receiving another lipid lowering agent, like a statin, or had previously used a monoclonal antibody-PCSK-9 inhibitor. Those without prior use of PCSK-9 inhibitors were also analyzed. Average pre-LDL-C was 109.5 mg/dL [CI: 15.8] while post-LDL-C was 39.8 mg/dL [CI: 17.2], which revealed a 64% decrease in LDL-C levels. The main reason for discontinuation of Inclisiran was insurance denial followed by individual preference. Only one subject discontinued Inclisiran due to experiencing a generalized rash. Conclusions: Inclisiran is an effective and overall well-tolerated medication indicated for the management of elevated LDL cholesterol. Our study revealed that for individuals with above goal LDL-C, despite maximum tolerated therapy with a statin, additional LDL-C lowering benefits can be seen with Inclisiran use. However, insurance approval and cost burden seem to be the main barriers for access. Presentation: 6/3/2024

Optimizing the Diagnosis and Management of Pediatric Inducible Laryngeal Obstruction.

Pediatric inducible laryngeal obstruction (ILO) is difficult to diagnose and treat. Patients often undergo multiple specialist referrals, and long-term outcomes are not well reported. To investigate the patterns of presentation, workup, and management of children who were diagnosed with ILO at the Stollery Children's Hospital. Retrospective review with a prospective cohort of pediatric patients diagnosed with ILO from 2015 to 2023. We collected the demographic data, diagnostic tests, specialist referrals, time to diagnosis, symptom burden, associated comorbidities and aggravating factors, management, and treatment outcomes. A subset of patients was followed prospectively to determine treatment outcomes. A basic descriptive analysis was performed, and factors associated with time to resolution were studied. Seventy-eight patients met the criteria for inclusion, with 22 completing prospective questionnaires. The average age was 14 years old, and 75% were female. The majority required multiple specialist referrals. The majority were associated with exercise. Thirty-two (41%) patients had a presumed diagnosis of asthma, despite only four pulmonary function tests being consistent with asthma. Abortive breathing exercises were the most commonly employed (95%) and most successful (61%) nonsurgical management technique. Surgery was highly successful in a small cohort of patients. Median time to symptom resolution was 12 months, with 36% reporting symptoms persistent beyond 3 years. Pediatric ILO often goes undiagnosed for prolonged periods. Exercise-related symptoms are the most common. Management strategies have varied levels of success and a large proportion of patients have prolonged symptoms despite treatment, as supported by other recent evidence. 3 Laryngoscope, 2024.

9376 Successful Implementation Of Continuous Glucose Monitoring In An Internal Medicine Residency Clinic

Abstract Disclosure: A.E. Manov: None. A. Donepudi: None. A.S. Dhaliwal: None. J. Tam: None. Y. Badi: None. M. Sharaf: None. R. Haddadin: None. A. Wang: None. K. Mefferd: None. Abstract In this 3-year retrospective observational cohort study, data from fifty-one patients with type 1 or type 2 Diabetes Mellitus (DM), receiving a minimum of 3-to 4 insulin injections per day, and self-monitoring their blood glucose (SMBG) 4-times a day, were derived from our internal medicine residency primary care clinic. The patients were equipped with a Continuous Glucose Monitoring (CGM) device that shared 24-hour glucose data with the clinic. They were assigned to members of our CGM team which included internal medicine or transitional year medical residents who functioned under the supervision of a board-certified endocrinologist. In consultation with our endocrinologist, the resident assessed the patients' glucose management data and adjusted their treatment regimens bi-weekly by calling the patients, and monthly by seeing them in the clinic. The rationale of the study which was confirmatory was to show that in the Internal Medicine Residency clinic in a project governed by the medicine residents, the CGM will lead to improvement in diabetes mellitus control compared to SMBG and this can be done not only in specialized endocrine clinics. The inclusion criteria for selecting the patients were as follows: Age-18-90, diagnosis of Type 1 or type 2 Diabetes Mellitus using 3-4 Injections of Insulin per day +/- other per oral antidiabetic medications and SMBG 4 times a day, HbA1c above 7% while using SMBG, patients who can use the CGM device and receive their primary medical care in our Internal medicine Residency clinic.To assess for differences in A1C, TIR, average blood glucose, percent of time spent in mild hypoglycemia, and percent of time spent in pronounced hypoglycemia, five paired t-tests were conducted. A Bonferroni correction set the new accepted alpha level at 0.01. Significant results from the study include a reduction of HbA1c from 9.9% to 7.6%, average blood glucose decrement from 242 mg/dL to 169 mg/dl, reduction of the incidence of mild hypoglycemia below 70 mg/dl to 54 mg/dl from 4.68% to 0.76% per day, and more pronounced hypoglycemia with glucose less than 54 mg/dl from 3.1% per day to 0.2% per day. We observed a significant increase in the time in the range of blood glucose from 33% to 67% per day. Furthermore, 9.5% of the patients in this study eventually discontinued daily insulin injections and continued treatment with oral diabetic medications with or without the use of injectable GLP-1 receptors once a week.This study affirms that CGM devices significantly improved glycemic control compared to SMBG, supporting its efficacy in optimizing glycemic control in real-world clinical practice. The results imply this can be accomplished in internal medicine residency clinics and not exclusively in specialized endocrine clinics. As far as we know, this is the first study of this kind in a residency clinic in the USA. Presentation: 6/1/2024

7472 Estrogen Monotherapy for Testosterone Suppression in Gender Diverse Patients

Abstract Disclosure: C. Zhou: None. Q. Jones: None. S. Kokosa: None. C. Kelley: None. Background: For gender diverse individuals assigned male at birth (AMAB), gender-affirming hormone therapy consists of estrogen in combination with anti-androgen medications. Exogenous estrogen use results in the development of feminine secondary sex characteristics while indirectly decreasing testosterone. Anti-androgens such as spironolactone, leuprolide, finasteride, or dutasteride work to further suppress testosterone with successful suppression levels <50ng/dL. However, use of these agents increases the risk of adverse side effects like hyperkalemia, polyuria, and orthostatic hypotension, thus is not suitable for everyone. Anecdotally, estrogen monotherapy has been sufficient in reducing testosterone levels to goal in some patients, however at this time there are no known studies which evaluate estrogen monotherapy and suppression of testosterone. The purpose of this study is to retrospectively review estrogen formulations and dosages in patients who have adequate testosterone suppression in the absence of anti-androgen medications. Methods: The study was a retrospective chart review of adult patients ages 18- 84.99 AMAB receiving gender-affirming estrogen between 9/2020 and 12/2023 seen within an endocrine clinic at a single academic institution. Patients younger than 18, those receiving anti-androgen medications, and those with history of orchiectomy were excluded from the study. Charts were reviewed for estrogen formulations and dosages and total serum testosterone levels. Retrospective chart review will continue with additional data expected in 2024. Results: Ten patients between the ages of 19-81 met the inclusion criteria. Of these, 7 patients identified as transfeminine and 3 identified as nonbinary. The 3 patients who identified as non-binary were not included in analysis as their treatment goals may not align with full feminization or testosterone suppression (total serum testosterone <50ng/dL). Testosterone suppression from estrogen monotherapy was achieved in 100% (n=7) of the transfeminine patients when serum estradiol was >100pg/mL. In those who achieved testosterone suppression, 5 used injectable formulations (estradiol valerate 4-6mg weekly) and 2 used transdermal patches (range of estradiol from 0.2mg twice weekly to 0.3mg three times weekly). Conclusions: Estrogen monotherapy may be effective in suppressing testosterone without the need for anti-androgen medications. So far, this was noted most commonly with use of injectable estrogen formulations. A limitation of the study is the small sample size, however ongoing data collection is anticipated. Additional research evaluating estrogen monotherapy and testosterone suppression is needed and has potentially significant implications for simplified treatment protocols for transfeminine patients. Presentation: 6/2/2024

7239 Natural history of cystic pituitary lesions

Abstract Disclosure: B. Graner: None. D.Z. Erickson: None. D. Donegan: None. Introduction: Pituitary lesions are a common incidental finding on brain MRI, the majority of which are cystic. The natural history and management of cystic pituitary lesions have not been clearly established. Purpose: The purpose of this study is to determine the natural history of incidentally identified cystic pituitary lesions, risk factors for growth and the proportion of patients who develop clinically significant symptoms requiring surgical intervention. Methods: Pituitary MRI reports between 01/01/2015 and 12/31/2022 in patients aged 18 years and older were searched for using Dig Our Radiology Information System (DORIS) using the words “cyst” or “cystic.” Additional inclusion criteria included a follow-up pituitary MRI of at least one year duration, clinical evaluation by Endocrinology, and the presence of a cystic pituitary lesion. Patients with non-contrast exams, excessive pituitary hormone secretion, and surgery within 1 year of presentation were excluded. Patient demographics, imaging characteristics of the lesion and clinical outcomes were collected. All pituitary MRI exams were reviewed by a single neuroradiologist. Results: A total of 157 MRIs in 56 patients with a mean age of 48 ±15 years were included, 39 (70%) were female. The mean follow-up was 2.3 ± 1.4 years. The most common indication for MRI was headache (n= 18, 32%). There was no significant difference in mean maximum (max) diameter at last follow-up compared to baseline (7.45 ±4.23 vs 7.04 ±4.35 mm, p=0.06) or mean cyst volume (197.08 ±252.68 vs 201.43 ±326.18 mm3). Nine (16%) of the lesions increased in volume with a mean change in volume of 105 ±133.64 mm3/yr, note 11 (20%) decreased volume and 36 (64%) remained the same size. Using univariate logistic regression, the odds of cyst growth was greater the larger the max diameter (p= 0.03) or volume was at baseline (p= 0.02)/ Female sex (p=0.32), age at diagnosis (p=0.70) or whether the lesion was thought to be a Rathke cleft cyst or a cystic adenoma (p=0.80) were not associated with increased odds of growth. The risk of growth was higher (42 vs 9%, p=0.016) and the volume change per year was greater (67.2 ±134 vs -7 ±28 mm3, p=0.04) in those with a baseline max diameter of >10 mm. Surgery was performed in 4 patients (7%), 3 of which demonstrated lesion growth (baseline size 12-15 mm and growth rates of 59-341mm3/yr). Pathology revealed one Rathke cleft cyst, one cystic adenoma and fibrotic pituitary changes. The fourth surgical patient opted for resection at an outside facility without a demonstrated increase in size (Rathke cleft cyst). Conclusion: The majority of incidentally found cystic pituitary lesions do not increase after an average follow-up 2-3 years. Growth necessitating surgical intervention was only required in 5% of patients over the study period. A pituitary cyst >10 mm at diagnosis was associated with an increased risk of growth and therefore warrants closer follow-up. Presentation: 6/1/2024

7428 Clinical and Radiological Characterization and Outcomes of Lipid-Poor Adrenal Masses- A Multi-Center Retrospective Study

Abstract Disclosure: V. Balderrama-Brondani: None. R. Al-ward: None. K. Kiseljak-Vassiliades: None. L.M. Fishbein: None. D.A. Kirelik: None. O. Hamidi: None. R. Pishdad: None. H.K. Ghayee: None. M. Sukkari: None. S.S. Bedrose: None. A.H. Hamrahian: None. M.A. Habra: None. Background: Lipid-poor adrenal masses (LPAMs) with pre-contrast radiodensity >10 Hounsfield Units (HU) on computed tomography (CT) represent ∼25% of adrenal tumors. There is limited data about the natural history of LPAMs; therefore, we evaluated a large series of patients with LPAMs to describe the radiological and clinical features and outcomes of these cases. Methods: We conducted a multi-center retrospective cohort study of patients with LPAMs with a baseline diameter of 10-39 mm and derived from 6 institution members of the American-Australian-Asian Adrenal Alliance (A5). We excluded suspected or proven adrenal metastasis, pheochromocytoma, sarcoma, lymphoma, myelolipoma, infiltrative lesions, and adrenal hemorrhage, as well as patients with personal/familial history of genetic predisposition to adrenal neoplasms. The data is presented in percentage and median (range). Results: A total of 242 adrenal masses from 218 patients were evaluated, but only 225 (93%) masses met the inclusion criteria and were analyzed. The age was 58 (23-92), and 61% were women. LPAMs were incidentally discovered in 155 (71.1%) cases, 32 (14.7%) cases were diagnosed due to hormonal overproduction, and 17 (7.8%) due to pain/mass effect. Forty-six (21.1%) patients were on surveillance for a history of extra adrenal malignancy. Masses were unilateral in 89.9% (left side, 57.1%), with size 21 (10-38) mm, with a pre-contrast density of 24 (11-136) HU. Absolute washout was reported in 107 LPAMs and was >60% in 73 (68.2%) cases. The follow-up time was 44.4 (0.9-241) months. Hormonal overproduction developed during the follow-up in 23 (10.5%) cases as follows: cortisol in 15 (6.9%), aldosterone in 4 (1.8%), and sex hormones in 3 (1.4%) cases. LPAM growth rate was 0.03 (-2.18-11.59) cm/year. Seventy-one masses (31.5%) underwent diagnostic procedures (surgery/biopsy) with adrenocortical adenoma (n=37; 52.1%) and adrenocortical carcinoma (ACC) (n=25; 35.2%) being the two most common diagnoses. The tumor growth rate of pathologically confirmed adenomas was 0.03 (-0.30-10.50) cm/year, and of ACC was 1.31 (0.03-11.59) cm/year. A total of 154 (68.4%) LPAMs remained under surveillance at the end of the study, with a follow-up time of 51.8 (6-241) months and a tumor growth rate of 0.02 (-2.18-1.36) cm/year. Forty-five (20.6%) LPAMs decreased by 2 mm (1-13) during the study period. Cases that proved to be ACC had the most significant tumor growth rate over the study (p<0.001). The median time between the initial discovery of LPAM and the surgical resection of ACC cases was 34 (6-128) months. Conclusion: Our study showed that LPAMs carry significant malignant potential, and close long-term follow-up is warranted when surgical resection is not pursued. Prospective studies are critically needed to validate our findings and to establish high-risk molecular, imaging, and biochemical features associated with malignancy. Presentation: 6/2/2024

7128 Efficacy and Safety of Leuprolide Acetate 3M Depot in Chinese Children with Central Precocious Puberty: Interim Analysis of Multicenter, Single-Arm, Prospective Study

Abstract Disclosure: X. Luo: Advisory Board Member; Self; Takeda. L. Hou: Advisory Board Member; Self; Takeda. Y. Li: Advisory Board Member; Self; Takeda. Y. Sun: Advisory Board Member; Self; Takeda. X.K. Jin: Employee; Self; Takeda. Background: Central precocious puberty (CPP) due to early activation of the hypothalamic-pituitary-gonadal axis leads to early puberty. CPP has a negative impact on adult height. Leuprolide acetate (LA), a gonadotropin-releasing hormone agonist (GnRHa) is the standard treatment for CPP. As CPP requires prolonged treatment, a 3-month (3M) depot formulation would increase patient compliance and reduce the injection burden. This interim analysis presents the effect of LA 3M depot on the gonadotropic axis and assesses safety in children with CPP. Methods: In this open-label, multicenter, single-arm, and prospective study, 31 children with CPP were included. Key inclusion criteria were the appearance of secondary sexual characteristics below the age of eight years in girls and nine years in boys with a confirmed diagnosis of CPP. Children treated with prior GnRHa and/or having underlying medical conditions were excluded. Eligible children were treated with LA 11.25 mg subcutaneously every 12 weeks. The primary endpoint of this interim analysis was the proportion of children achieving inhibition of peak LH defined as peak LH ≤ 3.0 IU/L in the GnRH stimulation test at weeks 24. The secondary endpoint was safety analysis in the children receiving at least one dose of LA 3M depot. Results: At baseline, 30 girls and one boy were enrolled. The median (95% CI) chronological age (CA) of the girls was 8.0 (7.0, 9.0) years and the boy was 10 years old. Girls had a median height of 136.95 (131.5, 139.7) cm, weight of 30 (27, 34) kg, and BMI of 16.4 (15.1, 17.9) kg/m2. Baseline bone (BA) age was 11 (10, 11) years, and BA/CA was 1.24 (1.2, 1.3). Boy’s characteristics at baseline differed in CA (10 years), height (144 cm), and BMI (17.4 kg/m2) from girls of this cohort. Due to the data collection time points for the interim analysis, 8 out of the 31 enrolled subjects had a visit at week 24, and 30 subjects reached the week 12 visit time point and had a visit at week 12. The percentage of children achieving inhibition of peak LH (≤ 3.0 IU/L) in the GnRH stimulation test at week 12 was 100 (88.4, 100) %. At week 24, all of them achieved inhibition of LH in the GnRH stimulation test 100 (63, 100) %. Decreases in BA/CA from baseline at weeks 12 and 24 are 93 (77.9, 99.2) % and 50 (15.7, 84.3) % respectively. No progression of the Tanner stage was observed in 96.7 (82.8, 99.9) % and 100 (63, 100) % at weeks 12 and 24. At the data cut-off, 4 (13.33%) patients experienced a total of 5 treatment-emergent adverse events (TEAEs) in the safety population of 30 subjects. No grade ≥3 AE or serious AE was reported. The incidence of injection site reaction was 3.33%. Conclusion: LA at 11.25mg/3M depot effectively suppresses the gonadotropic axis at weeks 12 and 24, normalizing growth and reversibly slowing the early onset of puberty in children with CPP. LA in a 3-month injecting frequency is a safe and convenient treatment option to improve patient compliance. Presentation: 6/3/2024

12503 An Observational Study Of The Glycemic Variability In Type 1 Diabetes Mellitus Women Preconception And During Pregnancy And Its Associations With Adverse Maternal And Neonatal Outcomes

Abstract Disclosure: S. Avula: None. A.R. Ankireddypalli: None. K. Tessier: None. E.R. Seaquist: None. Background: Pregnancy in T1 diabetes mellitus (T1DM) women is associated with increased risk of maternal/fetal complications. Despite glycemic optimization during pregnancy in T1DM, offspring are at increased risk for neonatal complications. Aim: To examine glycemic variability by continuous glucose monitor (CGM) preconception and during pregnancy by trimester and assess the association with adverse maternal/fetal outcomes. Methods: This was a retrospective cohort study of pregnant patients with T1DM who used real-time CGM and delivered at a U.S. tertiary center (2012-2023). Multiple gestations, Cystic fibrosis-related diabetes (CFRD), twin or multiple births, and no valid CGM data for at least one trimester were excluded. 63 met the inclusion criteria. The primary outcome was composite neonatal morbidity (CNM), including large or small for gestational age (LGA/SGA), NICU admission, neonatal hypoglycemia, shoulder dystocia, respiratory distress syndrome, APGAR 1 or 5 minutes < 7, prematurity (<37 weeks), intrauterine growth restriction (IUGR), CPAP, and ventilator. We also collected data about maternal outcomes. Results:54 patients (86%) met at least one outcome included in the CNM. 20 patients (32%) were LGA, 3 (5%) were SGA, 32 (51%) premature, 29 (46%) required NICU admission, 44 (70%) had neonatal hypoglycemia, 3 (5%) had shoulder dystocia, 23 (37%) had respiratory distress, 22 (35%) needed CPAP, 3 (5%) were on ventilator, 11 (18%) had APGAR 1 minute <7. Among maternal outcomes, 18 (29%) developed pre-eclampsia, and 46 (73%) had a cesarean delivery. Overall, individuals with neonatal morbidity had a lower target in range (TIR) and higher target above range(TAR), average glucose, standard deviation(SD), and coefficient of variation (CV) compared with those without the primary composite, but statistical significance was seen for average glucose and TAR. For every 5 mg/dl increase in average glucose (mean of the 3-trimester values), there was a 25% increase in odds of neonatal morbidity (OR 1.25; 95% CI 1.04-1.56; p=0.028). There was a significant association between 1st trimester SD and neonatal morbidity (OR 1.11; 95% CI 1.02-1.24; p=0.027). There was a trend toward significance between the 3rd-trimester average blood glucose and neonatal morbidity (OR 1.26; 95% CI 1.02-1.63; p=0.051). Conclusion: In our single-center cohort, we found maternal average glucose and TAR, as well as first trimester SD, were significantly associated with CNM. This confirms that maternal hyperglycemia and demonstrates that first trimester SD are associated with poorer neonatal outcomes. Presentation: 6/1/2024

7472 Estrogen Monotherapy for Testosterone Suppression in Gender Diverse Patients

Abstract Disclosure: C. Zhou: None. Q. Jones: None. S. Kokosa: None. C. Kelley: None. Background: For gender diverse individuals assigned male at birth (AMAB), gender-affirming hormone therapy consists of estrogen in combination with anti-androgen medications. Exogenous estrogen use results in the development of feminine secondary sex characteristics while indirectly decreasing testosterone. Anti-androgens such as spironolactone, leuprolide, finasteride, or dutasteride work to further suppress testosterone with successful suppression levels <50ng/dL. However, use of these agents increases the risk of adverse side effects like hyperkalemia, polyuria, and orthostatic hypotension, thus is not suitable for everyone. Anecdotally, estrogen monotherapy has been sufficient in reducing testosterone levels to goal in some patients, however at this time there are no known studies which evaluate estrogen monotherapy and suppression of testosterone. The purpose of this study is to retrospectively review estrogen formulations and dosages in patients who have adequate testosterone suppression in the absence of anti-androgen medications. Methods: The study was a retrospective chart review of adult patients ages 18- 84.99 AMAB receiving gender-affirming estrogen between 9/2020 and 12/2023 seen within an endocrine clinic at a single academic institution. Patients younger than 18, those receiving anti-androgen medications, and those with history of orchiectomy were excluded from the study. Charts were reviewed for estrogen formulations and dosages and total serum testosterone levels. Retrospective chart review will continue with additional data expected in 2024. Results: Ten patients between the ages of 19-81 met the inclusion criteria. Of these, 7 patients identified as transfeminine and 3 identified as nonbinary. The 3 patients who identified as non-binary were not included in analysis as their treatment goals may not align with full feminization or testosterone suppression (total serum testosterone <50ng/dL). Testosterone suppression from estrogen monotherapy was achieved in 100% (n=7) of the transfeminine patients when serum estradiol was >100pg/mL. In those who achieved testosterone suppression, 5 used injectable formulations (estradiol valerate 4-6mg weekly) and 2 used transdermal patches (range of estradiol from 0.2mg twice weekly to 0.3mg three times weekly). Conclusions: Estrogen monotherapy may be effective in suppressing testosterone without the need for anti-androgen medications. So far, this was noted most commonly with use of injectable estrogen formulations. A limitation of the study is the small sample size, however ongoing data collection is anticipated. Additional research evaluating estrogen monotherapy and testosterone suppression is needed and has potentially significant implications for simplified treatment protocols for transfeminine patients. Presentation: 6/2/2024

Anterior Disc Displacement and Cortication Patterns in the Temporomandibular Joint.

BACKGROUND Anterior reduction disc displacement (ARDD) of the temporomandibular joint (TMJ) can present with pain and clicking of the jaw when chewing. This study aimed to evaluate the relationship between articular eminence cortication (AEC) and mandibular condyle cortication (MCC) in 81 patients with ARDD of the TMJ using cone beam computed tomography (CBCT) imaging. MATERIAL AND METHODS We examined images of 142 patients who applied to the outpatient clinic between 2022 and 2024 for various reasons and whose radiographic records included CBCT and MRI images. Sixty-one patients who did not meet the inclusion criteria were excluded from the study. MRI images of the remaining 81 patients were analyzed and evaluated for the presence of ARDD. Subsequently, all mandibular condylar processes and articular eminences included in the study were examined by CBCT and the degree of cortication was classified and noted. The relationship between MCC and AEC and ARDD was evaluated with the SPSS 23.0 program (SPSS, Chicago, IL, USA). RESULTS ARDD was observed in 46 (28.4%) of 162 condyles examined. Type 1 cortications were observed in 8 (17.4%), type 2 in 36 (78.3%), and type 3 in 2 (4.3%) of the condyles with disc displacement; 80.0% (8) of type 2 cortications were found in patients with ARDD (P<0.001), and 75.0% of type 3 cortication was observed in intact condyles (P<0.001). CONCLUSIONS This study shows that loss of AEC and MCC may be a significant factor in the diagnosis of ARDD, and decreased AEC and MCC may be a criterion for the diagnosis of ARDD.

8263 Long-term Imaging Follow-up of Non-functioning Pituitary Adenomas

Abstract Disclosure: N. Mehrotra: None. M.M. Ross: None. A.S. Chilukuri: None. S. Eljamri: None. C. Ewing: None. S. Patel: None. V. Patel: None. L.B. Siegel: None. D. Sistla: None. R.K. Shariff: None. P.K. Fazeli: None. Pituitary adenomas are common, affecting ∼15% of the population. Once a pituitary adenoma has been identified on imaging, an evaluation is undertaken for pituitary hormone excess and for pituitary hormone deficiency in the setting of larger adenomas (typically 1cm in size or greater). Hormone-producing or functioning pituitary adenomas are typically treated with medical or surgical therapy, but non-functioning pituitary adenomas can be followed conservatively if they are not contributing to morbidity. The natural history of non-functioning pituitary adenomas has not been well characterized and therefore although guidelines recommend follow-up pituitary imaging, there are no specific guidelines addressing how frequently or for how long these lesions should be followed. Our aim was to describe the clinical history of non-functioning pituitary adenomas using long-term clinical data from a large academic health system. We identified 791 patients who met our inclusion criteria of having more than one brain/pituitary MRI performed at least 3 months apart with a suspected non-functioning adenoma identified on the initial MRI. Each medical record was individually reviewed to confirm whether the adenoma was non-functioning based on clinical/biochemical evaluation. Patients were a median [interquartile range] of 48.3 [34.4, 63.6] years of age at the time of first MRI and 65% (n=517) were women. At presentation, 66% (n=523) of the pituitary adenomas were microadenomas (&amp;lt; 1 cm in size) and 34% were macroadenomas (&amp;gt; 1 cm). All patients had an MRI repeated at least 3 months after the initial MRI with median time of total imaging follow-up of 39.8 [17.0, 75.6] months. During follow-up, 658 patients were noted to have a stable lesion or a decrease in size of the adenoma. Patients whose lesion was noted to grow on MRI were slightly older than those who did not have growth (growth: 57.1 [41.9, 70.3] years versus no growth: 46.8 [33.7, 62.3] years, p&amp;lt; 0.0001). There were no differences with respect to BMI, hypopituitarism, smoking history or alcohol use between those with growth versus those without growth. Seventy-eight patients (9.9%) had surgical resection of their adenoma during follow-up. The most common indication for surgery was growth of the lesion (n=27), followed by visual changes (n=22). In the patients with a microadenoma at presentation, 90.8% remained stable in size or decreased in size during a median follow-up of 43.2 [20.5, 78.6] months. Only 2.3% of patients with a microadenoma at presentation underwent surgical resection during follow-up. In conclusion, the majority of non-functioning pituitary adenomas remain stable during prolonged imaging follow-up. Further study is needed to determine predictors of growth of non-functioning pituitary adenomas. Presentation: 6/2/2024

12426 Performance Of Dehydroepiandrosterone-Sulphate In Diagnosing Mild Autonomous Cortisol Secretion: A Systematic Review And Meta-Analysis

Abstract Disclosure: J. Saini: None. B. Salama: None. S.R. Chacko: None. K. Yu: None. I. Bancos: None. Objective: Measurement of baseline dehydroepiandrosterone sulfate (DHEAS) is suggested by the guidelines in support of diagnosing mild autonomous cortisol secretion (MACS). However, evidence on the diagnostic accuracy of DHEAS in MACS is difficult to interpret due to differences in the diagnostic cutoffs, small sample size, and heterogeneous reference standards. We aimed to conduct a systematic review and meta-analysis of published literature to assess the performance of DHEAS in diagnosing MACS, as defined in the 2023 guidelines. Methods: A comprehensive search was conducted using several databases from each database’s inception to January 8th, 2024. Databases include Ovid MEDLINE (R) and Epub Ahead of Print, In-Process &amp; Other Non-Indexed Citations, and Daily, Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Databases of Systematic Reviews, and Scopus. Only original studies of at least 20 participants were included. MACS was defined as post-dexamethasone cortisol &amp;gt;1.8 mcg/dL. QUADAS-2 was used to assess the risk of bias. Bivariate and random effects meta-analysis was used to generate pooled diagnostic accuracy estimates. Results: The initial search yielded 285 articles, and only 7 studies met the inclusion criteria. In 7 studies (1 from North America, 3 from Asia, and 3 from Europe), a total of 574 patients with MACS and 830 referent subjects (patients with adrenal tumors without MACS) were included. The mean age was specified only in 5 studies and was similar in patients with MACS (55.5 years) and referent group (53.3 years). Patients with MACS had a higher number of women (323/472, 68.4%) as compared to the referent group (352/658, 53.4%). DHEAS cutoffs studied included: lower cutoff of age-and sex-specific ranges (3 studies), 40 mcg/dL (3 studies), 60 mcg/dL (1 study), and 67.5 mcg/dL (1 study). With increasing DHEAS cutoff, sensitivity for MACS diagnosis increased, and specificity decreased. Most studies (4 studies) used the chemiluminescent immunoassay to measure DHEAS. A meta-analysis of studies using DHEAS cut-off between 40-70 mcg/dL was performed, with a pooled sensitivity of 68% (95% CI: 51-81) and a pooled specificity of 85% (78-89). The positive likelihood ratio was 4 (95% CI: 3-6; I2=36.94, P=0.175) and the negative likelihood ratio was 0.4 (0.3-0.6; I2=49.97, P=0.092). Most studies were at a high risk of bias for selection of patients, index, or reference standard. Conclusion: Based on limited heterogeneous evidence, measurement of DHEAS provides additional value in diagnosing MACS. Further larger diagnostic accuracy studies should explore various DHEAS cutoffs and consider assay variability. Presentation: 6/3/2024

Deep Learning Models for Early Detection of Ovarian Cancer: A Systematic Review of Ultrasound-Based Diagnostic Tools

Ovarian Cancer (OC) remains one of the most lethal gynecological malignancies, with a global 5-year survival rate of only 45%. This project aimed to assess the potential of deep learning-based diagnostic tools in improving early detection of ovarian cancer, particularly through ultrasound imaging. The primary research problem lies in the challenge of accurately diagnosing OC at an early stage, as traditional imaging techniques often rely on subjective interpretations, leading to inconsistent results. To address this issue, a systematic review was conducted following PRISMA guidelines, evaluating studies published between January 2018 and May 2023 in the Scopus and PubMed databases. These studies employed deep learning or artificial intelligence models for the diagnosis, prognosis, or identification of OC from ultrasound images. Of the 101 studies screened, 9 met the inclusion criteria. The included studies reported diagnostic accuracies of deep learning models ranging from 75% to 100%, with sensitivities between 85% and 99%. The conclusions indicate that deep learning models significantly enhance the diagnostic accuracy of ovarian cancer, offering a promising non-invasive tool for early detection. This research underscores the importance of integrating AI technologies into clinical practice to improve survival outcomes for OC patients.

8687 The Efficacy of GLP1 Receptor Agonists in Obese Women with PCOS in Promoting Weight Loss and Hormonal Regulation: A Systematic Review and Meta-Analysis

Abstract Disclosure: B. Austregesilo Athayde H Morais: None. V.M. Prizão: None. B. Ximenes Mendes: None. M.L. Defante: None. O.C. Martins: None. T.L. Correa: None. M.D. De Moura de Souza: None. Background: GLP1 receptor antagonists (GLP1a) are known for their efficacy in promoting weight loss among obese and diabetic patients. However, their impact on weight reduction and hormonal regulation in obese females with polycystic ovarian syndrome (PCOS) remains understudied. Therefore, we aimed to perform a meta-analysis exploring the efficacy of GLP1a against placebo for ameliorating symptoms of PCOS. Hypothesis: The use of GLP1 receptor agonists in obese women with PCOS reduces body mass index and waist circumference as well as normalizes hormone levels such as total testosterone, total cholesterol, and HOMA-IR. Methods: We conducted a comprehensive search of PubMed, Cochrane, and Scopus databases to identify trials comparing GLP1a against placebo among women diagnosed with PCOS based on the Rotterdam Criteria. Our primary outcomes of interest included body mass index (BMI), triglycerides, waist circumference, total testosterone, total cholesterol, and HOMA-IR. We performed data extraction and quality assessment for studies that met the inclusion criteria. Subsequently, we conducted a statistical analysis using Review Manager 5.1.7 (Cochrane Collaboration). We evaluated heterogeneity using I² statistics. Results: We included 176 participants from 4 studies, which all were RCTs. GLP1a was used to treat 111 (63.06%) patients. Analyzed outcomes included waist circumference (MD: −5.16 cm; 95% CI: −6.11 to −4.21; p &amp;lt; 0.00001), total testosterone (MD: −1.33; 95% CI: −2.55 to −0.12; p =0.03), BMI (MD: -2.42; 95% CI: -3.10 to -1.74; p &amp;lt; 0.00001), total cholesterol (MD: −0.04; 95% CI: −0.10 to 0.01; p =0.15), HOMA-IR (MD: −0.30; 95% CI: −0.92 to 0.32; p =0.35), Triglycerides (MD: −0.20; 95% CI: −0.30 to −0.11; p &amp;lt; 0.00001) were lower in patients treated with GLP1a compared with placebo. Most patients who discontinued the trials did so because of a nausea side effect. Conclusion: The utilization of GLP1a demonstrates efficacy in reducing body mass index (BMI), triglycerides, waist circumference, total testosterone, total cholesterol, and HOMA-IR. These results signify its viability as a favorable treatment option for managing PCOS in obese females. Presentation: 6/3/2024

The role of aryl hydrocarbon receptor agonists in the treatment of vitiligo.

Vitiligo is a chronic autoimmune disorder characterized by progressive skin depigmentation. Vitiligo significantly impacts patients' quality of life, contributing to psychological and social burdens. Despite readily available therapeutic options, many cases remain refractory to treatment, highlighting the critical need for safer and more effective therapies. Currently, ruxolitinib is the only FDA-approved medication for vitiligo; however, it carries a black box warning for serious adverse effects, including infections, malignancy, and major cardiovascular events, limiting its use. Recent studies have identified the aryl hydrocarbon receptor (AhR) as a promising therapeutic target, suggesting that AhR agonists could address the multifaceted pathogenesis of vitiligo. Adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a comprehensive search to analyze the role of AhR agonists in the treatment of vitiligo on PubMed, Cochrane, Embase, MEDLINE, and Web of Science databases on April 15, 2024. Fourteen studies met the inclusion criteria, comprising two clinical trials, two case reports, and nine basic science studies. Our search revealed that culturing AhR agonists with melanocytes upregulates melanin-synthesizing enzymes, reduces reactive oxygen species, and modulates pro-inflammatory cytokines such as IL-17A and IL-22. Tapinarof, a topical AhR agonist used commonly for the treatment of psoriasis, demonstrated clinical efficacy in repigmentation with a favorable safety profile compared to long-term steroid use. Although limited by the number of clinical studies, this review underscores the potential of using AhR agonists, such as tapinarof, as a transformative approach to vitiligo management. Future clinical trials are necessary to evaluate the safety, efficacy, and long-term outcomes of AhR agonists.

7525 Impact of Medicaid Policy Change on CGM Uptake in a Federally Qualified Health Center

Abstract Disclosure: W. Solorzano: None. L. Scarlett: None. K.P. Santiago Mangual: None. J. Borrell: None. B. Brumley: None. M. Tavares: None. C. Santana: None. T. Moin: None. E.M. Everett: None. Background: Despite the numerous benefits of CGMs in diabetes management, studies have consistently reported inequities in CGM use in racial-ethnic minorities, lower socioeconomic status, and with public insurance. In January 2022, a new California Medicaid policy switched coverage of CGMs from a Durable Medical Equipment benefit to a pharmacy benefit, creating less stringent insurance related criteria for CGM approval. We aim to evaluate the utilization of CGM use after the aforementioned policy change in an urban, multi-centered, federally qualified health center. Methods: We performed a retrospective study of patients with diabetes seen by diabetes NPs in three different clinics from January 1, 2022, through June 30, 2023. We excluded patients not managed on insulin. Patients were stratified by CGM status (current user, former user, never user). We used descriptive statistics to report patient demographics and clinical characteristics. Chi-squared test was used to evaluate differences between groups. We performed multivariate logistic regression to evaluate predictors of never using CGM. Results: We identified 239 patients who met inclusion criteria. They were primarily between the ages of 45-64 (60%), female (57%), Hispanic (84%), Spanish speaking (70%), and on Medicaid insurance (63%). Majority had a diagnosis of type 2 diabetes (93%) and managed on basal insulin plus other antidiabetic medication(s) (48%) with a mean HbA1c ≥ 10% (31%). At the end of the study period, 37% were current CGM users, 13% were former users and 51% were never users. Almost all (98%) of those who used CGMs started after January 2022.There was a statistically significant difference between CGM groups and treatment regimen (p = 0.000), insurance type (p = 0.000), type of diabetes (p = 0.000), and clinic site (p = 0.029). There was no statistically significant association between age, birth sex, race, primary language, or mean Hba1c. Most current and former users were/are on Freestyle Libre 2 (61% and 93%, respectively). Among never users, 55% had no discussion about CGM use documented in their charts. In an adjusted analysis, insurance type was the strongest predictor of never using CGM. Those without insurance on a county program, My Health LA (OR 15.5, 95% CI 3.7-65.6) or self-pay (OR 10.0, 95% CI 1.77-56.3) were more likely to be a never user. Conclusion: In an underserved population with diabetes, insurance status was the primary barrier to CGM use as demonstrated by the large uptake of CGM use after the policy change and that insurance status was the largest predictor of use. Additional studies are needed to evaluate other barriers impacting CGM uptake and adherence, clinical impact of CGM use, and patient experience. This will improve the utilization and adherence of this diabetes technology in this patient population who historically experiences more challenges with diabetes and obtaining optimal glycemic control. Presentation: 6/1/2024

Scoping review on the genotoxicity of silver nanoparticles in endodontics: therapeutic saviors or genetic saboteurs?

Silver nanoparticles (AgNPs) have gained prominence in endodontics due to their exceptional antimicrobial properties. However, concerns regarding their genotoxic potential have prompted investigations into their safety profiles. This scoping review aims to consolidate current knowledge on the genotoxic effects of AgNPs in the field of endodontics. A thorough literature search across seven electronic databases was conducted using specific keywords. Inclusion criteria included experimental studies published in English from January 1960 to March 2024, addressing the genotoxicity of AgNPs in endodontic applications. Study selection and data extraction were conducted independently. The Quality Assessment Tool For In Vitro Studies (QUIN) tool was employed to evaluate the risk of bias in each study. 5 articles were selected, of which 3 were in vitro experimental designs, while the remaining were ex vivo studies. All were published between 2009 and 2021. AgNPs have been used as root canal irrigating solutions, pulp-capping materials, and root canal sealers. Most studies employed the comet assay for genotoxic evaluation. One study was found to have a low risk of bias, while others were categorized as having a medium risk. Mixed findings were noted on the genotoxic effects of AgNPs using various assays. The genotoxic potential of AgNPs somewhat poses concerns for endodontic practices. This review highlights the need for further research to develop safer alternatives and optimize their concentrations and exposure durations.

Cats and dogs as hosts of Blastocystis – What is the evidence?

Blastocystis is one of the most common intestinal parasites observed in human and non-human hosts. Recent meta-analyses have indicated a potential role for pets such as dogs and cats as reservoir hosts of Blastocystis, but the data underpinning this hypothesis are of mixed quality. Reviewing data for 45,894 samples tested for Blastocystis by DNA-based methods and 11,908 subtype observations, a model was developed for calculating indices that could be used for evaluating individual species as natural hosts of Blastocystis, based on weighted products of positivity rates and subtype distributions. Data from cats and dogs were analysed, using other well-sampled hosts (pig, cattle, sheep, goat, and human) as references. Data from cats and dogs meeting the inclusion criteria were entered into the model. The overall positivity rates for pigs, cattle, sheep, goats, humans, dogs, and cats were 40 %, 40 %, 35 %, 28 %, 25 %, 6 %, and 5 %, respectively, with statistically significant lower positivity rates in cats and dogs (p < 0.0001). Indices indicating Blastocystis specificity to host ranged between 0.16 (humans) and 0.49 (cattle) for the reference hosts, whereas indices for cats and dogs were only 0.01 and 0.02, respectively. Finally, indices for ST specificity to host were higher for reference hosts (range, 0.66–0.93) than for cats (0.62) and dogs (0.56). Taken together, the analyses indicate that cats and dogs are not natural or reservoir hosts of Blastocystis and that the sporadic subtype pattern observed in these hosts might indicate exposure to Blastocystis through contaminated water/feed, including Blastocystis colonizing prey animals.

6711 Single Nuclei RNA-seq To Map Adipose Cellular Populations And Senescent Cells In Response To A Lifestyle Or Senolytic Intervention In Older Adults With Obesity: A Double-Blind, Placebo-Controlled, Randomized Trial

Abstract Disclosure: A. Aslamy: None. G. Connolly: None. J. Nie: None. S. Espinoza: None. M. Serra: None. N. Musi: None. It is well established that obese and older individuals are at significantly increased risk for diabetes and metabolic syndrome. However, the underlying molecular mechanisms by which increased adiposity and aging predisposes individuals to metabolic disease are not well understood. Recent data suggests that variations in adipocyte cellular populations and subpopulations influence whole body metabolism. Particularly, an increased burden of adipocyte senescent cells (cells that are in a state of replicative arrest) have been implicated in metabolic diseases. To investigate the relationship between adipose molecular signatures and cellular senescence on metabolic outcomes, we will use a novel, high-throughput, high-resolution methodology called single nuclei RNA sequencing (SnRNA-seq) to develop a transcriptomic atlas of human adipose tissue and analyze molecular profiles before and after interventions of lifestyle vs. senolytic vs. placebo. We will recruit a cohort of older obese participants (≥65 years of age; BMI = 30-39.9 kg/m2; n = 72), and conduct a double-blinded, placebo-controlled, randomized trial in which we obtain adipose biopsies to analyze cellular/molecular profiling via snRNA-seq as it relates to phenotypic measures of insulin sensitivity, glucose tolerance, beta cell function, and hepatic lipid content compared to cohorts of younger lean (18-30 years of age; BMI = 18.5-24.9 kg/m2; n = 24) and older lean (≥65 years of age; BMI = 18.5-24.9 kg/m2; n = 24) participants. Older obese participants will be randomized to one of three groups for a 10-week period: lifestyle (diet- and exercise-induced weight loss of 8-10% of body mass), senolytic (dasatinib and quercetin), or placebo. Repeat adipose biopsies and metabolic testing will be analyzed before and after intervention to assess potential changes in gene expression and associated phenotypic measures. Inclusion criteria for the older obese participants are the following: ≥65 years of age, BMI 30-39.9 kg/m2, any sex, race and ethnic group, sedentary (≤1.5h of exercise per week), and nondiabetic. Exclusion criteria include history of diabetes, participation in structured exercise &amp;gt;1.5h per week, chronic inflammatory/neurologic/autoimmune/pulmonary disorders, GI or heart disease, use of anti-arrhythmic or weight altering medications, smoking/alcohol use, previous bariatric surgery, and use of/allergy to senolytic agents. Preliminary snRNA-seq analyses of adipose biopsies from our pilot study with non-diabetic participants identified cells with elevated expression of positive regulators of senescence (CDKN1A, CDKN2A, ARG2); notably, one subpopulation of senescent adipocytes, termed NewA1, was increased with higher BMI. Overall, the findings from this study may help us gain better understanding of the aging process and identify potential molecular targets for prevention of metabolic disease. Presentation: 6/1/2024

Performance of Predictive Models in Cervical Cancer Recurrence: A Systematic Review and Meta-Analysis of Biomarkers and Prognosis

This study investigates the use of Predictive Analytics Frameworks (PAF) for identifying biomarkers of recurrent cervical cancer and predicting prognosis. It addresses the limited comprehensive evaluations of the effectiveness of predictive models in this area, despite the growing application of machine learning in healthcare. The purpose of this systematic review and meta-analysis is to assess the performance of predictive analytics models in terms of sensitivity, accuracy, specificity, and the area under the curve (AUC-ROC) for identifying cervical cancer biomarkers and predicting prognosis. To address this research problem, a systematic review and meta-analysis was conducted, covering studies published between 2014 and 2024. A total of 1,515 studies were initially identified from the PubMed and Scopus databases, with 50 research studies meeting the inclusion criteria. Repeated measures ANOVA and meta-analysis were applied using data collected over an 8-year period to evaluate recurrence trends and the predictive power of various models. The findings suggest that predictive analytics models show significant potential for improving diagnostic accuracy in identifying cervical cancer biomarkers. However, the review also highlights several limitations, including the small number of included studies, heterogeneity across studies, and potential bias in retrospective analyses. In conclusion, while predictive analytics frameworks demonstrate promise in improving cervical cancer prognosis and biomarker identification, further research is required to validate these findings and assess their broader clinical utility. The study underscores the importance of continued exploration of predictive models to enhance decision-making in oncology.