Mean Age Of Diagnosis Research Articles

#2659 Clinical characteristics of patients with minimal change disease (MCD) that evolved to focal sclerosing glomerulosclerosis (FSGS)

Abstract Background and Aims Minimal change disease (MCD) and focal sclerosing glomerulosclerosis (FSGS) are both podocytopathies and are possibly diseases that lie on a similar spectrum with FSGS being the severe form. We aim to describe the clinical and laboratory parameters along with treatment and outcomes of MCD that were found to be FSGS on repeated biopsy. Method All patients who had undergone renal biopsy in Hospital Serdang and had documented diagnosis of FSGS from January 2007 until December 2022 were identified. Data was collected and analysed using SPSS version 17. Results were expressed in mean ± standard deviation (SD) unless stated otherwise. Results Total minimal change disease were 70 patients. A total of 14 were identified as FSGS on repeated biopsy. At time of biopsy, all patients presented as relapse in nephrotic syndrome (NS). Mean age of diagnosis was 18 years for MCD while mean age of FSGS diagnosis was 23.8 years. 11 were males and two patients had positive family history of kidney disease while 10 had some form of haematuria. All patients were on steroids with 4 of them developing steroid resistance. 11 patients were on second line agents either due to steroid resistance or toxicity. Majority of patients were on azathioprine followed by cyclosporine and mycophenolate mofetil. Mean follow up was 5.7 years. Those with MCD had higher platelet (mean 462) and total cholesterol (mean 14.2) values at diagnosis of FSGS. Mean relapse after diagnosis of FSGS was 2.2 episodes. (Patients remain in remission for 31 months before relapsing) As of December 2022, 9(65%) patients had normal kidney function, 2 end stage renal disease on dialysis while 3 CKD V had passed away due to acute coronary syndrome. Conclusion Minimal change disease is part of a spectrum podocytopathies along with FSGS. Those with frequent relapses in MCD, older children with nephrotic syndrome and those with presence of haematuria may be warranted for a repeated biopsy to rule out evolution to FSGS.

#2068 Factors affecting disease progression in individuals with heterozygous COL4A3/COL4A4 pathogenic variants

Abstract Background and Aims Individuals with heterozygous pathogenic variants in COL4A3/COL4A4 or also known as autosomal dominant Alport syndrome (ADAS) are increasingly diagnosed and show a wide spectrum of disease. Factors contributing to these different outcomes are not well understood. Here we study a cohort of patients with pathogenic (P) or likely pathogenic (LP) variants in COL4A3/COL4A4 with slow and rapid progression to evaluate risk factors associated with the condition. Method A retrospective observational multicenter study was performed in a cohort of individuals with heterozygous P and LP in COL4A3/COL4A4. Criteria were established to classify patients into rapid (RP) and slow progression (SP) (Fig. 1). In this study, we compared both cohorts and identified risk factors of rapid progression using T-score for numeric variables or Chi square for categoric variables. For the numerical variables that were correlated with RP, a cut-off point was established fitting the data with a regression curve. Further analyses are ongoing. Results A total of 374 patients were studied, the progression of the disease was classified in 135 individuals: 82 with RP (60.7%) and 53 SP (39.3%). The remaining patients couldn't be classified due to age or missing data during follow-up. The mean age at diagnosis of classified patients was 46.61 years (SD 17.46), with 65% being women. Genetic variant distribution was COL4A3 38%, COL4A4 58%, and digenic 4%. At diagnosis, 72% of patients had albuminuria or proteinuria (mean age of diagnosis: 50 years). Among these, 52.7% had ACR or PCR greater than 300 or 500 mg/gCr, with mean ACR at 445.92 mg/gCr (SD 587.54, max 2240 mg/g) and mean PCR at 968.38 (SD 1422, max 10633). 94% individuals had hematuria (mean age at diagnosis: 36.27 years). Forty-nine patients (36%) had CKD G-5, with a mean age of diagnosis of 53.08 years (SD 12.42). The mean eGFR was 67.56 (SD 30.56 ml/min). Results of kidney biopsy were available for 51 patients. 73 individuals had hypertension (HTN) with a mean age at diagnosis of 46.30 years (SD 13.81). A total of 82 patients responded to personal habits questionnaire. With all the variables studied, a total of 4 main variables were associated with RP. Conclusion The main variables associated with a worse outcome in individuals with heterozygous pathogenic variants in COL4A3/COL4A4 is the presence of albuminuria/proteinuria, HTN, age at diagnosis of HTN and age at diagnosis of the disease. Smoking has also been associated with a worse outcome when an exposure time over 11.8 years. More studies are still needed to understand the reasons for the huge phenotypic variability of this condition.

Abstract GS02-04: Surgical Treatment of Women with Breast Cancer and a BRCA1 Mutation: An International Analysis of the Impact of Bilateral Mastectomy on Survival

Abstract Background: Women with breast cancer and a BRCA1 mutation face a high risk of contralateral breast cancer. For this reason, many women with a unilateral breast cancer opt for bilateral mastectomies. Some will have a contralateral prophylactic mastectomy as a second surgery. However, it is not clear to what extent this operation impacts breast cancer mortality. The objective of the current study was to evaluate the differences in survival by surgical treatment in an international cohort of women with a BRCA1 mutation and unilateral breast cancer. Methods: Eligible participants were identified from a large international cohort of women with breast cancer and a BRCA1 mutation, from 26 collaborating centres. Patients with DCIS and stage IV breast cancer were excluded. Patients with synchronous bilateral cancer were excluded. Demographic data were patient reported and clinical and treatment data were collected from medical records. Women were followed from date of breast cancer diagnosis to either date of last follow-up or date of death. Results: There were 2482 eligible participants from 26 centres from 11 countries. The mean age of breast cancer diagnosis was 43.1 years (range 18-70 years). Among those who had a unilateral mastectomy or lumpectomy, the risk of contralateral breast cancer at 20 years was 27.5%. After experiencing a contralateral cancer the hazard ratio for breast cancer death was 2.14 (95%CI 1.43-3.18), P=0.0002. The fifteen-year breast cancer specific survival in the entire cohort was 82.9%. The survival was 78.7% for those who had a unilateral mastectomy, 86.2% for those who had a lumpectomy, and 88.7% for those who had bilateral mastectomies. 529 of the women who initially underwent a unilateral surgery subsequently had a contralateral or bilateral preventive mastectomy in the follow up period. 529 of the women with unilateral surgery had a contralateral or bilateral preventive mastectomy in the follow up period. After adjusting for age of diagnosis, tumor size, nodal status, chemotherapy (yes/no) and preventive mastectomy (time dependent) the hazard ratio for breast cancer mortality for bilateral surgery versus unilateral surgery was 0.78 (95% CI 0.55-1.13), p = 0.19. Discussion: Women with a BRCA1 mutation and breast cancer who develop a contralateral breast cancer have double the risk of mortality compared to women who do not develop contralateral breast cancer. We observed a small non-significant reduction in mortality for those who had bilateral mastectomies as initial treatment, but the cohort will require longer follow up for definitive results. Women with a BRCA1 mutation should be counselled on the risks of contralateral breast cancer and make surgical decisions with this knowledge. Citation Format: Kelly Metcalfe, Jan Lubinski, Jana Soukupová, Rinat Bernstein-Molho, Mina Lee, Evans Gareth, Arvids Irmejs, Robert Fruscio, Cynthia Villareal Garza, Joanne Ngeow, Jennifer Plichta, Rinat Yerushalmi, Steven Narod. Surgical Treatment of Women with Breast Cancer and a BRCA1 Mutation: An International Analysis of the Impact of Bilateral Mastectomy on Survival [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr GS02-04.

Keratoconus presentation with respect to age, gender, and severity in Western India

Purpose: To study the demographic profile of keratoconus (KC) patients visiting a tertiary eye care hospital in Western India. Materials and Methods: This cross-sectional, observational study included newly diagnosed KC patients visiting our hospital between January 2018 and October 2022. Patient’s demographic details (self-reported age at first presentation, age at diagnosis, and sex) and mean maximum curvature (K Max) were collected. The patients were divided into age band of 5-year groups. A subanalysis of gender and severity was performed among groups. Spearman’s correlation coefficient was used to evaluate the relationship between KC severity and age. Results: A total of 536 patients with clinical KC were included. A self-reported age at first presentation was 19.4 ± 6.2 years. The mean age of diagnosis was 20.5 ± 6.0 years (range: 4–43 years). There were 61.6% (330) of males and 38.4% (206) of females (P < 0.01). The mean K Max value was 59.2 ± 13.3 diopter (D). The mean K Max was not significantly different between the sexes, with the exception of the age range of 24–28 years, where females had more severe KC than males (P = 0.02). Among the included patients, 38.6% (207) of patients were pediatrics (≤18 years), while 61.4% (329) were adults (>18 years). The mean K Max in pediatric KC (62.3 ± 15.1 D) was significantly higher than adult KC (57.3 ± 11.5), P < 0.01. Severity of KC did not correlate with the age of the patients (r = −0.20, P = 0.04). Conclusion: KC presented at a younger age with moderate-to-severe stage of the disease, indicating the need for early KC detection in our population.

The relationship between acrochordons, obesity, and metabolic syndrome in the pediatric population: A retrospective cohort study.

Acrochordons or skin tags are common benign skin growths. Several studies explored the relationship between obesity and metabolic syndrome in adults but remains unexplored in children. This was a single-center retrospective cohort study of outpatient dermatology patients between 1 January 2000 to 1 January 2021. Children under 18 years old diagnosed with acrochordons using diagnostic codes International Classification of Diseases, 10th Revision (ICD-10) L91.8 and 9th Revision (ICD-9) 701.8 were included. We collected patient demographics, past medical history, laboratory values, vital signs, and physical exam. Body mass index (BMI) was calculated and stratified into categories based on the Center for Disease Control's BMI-for-Age Growth Charts. Metabolic syndrome was diagnosed when three of the five criteria were met. Data were propensity-matched and compared with NHANES (National Health and Nutrition Examination Survey), which offered a generalizable sample to the US population. Fifty-five patients under 18 years old with a diagnosis of acrochordons were mostly Caucasian (76%) and female (64%). The mean BMI was 27.3, with 49.5% categorized as obese and 20% as overweight. The mean age of diagnosis was 10.1 years. Acrochordon predominantly appeared in the axilla. In our cohort, three patients (5.5%) met the criteria for metabolic syndrome. The prevalence of obesity (42% vs. 21%), type 2 diabetes mellitus (4.8% vs. 0.6%), hyperlipidemia (8.1% vs. 0%), and hypertension (1.6% vs. 0%) was greater in our cohort compared with NHANES. Like the adult population, acrochordons may serve as marker for metabolic disease in the pediatric population.

Head and Neck Paragangliomas: Overview of Institutional Experience.

Head and neck paragangliomas (HNPGLs) are rare and have high rates of genetic mutations. We conducted a retrospective review of 187 patients with 296 PGLs diagnosed between 1974 and 2023. The mean age of diagnosis was 48.8 years (range 10 to 82) with 69.0% female and 26.5% patients with multiple PGLs. Among 119 patients undergoing genetic testing, 70 (58.8%) patients had mutations, with SDHB (30) and SDHD (26) being the most common. The rates of metastasis and recurrence were higher among patients with SDHB mutations or SDHD mutations associated with multiple PGLs. Metabolic evaluation showed elevated plasma dopamine levels were the most common derangements in HNPGL. MRI and CT were the most common anatomic imaging modalities and DOTATATE was the most common functional scan used in this cohort. Most patients (81.5%) received surgery as the primary definitive treatment, while 22.5% patients received radiation treatment, mostly as an adjuvant therapy or for surgically challenging or inoperable cases. Systemic treatment was rarely used in our cohort. Our single-center experience highlights the need for referral for genetic testing and metabolic evaluation and for a team-based approach to improve the clinical outcomes of patients with HNPGLs.

Abstract 3404: Body weight trajectory among patients with non-small-cell lung cancer receiving immune checkpoint inhibitors

Abstract Objectives: Body weight is an important prognostic factor in patients with lung cancer. As immunotherapy involves toxicities, body weight may be affected during the treatment course. The objective of this study is to examine the trajectory of weight changes at 180 and 365 days after the initiation of immune checkpoint inhibitors (ICIs) among patients with NSCLC. Methods: Retrospective chart review and data extraction were performed among patients receiving ICIs at the Ohio State University Comprehensive Cancer Center between 2015 and 2021. Patients with NSCLC were included in this study if their initial treatment entailed a PD-1/PD-L1 ICI), either alone or in combination with chemotherapy/targeted cancer drugs, and if they also had their body weights recorded on ICI initiation and 180 days after (± 30 days) treatment initiation. A subset of these patients who had body weight data on day 365 of ICI initiation were included in additional analysis. Percentages of change in body weight relative to pre-ICI were calculated ([weight at 180 or 360 days minus pre-ICI weight] divided by pre-ICI weight x 100%) and examined by treatment regimen and pre-ICI body mass index (BMI) using t-tests. A sensitivity analysis was performed by excluding 11 patients with cachexia defined by the presence of ICD-9 (799.4) or 10 (R64) codes in their medical records. Results: A total of 554 patients with NSCLC received any ICI; 139 patients met the inclusion criteria, of which 96 had body weight data on day 365. The mean age of diagnosis was 63.8 (SD=10.1); 80% were White and 18.7% were Black. The median time on ICI was 195 days (inter-quartile range, 55-392 days) among patients with ICI only and 255 days (inter-quartile range, 126-479 days) among patients with ICI combined with chemotherapy or targeted cancer drugs. Among patients receiving ICI only, body weight increased among those with normal weight (BMI <25.0; mean change = +7.57%, P=0.013) but decreased among those classified as overweight (BMI = 25.0 to 29.9; −5.2%, P=0.037) or obese (BMI ≥30; −6.5%, P=0.025). Decreases in weight were also observed for patients with obesity and receiving a combined treatment (−9.65%, P=0.043). After one year of treatment, weight changes among patients receiving ICI only remained significant in the normal weight group (+15.6%, P=0.007), but not among patients with other BMIs and treatment regimens. These associations remained similar after excluding the patients with cachexia. Conclusions: Body weight change during ICI therapy may vary by treatment regimen and pre-ICI BMI among patients with NSCLC. Whether the weight changes are related to toxicities and survival warrants further research to shed light on weight management, ICI efficacy, and prevention of treatment-related adverse events. Funding: The study was in part funded by NIH/NCI R37CA248371, OSUCCC CCSG P30CA016058, and Pelotonia Institute for Immuno-Oncology (PIIO) at OSUCCC. Citation Format: Ting-Yuan David Cheng, Ben Kinder, Rand T. Akasheh, Cuthbert Mario Mahenge, Carolyn J. Presley, Peter G. Shields, Xuan Nguyen, Aditi Shendre, Zihai Li, Lang Li. Body weight trajectory among patients with non-small-cell lung cancer receiving immune checkpoint inhibitors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3404.

Age of Alzheimer's disease diagnosis in people with Down syndrome and associated factors: Results from the Horizon 21 European Down syndrome consortium.

People with Down syndrome (DS) have high risk of developing Alzheimer's disease (AD). This study examined mean ages of AD diagnosis and associations with co-occurring conditions among adults with DS from five European countries. Data from 1335 people with DS from the Horizon 21 European DS Consortium were used for the analysis. Mean ages of AD diagnosis ranged between 51.4 (SD 7.0) years (United Kingdom) and 55.6 (SD 6.8) years (France). Sleep-related and mental health problems were associated with earlier age of AD diagnosis. The higher number of co-occurring conditions the more likely the person with DS is diagnosed with AD at an earlier age. Mean age of AD diagnosis in DS was relatively consistent across countries. However, co-occurring conditions varied and impacted on age of diagnosis, suggesting that improvements can be made in diagnosing and managing these conditions to delay onset of AD in DS. Mean age of AD diagnosis was relatively consistent between countries Sleep problems and mental health problems were associated with earlier age of AD diagnosis APOE ε4 carriers were diagnosed with AD at an earlier age compared to non-carriers Number of co-occurring conditions was associated with earlier age of AD diagnosis No differences between level of intellectual disability and mean age of AD diagnosis.

Abstract P142: Trends and Racial/Ethnic Differences in Age at Diagnosis of Type 1 and Type 2 Diabetes Among Adults in the United States, 2016-2022

Introduction: Age at diagnosis of diabetes and diabetes type are associated with medical costs, lost productivity, vascular complications, and premature mortality that affect people disproportionately by race/ethnicity. However, age at diagnosis of diabetes by diabetes type and race/ethnicity along with their temporal trends are unclear. Hypothesis: We assessed the hypothesis that different trends and racial/ethnic differences in age at diagnosis of diabetes by diabetes type existed between 2016 and 2022. Methods: Adults aged 18 years or more were included from the National Health Interview Survey, 2016-2022. Type and age at diagnosis of diabetes were self-reported. Trends in age at diagnosis of type 1 diabetes (T1D) and type 2 diabetes (T2D) and in proportions of people with T1D or T2D diagnosed at different ages were assessed by linear and logistic regressions adjusted for sex and race/ethnicity, respectively. Racial/ethnic differences in age at diagnosis of T1D and T2D were estimated using Rao-Scott chi-square test. Results: Of 16,063 participants, 1,551 individuals had T1D with a mean [SE] age of 53.1 [0.6] years; 48.7% were women and 57.9% non-Hispanic White. T2D was found in 14,512 individuals with a mean [SE] age of 62.5 [0.2] years; 48.5% were women and 53.7% non-Hispanic White. The mean [SE] diagnosis age of T1D decreased from 37.5 [1.4] years in 2016 to 35.6 [1.4] years in 2022 ( P for trend = 0.03). During the same period for T2D, the mean [SE] diagnosis age increased from 48.7 [0.4] years to 49.2 [0.3] years ( P for trend <0.001). From 2016 to 2022, the proportion of people with T1D and T2D diagnosed at <45 years increased by 8% and decreased by 3% annually, respectively ( P for trend ≤0.01); the proportion of people with T1D and T2D diagnosed at ≥60 years decreased by 9% and increased by 3% annually, respectively ( P for trend ≤0.03). All results were adjusted for sex and race/ethnicity. Compared with non-Hispanic Whites, the mean diagnosis age of T1D was 7.8, 7.9, and 11.2 years higher whereas of T2D was 5.0, 6.4, and 2.5 years lower, respectively, in non-Hispanic Black, Hispanic, and non-Hispanic Asian people (all P for difference ≤0.002). Conclusions: In US adults, the mean age at diagnosis of T1D significantly decreased, whereas of T2D significantly increased from 2016 to 2022. Substantial differences in diagnosis age of T1D and T2D by race/ethnicity existed.

Developmental outcome of electroencephalographic findings in SYNGAP1 encephalopathy.

SYNGAP1 haploinsufficiency results in a developmental and epileptic encephalopathy (DEE) causing generalized epilepsies accompanied by a spectrum of neurodevelopmental symptoms. Concerning interictal epileptiform discharges (IEDs) in electroencephalograms (EEG), potential biomarkers have been postulated, including changes in background activity, fixation-off sensitivity (FOS) or eye closure sensitivity (ECS). In this study we clinically evaluate a new cohort of 36 SYNGAP1-DEE individuals. Standardized questionnaires were employed to collect clinical, electroencephalographic and genetic data. We investigated electroencephalographic findings, focusing on the cortical distribution of interictal abnormalities and their changes with age. Among the 36 SYNGAP1-DEE cases 18 presented variants in the SYNGAP1 gene that had never been previously reported. The mean age of diagnosis was 8 years and 8 months, ranging from 2 to 17years, with 55.9% being male. All subjects had global neurodevelopmental/language delay and behavioral abnormalities; 83.3% had moderate to profound intellectual disability (ID), 91.7% displayed autistic traits, 73% experienced sleep disorders and 86.1% suffered from epileptic seizures, mainly eyelid myoclonia with absences (55.3%). A total of 63 VEEGs were revised, observing a worsening of certain EEG findings with increasing age. A disorganized background was observed in all age ranges, yet this was more common among older cases. The main IEDs were bilateral synchronous and asynchronous posterior discharges, accounting for ≥50% in all age ranges. Generalized alterations with maximum amplitude in the anterior region showed as the second most frequent IED (≥15% in all age ranges) and were also more common with increasing age. Finally, diffuse fast activity was much more prevalent in cases with 6years or older. To the best of our knowledge, this is the first study to analyze EEG features across different age groups, revealing an increase in interictal abnormalities over infancy and adolescence. Our findings suggest that SYNGAP1 haploinsufficiency has complex effects in human brain development, some of which might unravel at different developmental stages. Furthermore, they highlight the potential of baseline EEG to identify candidate biomarkers and the importance of natural history studies to develop specialized therapies and clinical trials.

Linear IgA Bullous Dermatosis in Korea Using the Nationwide Health Insurance Database.

(1) Background: Linear immunoglobulin A bullous dermatosis (LABD) is a rare autoimmune, subepidermal blistering disease, characterized by linear IgA deposits along the epidermal basement membrane. LABD is idiopathic and is associated with medication and systemic autoimmune diseases. (2) Methods: We investigated the demographic characteristics, disease course, causative agents, and associated diseases in Korean patients with LABD. The Korean Health Insurance Review and Assessment Service database was used to obtain data. We identified 670 LABD cases between 2010 and 2022. (3) Results: The annual incidence of LABD was 1.3 per 100,000 persons, with a higher prevalence in individuals ≥60 years old. The patients were treated with dapsone for 30.7 ± 56.7 days, had 1.3 ± 0.7 hospital visits, and were hospitalized for 19.8 ± 19.7 days. Risk factors, including malignancy, commonly preceded LABD. Antibiotic use, specifically vancomycin and third-generation cephalosporins, was a risk factor. The mean age of LABD diagnosis was 55.9 ± 21.7 years. (4) Conclusion: This is the first published study to assess a nationwide cohort for LABD. The incidence of LABD was higher than that in other studies. Most case reports have linked LABD with the administration of specific antibiotics; however, this study shows there were more associations with other conditions.

A285 COMPARISON OF ADVERSE OUTCOMES IN PATIENTS WITH COMBINED INFLAMMATORY BOWEL DISEASE AND PRIMARY SCLEROSING CHOLANGITIS VERSUS ISOLATED PRIMARY SCLEROSING CHOLANGITIS

Abstract Background Primary sclerosing cholangitis (PSC) results in progressive inflammation and fibrosis of bile ducts causing chronic cholestasis. PSC is associated with an increased risk of malignancy [hepatobiliary and colorectal cancers (CRC)] compared to the general population, in addition to an increased risk of developing end-stage liver disease, often requiring liver transplantation at a relatively young age. The increased risk of adverse outcomes confers an increased risk of premature death of patients with PSC. PSC is commonly associated with IBD, particularly ulcerative colitis (UC), which in itself carries a higher rate of CRC. A study of the impact of PSC with IBD on development of cancer and survival outcomes is imperative. Aims To compare the risk of cancer, liver transplantation, and mortality in PSC-IBD versus isolated PSC. Methods Retrospective data from PSC patients from two hospital sites in Vancouver, British Columbia was analyzed to compare the relative risk of death, transplantation, and malignancy in PSC-IBD versus isolated PSC. Results 169 patients with PSC were included in the analysis [mean age of diagnosis of PSC 37 (SD 16.92) years, 41.4% (70) female]. Out of the 169 patients with PSC, 102 had IBD [29.4% (30) with Crohn’s Disease (CD); 70.6% (72) with UC]. The mean age of IBD diagnosis was 28.96 (SD 14.46) years. Death occurred in 31 [64.5% (20) with IBD; RR 1.19, 95% CI 0.61-2.32, p=0.60] patients, 35 [57.1% (20) with IBD; RR 0.88, 95% CI 0.48-1.59, p=0.66] patients developed cancer, and 33 [66.7% (22) with IBD; RR 1.31, 95% CI 0.68-2.52, p=0.41] patients required liver transplantation. The cause of death was malignancy in 15 [53.3% (8) with IBD] patients, liver failure in 5 [80% (4) with IBD] patients, sepsis in 2 [100% (2) with IBD] patients, and unknown cause of death in 9 [77.7% (7) with IBD] patients. For malignancy types, 16 [68.75% (11) with IBD] patients had cholangiocarcinoma (CCA), 4 [50% (2) with IBD] had CRC, 2 [50% (1) with IBD] had gallbladder cancer, 1 [0% (0) with IBD] had pancreatic cancer, 1 [0% (0) with IBD] had esophageal cancer, and 11 [54.5% (6) with IBD] had other malignancies not involving the hepatobiliary or gastrointestinal system. Of the patients who died due to malignancy, 73.3% (11) had CCA. Conclusions Although we do not observe any statistically significant difference in risk of cancer, transplantation, or all-cause mortality in patients with PSC-IBD when compared to isolated PSC, we do observe that 59% of all-included patients experienced one or more adverse outcome. It is important for clinicians to recognize the high rates of adverse outcomes in PSC-IBD and isolated PSC patients, potentially warranting earlier or more frequent screening for outcomes such as malignancy and liver dysfunction. Funding Agencies None

Extracranial Meningioma Metastasis: A Systematic Review of Clinical Characteristics, Management Strategies, and Outcomes

Background: Meningioma is the most common type of intracranial neoplasm, accounting for approximately 40% of all primary brain tumors. Although these tumors are usually benign and slow-growing, extracranial metastasis can occur in less than 1% of cases. Due to the rarity, diagnosis can pose a challenge. In this systematic review, we summarize and analyze patient demographics, clinical characteristics, management strategies, and outcomes of patients with extracranial meningioma metastasis.
 Project Methods: A systematic review was performed following the (PRISMA) guidelines. PubMed, Ovid EMBASE, Cochrane, Scopus, and Web of Science databases were searched. Clinical characteristics, management, and outcomes were analyzed.
 Results: A total of 127 studies with 164 patients were included. There were 51% males and mean age of primary tumor diagnosis was 48 years (range, 8-91). Primary tumors were mostly located on the convexity of the brain (52%) and WHO grade 1 (38%) or grade 2 (37%). Histological findings were predominantly atypical (37%). Mean number of intracranial recurrences was 2 (range, 0-7) and occurred in 81% of cases. Average time between primary tumor and the first extracranial metastasis was 103 months (range, 2-450). The top three most common locations of metastases were the lungs (39%), spine (15%), and liver (12%). Most often, there was no change in grade (68%) from the primary tumor to the first metastasis. Gross total resection of the primary tumor was achieved in 76% of cases. Mean survival from primary diagnosis and survival from first metastasis was 118 and 31 months, respectively.
 Conclusion/Impact: Mechanisms by which extracranial meningioma metastasis occur are still unclear, though do not appear to involve evolution into a more aggressive histologic type in most cases. In a patient with a history of intracranial meningioma recurrence and symptoms of lung, spine, or liver, dysfunction, extracranial meningioma metastasis should be considered within the differential.

Cerebrotendinous Xanthomatosis patients with late diagnosed in single orthopedic clinic: two novel variants in the CYP27A1 gene

BackgroundCerebrotendinous Xanthomatosis (CTX) is a rare autosomal recessive lipid storage disorder caused by loss of function variants in the CYP27A1 gene which encodes sterol 27-hydroxylase, on chromosome 2q35. Although the symptoms begin commonly in infancy, CTX diagnosis is often delayed. The aim of this study is to review the orthopedic findings of the disease by providing an overview of the clinical features of the disease. It is to raise awareness of this condition for which early diagnosis and treatment are important.MethodsWe retrospectively evaluated the clinical, laboratory, radiological, and genetic findings of eight patients from four families who were admitted to our Orthopedics and Traumatology Department between 2017 and 2022 due to bilateral Achilles tendon xanthomas, were found to have high cholestanol and CYP27A1 gene mutations.ResultsThe mean age of patients was 37, and five of them were male. The mean age at the onset of symptoms was 9.25 years. The mean age of initial diagnosis was 33.75 years. Between symptom onset and clinical diagnosis, an average delay of 24.5 years was observed. All patients had bilateral Achilles tendon xanthoma. Notably, a novel variant (c.670_671delAA) in CYP27A1 gene was identified in three patients who also presented with peripheral neuropathy and bilateral pes cavus. One patient had osteoporosis and four patients had osteopenia. Five patients had a history of bilateral cataracts. Furthermore, three of the patients had early-onset chronic diarrhea and three of the patients had ataxia. Two of the patients had epilepsy and seven of the patients had behavior-personality disorder. All patients had low intelligence, but none of them had cardiac disease.ConclusionWe present the diagnostic process and clinical features which the largest CTX case series ever reported from single orthopedic clinic. We suggest that patients with normal cholesterol levels presenting with xanthoma being genetically analyzed by testing at their serum cholestanol level, and that all siblings of patients diagnosed with CTX be examined.

Clinical and imaging features of women with polygenic partial lipodystrophy: a case series.

Familial partial lipodystrophy (FPLD) is an inherited disorder of white adipose tissue that causes premature cardiometabolic disease. There is no clear diagnostic criteria for FPLD, and this may explain the under-detection of this condition. This pilot study aimed to describe the clinical features of women with FPLD and to explore the value of adipose tissue measurements that could be useful in diagnosis. In 8 women with FPLD and 4 controls, skinfold measurements, DXA and whole-body MRI were undertaken. Whole genome sequencing was negative for monogenic metabolic causes, but polygenic scores for partial lipodystrophy were elevated in keeping with FPLD type 1. The mean age of diagnosis of DM was 31 years in the FPLD group. Compared with controls, the FPLD group had increased HOMA-IR (10.3 vs 2.9, p = 0.028) and lower mean thigh skinfold thickness (19.5 mm vs 48.2 mm, p = 0.008). The FPLD group had lower percentage of leg fat and an increased ratio of trunk to leg fat percentage on DXA. By MRI, the FPLD group had decreased subcutaneous adipose tissue (SAT) volume in the femoral and calf regions (p < 0.01); abdominal SAT, visceral adipose tissue, and femoral and calf muscle volumes were not different from controls. Women with FPLD1 in Singapore have significant loss of adipose but not muscle tissue in lower limbs and have early onset of diabetes. Reduced thigh skinfold, and increased ratio of trunk to leg fat percentage on DXA are potentially clinically useful markers to identify FPLD1.

Abstract A028: Disparities in suppressive immunity in Hispanic/Latina patients with hormone receptor positive breast cancer

Abstract In the US, breast cancer is the number one cancer diagnosed, and it is responsible for the most cancer related deaths among Hispanic/Latina (H/L) women. The mean age of diagnosis of breast cancer in H/L patients is 3.7 years younger than their Non-Hispanic White (NHW) counterparts. Despite being diagnosed with breast cancer at a younger age, the H/L population has a better overall survival rate across all breast cancer subtypes. This study investigates whether the immune response mounted against tumor cells in the H/L population differs from that mounted by NHW patients. We recruited and received consent from patients diagnosed with stage I- III (early stage), or stage IV/advanced (metastatic), hormone receptor positive (HR+) breast cancer. We collected blood from 66 patients (38 H/L, 28 NHW) across all stages of disease, and tumor tissue from 14 unmatched patients (7 H/L, 7 NHW), with early stage disease, at the time of tumor resection, none of whom had received neoadjuvant chemotherapy. We utilized multiparameter flow cytometry to analyze peripheral blood mononuclear cells (PBMCs), and 10X Visium for spatial transcriptomic and proteomic evaluation of patient’s tumor tissue to characterize differences in immune composition by race. We hypothesize that evaluation of intra-tumoral immune composition will reveal fewer immune suppressor cells and increased infiltration of cytotoxic immune cells in tumors from H/L patients. We also hypothesize evaluation of immune cells in circulation will mirror findings from within tumors. Suppressor immune cells, comprised of M2-polarized macrophages, myeloid derived suppressor cells (MDSCs), and T regulatory cells (Tregs) modulate T cell proliferation and cytotoxicity to affect anti-tumor immunity. We report a significant difference in the levels of both anti-tumoral and suppressive immune cells in the periphery within the H/L patient population when comparing early vs. metastatic HR+ breast cancer. This was not observed in the NHW group and there were no differences when comparing peripheral suppressor and T cell populations in H/L vs. NHW at any stage. Comparisons of intra-tumoral immune cell infiltration and differences in transcription profiles are forthcoming. The findings from this study will be some of the first to look at the immune composition in H/L women with HR+ disease, and could provide data to support larger studies leading to a paradigm shift in how we approach clinical trial design for immune checkpoint inhibition. Citation Format: Sabrina Carrel, Michelle Li, Batul Al-Zubeidy, Dominic Zavala, Edgar Gonzales, Aaron Baugh, Sofi Castanon, Robert Hsu, Dimitrios N Sidiropoulos, Yanling Ma, Michael Press, Evanthia T Roussos Torres. Disparities in suppressive immunity in Hispanic/Latina patients with hormone receptor positive breast cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Breast Cancer Research; 2023 Oct 19-22; San Diego, California. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_1):Abstract nr A028.

Clinical and Pathological Features of Pit1/SF1 Multilineage Pituitary Neuroendocrine Tumor.

Lineage-based classification has critical clinical implications in pituitary neuroendocrine tumor (PitNET). As the most prevalent subtype of multilineage PitNET, PitNET originating from both pituitary-specific positive transcription factor 1 (Pit1) and steroidogenic factor-1 (SF1) lineages (Pit1/SF1-adenoma) is expected to exhibit rich and varied clinical behaviors. A comprehensive understanding of the clinical and pathological characteristics of Pit1/SF1-adenoma will provide mechanistic insight and influence the prognosis and treatment of PitNET. A retrospective study was conducted by reviewing 57 cases of Pit1/SF1-adenoma between 2018 and 2022. We also included 88 cases of PitNET arising from Pit1 cell lineage (Pit1-adenoma) and 70 cases of PitNET arising from SF1 cell lineage (SF1-adenoma) as controls. Comprehensive data, including demographic, symptom, endocrinal, radiological, surgical, pathological, and prognostic information, were systematically collected. All specimens were immunostained for pituitary transcription factors (PTFs) and pituitary hormones. The detection rate was 8.0% for Pit1/SF1-adenoma within PitNET surgical specimens. Pit1/SF1-adenoma displayed a male predominance, with the mean diagnosis age falling between Pit1-adenoma and SF1-adenoma. The endocrine activity of Pit1/SF1-adenoma was lower than Pit1-adenoma but higher than SF1-adenoma. Pit1/SF1-adenoma had a higher incidence of cavernous sinus invasion (56.1%) than both Pit1-adenoma (38.6%, P = .039) and SF1-adenoma (27.1%, P = .001). Furthermore, Pit1/SF1-adenoma showed more postoperative complications than Pit1-adenoma (29.8% vs 8.0%, P = .001). Nonfunctional Pit1/SF1-adenoma had a higher radiological tumor recurrence rate than nonfunctional SF1-adenoma (34.8% vs 10.9%, P = .021). Notably, the immunostaining pattern was diverse in Pit1/SF1-adenoma, with various combinations of staining intensity for PTFs and 15 combinations for 6 pituitary hormones. Intriguingly, various PTFs combinations had no different impact on the outcome of Pit1/SF1-adenoma. Pit1/SF1-adenoma represents a unique pathological subtype of PitNET, characterized by distinctive clinical behaviors. Identifying Pit1/SF1-adenoma can facilitate more precise management of PitNET by the practical use of Pit1/SF1 immunostaining.

Clinical Characteristics and Treatment Outcomes of Prurigo Nodularis: A Retrospective Study.

Prurigo nodularis (PN) is a complex chronic skin disease characterized by severe pruritic nodules. PN is often associated with mental health disorders and chronic medical comorbidities. Until recently, PN treatment has been challenging and difficult. This study aims to describe the demographic, clinical characteristics, and comorbidities associated with PN. Also, we aim to describe the effectiveness of systemic therapies, including methotrexate, cyclosporine, and narrow band ultraviolet (NB-UVB) in adult patients with PN. This is a retrospective chart review of adult patients diagnosed with PN at Hamilton Health Science Center and/or McMaster University in Hamilton, Ontario, between 2015 and 2023. The study included 81 patients (57% female). The mean age was 52.8 years, and the mean age of PN diagnosis was 50 years. Reported symptoms included: itching (100%), dry skin (53%), pain (17%), and burning sensation (5%). Lower and upper extremities were the most common areas involved in 93% and 69%, respectively. Mental health disorders were present in 79% of patients, with depression (58%) and anxiety (52%) being the most common. Atopic dermatitis was the most common skin comorbidity noted. Treatments used included cyclosporine, and NB-UVB, and MTX, which resulted in significant improvement of pruritus in 38%, 35%, and 31% of patients, respectively, at week 16. PN is associated with increased risk of mental health disorders and other medical comorbidities. Cyclosporine, methotrexate, and NB-UVB therapy may be effective treatment options, however clinicians must consider the potential short- and long-term adverse effects of these treatments.

P1025 Analysis of the Clinical Characteristics of Elderly-onset Crohn's Disease

Abstract Background The prevalence of Crohn's disease in the elderly is increasing today. The purpose of this study was to analyze the clinical characteristics of elderly-onset patients with Crohn's disease and compare with non-elderly-onset adult patients. Methods All Crohn's disease patients with onset aged 60 years and older at our Inflammatory Bowel Disease Center in recently ten years were retrospectively included. The elderly were compared with adult patients aged 18-59 at the time of onset, who were matched according to diagnosis time and gender by a 1:3 ratio of propensity score matching. After matching, the clinical data were recorded and analyzed to compared between the two groups of patients. Results A total of 68 patients were included, including 17 patients in the elderly-onset group and 51 patients in the non-elderly-onset adult group. The mean age of diagnosis in the two groups was 30.3±8.7 years and 63.9±4.24 years, and the mean course of disease was 30.3 months and 63.9 months, respectively. According to the Montreal classification, most elderly patients presented with L3 (70.6%) and B1 (58.8%), no cases involving the upper digestive tract or multiple lesion sites, showed mild disease activity (76.5%). The elderly group had fewer intestinal complications and parenteral manifestations. The medication types of elderly are 5-aminosalicylates (52.9%), traditional immunosuppressive agents (45.6%) and enteral nutrition preparations (29.4%) being the more frequent types of medications used, and glucocorticoids and biologics being used less frequently. Exposure to two or more IBD medications was 31.4% and 52.9% in the non-elderly onset adult group versus the elderly onset group, respectively (p=0.110). During follow-up, symptoms such as diarrhea (11.8 vs 5.9%), abdominal pain (35.3% vs 17.6%) and weight loss (11.8% vs 3.9%) were more common in the elderly-onset group. Elderly patients had more hospitalizations on average (0.22 vs. 1.12). 40.7% of elderly patients underwent CD-related surgery during the duration of their disease, with 50.0% of patients undergoing reoperation. Conclusion Compared with non-elderly-onset adult patients, elderly-onset patients with Crohn's disease are more common in women, and the lesion mainly in the ileum and ilecolon; the disease behavior is mainly B1; nearly half of the patients have intestinal complications The elderly have atypical clinical manifestations, basically haven’t family history of IBD, take longer to diagnose, have more underlying diseases, more hospitalizations on average, and are more likely to have complications. They are more likely to receive conservative treatment, but with more frequent medication adjustments and a higher likelihood of undergoing CD-related surgery.

P607 Increased rates of fractures and malignancy in elderly onset IBD in Singapore

Abstract Background Elderly onset inflammatory bowel disease (EOIBD) has variable characteristics in the published literature. We performed this study to report the disease characteristics, treatment exposure, and clinical outcomes of EOIBD compared to adult onset IBD (AOIBD) in Singapore. Methods This is a retrospective study involving IBD patients seen at two tertiary hospitals in Singapore from January 2020 to September 2023. Patients were identified from the Singapore National IBD registry. Those with missing data on age of IBD diagnosis were excluded. Data on baseline demographics, disease characteristics, treatment and disease-related complications were collected. EOIBD is defined as age of diagnosis ≥ 60 years old and AOIBD as those diagnosed from age 18 to 59 years old. The characteristics was compared between these two groups. Data was analysed using SPSS version 27.0. Results 1116 patients were included in the final analysis, 10.6% (n =118) were EOIBD as shown in Figure 1. 50% were male with a mean age of diagnosis at 68 years old. The comparison between EOIBD and AOIBD are shown in Figure 1 and Table 1. There is a higher proportion of Crohn’s disease (CD) (45.7% vs 37.4%) in EOIBD. In terms of treatment, there is significantly lower use of thiopurines amongst EOIBD (34.5% vs 46.8%, p = 0.012). There was a trend of higher use of methotrexate among EIOBD (19.6% vs 10.6%, p = 0.067) although this was not statistically significant and this is similarly observed in the use of biologics (32.8% in EOIBD vs 27.1% in AOIBD, p = 0.205). There were no significant differences in corticosteroids (CS) exposure, CS dependence and mean number of CS courses used. There was a lower proportion of IBD-related surgery in EOIBD (12.1 vs 18.5%, p = 0.094) with EOID having a significantly lower mean number of IBD-related surgery (1.1 vs 1.6, p &amp;lt;0.001). Among EOIBD, there were significantly higher rates of malignancy (17% vs 6%, p &amp;lt;0.001) and fractures (18.1% vs 9.2%, p = 0.02); the latter despite a statistically higher mean level of vitamin D (20.9 ng/ml vs 18.3 ng/ml, p = 0.026). There were no differences in IBD-related hospitalization. Conclusion EOIBD is associated with increased rates of fractures and malignancy compared to AOIBD. Therefore, bone health and malignancy screening should be regularly performed in this group of patients to clinical outcomes.