Age At Diagnosis Research Articles

Genetics of C-peptide and Age at Diagnosis in Type 1 Diabetes

Identified genetic loci for C-peptide and age at diagnosis (AAD) in individuals with type 1 diabetes (T1D) explain only a small proportion of their variation. Here, we aimed to perform large metagenome-wide association studies (GWAS) of C-peptide and AAD in T1D; and to identify the HLA allele/haplotypes associated with C-peptide and AAD. 7,252 and 7,923 European individuals with T1D were included in C-peptide and AAD GWAS, respectively. HLA-DQB1*06:02 which is strongly protective against T1D was associated with higher C-peptide. HLA-DQB1*03:02, HLADRB1*03:01 and HLA-A*24:02 which increase T1D risk were independently associated with younger AAD. HLA-DR3-DR4 haplotype combination, the strongest T1D susceptibility factor, was associated with younger AAD. Outside HLA region, rs115673528 on Chr5 (GABRG2) was associated with C-peptide, and an indel, rs111970692, on Chr15 within CTSH, a known T1D locus, was associated with AAD. Genetically predicted CTSH expression, methylation and protein levels were associated with AAD; Mendelian randomization analysis suggested that higher levels of procathepsin H reduce AAD. In conclusion, some HLA allele/haplotypes associated with T1D also contribute to variability of C-peptide and AAD. Outside HLA, T1D loci are generally not associated with C-peptide or AAD. CTSH could be a potential therapeutic target to delay development/progression of type 1 diabetes.

Female-Specific Association between the Apolipoprotein E E4 Allele and Age at Diagnosis of Glaucoma in UK Biobank

ObjectiveTo explore the impact of the apolipoprotein E (APOE) E4 allele in the gender-specific aging process in glaucoma by illustrating the interaction between risk factors, including the APOE E4 allele, gender and intraocular pressure (IOP), for age at diagnosis (AAD) of glaucoma. DesignA cross-sectional study included UK Biobank participants with complete data (2006-2010) for analysis. Data were analyzed in December 2023. Participants2,236 glaucoma patients and 103,232 controls. MethodsWe evaluated multivariable-adjusted associations of AAD of glaucoma, APOE E4 allele (0: absence; 1: presence), and IOP using linear mixed model (LMM) analyses across groups stratified by AAD of mean age of menopause (50 years) and gender. Main Outcomes MeasuresAAD of glaucoma, APOE E4 allele and IOP. ResultsGlaucoma patients were older and had a higher percentage of males and a higher mean IOP compared to controls (all P < 0.001). Further stratifying the glaucoma patients by AAD of 50 and gender, lower IOP (Model 1 adjusted by age, βIOP=-0.096±0.041, P=0.019) and positive APOE E4 allele (Model 2 adjusted by age and IOP, βe4=1.093±0.488, P=0.026) were associated with an older AAD in females with an AAD < 50 years under univariate LMM. In multivariate LMM adjusted by age (Model 3), the effect size of both factors increased in the multivariate model as the beta-value increased. (βIOP=-0.111±0.040, P=0.007; βe4=1.235±0.485, P=0.012) (Model 1 vs Model 3: P=0.011). In females with an AAD ≥50 years, only positive APOE E4 allele (adjusted by age and IOP, βe4=-1.121±0.412, P=0.007) was associated with a younger AAD. In males, only higher IOP was associated with an older AAD in those with an AAD ≥50 years (βIOP=0.088±0.032, P=0.006). ConclusionsAPOE E4 allele may initially delay and later accelerate the development of glaucoma in females around the transition period of 50 years, which is the mean age of menopause, and importantly, this is independent of IOP. Understanding the specific transition states and modifiable factors within each age phase is crucial for developing interventions or strategies that promote healthy aging.

Adults with FPIES may face delayed diagnoses

BackgroundFood protein-induced enterocolitis (FPIES) is a non-IgE-mediated food allergy that is becoming increasingly recognized in adults. The time between age at symptom onset (ASO) and age at diagnosis (AD) along with factors impacting this gap have not been fully studied. ObjectiveWe sought to investigate the latency between ASO and AD in adults with FPIES. We also sought to evaluate whether those with symptom onset in earlier years and those with comorbid gastrointestinal disease had greater mean latency. MethodsWe conducted a retrospective chart review for FPIES patients seen in the University of Michigan Allergy and Immunology clinic from 2015 to 2022. Patients 18 years and older diagnosed with FPIES by an allergist were included (N=19). Data including characteristics of patients’ prior FPIES reactions and past medical history were collected. ResultsThe median FPIES ASO was 26 years and median AD was 35 years. The median difference between ASO and AD was 10 years and statistically significant via paired t-test (p=0.003). There was a negative correlation of -0.99 between year of symptom onset and latency between ASO and AD (p<0.0001). Those with previously diagnosed GI conditions had higher mean latency between ASO and AD than those without (p=0.124). ConclusionsWe noted a gap between ASO and AD in adults with FPIES. This may be due to under recognition of adult FPIES in the past given the negative correlation with mean latency between ASO and AD. Furthermore, co-morbid GI illnesses may be masking FPIES symptoms in adults and delaying diagnosis.

Genomic variants associated with age at diagnosis of childhood-onset type 1 diabetes.

Age at diagnosis (AAD) of Type 1 diabetes (T1D) is determined by the age at onset of the autoimmune attack and by the rate of beta cell destruction that follows. Twin studies found that T1D AAD is strongly influenced by genetics, notably in young children. In young UK, Finnish, Sardinian patients AAD-associated genomic variants were previously identified, which may vary across populations and with time. In 1956 children of European ancestry born in mainland France in 1980-2008 who declared T1D before 15 years, we tested 94 T1D-associated SNPs for their association with AAD using nonparametric Kruskal-Wallis test. While high-risk HLA genotypes were not found to be associated with AAD, fourteen SNPs located in 12 non-HLA loci showed a strong association (2.9 × 10-12 < P < 1.4 × 10-3 after FDR correction). Four of these loci have been associated with AAD in previous cohorts (GSDMB, IL2, TNFAIP3, IL1), supporting a partially shared genetic influence on AAD of T1D in the studied European populations. In contrast, the association of 8 new loci CLEC16A, TYK2, ERBB3, CCR7, FCRL3, DNAH2, FGF3/4, and HPSE2 with AAD is novel. The 12 protein-coding genes located within these loci are involved in major immune pathways or in predisposition to other autoimmune diseases, which suggests a prominent role for these genes in the early immune mechanisms of beta cell destruction.

Reappraisal of prognostic factors used in the European Pediatric Soft Tissue Sarcoma Study Group RMS 2005 study for localized rhabdomyosarcoma to optimize risk stratification and generate a prognostic nomogram.

The objective of this study was to investigate the role of clinical factors together with FOXO1 fusion status in patients with nonmetastatic rhabdomyosarcoma (RMS) to develop a predictive model for event-free survival and provide a rationale for risk stratification in future trials. The authors used data from patients enrolled in the European Pediatric Soft Tissue Sarcoma Study Group (EpSSG) RMS 2005 study (EpSSG RMS 2005; EudraCT number 2005-000217-35). The following baseline variables were considered for the multivariable model: age at diagnosis, sex, histology, primary tumor site, Intergroup Rhabdomyosarcoma Studies group, tumor size, nodal status, and FOXO1 fusion status. Main effects and significant second-order interactions of candidate predictors were included in a multiple Cox proportional hazards regression model. A nomogram was generated for predicting 5-year event-free survival (EFS) probabilities. The EFS and overall survival rates at 5years were 70.9% (95% confidence interval, 68.6%-73.1%) and 81.0% (95% confidence interval, 78.9%-82.8%), respectively. The multivariable model retained five prognostic factors, including ageat diagnosis interacting with tumor size, tumor primary site, Intergroup Rhabdomyosarcoma Studies clinical group, and FOXO1 fusion status. Based on each patient's total score in the nomogram, patients were stratified into four groups. The 5-year EFS rates were 94.1%, 78.4%, 65.2%, and 52.1% in the low-risk, intermediate-risk, high-risk, and very-high-risk groups, respectively, and the corresponding 5-year overall survival rates were 97.2%, 91.5%, 74.3%, and 60.8%, respectively. The results presented here provide the rationale to modify the EpSSG stratification, with the most significant change represented by the replacement of histology with fusion status. This classification was adopted in the new international trial launched by the EpSSG.

Deciphering the complex links between inflammatory bowel diseases and NAFLD through advanced statistical and machine learning analysis

Background and Objective:Accurate classification of liver disease stages provides crucial insights into patient prognosis, aiding in the prediction of disease outcomes and influencing clinical decision-making. There is an urgent need for non-invasive methods to diagnose various stages of liver dysfunction and uncover hidden pattern based on individual disease characteristics. Method:One popular and effective approach is collecting serum biomarker samples. The study was conducted on collected serum biomaker samples of 81 patients with Inflammatory Bowel Disease (IBD) of Changhua Christian Hospital in China, including 36 with Crohn’s disease (CD) and 45 with Ulcerative Colitis (UC) using Latent Semantic Analysis(LSA) and machine learning (ML) techniques.Machine Learning algorithms Random Forest (RF), Logistic Regression (LR), XGBoost (XGB), and Support Vector Classifier (SVC), were utilized to predict liver risk associated with conditions including Hepatitis, Autoimmune Hepatitis (AIH), Alcoholic Liver Disease (ALD), and Non-Alcoholic Fatty Liver Disease (NAFLD). Models’ accuracy was assessed using K-Fold Cross-Validation (CV).Distinct pattern were identified using Latent Semantic Analysis(LSA). Furthermore, SHAP plots were utilized for enhanced interpretability, highlighting essential features for liver dysfunction levels. Results:The inflammatory profile, mixed disease profile, and healthy profile were the three distinct clusters were identified with LSA. The RF model achieved high accuracy of 0.94±0.06. Serum Glutamate Pyruvate Transaminase (GPT), Age at Diagnosis (AAD), Erythrocyte Sedimentation Rate (ESR), C-reactive protein (CRP) were found the most key important features in liver disease staging increment. Conclusion:The research significantly contributes to the fields of biomedical informatics and clinical decision-making. The developed model offers valuable decision-making tools for clinicians, enabling early and targeted interventions.

Outcome of two cohorts with nephroblastoma treated with consecutive International Society of Paediatric Oncology protocols in a South African paediatric oncology unit

Background. Nephroblastoma is a common childhood solid tumour in South Africa.Objective. The aim was to determine outcomes of patients diagnosed with nephroblastoma between 1990 and 2018 and compare outcomes of two cohorts treated with consecutive International Society of Paediatric Oncology (SIOP) nephroblastoma protocols.Methods. This was a retrospective, descriptive study of two cohorts in Tygerberg Hospital. Cohort 1 (1990 - 2007) was treated with theSIOP 9 and SIOP 93-01 protocols, and Cohort 2 (2008 - 2018) with the SIOP 2001 protocol. Data included demographic data (age atdiagnosis, sex), HIV status, pre- and postoperative staging, surgical complications, histological types, lymph node sampling, overallsurvival (OS) and event-free survival (EFS) with the end point two years after diagnosis.Results. There were 60 children (M:F ratio 1:1.14) in Cohort 1 with an older mean age of 42 months (interquartile range (IQR)16.25 - 56.5 months) v. 45 children (M:F ratio 1:0.8) in Cohort 2 with a mean age of 37 months (IQR 22 - 45.5 months). Cohort 2 hadmore patients with localised disease (76%) than Cohort 1 (55%) (trend towards significance p=0.076). Both cohorts had a good OS(respectively 88% and 93%) and EFS (respectively 82% and 80%). Half of Cohort 1 (50%; n=30/60) did not have lymph nodes sampledwith four subsequent relapses, significantly associated with OS (p&lt;0.001) and EFS (p=0.006). There was a significant associationbetween OS and EFS and underlying histology (respectively p=0.006 and p=0.015) for Cohort 1, but only for EFS and histology (p=0.02)for Cohort 2.Conclusion. There was good OS for children with nephroblastoma treated with consecutive SIOP protocols in a single institution inSouth Africa.

THU216 The Influence Of Age At Diagnosis On Clinical Presentation And Prognosis Of Childhood-onset Craniopharyngioma

Abstract Disclosure: J. Beckhaus: None. C. Friedrich: None. S. Boekhoff: None. G. Calaminus: None. B. Bison: None. M. Eveslage: None. B. Timmermann: None. J. Flitsch: None. H.L. Muller: None. The association between age at diagnosis (AaD) and clinical presentation and prognosis of pediatric patients with craniopharyngioma (CP) is not clear. Seven hundred and nine patients diagnosed with adamantinomatous CP have been recruited between 1999 and 2021 in HIT-ENDO, KRANIOPHARYNGEOM 2000/2007, KRANIOPHARYNGEOM Registry 2019 and prospectively observed. In our cohort study, we analyzed clinical presentation and outcome in these CP patients with regard to different AaD: Infants and toddlers (under 2 years), early childhood (2-6 years), middle childhood (6-12 years), and early adolescence (12-18 years). Following a median follow-up of 8.4 years, functional capacity (FMH), overall and event-free survival (EFS), and quality of life (QoL) (PEDQOL) were evaluated. 45.4% of the patients presented with severe obesity (BMI &amp;gt; 3SDS) at last visit. Children with AaD &amp;lt;6y showed lower EFS but higher QoL than children with AaD &amp;gt;6y. Reduced functional capacity (FMH) percentiles were linked to higher BMI-SDS at last visit (rho=-0.125, 95% CI [-0.21; -0.04]). Posterior hypothalamic involvement and surgical lesion were independent risk factors for both, severe obesity at last visit (OR=2.94, 95% CI [1.73;5.08]) and events (HR=1.59, 95% CI [1.12;2.26]). In the PEDQOL body image domain, patients with posterior hypothalamic involvement and lesion report lower scores. Nearly half of all patients suffer from sequelae of severe obesity and the hypothalamic syndrome. A diagnosis of CP before the age of 6 years may enable patients to adjust to their limitations earlier, but it may also increase the risk of relapse. The cause of severe obesity and a lower QoL is not AaD but posterior hypothalamic involvement of CP. Presentation: Thursday, June 15, 2023

Gender Difference in Liver Enzymes in Newly Defined Subgroups of Diabetes Revealed by a Data-Driven Cluster Analysis.

Recently, a newly proposed data-driven approach for classifying diabetes has challenged the status quo of the classification of adult-onset patients with diabetes. This study investigated the association between liver injury and diabetes, classified by data-driven cluster analysis, as liver injury is a significant risk factor for diabetes. We enrolled 822 adult patients with newly diagnosed diabetes. Two-step cluster analysis was performed using six parameters, including age at diagnosis, body mass index, hemoglobin A1C, homoeostatic assessment model 2 estimates about insulin resistance (HOAM2-IR) and beta-cell function (HOMA2-B), and glutamic acid decarboxylase antibodies (GADA) positivity. Patients were allocated into five clusters. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity were compared as indicators of liver injury among clusters. Serum ALT and AST activities were significantly different among clusters (P=0.002), even among those without GADA positivity (P=0.004). Patients with severe insulin-resistant diabetes (SIRD) and mild obesity-related diabetes (MOD) had a more severe liver injury. Gender dimorphism was also found for serum ALT and AST activities among subgroups. Female patients had better liver function than males with SIRD and MOD. We verified the feasibility of a newly proposed diabetes classification system and found robust and significant relationship and gender differences between serum ALT and AST activities and diabetes in some specific subgroups. Our findings indicate that more attention should be paid to diabetes subgroups when studying risk factors, indicators, or treatment in diabetic research.

Pandemic's impact on inguinal hernia management in infants.

The SARS-CoV-2 pandemic brought about a reduction in surgical activity. The objective of this work was to analyze its impact on inguinal hernia morbidity. A retrospective study of cases and controls was carried out. Patients under 18 months of age undergoing inguinal hernia surgery from January 1, 2019 to August 31, 2020 were included. They were divided into two groups: patients undergoing surgery before (group A) or after (group D) the state of alarm was declared in Spain. Primary variables: episodes of incarceration and postoperative complications. Secondary variable: urgent or scheduled surgery. Demographic variables: sex, gestational age (GA), previous pathologies, age at diagnosis (AD), and age at surgery (AS) (months). 64 patients were included - 43 in group A and 21 in group D. In group A, median GA was 37+3, 90.5% of patients were male, median AD was 2.33, and median AS was 3.27. In group D, median GA was 31+2, 72.1% of patients were male, median AD was 3, and median AS was 3.63. There were no statistically significant differences. However, differences in terms of previous pathologies were significant (16.3% for Group A vs. 38.1% for group D) (p = 0.05). Regarding the primary variable, 25.6% of patients in group A had incarcerations vs. 33.3% of patients in group D (p = 0.51), whereas 9.3% of patients in group A had postoperative morbidity vs. 14.3% of patients in group D (p = 0.41). Regarding the secondary variable, 88.4% of surgeries in group A were scheduled vs. 90.5% of surgeries in group D (p = 0.583). In spite of reduced surgical activity, inguinal hernia morbidity did not surge in our environment. An increase in patients with previous pathologies was noted, which means severe patients should be prioritized.

Differential risk factors between uterine sarcomas and malignant mixed Müllerian tumors.

e23551 Background: Uterine sarcomas are malignant tumors of the smooth muscle or connective tissue of the uterus. Its main histological types are leiomyosarcomas and endometrial stromal sarcomas, with recent classifications considering malignant mixed müllerian tumors (MMMT) as a dedifferentiated endometrial carcinoma rather than a primary uterine sarcoma. We hypothesize there are different risk factors which predispose to MMMT as compared to uterine sarcomas. This study investigates these risk factors to determine if they contribute to the development of either disease. Methods: Under an IRB-approved protocol, we identified patients with uterine sarcomas and MMMT treated at Sylvester Comprehensive Cancer Center and University of Miami Hospital between 2010 and 2020 by Patient Atlas (clinical database tool; Miami, FL). We compared the risk factors known to be associated with endometrial carcinomas between uterine sarcomas and MMMT using independent sample t-test, Chi Square, Spearman Rho and Pearson correlation. Results: A total of 59 patients with MMMT and 115 cases of uterine sarcoma were identified in our database. In the sarcoma group, the most common histology was leiomyosarcoma (n = 76, 66%). Upon analysis of the characteristics of the sarcoma and MMMT cohorts respectively, 38 (33%) vs 16 (27%) were Hispanics, 18 (15%) vs 13 (22%) had diabetes, 26 (22%) vs 20 (34%) used contraception or hormonal replacement therapy (HRT), 35 (30%) vs 17 (28%) were alcohol users, 26 (22%) vs 15 (25%) were smokers, and 54 (47%) vs 31 (52%) had a positive family history of cancer, with no statistically significant differences found (p &gt; 0.05). The sarcoma group had a significantly lower age at diagnosis (AAD) (53 vs. 65, P &lt; 0.001) and a larger tumor size (11.3 vs. 7.3 cm, p &lt; 0.0005). Use of contraception or HRT was not significantly different among the 2 groups (χ(1) = 0.699, p = 0.4). Similarly, no significant difference was found in the mean age of menarche/menopause, patient’s weight, median gravidity and parity (p &gt; 0.05). The patient’s weight and BMI negatively correlated with the AAD in the MMMT group (ρ = - 0.279, p = 0.043 and r = -0.274, p = 0.041 respectively). Older age at menopause was associated with older AAD in the sarcoma group (ρ = 0.571, p = 0.0001). Patients with higher gravidity and parity had an older AAD among the 2 groups (p ≤ 0.05). Conclusions: The uterine sarcoma patients had significantly younger AAD than the MMMT group, with the age at menopause being positively correlated with the AAD. The use of contraception or HRT were not significantly different among the 2 cohorts, suggesting that there could be an overlap of the risk factors of MMMT and uterine sarcomas. Interestingly, higher gravidity and parity were associated with an older AAD. In the MMMT group, patient’s weight and BMI were inversely associated with the AAD. Larger studies are needed to investigate whether similarities or discrepancies in the studied risk factors truly exist.

Distinct Prognostic Factors in Sporadic and Multiple Endocrine Neoplasia Type 1-Related Pancreatic Neuroendocrine Tumors.

Pancreatic neuroendocrine tumors (PNET) may develop sporadically or in the context of hereditary syndromes. In patients with multiple endocrine neoplasia type 1 (MEN1), PNET is the leading cause of death. Our aim was to compare the mortality risk in sporadic and MEN1-related PNETs and identify high-risk populations. A retrospective Surveillance, Epidemiology, and End Results database analysis of patients with PNET was used. Patients with MEN1 were defined by syn/metachronous pituitary adenoma. Clinical data were retrieved, and all-cause mortality (ACM) risk was compared in univariate and multivariable analyses. The cohort included 569 patients (46.6% males) with sporadic (n=542) and MEN1-related (n=27) PNETs. Age at diagnosis of MEN1-related PNET was significantly younger than with sporadic PNETs (mean age 49.2±16.7 vs. 61.6±12.7 years, respectively; p < 0.001). Survival analysis showed a trend for a better outcome in patients with MEN1-related vs. sporadic PNET (Log-rank, p=0.09) and in subgroup analysis for patients with advanced disease (p=0.08). Furthermore, among patients followed expectantly, those with MEN1-related PNET had lower ACM risk than their sporadic counterparts (p=0.08). Multivariable analysis demonstrated lower ACM risk in patients diagnosed with MEN1 (hazard ratio 0.35, 95% confidence interval 0.11-1.2, p=0.09), further supporting the trend detected in the univariate analysis. In conclusion, our study demonstrates the distinct clinical profile of patients with MEN1-related PNET compared to sporadic disease and emphasizes the expertise required to accurately manage patients with PNET in this rare context. The cautious decision-making required before embarking on surgical intervention is further emphasized in this robust analysis of a large cancer database.

Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL): A Review and the Caribbean Perspective

ABSTRACT Objectives Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL) is a rare CD-30 positive, Anaplastic Lymphoma Kinase Negative Non-Hodgkins lymphoma. The current estimated incidence is one to three cases per million implanted women. However, this is likely to rise with the increasing popularity of breast augmentation. This article contains a brief literature review and describes the Caribbean response to BIAALCL. Methods A literature search was done on the PUBMED Database. Keywords included ‘breast implant-associated anaplastic large cell lymphoma’, ‘brentuximab vedotin’, ‘breast implant’, ‘texturized implants’. The Caribbean Association of Plastic and Reconstructive Surgeons (CAPRS) formulated a regional response to BIA-ALCL during their meeting in August 2019. Results The Food and Drug Administration (FDA) has received 573 unique medical device reports of BIA-ALCL worldwide. The time from implantation to diagnosis, ranges from 7.5 to 10 years and the median age at diagnosis ranges from 47 to 58 years. The pathophysiology of BIA-ALCL is likely multifactorial and involves chronic inflammation in response to textured implants and chronic biofilm, in a genetically susceptible person. Early presentation has a good prognosis with treatment (5-year survival rate of 70-90%). Conclusion Recommendations included development of a regional breast implant registry, which will facilitate study on implant use and its complications. They also concluded that texturized devices should be avoided and utilization of smooth alternatives or autologous reconstruction be performed. Additionally, if requested by asymptomatic women, explant of textured implants and total capsulectomy is not unreasonable. However, these patients must be appropriately counselled.

129 - Age at Diagnosis, Glycemic Control and Responses to Oral Blood Glucose Lowering Drugs in Type 2 Diabetes: A Population-Based Study

Lifetime glycemic exposure or its relationship with age at diagnosis (AAD) in type 2 diabetes (T2D) is unknown. We studied how AAD of T2D affects glycemic exposure, glycemic deterioration and responses to oral glucose-lowering drugs (OGLDs).

Role of radiotherapy in Masaoka stage II and III thymomas - single center experience

Aim: Thymomas are rare neoplasms. Complete surgical resection is the cornerstone of the treatment. The role of adjuvant radiotherapy (RT) in Masaoka stage II disease is controversial, but in more advanced stages and the role of radical RT in inoperable cases are clear. This study is conducted to evaluate local control, relapse free survival and overall survival rates in Masaoka stage II and III thymoma patients after adjuvant or radical RT.Materials and Methods: The medical records of thymoma patients who were treated and completed their RT course between January 2010 and August 2016 in a single center were evaluated retrospectively.Results: Twenty-two patients were available for analysis. Treatment planning was adjuvant in 18 patients and radical in 5 patients. Median age at diagnosis was 59 (50-62). Type of resection was R0 in all cases. The adjuvant RT dose was 50 Gy; radical RT dose was 60-66 Gy. The most common acute toxicity was grade 1 pneumonitis which was reported in 9 patients (39%). Grade 2 acute pneumonitis was experienced by 3 patients (13%), grade 2 acute esophagitis was experienced by 2 patients (9%). One patient had late grade 3 esophageal toxicity. Follow-up time ranged from 6 to 99 months, median 18 months, local control rate was 100%, relapse free survival (RFS) was 96%, cancer specific survival was 96%, 2 years overall survival (OS) was 83%. Conclusion: Although our results seem to be in concordance with the literature, longer follow-up is needed to be able to make a conclusion in terms of LC, RFS and OS, since thymoma has an indolent course with low relapse rate and long RFS.

MON-LB090 Red-Hipopara, Real Life Experience in 322 Patients with Hypoparathyroidism in Argentina

Hypoparathyroidism (HPT) is a rare disorder characterized by hypocalcemia and absent or deficient PTH. Few data are available on the natural history and correct management of this disease. Aim: Describe clinical characteristics, treatment, and complications in a group of patients with hypoparathyroidism from 6 referral centers for endocrinological diseases. Secondary, describe how many patients reached guidelines recommendations for rhPTH (1-84) treatment (Brandi ML. JCEM. 2016). M & M: In this retrospective study patients with a diagnosis of HPT of ≥6 months were eligible for inclusion. Patients with pseudohypoparathyroidism were excluded. Demographics, etiology, management, hospitalizations, clinical manifestations and biochemical and DXA values were collected.Results:322 HPT patients were included; mean age was 55.2 ± 16.8 years, 85,7% were women. Mean ageat diagnosis was 43.8 ± 16.8 years and mean follow up time was 4.9 ± 5.1 years. Regarding etiology 90%were post-surgical (50.3% for thyroid cancer, 41% for multinodular goiter, 2.7% primary hyperparathyroidism;3.4% secondary hyperparathyroidism and 2.3% cervical cancer). Non-surgical etiology included: 5 DiGeorge Syndrome, 9 autoimmune and 16 idiopathic. Non-surgical patients were significantly younger (45 ± 19.5 vs.56.3 ± 16.1 years; p<0.01) and were younger at diagnosis (45.1 ± 15.9 vs. 31.4 ± 20.5 years;p<0.01).Treatment regimens were determined by the patients’ physician, per usual clinical practice, and most patients were receiving calcium supplementation (mean daily dose:2019 ± 1426 mg), vitamin D ( mean weekly dose 34.368 ± 55.278 UI) and calcitriol ( mean daily dose: 0.498 ± 0.279 mcg). 13 patients were receiving teriparatide ( 1-34 human parathyroid hormone). 25.7% had a history of hypocalcemia requiring hospitalization, 4.6% had fragility fracture history (wrist, hip, humerus, vertebra or tibia) and 4.3% has a history of seizures. Only 41.9% had a renal ultrasound done and 15.5 % had positive findings ( kidney stones and nephrocalcinosis). 54% had 24-hour urine calcium excretion measured and almost half of them had hypercalciuria confirmed (56.3%). Only 18,3% patients had central nervous system imaging performed,and 38.9% had basal ganglia calcification. Finally, 38.8% met criteria to rhPTH (1-84) treatment according to the guideline; most of them because their daily oral calcium requirements exceeded 2.5 g of calcium. Conclusion: Although these patients were followed by experienced physicians, clinical management and monitoring was heterogeneous and probably insufficient to assess all the potential complications of this chronic disease. Being aware of this situation is the first step to improve our medical management of HPT in the future Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

Prognostic evaluation of patients with metastatic spinal tumors using modified Tokuhashi's score: A retrospective study

Introduction: Tokuhashi's scoring has been used as a presurgical tool for prediction of survival in patients with spinal metastases (SM). It evaluates prognostic factors such as performance status, number of extraspinal bone metastasis, metastasis to visceral organs, site of primary, and neurological status that determine the survival in these patients. To the best of our knowledge, only limited studies are available to use this scoring system to determine survival outcomes in patients with SMs undergoing palliative radiotherapy. Aim: The purpose of our study was to determine the patient characteristics and usefulness of modified Tokuhashi's score in determining survival in patients with SM. Methods: This is a retrospective study of patients who underwent radiotherapy for SM from January 2013 to December 2017. Results: Seventy patients with SM from solid tumors were included in the study. The male to female ratio was 1.3:1. The median ageat diagnosis of SM was 50 years. The median survival was 7 months. The modified Tokuhashi's score ranged from 0 to 13, and the mean score was 6. In our study, 46 belonged to the poor prognostic group, 20 belonged to the moderate prognostic group, and 4 patients belongedto good prognostic group with a median survival of 4.8, 13.5, and 28 months, respectively. There was a statistical significance in the difference in survival in three prognostic groups. Conclusion: Our study confirms the usefulness of modified Tokuhashi's score in determining the survival outcomes in patients with metastatic spinal tumors.

Are early prognostic indicators reliable in posterior urethral valves management?

ObjectiveTo identify indicators that predict outcome in posterior urethral obstruction management in a resource-constrained environment with emphasis on the importance of early indicators. Subjects and methodsA retrospective review of all children who were managed for posterior urethral obstruction from 2002 to 2012 was done. Variables studied were: age at diagnosis (AgD) and of ablation, creatinine at diagnosis (CrD), nadir creatinine (CrN), vesicoureteric reflux (VUR), urinary diversion, and urodynamic study (UDS) findings. These were evaluated against two groups of patients—those with end stage renal disease (ESRD)-Group A and those with normal renal function-Group B. Significant variables were entered into a multivariate logistic regression to identify the independent prognostic factors that determine progression to ESRD. The independent factors were further analyzed with the receiver operating characteristics (ROC) to identify cutoff levels. The data is expressed as mean ± SD and median (IQR). A p-value of 0.05 was regarded as significant. ResultsSixty patients had adequate documents for evaluation. ESRD was identified in 30% of the cases. The AgD was 2.5 weeks (1–18 weeks). CrD, CrN, abnormal UDS, and VUR were significant prognostic indicators of ESRD (p = 0.0001), with CrN and CrD being independent factors on regression analysis. CrD value of ≥102 μmol/L had sensitivity of 94.4% and specificity of 68.3%, with a PPV of 56.7% (CI: 37.4–74.5) and a NPV of 96.6% (CI: 82.2–99.9). CrN of ≥89 μmol/L had sensitivity of 27.8% and a specificity of 95.1% with a PPV of 71.4% (CI: 29%–96.3%) and NPV of 75% (CI: 61.1%–86%) in predicting ESRD. ConclusionIn our environment, a child with initial creatinine value of less than 102 μmol/L may be classified as unlikely to develop ESRD. Additionally, a nadir creatinine greater than 89 μmol/L may increase the probability of developing ESRD. While nadir creatinine has consistently been identified as independent indicator of outcome, its value is evaluated after a year of management; however, early indicator like creatinine at diagnosis may provide essential monitoring information at the onset of treatment.

The chromosome 6q22.33 region is associated with age at diagnosis of type 1 diabetes and disease risk in those diagnosed under 5\xa0years of age

Aims/hypothesisThe genetic risk of type 1 diabetes has been extensively studied. However, the genetic determinants of age at diagnosis (AAD) of type 1 diabetes remain relatively unexplained. Identification of AAD genes and pathways could provide insight into the earliest events in the disease process.MethodsUsing ImmunoChip data from 15,696 cases, we aimed to identify regions in the genome associated with AAD.ResultsTwo regions were convincingly associated with AAD (p < 5 × 10−8): the MHC on 6p21, and 6q22.33. Fine-mapping of 6q22.33 identified two AAD-associated haplotypes in the region nearest to the genes encoding protein tyrosine phosphatase receptor kappa (PTPRK) and thymocyte-expressed molecule involved in selection (THEMIS). We examined the susceptibility to type 1 diabetes at these SNPs by performing a meta-analysis including 19,510 control participants. Although these SNPs were not associated with type 1 diabetes overall (p > 0.001), the SNP most associated with AAD, rs72975913, was associated with susceptibility to type 1 diabetes in those individuals diagnosed at less than 5 years old (p = 2.3 × 10−9).Conclusion/interpretationPTPRK and its neighbour THEMIS are required for early development of the thymus, which we can assume influences the initiation of autoimmunity. Non-HLA genes may only be detectable as risk factors for the disease in individuals diagnosed under the age 5 years because, after that period of immune development, their role in disease susceptibility has become redundant.

Family History of Early Infant Death Correlates with Earlier Age at Diagnosis But Not Shorter Time to Diagnosis for Severe Combined Immunodeficiency.

Severe combined immunodeficiency (SCID) is fatal unless treated with hematopoietic stem cell transplant. Delay in diagnosis is common without newborn screening. Family history of infant death due to infection or known SCID (FH) has been associated with earlier diagnosis. The aim of this study was to identify the clinical features that affect age at diagnosis (AD) and time to the diagnosis of SCID. From 2005 to 2016, 147 SCID patients were referred to the Asian Primary Immunodeficiency Network. Patients with genetic diagnosis, age at presentation (AP), and AD were selected for study. A total of 88 different SCID gene mutations were identified in 94 patients, including 49 IL2RG mutations, 12 RAG1 mutations, 8 RAG2 mutations, 7 JAK3 mutations, 4 DCLRE1C mutations, 4 IL7R mutations, 2 RFXANK mutations, and 2 ADA mutations. A total of 29 mutations were previously unreported. Eighty-three of the 94 patients fulfilled the selection criteria. Their median AD was 4 months, and the time to diagnosis was 2 months. The commonest SCID was X-linked (n = 57). A total of 29 patients had a positive FH. Candidiasis (n = 27) and bacillus Calmette-Guérin (BCG) vaccine infection (n = 19) were the commonest infections. The median age for candidiasis and BCG infection documented were 3 months and 4 months, respectively. The median absolute lymphocyte count (ALC) was 1.05 × 109/L with over 88% patients below 3 × 109/L. Positive FH was associated with earlier AP by 1 month (p = 0.002) and diagnosis by 2 months (p = 0.008), but not shorter time to diagnosis (p = 0.494). Candidiasis was associated with later AD by 2 months (p = 0.008) and longer time to diagnosis by 0.55 months (p = 0.003). BCG infections were not associated with age or time to diagnosis. FH was useful to aid earlier diagnosis but was overlooked by clinicians and not by parents. Similarly, typical clinical features of SCID were not recognized by clinicians to shorten the time to diagnosis. We suggest that lymphocyte subset should be performed for any infant with one or more of the following four clinical features: FH, candidiasis, BCG infections, and ALC below 3 × 109/L.