Median Age Of Onset Research Articles

Clinical Characteristics of Myasthenia Gravis Patients with COVID-19 in Guangxi, China: A Case-Control Study.

With the adjustment of prevention strategies in December 2022, coronavirus disease 2019 (COVID-19) became widely prevalent in China. This study is aimed to describe the clinical characteristics of myasthenia gravis (MG) patients with COVID-19 and identify risk factors of exacerbation in MG patients with COVID-19 in Guangxi. A total of 489 MG patients and 587 control subjects in Guangxi during the COVID-19 pandemic were enrolled in this case-control study. After contacting the participants, the clinical data of MG patients and the control group were analyzed. The clinical characteristics of MG patients with COVID-19 were described. Multivariable logistic regression analysis was used for discovering independent risk factors of MG exacerbation in the patients with MG and COVID-19. A total of 311 (75.30%) MG patients and 428 (72.91%) control subjects were infected with COVID-19, and 64.31% of MG patients with COVID-19 were women. The median age at the time of interview was 41 (IQR: 28, 54) years old, and median onset age was 36 (IQR: 24, 51), both of which were lower than those in MG patients without COVID-19. MG duration was 24 (IQR: 9, 72) months. About 44.69% of patients were generalized MG (GMG). About 11.90% of MG patients with COVID-19 showed severe COVID-19 symptoms and the duration of symptomatic COVID-19 was 9.57 ± 6.79 days, higher than those in the control group. About 35.69% MG patients with immunosuppressive drugs were infected with COVID-19, which is higher than those in the non-infected MG patients (21.57%). A total of 120 (38.59%) MG patients with COVID-19 had comorbidities. About 21 (20.19%) of the 104 MG patients without vaccination showed severe COVID-19 symptoms. Multivariable logistic regression analysis showed that baseline MG activities of daily living profile (MG-ADL, OR 1.280, 95% CI: 1.010-1.621, p = 0.041), duration of COVID-19 (OR 1.158, 95% CI: 1.100-1.220, p < 0.001), GMG (OR 2.331, 95% CI: 1.228, 4.426, p = 0.010), and lack of COVID vaccination (OR 2.075, 95% CI: 1.152, 3.738, p = 0.015) were independent factors of exacerbation in MG patients with COVID-19. MG patients with immunosuppressive drugs, younger onset, longer MG duration, or comorbidities are more susceptible to COVID-19. The baseline MG-ADL, duration of symptomatic COVID-19, GMG, and lack of COVID-19 vaccination are independent risk factors of exacerbation in MG patients with COVID-19.

Long-term analysis of adrenocorticotropic hormone monotherapy for infantile epileptic spasms syndrome with periventricular leukomalacia.

Infantile epileptic spasms syndrome (IESS) with periventricular leukomalacia (PVL) has a poor neurological prognosis. Adrenocorticotropic hormone (ACTH) and vigabatrin therapies are the recommended first-line treatments for IESS. However, ACTH monotherapy for IESS with PVL has not been studied in detail. We analysed long-term outcomes of ACTH monotherapy for IESS with PVL. We retrospectively examined 12 patients with IESS and PVL at Saitama Children's Medical Center between January 1993 and September 2022. We evaluated seizure outcomes 3 months post-ACTH therapy and at the last visit. We also assessed electroencephalography findings and developmental outcomes. A positive response was defined as complete remission of epileptic spasms, no other seizure types, and hypsarrhythmia resolution post-ACTH therapy. The median onset age of epileptic spasms was 7 (range: 3-14) months. The median age at initiation of ACTH therapy was 9 (7-17) months. Seven of 12 patients (58.3%) showed a positive response. The median age at the last visit was 5 years and 6 months (1 year and 5 months-22 years and 2 months). At the last visit, only 2 of 7 initial responders remained seizure-free who demonstrated normal electroencephalography findings within 1-month post-ACTH therapy. Patients with epileptic discharge in the parieto-occipital region within 1-month post-ACTH therapy showed relapse of epileptic spasms or other seizure types. Patients having epileptic discharge in the parietal or occipital regions on electroencephalography within 1-month post-ACTH therapy may be at a high risk of epileptic spasm recurrence or other seizure types in the long term.

Biological therapy of seropositive juvenile idiopathic arthritis: Results of a retrospective single-center study

Seropositive juvenile idiopathic arthritis (JIA) is one of the rarest and most unfavorable subtypes of juvenile arthritis, characterized by an increased frequency of inefficacy of therapy. Objective – to characterize biologic therapy in patients with seropositive JIA, to identify factors influencing the choice of a biological agents (BA) and the need to replace it, to evaluate the value of the JADI damage index for predicting the response to BA.Material and methods. The diagnosis of seropositive JIA for the period from 2010 to 2022 was verified in 92 patients, 10.9% were boys. The median age of JIA onset in the study group was 12.0 [7.7; 14.0] years. BA were prescribed to 89.1% of patients in the study group, 31.7% of them for a period of less than 1 year from the onset. The median number of active joints at the time of BA initiation was 15 [10; 22], median ESR – 29 [18; 43] mm/h, CRP – 15.0 [5.3; 31.0] mg/l. Extra-articular manifestations at the time of prescribing BA occurred in 29.0% of patients. The analysis of factors that could influence the need to switch BA was carried out: age of onset, timing of diagnosis verification and initiation of BA, gender, the number of active joints at the start of BA, ACCP positivity, RF, ACCP, ESR and CRP values – at the time of BA appointment, the presence of secondary Sjögren’s syndrome. Since 2021, the complex of examinations included the calculation of the JADI (The Juvenile Arthritis Damage Index) damage index in all patients from the study group who were admitted to the hospital (28 in total; 17.9% – boys). The median age of JIA onset among them was 10.5 [6.31; 13.0] years, 81.2% received BA. The JADI index was compared with the ACCP, RF, CRP, ESR and the need to prescribe and switch BA. The design of the study was a retrospective, open-label, non-randomized, uncontrolled study. Results. In the study group of patients, 29% had experience with more than 1 BA. Abatacept (45.1%), TNF-inhibitors (40.3%) were most often used as the first BA; tocilizumab and rituximab were predominantly used in the 2nd–4th line of therapy, with a trend towards their more frequent prescription in recent years. The main reason for switching from one BA to another is the secondary failure of therapy, 4.9% of patients have serious adverse reactions (AE). In general, AEs that did not require discontinuation of therapy were recorded in 24.6% of patients. Patients who received more than 1 BA had relatively higher values of RF, ACCP and significantly higher CRP. The mean value of JADI-A was 2.39 points, 50% of patients had significant JADI-A scores, 92.8% of whom received BA with experience of more than 1 prescription of BA in 28.6% of them. A direct correlation of the JADI index with ACCP, ESR and CRP was revealed. Conclusions. Seropositive JIA is characterized by a high need for prescribing BA, the frequency of prescribing BA is associated with significant indicators of the JADI damage index. The choice of a specific BA is determined, first of all, by the presence of systemic manifestations or secondary Sjögren’s syndrome. In patients with high surrogate measures of activity (especially CRP), given the high risk of secondary failure of TNF-inhibitors, tocilizumab in the first line of therapy may be considered as the preferred choice. Our data did not reveal an effect of ACCP positivity on the preferred choice or frequency of BA replacement. Attention was drawn to the trend towards higher RF and ACCP values in patients treated with more than one BA. A correlation was established between the JADI index and ACCP, ESR, and CRP, which indirectly leads to the conclusion that it is necessary to prescribe BA earlier in this category of patients in order to avoid permanent damage and increase the effectiveness of thera py. The use of BA had an acceptable safety profile.

Epidemiology of depressive disorders among youth during Gaokao to college in China: results from Hunan Normal University mental health survey

BackgroundGiven the serious consequences of depression and the lack of information about it during the crucially developmental period from the National College Entrance Exam (CEE, i.e., Chinese gaokao) to college, this study aimed to estimate the cumulative incidence, prevalence, age of onset, correlates, and service use of depressive disorders (DDs) among youth who passed the CEE and were enrolled at Hunan Normal University in China.MethodsA two-stage cross-sectional epidemiological survey of DDs was conducted from October to December, 2017 among 6,922 incoming college students (98.5% effective response, N = 6,818, 71.4% female, age range: 16–25 years, mean age = 18.6). Using a stratified sampling method based on the risk of depression, 926 participants (mean age = 18.5, 75.2% female) were selected and subsequently interviewed with the Kiddie–Schedule for Affective Disorders and Schizophrenia–Present and lifetime version (K-SADS-PL).ResultsThe sex-adjusted 9-month (i.e., 3 months pre-CEE, 3 months after CEE, and 3 months post-matriculation) incidence of new-onset DDs was 2.3% (standard error [S.E.] 0.3%), and the sex-adjusted 1-month, 6-month and lifetime prevalence were 0.7 (S.E. 0.3%), 1.7 (S.E. 0.2%) and 7.5% (S.E. 1.3%), respectively. The median age of onset was 17 (interquartile range: 16–18) years. Critically, over one-third (36.5%, S.E. 0.6) of depressed youth had their new onset during the 9-month period. The risk factors for depression included having mothers with higher education, experiencing major life events, being female, and experiencing parental divorce or death. The adjusted lifetime treatment rate was 8.7%.ConclusionThe 9-month incidence of new-onset depression from gaokao to college among the youth sample in China is similar to the global annual incidence (3.0%), but the 1-month and lifetime prevalence are significantly lower than the global point (7.2%) and lifetime prevalence (19%). These findings suggest a high proportion of new-onset depression during the CEE to college among the sample youth in China. The risk of depression is associated with familial and stress correlates. Low treatment is a serious concern. Emphasis on early prevention and available treatment for adolescent and young adult depression is a critical need in China.

The phenotype and genotype of Chinese adult patients with NLRP3-associated autoinflammatory disease.

NLRP3-associated autoinflammatory disease (NLRP3-AID) is a spectrum of autosomal dominant inherited diseases associated with NLRP3 gene mutations. Reports of Chinese NLRP3-AID cases are limited to date. In the present study, we aim to describe the phenotype and genotype of a cohort of Chinese adult NLRP3-AID patients METHODS: This single-center study included sixteen adult patients diagnosed with NLRP3-AID at Department of Rheumatology, Peking Union Medical College Hospital from April 2015 to September 2021. Whole-exome sequencing using next-generation sequencing was performed in each patient. Clinical data and mutational information were compared with a European cohort. The median age of disease onset was 16 (0-46) years old, and adult-onset was observed in 4 patients (25%). The median time of diagnosis delay was 20 (0-39) years. Five patients (31.3%) had family history of similar symptoms. The most common clinical manifestations were recurrent fever (93.8%), arthralgia/arthritis (81.3%), skin rash (75%), myalgia (62.5%), and central nervous system manifestations (50%). Heterozygous NLRP3 variants detected in these patients were p.T348M (n = 4, 25%), Q703K, V70M, K129R, M116I, P38S, V442I, D303G, G326E, A439V, K829T, L632F and V198M (n = 1, separately). All the variants were missense mutations. We reported the largest case series of Chinese adult NLRP3-AID patients. The distinct symptoms of NLRP3-AID patients suggest the heterogeneity of disease. P38S, M116I, K129R, V442I and K829T were identified as novel NLRP3 variants. These data expand the clinical phenotypic and genotypic profiles of NLRP3-AID. Key Points • We characterized the clinical and genetic features of sixteen Chinese adult NLRP3-AID patients. • Thirteen NLRP3 gene variants were confirmed in this cohort, and P38S, M116I, K129R, V442I and K829T were identified as novel variants. • Clinical data and mutation information were compared with a European cohort. • We hope these data would expand the phenotypic and genotypic profile of NLRP3-AID and raise the awareness of early diagnosis and accurate treatment among rheumatologists.

Cerebral venous thrombosis (CVT) complicating tubercular meningitis

BackgroundTuberculous meningitis (TBM), complicated with cerebral venous thrombosis (CVT), has been sparsely reported and needs to be investigated further.MethodsAmong those with tuberculous meningitis in Haihe Hospital, Tianjin University, 3 patients with venous sinus thrombosis were identified retrospectively. “Tuberculous meningitis” and “cerebral venous thrombosis” were used as keywords, and the retrieved literature was summarized and analyzed. Our data were combined with previously reported case data to describe this new condition.ResultsAmong 28 patients with a median onset age of 31 years for TBM, 17 were females. The manifestations were fever, headache, and seizure. Magnetic resonance imaging (MRI) venography showed that the most common site of venous sinus thrombosis involved superior sagittal sinus, left transverse sinus, left sigmoid sinus, cavernous sinus, and straight sinus. The abnormalities found on MRI include hydrocephalus, exudates, hemorrhage, meningeal enhancement, infarction, and tuberculoma. In the acute phase, all patients received standard anti-TB treatment, and 14/28 patients received anticoagulant treatment. The mortality rate of these patients was 17.9%, and 21/28 (75%) became functionally independent.ConclusionsCVT is one of the rare complications of TMB and must be considered a differential diagnosis in patients with TBM who show poor clinical features and/or develop new neurological signs.

Clinicopathological Features and Prognosis of Lung Adenocarcinoma Patients With K-RAS Gene Mutation.

To investigate the relationship between K-RAS gene mutation and clinicopathological features and prognostic factors in lung adenocarcinoma. A total of 795 patients with lung adenocarcinoma diagnosed and tested for ten genes from January 1, 2016, to December 31, 2019, were reviewed. One hundred forty patients with K-RAS gene mutation lung adenocarcinoma were screened, of which 82 cases were included in this group, and complete follow-up data were obtained. PD-L1 immunohistochemistry was further performed, and the correlation between K-RAS mutation patients and clinicopathological features and related driver genes was analyzed. The survival curve was drawn by Kaplan-Meier curve. The effects of clinicopathological features on patients' survival were analyzed by Cox univariate and multivariate analysis. The age of onset of 82 patients with K-RAS gene mutation lung adenocarcinoma was 46 to 89 years old, and the median age of onset was 69 years old. There were 64 male patients (78.05%) and 18 female patients (21.95%), including 68 smokers (82.93%). Tumor size: 2 to 5.5 cm, with an average tumor size of 3.5 cm. Histopathologic types: solid type in 60 cases (73.17%), micropapillary type in 2 cases (2.43%), and invasive mucinous type in 20 cases (24.39%). The degree of tumor differentiation: well-differentiated: 0 cases, moderately differentiated: 10 cases (12.20%), poorly differentiated: 72 cases (87.80%). Fifty cases (60.98%), 29 cases (35.37%), 29 cases (35.37%), 59 cases (71.95%), and 35 cases (42.68%) were complicated with nerve invasion, vascular invasion, visceral pleura invasion, lymph node metastasis, and distant organ metastasis, respectively. Among them, distant organ metastasis included 24 cases (68.57%) of bone metastasis and 11 cases (36.67%) of brain metastasis. Tumor Ki-67 proliferation index ≥50%: 54 cases (65.85%). Related driver gene mutations: There were 6 cases (7.31%) with a deletion mutation of exon 19 in EGFR or L858R mutation of exon 21 in EGFR, respectively. Immune factor PD-L1 ≥50%: 65 cases (79.27%). The patients were followed up for 402 to 1221 days, with a median follow-up of 612 days. Thirty-five cases died during the follow-up. The 1-, 3-, and 5-year overall survival rates were 100%, 62.20%, and 57.31%, respectively. Cox univariate analysis showed that the degree of tumor differentiation, vascular invasion, distant organ metastasis, Ki-67 index, deletion mutation of exon 19 in EGFR, and high expression of PD-L1 (≥50%) could all affect the prognosis of patients ( P < 0.05). Cox multivariate analysis showed that high expression of PD-L1 (≥50%) was an independent predictor of prognosis in patients with K-RAS gene mutation in lung adenocarcinoma. K-RAS mutant lung adenocarcinoma is a malignant tumor with high invasiveness and high mortality. The degree of tumor differentiation, vascular invasion, distant organ metastasis, Ki-67 index, deletion mutation of exon 19 in EGFR, and high expression of PD-L1 (≥50%) in patients with K-RAS mutation lung adenocarcinoma can affect the overall survival time of patients. The high expression of PD-L1 (≥50%) is an independent risk factor affecting the prognosis (survival time).

215-LB: Comparison of Clinical and Serological Features among Type III APS, Isolated T1DM, and LADY/LADA

Type III autoimmune polyendocrine syndromes (APS) is characterized by the coexistence of autoimmune thyroid disease (AITD) and T1DM. There is a rare series of studies on APS in Chinese population. This paper retrospectively analyzed the clinical and serological features of Chinese patients with type III APS who admitted to our center from Sept 2018 to Oct 2022, and compared the similarities and differences with isolated T1DM, LADY/LADA patients at the same time. The study included 69 patients, 18 patients with type III APS, 20 patients with T1DM, and 31 patients with LADY/LADA. Type III APS was predominantly female, while T1DM and LADY/LADA groups were the opposite (72.22% vs 35.00% vs 38.71%, P = 0.037). The median age of onset of diabetes in the three groups was 30.50, 23.00 and 41.00 years, respectively (P &amp;lt; 0.001). Hashimoto's thyroiditis (HT) (n=13, 72.22%) was the main AITD in type III APS group, followed by Graves’ disease (Table 1). The median of GADAb in the three groups were 1501.43, 115.01 and 301.02 U/mL, respectively (P = 0.022). And the levels of TPOAb and TGAb in type III APS group were significantly higher than those in the other two groups (P &amp;lt;0.05). Type III APS is more common in women with diabetes onset later than those with isolated T1DM and earlier than those with LADY/LADA. HT is the main AITD in type III APS patients, and the levels of GADAb and thyroid autoantibodies in patients with type III APS are often higher. Disclosure Y. Qiu: None. J. Guo: None. P. Wei: None. H. He: None. M. Jin: None. H. Zhao: None. H. Li: None. Q. Li: None.

Clinical and endoscopic features of primary small bowel lymphoma: a single-center experience from mainland China.

The worldwide incidence of primary small intestinal lymphoma (PSIL) is increasing. However, little is known about the clinical and endoscopic characteristics of this disease. The aim of this study was to investigate the clinical and endoscopic data of patients with PSIL, with the goal of enhancing our understanding of the disease, improving diagnostic accuracy, and facilitating more accurate prognosis estimation. Ninety-four patients diagnosed with PSIL were retrospectively studied at Qilu Hospital of Shandong University between 2012 and 2021. The clinical data, enteroscopy findings, treatment modalities, and survival times were collected and analyzed. Ninety-four patients (52 males) with PSIL were included in this study. The median age of onset was 58.5 years (range: 19-80 years). Diffuse large B-cell lymphoma (n=37) was the most common pathological type. Abdominal pain (n=59) was the most frequent clinical presentation. The ileocecal region (n=32) was the most commonly affected site, and 11.7% of patients had multiple lesions. At the time of diagnosis, the majority of patients (n=68) were in stages I-II. A new endoscopic classification of PSIL was developed, including hypertrophic type, exophytic type, follicular/polypoid type, ulcerative type, and diffusion type. Surgery did not show a significant increase in overall survival; chemotherapy was the most commonly administered treatment. T-cell lymphoma, stages III-IV, "B" symptoms, and ulcerative type were associated with poor prognosis. This study provides a comprehensive analysis of the clinical and endoscopic features of PSIL in 94 patients. This highlights the importance of considering clinical and endoscopic characteristics for accurate diagnosis and prognosis estimation during small bowel enteroscopy. Early detection and treatment of PSIL is associated with a favorable prognosis. Our findings also suggest that certain risk factors, such as pathological type, "B" symptoms, and endoscopic type, may affect the survival of PSIL patients. These results underscore the need for careful consideration of these factors in the diagnosis and treatment of PSIL.

HOGA1 variants in Chinese patients with primary hyperoxaluria type 3: genetic features and genotype-phenotype relationships.

The aim of our study is to describe the genetic features and correlation between the genotype and phenotype of Chinese patients with primary hyperoxaluria type 3 (PH3). The genetic and clinical data of PH3 patients in our cohort were collected and analyzed retrospectively. All published studies of Chinese PH3 populations between January 2010 and November 2022 were searched and enrolled based on inclusive standards. A total of 60 Chinese PH3 patients (21 cases from our cohort and 39 cases from previous studies) were included. The mean age of onset was 1.62 ± 1.35 (range 0.4-7) years. A total of 29 different variants in the HOGA1 gene were found. The mutations were most commonly clustered in exons 1, 6, and 7. Among the genotypes, exon 6 skipping (c.834G > A and c.834_834 + 1GG > TT mutations) was the most common, followed by c.769T > G; the allele frequencies (AFs) were 48.76% and 12.40%, respectively. Patients homozygous for exon 6 skipping exhibited a median age of onset of 0.67 (0.58-1) years, which was significantly lower than that observed among heterozygotes and nonexon 6 skipping patients (p = 0.021). A total of 22.5% (9/40) of PH3 patients had a decreased estimated glomerular filtration rate, and one patient with homozygous exon 6 skipping developed end-stage renal disease. A hotspot mutation, potential hotspot mutation and genotype-phenotype correlation were found in Chinese PH3 patients. This study expands the mutational spectrum and contributes to the understanding of genotypic profiles of PH3, which may provide a potential diagnostic and therapeutic target.

Evaluation of the clinical, biochemical, genotype and prognosis of mut-type methylmalonic acidemia in 365 Chinese cases

BackgroundMethylmalonic acidemia (MMA), which results from defects in methylmalonyl-CoA mutase (mut type) or its cofactor, is the most common inherited organic acid metabolic disease in China. This study aimed to...

Clinical Profile of Congenital Factor XIII Deficiency in Children.

Congenital Factor 13 Deficiency (FXIIID) is a rare bleeding disorder (RBD) of autosomal recessive inheritance, with an incidence of 1 in 3-5million. The clinical symptomatology, diagnosis, and management of FXIIID are described. A retrospective chart review of children with FXIIID was performed from January 2000 through October 2021 at a tertiary care center in Southern India. The diagnosis was performed by the Urea clot solubility test (UCST) and Factor XIII antigen assay. Twenty children (representing 16 families) were included. Male: Female ratio was 1.5:1. The median age of symptom onset was 6 mo, and the median age of diagnosis was 1 y, demonstrating a delay in diagnosis. Consanguinity was present in 15 (75%) with 4 children having affected siblings. Clinical symptomatology ranged from mucosal bleeds to intracranial bleeds and hemarthrosis, with many children having a history of prolonged umbilical bleeding in their neonatal period. Fourteen children were on cryoprecipitate prophylaxis. Four children had breakthrough bleeds due to irregular prophylaxis, including one intracranial bleed due to a delay in cryoprecipitate prophylaxis during the covid pandemic. Congenital FXIIID presents with a wide range of bleeding manifestations. The high prevalence of consanguinity in Southern India can be a cause of FXIIID's high prevalence in this region. There is a propensity for intracranial bleeding with a significant number having this at first presentation. Regular prophylaxis is required and feasible to prevent potentially fatal bleeds.

#3295 RAPIDLY PROGRESSIVE AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE : RISK FACTORS FOR DISEASE SEVERITY DURING CHILDHOOD AND EARLY ADULTHOOD

Abstract Background and Aims Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic kidney disease and is characterized by genetic complexity and phenotypic variability. The age of reaching kidney failure (KF) is variable and covers the complete age-spectrum. There is an unmet need for early biomarkers to differentiate between rapid and slow progressors. The PROPKD score identified hypertension before the age of 35 years as a risk factor for rapid kidney function decline. We aim to identify earlier risk factors for rapid disease progression by studying a population of ADPKD patients who reached kidney failure (KF) before the age of 40y. Method This multicentric retrospective study focusses on a unique population (n = 200) of ADPKD patients who reached KF before 40y. Kidney failure (KF) was defined as CKD5 or start of Kidney Replacement Therapy (KRT), whichever came first. Longitudinal data on childhood history, comorbidities and kidney function were collected. Life table and Proportional Hazards analysis were used to assess associations between clinical parameters and time to KF. Results Median age of ADPKD diagnosis was 22.3 (16.5 – 28.6) and median age of KF onset was 36.2 years (32.9-38.7 years). Fourty-seven patients were genotyped (23.5%) of which 38 patients (81.0%) were PKD1T and 8 (17.0%) were PKD1NTand only 1 patient (2.1%) was PKD2. Median age at first urological event was 27.0 (20.7 – 32.0) years. 71 patients (35.5%) had history of UTI's, 67 patients (33.5%) had hemorrhagic cysts on abdominal imaging, 66 patients (33.0%) presented with gross hematuria and 40 patients (25.0%) presented with kidney stones. There was a high prevalence of hypertension (N = 128, 64.0%). Four patients (N = 4/128, 3.1%) had a very early diagnosis of hypertension before the age of 10 years. Hypertension-onset before the age of 18 years correlated with a significantly faster progression (UV HR: 2.07 (1.32 – 3.25)). Conclusion This study describes a unique cohort of ADPKD patients with rapid disease progression. Hypertension at young age (&amp;lt;18) correlated with rapid disease progression, suggesting that ambulatory blood pressure in children might be useful to identify patients at risk for rapidly progressive ADPKD.

HGG-27. THE IMPACT OF MISMATCH REPAIR DEFICIENCY ON GLIOMAS IN CHILDREN, ADOLESCENTS, AND YOUNG ADULTS; A REPORT FROM THE IRRDC AND THE GLIOMA TASK FORCE

Abstract Mismatch repair deficiency (MMRD) is a pan-cancer mechanism resulting in universal hypermutation. MMRD-gliomas are resistant to chemoradiation but respond to immunotherapy. MMRD can occur somatically or be inherited as part of Lynch Syndrome (LS) or Constitutional Mismatch Repair Deficiency (CMMRD). However, the prevalence of MMRD in gliomas of children, adolescents, and young adults (CAYA), and impact of germline inheritance is unknown. We utilized functional genomic tools on population-based and validation cohorts from 3 large databases (Toronto, St-Jude and CBTN) to determine the prevalence, subgroup, and impact of germline mutations on MMRD-gliomas. Ongoing data on 998 pediatric-gliomas from Toronto reveals that MMRD is extremely rare in pediatric low-grade gliomas (PLGG) but common in pediatric high-grade gliomas (PHGG) (9%, p&amp;lt;0.0001). Similarly, data from St-Jude and CBTN (n=374) reveals that MMRD exists only in PHGG (8%). In both cohorts, MMRD-PHGG are enriched for RAS/MAPK, IDH, and TP53 mutations while pediatric-type fusions, BRAF-V600E and histone mutations are absent. In AYA-HGG (n=884), the most common groups include glioblastomas without chromosome-7/10 alterations (9%) and IDH1-astrocytomas, while MMRD is not present in IDH-oligodendrogliomas. All but 1 CAYA-MMRD-gliomas harbored germline MMR mutations. Data from the IRRDC on 174 patients reveal that LS is more common than CMMRD in gliomas, with the median age of onset 11 and 29 years in CMMRD and LS, respectively (p&amp;lt;0.001). Furthermore, CMMRD gliomas are commonly caused by germline PMS2 and MSH6 mutations, enriched for secondary polymerase mutations (60%, p&amp;lt;0.001), and exhibit ultra-hypermutation. In contrast, LS-gliomas are caused by MSH2 and MLH1 mutations, and enriched for IDH1 mutations (32%, p&amp;lt;0.025) with a lower mutational burden. Our data reveals high prevalence of MMRD in CAYA-HGG with alarming impact of germline predisposition. Specifically, unrecognized LS patients with AYA MMRD-HGG. These findings support universal screening for MMRD in HGG to identify patients for immunotherapy and surveillance.

Pediatric myelin oligodendrocyte glycoprotein antibody-associated disease in southern China: analysis of 93 cases.

To study the clinical features of children diagnosed with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) in southern China. Clinical data of children diagnosed with MOGAD from April 2014 to September 2021 were analyzed. A total of 93 children (M/F=45/48; median onset age=6.0 y) with MOGAD were involved. Seizures or limb paralysis was the most common onset or course symptom, respectively. The most common lesion locations in brain MRI, orbital MRI, and spinal cord MRI were basal ganglia and subcortical white matter, the orbital segment of the optic nerve, and the cervical segment, respectively. ADEM (58.10%) was the most common clinical phenotype. The relapse rate was 24.7%. Compared with the patients without relapse, relapsed patients had a longer interval from onset to diagnosis (median: 19 days VS 20 days) and higher MOG antibody titer at onset (median: 1:32 VS 1:100) with longer positively persistent (median: 3 months VS 24 months). All patients received IVMP plus IVIG at the acute phase, and 96.8% of patients achieved remission after one to three courses of treatment. MMF, monthly IVIG, and maintaining a low dose of oral prednisone were used alone or in combination as maintenance immunotherapy for relapsed patients and effectively reduced relapse. It transpired 41.9% of patients had neurological sequelae, with movement disorder being the most common. Compared with patients without sequelae, patients with sequelae had higher MOG antibody titer at onset (median: 1:32 VS 1:100) with longer persistence (median: 3 months VS 6 months) and higher disease relapse rate (14.8% VS 38.5%). Results showed the following about pediatric MOGAD in southern China: the median onset age was 6.0 years, with no obvious sex distribution difference; seizure or limb paralysis, respectively, are the most common onset or course symptom; the lesions of basal ganglia, subcortical white matter, the orbital segment of the optic nerve, and cervical segment were commonly involved in the CNS MRI; ADEM was the most common clinical phenotype; most had a good response to immunotherapy; although the relapse rate was relatively high, MMF, monthly IVIG and a low dose of oral prednisone might effectively reduce relapse; neurological sequelae were common, and possibly associated with MOG antibody status and disease relapse.

Analysis of clinical characteristics of thyroid phenotype in Pendred syndrome based on multiple databases.

This study aimed to provide statistical data support for the development of thyroid phenotype-related follow-up and reference for follow-up duration and project selection by analyzing the clinical characteristics of thyroid phenotype in Pendred syndrome (PDS) based on multiple databases. PDS-related pathogenic or possibly/pathogenic mutations were searched by Deafness Variation Database (DVD), ClinVar, and PubMed databases, the mutation sites were counted and the characteristics and thyroid phenotypes were analyzed. The median age of hearing phenotype onset in PDS cases reported in multiple databases was 1.0 (1.0, 2.0) years, the median age of thyroid phenotype onset was 14.5 (5.8, 21.0) years, and the median age that thyroid phenotype was more delayed than hearing phenotype was 10.0 (4.0, 17.0) years. There were significant differences in the distribution of onset time between the two phenotypes (Z=-4.560, p<0.01). In these patients, the positive rates of goiter, thyroid nodules, abnormal thyroid function, and perchlorate discharge test (PDT) were 78%, 78%, 69%, and 78%, respectively. Moreover, the number of thyroid phenotype-positive items in the genotype group with frameshift mutation was not significantly higher than that in the group without frameshift mutation (Z=-1.452, p=0.147). The early missed diagnosis of PDS may be due to the late onset of thyroid phenotype and the non-100% positive rate of examination items. Therefore, multi-item follow-up of the thyroid gland into adulthood will benefit patients. At present, the relationship between genotype and phenotype is still unclear, and prognosis cannot be determined according to genotype.

Clinicopathological analysis of 18 cases of secretory carcinoma of the salivary glands

Background/purposeSecretory carcinoma (SC) is a rare salivary gland tumor that featured by ETV6::NTRK3 gene fusion, and was included in the WHO Classification of Head and Neck Tumors since 2017. Nevertheless, the description of SCs by WHO is still vague. This study examined 18 SC cases by using both histomorphology and molecular pathology for diagnostic determination, especially immunohistochemical features of SCs. Materials and methodsBased on WHO characteristics, 18 patients with SC admitted between 2001 and 2022 were included in this study. Main histomorphological patterns, FISH analyses of the ETV6::NTRK3 gene fusion, and immunohistochemical analyses of S100, mammaglobin, DOG1, ADFP, CA6 and Ki-67 were performed. ResultsAmong the 18 SC patients, the median age of onset was 39.22 years. Grossly, the average tumor size in 2.96 cm with various texture from soft to tough. The majority patients were positive for S100, mammaglobin, and negative for DOG1, except for one patient negative for S100 (Case 18). All patients were positive for ADFP, and the majority patients were negative for CA6, except for Case 9. Two cases were found recurrence, and the tumor were found both in parotid gland with local invasion. ConclusionCombined with the results of previous studies, we proposed that the combination of all five markers, S100, mammaglobin, DOG1, ADFP and CA6, could contribute more to differential diagnosis of SCs with other salivary carcinomas, especially with AciCC. The prognosis of SCs is optimistic in most cases, but larger patient cohort and long-term follow-up are still needed.

Intraosseous extension of supraspinatus calcific tendonitis in a young patient with severe shoulder pain: a rare case report

Abstract Calcific tendinopathy is one of the causes of shoulder pain and limited range of motion when it affects the rotator cuff tendons. Complications of such a condition are rare and include intraosseous and intramuscular migration. Calcific tendonitis can be classified as acute, subacute or chronic based on the onset of symptoms. The incidence of calcific tendonitis affects females more than males, with the median age of onset being between 40 and 60 years old. Diagnostic modalities include radiographs and computed tomography (CT); however, these are suboptimal when compared to the sensitivity of magnetic resonance imaging. Ninety percent of these cases are treated non-surgically. We present a rare case of a young female patient with right shoulder pain and limited range of motion secondary to the intraosseous migration of calcific tendonitis. The patient’s symptoms were resolved after a CT-guided percutaneous bone biopsy of the lesion. Clinical correlation with the aid of imaging and histopathology is a multimodal approach to help diagnose and treat such conditions.

P295 The results of colorectal cancer screening in patients with cystic fibrosis in Wales

The Cystic Fibrosis Colorectal Cancer Screening Consensus Recommendations reports the median age of onset of colorectal cancer (CRC) in patients with Cystic Fibrosis (PwCF) is 20–30 years younger than the general population and advocates colonoscopy as the screening method of choice. The All Wales Adult Cystic Fibrosis Centre (AWACFC) have developed local guidelines in response. Results of patients who have had CRC screening were reviewed to help inform future investigations.

Characterizing the molecular landscape of early onset and average onset prostate cancer.

5059 Background: Prostate cancer (PC) has a median onset age of 66, however, recent evidence suggests an increase in incidence of PC diagnosis in males &lt;55 years of age. Family history and increased mutational burden has been associated with early onset PC (EOPC), nonetheless, comprehensive molecular and immune signatures that cluster in EOPC and average onset PC (AOPC) is poorly understood. Here, we characterized EOPC and AOPC, and their association with molecular and immune signature. Methods: 5,305 PC samples (&lt;55 yrs, n=575; ≥65 yrs, n=4730) were tested by NGS (592, NextSeq; WES, NovaSeq), WTS (NovaSeq) (Caris Life Sciences, Phoenix, AZ). PC Patients with age &lt;55 and ≥65 was classified as EOPC and AOPC, respectively. Microsatellite-instability (MSI) was tested by IHC and NGS. Tumor mutational burden (TMB) totaled somatic mutations per tumor (high≥10 mt/MB). Androgen receptor (AR) signature and Neuroendocrine Prostate Cancer (NEPC) score was calculated based on expression of a list of previously defined genes (Hieronymus et al. 2006, Beltran et al. 2016). Pathway enrichment determined by Gene Set Enrichment Analysis (Broad Inst). Immune cell fractions were calculated by deconvolution of WTS: Quantiseq. Statistical significance was determined using chi-square and Mann-Whitney U test (p &lt;0.05) along with FDR-corrected p-values (q)&lt;0.05. Results: EOPC had higher frequency of TMPRSS2 (35.8% vs 29.7%), ETV1 (5.2% vs 2.8%), ETV4 (3.4% vs 1.6%), and BRAF (1.9 vs 0.7%) fusions, but lower frequency of APC (4% vs 8%), CTNNB1 (2.4% vs 4.6%), RB1 (2.3% vs 4.7%) and AR (1% vs 4.9%) mutation, TMB high (2.1% vs 4.6%) and dMMR/MSI-H (2.1% vs 4%) compared to AOPC (all p&lt;0.05). EOPC had pathway enrichment of myogenesis (NES: 1.5, q&lt;0.01), but no difference in hedgehog signaling (NES:1.3, q=0.09) and epithelial mesenchymal transition (NES: 1.3, q=0.09) pathways compared to AOPC. EOPC had higher median NEPC score (0.359 vs 0.353, q=0.04), higher MAPK pathway activity score (MPAS) (3-fold, q=0.02) but no difference in median AR signature (q=0.39) compared to AOPC. In addition, EOPC had higher expression of PSA (1.2-fold, q&lt;0.01) and immunomodulatory genes ( IL12A, CTLA4, FC:1.2, q&lt;0.05) with reduced AR expression (1.3-fold, q&lt;0.01), however there was no difference in IHC-AR (q=1) and PD-L1 (q=0.57). Analysis of inferred immune cell infiltrates showed that EOPC had increased infiltration of NK cells (4.5% vs 4.1%, q&lt;0.01) and dendritic cells (1.9% vs 1.8% q&lt;0.05) compared to AOPC. Conclusions: Our data suggest that EOPC is enriched in fusion events including TMPRSS2, ETV1, ETV4 and BRAF. Distinct transcriptomic features seen in EOPC included neuroendocrine differentiation, MAPK activations, immunomodulatory gene expression, and increased infiltration of NK cells and dendritic cells, suggesting inherent molecular differences and differential tumor immune microenvironment in EOPC and AOPC.