Median Age Of Onset Research Articles

Study of Late-Onset Stargardt Type 1 Disease: Characteristics, Genetics, and Progression

Late-onset Stargardt disease is a subtype of Stargardt disease type 1 (STGD1), defined by an age of onset of 45 years or older. We describe the disease characteristics, underlying genetics, and disease progression of late-onset STGD1 and highlight the differences from geographic atrophy. Retrospective cohort study. Seventy-one patients with late-onset STGD1. Medical files were reviewed for clinical data including age at onset, initial symptoms, and best-corrected visual acuity. A quantitative and qualitative assessment of retinal pigment epithelium (RPE) atrophy was performed on fundus autofluorescence images and OCT scans. Age at onset, genotype, visual acuity, atrophy growth rates, and loss of external limiting membrane, ellipsoid zone, and RPE. Median age at onset was 55.0 years (range, 45-82 years). A combination of a mild and severe variant in ATP-binding cassette subfamily A member 4 (ABCA4) was the most common genotype (n= 49 [69.0%]). The most frequent allele, c.5603A→T (p.Asn1868Ile), was present in 43 of 71 patients (60.6%). No combination of 2 severe variants was found. At first presentation, all patients have flecks. Foveal-sparing atrophy was present in 33.3% of eyes, whereas 21.1% had atrophy with foveal involvement. Extrafoveal atrophy was present in 38.9% of eyes, and no atrophy was evident in 6.7% of eyes. Time-to-event curves showed a median duration of 15.4 years (95% confidence interval, 11.1-19.6 years) from onset to foveal involvement. The median visual acuity decline was -0.03 Snellen decimal per year (interquartile range [IQR], -0.07 to 0.00 Snellen decimal; 0.03 logarithm of the minimum angle of resolution). Median atrophy growth was 0.590 mm2/year (IQR, 0.046-1.641 mm2/year) for definitely decreased autofluorescence and 0.650 mm2/year (IQR, 0.299-1.729 mm2/year) for total decreased autofluorescence. Late-onset STGD1 is a subtype of STGD1 with most commonly 1 severe and 1 mild ABCA4 variant. The general patient presents with typical fundus flecks and retinal atrophy in a foveal-sparing pattern with preserved central vision. Misdiagnosis as age-related macular degeneration should be avoided to prevent futile invasive treatments with potential complications. In addition, correct diagnosis lends patients with late-onset STGD1 the opportunity to participate in potentially beneficial therapeutic trials for STGD1. The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Histopathological Subtypes of Primary Nephrotic Syndrome in Paediatric Patients at the University Teaching Hospital in Lusaka, Zambia

Background: Minimal change disease (MCD) has been shown to be a common histological presentation in children presenting with nephrotic syndrome (NS) in developed countries. In Africa, information on clinical and histological characteristics of paediatric NS is scarce. This study assessed the characteristics and histological subtypes of NS.
 Methods: This was a prospective study that consecutively indexed children aged 2-16 years with the diagnosis of NS who were referred to the largest tertiary teaching hospital, Lusaka, Zambia. Thirteen children presenting with NS were biopsied under ultrasound guidance after ethical approval. The primary outcome of the study was to describe the histological characteristics of paediatric NS.
 Results: Thirteen children of African descent with a median age of onset of NS of 9.25 years (2.0-15.0) were enrolled in the study. The histopathologic lesions were as follows; four had MCD, four had focal segmental glomerulosclerosis (FSGS), one had immune complex mediated glomerulonephritis (ICMN) and four were inconclusive. Haematuria was present in eight out of 13 patients (61.5%) and hypertension was present in five of 13 patients (38.0%). Three children did not have either haematuria or hypertension. Ten of the 13 participants had primary steroid resistance. 
 Conclusion: This study has demonstrated the need to perform a pre-treatment renal biopsy in paediatric patients presenting with NS in view of the atypical presentation, variable histopathologic findings, and unpredictable response to steroid therapy.

Clinical characteristics and prognostic factors of patients with anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis associated interstitial lung disease

Objective: To analyze the clinical characteristics and prognostic factors of patients with anti-melanoma differentiation-associated gene 5 (anti-MDA5)-positive dermatomyositis associated interstitial lung disease (DM-ILD). Methods: The patients with MDA5+DM-ILD who were admitted to Department of Respiratory Medicine, Nanjing Drum Tower Hospital from January 2017 to March 2021 were enrolled. The clinical data and survival information were analyzed retrospectively. Patients were divided into survival group or death group, and rapid progressive ILD (RP-ILD) group or non-rapid progressive ILD group, according to their survival status and clinical progression. Results: A total of 105 patients with anti-MDA5+DM-ILD (median age of onset 54 years) were enrolled, 58% being female (61 cases). The main sub-type of dermatomyositis was amyopathic dermatomyositis (n=74, 70%), followed by dermatomyositis (n=31, 30%). The main extrapulmonary manifestations were skin lesions (n=60, 57.1%), muscle manifestations(n=20, 19%) and arthralgia/arthritis (n=20, 19%). 15.4% of the patients had positive ANA (antibody titer≥1∶320), and 61.9% of the patients had anti-RO-52 kDa antibody. A total of 66 patients (62.8%) developed RP-ILD, and 58 patients (56.3%) died. Lower oxygenation index (OR=0.974, 95%CI:0.954-0.994, P=0.012) and no joint pain (OR=0.032, 95%CI: 0.002-0.663 P=0.026) were independent risk factors for RP-ILD. Cox regression analysis showed that RP-ILD (HR=3.194, 95%CI:1.025-9.954, P=0.045), older than 53 years (HR=3.450, 95%CI: 1.388-8.577, P=0.008), ferritin level more than 1 330.5 ng/ml (HR=3.032, 95%CI 1.208-7.610, P=0.018) and C-reactive protein (CRP) above 16.95 mg/L (HR=2.794, 95%CI:1.102-7.084, P=0.030) were independent predictors of mortality. Conclusions: The clinical manifestations of patients with anti-MDA5+DM-ILD presenting to the respiratory department were heterogeneous, with most being amyopathic dermatomyositis, and both the incidence of RP-ILD and the risk of death were high. Even in the absence of associated rash, joint, or muscle manifestations, anti-MDA5 antibody screening should be considered in patients with rapidly progressive ILD who were negative on baseline autoantibody screening but positive for anti-RO52kDa antibody.

Diagnosis and treatment of Shwachman-Diamond syndrome in Chinese children: An evidence-based study

To explore the characteristics of Shwachman-Diamond syndrome (SDS) in Chinese children in order to provide a reference for early diagnosis. With Shwachman-Diamond syndrome, SDS, SBDS gene and inherited bone marrow failure as the keywords, the search period was set from January 2002 to October 2022. Relevant literature was retrieved from the Wanfang Database and China National Knowledge Infrastructure (CNKI) database. In addition, by using Shwachman-diamond syndrome as a keyword, the search period was also retrieved from the Web of Science, PubMed, and MEDLINE databases from January 2002 to October 2022. A child with SDS treated at the Tongji Hospital was also included. A total of 44 cases with complete clinical data were analyzed with reference to the International Standard for SDS Diagnosis. Chi-square test and t test were used for statistical analysis. Evidence-based research was carried out in the form of systematic review. The epidemiology, clinical characteristics and key points of early diagnosis of the Chinese SDS children were summarized and compared with the international data. The main characteristics of SDS in Chinese children were summarized as follows: The ratio of males to females was about 1.3 : 1, the median age of onset was 3 months, and the median age of diagnosis was 14 months. The first symptoms were often exocrine pancreatic insufficiency (31.8%) and granulocytopenia with infection (31.8%). According to the international consensus, the incidence rates of the three major diseases of SDS were hemocytopenia (95.4%), pancreatic disease (72.7%), and bone abnormality (40.9%). The common factors underlying SDS disease were variants of the SBDS gene (c.258+2T>C and c.183_184TA>CT), albeit there was no significant correlation between genotype and phenotype (P > 0.05). Compared with international reports, the clinical manifestations and genotypes of Chinese SDS children are different (P < 0.05). The SDS children have an early age of onset and significant individual difference. It is necessary to analyze the case-related data to facilitate early recognition, diagnosis and clinical intervention.

E19 Gamma-glutamyl transpeptidase level is correlated with disease activity in oligoarticular and polyarticular Juvenile idiopathic arthritis

Abstract Introduction Gamma-glutamyl transpeptidase (GGT) level was found to be correlated with disease activity indexes in rheumatoid arthritis [1]. This association was not yet investigated in children with oligoarticular and polyarticular Juvenile idiopathic arthritis (JIA). Objectives The present study aims to investigate the correlation between GGT level and disease-related parameters in oligoarticular and polyarticular JIA. Methods We performed a retrospective study including patients with oligoarticular and polyarticular JIA responding to the 2001 International League of Associations for Rheumatology (ILAR) classification. Sociodemographic, disease-related parameters (age of onset, disease duration, patient global assessment (PGA), Pain Visual Analogue Scale (VAS), C-Reactive protein (CRP) level, Erythrocyte Sedimentation Rate (ESR), disease activity assessed using the Juvenile Arthritis Disease Activity Score (JADAS) based on ESR), and GGT level were collected. Continuous variables were expressed with median and Interquartile range (IQR). Spearman correlation was used to assess the association between GGT levels and disease-related data. Results Eleven patients were included with a median age of 12 (IQR: 10–15) years and 8 females. Median disease duration was 4 (IQR: 4–7) years and median age of onset was 8 (IQR: 5–10) years. Five patients had oligoarticular JIA, 3 had a polyarticular with positive Rheumatoid Factor (RF) form, 2 had a polyarticular with negative RF form and one had an undifferentiated JIA. Median JADAS was 3.6 (IQR: 0–9). Median ESR, CRP, and GGT levels were 14 (10–19) mm/H, 1.8 (2–6.4) mg/l, and 14 (12–16) IU/l, respectively. A strong positive correlation was found between GGT level and JADAS (r = 0.749, P = 0.008). Level of CRP and ESR were not correlated with GGT level. Besides, patient global assessment and pain VAS were positively correlated with GGT level (r = 0.670, P = 0.049; r = 0.814, P = 0.014, respectively). No correlation was found between GGT level and disease duration and number of tender or swollen joints. Conclusion The GGT level was significantly higher in patients with more active disease, higher pain, and global assessment. This suggests that GGT level can be used as a marker of disease activity as in JIA. References 1 Vergneault H, Vandebeuque E, Codullo V, Allanore Y, Avouac J. Disease Activity Score-28 using γGT permits a dual evaluation of joint activity and cardiovascular risk. J Rheumatol 2020.

Determinants of Kidney Failure in Primary Hyperoxaluria Type 1: Findings of the European Hyperoxaluria Consortium

Primary hyperoxaluria type 1 (PH1) has a highly heterogeneous disease course. Apart from the c.508G>A (p.Gly170Arg) AGXT variant, which imparts a relatively favorable outcome, little is known about determinants of kidney failure. Identifying these is crucial for disease management, especially in this era of new therapies. In this retrospective study of 932 patients with PH1 included in the OxalEurope registry, we analyzed genotype-phenotype correlations as well as the impact of nephrocalcinosis, urolithiasis, and urinary oxalate and glycolate excretion on the development of kidney failure, using survival and mixed model analyses. The risk of developing kidney failure was the highest for 175 vitamin-B6 unresponsive ("null") homozygotes and lowest for 155 patients with c.508G>A and c.454T>A (p.Phe152Ile) variants, with a median age of onset of kidney failure of 7.8 and 31.8 years, respectively. Fifty patients with c.731T>C (p.Ile244Thr) homozygote variants had better kidney survival than null homozygotes (P= 0.003). Poor outcomes were found in patients with other potentially vitamin B6-responsive variants. Nephrocalcinosis increased the risk of kidney failure significantly (hazard ratio [HR] 3.17 [2.03-4.94], P< 0.001). Urinary oxalate and glycolate measurements were available in 620 and 579 twenty-four-hour urine collections from 117 and 87 patients, respectively. Urinary oxalate excretion, unlike glycolate, was higher in patients who subsequently developed kidney failure (P= 0.034). However, the 41% intraindividual variation of urinary oxalate resulted in wide confidence intervals. In conclusion, homozygosity for AGXT null variants and nephrocalcinosis were the strongest determinants for kidney failure in PH1.

Age of onset and cumulative risk of mental disorders: a cross-national analysis of population surveys from 29 countries

Information on the frequency and timing of mental disorder onsets across the lifespan is of fundamental importance for public health planning. Broad, cross-national estimates of this information from coordinated general population surveys were last updated in 2007. We aimed to provide updated and improved estimates of age-of-onset distributions, lifetime prevalence, and morbid risk. In this cross-national analysis, we analysed data from respondents aged 18 years or older to the World Mental Health surveys, a coordinated series of cross-sectional, face-to-face community epidemiological surveys administered between 2001 and 2022. In the surveys, the WHO Composite International Diagnostic Interview, a fully structured psychiatric diagnostic interview, was used to assess age of onset, lifetime prevalence, and morbid risk of 13 DSM-IV mental disorders until age 75 years across surveys by sex. We did not assess ethnicity. The surveys were geographically clustered and weighted to adjust for selection probability, and standard errors of incidence rates and cumulative incidence curves were calculated using the jackknife repeated replications simulation method, taking weighting and geographical clustering of data into account. We included 156 331 respondents from 32 surveys in 29 countries, including 12 low-income and middle-income countries and 17 high-income countries, and including 85 308 (54·5%) female respondents and 71 023 (45·4%) male respondents. The lifetime prevalence of any mental disorder was 28·6% (95% CI 27·9-29·2) for male respondents and 29·8% (29·2-30·3) for female respondents. Morbid risk of any mental disorder by age 75 years was 46·4% (44·9-47·8) for male respondents and 53·1% (51·9-54·3) for female respondents. Conditional probabilities of first onset peaked at approximately age 15 years, with a median age of onset of 19 years (IQR 14-32) for male respondents and 20 years (12-36) for female respondents. The two most prevalent disorders were alcohol use disorder and major depressive disorder for male respondents and major depressive disorder and specific phobia for female respondents. By age 75 years, approximately half the population can expect to develop one or more of the 13 mental disorders considered in this Article. These disorders typically first emerge in childhood, adolescence, or young adulthood. Services should have the capacity to detect and treat common mental disorders promptly and to optimise care that suits people at these crucial parts of the life course. None.

Clinical manifestations and computed tomography angiography features of anomalous left coronary artery from the pulmonary artery syndrome.

Anomalous left coronary artery from the pulmonary artery (ALCAPA) syndrome is a rare congenital coronary artery malformation with a high rate of clinical missed diagnosis and misdiagnosis. At present, there is a lack of reports on the clinical manifestations of ALCAPA and the imaging features of coronary computed tomography angiography (CTA). This study aims to summarize the clinical characteristics and coronary CTA imaging features of ALCAPA to improve the clinical diagnosis and treatment. The clinical data of 24 ALCAPA syndrome patients were retrospectively collected, analyzed and summarized from January 1, 2013 to February 1, 2023 in the Second Xiangya Hospital of Central South University. According to the left and right coronary collateral circulation, the patients were classified into infantile type (7 cases) and adult type (17 cases). The differences of clinical manifestations and CTA imaging features were compared between the 2 types of patients. Of the 24 patients, a male-to-female ratio was at 1꞉5, and the median age of onset was 3.22 months for the infant type and 22.0 years for the adult type. The infantile type showed symptoms of left heart insufficiency at an early stage, while the adult type had a variety of clinical manifestations in 7 patients being asymptomatic and presented with a cardiac murmur on physical examination, 6 with symptoms of chronic myocardial ischemia, and 2 with malignant arrhythmias. CTA showed that 11 patients' the left coronary artery originated from the left posterior sinus of the pulmonary artery. All 7 infantile type patients had an enlarged left heart, left ventricular hypertrophy, reduced left heart function, lack of collateral circulation between the left and right coronary arteries, and normal coronary artery diameter. All 17 adult type patients showed dilated and tortuous coronary arteries with rich collateral circulation, and 7 adult type patients had preserved left heart function. The clinical manifestations and CTA imaging features of patients with the 2 types of ALCAPA are different, while CTA performance is characteristic and can be used as a means of definitive diagnosis, staging, surgical evaluation, and postoperative follow-up of ALCAPA syndrome.

Clinical and Ultrasonographic Characterization of Hidradenitis Suppurativa in Female Patients: Impact of Early Recognition of the Disease.

Hidradenitis suppurativa (HS) is considered a post-pubertal disease; however, earlier onset is not infrequent. The burden of HS on the female population is very relevant, and early identification might reduce the quality of life impairment and improve the therapeutic approach. In this study, we investigated clinical biomarkers of HS that could impact the management of patients affected by HS. Female patients affected by stable HS were prospectively included in this study. Anamnestic data, clinical and ultrasonographic features were collected and analyzed. Overall, 53 patients were included in this study. The median age of onset was 19 (IQR: 14-25). Early onset was reported by 22/53 patients (median age of onset: 14; IQR: 11-16). Four patients had pre-menstruation occurrence. Early-onset patients had an earlier first-menstrual-cycle age and more frequent genital localization of HS, and were more often treated with biologics. Patients with early-onset-HS and genital localization had more severe disease with a higher number of areas affected, Hurley, and IHS4 scores. Genital involvement might be prevalent in patients with early-onset HS, leading to a worse impact on the global severity of the disease and tailored treatment protocols, including multidisciplinary approaches, in order to improve the early recognition of hidden lesions.

Clinical Characterization of Pediatric Erythromelalgia: A Single-Center Case Series.

Erythromelalgia is a descriptive term for severe burning pain and erythema in the distal extremities relieved by cold and exacerbated by heat. Pediatric case series to date are relatively small. We extracted and analyzed medical record data for 42 pediatric patients to describe clinical characteristics, associated conditions, and responses to treatments. Informed consent was obtained according to an IRB-approved protocol that included gene discovery. Three patients had confirmed Nav1.7 sodium channelopathies, with six additional patients under investigation with novel gene candidates. There was a female predominance (2.5:1), and the median onset age was 12 years (IQR = 3-14). Patients saw a median of three specialists (IQR = 2-3) for a diagnosis. The majority (90%) reported bilateral symptoms. Cooling methods usually provided partial relief, while heat and exercise exacerbated pain. No medication appeared to be consistently effective; commonly prescribed medications included sodium channel blockers (n = 37), topical analgesics (n = 26), gabapentin (n = 22), and aspirin (n = 15). Based on the currently published literature, we believe this cohort is the largest pediatric study of erythromelalgia to date. Many findings are consistent with those of previously published case series. Work is in progress to establish a prospective cohort and multi-center registry.

NCSTN In-Frame Deletion in Maltese Patients With Hidradenitis Suppurativa

Hidradenitis suppurativa (HS) is a complex trait that has a monogenic etiology in a subset of patients. Variation in genes that encode proteins of the γ secretase complex, particularly NCSTN, account for few patients who exhibit familial forms of HS. Thus far, extensive genotype-phenotype correlations have been lacking. To establish the prevalence of the NCSTN:c.671_682del variant and explore potential genotype-phenotype associations in an ethnically Maltese HS cohort. This cross-sectional study conducted from December 2021 to September 2022 included patients 18 years or older with a diagnosis of HS as defined by recurrent nodules, abscesses, and/or draining tunnels in typical (axilla, breast, groin, buttock, thighs, and inframammary folds) and less typical (scalp, ear pinnae, neck, arms, antecubital fossae) sites who were recruited from the sole national dermatology reference center servicing the Maltese archipelago. Clinical examination and targeted genetic analysis for an NCSTN deletion that was originally identified through whole-exome sequencing in a family with multigenerational disease were performed. Recruited patients were phenotyped and genotyped for the NCSTN:c.671_682del variant. To determine the prevalence of the NCSTN:c.671_682del variant and establish possible genotype-phenotype associations in the ethnically Maltese HS cohort. A total of 113 patients with HS (56 women [49.6%]) met the inclusion criteria and were enrolled in this study. The median age of disease onset was 18 years (range, 7-62 years), and the median International Hidradenitis Suppurativa Severity Score System score was 4.39 (range, 1.0-64.0). The NCSTN variant was identified in the heterozygous state in 14 patients (12.4%) from 5 unrelated, nonconsanguineous families of Maltese ethnicity. The variant was not identified in an ethnically matched reference genomic data set of disease-free individuals. Variant carriers manifested HS symptoms earlier and were more likely to exhibit a distinctive HS phenotype, which was characterized by involvement of the scalp, neck, torso, and antecubital fossae. Despite manifesting similar clinical disease severity, variant carriers were more likely to require treatment with adalimumab. The results of this cross-sectional study suggest that monogenic variation in NCSTN is associated with HS in a subset of patients who have a distinct, atypical phenotype.

"Sandwich" protocol based on modified SMILE regimen for children with newly extranodal NK/T cell lymphoma, nasal type: a single-arm, single-center clinical study.

Extranodal NK/T-cell lymphoma, nasal type (ENKTL), which is a rare form of mature T/NK cell lymphoma in children, currently lacks a standardized first-line treatment approach. However, a treatment protocol known as the "sandwich" regimen has been used in children newly diagnosed with ENKTL. This protocol combines the administration of methotrexate, ifosfamide, etoposide, pegaspargase, and dexamethasone (referred to as SMILE) with the addition of radiotherapy (RT). From September 2017 to December 2020, a total of five patients were included in the study, consisting of three males and two females. The median age of onset was 10.6 years (range, 9.8 to 14.0 years). Among the patients, four had nasal/nasopharyngeal disease at stage II, while one patient had extra nasal disease involving the skin at stage IV. The median EBV-DNA level in plasma was 1.68 × 103 copies/ml (range, 0.44 to 21.1 × 103copies/ml). All the patients had good overall response after 2 cycles of chemotherapy and radiotherapy, including 4 of the patients who had a complete response and 1 of the patients with partial remission. The patient with stage IV received allogeneic hematopoietic stem cell transplantation after the EBV-DNA level was elevated again during treatment. One patient in the low-risk group experienced grade 4 oral mucositis, while no other severe complications or treatment-related deaths were observed. The median follow-up period was 22 months (range, 5 to 57 months). All five patients successfully completed their treatment, with four patients achieving event-free survival, and one patient was lost to follow-up. The median OS time and EFS time was 33 months (range: 18-57 months) and 20 months (range: 5-47 months), respectively. The sandwich protocol has demonstrated a high response rate, good tolerance to chemotherapy, and no treatment-related fatalities. However, further confirmation is necessary through additional clinical studies involving larger sample sizes. Clinical trial registration number: Due to modified SMILE regimens with sandwiched radiotherapy yielded promising outcomes in children ENKTL, we have carried out a phase II multicenter clinical trial (ChiCTR220005954) for children ENKTL in China to further verify the efficacy and safety.

Sarcoidosis: experience in a Mexican ophthalmological clinic

BackgroundSarcoidosis is an inflammatory disorder in which patients frequently develop ocular manifestations that precede systemic involvement, sometimes it even presents as an ocular isolated form of the disease. The purpose of this study is to report the ocular and systemic manifestations of sarcoidosis in a series of Mexican patients, as there is a low incidence of the disease in this population.MethodsA retrospective case series of patients with positive classification criteria for sarcoidosis who attended Asociacion Para Evitar la Ceguera en Mexico, IAP between 2011 and 2022. Descriptive statistics were used to report the clinical, laboratory, and imaging findings and treatment. Numerical results were presented using median values and first and third quartiles for distribution.ResultsFourteen patients were included in this study, 10 of them had definite ocular sarcoidosis (biopsy-proven), 4 had presumed ocular sarcoidosis. The median age of onset was 52 (34; 67), with a predominance of female patients (71.4%). Ten patients (71.4%) debuted with ocular manifestations. The most common forms of ocular involvement were bilateral anterior uveitis (50%) and panuveitis (28.6%). Median follow-up was 24 (13–49) months.ConclusionsSarcoidosis is a rare, underdiagnosed condition in Mexico and ocular involvement can be an early manifestation of the disease. Ophthalmologists should be alert to the signs of ocular sarcoidosis and collaborate with a multidisciplinary team to screen for systemic involvement if suspicion is high.

Outcome of Absence Epilepsy With Onset at 8-11 Years of Age: Watershed Ages When Syndromes Overlap.

Introduction: Absence seizures occur in various epilepsy syndromes, including childhood and juvenile absence epilepsy and juvenile myoclonic epilepsy. When children present with absence seizures at ages when syndromes overlap, initial syndrome designation is not always possible, making early prognostication challenging. For these children, the study objective is to determine clinical and initial electroencephalograph (EEG) findings to predict the development of generalized tonic-clonic seizures, which is a factor that affects outcome. Methods: Children with new-onset absence seizures between 8 and 11 years of age with at least 5 years of follow-up data were studied through the review of medical records and initial EEG tracings. Results: Ninety-eight patients were included in the study. The median age of absence seizure onset was 9 years (interquartile range [IQR] = 8.00, 10.00) and follow-up was 15 years (IQR = 13.00, 18.00). Forty-six percent developed generalized tonic-clonic seizures and 20% developed myoclonic seizures. On multiple regression analysis, a history of myoclonic seizures, anxiety, as well as bifrontal slowing and mild background slowing on initial EEG (P < .05) were associated with generalized tonic-clonic seizures. Although not statistically significant, a shorter duration of shortest EEG burst on baseline EEG was also associated with generalized tonic-clonic seizures. Conclusion: On initial EEG, bifrontal and background slowing and myoclonic seizures and anxiety are associated with developing generalized tonic-clonic seizures, which is of prognostic significance when early syndrome designation is difficult.

Clinical characteristics of primary hemophagocytic lymphohistiocytosis associated with perforin gene deficiency: a single-center retrospective study

Objective: This study aimed to investigate the clinical characteristics of patients diagnosed with primary hemophagocytic lymphohistiocytosis (pHLH) associated with perforin gene deficiency. Methods: We retrospectively analyzed the clinical data of 16 pHLH patients associated with perforin gene deficiency at Beijing Friendship Hospital, Capital Medical University, from April 2014 to August 2021. The mutation sites, mutation types, family history, clinical characteristics, and prognosis of the patients were assessed. Results: A total of 16 patients, including ten males and six females, with a median onset age of 17.5 years (range: 4-42 years), were enrolled in this study. Sixteen different mutations were identified, consisting of 11 missense mutations, one nonsense mutation, two frameshift mutations, and two in-frame mutations. All patients harbored at least one deleterious missense mutation, with the most common mutation sites being c.1349C>T (p.T450M) and c.503G>A (p.S168N). Decreased natural killer (NK) cell activity was observed in 11 patients, reduced perforin protein expression in ten patients, concurrent Epstein-Barr virus (EBV) infection at onset in eight patients, a family history in two patients, and central nervous system involvement in four patients. Eleven cases underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), with eight cases surviving. The median survival time of non-transplanted patients was eight months (range: 4-18 months), while that of transplanted patients was reported as "not reached". Conclusions: Emphasizing the diagnosis of pHLH in adults with perforin gene deficiency. In addition, it should be noted that EBV infection can potentially act as a triggering factor in such disease, and allo-HSCT exerts a substantial effect on the prognosis of patients.

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.

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.