Earlier Age Of Disease Onset Research Articles

Гендерные различия и клинические особенности заболеваний печени и желчевыводящих путей

The purpose — to reveal the clinical and socio-demographic characteristics of patients with liver and biliary tract diseases depending on nosology; to determine gender differences of the patients. Material and methods. 292 patients with liver and biliary tract diseases were examined. The patients were on inpatient treatment in the Gastroenterology Department of the Republic Clinical Hospital or observed in the outpatient department. Results. Among 292 patients, 123 (42,1%) had steatosis, 11 (3,8%) — cholelithiasis, 6 (2,1%) — Gilbert’s syndrome, 152 (52,0%) — autoimmune liver disease (AILD). The prevalence of females was revealed among patients with both hepatic steatosis (67,9%) and AILD (91%). Male patients with non-alcoholic fatty liver disease (NAFLD) had an earlier age of disease onset compared to female patients (47,1 (2,6) vs 53,8 (1,6)). Associated conditions in patients with NAFLD included obesity, cholelithiasis, acid-related diseases, dyslipidemia, impaired motility of the digestive tract, etc.; in patients with AILD — arthralgia, autoimmune thyroiditis, inflammatory bowel disease and other autoinflammatory conditions. The main focus in the management of NAFLD patients was made on non-drug therapy methods, including changes in eating behavior and prevention of hypodynamia, while in patients with AILD drug therapy (immunosuppressants, corticosteroids) played the main role. Patients with NAFLD had a more favorable course of the disease, which made it possible to observe them in the outpatient department, while patients with AILD mostly got inpatient treatment.

Deficiency of Adenosine Deaminase 2 in Adults and Children: Experience From India

Deficiency of adenosine deaminase 2 (DADA2) is a potentially fatal monogenic syndrome characterized by variable manifestations of systemic vasculitis, bone marrow failure, and immunodeficiency. Most cases are diagnosed by pediatric care providers, given the typical early age of disease onset. This study was undertaken to describe the clinical phenotypes and treatment response both in adults and in children with DADA2 in India. A retrospective analysis of pediatric and adult patients with DADA2 diagnosed at various rheumatology centers across India was conducted. Clinical characteristics, diagnostic findings, and treatment responses were analyzed in all subjects. In total, 33 cases of DADA2 were confirmed in this cohort between April 2017 and March 2020. Unlike previous studies, nearly one-half of the confirmed cases presented during adulthood. All symptomatic patients exhibited features of vasculitis, whereas constitutional symptoms and anemia were more common in pediatric patients. Cutaneous and neurologic involvement were common, and 18 subjects had experienced at least one stroke. In addition, the clinical spectrum of DADA2 was expanded by recognition of novel features in these patients, including pancreatic infarction, focal myocarditis, and diffuse alveolar hemorrhage. Treatment with tumor necrosis factor inhibitors (TNFi) was initiated in 25 patients. All of the identified disease manifestations showed marked improvement after initiation of TNFi, and disease remission was achieved in 19 patients. Two cases were complicated by tuberculosis infection, and 2 deaths were reported. This report presents the first case series of patients with DADA2 from India, diagnosed by adult and pediatric care providers. The findings raise awareness of this syndrome, particularly with regard to its presentation in adults.

Old Age Dementias: Factors Associated with Dementia Progression Rate. Part 2

Background: steady progression of dementia is characterized with various rates, which specified clinical differentiation of dementias with rapid and slow increase of cognitive decline severity. The search for clinical factors, hypothetically responsible for differences in late age dementia progression rate, is one of the aspects of investigation of late age dementias.The objectivewas to generalize the results of the study of separate clinical factors effect on the differences in the late age dementia progression rate.Material and methods: papers in MEDLINE/PubMed bases from 1990 to 2020 were selected and analyzed according to the key words: “late age”, “dementia”, “progression rate”, “age of onset”, “non-cognitive disorders”, “nosomodifying therapy”, as well as relevant papers in the literature of the analyzed works.Conclusion: various parameters of the disease were studied as associated with dementia progression pattern. As regards part of them the results achieved compliance in recognition of association with dementia progression rate. As for the others this evidence is ambiguous. There are large discrepancies in attitudes to gender differences, while early age of disease onset, initially great intensity of neuropsychiatric disorders are concordantly admitted as associated with dementia rapid progression. The researchers are united with steady idea of nonlinear character of dementia progression at the stages of mild, moderate and severe dementia.The resultsof study of comorbidity are basically similar with regard to recognition of SFD influence, first of all, of arterial hypertension on dementia progression rate. The evidence of the efficacy of nosomodifying therapy, decelerating dementia progression, is unanimously considered an urgent problem. The development of new dementia pathogenesis concepts and the search for new therapy targets, are conducive to the solution of this problem. The results of the investigated direction of studies confirm the hypothesis of the fact that dementia progression occurs according to various pathogenetic mechanisms, which determine the dementia increasing rate. The management of patients with dementia in practice presupposes taking into account of various factors, influencing dementia progression rate, for planning of the volume and character of medical care.

Articular manifestations in Egyptian children with familial Mediterranean fever

BackgroundFamilial Mediterranean fever (FMF) is an autosomal recessive auto-inflammatory disease. Arthritis in early-onset FMF is a common finding. The aim of this study was to assess frequency of arthritis in 200 Egyptian children with FMF and also to detect its clinical characteristics, response to colchicine treatment, its effect on disease severity, and the most common MEFV gene mutations in patients with arthritis.ResultsWe studied 200 children with FMF. We analyzed joint involvement in FMF attacks regarding its clinical characteristics, its effect on the disease severity, and response to colchicine treatment. We found arthritis in 20.5% of the studied population. Most of the children with arthritis had mono-articularjoint involvement during the FMF attack (73.1%), followed by oligo-articularjoint (22%). The knees and ankles were the most commonly affected joints. Arthritis was the presenting symptom in only 4%. We observed redness of the affected joints in 70.7%, and persistence of swelling after the attacks only in 17.1%. The majority of patients (85.4%) had a 75–100% decrease in the frequency of arthritic attacks after colchicine treatment. We did not find any joint disability in all studied patients, and arthritis was only present during attacks. The most frequent MEFV gene mutations in arthritic patients wereV726A and E148Q, each occurring in 28.6%. We observed an earlier age of disease onset and a more disease severity in patients with arthritis (p = 0.031 and p ≤ 0.001, respectively). We also observed that chest pain, erysipelas-like-erythema, and testicular affection were more observed in patients with arthritis (p values 0.001, 0.001, and 0.006, respectively).ConclusionThis study showed that around 20% of Egyptian children with FMF can develop arthritis during the attacks, which usually runs a benign course. The presence of arthritis can denote a more severe disease course.

P038 Factors Associated with Impaired Patient-Reported Outcomes and Work Productivity Among Patients with Ulcerative Colitis in Remission.

BACKGROUND: Real-world patients with ulcerative colitis (UC) in remission have reported impairment in many patient-reported outcome (PRO) measures. This study examined factors associated with PROs among UC patients in the Corrona Inflammatory Bowel Disease (IBD) Registry who were in remission. METHODS: Analysis included patients enrolled in the Corrona IBD Registry from May 3, 2017 through September 3, 2019 with a diagnosis of UC who were in remission (defined as partial Mayo score of <2) at the time of enrollment. Patient-Reported Outcomes Measurement Information System (PROMIS) and the Work Productivity and Activity Impairment (WPAI) questionnaires were collected at enrollment. Descriptive statistics were used to describe patient enrollment characteristics and were stratified by PROMIS status (moderate/severe ≥60 vs normal/mild <60) for Fatigue, Pain Interference, and Anxiety domains, and by WPAI impairment status (any vs none) for Presenteeism, Work Productivity Loss, and Activity Impairment domains. Characteristics with absolute standardized mean differences >0.10 suggest meaningful differences between groups defined by PRO impairment. RESULTS: Among patients enrolled in the registry, 731 were diagnosed with UC and 385 were in remission. UC patients in remission who reported moderate/severe fatigue were more likely to have a history of arthritis (n = 10/54,18.5% vs n = 26/325, 8.0%), had an earlier age of disease onset (mean, 33.4 vs 39.0 years), and increased urgency of defecation (n = 16/54, 29.6% vs n = 52/325, 16.0%) than those with normal/mild fatigue. Additionally, a higher proportion of patients with moderate/severe fatigue reported a history of corticosteroid use (n = 33/54, 61.1% vs n = 156/325, 48.0%), a history of antibiotic use (n = 15/54, 27.8% vs n = 49/325, 15.1%), as well as a shorter duration of current IBD treatment (mean, 2.3 vs 3.3 years).These treatment trends were also seen in patients who reported moderate/severe pain interference and anxiety vs normal/mild. A higher proportion of patients with moderate/severe fatigue reported current biologic treatment (n = 23/54, 42.6% vs n = 109/325, 33.5%) compared with those who reported normal/mild scores. Overall, those in remission reporting any Presenteeism impairment were more likely to have a history of arthritis (n = 11/97, 11.3% vs n = 11/157, 7.0%), to have greater urgency of defecation (n = 26/97, 26.8% vs n = 24/157, 15.3%), and to be currently treated with corticosteroids (n = 11/97, 11.3% vs n = 11/157, 7.0%) compared with those who reported none. The same trends were seen in those reporting any Work Productivity Loss: history of arthritis, n = 10/93 (10.8%) vs n = 10/144 (6.9%); urgency of defecation, n = 26/93 (28.0%) vs n = 23/144 (16.0%); and current corticosteroid treatment, n = 10/93 (10.8%) vs n = 10/144 (6.9%). In UC patients in remission reporting any Activity Impairment, the trend was seen for history of arthritis (n = 19/167, 11.4% vs n = 18/217, 8.3%), and urgency of defecation (n = 43/167, 25.7% vs n = 28/217,12.9%). CONCLUSION: Despite being in remission based on partial Mayo Score, patients with UC who reported impaired work productivity or had elevated fatigue, anxiety, or pain interference were more likely to have a history of arthritis and urgency. History of steroid use was seen more often in patients with impaired PROMIS scores. Further investigation is needed to address the unmet medical needs in these patients.

Genome-Wide Analysis of Copy Number Variation in Latin American Parkinson's Disease Patients.

Parkinson's disease is the second most common neurodegenerative disorder and affects people from all ethnic backgrounds, yet little is known about the genetics of Parkinson's disease in non-European populations. In addition, the overall identification of copy number variants at a genome-wide level has been understudied in Parkinson's patients. The objective of this study was to understand the genome-wide burden of copy number variants in Latinos and its association with Parkinson's disease. We used genome-wide genotyping data from 747 Parkinson's disease patients and 632 controls from the Latin American Research Consortium on the Genetics of Parkinson's disease. Genome-wide copy number burden analysis showed that patients were significantly enriched for copy number variants overlapping known Parkinson's disease genes compared with controls (odds ratio, 3.97; 95%CI, 1.69-10.5; P = 0.018). PRKN showed the strongest copy number burden, with 20 copy number variant carriers. These patients presented an earlier age of disease onset compared with patients with other copy number variants (median age at onset, 31 vs 57 years, respectively; P = 7.46 × 10-7 ). We found that although overall genome-wide copy number variant burden was not significantly different, Parkinson's disease patients were significantly enriched with copy number variants affecting known Parkinson's disease genes. We also identified that of 250 patients with early-onset disease, 5.6% carried a copy number variant on PRKN in our cohort. Our study is the first to analyze genome-wide copy number variant association in Latino Parkinson's disease patients and provides insights about this complex disease in this understudied population. © 2020 International Parkinson and Movement Disorder Society.

Truncated stathmin-2 is a marker of TDP-43 pathology in frontotemporal dementia.

No treatment for frontotemporal dementia (FTD), the second most common type of early-onset dementia, is available, but therapeutics are being investigated to target the 2 main proteins associated with FTD pathological subtypes: TDP-43 (FTLD-TDP) and tau (FTLD-tau). Testing potential therapies in clinical trials is hampered by our inability to distinguish between patients with FTLD-TDP and FTLD-tau. Therefore, we evaluated truncated stathmin-2 (STMN2) as a proxy of TDP-43 pathology, given the reports that TDP-43 dysfunction causes truncated STMN2 accumulation. Truncated STMN2 accumulated in human induced pluripotent stem cell-derived neurons depleted of TDP-43, but not in those with pathogenic TARDBP mutations in the absence of TDP-43 aggregation or loss of nuclear protein. In RNA-Seq analyses of human brain samples from the NYGC ALS cohort, truncated STMN2 RNA was confined to tissues and disease subtypes marked by TDP-43 inclusions. Last, we validated that truncated STMN2 RNA was elevated in the frontal cortex of a cohort of patients with FTLD-TDP but not in controls or patients with progressive supranuclear palsy, a type of FTLD-tau. Further, in patients with FTLD-TDP, we observed significant associations of truncated STMN2 RNA with phosphorylated TDP-43 levels and an earlier age of disease onset. Overall, our data uncovered truncated STMN2 as a marker for TDP-43 dysfunction in FTD.

Epidemiology of moderate-to-severe psoriasis: a comparison between psoriasis patients treated with biological agents, conventional systemic drugs and topical agents

Introduction Understanding how different comorbidities and epidemiological factors are related to psoriasis severity can help us estimating patients’ clinical outcome. Aim Establish possible prognostic factors of severe psoriasis. Methods Three groups of patients were included: 118 were on topical therapy, 83 used conventional systemic drugs, and 112 were treated with biological agents. Based on the fact that patients on topical therapy have a lower grade of disease severity than patients treated systemically, we compared a variety of comorbidities and epidemiological parameters between the three groups. Results Patients treated more aggressively have an increased risk of cardiovascular disease (p = .044), suffer more from depression (p = .020), hyperuricemia (p = .031) and nonspecific noninfectious liver disease (p = .005). Male gender (p < .001), increased height (p < .001), early age of disease onset (p < .001), viral upper respiratory infections (p = .049) and periods of hormonal changes (p = .045) are associated with these therapies. Conclusion Psoriasis severity is directly related to an increased risk of cardiovascular disease, depression, hyperuricemia and nonspecific noninfectious liver disease. Male gender, increased height, early age of disease onset, viral upper respiratory infections and periods of hormonal changes seem to be prognostic of higher degrees of psoriasis severity. We are pioneering the use of increased height and puberty, menopause/andropause as independent prognostic factors of psoriasis severity.

Ascites in children with extrahepatic portal venous obstruction: Etiology, risk factors and outcome

BackgroundAscites in extrahepatic portal venous obstruction (EHPVO) is uncommon. We studied the etiology and natural history of ascites and risk factors of post-bleeding ascites in children with EHPVO. MethodsAll admitted EHPVO patients with clinically detectable ascites and/or gastrointestinal (GI) bleeding in previous 6 weeks were analysed. Subjects with ascites were classified as post-bleeding ascites and de-novo ascites (no GI bleeding) Post-bleeding ascites group was compared with controls (GI bleeding without ascites) for risk factors of developing ascites. ResultsOf the total 307 analysed EHPVO patients, 26% (n=79) had ascites. Majority (n=66, 83%) were post-bleeding ascites and 17% (n=13) had de-novo ascites due to secondary causes. Risk factors of ascites in post-bleeding ascites (n=56) versus controls (n=188) were younger age of disease onset, lower height z-scores and greater reduction in serum protein, albumin and hemoglobin from baseline non-bled state. 32%, 39%, and 29% of patients with post-bleeding ascites had ascites resolution with salt restriction, additional diuretics and large volume paracentesis respectively. ConclusionsMajority of ascites in EHPVO children is after GI bleeding where early age of disease onset, large volume of blood loss and poor nutritional status are risk factors. Overall outcome of EHPVO with ascites is favourable.

Spine and Sacroiliac Joints Lesions on Magnetic Resonance Imaging in Early Axial-Spondyloarthritis During 24-Months Follow-Up (Italian Arm of SPACE Study).

Objectives: Our study aimed to identify: (1) the prevalence of spine and pelvis magnetic resonance imaging (MRI-spine and MRI-SIJ) inflammatory and structural lesions in patients (pts) with a diagnosis of axial spondyloarthritis (axSpA); (2) the predictive factors for a severe disease pattern with a higher probability of radiographic progression.Materials and Methods: Seventy-five pts with low back pain (LBP) (≥3 months, ≤2 years, onset ≤45 years) underwent physical examination, questionnaires, laboratory tests, X-rays, MRI-spine, and MRI-SIJ at baseline (T0) and during a 24-months follow-up. Two expert rheumatologists made axSpA diagnosis and classification (according ASAS criteria). MRI-spine, MRI-SIJ and X-rays were scored independently by 2 readers following the SPARCC, mSASSS, and mNY-criteria. According to ASAS criteria, 21 pts fulfilled imaging arm only and 29 clinical arm with/without imaging arm; 25 pts did not fulfill ASAS criteria.Results: At T0 the mean ± SD LBP onset was 28.51 ± 8.05 years, 45.3% pts were male, 38.7% were HLA-B27+; 56% showed bone marrow oedema (BMO) at MRI-spine and 64% at MRI-SIJ. Signs of enthesitis were found in 58% pts in the thoracic spine. Eighteen (24%) pts presented BMO at MRI-spine with a negative MRI-SIJ. The prevalence of BMO lesions and the SPARCC SIJ and spine score decreased during the follow-up in the 2 cohorts meeting ASAS criteria. An early onset of LBP, a lower use of NSAIDs, a BASDAI>4 were identified as predictors of spine structural damage; the high SPARCC SIJ score appeared to be a predictor of SIJ structural damage. A higher mSASSS was predicted by a lower age of onset of LBP. Predictor of higher SPARCC spine was a higher NSAIDs and of higher SPARCC SIJ score the HLA-B27 positivity with increased inflammatory biomarkers.Conclusions: At T0 a significant prevalence of BMO lesions was observed both in SIJ and spine, with predominant involvement of thoracic district. Since positive MRI-spine images were observed in the absence of sacroiliitis, these findings seem to be relevant in the axSpA diagnosis. Early age of disease onset, long duration of LBP, increased inflammatory biomarkers, higher use of NSAIDs, male gender, HLA-B27 positivity, SPARCC SIJ score>2 appeared predictors of radiological damage and activity.

Comorbidities and phenotype-genotype correlation in children with familial Mediterranean fever.

Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease manifesting with phenotypic heterogeneity. The phenotype-genotype correlation is not established clearly yet. Furthermore, some comorbidities such as vasculitis and inflammatory arthritis may accompany FMF. Herein, we aimed to define phenotype-genotype correlation and comorbid diseases of children with FMF. The medical records of 1687 children diagnosed and followed up as FMF were reviewed retrospectively. Disease severity was assessed by PRAS score. A total of 1687 children (841 girls, 846 boys) were involved in the study. The mean ± standard deviation of current age, age at symptom onset, and age at diagnosis were 13.1 ± 5.4, 5.4 ± 4, and 8 ± 4.2years, respectively. Median (min-max) follow-up period was 3 (0.5-18) years. Among them, 118 (7%) patients had at least one concomitant disease and 72% of them were carrying at least one M694V mutation. Patients with a concomitant disease expressed a more severe course of disease when compared to ones without a concomitant disease (23.7% vs 8.8%, p < 0.001). Children carrying homozygous M694V mutation had significantly earlier age of disease onset and severe disease course (p < 0.001). Forty-four patients (2.6%) were colchicine resistant and most of them were carrying homozygous M694V mutation. Sixteen colchicine-resistant patients were treated with anakinra while 28 received canakinumab. Juvenile idiopathic arthritis (JIA) and immunoglobulin A vasculitis were the most commonly seen associated diseases and the patients with a concomitant disease demonstrated more severe course. This is the largest pediatric cohort studied and presented since now. We confirmed that carrying M694V mutation is associated both with a severe disease course and a predisposition to comorbidities.

The coexistence of psychogenic nonepileptic and epileptic seizures in the same patient is more frequent than expected: Is there any clinical feature for defining these patients?

ObjectivesThis study aimed to investigate the prevalence of psychogenic nonepileptic seizures (PNES) and PNES-epilepsy coexistence within all video-electroencephalography (EEG) monitoring unit (VEMU) referrals and to identify semiological and electrophysiological features to differentiate patients with PNES-epilepsy coexistence from PNES-only. MethodsWe retrospectively reviewed medical files, VEMU reports, and videos of 1983 adult patients. Demographical, historical, clinical, neuroimaging, and electrophysiological parameters of all patients were recorded. We classified patients into five groups as definite PNES-only, definite PNES-epilepsy coexistence, definite PNES-probable epilepsy coexistence, probable PNES-definite epilepsy coexistence, and probable PNES-only. We defined a “definite” group when we saw the ictal EEG and/or video recording of the seizure. The “probable” term is used when there is strong evidence from the history of a particular seizure type and suggestive interictal EEGs without video recordings. ResultsTwo hundred and three of 1983 patients (10.23%) had PNES. Sixty-six of patients with PNES (32.51%) had definite PNES-epilepsy coexistence. When probable cases were included, the PNES-epilepsy coexistence ratio was 53.69% within all patients with PNES. The prevalence of PNES-epilepsy coexistence was 3.32% within all our VEMU referrals. Lower high school graduation rate, earlier age of disease onset, history of status epilepticus, febrile convulsion and brain surgery, use of three or more antiepileptic drugs, and abnormal magnetic resonance imaging (MRI) findings supported PNES-epilepsy coexistence (p < 0.05). On the contrary, seizure duration longer than 10 min was in favor of PNES-only (p < 0.05). ConclusionsThe prevalence of PNES-epilepsy coexistence might be more frequent in VEMUs than expected. Some demographic and semiological features and electrophysiological findings might be useful in differentiating patients with PNES-epilepsy coexistence from patients with PNES-only.

Natural history and genotype-phenotype correlation of pantothenate kinase-associated neurodegeneration.

AimsTo investigate the natural history and genotype‐phenotype correlation of pantothenate kinase‐associated neurodegeneration.MethodsWe collected data of patients with PKAN by searching from available publications in English and Chinese. Patients diagnosed in our center (Peking University First Hospital) were also included. The difference in natural history and genotype between early‐onset (<10 year of age at onset) and late‐onset patients (≥10 year of age at onset) with PKAN was compared.ResultsA total of 248 patients were included. The median age at onset was 3.0 years in the early‐onset group and 18.0 years in the late‐onset group. Dystonia in lower limbs was the most common initial symptom in both groups. In the early‐onset group, the median interval between the disease onset and occurrence of oromandibular dystonia, generalized dystonia, loss of independent ambulance was 6.0 years, 5.0 years, and 5.0 years. The corresponding values in late‐onset group were 1.0 year, 4.0 years, and 6.0 years. About 20.0% died at median age of 12.5 years and 9.5 years after the onset in early‐onset group. About 2.0% of the late‐onset patients died during the follow‐up. A total of 176 mutations were identified. Patients carrying two null alleles in PANK2 showed significantly earlier age of disease onset and progressed more rapidly to loss of independent ambulance.ConclusionsThis study provided a comprehensive review on the natural history and genotype of 248 patients with PKAN. The results will serve as a historical control data for future clinical trial on PKAN.

Assessment of Mortality Rate in 10 Years and the Associated Risk Factors in Schizophrenia.

The aim of the study was to explore the mortality rate and the associated risks factors in patients with schizophrenia during a10- year follow up period. We searched the records of patients with schizophrenia receiving treatment as outpatients and/or inpatients in the psychiatric clinic of a university hospital between 2004 and 2008 and determine the survival of these patients by the end of 2018. The results were compared with the all cause mortality rate in the general population during the same period. Also, the risk factors affecting the mortality rate among the patients were investigated. Out of a total of 626 registered patients 506 were included in the study. The mortality rate within 10 years was found to be 10.6%, with a mean age of 53.1 years at the time of death. The overall expected life expectancy was 73.4 years; varying between 66.6 years among the males and 77.6 years among the females; and 64.7 and 76.5 years among smokers and non-smokers, respectively. The overall standardized mortality rate (SMR) was 3.7, being 3.9 among the males and 3.3 among the females. The risk factors that were associated with the death were old age, male gender, smoking, not working, and early age of disease onset. Smoking is a significant risk factor for mortality. Giving priority to programs for stopping smoking, and supporting rehabilitation services that enables patients to get involved in could help reducing the mortality risk.

Characteristics of patients with systemic sclerosis living in Qatar.

Objective: The aim of this study was to determine the demographic, clinical, and immunological characteristics of patients with systemic sclerosis living in Qatar. Method: This retrospective study included 42 patients with systemic sclerosis who attended Rheumatology Clinics at Hamad General Hospital in Doha, Qatar, between January 2000 and December 2014. All patients fulfilled the 1980 American College of Rheumatology (ACR) classification criteria for systemic sclerosis. Results: The 42 consecutively recruited patients of mixed ethnicities consisted of 37 (88.1%) females and 5 (11.9%) males. Of the total 42 patients, 22 (52.4%) had diffuse cutaneous systemic sclerosis (dcSSc) and 20 (47.6%) had limited cutaneous systemic sclerosis (lcSSc). Mean age at onset of first symptoms was 34.5 ± 12 years, and mean age at diagnosis was 36.1 ± 11.5 years. During follow-up, Raynaud's phenomenon occurred in 36 (85.7%) patients, sclerodactyly in 39 (92.9%) patients, digital ulcers in 16 (38.1%) patients, calcinosis in 6 (14.3%) patients, telangiectasia in 16 (38.1%) patients, and arthritis in 13 (31%) patients. The gastrointestinal and respiratory systems were the most frequently affected internal organs. Gastrointestinal involvement was present in 36 (85.7%) patients, and respiratory involvement was found in 30 (71.4%) patients. The majority of patients had positive antinuclear antibodies (ANA; 97.6%). Anti-Scl-70 antibody was found in 66.7% and anti-centromere antibody (ACA) was detected in 14.3% of the patients. Conclusion: To our knowledge, this is the first study that describes the clinical and immunological profile of patients with systemic sclerosis living in Qatar. This study cohort showed an earlier age of disease onset and diagnosis than that reported in other international studies. Furthermore, in contrast to several other studies, the diffuse type of scleroderma was more commonly observed than the limited type, which resulted in a high frequency of anti-Scl-70 antibody and interstitial lung disease.

Familial mediterranean fever: assessment of clinical manifestations, pregnancy, genetic mutational analyses, and disease severity in a national cohort.

The aims of this study were to investigate the main clinical and laboratory features, including pregnancy and genetic analysis, of Turkish Familial Mediterranean Fever (FMF) patients and to analyze the relationships between genotypic features, age of disease onset, clinical findings, and disease severity. A study was planned within a national network of 22 different centers. Demographics, clinical and laboratory findings, attack characteristics, drugs, pregnancy and birth history, disease severity, and gene mutation analyses were evaluated. Disease severity, assessed using a scoring system developed by Pras et al., was evaluated in relation to gene mutations and age of disease onset. A total of 979 patients (643 females and 336 males; mean age: 35.92 ± 11.97years) with FMF were included in the study. Of a total of 585 pregnancies, 7% of them resulted in preterm birth and 18.1% resulted in abortions. During pregnancy, there was no FMF attack in 61.4% of patients. Of the MEditerranean FeVer (MEFV) mutations, 150 (24.3%) cases were homozygous, 292 (47.3%) cases were heterozygous, and 175 (28.4%) were compound heterozygous. Patients with homozygous gene mutations had more severe disease activity, earlier age of disease onset, higher rates of joint and skin involvement, sacroiliitis, and amyloidosis. Patients with compound heterozygous genotype displayed severe disease activity in close resemblance to patients with homozygous mutation. In addition, patients with compound heterozygous mutations had higher rates of protracted febrile myalgia and elevated fibrinogen levels. In 63.9% of compound heterozygous patients, age of onset was < 20years, with greater disease severity, and high rates of attack frequency and colchicine resistance. Our results suggest that indicators for disease severity include early onset of disease and homozygous gene mutations. Furthermore, patients with compound heterozygous mutations displayed significant presentations of severe disease activity.

Microcatheter-assisted Trabeculotomy for Primary Congenital Glaucoma After Failed Glaucoma Surgeries.

To evaluate the effectiveness of microcatheter-assisted trabeculotomy (MAT) to treat primary congenital glaucoma after failed previous glaucoma surgeries. Retrospective, noncomparative, interventional case series conducted at Beijing Tongren Eye Center, China. Outcome measures were compared between 3 groups: successful and complete (≥330 degrees) MAT; successful and partial (<330 degrees) MAT; or cases converted to traditional trabeculotomy when the Schlemm's canal could not be catheterized >180 degrees. Success was defined as final intraocular pressure ≤21 mm Hg, with (qualified success) or without (complete success) glaucoma medications. In total, 74 eyes of 63 consecutive patients were included. MAT was performed in 50 eyes (67.6%). Postoperative intraocular pressure and number of glaucoma drops (17.7±8.6 mm Hg, 0.6±1.2 medications) was significantly less than the preoperative values (35.3±7.2 mm Hg, 2.7±0.8 medications; P<0.001). Cumulative probabilities of qualified and complete success were 84.0% and 80.0% at 3-year follow-up with no difference between complete and partial trabeculotomies. MAT was not successfully performed in 24 eyes (32.4%), requiring conversion to traditional trabeculotomy and associated with greater incidence of previous surgeries (P<0.001), earlier age of disease onset (P=0.024) and worse corneal transparency (P=0.010). Cumulative probabilities of qualified and complete success were 37.0% and 29.2% at 3-year follow-up. Both complete and partial MAT achieved significant pressure reduction in cases of primary congenital glaucoma with previous failed glaucoma surgeries in intermediate term.

Complement C7 is a novel risk gene for Alzheimer's disease in Han Chinese.

Alzheimer's disease is the most common neurodegenerative disease, and has a high level of genetic heritability and population heterogeneity. In this study, we performed the whole-exome sequencing of Han Chinese patients with familial and/or early-onset Alzheimer's disease, followed by independent validation, imaging analysis and function characterization. We identified an exome-wide significant rare missense variant rs3792646 (p.K420Q) in the C7 gene in the discovery stage (P = 1.09 × 10−6, odds ratio = 7.853) and confirmed the association in different cohorts and a combined sample (1615 cases and 2832 controls, Pcombined = 2.99 × 10−7, odds ratio = 1.930). The risk allele was associated with decreased hippocampal volume and poorer working memory performance in early adulthood, thus resulting in an earlier age of disease onset. Overexpression of the mutant p.K420Q disturbed cell viability, immune activation and β-amyloid processing. Electrophysiological analyses showed that the mutant p.K420Q impairs the inhibitory effect of wild type C7 on the excitatory synaptic transmission in pyramidal neurons. These findings suggested that C7 is a novel risk gene for Alzheimer's disease in Han Chinese.

HLA-B*39:06 Efficiently Mediates Type 1 Diabetes in a Mouse Model Incorporating Reduced Thymic Insulin Expression.

Type 1 diabetes (T1D) is characterized by T cell-mediated destruction of the insulin-producing β cells of the pancreatic islets. Among the loci associated with T1D risk, those most predisposing are found in the MHC region. HLA-B*39:06 is the most predisposing class I MHC allele and is associated with an early age of onset. To establish an NOD mouse model for the study of HLA-B*39:06, we expressed it in the absence of murine class I MHC. HLA-B*39:06 was able to mediate the development of CD8 T cells, support lymphocytic infiltration of the islets, and confer T1D susceptibility. Because reduced thymic insulin expression is associated with impaired immunological tolerance to insulin and increased T1D risk in patients, we incorporated this in our model as well, finding that HLA-B*39:06-transgenic NOD mice with reduced thymic insulin expression have an earlier age of disease onset and a higher overall prevalence as compared with littermates with typical thymic insulin expression. This was despite virtually indistinguishable blood insulin levels, T cell subset percentages, and TCR Vβ family usage, confirming that reduced thymic insulin expression does not impact T cell development on a global scale. Rather, it will facilitate the thymic escape of insulin-reactive HLA-B*39:06-restricted T cells, which participate in β cell destruction. We also found that in mice expressing either HLA-B*39:06 or HLA-A*02:01 in the absence of murine class I MHC, HLA transgene identity alters TCR Vβ usage by CD8 T cells, demonstrating that some TCR Vβ families have a preference for particular class I MHC alleles.

Cesarean delivery and artificial lactation are associated with an earlier age of disease onset in multiple sclerosis (P2.350)

Cesarean delivery and artificial lactation are associated with an earlier age of disease onset in multiple sclerosis (P2.350)