Early-onset Patients Research Articles

Late Onset Ankylosing Spondylitis: Clinical and Biological Features Comparison With Early-Onset Patients

Late Onset Ankylosing Spondylitis: Clinical and Biological Features Comparison With Early-Onset Patients

Peripheral blood mononuclear cells reactivity in recent-onset type I diabetes patients is directed against the leader peptide of preproinsulin, GAD65271-285 and GAD65431-450.

T cell reactivity against pancreatic autoantigens is considered one of the main contributors to the destruction of insulin-producing cells in type 1 diabetes (T1D). Over the years, peptide epitopes derived from these autoantigens have been described in NOD mice and in both HLA class II transgenic mice and humans. However, which ones are involved in the early onset or in the progressive phases of the disease is still unclear. In this work we have investigated, in early-onset T1D pediatric patients and HLA-matched controls from Sardinia, the potential of preproinsulin (PPI) and glutamate decarboxylase 65 (GAD65)-derived peptides to induce spontaneous T cell proliferation responses of peripheral blood mononuclear cells (PBMCs). Significant T cell responses against PPI1-18, PPI7-19 and PPI31-49, the first two belonging to the leader sequence of PPI, and GAD65271-285 and GAD65431-450, were found in HLA-DR4, -DQ8 and -DR3, -DQ2 T1D children. These data show that cryptic epitopes from the leader sequence of the PPI and GAD65271-285 and GAD65431-450 peptides might be among the critical antigenic epitopes eliciting the primary autoreactive responses in the early phases of the disease. These results may have implications in the design of immunogenic PPI and GAD65 peptides for peptide-based immunotherapy.

Early- and late-onset of isolated rapid eye movement sleep behavior disorder: A retrospective cohort study

ObjectiveAge at onset of neurodegenerative disease has significant implications in differentiating disease profiles. We aimed to determine whether age at onset could identify clinical and neurodegenerative profiles in patients with isolated/idiopathic rapid eye movement sleep behavior disorder (iRBD) - a prodromal stage of α-synucleinopathies. MethodsIn this retrospective cohort study, the time of the first episode of dream-enactment behaviors that the patient/bed-partners recalled at the time of the patient's first visit to sleep clinic was collected. The distribution of age at onset was examined and patients were dichotomized into early- and late-onset groups based on the intersection point of underlying two Gaussian distributions of onset age. ResultsA total of 241 patients were included. The intersection of underlying two Gaussian models of onset age was 64.6 years, yielding 168 early- (median onset age: 58.0 years, range: 38.0–64.0) and 73 late-onset patients (median onset age: 70.0 years, range: 65.0–82.0). Among them, 154 of early- and 68 late-onset patients were followed-up. Late-onset patients had milder RBD symptoms, but worse sleep, cognition, olfactory and motor functions, and a higher risk of phenoconversion (adjusted hazard ratio (aHR) = 2.2, 95% confidence interval (CI) = 1.2–3.9), especially to probable dementia with Lewy bodies (DLB) (aHR = 8.9, 95% CI = 3.0–26.2), than early-onset patients. ConclusionsLate-onset iRBD was associated with a higher level of neurodegenerative markers and a quicker phenoconversion, especially to probable DLB. Age at onset of iRBD could help identify clinical features and predict prognosis of iRBD.

Things I need you to know: a qualitative analysis of advice-giving statements in early-onset colorectal cancer patients’ personal accounts published online

ObjectivePeople with early-onset colorectal cancer (EOCRC), defined as colorectal cancer (CRC) before the age of 50, now constitute a significant patient population. In empirical and grey literature EOCRC patients report...

Genetic Basis of Early Onset Atrial Fibrillation in Patients without Risk Factors.

Atrial fibrillation (AF) is the most common arrhythmia and typically occurs in elderly patients with other cardiovascular and extracardiac diseases. However, up to 15% of AF develops without any related risk factors. Recently, the role of genetic factors has been highlighted in this particular form of AF. The aims of this study were to determine the prevalence of pathogenic variants in early-onset AF in patients without known disease-related risk factors and to identify any structural cardiac abnormalities in these patients. We conducted exome sequencing and interpretation in 54 risk factor-free early-onset AF patients and further validated our findings in a similar AF patient cohort from the UK Biobank. Pathogenic/likely pathogenic variants were found in 13/54 (24%) patients. The variants were identified in cardiomyopathy-related and not arrhythmia-related genes. The majority of the identified variants were TTN gene truncating variants (TTNtvs) (9/13 (69%) patients). We also observed two TTNtvs founder variants in the analysed population-c.13696C>T p.(Gln4566Ter) and c.82240C>T p.(Arg27414Ter). Pathogenic/likely pathogenic variants were found in 9/107 (8%) individuals from an independent similar AF patient cohort from the UK Biobank. In correspondence with our Latvian patients, only variants in cardiomyopathy-associated genes were identified. In five (38%) of the thirteen Latvian patients with pathogenic/likely pathogenic variants, dilation of one or both ventricles was identified on a follow-up cardiac magnetic resonance scan. We observed a high prevalence of pathogenic/likely pathogenic variants in cardiomyopathy-associated genes in patients with risk factor-free early-onset AF. Moreover, our follow-up imaging data indicate that these types of patients are at risk of developing ventricular dilation. Furthermore, we identified two TTNtvs founder variants in our Latvian study population.

The levels of peripheral blood TNF-α, Decorin and neutrophils MAPK1 mRNA levels of patients with preeclampsia and their clinical significance

Objective This study analyzed the levels of peripheral blood tumor necrosis factor-α (TNF-α), Decorin (DCN) and Mitogen-activated protein kinase 1 (MAPK1) mRNA in neutrophils of patients with preeclampsia and their correlations, in order to provide more thoughts on the diagnosis and treatment of clinical patients. Methods 81 patients with preeclampsia who had regular prenatal checkups and delivered in our hospital from June 2020 to April 2022 were analyzed, including 26 patients with early-onset and 55 patients with late-onset, and 50 pregnant women with normal pregnancy who had prenatal checkups and delivered in our hospital during the same period were selected as the control group. Record the clinical data of patients, record the expression of peripheral blood TNF-α, DCN and neutrophils MAPK1 mRNA of patients with early-onset, late-onset and the control group, and record the correlation between DCN level, MAPK1 mRNA expression and TNF-α level of patients with preeclampsia. Results The diastolic and systolic blood pressures were significantly higher in early-onset and late-onset patients, and the gestational week of delivery was significantly lower in early-onset and late-onset patients, respectively (p < .05); there was no statistically significant difference in the average age, BMI, average pregnancy time, and average births between the three groups (p > .05). The expressions of peripheral blood TNF-α, DCN, and neutrophils MAPK1 mRNA of the early-onset and late-onset groups were all higher than those in the control group (p < .05); and the expressions of TNF-α, DCN, and MAPK1 mRNA in the peripheral blood of the early-onset group were all higher than those in the late-onset group (p < .05); Pearson correlation analysis showed that DCN level and TNF-α level in patients with preeclampsia were positively correlated (r = 0.98639, p < .05); Neutrophils MAPK1 mRNA expression and TNF-α level were positively correlated (r = 0.9611, p < .05). Conclusion TNF-α, DCN and neutrophils MAPK1 mRNA were all highly expressed in the peripheral blood of patients with pre-eclampsia and were more significantly elevated in patients with early-onset preeclampsia, and the expression levels of DCN and MAPK1 mRNA were positively correlated with TNF-α levels. It is possible that all three factors are involved in the pathogenesis of preeclampsia, and are expected to be used as indicators for early prediction and diagnosis.

Influence of aldo–keto reductase 1C3 polymorphisms in early-onset female psoriasis patients

The principal pathology of psoriasis is impaired skin barrier function, epidermal thickening, and granular layer loss. Exposure to extrinsic factors such as tobacco smoke and air pollutants is associated with the development of psoriasis. Aryl hydrocarbon receptors (AHRs) are activated by extrinsic factors associated with the development of psoriasis and act as transcriptional regulators. Expression of aldo–keto reductase (AKR) 1C3 in the epidermal spinous layer regulates epidermal keratinocyte differentiation via the AHR signaling pathway. We investigated whether single nucleotide polymorphisms (SNPs) in AKR1C3 are associated with the pathogenesis of psoriasis. The proportions of rs12529 G/C, C/C variants, and rs12387 A/A, A/G variants were twofold higher in Japanese psoriasis patients (n = 231) compared with a Japanese healthy cohort. The SNPs were significantly more common than the majority variants in female patients with disease onset ≤ 22 years of age. Patients with rs12529 G > C and rs12387 A > G SNPs exhibited significantly lower AKR1C3 expression and higher expression of late differentiation markers. In conclusion, AKR1C3 downregulation caused by rs12529 G > C and rs12387 A > G SNPs in the epidermis induces abnormal early differentiation of keratinocytes and skin barrier dysfunction, which may contribute to the genetic pathogenesis of psoriasis in young females.

The role of indoleamine 2,3-dioxygenase 1 in early-onset post-stroke depression.

The immune-inflammatory response has been widely considered to be involved in the pathogenesis of post-stroke depression (PSD), but there is ambiguity about the mechanism underlying such association. According to Diagnostic and Statistical Manual of Mental Disorders (5th edition), depressive symptoms were assessed at 2 weeks after stroke onset. 15 single nucleotide polymorphisms (SNPs) in genes of indoleamine 2,3-dioxygenase (IDO, including IDO1 and IDO2) and its inducers (including pro-inflammatory cytokines interferon [IFN]-γ, tumor necrosis factor [TNF]-α, interleukin [IL]-1β, IL-2 and IL-6) were genotyped using SNPscan™ technology, and serum IDO1 levels were detected by double-antibody sandwich enzyme-linked immune-sorbent assay. Fifty-nine patients (31.72%) were diagnosed with depression at 2 weeks after stroke onset (early-onset PSD). The IDO1 rs9657182 T/T genotype was independently associated with early-onset PSD (adjusted odds ratio [OR] = 3.008, 95% confidence interval [CI] 1.157-7.822, p = 0.024) and the frequency of rs9657182 T allele was significantly higher in patients with PSD than that in patients with non-PSD (χ2 = 4.355, p = 0.037), but these results did not reach the Bonferroni significance threshold (p > 0.003). Serum IDO1 levels were also independently linked to early-onset PSD (adjusted OR = 1.071, 95% CI 1.002-1.145, p = 0.044) and patients with PSD had higher serum IDO1 levels than patients with non-PSD in the presence of the rs9657182 T allele but not homozygous C allele (t = -2.046, p = 0.043). Stroke patients with the TNF-α rs361525 G/G genotype had higher serum IDO1 levels compared to those with the G/A genotype (Z = -2.451, p = 0.014). Our findings provided evidence that IDO1 gene polymorphisms and protein levels were involved in the development of early-onset PSD and TNF-α polymorphism was associated with IDO1 levels, supporting that IDO1 which underlie strongly regulation by cytokines may be a specific pathway for the involvement of immune-inflammatory mechanism in the pathophysiology of PSD.

The Combined Effect of Polygenic Risk Score and Prostate Health Index in Chinese Men Undergoing Prostate Biopsy

To date, the combined effect of polygenic risk score (PRS) and prostate health index (phi) on PCa diagnosis in men undergoing prostate biopsy has never been investigated. A total of 3166 patients who underwent initial prostate biopsy in three tertiary medical centers from August 2013 to March 2019 were included. PRS was calculated on the basis of the genotype of 102 reported East-Asian-specific risk variants. It was then evaluated in the univariable or multivariable logistic regression models that were internally validated using repeated 10-fold cross-validation. Discriminative performance was assessed by area under the receiver operating curve (AUC) and net reclassification improvement (NRI) index. Compared with men in the first quintile of age and family history adjusted PRS, those in the second, third, fourth, and fifth quintiles were 1.86 (odds ratio, 95% confidence interval (CI): 1.34-2.56), 2.07 (95%CI: 1.50-2.84), 3.26 (95%CI: 2.36-4.48), and 5.06 (95%CI: 3.68-6.97) times as likely to develop PCa (all p < 0.001). Adjustment for other clinical parameters yielded similar results. Among patients with prostate-specific antigen (PSA) at 2-10 ng/mL or 2-20 ng/mL, PRS still had an observable ability to differentiate PCa in the group of prostate health index (phi) at 27-36 (Ptrend < 0.05) or >36 (Ptrend ≤ 0.001). Notably, men with moderate phi (27-36) but highest PRS (top 20% percentile) would have a comparable risk of PCa (positive rate: 26.7% or 31.3%) than men with high phi (>36) but lowest PRS (bottom 20% percentile positive rate: 27.4% or 34.2%). The combined model of PRS, phi, and other clinical risk factors provided significantly better performance (AUC: 0.904, 95%CI: 0.887-0.921) than models without PRS. Adding PRS to clinical risk models could provide significant net benefit (NRI, from 8.6% to 27.6%), especially in those early onset patients (NRI, from 29.2% to 44.9%). PRS may provide additional predictive value over phi for PCa. The combination of PRS and phi that effectively captured both clinical and genetic PCa risk is clinically practical, even in patients with gray-zone PSA.

Retrospective analysis of risk factors for distant metastasis of early-onset gastric cancer during the perioperative period.

Although the overall global incidence of gastric cancer has been declining, the number of new cases in people under the age of 50 is increasing, which is related to metastasis, late pathological stages, and poor prognosis. There is a scarcity of large-scale studies to evaluate and predict distant metastasis in patients with early-onset gastric cancer. From January 2010 to December 2019, data on early-onset GC patients undergoing surgery were gathered from the Surveillance, Epidemiology, and End Results (SEER) database. We investigated the independent risk factors for distant metastasis in patients with early-onset gastric cancer. Based on these risk factors, we developed a nomogram to predict distant metastasis. The model underwent internal validation on the test set and external validation on 205 patients from the First Affiliated Hospital of Sun Yat-sen University and the seventh Affiliated Hospital of Sun Yat-sen University. The novel nomogram model was then evaluated using the receiver operating characteristic (ROC) curve, calibration, the area under the curve (AUC), and decision curve analysis (DCA). The training set nomogram score was used to classify the different risk clusters of distant metastasis. Our study enrolled 2217 patients after establishing the inclusion and exclusion criteria, with 1873 having no distant metastasis and 344 having distant metastasis. The tumor size, total lymph nodes, whether or not receiving radiotherapy and chemotherapy, T stage, and N stage were significant predictors of advanced distant metastasis (p < 0.05). The AUC of the ROC analysis demonstrated our model's high accuracy. Simultaneously, the prediction model shows high stability and clinical practicability in the calibration curve and DCA analysis. We developed an innovative nomogram containing clinical and pathological characteristics to predict distant metastasis in patients younger than 50 years old with gastric cancer. The tool can alert clinicians about distant metastasis and help them develop more effective clinical treatment plans.

Racial/ethnic differences of germline pathogenic variants in cancer susceptibility genes among patients with early-onset colorectal cancer.

19 Background: The burden of early-onset colorectal cancer (CRC diagnosed before age 50 years) differs across racial/ethnic groups. Yet the distinct prevalence and spectrum of germline pathogenic variants associated with early-onset CRC by race/ethnicity is uncharacterized. Methods: We identified 3,980 early-onset CRC patients unselected for family CRC history who underwent clinical multi-gene panel testing of 14 CRC susceptibility genes ( MLH1, MSH2, MSH6, PMS2, SMAD4, APC, BMPR1, CHEK2, EPCAM, MUTYH, PTEN, STK11, CDH1, and TP53) performed by a nationwide clinical testing laboratory from 2012 to 2016 and identified as Ashkenazi Jewish, Asian, Black, Hispanic, or White. Multi-gene panel testing was performed by targeted custom capture and sequencing and chromosome rearrangement analysis. Clinical and individual/family histories were ascertained from clinician-completed test requisition forms. Germline variant prevalence and spectrum in early-onset CRC was determined by race/ethnicity. Pathogenic variant comparisons by race/ethnicity were evaluated using chi-square tests and multivariable logistic regression adjusted for sex, age, CRC site and sequence. Results: Among 3,980 early-onset CRC patients, a total of 503 germline genetic variants were identified in 481 individuals (12.1%). By race/ethnicity, 12.7% of Ashkenazi Jewish, 8.6% of Asian, 10.3% of Black, 14.0% of Hispanic, and 12.3% of White individuals presented with a pathogenic variant in a CRC susceptibility gene. Nearly 7% of early-onset CRC patients (n = 268) presented with a germline pathogenic mutation in a mismatch repair gene—with the prevalence of Lynch Syndrome in early-onset CRC differing across racial/ethnic groups ( P= 0.037). The prevalence of germline APC, CHEK2, MLH1, monoallelic MUTYH, and PTEN variants also varied by race/ethnicity (all P&lt; 0.02). Overall, Asian individuals with early-onset CRC had 49% lower odds of carrying a pathogenic germline variant in a CRC susceptibility gene versus White individuals in adjusted models (Odds Ratio [OR] = 0.51, 95% Confidence Interval [CI]: 0.26-0.99, P= 0.046). Ashkenazim and Hispanic individuals had higher odds of presenting with pathogenic APC and MLH1 variants, respectively, compared with White individuals in adjusted models ( APC: OR = 8.69, 95% CI: 2.68-28.21, P= 0.0003; MLH1: OR = 2.67, 95% CI: 1.30-5.49, P= 0.007). Conclusions: Of 3,980 patients with early-onset CRC unselected for family history, the prevalence and spectrum of pathogenic germline variants differed across racial/ethnic populations. Beyond multigene panel testing for all early-onset CRC patients, further study is needed to optimize genes selected for germline genetic testing in early-onset CRC across diverse groups—which would have clinical implications for disease surveillance and intervention.

Radiation exposure from diagnostic CT for young patients with colon cancer in the first 5 years after diagnosis.

90 Background: Given the rise in colorectal cancer (CRC) in younger patients, this study aims to analyze the radiation exposure received by early onset colorectal cancer patients from diagnostic imaging performed in the first 5-years from diagnosis. Methods: A retrospective review of all patients (age ≤ 50 y) with stage I-III CRC who received at least 5 surveillance or staging body computed tomography (CT) scans in the 5 years from diagnosis was performed beginning in October 2015. The volume CT dose index (CTDIvol) and dose length product (DLP) were extracted; a previously validated Monte Carlo (MC) based software, VirtualDose (Virtual Phantoms, Inc., Albany, NY), was used to estimate organ dose to 19 organs based on the imaging mode parameters. The effective doses were calculated based on methods set forth in the International Commission on Radiological Protection ICRP No. 103 Publication. Results: A total of 107 patients were included (age range 25-50 years, median 44 years). The average effective dose per CT scan was 15.0 mSv range: 11.6 to 22.6 mSv) for male (n = 62) and 13.4 mSv (8.04 to 17.5 mSv) for female (n = 45) patients. The cumulative effective dose was greater than 100 mSv for 9 (8.4%) of patients and between 50 to &lt; 100 mSv for 28 (26.2%) of the patients in this study. Of the 107 patients, 23% (n = 25) of the patients recurred during the first 5 years. Conclusions: The majority of early-onset colorectal cancer patients in this study received a cumulative dose under 100 mSv, which is considered low risk according to a policy statement by the International Organization for Medical Physics. Since the majority of patients in this study received what is considered a low cumulative radiation dose from repeated CT imaging during the 5-year period after diagnosis, this may provide reassurance that repeated CT imaging, particularly for surveillance, is warranted. Individual risk will vary but the clinical benefits of clinical imaging outweigh the small, if any, risk of radiation-induced cancers in this patient cohort. [Table: see text]

Comparative analyses of intratumoral microbiome with diet in patients with early- vs late-onset colorectal cancer.

208 Background: Early-onset colorectal cancer (CRC) is a growing public health problem with an incidence rate increase of 7.9% in individuals aged 20-29, 4.9% in those aged 30-39, and 1.6% in those aged 40-49 during 2004-2016. The etiology of this rise is not well established, but there is emerging evidence that the intra-tumoral microbiome may be implicated. We sought to categorize the interaction between diet and intra-tumoral microbiome in early- vs. late-onset CRC. Methods: Intra-tumoral microbiome data were collected from patients enrolled in a retrospective/prospective study of early ( &lt; 45 years) vs. late-onset (≥ 65 years) CRC. Formalin-fixed paraffin-embedded tumor samples were microdissected for tumor vs. non-tumor, then DNA was extracted and analyzed using 16S ribosomal gene sequencing. The DHQ3 diet questionnaire was used to ascertain diet history for a period of 12 months prior to diagnosis. Twelve bacteria of interest were selected for analysis based on increased prevalence and known potential association with CRC. Diet groups of interest for analysis included high-risk groups: fried foods, red meat, and alcohol. Results: A subset of 3 bacteria were further analyzed, Bacillus sp., Fusobacterium nucleatum, and Moraxella osloensis, based on relation to the group of patients diagnosed with CRC before the age of 45 (N = 8) and after age 65 (N = 12). Bacteria of interest had a similar prevalence in early- (38%, 3/8) and late-onset patients (33%, 4/12). Fifteen of the 20 patients had one or more of the bacteria of interest present. 71% (5/7) of both early- and late-onset patients who had Bacillus present had no alcohol in their diets. 100% (4/4) of the late onset patients with Bacillus present all had the same diet pattern: no tree nuts, high amounts of potato chips, no alcohol, and no red meat. 83% (5/6) of the early onset patients with 1 or more bacteria present had a high amount of potato chips in their diets. 80% (4/5) patients who had none of the bacteria of interest present also had no red meat in their diet. All early- and late-onset patients with Moraxella had a diet that consisted of more high-risk food groups, in particular potato chips. Conclusions: There were no significant differences in intra-tumoral microbiome in patients with early- vs. late-onset CRC. However, there may be an association between certain bacteria and high-risk diets. Results were limited by a small sample size, and further research should be done to better understand the relationship between intra-tumoral microbiome and diet.

Cover Image

The cover image is based on the Research Article Clinical spectrum of rectal cancer identifies hallmarks of early-onset patients and next-generation treatment strategies by Dingcheng Shen et al., https://doi.org/10.1002/cam4.5120.

Evaluating the Genetic Role of Circadian Clock Genes in Parkinson's Disease.

Increasing evidence suggests that circadian dysfunction is related to Parkinson's disease (PD). However, the role of circadian clock genes in PD is still poorly understood. This study aimed to illustrate the association between genetic variants of circadian clock genes and PD in a large Chinese population cohort. Ten circadian clock genes were included in this study. Whole-exome sequencing (WES) was conducted in 1997 early-onset or familial PD patients and 1652 controls (WES cohort), and whole-genome sequencing (WGS) was conducted in 1962 sporadic late-onset PD patients and 1279 controls (WGS cohort). Analyses were completed using the optimized sequence kernel association test and regression analyses. In the burden analysis of the circadian clock gene set, we found suggestive significant associations between the circadian clock genes and PD in the WES cohort when considering missense, damaging missense (Dmis), and deleterious variants. Moreover, the burden analysis of single genes revealed suggestive significant associations between PD and the loss-of-function variants of the CRY1 gene, missense, Dmis, and deleterious variants of the PER1 gene, and Dmis and deleterious variants of the PER2 gene in the WES cohort.Rare variants in the WGS cohort and all common variants in the WGS and WES cohorts were unrelated to PD. Phenotypic analysis indicated that deleterious variants of the PER1 gene were associated with dyskinesia in the WES cohort. Our study provides evidence of a potential link between circadian clock genes and PD from a genetic perspective.

ANXA1 mutation analysis in Italian patients with early onset PD

Recently, a novel pathogenic variant in Annexin A1 protein (c.4G > A, p.Ala2Thr) has been identified in an Iranian consanguineous family with autosomal recessive parkinsonism. The deficiencies of ANXA1 could lead to extracellular SNCA accumulation, defects in intracellular signaling pathways and synaptic plasticity causing parkinsonism. The aim of this study was to identify rare ANXA1 variants in 95 early-onset PD patients from South Italy. Sequencing analysis of ANXA1 gene revealed only 2 synonymous variants in PD patients (rs1050305, rs149033255). Therefore, we conclude that the recently published ANXA1 mutation is not a common cause of EOPD in Southern Italy.

Post-Stroke Status Epilepticus: Time of Occurrence May Be the Difference?

(1) Background: Stroke is one of the most frequent causes of status epilepticus (SE) in adults. Patients with stroke and SE have poorer prognosis than those with stroke alone. We described characteristics and prognosis of early- and late-onset post-stroke SE (PSSE). (2) Methods: We retrospectively analyzed consecutive stroke patients who experienced a first SE between August 2012 and April 2021, comparing clinical characteristics, stroke, and SE features between early- versus late-onset SE in relation to patients' outcome. (3) Results: Forty stroke patients experienced PSSE. Fourteen developed an early-onset SE (35%) and twenty-six a late-onset SE (65%). Early-onset SE patients had a slightly higher NIHSS score at admission (6.9 vs. 6.0; p = 0.05). Early-onset SE was more severe than late-onset, according to STESS (Status Epilepticus Severity Score) (3.5 vs. 2.8; p = 0.05) and EMSE (Epidemiology-based Mortality score in Status Epilepticus) score (97.0 vs. 69.5; p = 0.04); furthermore, it had a significant impact on disability at 3-month and 1-year follow-up (p = 0.03 and p = 0.02). SE recurrence and seizures relapse were observed mainly in cases of late-onset SE. (4) Conclusions: Early-onset SE seems to be associated with higher disability in short- and long-term follow-up as possible expression of severe acute brain damage.

Prevalence of suicide attempts and correlates among first-episode and untreated major depressive disorder patients with comorbid dyslipidemia of different ages of onset in a Chinese Han population: a large cross-sectional study

BackgroundPatients with dyslipidemia are at increased risk for suicide, especially those with major depressive disorder (MDD). Few studies have investigated the independent effects of suicide attempts on comorbid dyslipidemia in patients with MDD. Moreover, there are no comparisons of differences in factors associated with suicide attempts among patients with MDD with dyslipidemia at different ages of onset. The aim of this study was to investigate the prevalence of suicide attempts and associated variables in first episode and untreated patients with MDD with comorbid dyslipidemia at different ages of onset.MethodsWe recruited 1718 patients with first-episode untreated MDD in this study. Demographical and clinical data were collected, and lipid profiles, thyroid function, and blood glucose levels were measured. The Hamilton Depression Scale 17 (HAMD-17), Hamilton Anxiety Scale (HAMA), Clinical Global Impression Severity Scale (CGI), and Positive and Negative Syndrome Scale (PANSS) positive subscale were assessed for depression, anxiety and illness severity, as well as psychotic symptoms, respectively.ResultsThe percentage of patients with MDD with comorbid dyslipidemia was 61% (1048/1718). Among patients with MDD with comorbid dyslipidemia, the incidence of suicide attempts was 22.2% (170/765) for early adulthood onset and 26.5% (75/283) for mid-adulthood onset. Independent factors associated with suicide attempts in early adulthood onset patients with MDD with dyslipidemia were as follows: HAMA score (B = 0.328, P < 0.0001, OR = 1.388), Suspicion /persecution (B = -0.554, P = 0.006, OR = 0.575), CGI (B = 0.878, P < 0.0001, OR = 2.406), systolic blood pressure (B = 0.048, P = 0.004, OR = 1.049), hallucinatory behavior (B = 0.334, P = 0.025, OR = 1.397), and TPOAb (B = 0.003, p < 0.0001, OR = 1.003). Independent factors associated with suicide attempts in mid-adulthood onset patients with MDD with comorbid dyslipidemia were as follows: HAMA score (B = 0.182, P < 0.0001, OR = 1.200), CGI (B = 1.022, P < 0.0001, OR = 2.778), and TPOAb (B = 0.002, P = 0.009, OR = 1.002).ConclusionOur findings suggest an elevated risk of suicide attempts in patients with MDD with comorbid dyslipidemia. The incidence of suicide attempts was similar in the early- and mid-adulthood onset subgroups among patients with MDD with dyslipidemia, but the factors associated with suicide attempts were different in these two subgroups.

High Throughput Sequencing Analysis of Exosomal miRNA Expressions in Early-Onset Preeclampsia Patients.

The goal of this study was to screen for differentially expressed exosomal miRNAs in peripheral blood samples of early-onset preeclampsia and normal pregnant patients using high-throughput sequencing methods and explore their effects on the pathogenesis of preeclampsia. Peripheral blood samples from 5 patients with early-onset preeclampsia and 5 normal pregnant women (control group) were enrolled. Then, exosomes were extracted from each sample, and the procedure was replicated three times. An Illumina HiSeq4000 sequencing platform was used to analyze exosomal miRNAs in all samples before comparison. The target genes and signaling pathway predictions and the biological function enrichments of significant and differentially expressed miRNAs were assessed using Miranda and Starbase software, as well as GO and KEGG databases. Compared with the control, patients in the early-onset preeclampsia group had 65 significantly and differentially expressed exosomal miRNAs in their peripheral blood samples. The results have shown that of the 65 differentially expressed miRNAs, 17, including has-miR-6855, has-miR-7151, and has-miR-6777, were up-regulated, and 48, including has-miR-1247, has-miR-29B2, and has-miR-941, were down-regulated (p < 0.05). The Miranda and TargetScanS algorithms predicted a total of 2,231 target genes from the differentially expressed miRNAs. The Go and KEGG analyses showed that the principal biological function of these target genes was the regulation of Ras protein signal transduction, histone modification, GTPase-mediated signal transduction, and transforming growth factor (TGF)-β. Additionally, the results also showed that the major pathways involved in the regulation of these functions were the PI3K Akt, MAPK, tumor necrosis factor, and EGFR tyrosine kinase inhibition signaling pathways. There are significant differences in the expression profiles of exosomal miRNAs between early-onset preeclampsia patients and normal pregnant women. These differentially expressed miRNAs may not only play an important regulatory role in the occurrence of early-onset preeclampsia but also participate in its pathophysiological process through genetic regulation of a variety of biological functions and signal pathways.

Very Late Onset Lupus Nephritis: Single-Centre Experience and A Review of the Literature

Background: In the majority of lupus patients, lupus nephritis (LN) develops within the first five years of diagnosis. Here we evaluated patients treated in our department during the past 40 years distinguishing those with very early onset [within one year of diagnosis]; early onset [ two to five years post diagnosis]; medium-term onset [between six to ten years after diagnosis]; late onset [presenting six to 15 years after diagnosis] and very late onset LN [presenting 16 years or later after diagnosis]. Early onset [ two to five years post diagnosis]; medium-term onset [between six to ten years after diagnosis]; late onset [presenting six to 15 years after diagnosis] and very late onset LN [presenting 16 years or later after diagnosis].early onset [within two years of diagnosis]; medium-term onset [between two and five years after diagnosis]; late onset [presenting five to ten years after diagnosis] and very late onset LN [presenting ten years after diagnosis]. Aim: To compare the differences in demography, clinical data, serological profile and follow up of patients with LN of early, medium, late and very late onset. Methods: This was a retrospective study of 226 systemic lupus erythematosus (SLE) patients with biopsy proven nephritis. We focused on a comparison of their epidemiology, serology, clinical and follow-up data. Results: We identified 97 (43%) very early-onset patients; 69 (31%) early-onset; 28 (12%) medium onset; 22 (10%) late-onset and 10 (4%) very late-onset LN patients. Comparing those patients whose LN was delayed by&gt; 10 years post their lupus diagnosis compared to those with LN onset &lt;10 years we found that these patients were statistically significantly more likely to be Caucasian [p=0.04]; to have arthritis [p=0.001] and to be leucopaenic [p=0.004]. There were no other difference between the groups. Among the 10 patients with very late onset LN there was an increase trend towards them having higher ANA titer (&gt;1:640) [p=0,044] and having biopsy-proven combined type of LN (III+V, IV+V) [p=0.034]. Conclusion: Although the majority of SLE patients who get LN do so within 10 years of diagnosis in our experience 14% [approximately 1:7] developed renal involvement 10 years or more after SLE diagnosis. The observation emphasis the need to be vigilant when caring for SLE patients long term.