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OBJECTIVE: This study explored the mediating effect of diabetes on the relationship between nonalcoholic fatty liver disease (NAFLD) and atherosclerotic cardiovascular disease (ASCVD). METHODS: In this prospective community cohort study, 82 975 participants were enrolled, with the primary outcome being the incidence of new-onset ASCVD. Using the Cox proportional hazards model, the hazard ratio (HR) and 95% confidence interval (CI) for ASCVD occurrence were computed between NAFLD and non-NAFLD groups. The correlation between NAFLD and diabetes was assessed using a binary logistic regression model, and that between NAFLD, diabetes and ASCVD using a mediation model. RESULTS: During follow-up, 9471 ASCVD cases were observed. Compared with individuals without NAFLD, those with NAFLD showed an increased ASCVD risk (HR: 1.424; 95% CI: 1.363-1.488; Pâ <â 0.001). Stratifying NAFLD based on metabolic subphenotypes revealed a higher ASCVD risk in the NAFLD combined with diabetes subgroup than in the non-NAFLD subgroup (HR: 1.960; 95% CI: 1.817-2.115; Pâ <â 0.001). NAFLD was positively associated with baseline diabetes (odds ratio: 2.983; 95% CI: 2.813-3.163; Pâ <â 0.001). Furthermore, NAFLD severity was positively correlated with diabetes risk. Mediation analysis indicated that diabetes partially mediated the effect of NAFLD on ASCVD incidence, accounting for 20.33% of the total effect. CONCLUSION: NAFLD is an independent predictor of increased ASCVD risk, which may be slightly mediated by diabetes in patients with NAFLD. Evaluating NAFLD and diabetes may be crucial in the early screening and prevention of ASCVD.
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Aterosclerose , Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/complicações , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Prospectivos , Incidência , Aterosclerose/epidemiologia , Fatores de Risco , Idoso , Diabetes Mellitus/epidemiologia , Modelos de Riscos Proporcionais , Análise de Mediação , Medição de Risco , Modelos Logísticos , AdultoRESUMO
AIMS: The relationship between uric acid (UA) concentrations and the risk of cardiovascular disease (CVD), especially for subtypes of CVD among individuals with chronic kidney disease (CKD) is not well understood. This study aimed to investigate whether uric acid concentration was associated with subtypes of CVD and all-cause mortality among individuals with CKD. METHODS: A total of 27,707 individuals with CKD, free of CVD at recruitment from the Kailuan Study, were included. Cox proportional hazards regression models were used to compute hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Over a median follow-up of 11-12 years, we documented 674 myocardial infarctions, 1197 heart failures, 2406 strokes, and 5676 total deaths. Among participants with CKD, compared with those in the lowest tertile of UA, the HRs (95% CIs) of participants in the highest UA tertile were 1.38 (1.13-1.67) for myocardial infarction, 1.60 (1.38-1.85) for heart failure, 1.01 (0.91-1.12) for stroke, and 1.29 (1.21-1.38) for all-cause mortality. Subgroup analyses showed that the associations between UA and heart failure and all-cause mortality were stronger in individuals with eGFR <45 mL/min/1.73m2 compared to their counterparts (Pinteraction<0.05). Additionally, the association between UA and all-cause mortality was stronger among individuals without diabetes than those with diabetes (Pinteraction<0.05). CONCLUSIONS: In individuals with CKD, a higher concentration of UA was associated with a higher risk of myocardial infarction, heart failure, and all-cause mortality, following a dose-response relationship. Our data underscore the importance of UA screening among individuals with CKD for CVD and premature death prevention.
This study investigated the relationship between uric acid (UA) concentrations and the risk of cardiovascular disease and all-cause mortality in individuals with chronic kidney disease (CKD) using the Kailuan Study. A higher concentration of UA was associated with a higher risk of myocardial infarction, heart failure, and all-cause mortality among individuals with CKD, following a dose-response manner.The associations between concentrations of UA and the risk of heart failure and all-cause mortality were more pronounced in individuals with severe kidney impairment (estimated glomerular filtration rate <45 mL/min/1.73m2). Furthermore, the association between UA and all-cause mortality was stronger among individuals without diabetes compared to those with the condition.
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BACKGROUND AND AIMS: Uric acid (UA) and C-reactive protein (CRP) may interact synergistically to accelerate the initiation and progression of cardiovascular disease (CVD). This study investigated the effects of a combination of high UA and high CRP on the risks of CVD. METHODS AND RESULTS: A total of 90,270 participants recruited from the Kailuan study were included, who were divided into four groups according to the presence/absence of hyperuricemia and inflammation. Cox regression was applied to evaluate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) of CVD. C-statistics, net classification index (NRI), and integrated discrimination improvement (IDI) were used to compare the incremental predictive of UA, CRP, and their combined effects on CVD. Mediation analysis was to explore the impact of CRP on the association between UA and CVD. Over a median follow-up of 14.95 years, we identified 11398 incident CVD cases. Compared to the low UA/low CRP group, the high UA/low CRP, low UA/high CRP and high UA/high CRP groups showed progressively higher risks of CVD, HR (95% CI): 1.18(1.10-1.27), 1.27(1.21-1.33) and 1.50 (1.33-1.69), respectively. The incorporation of UA and CRP into the traditional China-PAR model led to improvement in the C-statistic, NRI, and IDI, and was better than incorporation of either UA or CRP alone. Mediation analysis showed that CRP mediated the association between UA and CVD, accounting for 11.57% of the total effects. CONCLUSIONS: High UA/high CRP is associated with increased risks of CVD. Incorporation of both UA and CRP provided additional value for risk stratification.
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Biomarcadores , Proteína C-Reativa , Doenças Cardiovasculares , Fatores de Risco de Doenças Cardíacas , Hiperuricemia , Mediadores da Inflamação , Regulação para Cima , Ácido Úrico , Humanos , Proteína C-Reativa/análise , Ácido Úrico/sangue , Masculino , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico , Pessoa de Meia-Idade , Feminino , Estudos Prospectivos , Biomarcadores/sangue , China/epidemiologia , Medição de Risco , Hiperuricemia/sangue , Hiperuricemia/epidemiologia , Hiperuricemia/diagnóstico , Fatores de Tempo , Adulto , Incidência , Mediadores da Inflamação/sangue , Prognóstico , Idoso , Análise de MediaçãoRESUMO
Neuro-COVID, a condition marked by persistent symptoms post-COVID-19 infection, notably affects various organs, with a particular focus on the central nervous system (CNS). Despite scant evidence of SARS-CoV-2 invasion in the CNS, the increasing incidence of Neuro-COVID cases indicates the onset of acute neurological symptoms early in infection. The Omicron variant, distinguished by heightened neurotropism, penetrates the CNS via the olfactory bulb. This direct invasion induces inflammation and neuronal damage, emphasizing the need for vigilance regarding potential neurological complications. Our multicenter study represents a groundbreaking revelation, documenting the definite presence of SARS-CoV-2 in the cerebrospinal fluid (CSF) of a significant proportion of Neuro-COVID patients. Furthermore, notable differences emerged between RNA-CSF-positive and negative patients, encompassing aspects such as blood-brain barrier integrity, extent of neuronal damage, and the activation status of inflammation. Despite inherent limitations, this research provides pivotal insights into the intricate interplay between SARS-CoV-2 and the CNS, underscoring the necessity for ongoing research to fully comprehend the virus's enduring effects on the CNS. The findings underscore the urgency of continuous investigation Neuro-COVID to unravel the complexities of this relationship, and pivotal in addressing the long-term consequences of COVID-19 on neurological health.
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OBJECTIVES: To investigate the immunopathogenic mechanisms of anti-N-methyl-D-aspartate receptor encephalitis (NMDAR-E) by characterizing the changes of immune cells in both peripheral blood (PB) and cerebrospinal fluid (CSF) of patients with NMDAR-E. METHODS: Cytology and flow cytometry were used to explore and compare different immunological parameters in PB and CSF of patients with NMDAR-E, viral encephalitis (VE) and healthy volunteers. Moreover, different models were established to assess the possibility of identifying NMDAR-E patients based on PB and CSF parameters. RESULTS: The neutrophil counts and monocyte-to-lymphocyte ratios (MLR) in PB are higher in NMDAR-E patients than in both VEs and controls (P < 0.001, respectively), while the percentages of CD3 + T, CD4 + T lymphocytes, and the leukocytes count in CSF were lower in NMDAR-Es than in VEs (P < 0.01, respectively). The higher percentages of CD8 + T cells in blood and CSF were both correlated with more severe NMDAR-E (P < 0.05, respectively). The poor neurological status group had significantly higher PB leukocytes but lower CSF leukocyte count (P < 0.05). Longitudinal observations in patients with NMDAR-E showed a decreasing trend of leukocyte count, neutrophils count, neutrophil-to-monocyte ratios (NMR), and neutrophil-to-lymphocyte ratios (NLR) with the gradual recovery of neurological function. CONCLUSIONS: The expression patterns of T lymphocyte subsets were different in patients with NMDAR-E and viral encephalitis. The changing trends of leukocyte and lymphocyte populations in peripheral blood and cerebrospinal fluid may provide clues for the diagnosis of different types of encephalitides, including NMDARE, and can be used as immunological markers to assess and predict the prognosis.
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Encefalite Antirreceptor de N-Metil-D-Aspartato , Encefalite Viral , Humanos , Encefalite Antirreceptor de N-Metil-D-Aspartato/diagnóstico , Prognóstico , Linfócitos T CD4-Positivos , Imunidade CelularRESUMO
BACKGROUND: The association of longitudinal uric acid (UA) changes with cardiac conduction block risk is unclear. We aimed to identify the trajectories of UA and explore its association with cardiac conduction block. METHODS: A total of 67,095 participants with a mean age of 53.12 years were included from the Kailuan cohort in Tangshan, China, who were free of cardiac conduction block and with repeated measurements of UA from 2006 to 2012. UA trajectories during 2006 to 2012 were identified by group-based trajectory modeling. Cox proportional hazard regression models were used to assess the association of UA trajectories with cardiac conduction block. RESULTS: We categorized three observed discrete trajectories of UA during 2006-2012 period: low-stable, moderate-stable, and high-stable. Over a median follow-up of 6.19 years, we identified 1405 (2.09%) incident cardiac conduction block. Compared to those in the low-stable trajectory, the adjusted hazard ratios (HRs) (95% confidence interval [CI]) of cardiac conduction block in the moderate-stable and high-stable trajectory were 1.30 (1.16-1.47) and 1.86 (1.56-2.22), and HRs of atrioventricular block were 1.39 (1.12-1.72) and 2.90 (2.19-3.83), and HRs of bundle branch blocks were 1.27 (1.10-1.47) and 1.43 (1.13-1.79). Notably, although the average UA level in the moderate-stable UA trajectory group is within the normal range, the risk of cardiac conduction block has increased. CONCLUSIONS: The moderate-stable and high-stable trajectories are associated with increased risk for new-onset cardiac conduction block. Monitoring UA trajectories may assist in identifying subpopulations at higher risk for cardiac conduction block.
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Ácido Úrico , Humanos , Pessoa de Meia-Idade , China/epidemiologia , Fatores de RiscoRESUMO
BACKGROUND: The identification of patients with seizures of unknown etiology who would benefit from neural antibody testing necessitates effective assessment tools. The study aimed to compare the performance of the Antibody Prevalence in Epilepsy and Encephalopathy (APE2) score and the "Obvious" Indications for Neural Antibody Testing in Epilepsy or Seizures (ONES) checklist. We also intended to evaluate whether the performance of the tools varied by types of antibody. METHODS: Patients diagnosed with epilepsy, seizures, or status epilepticus of unknown etiology at West China Hospital from January 2019 to December 2021 were included. Paired serum/cerebrospinal fluid samples were analyzed for antineuronal and antiglial antibodies. The APE2 score and ONES checklist were applied, and their outcomes were compared to laboratory antibody test results. Possible false positive neuronal antibody results were excluded in sensitivity/specificity analysis reasonably. RESULTS: A total of 113 antibody-positive and 159 antibody-negative patients were enrolled in sensitivity/specificity analysis. The ONES checklist showed superior sensitivity than APE2 score (95.6 % vs.79.6 %, P < 0.001). Specificity was not statistically different (60.4 % vs. 57.9 %, P = 0.557). The negative predictive value (NPV) of ONES checklist was higher than that of APE2 score (94.8 % vs 80.7 %, P < 0.001). The positive predictive value of them was not statistically different (61.7 % vs 58.8 %, P = 0.557). APE2 score exhibited lower sensitivity for predicting LGI-Abs (52.9 % vs. 80.3 %, P = 0.022) compared to NMDAR-Abs. Similarly, ONES checklist showed lower sensitivity for LGI1-Abs than NMDAR-Abs (82.4 % vs. 100.0 %, P = 0.009). CONCLUSIONS: The ONES checklist demonstrates superior sensitivity for neural antibody positivity than APE2 score. Specificity of the two assessment tools was similar. ONES checklist performed better NPV than the APE2 score. Both assessment tools performed less well in predicting the presence of LGI1- Abs when compared to NMDAR-Abs.
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Encefalopatias , Epilepsia , Humanos , Autoanticorpos , Convulsões , Epilepsia/complicações , NeurôniosRESUMO
BACKGROUND: We aimed to explore the prevalence of autoimmune antibodies (Abs) in a large consecutive series with "chronic" epilepsy and without symptoms of autoimmune encephalitis; and to compare the immunopathology of brain tissue from drug-resistant epilepsy (DRE) with and without Abs positivity. METHODS: Neuronal and glial antibodies were detected in the serum of patients who were admitted to the wards of West China Hospital from October 2016 to September 2019 and had epilepsy by cell-based assays and tissue-based assays. RESULTS: Twenty-one (6.8 %) of 328 patients had positive Ab findings for the following: dipeptidyl-peptidase-like protein-6 (n = 7), contactin-associated protein-like 2 (n = 5), glutamic acid decarboxylase 65 (n = 4), gamma aminobutyric acid beta receptor (n = 2), N-methyl-d-aspartate receptor (n = 2), and dopamine D2 receptor (n = 1). Antibodies were detected in 6.9 % (13/187) of epilepsy people with unknown etiology and 5.6 % (8/141) of patients with known etiology, respectively. Among 190 patients with DRE, 14 (7.3 %) patients were Abs-positive. There was no significant difference between individuals with seropositive and seronegative results in clinical manifestations, except that the history of febrile seizure was significantly more frequent in the seropositive group. Moreover, brain samples from 3 patients with Abs-positive DRE (with DPPX in 2 patients, and CASPR2 in 1 patient) and 18 patients with Abs-negative DRE were analyzed for immunopathology. We found higher expression of CD8-positive T-cells in the hippocampus of Abs-positive DRE group. CONCLUSIONS: Neuronal antibodies are potentially involved in the process of "chronic" epilepsy, and CD8-positive T-cells may play an important role in this process.
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Epilepsia Resistente a Medicamentos , Encefalite , Epilepsia , Humanos , Autoanticorpos , Prevalência , Epilepsia/diagnóstico , Encéfalo/patologia , Epilepsia Resistente a Medicamentos/patologiaRESUMO
BACKGROUND: Although bundle branch block and atrioventricular block are recognized to be association with cardiovascular disease (CVD) and mortality, the relationship between cardiac conduction block (CCB) and both CVD and all-cause mortality has yet to be explored. AIMS: To explore the relationship between CCB and CVD and all-cause mortality. METHODS AND RESULTS: We included 145,805 subjects (mean age 49.7 years, 81.2% males) from the kailuan study. CCB was diagnosed through a 12lead electrocardiograph (ECG). Mortality and CVD events were ascertained through multiple sources, including a municipal social insurance institution, hospital records, death certificates, and regular active follow-ups. After a mean follow-up of 12.5 years, 18,301 cases developed all-cause mortality. After excluding 4443 subjects with CVD presence at baseline, 13,208 cases of CVD occurred among the 141,362 study subjects during follow-up. Compared with non-CCB group, the cumulative incidence of CVD and all-cause mortality for CCB group was 18.38% VS 12.14% and 33.45% VS 14.18%, respectively. The multivariable-adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) with CCB group were 1.25(1.17-1.34) for CVD, and 1.31(1.25-1.38) for all-cause mortality. Additionally, there were generally stronger associations for CCB with all-cause mortality and CVD in younger participants compared with their older counterparts (Ps-interaction <0.001). CONCLUSION: CCB can increase the risk of CVD and all-cause mortality in the general population. Our findings highlight the importance of strategies for preventing CCB to reduce the risk of CVD and mortality.
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Bloqueio Atrioventricular , Doenças Cardiovasculares , Masculino , Humanos , Pessoa de Meia-Idade , Feminino , Doenças Cardiovasculares/epidemiologia , Bloqueio de Ramo , Doença do Sistema de Condução Cardíaco/diagnóstico , Bloqueio Atrioventricular/diagnóstico , Fatores de RiscoRESUMO
Background: To evaluate the associations between a new definition of metabolic dysfunction-associated fatty liver disease (MAFLD) and extrahepatic cancers and compare with nonalcoholic fatty liver disease (NAFLD). Methods: We enrolled 151,391 Chinese participants in the Kailuan cohort. Hepatic steatosis was detected by abdominal ultrasound. Fine and Gray competing risk regression models were used to estimate hazard ratios (HRs) and 95% confidence interval (CI) between MAFLD and extrahepatic cancers. Results: MAFLD was associated with increased risk of prostate (HR =1.49, 95% CI: 1.07-2.08) and obesity-related cancers, including thyroid (HR =1.47, 95% CI: 1.01-2.12), kidney (HR =1.54, 95% CI: 1.18-2.00), colorectal (HR =1.15, 95% CI: 0.98-1.34) and breast cancer (HR =1.31, 95% CI: 1.04-1.66). The results were consistent in NAFLD vs. non-NAFLD and MAFLD-NAFLD vs. neither FLD. Compared with the neither FLD group, the NAFLD-only group had a higher risk of extrahepatic cancers (HR =1.57, 95% CI: 1.18-2.09), esophageal (HR =5.11, 95% CI: 2.25-11.62), and bladder cancer (HR =3.36, 95% CI: 1.23-9.17). The additional risk of extrahepatic cancers (HR =1.42, 95% CI: 1.17-1.73), esophageal (HR =4.37, 95% CI: 2.55-7.49), and breast cancer (HR =1.99, 95% CI: 1.01-3.92) was observed in MAFLD with metabolic dysregulation, and kidney (HR =1.83, 95% CI: 1.38-2.43), prostate (HR =1.46, 95% CI: 1.00-2.14) and breast cancer (HR =1.33, 95% CI: 1.02-1.74) was observed in MAFLD with overweight and metabolic dysregulation, as well as colorectal (HR =1.45, 95% CI: 1.07-1.96) and prostate cancer (HR =2.44, 95% CI: 1.42-4.21) in MAFLD with three risk factors. Additionally, MAFLD with excessive alcohol consumption would increase extrahepatic cancers (HR =1.14, 95% CI: 1.01-1.29) and breast cancer (HR =7.27, 95% CI: 2.33-22.69) risk. Conclusions: MAFLD and NAFLD shared similar excessive risks of obesity-related cancers, suggesting a driving role of FLD in these cancers. Metabolic dysregulation beyond obesity may play additional kidney, colorectal, and prostate cancer risks in MAFLD patients. It may be helpful in the clinic to relieve symptoms by treating metabolic disorders and preventing adverse outcomes of extrahepatic cancers.
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Proton-pump rhodopsin (PPR) in marine microbes can convert solar energy to bioavailable chemical energy. Whereas bacterial PPR has been extensively studied, counterparts in microeukaryotes are less explored, and the relative importance of the two groups is poorly understood. Here, we sequenced whole-assemblage metatranscriptomes and investigated the diversity and expression dynamics of PPR in microbial eukaryotes and prokaryotes at a continental shelf and a slope site in the northern South China Sea. Data showed the whole PPRs transcript pool was dominated by Proteorhodopsins and Xanthorhodopsins, followed by Bacteriorhodopsin-like proteins, dominantly contributed by prokaryotes both in the number and expression levels of PPR unigenes, although at the continental slope station, microeukaryotes and prokaryotes contributed similarly in transcript abundance. Furthermore, eukaryotic PPRs are mainly contributed by dinoflagellates and showed significant correlation with nutrient concentrations. Green light-absorbing PPRs were mainly distributed in >3 µm organisms (including microeukaryotes and their associated bacteria), especially at surface layer at the shelf station, whereas blue light-absorbing PPRs dominated the <3 µm (mainly bacterial) communities at both study sites, especially at deeper layers at the slope station. Our study portrays a comparative PPR genotype and expression landscape for prokaryotes and eukaryotes in a subtropical marginal sea, suggesting PPR's role in niche differentiation and adaptation among marine microbes.
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BACKGROUND: Hypertension and enlarged perivascular spaces (EPVS) are thought to be associated with cognitive impairment. However, the correlations among hypertension, EPVS, and cognitive impairment have not been studied yet. We aimed to investigate the relationships between cumulative blood pressure (cBP) exposure with EPVS and cognitive impairment and whether EPVS may mediate the relationship between cBP and cognitive impairment. METHODS: A total of 1507 subjects from the Kailuan prospective cohort study were enrolled. cBP was calculated from 2006 to 2022. The effects of cBP, EPVS scores, and cognitive impairment were evaluated using a logistic regression model. The relationships among cBP, EPVS score, and cognitive impairment were analyzed using a mediation model. RESULTS: An increase in cBP was positively correlated with an increase in EPVS score. For every SD increase in cBP, the odds ratios (95% CI) of increased EPVS score of the centrum semiovale were 1.67 (1.43-1.95), 1.63 (1.4-1.9), and 1.35 (1.17-1.56), respectively; the odds ratios (95% CI) of increased EPVS score of the basal ganglia were 1.83 (1.56-2.15), 2.01 (1.7-2.36), and 1.31 (1.13-1.52), respectively; and the odds ratios (95% CI) of developing cognitive impairment were 1.28 (1.06-1.53), 1.13 (0.95-1.34), and 1.28 (1.07-1.5), respectively. Basal ganglia-EPVS score accounted for 10.46% to 18.32% of the mediating effects on the relationships of cBP/SD with cognitive impairment. CONCLUSIONS: High cBP exposure was an independent risk factor for EPVS, and basal ganglia-EPVS score mediated the effects of cBP on cognitive impairment. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: ChiCTR-TNRC-11001489.
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Disfunção Cognitiva , Hipertensão , Humanos , Pressão Sanguínea , Imageamento por Ressonância Magnética , Estudos Prospectivos , Disfunção Cognitiva/etiologiaRESUMO
OBJECTIVE: Anti-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) encephalitis is a rare subtype of autoimmune encephalitis. We report patients diagnosed with anti-AMPAR encephalitis in western China, focusing on their clinical presentations, imaging results, treatment strategies, and prognosis. METHODS: Data from patients diagnosed with anti-AMPAR encephalitis in the neurology center of West China Hospital from August 2018 to July 2021 were retrospectively collected and analyzed. Based on the diagnostic criteria of autoimmune encephalitis, nine cases were included. RESULTS: Four patients (44%) were males, and the median age at presentation was 54 years (range, 25-85). Short-term memory loss was the most common initial symptom. Additional types of autoantibodies were identified in three patients. After presentation, four patients were found to have tumors: two with small cell lung cancer, one with ovarian teratoma, and one with thymoma. All patients accepted first-line immune therapy, and follow-up was available from 8 patients (median 20 weeks, range 4-78). At the last follow-up, three patients showed good outcomes (modified Rankin scale [mRS] 0-2; 37.5%). Five patients showed poor outcomes (mRS 3-6; 62.5%): two had minimal changes and remained hospitalized, two had residual severe cognitive impairments, and one patient died during follow-up. Outcomes were worse among patients with tumors. Finally, only one patient experienced relapse during follow-up. CONCLUSION: Anti-AMPAR encephalitis should be considered in the differential diagnosis for middle- and senior-aged patients who present with predominantly acute or subacute short-term memory impairment. The long-term prognosis is correlated with the presence of a tumor.
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Encefalite Antirreceptor de N-Metil-D-Aspartato , Doenças Autoimunes do Sistema Nervoso , Encefalite , Neoplasias do Timo , Masculino , Feminino , Humanos , Idoso , Adulto , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Ácido alfa-Amino-3-hidroxi-5-metil-4-isoxazol Propiônico , Estudos Retrospectivos , Recidiva Local de Neoplasia , Encefalite/diagnóstico , Encefalite/terapia , AutoanticorposRESUMO
OBJECTIVE: To compare the efficacy of intravenous immunoglobulin (IVIG) added to antiretroviral therapy (ART) and ART alone in people living with human immunodeficiency virus-associated Guillain-Barré syndrome (HIV-associated GBS). METHODS: The study was a retrospective analysis of clinical records of HIV-associated GBS patients from department of neurology at West China Hospital between January 2015 and October 2020. Patients treated with ART alone were compared with those treated with IVIG + ART. The primary outcome was the GBS disability score at 4 weeks, which was assessed with multivariable ordinal regression. Additional outcomes include the GBS disability scale at 1 week, improvement of ≥ 1 point on the GBS disability score at 1 and 4 weeks, median change in the MRC sum score at 1 and 4 weeks, number of patients who were able to walk independently at 4 weeks. RESULTS: Two hundred and fifty-two (252) individuals living with HIV were recruited in the study. According to the inclusion and exclusion criteria, 21 HIV-associated GBS patients were finally included, of whom 8 were treated with IVIG + ART and 13 were treated with ART alone. At the fourth weeks after treatment, the GBS disability scale grade was significantly lower in patients treated with IVIG + ART than those with ART alone (1 vs. 2, P = 0.02). The adjusted OR for a lower GBS disability scale was 10.6 (95 % CI 1.15 to 98.05; P = 0.03) for the IVIG + ART group. Moreover, 6 of 8 (75 %) patients treated with IVIG + ART were able to walk independently at four weeks after treatment. CONCLUSIONS: The introduction of IVIG combined with ART may be efficacious in the treatment of HIV-infected GBS and may provide better clinical outcomes.
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Síndrome de Guillain-Barré , Infecções por HIV , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento , Síndrome de Guillain-Barré/tratamento farmacológico , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológicoRESUMO
Paraneoplastic neurological syndromes (PNSs) are a group of neurological disorders triggered by an underlying remote tumor. Ovarian teratoma (OT) is the most common histologic type of germ cell tumor in females. The most common PNSs associated with OT is anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. However, with the increasing number of new antibodies reported over the last decade, the clinical spectrum of OT-related PNSs is also expanding. Our knowledge of OT-related PNSs is still far from complete. Here, we provide a comprehensive review of the most recent findings in the field of OT-related PNSs, with a particular focus on their clinical and pathological characteristics. Overall, the description of neuronal antibodies in PNSs associated with OT strongly suggests that antibodies may be responsible for the clinical symptoms in some cases. OT-related PNSs are associated with various clinical manifestations, including anti-NMDAR encephalitis, limbic encephalitis, encephalomyelitis, progressive cerebellar syndrome and opsoclonus-myoclonus syndrome. The pathological characteristics of the OT suggest that the mechanism of PNSs is probably due to heteromorphic neurons in the tumor tissue, the ectopic expression of the antigens in neural tissue within the teratomas and patients' unusual immune response. Despite the severity of the neurological syndromes, most patients with OT-related PNSs showed good neurologic response to early tumor resection combined with immunotherapy. To further advance the management of OT-related PNSs, additional studies are needed to explore this complex topic.
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Objectives: This study reported a case of overlapping anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis and myelin oligodendrocyte glycoprotein (MOG) inflammatory demyelinating disease with human herpesviruses 7 (HHV-7) infection. Methods: The detailed clinical characteristics, neuroimaging features, and outcomes of the patient were collected. Polymerase chain reaction (PCR), cell-based assay (CBA) and the tissue-based indirect immunofluorescence assay (TBA) were used for diagnosis. Results: The clinical manifestations included headache, dizziness, fever, optic neuritis, and epileptic-seizures. Brain magnetic resonance imaging (MRI) showed hyperintensities involving the left frontal, orbital gyrus and bilateral optic nerve with substantial contrast enhancement. Moreover, test for HHV-7 DNA by using the next generation sequencing metagenomics and polymerase chain reaction showed positive result in CSF but not in the serum samples. Anti-HHV-7 IgM and IgG antibodies were detected in both the serum and cerebrospinal fluid. NMDAR antibodies (1:10) were found positive in the patient's CSF by a cell-based assay, and MOG antibodies were positive in the serum (1:10) and CSF (1:32). The patient appeared to respond well to immune therapy and it was found that the clinical symptoms including epileptic-seizure as well as headache were relieved and cerebral lesions almost disappeared after the treatment. However, his vision was not completely restored even at the 8-month follow-up, especially the vision in his right eye which was more seriously damaged. Discussion: We report a rare case of MOG antibodies and anti-NMDAR encephalitis overlapping syndrome (MNOS) with HHV-7 infection for the first time. The possibility of MNOS needs be considered when optic neuritis occurs in the patients diagnosed with anti-NMDAR encephalitis. Besides, immunotherapy should be initiated as early as possible to improve the treatment outcomes and facilitate complete cure.
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Encefalite Antirreceptor de N-Metil-D-Aspartato , Doenças do Tecido Conjuntivo , Doenças Desmielinizantes , Herpesviridae , Neurite Óptica , Infecções por Roseolovirus , Encefalite Antirreceptor de N-Metil-D-Aspartato/diagnóstico , Cefaleia , Humanos , Glicoproteína Mielina-Oligodendrócito , Neurite Óptica/diagnóstico , Neurite Óptica/etiologia , Infecções por Roseolovirus/complicações , Infecções por Roseolovirus/diagnóstico , Convulsões , SíndromeRESUMO
Facing phosphate deficiency, phytoplankton use alkaline phosphatase (AP) to scavenge dissolved organophosphate (DOP). AP is a multitype (e.g., PhoA, PhoD) family of hydrolases and is known as a promiscuous enzyme with broad DOP substrate compatibility. Yet, whether the multiple types differentiate on substrates and collaborate to provide physiological flexibility remain elusive. Here we identify PhoA and PhoDs and document the functional differentiation between PhoA and a PhoD (PhoD_45757) in Phaeodactylum tricornutum. CRISPR/Cas9-based mutations and physiological analyses reveal that (1) PhoA is a secreted enzyme and contributes the majority of total AP activity whereas PhoD_45757 is intracellular and contributes a minor fraction of the total AP activity, (2) AP gene expression compensates for each other after one is disrupted, (3) the DOPâPhoAâphosphate_uptake and the DOP_uptakeâPhoDâphosphate pathways function interchangeably for some DOP substrates. These findings shed light on the underpinning of AP's multiformity and have important implications in phytoplankton phosphorus-nutrient niche differentiation, physiological plasticity, and competitive strategy.
Assuntos
Diatomáceas , Fosfatase Alcalina/genética , Fosfatase Alcalina/metabolismo , Diatomáceas/genética , Organofosfatos/metabolismo , Fosfatos/metabolismo , Fósforo/metabolismo , Fitoplâncton/genéticaRESUMO
OBJECTIVE: To investigate the potential detection rate of anti-thyroid antibodies' (ATAbs) positivity, thyroid dysfunctions, and autoimmune thyroid diseases (AITDs) in autoimmune encephalitis (AE) and to analyze whether thyroid autoimmunity/dysfunction can affect the clinical course of AE. METHODS: Two hundred twenty-one AE patients and 229 age- and sex-matched controls were included in this study. We measured the levels of ATAbs (anti-thyroglobulin antibodies [TgAb], anti-thyroid peroxidase anti-bodies [TPOAb]) and thyroid hormones in all the individuals. In addition, the association of thyroid autoimmunity/dysfunctions with functional outcomes of AE was identified by using logistic regression and Kaplan-Meier analyses. RESULTS: The prevalence of TPOAb-positive and TgAb-positive was significantly higher in AE patients (16.3% and 16.7%, respectively) as compared with controls (9.6% and 7.4%, respectively; P = 0.034 and P = 0.002, respectively). In addition, the free triiodothyronine (fT3) level was significantly lower in AE patients as compared to the controls (P < 0.001). However, the frequency of AITDs (Hashimoto's thyroiditis and Graves' disease) did not significantly differ between AE patients and control subjects. Importantly, low fT3 was found to be associated with poor functional outcomes at the 3-month follow-up in AE. Adjustment of potential confounders did not change the association. However, the presence of ATAbs did not significantly alert the disease course of AE. CONCLUSIONS: ATAbs-positive and/or AITD patients with symptomatic encephalopathy should undergo proper surveillance for AE. Moreover, low fT3 could serve as a possible predictor of poor short-term outcome in AE, thereby suggesting that monitoring of thyroid function in AE may be necessary.
Assuntos
Encefalite , Doença de Hashimoto , Doenças da Glândula Tireoide , Autoanticorpos , Encefalite/diagnóstico , Doença de Hashimoto/diagnóstico , Humanos , Estudos Retrospectivos , Doenças da Glândula Tireoide/complicaçõesRESUMO
Background: Appendiceal goblet cell carcinoma (aGCC) is a rare neoplasm with mixed endocrine and exocrine features. No paraneoplastic neurological syndromes or autoantibodies have been identified in cases of aGCC or even appendiceal tumors. Amphiphysin-immunoglobulin G (IgG) autoimmunity was first described in stiff-person syndrome with breast cancer. We firstly described the clinical course and pathological findings of a patient with aGCC-associated amphiphysin-IgG autoimmunity. Case presentation: A 54-year-old man who developed aGCC was admitted for acute disturbance of consciousness, psychiatric symptoms, cognitive impairment, seizure and hypotension. Amphiphysin-IgG was detected in the patient's serum and CSF by immunoblotting and tissue-based indirect immunofluorescence assay confirming the diagnosis of definite paraneoplastic amphiphysin-IgG-positive encephalitis. Histopathology revealed amphiphysin protein expression and accompanying immune cell infiltration (predominantly CD20+ B cells, CD3+ and CD8+ T cells) within the tumor tissue, suggesting a possible paraneoplastic origin of amphiphysin-associated paraneoplastic neurological syndromes (PNSs) in this case. Although the patient's symptoms resolved after high-dose corticosteroid therapy, he experienced recurrence 6 months later, manifesting as paraneoplastic cerebellar dysfunction. Despite treatment with IV cyclophosphamide and oral mycophenolate mofetil, no improvement was noted. Conclusions: This case suggests that aGCC may trigger amphiphysin-IgG autoimmunity.