X region mutations of hepatitis B virus related to clinical severity

Chronic hepatitis B virus (HBV) infection remains a major health problem, with more than 240 million people chronically infected worldwide and potentially 650000 deaths per year due to advanced liver diseases including liver cirrhosis and hepatocellular carcinoma (HCC). HBV-X protein (HBx) contributes to the biology and pathogenesis of HBV via stimulating virus replication or altering host gene expression related to HCC. The HBV X region contains only 465 bp encoding the 16.5 kDa HBx protein, which also contains several critical cis-elements such as enhancer II, the core promoter and the microRNA-binding region. Thus, mutations in this region may affect not only the HBx open reading frame but also the overlapped cis-elements. Recently, several types of HBx mutations significantly associated with clinical severity have been described, although the functional mechanism in most of these cases remains unsolved. This review article will mainly focus on the HBx mutations proven to be significantly related to clinical severity via epidemiological studies.

β-Globin Gene Cluster Haplotypes and Clinical Severity in Sickle Cell Anemia Patients in Southern Brazil

Hematopoietic stem cell transplantation(HSCT)has emerged as a curative strategy for sickle cell anemia(SCA);it is necessary to find markers of SCA clinical severity to spare those SCA patients whose clinical course is mild from the morbidity and mortality associated with HSCT. Haplotypes have been correlated with the severity of clinical manifestations in SCA patients, and fetal hemoglobin(HbF)and socioeconomic status(SeS)have also been described as negative factors. We studied these factors and their impact on clinical manifestations in a population of Southern Brazilian patients attending the Center for Sickle Cell Anemia at Hospital de Clínicas de Porto Alegre/RS, Brazil. Clinical severity was defined as two or more veno-occlusive episodes per year. The βS haplotypes were determined by PCR in 75 SCA patients. Among the 150 βS chromosomes analyzed, 99(66%)were identified as Bantu(Ban), 41(27%)asBenin(Ben), and 10(7%)as other haplotypes. Most patients in our sample(62.7%)belonged to lower SeS groups, precluding meaningful statistical analysis of SeS impact on clinical severity. There was no correlation between haplotypes or HbF level and SCA clinical severity. Gene polymorphisms and environmental issues have to be taken into consideration.

Leukoaraiosis is associated with clinical symptom severity,poor neurological function prognosis and stroke recurrence in mild intracerebral hemorrhage:a prospective multi-center cohort study

Leukoaraiosis(LA)results from ischemic injury in small cerebral vessels,which may be attributable to decreased vascular density,reduced cerebrovascular angiogenesis,decreased cerebral blood flow,or microcirculatory dysfunction in the brain.In this study,we enrolled 357 patients with mild intracerebral hemorrhage(ICH)from five hospitals in China and analyzed the relationships between LA and clinical symptom severity at admission,neurological function prognosis at 3 months,and 1-year stroke recurrence.Patients were divided into groups based on Fazekas scale scores:no LA(n=83),mild LA(n=64),moderate LA(n=98)and severe LA(n=112).More severe LA,larger hematoma volume,and higher blood glucose level at admission were associated with more severe neurological deficit.More severe LA,older age and larger hematoma volume were associated with worse neurological function prognosis at 3 months.In addition,moderate-to-severe LA,admission glucose and symptom-free cerebral infarction were associated with 1-year stroke recurrence.These findings suggest that LA severity may be a potential marker of individual ICH vulnerability,which can be characterized by poor tolerance to intracerebral attack or poor recovery ability after ICH.Evaluating LA severity in patients with mild ICH may help neurologists to optimize treatment protocols.This study was approved by the Ethics Committee of Ruijin Hospital Affiliated to Shanghai Jiao Tong University(approval No.12)on March 10,2011.

Clinical features and risk factors of acute hepatitis E with severe jaundice

AIM:To compares the clinical features of patients infected with hepatitis E virus(HEV) with or without severe jaundice.In addition,the risk factors for HEV infection with severe jaundice were investigated.METHODS:We enrolled 235 patients with HEV into a cross-sectional study using multi-stage sampling to select the study group.Patients with possible acute hepatitis E showing elevated liver enzyme levels were screened for HEV infection using serologic and molecular tools.HEV infection was documented by HEV antibodies and by the detection of HEV-RNA in serum.We used χ2 analysis,Fisher's exact test,and Student's t test where appropriate in this study.Significant predictors in the univariate analysis were then included in a forward,stepwise multiple logistic regression model.RESULTS:No significant differences in symptoms,alanine aminotransferase,aspartate aminotransferase,al-kaline phosphatase,or hepatitis B virus surface antigen between the two groups were observed.HEV infected patients with severe jaundice had significantly lower peak serum levels of γ-glutamyl-transpeptidase(GGT)(median:170.31 U/L vs 237.96 U/L,P = 0.007),significantly lower ALB levels(33.84 g/L vs 36.89 g/L,P = 0.000),significantly lower acetylcholine esterase(CHE) levels(4500.93 U/L vs 5815.28 U/L,P = 0.000) and significantly higher total bile acid(TBA) levels(275.56 μmol/L vs 147.03 μmol/L,P = 0.000) than those without severe jaundice.The median of the lowest point time tended to be lower in patients with severe jaundice(81.64% vs 96.12%,P = 0.000).HEV infected patients with severe jaundice had a significantly higher viral load(median:134 vs 112,P = 0.025) than those without severe jaundice.HEV infected patients with severe jaundice showed a trend toward longer median hospital stay(38.17 d vs 18.36 d,P = 0.073).Multivariate logistic regression indicated that there were significant differences in age,sex,viral load,GGT,albumin,TBA,CHE,prothrombin index,alcohol overconsumption,and duration of admission between patients infected with acute hepatitis E with and without severe jaundice.CONCLUSION:Acute hepatitis E patients may naturally present with severe jaundice.

Head-to-head comparison of plasma and PET imaging ATN markers in subjects with cognitive complaints

Background Gaining more information about the reciprocal associations between different biomarkers within the ATN(Amyloid/Tau/Neurodegeneration)framework across the Alzheimer’s disease(AD)spectrum is clinically relevant.We aimed to conduct a comprehensive head-to-head comparison of plasma and positron emission tomography(PET)ATN biomarkers in subjects with cognitive complaints.Methods A hospital-based cohort of subjects with cognitive complaints with a concurrent blood draw and ATN PET imaging(18F-florbetapir for A,18F-Florzolotau for T,and 18F-fluorodeoxyglucose[18F-FDG]for N)was enrolled(n=137).Theβ-amyloid(Aβ)status(positive versus negative)and the severity of cognitive impairment served as the main outcome measures for assessing biomarker performances.Results Plasma phosphorylated tau 181(p-tau181)level was found to be associated with PET imaging of ATN biomarkers in the entire cohort.Plasma p-tau181 level and PET standardized uptake value ratios of AT biomarkers showed a similarly excellent diagnostic performance for distinguishing between Aβ+and Aβ−subjects.An increased tau burden and glucose hypometabolism were significantly associated with the severity of cognitive impairment in Aβ+subjects.Additionally,glucose hypometabolism-along with elevated plasma neurofilament light chain level-was related to more severe cognitive impairment in Aβ−subjects.Conclusion Plasma p-tau181,as well as 18F-florbetapir and 18F-Florzolotau PET imaging can be considered as interchangeable biomarkers in the assessment of Aβstatus in symptomatic stages of AD.18F-Florzolotau and 18F-FDG PET imaging could serve as biomarkers for the severity of cognitive impairment.Our findings have implications for establishing a roadmap to identifying the most suitable ATN biomarkers for clinical use.

Highly Prevalent SARS-CoV-2 Antigenemia in COVID-19 Patients

Background:Many issues,such as severity assessment and antibody responses,remain to be answered eagerly for evaluation and understanding of COVID-19.Immune lesion is one of key pathogenesis of the disease.It would be helpful to understand the disease if an investigation on antigenemia and association was conducted in the patients with SARS-CoV-2 infection.Methods:A total of 156 patients admitted to the First People’s Hospital of Hefei or Anhui Provincial Hospital on January to February 2020 were involved in this study.SARS-CoV-2 nucleocapsid(NP)antigen,specific IgM/IgG antibodies,and RNA were detected in sequential sera from three COVID-19 patients,and additional 153 COVID-19 patients by means of NP-antigen capture enzyme-linked immunosorbent assay,colloidal gold quick diagnosis,and real-time RT-PCR,respectively.The clinical types of COVID-19 patients were classified into asymptomatic,mild,moderate,severe,and critical,following on the Chinese guideline of COVID-19 diagnosis and treatment.The demographic and clinical data of patients were obtained for comparable analysis.Results:NP antigen was detected in 5 of 20 sequential sera collected from three COVID-19 patients with typically clinical symptoms,and 60.13%(92/153)expanded samples collected within 17days after illness onset.No SARS-CoV-2 RNA segment was detected in these sera.The NP positive proportion reached a peak(84.85%,28/33)on 6 to 8days after illness onset.Both NP concentration and positive proportion were increased with the increase of clinical severity of COVID-19.Compared to NP negativepatients,NP positive patients had older age[years,medians(interquartileranges(IQR)),49(6)vs.31(11)],lowerpositive proportion of NP specific IgM[27.17%(25/92)vs.59.02%(36/61)],and IgG[21.74%(20/92)vs.59.02%(36/61)]antibodies,and longer duration[days,medians(IQR),24(10)vs.21(13)]from illness to recovery.Conclusions:SARS-CoV-2 NP antigenemia occurred in COVID-19,and presented highly prevalent at early stage of the disease.The antigenemia was related to clinical severity of the disease,and may beresponsible for the delay of detectable SARS-Cov-2IgM.

A hospital outbreak of severe acute respiratory syndrome in Guangzhou,China

Objective To describe a hospital outbreak of severe acute respiratory syndrome (SARS) and summarize its clinical features and therapeutic approaches.Methods The outbreak started with a SARS patient from the community, and a total of 96 people (76 women and 20 men, mean age (29. 5±10. 3) years, 93. 8% of whom were health care workers) who had exposure to this source patient became infected in a short time. Clinical data in this cohort were collected prospectively as they were identified.Results (1) The incubation period ranged from 1 to 20 (mean: 5. 9±3. 5) days. The duration of hospitalization was (17. 2±8. 0) days. (2) The initial temperature was (38. 3±0. 6)℃, while the highest was (39. 2 ±0. 6)℃( P<0. 001), with fever duration of (9. 0±4. 2) days. (3) Other most common symptoms included fatigue (93. 8%), cough (85. 4%), mild sputum production (66. 7%), chills (55.2%), headache (39.6%), general malaise (35.4%) and myalgia (21.9%). (4) The radiographic changes were predominantly bilateral in the middle or lower lung zones. The number of affected lung fields was 1. 2±0. 8 on presentation, which increased to 2. 9 ?1. 4 after admission (P<0. 001). The interval from the beginning of fever to the onset of abnormal chest radiographs was (3. 5±2. 3) days, which increased in size, extent, and severity to the maximum (6. 7±3. 5) days later. The time before the lung opacities were basically absorbed was (14.9±7.8) days. (5) Leukopenia was observed in 67. 7% of this cohort. The time between the onset of fever and leukopenia was (4. 4±2. 3) days, with the lowest white blood cell count of (2. 80±0. 72)×10~9/L (6) The lowest arterial oxygen saturation was (94.8±3.1 )% with supplementary oxygen. (7) Antibiotical therapies included tetracyclines ( 91. 0%), aminoglycosides ( 83. 3%), quinolones (79. 2%); 18. 8% of the patients received a combination of tetracyclines and aminoglycosides, while 11. 5% received a combination of tetracyclines and quinolones, and 63. 5% received a combination of tetracyclines, aminoglycosides and quinolones. Vancomycin was used in 13. 5% of the patients. (8) 68. 8% of the patients were treated with methylprednisolones for a mean interval of (4. 9±2. 4) days. The initial dose was (67. 3±28. 2) mg/d and the maximal dose was (82. 4 ±30. 5) mg/d. (9) Human y-globulin, interferon-α, antiviral drugs (oral ribavirin or oseltamivir) were used respectively in 68.6%, 46.9% and 92.7% of the patients. (10) Ninety-five patients (99.0%) had a complete clinical recovery, and only 1 patient (1.0%) died. Conclusions SARS appears to be quickly infectious and potentially lethal among health care workers, characterized by acute onset and rapid progression, and mostly bilateral lung involvement on chest radiographs. Proper administration of glucocorticosteroids seems to be of some benefits. Antibiotics, human y-globulin, interferon-α, and antiviral drugs, although empirically, might be useful to shorten the clinical course.