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Vaccine Jul 2024For the rational design of epitope-specific vaccines, identifying epitopes that can be processed and presented is essential. As algorithm-based epitope prediction is...
For the rational design of epitope-specific vaccines, identifying epitopes that can be processed and presented is essential. As algorithm-based epitope prediction is frequently discordant with actually recognized CD8 T-cell epitopes, we developed an in vitro CD8 T-cell priming protocol to enable the identification of truly and functionally expressed HLA class I epitopes. The assay was established and validated to identify epitopes presented by hepatitis C virus (HCV)-infected cells. In vitro priming of naïve CD8 T cells was achieved by culturing unfractionated PBMCs in the presence of a specific cocktail of growth factors and cytokines, and next exposing the cells to hepatic cells expressing the NS3 protein of HCV. After a 10-day co-culture, HCV-specific T-cell responses were identified based on IFN-γ ELISpot analysis. For this, the T cells were restimulated with long synthetic peptides (SLPs) spanning the whole NS3 protein sequence allowing the identification of HCV-specificity. We demonstrated that this protocol resulted in the in vitro priming of naïve precursors to antigen-experienced T-cells specific for 11 out of 98 SLPs tested. These 11 SLPs contain 12 different HLA-A*02:01-restricted epitopes, as predicted by a combination of three epitope prediction algorithms. Furthermore, we identified responses against 3 peptides that were not predicted to contain any immunogenic HLA class I epitopes, yet showed HCV-specific responses in vitro. Separation of CD8 and CD8 T cells from PBMCs primed in vitro showed responses only upon restimulation with short peptides. We established an in vitro method that enables the identification of HLA class I epitopes resulting from cross-presented antigens and that can cross-prime T cells and allows the effective selection of functional immunogenic epitopes, but also less immunogenic ones, for the design of tailored therapeutic vaccines against persistent viral infections and tumor antigens.
PubMed: 38964950
DOI: 10.1016/j.vaccine.2024.05.080 -
Neurotherapeutics : the Journal of the... Jul 2024The mechanisms of action of Vagus Nerve Stimulation (VNS) and the biological prerequisites to respond to the treatment are currently under investigation. It is...
The mechanisms of action of Vagus Nerve Stimulation (VNS) and the biological prerequisites to respond to the treatment are currently under investigation. It is hypothesized that thalamocortical tracts play a central role in the antiseizure effects of VNS by disrupting the genesis of pathological activity in the brain. This pilot study explored whether in vivo microstructural features of thalamocortical tracts may differentiate Drug-Resistant Epilepsy (DRE) patients responding and not responding to VNS treatment. Eighteen patients with DRE (37.11 ± 10.13 years, 10 females), including 11 responders or partial responders and 7 non-responders to VNS, were recruited for this high-gradient multi-shell diffusion Magnetic Resonance Imaging (MRI) study. Using Diffusion Tensor Imaging (DTI) and multi-compartment models - Neurite Orientation Dispersion and Density Imaging (NODDI) and Microstructure Fingerprinting (MF), we extracted microstructural features in 12 subsegments of thalamocortical tracts. These characteristics were compared between responders/partial responders and non-responders. Subsequently, a Support Vector Machine (SVM) classifier was built, incorporating microstructural features and 12 clinical covariates (including age, sex, duration of VNS therapy, number of antiseizure medications, benzodiazepine intake, epilepsy duration, epilepsy onset age, epilepsy type - focal or generalized, presence of an epileptic syndrome - no syndrome or Lennox-Gastaut syndrome, etiology of epilepsy - structural, genetic, viral, or unknown, history of brain surgery, and presence of a brain lesion detected on structural MRI images). Multiple diffusion metrics consistently demonstrated significantly higher white matter fiber integrity in patients with a better response to VNS (p < 0.05) in different subsegments of thalamocortical tracts. The SVM model achieved a classification accuracy of 94.12%. The inclusion of clinical covariates did not improve the classification performance. The results suggest that the structural integrity of thalamocortical tracts may be linked to therapeutic effectiveness of VNS. This study reveals the great potential of diffusion MRI in improving our understanding of the biological factors associated with the response to VNS therapy.
PubMed: 38964949
DOI: 10.1016/j.neurot.2024.e00422 -
Zhonghua Xue Ye Xue Za Zhi = Zhonghua... May 2024To explore the efficacy and safety of cryopreservation-free integrated autologous hematopoietic stem cell transplantation (HSCT) model for patients with multiple...
To explore the efficacy and safety of cryopreservation-free integrated autologous hematopoietic stem cell transplantation (HSCT) model for patients with multiple myeloma. A total of 96 patients with newly diagnosed multiple myeloma (NDMM) between July 31, 2020, and December 31, 2022, were retrospectively analyzed, of which 41 patients in the observation group received integrated non-cryopreserved transplantation mode. After hematopoietic stem cells were mobilized and collected, melphalan was started immediately for pre-transplant conditioning, and non-cryopreserved grafts from the medical blood transfusion refrigerator were directly injected intravenously into the patient within 24-48 h after the melphalan conditioning. The control group consisted of 55 patients who received traditional transplantation mode. After hematopoietic stem cells were collected, stem cell cryopreservation was performed in liquid nitrogen, and then the transplant plans were started at the right time. All patients received mobilization of autologous hematopoietic stem cells using the G-CSF combined with the plerixafor. ① A total of 34 patients (82.9% ) with VGPR plus CR in the observation group were significantly higher than 33 patients (60.0% ) in the control group (=0.016). ②Compared with the control group, the incidence of grade 1 oral mucosal inflammation was higher in the observation group (<0.001) ; however, the incidence of grades 2 and 3 oral mucosal inflammation was lower (=0.004, =0.048), and neither group experienced grade 4 or above oral mucosal inflammation. The incidence of grade 1 diarrhea was higher in the observation group (=0.002), whereas the incidence of grade 3 diarrhea was lower (=0.007). No statistically significant difference was observed in the incidence of grade 4 diarrhea (=0.506), and neither group experienced grade 5 diarrhea. ③ The incidence of bacterial infection in the observation group was lower than that in the control group (34.1% 65.5%, =0.002), whereas no statistically significant difference was observed in the incidence of fungal infection (29.3% 31.4%, =0.863) and viral infection (4.88% 3.64%, =0.831). ④No statistically significant difference was observed in the implantation time of granulocytes and platelets between the observation and control groups [10 (8-20) days 11 (8-17) days, =0.501; 13 (10-21) days 15 (10-20) days, =0.245]. ⑤ All patients did not receive lenalidomide treatment 100 days post-transplantation. At 30 days post-transplantation, the CTL, NK, and Th cell counts in the observation group were lower than those in the control group (<0.001, =0.002, =0.049), and the NKT cell counts were higher than those in the control group (=0.024). At 100 days post-transplantation, the CTL, NKT, and Th cell counts in the observation group were higher than those in the control group (=0.025, =0.011, =0.007), and no statistically significant difference in NK cell counts was observed between the two groups (=0.396). ⑥ The median follow-up was 18 (4-33) months. The overall 2-year survival rates of the observation and control groups post-transplantation were 91.5% and 78.2%, respectively (=0.337). The recurrence-free survival rates were 85.3% and 77.6%, respectively (=0.386), and the cumulative recurrence rates were 9.8% and 16.9%, respectively (=0.373) . In NDMM, the cryopreservation-free integrated autologous HSCT model can achieve similar therapeutic effects as traditional transplantation models, with lower rates of severe mucosal inflammation and infection compared with traditional transplantation models.
Topics: Humans; Multiple Myeloma; Hematopoietic Stem Cell Transplantation; Retrospective Studies; Transplantation, Autologous; Cryopreservation; Hematopoietic Stem Cell Mobilization; Granulocyte Colony-Stimulating Factor; Male; Female; Middle Aged
PubMed: 38964924
DOI: 10.3760/cma.j.cn121090-20230929-00152 -
Zhonghua Gan Zang Bing Za Zhi =... Jun 2024
[Is it appropriate for the "Guidelines for the Prevention and Treatment of Chronic Hepatitis B (version 2022)" to require HBeAg-negative chronic HBV-infected patients to be HBV DNA-negative?].
Topics: Humans; Hepatitis B, Chronic; Hepatitis B e Antigens; Hepatitis B virus; DNA, Viral; Practice Guidelines as Topic
PubMed: 38964900
DOI: 10.3760/cma.j.cn501113-20240130-00065 -
Zhonghua Gan Zang Bing Za Zhi =... Jun 2024To systematically evaluate the effect of hepatitis B virus (HBV) infection on the risk of adverse pregnancy outcomes. We searched PubMed, Embase, Web of Science, and... (Meta-Analysis)
Meta-Analysis
To systematically evaluate the effect of hepatitis B virus (HBV) infection on the risk of adverse pregnancy outcomes. We searched PubMed, Embase, Web of Science, and Cochrane databases. Two researchers independently screened the literature, extracted data, and evaluated the quality. Meta-analysis and cumulative meta-analysis were performed using R4.4.1 software. Fixed/random effects models were used to analyze heterogeneous and non-heterogeneous results. Heterogeneous modifiers were identified by subgroup analysis. Funnel plots and Peters' test were used to analyze potential publication bias. A total of 48 studies involving 92 836 HBsAg-positive pregnant women and 7 123 292 HBsAg-negative pregnant women were included. In terms of adverse pregnancy outcomes, HBV infection was significantly correlated with the occurrence of gestational diabetes mellitus [odds ratio ()=1.34, 95% confidence interval (): 1.17-1.53] and intrahepatic cholestasis (=2.48, 95%: 1.88-3.29), with statistically significant differences. In terms of adverse neonatal outcomes, HBV infection was significantly correlated with the occurrence of neonatal asphyxia (=1.49, 95%: 1.20-1.86) and preterm birth (=1.22, 95%: 1.12-1.33), with statistically significant differences. In addition, the cumulative meta-analysis demonstrated that the risk of gestational diabetes mellitus and preterm birth both tended to be stable in pregnant women with HBV infection following 2009 and 2010, respectively. The supplementary questions answered for repeated studies had limited significance. Intrahepatic cholestasis, gestational diabetes mellitus, neonatal asphyxia, and preterm birth occurrence risk can be raised with HBV infection in pregnant women.
Topics: Humans; Pregnancy; Female; Hepatitis B; Pregnancy Outcome; Pregnancy Complications, Infectious; Hepatitis B virus; Diabetes, Gestational; Premature Birth; Infant, Newborn; Cholestasis, Intrahepatic; Risk Factors
PubMed: 38964896
DOI: 10.3760/cma.j.cn501113-20240204-00080 -
Zhonghua Gan Zang Bing Za Zhi =... Jun 2024This study aims to compare the antiviral treatment similarities and differences in the population covered by the 2024 version of the World Health Organization's (WHO)... (Comparative Study)
Comparative Study
This study aims to compare the antiviral treatment similarities and differences in the population covered by the 2024 version of the World Health Organization's (WHO) hepatitis B prevention and treatment guidelines and the current Chinese hepatitis B prevention and treatment guidelines, so as to explore their impact on the indications for antiviral therapy in Chinese patients with chronic hepatitis B (CHB). The information of patients with chronic hepatitis B virus infection who did not receive antiviral treatment was collected through the registration database of the China Clinical Research Platform for Hepatitis B Elimination. Descriptive statistics were conducted on the demographic, blood, biochemical, and virological levels of patients according to the treatment recommendations of the two versions of the guidelines. The Mann-Whitney U test and χ2 test were used to compare the differences and proportional distribution of the treatment populations covered by the two guidelines. The χ2 test was used to analyze the coverage rate of different antiviral treatment indications. A total of 21,134 CHB patients without antiviral treatment were enrolled. 69.4% of patients met the 2024 versions of the WHO guidelines' recommendations. 85.0% of patients met the current Chinese hepatitis B prevention and treatment guidelines. The WHO guidelines for antiviral therapy indications were met in younger patients with higher levels of ALT, AST, and APRI scores, as well as greater proportion of patients with higher viral loads (P<0.001). The WHO guidelines recommended a cut-off value of APRI>0.5, which raised the proportion of patients on antiviral therapy from 6.6% to 30.9%. 45.7% of patients met the antiviral indications for HBV DNA >2000 IU/ml with abnormal transaminase (ALT>30 U/L for males and ALT>19 U/L for females). The reduced APRI diagnostic cut-off value and ALT treatment threshold had further increased the treatment coverage rate by 91.6% in patients with chronic HBV infection in line with the 2024 versions of WHO guidelines. The reduction of the APRI diagnostic cut-off value and the ALT treatment threshold, based on the current hepatitis B guidelines of China, will further improve the treatment coverage of CHB patients.
Topics: Humans; Antiviral Agents; World Health Organization; Hepatitis B, Chronic; Adult; Female; Male; China; Middle Aged; Practice Guidelines as Topic; Young Adult; Adolescent; Aged; East Asian People
PubMed: 38964895
DOI: 10.3760/cma.j.cn501113-20240421-00218 -
Zhonghua Gan Zang Bing Za Zhi =... Jun 2024In order to achieve the early goal of "eliminating viral hepatitis as a public health threat by 2030" as proposed by the World Health Organization, the relevant issues...
In order to achieve the early goal of "eliminating viral hepatitis as a public health threat by 2030" as proposed by the World Health Organization, the relevant issues that have not yet reached consensus on the aspects of hepatitis B prevention and treatment, including population-wide screening, adult hepatitis B vaccination, the evaluation of quantitative values of hepatitis B virus DNA, the alanine aminotransferase threshold for initiating antiviral therapy, the treatment of patients in the "indeterminate phase," the treatment of patients with co-infections and comorbidities, and others. Thus, experts have formulated recommendations to further expand hepatitis B prevention and treatment, with the aim of accelerating the elimination of hepatitis B virus infection.
Topics: Humans; Hepatitis B; Hepatitis B virus; Hepatitis B Vaccines; Antiviral Agents; World Health Organization
PubMed: 38964891
DOI: 10.3760/cma.j.cn501113-20240407-00175 -
BMJ Case Reports Jul 2024Multisystem inflammatory syndrome in children (MIS-C) is a known complication of COVID-19. There is still limited knowledge about this condition. Here, we report the...
Multisystem inflammatory syndrome in children (MIS-C) is a known complication of COVID-19. There is still limited knowledge about this condition. Here, we report the case of a previously healthy toddler boy, who presented with acute liver failure and duodenal lesions resulting in severe haematemesis and haemorrhagic shock, requiring intensive care unit care. The patient had persistent transaminitis, a deranged coagulation profile, inflammatory markers were elevated, and laboratory tests were negative for common infectious hepatitis aetiologies as well as COVID-19 Reverse transcription polymerase chain reaction. His COVID-19 antibody was reactive. Upper gastrointestinal endoscopy revealed a Forrest grade III duodenal ulcer. Looking into the constellation of symptoms and laboratory findings a confirmed diagnosis of acute viral hepatitis caused by MIS-C was made. Hence, he was given intravenous methylprednisolone along with intravenous immunoglobulins, after which he improved clinically and transaminitis resolved. The patient was discharged on clinical improvement and was doing fine on follow-up up to 6 months.
Topics: Humans; Male; Systemic Inflammatory Response Syndrome; COVID-19; Liver Failure, Acute; Gastrointestinal Hemorrhage; Methylprednisolone; Immunoglobulins, Intravenous; Hematemesis; Duodenal Ulcer; SARS-CoV-2; Child, Preschool
PubMed: 38964873
DOI: 10.1136/bcr-2023-256643 -
Reviews in Medical Virology Jul 2024The question of whether patients in the immune-tolerant (IT) phase of chronic hepatitis B virus (HBV) infection should undergo antiviral therapy and determine the... (Meta-Analysis)
Meta-Analysis Review
Estimating the key outcomes and hepatocellular carcinoma risk in patients in immune-tolerant phase of chronic hepatitis B virus infection: A systematic review and meta-analysis.
The question of whether patients in the immune-tolerant (IT) phase of chronic hepatitis B virus (HBV) infection should undergo antiviral therapy and determine the optimal regimen remains unclear. A comprehensive search of PubMed, Embase, MEDLINE, Cochrane Library, and Wanfang Data from inception to 5 December 2023, was conducted. Studies reporting on key outcomes such as HBV DNA undetectability, HBeAg loss or seroconversion, HBsAg loss or seroconversion, and hepatocellular carcinoma (HCC) incidence in patients in the IT phase of chronic HBV infection were included. In total, 23 studies were incorporated. Approximately 4% of patients in the IT phase achieved spontaneous HBeAg loss over 48 weeks of follow-up. Antiviral therapy demonstrated a favourable impact on HBV DNA negative conversion (Children: risk ratios [RR] = 6.83, 95% CI: 2.90-16.05; Adults: RR = 25.84, 95% CI: 6.47-103.31) and HBsAg loss rates (Children: RR = 9.49, 95% CI: 1.74-51.76; Adults: RR = 7.35, 95% CI: 1.41-38.27) for patients in the IT phase. Subgroup analysis revealed that in adult patients in the IT phase, interferon plus nucleos(t)ide analogues (NA)-treated patients exhibited a higher pooled rate of HBsAg loss or seroconversion than those treated with NA monotherapy (9% vs. 0%). Additionally, the pooled annual HCC incidence for patients in the IT phase was 3.03 cases per 1000 person-years (95% CI: 0.99-5.88). Adult patients in the IT phase had a significantly lower HCC incidence risk than HBeAg-positive indeterminate phase patients (RR = 0.46, 95% CI: 0.32-0.66), with no significant differences observed between IT and immune-active phases. Presently, there is insufficient evidence solely based on reducing the risk of HCC incidence, to recommend treating patients in the IT phase of chronic HBV infection. However, both adult and paediatric patients in the IT phase responded well to antiviral therapy, showing favourable rates of HBsAg loss or seroconversion.
Topics: Humans; Carcinoma, Hepatocellular; Hepatitis B, Chronic; Liver Neoplasms; Antiviral Agents; Hepatitis B e Antigens; Hepatitis B virus; Incidence; Hepatitis B Surface Antigens; DNA, Viral; Immune Tolerance; Treatment Outcome; Seroconversion
PubMed: 38964866
DOI: 10.1002/rmv.2570 -
Sexually Transmitted Infections Jul 2024Sexually transmitted infections (STIs) have markedly increased over the last decade in Spain, calling for prevention and control innovative approaches. While there is...
OBJECTIVES
Sexually transmitted infections (STIs) have markedly increased over the last decade in Spain, calling for prevention and control innovative approaches. While there is evidence indicating the effectiveness of self-sampling for STI diagnosis, no kits for this purpose have been authorised in Spain.
METHODS
A prospective single-blind cross-sectional study carried out between November and December 2022 in an STI clinic in Madrid, Spain, to determine the validity, feasibility and acceptability of self-sampling kits used by non-healthcare professionals from vagina, pharynx, rectum and urethra to diagnose (CT) and (NG). Self-samples were compared with samples collected by healthcare professional (HC samples) and analysed by PCR. Frequency of CT and NG diagnosis by sample type was compared using McNemar's test for paired data. Sensitivity and specificity of self-samples for CT and NG diagnosis were also calculated.
RESULTS
306 self-samples from 51 participants were analysed. 80% were men with median age of 33 (IQR: 28-38) years. Self-samples and HC samples showed no significant statistical differences in CT and NG diagnosis. Self-samples had a sensitivity of 81% for CT and 93% for NG, with a specificity of 97% for CT and 95% for NG. More than 90% of participants had no difficulty understanding the kit instructions and 71% expressed high levels of satisfaction with the self-sampling kit.
CONCLUSION
Self-sampling kits for CT and NG diagnosis can be safely and effectively used by non-healthcare professionals in Spain. National strategies for STI prevention and control should prioritise self-sampling strategies.
PubMed: 38964838
DOI: 10.1136/sextrans-2024-056124