Association Between Time to Endovascular Therapy and Outcomes in Patients With Acute Basilar Artery Occlusion.

OBJECTIVE: To characterize the association of onset to puncture time (OPT) with clinical outcomes among patients with acute basilar artery occlusion receiving endovascular therapy (EVT) in clinical practice. METHODS: Using the EVT for Acute Basilar Artery Occlusion (BASILAR) study, we identified consecutive patients with acute basilar artery occlusion receiving EVT in 47 comprehensive stroke centers in China from January 2014 to May 2019. The primary outcome was favorable functional outcome (defined as modified Rankin Scale score [mRS] 0-3) at 90 days. Secondary outcomes included function independence (mRS 0-2), mortality, and symptomatic intracerebral hemorrhage. The associations of OPT with clinical outcomes were analyzed using multivariable logistic regression (OPT as a categorical variable) and restricted cubic spline regression (OPT as a continuous variable). RESULTS: Among 639 eligible patients, the median age was 64 years, and median OPT was 328 minutes (interquartile range 220-490). Treatment within 4-8 hours and 8-12 hours was associated with lower rates of favorable outcome (adjusted odds ratio, 0.63 [95% confidence interval (CI), 0.40-0.98] and 0.47 [95% CI, 0.23-0.93], respectively) compared with treatment within 4 hours. Restricted cubic spline regression analysis showed that the OPT had L-shaped associations with favorable outcome (p nonlinearity = 0.028) and functional independence (p nonlinearity = 0.025), with significant benefit loss throughout the first 9 hours, but then appeared relatively flat. The odds of mortality increased relatively for OPT up to 9 hours, but then leveled off (p nonlinearity = 0.042). The association between symptomatic intracerebral hemorrhage and OPT was not significant. CONCLUSION: Among patients with acute basilar artery occlusion in routine practice, earlier treatment with EVT was associated with better outcomes throughout the first 9 hours after onset, but benefit may sustain unchanged afterwards. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for patients with acute ischemic stroke due to basilar artery occlusion, earlier EVT is associated with better outcomes.

[The association of genetic polymorphism of dendritic cell-specific ICAM-grabbing nonintegrin and hepatitis C infection].

OBJECTIVE: To investigate the association of genetic polymorphism of dendritic cell-specific ICAM-grabbing nonintegrin (DC-SIGNR) and hepatitis C infection. METHODS: Patients with hepatitis C (n = 268) were genotyped and analysed for the repeat sequences polymorphism of DC-SIGNR using PCR and DNA sequencing. HCV virus load and HCV RNA genotypes were analyzed. Inter-group comparison was analyzed using LSD method. RESULTS: No significant correlation was found between DC-SIGNR genotypes/ alleles and HCV RNA genotypes in patients. HCV-infected patients with 7-repeat (medium) alleles had lower HCV RNA levels compared to patients with 9-repeat (onger) alleles (P = 0.036). HCV-infected patients with 7/7 genotype had lower HCV RNA levels compared to patients with 9/7 genotype (P = 0.025). These findings suggest that optimal attachment of hepatitis C virions to DC-SIGNR may be associated with longer alleles. CONCLUSION: The fact that DC-SIGNR polymorphism might affect HCV loads supports the concept that DC-SIGNR contributes to HCV replication efficacy. There is no significant correlation between the genetic polymorphism of DC-SIGNR and HCV-RNA genotypes.

Impact of incompatible killer cell immunoglobulin-like receptor and its ligand on the outcome of haploidentical bone marrow transplantation.

The purpose of study was to investigate the impact of killer immunoglobulin-like receptor (KIR) and its ligand on haploidentical bone marrow transplantation. 74 cases were analyzed for the distribution frequencies and characteristics of KIR and its ligand as well as the impact of KIR ligand for the haploidentical bone marrow transplantation in terms of the overall survival, disease-free survival (DFS), GVHD and relapse. The results showed that among the 19 KIR genotypes currently nominated KIR2DL1, KIR2DL4 and KIR3DL2-3 could be detected in all the cases. Other high frequency genotypes included KIR3DP1 (98.6%), KIR2DP1 (98.6%), KIR3DL1 (97.3%) and KIR2DL3 (97.3%). Inhibitory receptor genotypes were 1.37-fold of activating receptor genotypes. KIR2DL1, KIR3DL2, KIR3DL3 and KIR2DL4 were found in all haplotypes and at least one genotype of KIR2DL2 and/or KIR2DL3 existed in all haplotypes. Among the 14 genotypes found in the test, the HLA-Cw7 was the most popular (37.8%) and the group 2 (HLA-Cw1, 3, 7, 8, 13, 14) recognized by KIR2DL2/2DL3 counted for 43.2%. The incompatibility of KIR for 32 cases of haploidentical BMT was 43.8%, of which 9/14 were KIR2DL incompatible, 5/14 were KIR2DL2 or KIR3DL1 incompatible. Among the 46 cases of haploidentical BMT, 29 cases were HLA-Cw matched and 14 cases were mismatched. The completed mismatch ratio of HLA-Cw was 30.4% and the match ratio was 63.4%. The survival rate was higher for the 14 cases of KIR genotype compatible group than the 13 cases of KIR genotype incompatible group (p = 0.032). The disease-free survival was significantly higher for the 17 cases of mismatched KIR ligands (HLA-Cw) group than the matched group (p = 0.024). The survival rate was higher in GVHD group than that in non-GVHD group when the KIR ligand was missing. The acute and severe GVHD was related to the existence of activating receptor of KIR2DS1/2DS2. The incompatibility group was accompanied with frequent acute and severe GVHD and less relapse and vice versa for the compatibility group. One patient died after BMT among the 14 mismatched KIR ligand group suffering from myelogenous leukemia while 4 patients out of 12 patients died in the matched group. It is concluded that the haploidentical BMT is characterized by mismatch between donor and recipient and its immunological reactions also features by the incompatibility of KIR genotype and missing ligand. The missing ligand for the donor KIR has strong effect on the outcome of BMT and it means a lot to analyze the KIR genotype and its ligand for the selection of best donor and prognostic evaluation in haploidentical BMT.

[Genetic polymorphism of dendritic cell-specific ICAM-3 grabbing nonintegrin and DC-SIGNR's exon 4 in Chinese hepatitis C patients].

OBJECTIVE: To study into the genetic polymorphism of DC-SIGN and DC-SIGNR's exon 4 in Chinese hepatitis C patients and its relationship with HCV infection susceptibility. METHODS: Patients with hepatitis C (n=300, group A) and healthy subjects (n=520, group B) were genotyped and analysed for the repeat sequence of polymorphism of DC-SIGN and DC-SIGNR's exon 4 using PCR and DNA sequencing. RESULTS: The distribution of genotypes and alleles in DC-SIGN's exon 4 in the two groups did not differ significantly (P > 0.05). The difference of allele frequency in DC-SIGNR's exon 4 between the two groups was also not significant (P > 0.05). However, 9/5 genotype distribution frequency of DC-SIGNR's exon 4 in patients with hepatitis C was significantly higher than that in the healthy subjects (P < 0.05). CONCLUSION: There is no significant correlation between the genetic polymorphism of DC-SIGN's exon 4 and HCV infection susceptibility. 9/5 genotype distribution frequency of DC-SIGNR's exon 4 in patients with hepatitis C is significantly higher and may be associated with HCV infection susceptibility.

Expression of killer cell inhibitor receptors on immunocompetent cells with relation to graft-versus-host disease after hematopoietic stem cell transplantation.

The study was aimed at the exploration of relationship between T cells expressing killer cell inhibitor receptors (KIR, CD158 and CD94) and graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation. The expression rates of CD158a, CD158b and CD94 on T cells and NK cell were detected by flow cytometry and donor/recipient HLA-Cw was analyzed using PCR after peripheral blood stem cell transplantation (PBSCT) and umbilical cord blood transplantation (UCBT). After both PBSCT and UCBT, the rates of CD3(+)CD158a(+) and CD3(+)CD158b(+) T cells increased, especially the rate of CD8(+)CD158b(+) T cells. In both acute and chronic GVHD groups, the rate of CD3(+)CD158b(+) T cells increased, especially in acute GVHD. The CD94 mainly expressed on CD3(+)CD8(+) T cells. The percentage of the expression of CD94 on CD4(+) and CD8(+) cells after UCBT and PBSCT increased significantly. The expression of KIR in GVHD (early stage of transplantation) increased but the expression of KIR in chronic GVHD (advanced stage of transplantation) decreased. Five patients who HLA-Cw matched had no severe GVHD. In four patients who underwent allo-PBSCT and UCBT from related HLA-matched donors, only 2 patients had no aGVHD. Four patients underwent transplantation from unrelated HLA-matched donors had GVHD. These observations suggested that there is some relationship between GVHD and KIR expression on T cells. CD158b might be an inhibitory molecule of T cell activated at early stage after transplantation. Understanding the mechanism of GVHD with the expression of KIR on T cells, especially those binding the HLA-Cw might shed light on the establishment of the specific immunotolerance for the prevention of GVHD. To pay attention to HLA-Cw typing is very important to reduce GVHD and increase GVL effect in related or unrelated HLA-matched transplantation.

[Selection of donor in mismatched hematopoietic stem cell transplantation by CREG, residue match and HLA three-dimensional structure].

After search at hematopoietic stem cell banks for transplant donors, there may be several donors matched with given standards. To determine the most appropriate donor for a specific patient, the potential donors were analyzed and compared by three methods. The first is cross-reactive group (CREG) antigens, which defined as the public antigens that shared specific serological reaction patterns. The second is residue match theory, which concerned the three residues oriented upward toward the T-cell receptor. The third is comparing HLA three-dimensional structure models. The results of the three methods were not completely accorded in our case. However, some less matched donors could be excluded from the candidates and the range of selection was further reduced. It is concluded that combined application of three methods would contribute in selecting donor for hematopoietic stem cell transplantation in clinics.

[A New Criterion for Donor and Recipient Selection in Hematopoietic Stem Cell Transplantation - the Matching of Three-Dimensional Structure of HLA Molecular Modeling]

The purpose of the research is to provide a new standard for matching of HLA three-dimensional structure, and summarize the major permissible mismatch and immunogenic mismatch antigens. The molecular modeling method was used to create HLA molecular structures by Swiss Model Server, and the comparison of the differences among the alleles was done by SPDV software with the function of iterative magic fit. The results were recorded by relative mean square deviation (RMSD, nm). The differences among alleles were scattered below 0.06 nm for HLA-A and -B molecules, and below 0.03 nm for HLA-DRB1 molecules. On the basis of the statistical analysis, when RMSD is greater than 0.04 nm for -A and -B molecules and 0.02 nm for -DRB1 molecules, the difference is meaningful and can be related with graft versus host disease. When RMSD is lower than 0.02 nm for -A and -B molecules and 0.01 nm for -DRB1 molecules, the difference is decided unmeaningful. From the data, the permissible mismatch and immunogenic mismatch alleles within HLA-A, HLA-B and HLA-DRB1 molecules were summarized. Three-dimensional structure matching is a new area in the transplantation field, much research should be done in the future.