1.Pathogenesis and immunogenicity of an avian H9N2 influenza virus isolated from human.
LiQi LIU ; Li ZI ; JianFang ZHOU ; Yun ZHU ; Jie DONG ; Xiang ZHAO ; JunFeng GUO ; YueLong SHU
Biomedical and Environmental Sciences 2011;24(5):530-536
OBJECTIVETo investigate the pathogenesis and immunogenicity of H9N2 influenza virus A/Guangzhou/333/99 (a reassortant of G1 and G9 viruses isolated from a female patient in 1999) in a mouse model of infection.
METHODSMice were infected with increasing virus titers. Viral load in the lungs and trachea was determined by EID50 assay. Pulmonary histopathology was assessed by hematoxylin-eosin staining. Anti-HI antibody titers and T-cell responses to viral HA were determined by ELISPOT and confirmed by flow cytometry.
RESULTSMice presented a mild syndrome after intranasal infection with A/Guangzhou/333/99 (H9N2) influenza virus. Virus was detected in the trachea and lungs of mice harvested on days 3, 6, and 9 post-infection. A T-cell response to viral HA was detected on day 6 and H9 HA-specific CD(4+) T-cells predominated. Seroconversion was detected after 14 days and antibody persisted for at least 28 weeks.
CONCLUSIONOur results suggest that H9N2 (A/Guangzhou/333/99) can replicate in the murine respiratory tract without prior adaptation, and both humoral and cell-mediated immunity play an important role in the immune response.
Animals ; CD4-Positive T-Lymphocytes ; immunology ; CD8-Positive T-Lymphocytes ; immunology ; Cell Line ; Dogs ; Enzyme-Linked Immunospot Assay ; Female ; Hemagglutination Inhibition Tests ; Hemagglutinins, Viral ; immunology ; Humans ; Infant ; Influenza A Virus, H9N2 Subtype ; immunology ; isolation & purification ; pathogenicity ; Interferon-gamma ; immunology ; Lung ; virology ; Lymphocytes ; immunology ; Mice ; Mice, Inbred BALB C ; Orthomyxoviridae Infections ; immunology ; virology ; Spleen ; immunology ; Trachea ; virology ; Viral Load ; Virulence
2. Characterization and analysis of VH1-2-encoded heterosubtypic antibodies isolated from an avian H5N1 patient.
Ying SUN ; Tian BAI ; Zi LI ; Feier RUAN ; Lingling CHEN ; Jian LU ; Liqi LIU ; Dayan WANG ; Yuelong SHU ; Kun QIN ; Jianfang ZHOU
Chinese Journal of Experimental and Clinical Virology 2018;32(2):136-139
Objective:
To isolate the cross-reactive antibodies against hemagglutinin of influenza virus and identify its biological function.
Methods:
The antibodies gene reservoir of cross-reactive and H5N1 pseudotype particles neutralizing B cell circulating in peripheral blood of a human H5N1 case was recovered by
3.Trends in Venous Thromboembolism Readmission Rates after Ischemic Stroke and Intracerebral Hemorrhage
Liqi SHU ; Adam de HAVENON ; Ava L. LIBERMAN ; Nils HENNINGER ; Eric GOLDSTEIN ; Michael E. REZNIK ; Ali MAHTA ; Fawaz AL-MUFTI ; Jennifer FRONTERA ; Karen FURIE ; Shadi YAGHI
Journal of Stroke 2023;25(1):151-159
Background:
and Purpose Venous thromboembolism (VTE) is a life-threatening complication of stroke. We evaluated nationwide rates and risk factors for hospital readmissions with VTE after an intracerebral hemorrhage (ICH) or acute ischemic stroke (AIS) hospitalization.
Methods:
Using the Healthcare Cost and Utilization Project (HCUP) Nationwide Readmission Database, we included patients with a principal discharge diagnosis of ICH or AIS from 2016 to 2019. Patients who had VTE diagnosis or history of VTE during the index admission were excluded. We performed Cox regression models to determine factors associated with VTE readmission, compared rates between AIS and ICH and developed post-stroke VTE risk score. We estimated VTE readmission rates per day over a 90-day time window post-discharge using linear splines.
Results:
Of the total 1,459,865 patients with stroke, readmission with VTE as the principal diagnosis within 90 days occurred in 0.26% (3,407/1,330,584) AIS and 0.65% (843/129,281) ICH patients. The rate of VTE readmission decreased within first 4–6 weeks (P<0.001). In AIS, cancer, obesity, higher National Institutes of Health Stroke Scale (NIHSS) score, longer hospital stay, home or rehabilitation disposition, and absence of atrial fibrillation were associated with VTE readmission. In ICH, longer hospital stay and rehabilitation disposition were associated with VTE readmission. The VTE rate was higher in ICH compared to AIS (adjusted hazard ratio 2.86, 95% confidence interval 1.93–4.25, P<0.001).
Conclusions
After stroke, VTE readmission risk is highest within the first 4–6 weeks and nearly three-fold higher after ICH vs. AIS. VTE risk is linked to decreased mobility and hypercoagulability. Studies are needed to test short-term VTE prophylaxis beyond hospitalization in high-risk patients.
4. Generation and preliminary characterization of monoclonal antibodies against neuraminidase of H7N9 subtype influenza A virus
Yueyang YU ; Yiran XIE ; Yingzhu CHEN ; Ying SUN ; Heng ZHANG ; Jian LU ; Liqi LIU ; Dayan WANG ; Yuelong SHU ; Kun QIN ; Jianfang ZHOU
Chinese Journal of Experimental and Clinical Virology 2017;31(1):66-70
Objective:
To develop the monoclonal antibody (mAb) against neuraminidase of H7N9 subtype influenza A virus and identify its biological function.
Methods:
Female 8 week-old BALB/c mice were immunized and the splenocytes of the mice were fused with Sp2/0 myeloma cells. Indirect ELISA was used to screen hybridoma and the positive clones were subject to be subcloned. Positive clones were identified and the monoclonal antibodies(mAbs) were obtained by purifying the ascetic fluid of mice injected with the hybridoma. The NA-binding as well as neuraminidase-inhibition activity of these mAbs were determined.
Results:
Three mAbs against neuraminidase of H7N9 subtype influenza A virus, 1G8, 3C4 and 4E8, were obtained. They demonstrated different epitop-recognizing. 3C4 and 4E8 exhibited neuraminidase inhibitory activity, with a IC50 of 1.45 μg/ml and 8.65 μg/ml, respectively.
Conclusions
The results suggested that mAbs specific to neuraminidase of H7N9 subtype influenza A virus were developed, providing an useful tool in control and preventing the novel H7N9 influenza A virus.
5.Outcome Prediction in Cerebral Venous Thrombosis: The IN-REvASC Score
Piers KLEIN ; Liqi SHU ; Thanh N. NGUYEN ; James E. SIEGLER ; Setareh Salehi OMRAN ; Alexis N. SIMPKINS ; Mirjam HELDNER ; Adam de HAVENON ; Hugo J. APARICIO ; Mohamad ABDALKADER ; Marios PSYCHOGIOS ; Maria Cristina VEDOVATI ; Maurizio PACIARONI ; Rascha von MARTIAL ; David S. LIEBESKIND ; Diana Aguiar de SOUSA ; Jonathan M. COUTINHO ; Shadi YAGHI ;
Journal of Stroke 2022;24(3):404-416
We identified risk factors, derived and validated a prognostic score for poor neurological outcome and death for use in cerebral venous thrombosis (CVT). Methods We performed an international multicenter retrospective study including consecutive patients with CVT from January 2015 to December 2020. Demographic, clinical, and radiographic characteristics were collected. Univariable and multivariable logistic regressions were conducted to determine risk factors for poor outcome, mRS 3-6. A prognostic score was derived and validated. Results A total of 1,025 patients were analyzed with median 375 days (interquartile range [IQR], 180 to 747) of follow-up. The median age was 44 (IQR, 32 to 58) and 62.7% were female. Multivariable analysis revealed the following factors were associated with poor outcome at 90- day follow-up: active cancer (odds ratio [OR], 11.20; 95% confidence interval [CI], 4.62 to 27.14; P<0.001), age (OR, 1.02 per year; 95% CI, 1.00 to 1.04; P=0.039), Black race (OR, 2.17; 95% CI, 1.10 to 4.27; P=0.025), encephalopathy or coma on presentation (OR, 2.71; 95% CI, 1.39 to 5.30; P=0.004), decreased hemoglobin (OR, 1.16 per g/dL; 95% CI, 1.03 to 1.31; P=0.014), higher NIHSS on presentation (OR, 1.07 per point; 95% CI, 1.02 to 1.11; P=0.002), and substance use (OR, 2.34; 95% CI, 1.16 to 4.71; P=0.017). The derived IN-REvASC score outperformed ISCVT-RS for the prediction of poor outcome at 90-day follow-up (area under the curve [AUC], 0.84 [95% CI, 0.79 to 0.87] vs. AUC, 0.71 [95% CI, 0.66 to 0.76], χ2 P<0.001) and mortality (AUC, 0.84 [95% CI, 0.78 to 0.90] vs. AUC, 0.72 [95% CI, 0.66 to 0.79], χ2 P=0.03). Conclusions Seven factors were associated with poor neurological outcome following CVT. The INREvASC score increased prognostic accuracy compared to ISCVT-RS. Determining patients at highest risk of poor outcome in CVT could help in clinical decision making and identify patients for targeted therapy in future clinical trials.
6.Timing and Predictors of Recanalization After Anticoagulation in Cerebral Venous Thrombosis
Setareh SALEHI OMRAN ; Liqi SHU ; Allison CHANG ; Neal S. PARIKH ; Adeel S. ZUBAIR ; Alexis N. SIMPKINS ; Mirjam R. HELDNER ; Arsany HAKIM ; Sami Al KASAB ; Thanh NGUYEN ; Piers KLEIN ; Eric D. GOLDSTEIN ; Maria Cristina VEDOVATI ; Maurizio PACIARONI ; David S. LIEBESKIND ; Shadi YAGHI ; Shawna CUTTING
Journal of Stroke 2023;25(2):291-298
Background:
and Purpose Vessel recanalization after cerebral venous thrombosis (CVT) is associated with favorable outcomes and lower mortality. Several studies examined the timing and predictors of recanalization after CVT with mixed results. We aimed to investigate predictors and timing of recanalization after CVT.
Methods:
We used data from the multicenter, international AntiCoagulaTION in the Treatment of Cerebral Venous Thrombosis (ACTION-CVT) study of consecutive patients with CVT from January 2015 to December 2020. Our analysis included patients that had undergone repeat venous neuroimaging more than 30 days after initiation of anticoagulation treatment. Prespecified variables were included in univariate and multivariable analyses to identify independent predictors of failure to recanalize.
Results:
Among the 551 patients (mean age, 44.4±16.2 years, 66.2% women) that met inclusion criteria, 486 (88.2%) had complete or partial, and 65 (11.8%) had no recanalization. The median time to first follow-up imaging study was 110 days (interquartile range, 60–187). In multivariable analysis, older age (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.03–1.07), male sex (OR, 0.44; 95% CI, 0.24–0.80), and lack of parenchymal changes on baseline imaging (OR, 0.53; 95% CI, 0.29–0.96) were associated with no recanalization. The majority of improvement in recanalization (71.1%) occurred before 3 months from initial diagnosis. A high percentage of complete recanalization (59.0%) took place within the first 3 months after CVT diagnosis.
Conclusion
Older age, male sex, and lack of parenchymal changes were associated with no recanalization after CVT. The majority recanalization occurred early in the disease course suggesting limited further recanalization with anticoagulation beyond 3 months. Large prospective studies are needed to confirm our findings.
7.Borderzone Infarcts and Recurrent Cerebrovascular Events in Symptomatic Intracranial Arterial Stenosis: A Systematic Review and Meta-Analysis
Saurav DAS ; Liqi SHU ; Rebecca J. MORGAN ; Asghar SHAH ; Fayez H. FAYAD ; Eric D. GOLDSTEIN ; Dalia CHAHIEN ; Benton MAGLINGER ; Satish Kumar BOKKA ; Cory OWENS ; Mehdi ABBASI ; Alexandra KVERNLAND ; James E. SIEGLER ; Brian Mac GRORY ; Thanh N. NGUYEN ; Karen FURIE ; Pooja KHATRI ; Eva MISTRY ; Shyam PRABHAKARAN ; David S. LIEBESKIND ; Jose G. ROMANO ; Adam de HAVENON ; Lina PALAIODIMOU ; Georgios TSIVGOULIS ; Shadi YAGHI
Journal of Stroke 2023;25(2):223-232
Background:
and Purpose Intracranial arterial stenosis (ICAS)-related stroke occurs due to three primary mechanisms with distinct infarct patterns: (1) borderzone infarcts (BZI) due to impaired distal perfusion, (2) territorial infarcts due to distal plaque/thrombus embolization, and (3) plaque progression occluding perforators. The objective of the systematic review is to determine whether BZI secondary to ICAS is associated with a higher risk of recurrent stroke or neurological deterioration.
Methods:
As part of this registered systematic review (CRD42021265230), a comprehensive search was performed to identify relevant papers and conference abstracts (with ≥20 patients) reporting initial infarct patterns and recurrence rates in patients with symptomatic ICAS. Subgroup analyses were performed for studies including any BZI versus isolated BZI and those excluding posterior circulation stroke. The study outcome included neurological deterioration or recurrent stroke during follow-up. For all outcome events, corresponding risk ratios (RRs) and 95% confidence intervals (95% CI) were calculated.
Results:
A literature search yielded 4,478 records with 32 selected during the title/abstract triage for full text; 11 met inclusion criteria and 8 studies were included in the analysis (n=1,219 patients; 341 with BZI). The meta-analysis demonstrated that the RR of outcome in the BZI group compared to the no BZI group was 2.10 (95% CI 1.52–2.90). Limiting the analysis to studies including any BZI, the RR was 2.10 (95% CI 1.38–3.18). For isolated BZI, RR was 2.59 (95% CI 1.24–5.41). RR was 2.96 (95% CI 1.71–5.12) for studies only including anterior circulation stroke patients.
Conclusion
This systematic review and meta-analysis suggests that the presence of BZI secondary to ICAS may be an imaging biomarker that predicts neurological deterioration and/or stroke recurrence.
8.Prevalence and Associations of Dural Arteriovenous Fistulae in Cerebral Venous Thrombosis: Analysis of ACTION-CVT
Aaron SHOSKES ; Liqi SHU ; Thanh N. NGUYEN ; Mohamad ABDALKADER ; James GILES ; Jordan AMAR ; James E. SIEGLER ; Nils HENNINGER ; Marwa ELNAZEIR ; Sami Al KASAB ; Piers KLEIN ; Mirjam R. HELDNER ; Kateryna ANTONENKO ; Marios PSYCHOGIOS ; David S. LIEBESKIND ; Thalia FIELD ; Ava LIBERMAN ; Charles ESENWA ; Alexis SIMPKINS ; Grace LI ; Jennifer FRONTERA ; Lindsey KUOHN ; Aaron ROTHSTEIN ; Ossama KHAZAAL ; Yasmin AZIZ ; Eva MISTRY ; Pooja KHATRI ; Setareh Salehi OMRAN ; Adeel S. ZUBAIR ; Richa SHARMA ; Robert M. STARKE ; Jacques J. MORCOS ; Jose G. ROMANO ; Shadi YAGHI ; Negar ASDAGHI
Journal of Stroke 2024;26(2):325-329
9.Hemagglutinin stem reactive antibody response in individuals immunized with a seasonal influenza trivalent vaccine.
Xiaopeng ZHAO ; Kun QIN ; Jinlei GUO ; Donghong WANG ; Zi LI ; Wenfei ZHU ; Liqi LIU ; Dayan WANG ; Yuelong SHU ; Jianfang ZHOU
Protein & Cell 2015;6(6):453-457
Adult
;
Antibodies, Viral
;
blood
;
immunology
;
Cross Reactions
;
Hemagglutinin Glycoproteins, Influenza Virus
;
immunology
;
Humans
;
Influenza A Virus, H1N1 Subtype
;
immunology
;
Influenza A Virus, H3N2 Subtype
;
immunology
;
Influenza B virus
;
immunology
;
Influenza Vaccines
;
immunology
;
Orthomyxoviridae
;
immunology
;
Seasons
;
Vaccination
10.Endovascular Thrombectomy Versus Intravenous Thrombolysis of Posterior Cerebral Artery Occlusion Stroke
Silja RÄTY ; Thanh N. NGUYEN ; Simon NAGEL ; Davide STRAMBO ; Patrik MICHEL ; Christian HERWEH ; Muhammad M. QURESHI ; Mohamad ABDALKADER ; Pekka VIRTANEN ; Marta OLIVE-GADEA ; Marc RIBO ; Marios PSYCHOGIOS ; Anh NGUYEN ; Joji B. KURAMATSU ; David HAUPENTHAL ; Martin KÖHRMANN ; Cornelius DEUSCHL ; Jordi Kühne ESCOLÀ ; Jelle DEMEESTERE ; Robin LEMMENS ; Lieselotte VANDEWALLE ; Shadi YAGHI ; Liqi SHU ; Volker PUETZ ; Daniel P.O. KAISER ; Johannes KAESMACHER ; Adnan MUJANOVIC ; Dominique Cornelius MARTERSTOC ; Tobias ENGELHORN ; Anne BERBERICH ; Piers KLEIN ; Diogo C. HAUSSEN ; Mahmoud H. MOHAMMADEN ; Hend ABDELHAMID ; Isabel FRAGATA ; Bruno CUNHA ; Michele ROMOLI ; Wei HU ; Jianlon SONG ; Johanna T. FIFI ; Stavros MATSOUKAS ; Sunil A. SHETH ; Sergio A. SALAZAR-MARIONI ; João Pedro MARTO ; João Nuno RAMOS ; Milena MISZCZUK ; Christoph RIEGLER ; Sven POLI ; Khouloud POLI ; Ashutosh P. JADHAV ; Shashvat DESAI ; Volker MAUS ; Maximilian KAEDER ; Adnan H. SIDDIQUI ; Andre MONTEIRO ; Tatu KOKKONEN ; Francesco DIANA ; Hesham E. MASOUD ; Neil SURYADAREVA ; Maxim MOKIN ; Shail THANKI ; Pauli YLIKOTILA ; Kemal ALPAY ; James E. SIEGLER ; Italo LINFANTE ; Guilherme DABUS ; Dileep YAVAGHAL ; Vasu SAINI ; Christian H. NOLTE ; Eberhart SIEBERT ; Markus A. MÖHLENBRUCH ; Peter A. RINGLEB ; Raul G. NOGUEIRA ; Uta HANNING ; Lukas MEYER ; Urs FISCHER ; Daniel STRBIAN
Journal of Stroke 2024;26(2):290-299
Background:
and Purpose Posterior cerebral artery occlusion (PCAo) can cause long-term disability, yet randomized controlled trials to guide optimal reperfusion strategy are lacking. We compared the outcomes of PCAo patients treated with endovascular thrombectomy (EVT) with or without intravenous thrombolysis (IVT) to patients treated with IVT alone.
Methods:
From the multicenter retrospective Posterior cerebraL ArTery Occlusion (PLATO) registry, we included patients with isolated PCAo treated with reperfusion therapy within 24 hours of onset between January 2015 and August 2022. The primary outcome was the distribution of the modified Rankin Scale (mRS) at 3 months. Other outcomes comprised 3-month excellent (mRS 0–1) and independent outcome (mRS 0–2), early neurological improvement (ENI), mortality, and symptomatic intracranial hemorrhage (sICH). The treatments were compared using inverse probability weighted regression adjustment.
Results:
Among 724 patients, 400 received EVT+/-IVT and 324 IVT alone (median age 74 years, 57.7% men). The median National Institutes of Health Stroke Scale score on admission was 7, and the occluded segment was P1 (43.9%), P2 (48.3%), P3–P4 (6.1%), bilateral (1.0%), or fetal posterior cerebral artery (0.7%). Compared to IVT alone, EVT+/-IVT was not associated with improved functional outcome (adjusted common odds ratio [OR] 1.07, 95% confidence interval [CI] 0.79–1.43). EVT increased the odds for ENI (adjusted OR [aOR] 1.49, 95% CI 1.05–2.12), sICH (aOR 2.87, 95% CI 1.23–6.72), and mortality (aOR 1.77, 95% CI 1.07–2.95).
Conclusion
Despite higher odds for early improvement, EVT+/-IVT did not affect functional outcome compared to IVT alone after PCAo. This may be driven by the increased risk of sICH and mortality after EVT.