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Lupus Dec 2016The objective of this study was to conduct a systematic review of case reports documenting the development of antiphospholipid syndrome or antiphospholipid... (Review)
Review
OBJECTIVE
The objective of this study was to conduct a systematic review of case reports documenting the development of antiphospholipid syndrome or antiphospholipid syndrome-related features after an infection.
METHODS
We searched Medline, EMBASE, Web of Science, PubMed ePubs, and The Cochrane Library - CENTRAL through March 2015 without restrictions. Studies reporting cases of antiphospholipid syndrome or antiphospholipid syndrome-related features following an infection were included.
RESULTS
Two hundred and fifty-nine publications met inclusion criteria, reporting on 293 cases. Three different groups of patients were identified; group 1 included patients who fulfilled the criteria for definitive antiphospholipid syndrome (24.6%), group 2 included patients who developed transient antiphospholipid antibodies with thromboembolic phenomena (43.7%), and group 3 included patients who developed transient antiphospholipid antibodies without thromboembolic events (31.7%). The most common preceding infection was viral (55.6%). In cases that developed thromboembolic events Human immunodeficiency and Hepatitis C viruses were the most frequently reported. Parvovirus B19 was the most common in cases that developed antibodies without thromboembolic events. Hematological manifestations and peripheral thrombosis were the most common clinical manifestations. Positive anticardiolipin antibodies were the most frequent antibodies reported, primarily coexisting IgG and IgM isotypes. Few patients in groups 1 and 2 had persistent antiphospholipid antibodies for more than 6 months. Outcome was variable with some cases reporting persistent antiphospholipid syndrome features and others achieving complete resolution of clinical events.
CONCLUSIONS
Development of antiphospholipid antibodies with all traditional manifestations of antiphospholipid syndrome were observed after variety of infections, most frequently after chronic viral infections with Human immunodeficiency and Hepatitis C. The causal relationship between infection and antiphospholipid syndrome cannot be established, but the possible contribution of various infections in the pathogenesis of antiphospholipid syndrome need further longitudinal and controlled studies to establish the incidence, and better quantify the risk and the outcomes of antiphospholipid-related events after infection.
Topics: Antibodies, Anticardiolipin; Antiphospholipid Syndrome; Bacterial Infections; HIV Infections; Hepatitis C; Humans; Immunoglobulin Isotypes; Mycoses; Parasitic Diseases; Virus Diseases
PubMed: 27060064
DOI: 10.1177/0961203316640912 -
Frontiers in Immunology 2022Recombinant Adeno-associated virus (rAAV) is one of the main delivery vectors for gene therapy. To assess immunogenicity, toxicity, and features of AAV gene therapy in... (Meta-Analysis)
Meta-Analysis
Recombinant Adeno-associated virus (rAAV) is one of the main delivery vectors for gene therapy. To assess immunogenicity, toxicity, and features of AAV gene therapy in clinical settings, a meta-analysis of 255 clinical trials was performed. A total of 7,289 patients are planned to be dosed. AAV2 was the most dominantly used serotype (29.8%, n=72), and 8.3% (n=20) of trials used engineered capsids. 38.7% (n=91) of trials employed neutralizing antibody assays for patient enrollment, while 15.3% (n=36) used ELISA-based total antibody assays. However, there was high variability in the eligibility criteria with cut-off tiers ranging from 1:1 to 1:1,600. To address potential immunogenicity, 46.3% (n=118) of trials applied immunosuppressants (prophylactic or reactive), while 32.7% (n=18) of CNS and 37.5% (n=24) of ocular-directed trials employed immunosuppressants, possibly due to the immune-privileged status of CNS and retina. There were a total of 11 patient deaths across 8 trials, and 18 out of 30 clinical holds were due to toxicity findings in clinical studies. 30.6% (n=78) of trials had treatment-emergent serious adverse events (TESAEs), with hepatotoxicity and thrombotic microangiopathy (systemic delivery) and neurotoxicity (CNS delivery) being the most prominent. Additionally, the durability of gene therapy may be impacted by two distinct decline mechanisms: 1) rapid decline presumably due to immune responses; or 2) gradual decline due to vector dilution. The durability varied significantly depending on disease indication, dose, serotypes, and patient individuals. Most CNS (90.0%) and muscle trials (73.3%) achieved durable transgene expression, while only 43.6% of ocular trials had sustained clinical outcomes. The rAAV production system can affect rAAV quality and thus immunogenicity and toxicity. Out of 186 trials that have disclosed production system information, 63.0% (n=126) of trials used the transient transfection of the HEK293/HEK293T system, while 18.0% (n=36) applied the baculovirus/Sf9 (rBac/Sf9) system. There were no significant differences in TESAEs and durability between AAV generated by rBac/Sf9 and HEK293/HEK293T systems. In summary, rAAV immunogenicity and toxicity poses significant challenges for clinical development of rAAV gene therapies, and it warrants collaborative efforts to standardize monitoring/measurement methods, design novel strategies to overcome immune responses, and openly share relevant information.
Topics: Humans; Dependovirus; HEK293 Cells; Genetic Vectors; Genetic Therapy; Immunosuppressive Agents
PubMed: 36389770
DOI: 10.3389/fimmu.2022.1001263 -
Journal of Translational Medicine Oct 2023Myalgic encephalitis/chronic fatigue syndrome (ME/CFS) is a long-term disabling illness without a medically explained cause. Recently during COVID-19 pandemic, many... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Myalgic encephalitis/chronic fatigue syndrome (ME/CFS) is a long-term disabling illness without a medically explained cause. Recently during COVID-19 pandemic, many studies have confirmed the symptoms similar to ME/CFS in the recovered individuals. To investigate the virus-related etiopathogenesis of ME/CFS, we conducted a systematic assessment of viral infection frequency in ME/CFS patients.
METHODS
We conducted a comprehensive search of PubMed and the Cochrane Library from their inception through December 31, 2022, using selection criteria of viral infection prevalence in ME/CFS patients and controls. Subsequently, we performed a meta-analysis to assess the extent of viral infections' contribution to ME/CFS by comparing the odds ratio between ME/CFS patients and controls (healthy and/or diseased).
RESULTS
Finally, 64 studies met our eligibility criteria regarding 18 species of viruses, including a total of 4971 ME/CFS patients and 9221 control subjects. The participants included healthy subjects and individuals with one of 10 diseases, such as multiple sclerosis or fibromyalgia. Two DNA viruses (human herpes virus (HHV)-7 and parvovirus B19, including their co-infection) and 3 RNA viruses (borna disease virus (BDV), enterovirus and coxsackie B virus) showed odds ratios greater than 2.0 compared with healthy and/or diseased subjects. Specifically, BDV exceeded the cutoff with an odds ratio of ≥ 3.47 (indicating a "moderate association" by Cohen's d test) compared to both healthy and diseased controls.
CONCLUSION
This study comprehensively evaluated the risk of viral infections associated with ME/CFS, and identified BDV. These results provide valuable reference data for future studies investigating the role of viruses in the causation of ME/CFS.
Topics: Humans; Encephalitis; Fatigue Syndrome, Chronic; Fibromyalgia; Virus Diseases
PubMed: 37898798
DOI: 10.1186/s12967-023-04635-0 -
BMC Infectious Diseases Apr 2023Viral reactivations and co-infections have been reported among COVID-19 patients. However, studies on the clinical outcomes of different viral reactivations and...
BACKGROUND
Viral reactivations and co-infections have been reported among COVID-19 patients. However, studies on the clinical outcomes of different viral reactivations and co-infections are currently in limit. Thus, the primary purpose of this review is to perform an overarching investigation on the cases of latent virus reactivation and co-infection in COVID-19 patients to build collective evidence contributing to improving patient health. The aim of the study was to conduct a literature review to compare the patient characteristics and outcomes of reactivations and co-infections of different viruses.
METHODS
Our population of interest included confirmed COVID-19 patients who were diagnosed with a viral infection either concurrently or following their COVID-19 diagnosis. We extracted the relevant literature through a systematic search using the key terms in the online databases including the EMBASE, MEDLINE, Latin American Caribbean Health Sciences Literature (LILACS), from inception onwards up to June 2022. The authors independently extracted data from eligible studies and assessed the risk of bias using the Consensus-based Clinical Case Reporting (CARE) guidelines and the Newcastle-Ottawa Scale (NOS). Main patient characteristics, frequency of each manifestation, and diagnostic criteria used in studies were summarized in tables.
RESULTS
In total, 53 articles were included in this review. We identified 40 reactivation studies, 8 coinfection studies, and 5 studies where concomitant infection in COVID-19 patients was not distinguished as either reactivation or coinfection. Data were extracted for 12 viruses including IAV, IBV, EBV, CMV, VZV, HHV-1, HHV-2, HHV-6, HHV-7, HHV-8, HBV, and Parvovirus B19. EBV, HHV-1, and CMV were most frequently observed within the reactivation cohort, whereas IAV and EBV within the coinfection cohort. In both reactivation and coinfection groups, patients reported cardiovascular disease, diabetes, and immunosuppression as comorbidities, acute kidney injury as complication, and lymphopenia and elevated D-dimer and CRP levels from blood tests. Common pharmaceutical interventions in two groups included steroids and antivirals.
CONCLUSION
Overall, these findings expand our knowledge on the characteristics of COVID-19 patients with viral reactivations and co-infections. Our experience with current review indicates a need for further investigations on virus reactivation and coinfection among COVID-19 patients.
Topics: Humans; Coinfection; COVID-19 Testing; COVID-19; Virus Diseases; Cytomegalovirus Infections
PubMed: 37101275
DOI: 10.1186/s12879-023-08117-y -
Translational Vision Science &... Nov 2023This systematic review evaluates the safety and efficacy of ocular gene therapy using adeno-associated virus (AAV). (Meta-Analysis)
Meta-Analysis
PURPOSE
This systematic review evaluates the safety and efficacy of ocular gene therapy using adeno-associated virus (AAV).
METHODS
MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched systematically for controlled or non-controlled interventional gene therapy studies using key words related to retinal diseases, gene therapy, and AAV vectors. The primary outcome measure was safety, based on ocular severe adverse events (SAEs). Secondary outcome measures evaluated efficacy of the therapy based on best corrected visual acuity (BCVA) and improvements in visual sensitivity and systemic involvement following ocular delivery. Pooling was done using a DerSimonian Laird random effects model. Risk of bias was assessed using the Cochrane Risk of Bias Tool, version 1.
RESULTS
Our search identified 3548 records. Of these, 80 publications met eligibility criteria, representing 28 registered clinical trials and 5 postmarket surveillance studies involving AAV gene therapy for Leber congenital amaurosis (LCA), choroideremia, Leber hereditary optic neuropathy (LHON), age-related macular degeneration (AMD), retinitis pigmentosa (RP), X-linked retinoschisis, and achromatopsia. Overall, AAV therapy vectors were associated with a cumulative incidence of at least one SAE of 8% (95% confidence intervals [CIs] of 5% to 12%). SAEs were often associated with the surgical procedure rather than the therapeutic vector itself. Poor or inconsistent reporting of adverse events (AEs) were a limitation for the meta-analysis. The proportion of patients with any improvement in BCVA and visual sensitivity was 41% (95% CIs of 31% to 51%) and 51% (95% CIs of 31% to 70%), respectively. Systemic immune involvement was associated with a cumulative incidence of 31% (95% CI = 21% to 42%).
CONCLUSIONS
AAV gene therapy vectors appear to be safe but the surgical procedure required to deliver them is associated with some risk. The large variability in efficacy can be attributed to the small number of patients treated, the heterogeneity of the population and the variability in dosage, volume, and follow-up.
TRANSLATIONAL RELEVANCE
This systematic review will help to inform and guide future clinical trials.
Topics: Humans; Retinal Degeneration; Dependovirus; Macular Degeneration; Retinitis Pigmentosa; Genetic Therapy
PubMed: 37982768
DOI: 10.1167/tvst.12.11.24 -
Translational Research : the Journal of... Oct 2022Adeno-associated viruses (AAVs) represent some of the most commonly employed vectors for targeted gene delivery and their extensive study has resulted in the approval of... (Review)
Review
Adeno-associated viruses (AAVs) represent some of the most commonly employed vectors for targeted gene delivery and their extensive study has resulted in the approval of multiple gene therapies to treat human diseases. The intranasal route of vector application in gene therapy offers several advantages over traditional ways of administration. In addition to targeting local tissue like the olfactory epithelium, it provides minimally invasive access to various organ systems, including the central nervous system and the respiratory tract. Through a systematic literature review, a total of 53 articles that investigated the intranasal application of AAVs were identified, included, and summarized in this manuscript. Within these studies, AAV-based gene therapy was mainly investigated for its application in various infectious, pulmonary, or neurologic and/or psychiatric diseases. This review gives a comprehensive overview of the current technological state of the art regarding the intranasal application of AAVs for gene transfer and discusses remaining hurdles, which still have to be resolved before this approach can effectively be implemented in the routine clinical setting.
Topics: Administration, Intranasal; Dependovirus; Gene Transfer Techniques; Genetic Therapy; Genetic Vectors; Humans
PubMed: 35597541
DOI: 10.1016/j.trsl.2022.05.002 -
International Journal of Cancer Jul 2015Numerous studies have found the presence of viral DNA in colorectal tumor tissues. However, whether viral infections contribute to the risk of colorectal cancer (CRC) is... (Review)
Review
Numerous studies have found the presence of viral DNA in colorectal tumor tissues. However, whether viral infections contribute to the risk of colorectal cancer (CRC) is still under debate. We aimed to provide an overview of published epidemiological studies on the association between viral infections and CRC. A systematic literature search was performed in PubMed to find relevant studies published until 8 May 2014. Information collected included study population, sample type, laboratory method and prevalence of viral infection in cancer or precancer patients and controls. We found 41 studies that fulfilled the selection criteria, all of which had cross-sectional or case-control designs, and most of which were of small to moderate size. Viral infections included human papillomaviruses (HPV), human polyomaviruses, human herpesviruses, human bocavirus and Inoue-Melnick virus. Inconsistent results were observed across studies. Many studies reported higher viral DNA prevalence in tumor tissues than in normal noncancerous tissues either in the same patients or in CRC-free controls. However, potential contamination or temporal sequence of the infection and cancer development were often unclear. Seroprevalence studies assessing antibody titers indicative of viral infections did not find statistically significant differences between CRC cases and healthy controls. Overall published evidence on the role of viral infections in CRC etiology remains limited. Given the potential importance of viral infections and their implication for prevention, there is a strong need for large, methodologically rigorous epidemiological studies.
Topics: Colorectal Neoplasms; DNA Virus Infections; DNA, Viral; Human bocavirus; Humans; Papillomaviridae; Polyomavirus; PubMed; Seroepidemiologic Studies; Simplexvirus
PubMed: 25186851
DOI: 10.1002/ijc.29180 -
Asian Journal of Transfusion Science 2021Human parvovirus B19 (B19V) is one of the blood-borne viruses. The virus can be transmitted to susceptible individuals by blood or blood products. The virus is not... (Review)
Review
BACKGROUND
Human parvovirus B19 (B19V) is one of the blood-borne viruses. The virus can be transmitted to susceptible individuals by blood or blood products. The virus is not associated with significant disease in general population, while people with underlying problems such as immunodeficiency can cause anemia and arthritis. The current systematic review and meta-analysis aimed to estimate the overall prevalence of B19V DNA, anti-B19V IgG, and anti-B19V IgM antibodies in blood donors worldwide.
METHODS
A systematic search was carried out in online databases for relevant studies from inception until March 30, 2019. Study selection was performed based on predesigned eligibility criteria. The proportion of B19V DNA, anti-B19V IgG, and anti-B19V IgM antibodies were pooled using the inverse variance method. All statistical analyses were performed using the R version 3.5.3, package "meta."
RESULTS
According to the random-effects model, the pool prevalence of B19V DNA, anti-B19V IgM, and anti-B19V IgG among blood donors was calculated to be 0.4% (95% confidence interval [CI] =0.3%-0.6%), 2.2% (95% CI = 1.3%-3.7%), and 50.1% (95% CI = 43.1%-57.1%), respectively.
CONCLUSION
For the transmission of B19V through blood, the presence of the virus genome is required, and the present study showed that the prevalence of the virus genome in blood donors is <1%. Therefore, there is no need to screen donated blood for B19V infection.
PubMed: 34908757
DOI: 10.4103/ajts.ajts_185_20 -
Scientific Reports Apr 2021A significant number of studies invoked diabetes as a risk factor for virus infections, but the issue remains controversial. We aimed to examine whether non-autoimmune... (Meta-Analysis)
Meta-Analysis
A significant number of studies invoked diabetes as a risk factor for virus infections, but the issue remains controversial. We aimed to examine whether non-autoimmune diabetes mellitus enhances the risk of virus infections compared with the risk in healthy individuals without non-autoimmune diabetes mellitus. In this systematic review and meta-analysis, we assessed case-control and cohort studies on the association between non-autoimmune diabetes and viruses. We searched PubMed, Embase, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, and Web of Science with no language restriction, to identify articles published until February 15, 2021. The main outcome assessment was the risk of virus infection in individuals with non-autoimmune diabetes. We used a random-effects model to pool individual studies and assessed heterogeneity (I) using the χ2 test on Cochrane's Q statistic. This study is registered with PROSPERO, number CRD42019134142. Out of 3136 articles identified, we included 68 articles (90 studies, as the number of virus and or diabetes phenotype varied between included articles). The summary OR between non-autoimmune diabetes and virus infections risk were, 10.8(95% CI: 10.3-11.4; 1-study) for SARS-CoV-2; 3.6(95%CI: 2.7-4.9, I = 91.7%; 43-studies) for HCV; 2.7(95% CI: 1.3-5.4, I = 89.9%, 8-studies;) for HHV8; 2.1(95% CI: 1.7-2.5; 1-study) for H1N1 virus; 1.6(95% CI: 1.2-2.13, I = 98.3%, 27-studies) for HBV; 1.5(95% CI: 1.1-2.0; 1-study) for HSV1; 3.5(95% CI: 0.6-18.3 , I = 83.9%, 5-studies) for CMV; 2.9(95% CI: 1-8.7, 1-study) for TTV; 2.6(95% CI: 0.7-9.1, 1-study) for Parvovirus B19; 0.7(95% CI: 0.3-1.5 , 1-study) for coxsackie B virus; and 0.2(95% CI: 0-6.2; 1-study) for HGV. Our findings suggest that, non-autoimmune diabetes is associated with increased susceptibility to viruses especially SARS-CoV-2, HCV, HHV8, H1N1 virus, HBV and HSV1. Thus, these viruses deserve more attention from diabetes health-care providers, researchers, policy makers, and stakeholders for improved detection, overall proper management, and efficient control of viruses in people with non-autoimmune diabetes.
Topics: Case-Control Studies; Cohort Studies; Diabetes Complications; Humans; Risk Factors; Virus Diseases
PubMed: 33903699
DOI: 10.1038/s41598-021-88598-6 -
Ultrasound in Obstetrics & Gynecology :... Dec 2019To evaluate the performance of fetal middle cerebral artery peak systolic velocity (MCA-PSV) ≥ 1.5 multiples of the median (MoM) for the prediction of... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To evaluate the performance of fetal middle cerebral artery peak systolic velocity (MCA-PSV) ≥ 1.5 multiples of the median (MoM) for the prediction of moderate-severe anemia, in untransfused and transfused fetuses.
METHODS
A systematic search was performed to identify relevant observational studies reported in the period 2008-2018 that evaluated the performance of MCA-PSV, using a threshold of 1.5 MoM for the prediction of fetal anemia. Diagnosis of fetal anemia by blood sampling was the reference standard. A hierarchical summary receiver-operating characteristics (hSROC) curve was constructed using random-effects modeling. Subgroup and meta-regression analyses, according to the number of previous intrauterine transfusions, were performed.
RESULTS
Twelve studies and 696 fetuses were included in the meta-analysis. The area under the hSROC curve (AUC) for moderate-severe anemia was 83%. Pooled sensitivity and specificity (95% CI) were 79% (70-86%) and 73% (62-82%), respectively, and positive and negative likelihood ratios were 2.94 (95% CI, 2.13-4.00) and 0.272 (95% CI, 0.188-0.371). When considering only untransfused fetuses, prediction improved, achieving an AUC of 87%, sensitivity of 86% (95% CI, 75-93%) and specificity of 71% (95% CI, 49-87%). A decline in sensitivity for the prediction of moderate-severe anemia by MCA-PSV ≥1.5 MoM was observed (estimate, -5.5% (95% CI, -10.7 to -0.3%), P = 0.039) as the number of previous transfusions increased.
CONCLUSIONS
MCA-PSV ≥ 1.5 MoM for the prediction of moderate-severe anemia in untransfused fetuses shows moderate accuracy (86% sensitivity and 71% specificity), which declines with increasing number of intrauterine transfusions. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.
Topics: Anemia; Blood Flow Velocity; Blood Transfusion, Intrauterine; Female; Fetal Diseases; Fetus; Gestational Age; Humans; Middle Cerebral Artery; Observational Studies as Topic; Predictive Value of Tests; Pregnancy; Sensitivity and Specificity; Severity of Illness Index; Ultrasonography, Doppler, Color
PubMed: 30932276
DOI: 10.1002/uog.20273