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Reviews in Medical Virology Nov 2021Infectious diseases occur worldwide with great frequency in both adults and children, causing 350,000 deaths in 2017, according to the latest World Health Organization... (Review)
Review
Infectious diseases occur worldwide with great frequency in both adults and children, causing 350,000 deaths in 2017, according to the latest World Health Organization reports. Both infections and their treatments trigger mitochondrial interactions at multiple levels: (i) incorporation of damaged or mutated proteins into the complexes of the electron transport chain; (ii) impact on mitochondrial genome (depletion, deletions and point mutations) and mitochondrial dynamics (fusion and fission); (iii) membrane potential impairment; (iv) apoptotic regulation; and (v) generation of reactive oxygen species, among others. Such alterations may result in serious adverse clinical events with considerable impact on the quality of life of the children and could even cause death. Herein, we use a systematic review to explore the association between mitochondrial alterations in paediatric infections including human immunodeficiency virus, cytomegalovirus, herpes viruses, various forms of hepatitis, adenovirus, T-cell lymphotropic virus and influenza. We analyse how these paediatric viral infectious processes may cause mitochondrial deterioration in this especially vulnerable population, with consideration for the principal aspects of research and diagnosis leading to improved disease understanding, management and surveillance.
Topics: Antiviral Agents; Child; Communicable Diseases; DNA, Mitochondrial; Humans; Mitochondria; Pediatrics; Virus Diseases
PubMed: 33792105
DOI: 10.1002/rmv.2232 -
Survey of Ophthalmology 2022Cytomegalovirus (CMV) anterior uveitis is the most common form of ocular manifestation of CMV in immunocompetent individuals. The difficulty in diagnosing CMV anterior... (Meta-Analysis)
Meta-Analysis Review
Cytomegalovirus (CMV) anterior uveitis is the most common form of ocular manifestation of CMV in immunocompetent individuals. The difficulty in diagnosing CMV anterior uveitis may delay adequate treatment and affect outcomes. We sought to review systemically the overall clinical characteristics and compare treatment outcomes in CMV anterior uveitis and endotheliitis. A literature search was performed, and studies describing clinical characteristics, treatment regimens, and outcomes that included more than 5 treated eyes were included. In these 23 studies, acute CMV anterior uveitis commonly presented with high intraocular pressure (95.31%, 95% CI 90.45-98.60) and mild anterior chamber inflammation (cells >2+ = 3.18%, 95% CI 0.21-0.54). About two-thirds of CMV endotheliitis cases presented with high intraocular pressure and coin-shaped corneal lesions. Acute CMV anterior uveitis showed good clinical response to topical 0.15% ganciclovir (GCV) gel or oral valganciclovir (VGCV) (90%, 95% CI 74-100% and 95%, 95% CI 88-100%, respectively). For chronic CMV anterior uveitis, both topical GCV and oral VGCV yielded comparable results. Topical 0.5-2% GCV or a combination of topical and oral VGCV for CMV endotheliitis both resulted in good clinical response. Recurrence of inflammation was common after cessation of maintenance therapy. Overall, topical GCV resulted in an optimal outcome for CMV anterior uveitis. Escalated concentration and frequency of usage are needed for chronic CMV anterior uveitis and endotheliitis. Adequate induction and maintenance phases of anti-CMV treatment seem necessary to prevent recurrences.
Topics: Antiviral Agents; Aqueous Humor; Cytomegalovirus; Cytomegalovirus Infections; DNA, Viral; Eye Infections, Viral; Ganciclovir; Glaucoma; Humans; Inflammation; Treatment Outcome; Uveitis, Anterior; Valganciclovir
PubMed: 34954093
DOI: 10.1016/j.survophthal.2021.12.006 -
Surgical Oncology Dec 2023Pancreatic ductal adenocarcinoma (PDAC) is a challenging disease, with surgery being the only possible cure. However, despite surgery, the majority of patients... (Meta-Analysis)
Meta-Analysis Review
Prognostic utility of preoperative and postoperative KRAS-mutated circulating tumor DNA (ctDNA) in resected pancreatic ductal adenocarcinoma: A systematic review and meta-analysis.
BACKGROUND
Pancreatic ductal adenocarcinoma (PDAC) is a challenging disease, with surgery being the only possible cure. However, despite surgery, the majority of patients experience recurrence. Recent evidence suggests that perioperative KRAS-mutated circulating tumor DNA (ctDNA) may have prognostic value. Therefore, we conducted a systematic review and meta-analysis to explore the prognostic significance of preoperative and postoperative KRAS-mutated ctDNA testing in resected PDAC.
METHODS
We searched PubMed/MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases for studies that reported the effect of preoperative and postoperative KRAS-mutated ctDNA on overall survival (OS) and/or relapse-free survival (RFS) in resected PDAC. We used a random-effects model to determine the pooled OS and RFS hazard ratios (HR) and their corresponding 95 % confidence intervals (CI).
RESULTS
We identified 15 studies (868 patients) eligible for analysis. In the preoperative setting, positive ctDNA correlated with worse RFS in 8 studies (HR, 2.067; 95 % CI, 1.346-3.174, P < 0.001) and worse OS in 10 studies (HR, 2.170; 95 % CI, 1.451-3.245, P < 0.001) compared to negative ctDNA. In the postoperative setting, positive ctDNA correlated with worse RFS across 9 studies (HR, 3.32; 95 % CI, 2.19-5.03, P < 0.001) and worse OS in 6 studies (HR, 6.62; 95 % CI, 2.18-20.16, P < 0.001) compared to negative ctDNA.
CONCLUSION
Our meta-analysis supports the utility of preoperative and postoperative KRAS-mutated ctDNA testing as a prognostic marker for resected PDAC. Further controlled studies are warranted to confirm these results and to investigate the potential therapeutic implications of positive KRAS-mutated ctDNA.
Topics: Humans; Prognosis; Circulating Tumor DNA; Proto-Oncogene Proteins p21(ras); Mutation; Carcinoma, Pancreatic Ductal; Pancreatic Neoplasms; Biomarkers, Tumor
PubMed: 37852124
DOI: 10.1016/j.suronc.2023.102007 -
Artificial Intelligence in Medicine Sep 2023DNA methylation biomarkers have great potential in improving prognostic classification systems for patients with cancer. Machine learning (ML)-based analytic techniques... (Review)
Review
BACKGROUND
DNA methylation biomarkers have great potential in improving prognostic classification systems for patients with cancer. Machine learning (ML)-based analytic techniques might help overcome the challenges of analyzing high-dimensional data in relatively small sample sizes. This systematic review summarizes the current use of ML-based methods in epigenome-wide studies for the identification of DNA methylation signatures associated with cancer prognosis.
METHODS
We searched three electronic databases including PubMed, EMBASE, and Web of Science for articles published until 2 January 2023. ML-based methods and workflows used to identify DNA methylation signatures associated with cancer prognosis were extracted and summarized. Two authors independently assessed the methodological quality of included studies by a seven-item checklist adapted from 'A Tool to Assess Risk of Bias and Applicability of Prediction Model Studies (PROBAST)' and from the 'Reporting Recommendations for Tumor Marker Prognostic Studies (REMARK). Different ML methods and workflows used in included studies were summarized and visualized by a sunburst chart, a bubble chart, and Sankey diagrams, respectively.
RESULTS
Eighty-three studies were included in this review. Three major types of ML-based workflows were identified. 1) unsupervised clustering, 2) supervised feature selection, and 3) deep learning-based feature transformation. For the three workflows, the most frequently used ML techniques were consensus clustering, least absolute shrinkage and selection operator (LASSO), and autoencoder, respectively. The systematic review revealed that the performance of these approaches has not been adequately evaluated yet and that methodological and reporting flaws were common in the identified studies using ML techniques.
CONCLUSIONS
There is great heterogeneity in ML-based methodological strategies used by epigenome-wide studies to identify DNA methylation markers associated with cancer prognosis. In theory, most existing workflows could not handle the high multi-collinearity and potentially non-linearity interactions in epigenome-wide DNA methylation data. Benchmarking studies are needed to compare the relative performance of various approaches for specific cancer types. Adherence to relevant methodological and reporting guidelines are urgently needed.
Topics: Humans; DNA Methylation; Epigenome; Prognosis; Neoplasms; Machine Learning
PubMed: 37673571
DOI: 10.1016/j.artmed.2023.102589 -
Reviews in Medical Virology Jan 2023Several phase-1 clinical trials have been performed to evaluate the safety and efficacy of candidate anti-Zika vaccines. In this systematic review, we systematically... (Review)
Review
Several phase-1 clinical trials have been performed to evaluate the safety and efficacy of candidate anti-Zika vaccines. In this systematic review, we systematically evaluated the safety and immunogenicity of candidate vaccines, which would aid researchers in formulating an effective vaccination strategy for phase-2 trials based on current evidence. A literature search was conducted using the electronic databases MEDLINE through Pubmed, Web of Science, and Cochrane Database for relevant studies on candidate anti-zika vaccines. Studies on animal models were excluded from our study. Healthy individuals who were administered candidate Zika vaccines to evaluate the immune response and adverse events (AEs) compared to placebo were considered. Data were extracted, tabulated, and analysed using Microsoft Excel, while the risk of bias plots were generated using tidyverse and Robvis packages in R-studio. A total of five phase-1 clinical trials were included in our analysis comprising of studies on inactivated, viral vector, and DNA vaccines. Immunogenicity ranged from 10% to 100% after vaccination with the lowest seroconversion rate (10%) and geometric mean titre (GMT) (6.3; 95% confidence interval (CI):3.7-10.8) observed among recipients of single-dose inactivated anti-zika vaccine (ZPIV). For DNA vaccines, the seroconversion rate ranged from 60% to 100% with the highest seroconversion rate (100%) and GMT (2871; 95% CI:705.3-11688) observed among recipients of three shots of high dose GLS-5700 vaccine. For viral vector vaccine (Ad26.ZIKV.001) seroconversion rate (100%) and GMT peaked after two shots with both low and high-dose vaccines. In all those studies AEs were mostly local including injection site pain, erythema, and itching. The most common systemic AEs included fever, myalgia, nausea, and fatigue. In phase-1 clinical trials, all candidate vaccines were found to be highly immunogenic and relatively safe, especially when administered in higher doses and with the help of needle-free devices.
Topics: Animals; Zika Virus; Zika Virus Infection; Vaccines, DNA; Viral Vaccines; Vaccination; Antibodies, Viral
PubMed: 35986594
DOI: 10.1002/rmv.2385 -
Acta Biochimica Polonica Jun 2023Vitamin D has anti-proliferative, anti-inflammatory, and apoptotic abilities. Vitamin D deficiency can induce deoxyribonucleic acid (DNA) damage. The aim of the study...
Vitamin D has anti-proliferative, anti-inflammatory, and apoptotic abilities. Vitamin D deficiency can induce deoxyribonucleic acid (DNA) damage. The aim of the study was to create a systematic review to analyze the relationship between vitamin D and DNA damage in various populations. PubMed, Scopus, EbscoHost, Google Scholar, and Epistemonikos were used to identify literature regarding the relationship between vitamin D and DNA damage. Assessment of study quality was carried out by three independent reviewers individually. A total of 25 studies were assessed as eligible and included in our study. Twelve studies were conducted in humans consisting of two studies with experimental design and ten studies with observational pattern. Meanwhile, thirteen studies were conducted in animals (in vivo). It is found that the majority of studies demonstrated that vitamin D prevents DNA damage and minimizes the impact of DNA damage that has occurred (p<0.05). However, two studies (8%) did not find such an association and one research only found a specific association in the cord blood, not in maternal blood. Vitamin D has a protective effect against DNA damage. A diet rich in vitamin D and vitamin D supplementation is recommended to prevent DNA damage.
Topics: Humans; Animals; Vitamin D; Vitamins; Vitamin D Deficiency; Inflammation; DNA; Dietary Supplements
PubMed: 37329504
DOI: 10.18388/abp.2020_6641 -
Ultrasound in Obstetrics & Gynecology :... Jan 2024First, to determine the incremental yield of whole-genome sequencing (WGS) over quantitative fluorescence polymerase chain reaction (QF-PCR)/chromosomal microarray... (Meta-Analysis)
Meta-Analysis Review
Incremental yield of whole-genome sequencing over chromosomal microarray analysis and exome sequencing for congenital anomalies in prenatal period and infancy: systematic review and meta-analysis.
OBJECTIVES
First, to determine the incremental yield of whole-genome sequencing (WGS) over quantitative fluorescence polymerase chain reaction (QF-PCR)/chromosomal microarray analysis (CMA) with and without exome sequencing (ES) in fetuses, neonates and infants with a congenital anomaly that was or could have been detected on prenatal ultrasound. Second, to evaluate the turnaround time (TAT) and quantity of DNA required for testing using these pathways.
METHODS
This review was registered prospectively in December 2022. Ovid MEDLINE, EMBASE, MEDLINE (Web of Science), The Cochrane Library and ClinicalTrials.gov databases were searched electronically (January 2010 to December 2022). Inclusion criteria were cohort studies including three or more fetuses, neonates or infants with (i) one or more congenital anomalies; (ii) an anomaly which was or would have been detectable on prenatal ultrasound; and (iii) negative QF-PCR and CMA. In instances in which the CMA result was unavailable, all cases of causative pathogenic copy number variants > 50 kb were excluded, as these would have been detectable on standard prenatal CMA. Pooled incremental yield was determined using a random-effects model and heterogeneity was assessed using Higgins' I test. Subanalyses were performed based on pre- or postnatal cohorts, cases with multisystem anomalies and those meeting the NHS England prenatal ES inclusion criteria.
RESULTS
A total of 18 studies incorporating 902 eligible cases were included, of which eight (44.4%) studies focused on prenatal cohorts, incorporating 755 cases, and the remaining studies focused on fetuses undergoing postmortem testing or neonates/infants with congenital structural anomalies, constituting the postnatal cohort. The incremental yield of WGS over QF-PCR/CMA was 26% (95% CI, 18-36%) (I = 86%), 16% (95% CI, 9-24%) (I = 85%) and 39% (95% CI, 27-51%) (I = 53%) for all, prenatal and postnatal cases, respectively. The incremental yield increased in cases in which sequencing was performed in line with the NHS England prenatal ES criteria (32% (95% CI, 22-42%); I = 70%) and in those with multisystem anomalies (30% (95% CI, 19-43%); I = 65%). The incremental yield of WGS for variants of uncertain significance (VUS) was 18% (95% CI, 7-33%) (I = 74%). The incremental yield of WGS over QF-PCR/CMA and ES was 1% (95% CI, 0-4%) (I = 47%). The pooled median TAT of WGS was 18 (range, 1-912) days, and the quantity of DNA required was 100 ± 0 ng for WGS and 350 ± 50 ng for QF-PCR/CMA and ES (P = 0.03).
CONCLUSION
While WGS in cases with congenital anomaly holds great promise, its incremental yield over ES is yet to be demonstrated. However, the laboratory pathway for WGS requires less DNA with a potentially faster TAT compared with sequential QF-PCR/CMA and ES. There was a relatively high rate of VUS using WGS. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
Topics: Female; Humans; Infant, Newborn; Pregnancy; Cohort Studies; DNA; Exome Sequencing; Microarray Analysis; Prenatal Diagnosis; Ultrasonography; Infant
PubMed: 37725747
DOI: 10.1002/uog.27491 -
Clinical and Molecular Hepatology Jul 2023Chronic hepatitis B (CHB) and fatty liver (FL) often co-exist, but natural history data of this dual condition (CHB-FL) are sparse. Via a systematic review, conventional... (Meta-Analysis)
Meta-Analysis
BACKGROUND/AIMS
Chronic hepatitis B (CHB) and fatty liver (FL) often co-exist, but natural history data of this dual condition (CHB-FL) are sparse. Via a systematic review, conventional meta-analysis (MA) and individual patient-level data MA (IPDMA), we compared liver-related outcomes and mortality between CHB-FL and CHB-no FL patients.
METHODS
We searched 4 databases from inception to December 2021 and pooled study-level estimates using a random- effects model for conventional MA. For IPDMA, we evaluated outcomes after balancing the two study groups with inverse probability treatment weighting (IPTW) on age, sex, cirrhosis, diabetes, ALT, HBeAg, HBV DNA, and antiviral treatment.
RESULTS
We screened 2,157 articles and included 19 eligible studies (17,955 patients: 11,908 CHB-no FL; 6,047 CHB-FL) in conventional MA, which found severe heterogeneity (I2=88-95%) and no significant differences in HCC, cirrhosis, mortality, or HBsAg seroclearance incidence (P=0.27-0.93). IPDMA included 13,262 patients: 8,625 CHB-no FL and 4,637 CHB-FL patients who differed in several characteristics. The IPTW cohort included 6,955 CHB-no FL and 3,346 CHB-FL well-matched patients. CHB-FL patients (vs. CHB-no FL) had significantly lower HCC, cirrhosis, mortality and higher HBsAg seroclearance incidence (all p≤0.002), with consistent results in subgroups. CHB-FL diagnosed by liver biopsy had a higher 10-year cumulative HCC incidence than CHB-FL diagnosed with non-invasive methods (63.6% vs. 4.3%, p<0.0001).
CONCLUSION
IPDMA data with well-matched CHB patient groups showed that FL (vs. no FL) was associated with significantly lower HCC, cirrhosis, and mortality risk and higher HBsAg seroclearance probability.
Topics: Humans; Carcinoma, Hepatocellular; Hepatitis B Surface Antigens; Hepatitis B, Chronic; Liver Neoplasms; Hepatitis B virus; Antiviral Agents; Liver Cirrhosis; Fatty Liver; DNA, Viral
PubMed: 37157776
DOI: 10.3350/cmh.2023.0004 -
Journal of Neuro-oncology Dec 2023The blood-brain barrier can prevent circulating tumor DNA (ctDNA) derived from the central nervous system from entering the blood making it challenging to evaluate... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
The blood-brain barrier can prevent circulating tumor DNA (ctDNA) derived from the central nervous system from entering the blood making it challenging to evaluate molecular features of leptomeningeal metastasis (LM). Accordingly, we sought to systematically compare the diagnostic power or significance of ctDNA derived from cerebrospinal fluid (CSF) compared to plasma ctDNA in patients with LM.
METHODS
A systematic review and meta-analysis was performed under the PRISMA guideline. We used PubMed, EMBASE, and the EuroPMC to search the literature using combinations of the following terms: circulating tumor DNA, ctDNA, circulating tumor cell, brain metastasis, leptomeningeal metastasis, outcome(s), and prognosis. We included all available English language studies that compared the diagnostic significance of CSF derived and serum ctDNA. All eligible studies level of bias was assessed using the New Castle Ottawa Scale (NOS).
RESULTS
Our meta-analysis from 6 included studies (n = 226) that confirmed the diagnostic power of liquid biopsies in detecting genomic alteration is better when taking a CSF-derived samples than from the plasma (RR 1.46 [0.93; 2.29]; I = 92%; p-value < 0.01).
CONCLUSION
CSF ctDNA is better at describing molecular landscape for LM; such an understanding may ultimately help inform patient treatment and responses to therapy.
Topics: Humans; Circulating Tumor DNA; Meningeal Carcinomatosis; Liquid Biopsy; Neoplastic Cells, Circulating; Central Nervous System; Biomarkers, Tumor; Mutation
PubMed: 38019327
DOI: 10.1007/s11060-023-04519-9 -
Journal of the American Society of... Nov 2023Several recent studies identified mitochondrial mutations in patients with Gitelman or Fanconi syndrome. Mitochondrial cytopathies are generally not considered in the...
SIGNIFICANCE STATEMENT
Several recent studies identified mitochondrial mutations in patients with Gitelman or Fanconi syndrome. Mitochondrial cytopathies are generally not considered in the diagnostic workup of patients with electrolyte disorders. In this systematic review, we investigated the presence of electrolyte disorders in patients with mitochondrial cytopathies to determine the relevance of mitochondrial mutation screening in this population. Our analysis demonstrates that electrolyte disorders are commonly reported in mitochondrial cytopathies, often as presenting symptoms. Consequently, more clinical attention should be raised for mitochondrial disease as cause for disturbances in electrolyte homeostasis. Further prospective cohort studies are required to determine the exact prevalence of electrolyte disorders in mitochondrial cytopathies.
BACKGROUND
Electrolyte reabsorption in the kidney has a high energy demand. Proximal and distal tubular epithelial cells have a high mitochondrial density for energy release. Recently, electrolyte disorders have been reported as the primary presentation of some mitochondrial cytopathies. However, the prevalence and the pathophysiology of electrolyte disturbances in mitochondrial disease are unknown. Therefore, we systematically investigated electrolyte disorders in patients with mitochondrial cytopathies.
METHODS
We searched PubMed, Embase, and Google Scholar for articles on genetically confirmed mitochondrial disease in patients for whom at least one electrolyte is reported. Patients with a known second genetic anomaly were excluded. We evaluated 214 case series and reports (362 patients) as well as nine observational studies. Joanna Briggs Institute criteria were used to evaluate the quality of included studies.
RESULTS
Of 362 reported patients, 289 had an electrolyte disorder, with it being the presenting or main symptom in 38 patients. The average number of different electrolyte abnormalities per patient ranged from 2.4 to 1.0, depending on genotype. Patients with mitochondrial DNA structural variants seemed most affected. Reported pathophysiologic mechanisms included renal tubulopathies and hormonal, gastrointestinal, and iatrogenic causes.
CONCLUSIONS
Mitochondrial diseases should be considered in the evaluation of unexplained electrolyte disorders. Furthermore, clinicians should be aware of electrolyte abnormalities in patients with mitochondrial disease.
Topics: Humans; Mitochondrial Myopathies; Kearns-Sayre Syndrome; Mitochondrial Diseases; Mitochondria; DNA, Mitochondrial; Water-Electrolyte Imbalance
PubMed: 37678265
DOI: 10.1681/ASN.0000000000000224